
1: J Asthma. 2009 Feb;46(1):86-90.

Prevalence of asthma and allergic rhinitis among school children of Karachi,
Pakistan, 2007.

Hasnain SM, Khan M, Saleem A, Waqar MA.

Allergy and Aerobiology Research Unit, Department of Biological & Medical
Research King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi
Arabia.

In recent times, the incidence of allergic diseases, particularly bronchial
asthma, has been increasing worldwide. However, there appears to be no published 
data on the prevalence of allergic diseases among school children (3 to 16 years 
of age) in Karachi, Pakistan, with only limited data available among few age
groups under one ISAAC study. The objective of this project was to investigate
the prevalence of allergic diseases among school children (3 to 16 years of age) 
in the city of Karachi. The questionnaire that was used for data collection had
previously been used for a similar study in neighboring Saudi Arabia and the
U.A.E. In 2007, a total of 3,000 surveys were distributed in various schools of
Karachi, of which 2,325 completed surveys were obtained. SPSS was used to perform
statistical analysis on the collected data. Survey results showed that the
frequency of diagnosed (previously seen by physicians) cases of asthma stood at
15.8%, while the frequency of allergic rhinitis was found to be 28.50% among
these children. Other parameters that were analyzed included dry cough (20.1%),
wheezing (11.7%), breathlessness (15.40%), and eczema (21.8%). Furthermore,
smoking by family members was found to be associated with asthma (p value less
than 0.05), allergic rhinitis (p value less than 0.05), breathlessness (p value
less than 0.05), dry cough (p value 0.002), and wheezing (p value less than
0.05). This study reveals that there is a significant number of school children
in the metropolitan city of Karachi who have various allergic symptoms. It also
sheds light on the fact that exposure to indoor environmental factors as well as 
family atopy can play a key role in increasing the chances of an individual to
experience asthma and other allergy symptoms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19191144 [PubMed - indexed for MEDLINE]

2: Postgrad Med. 2009 Jan;121(1):122-31.

Diagnosis and management of nasal congestion: the role of intranasal
corticosteroids.

Benninger M.

The Cleveland Clinic, Head and Neck Institute, Cleveland, OH 44195, USA.
benninm@ccf.org

Nasal congestion is considered the most bothersome of allergic rhinitis (AR)
symptoms and can significantly impair ability to function at work, home, and
school. Effective management of AR-related nasal congestion depends on accurate
diagnosis and appropriate treatment. Many individuals with AR and AR-related
congestion remain undiagnosed and do not receive prescription medication.
However, new tools intended to improve the diagnosis of nasal congestion have
been developed and validated. Intranasal corticosteroids (INSs) are recommended
as first-line therapy for patients with moderate-to-severe AR and also when nasal
congestion is a prominent symptom. Double blind, randomized clinical trials have 
demonstrated greater efficacy of INSs versus placebo, antihistamines, or
montelukast for relief of all nasal symptoms, especially congestion. Patient
adherence to treatment also affects outcomes, and this may be influenced by
patient preferences for the sensory attributes of an individual drug. Increased
awareness of the effects of AR-related nasal congestion, the efficacy and safety 
of available pharmacotherapies, and barriers to adherence may improve clinical
outcomes.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 19179820 [PubMed - indexed for MEDLINE]

3: Isr Med Assoc J. 2008 Dec;10(12):869-72.

Safety and efficacy of allergen immunotherapy in the treatment of allergic
rhinitis and asthma in real life.

Zeldin Y, Weiler Z, Magen E, Tiosano L, Kidon MI.

Allergy Service, Clalit Health Services, Barzilai Medical Center, Ashkelon,
Israel.

BACKGROUND: Subcutaneous allergen immunotherapy is effective in treating allergic
airway disease. Disadvantages include immediate local and systemic adverse
reactions and poor compliance. OBJECTIVES: To obtain real-life efficacy and
safety data through a prospective observational study of SIT in the allergist's
office. METHODS: We prospectively collected data from all patients with a
diagnosis of allergic rhinitis and/or asthma and a specific immunoglobulin
E-mediated sensitization to one or more aeroallergens who began SIT during the 2 
year period 1 January 2005 to 31 December 2006. As part of the routine
immunotherapy care patients were asked to complete a disease activity
questionnaire before and yearly during the treatment. The primary outcome measure
was the combined rhinitis and asthma symptoms scores. Data from patients
completing at least 1 year of immunotherapy were analyzed. RESULTS: Altogether,
133 enrolled patients with a mean age of 22.7 years completed at least 1 year of 
SIT. The allergic rhinitis and asthma disease activity score decreased from a
mean of 8.1 to 3.3 (rhinitis) and from 4.8 to 2.4 (asthma) on a 10 cm visual
analogue scale after 1 year of SIT (P < 0.001 for all comparisons). Rhinitis
medication use in all patients and asthma medication use in asthmatics decreased 
significantly. Mild local adverse reactions were almost universal. There were 11 
patients (8%) who developed 14 immediate systemic, mild to moderate reactions.
All reactions were successfully treated in the clinic; none required additional
observation or hospitalization. CONCLUSIONS: In the hands of experienced
allergists subcutaneous allergy immunotherapy is a safe and efficacious option
for patients with allergic rhinitis and asthma.

PMID: 19160945 [PubMed - indexed for MEDLINE]

4: Isr Med Assoc J. 2008 Dec;10(12):856-7.

Ambrosia: a new impending disaster for the israeli allergic population.

Waisel Y, Eshel A, Keynan N, Langgut D.

Department of Plant Sciences, Tel Aviv University, Ramat Aviv, Israel.
waisel@post.tau.ac.il

The pollen of Ambrosia (ragweed) is one of the major causes of pollen-induced
allergy worldwide. This genus of plants has apparently evolved in North America
but later spread into Europe and Asia. Flowering of the Ambrosias starts in
mid-July and continues throughout the autumn and is a cause of major morbidity to
allergic sensitized patients. The invasion of new species of Ambrosia into Israel
is still in progress. Plants of Ambrosia artemisiifolia (American short ragweed),
Ambrosia trifida (American giant ragweed), Ambrosia confertifolia, Ambrosia grayi
and Ambrosia tenuifolia are increasingly found in Israel, mainly in the Hula
valley in the eastern Galilee and near the Alexander River in the Sharon plain.
From experience it is known that the time it takes to eradicate a new invasive
species is limited. Action should be taken immediately or this new invasion will 
spread and cause a significantly increased burden of morbidity and increased
health costs in Israel.

PMID: 19160941 [PubMed - indexed for MEDLINE]

5: J Allergy Clin Immunol. 2009 Jan;123(1):167-173.e7.

Safety and efficacy in children of an SQ-standardized grass allergen tablet for
sublingual immunotherapy.

Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Klimek L, Knecht R,
Stephan V, Tholstrup B, Weisshaar C, Kaiser F.

Experimental Pneumonology, Ruhr-University Bochum,
Bergmannsheil-University-Clinics, Bochum, Germany. albrecht.bufe@rub.de

BACKGROUND: Immunotherapy with the SQ-standardized grass tablet Grazax is
efficacious and well-tolerated in adult patients with rhinoconjunctivitis.
Allergic asthma and rhinoconjunctivitis are closely linked, and a strategy
combining treatment of the upper and lower airways is recommended. OBJECTIVE: To 
investigate the efficacy of treatment with the grass tablet on grass
pollen-induced rhinoconjunctivitis and asthma as well as the immunologic response
and the safety profile in children. METHODS: A total of 253 children age 5 to 16 
years, with grass pollen-induced rhinoconjunctivitis with/without asthma, were
randomized 1:1 to active treatment or placebo. Treatment was initiated 8 to 23
weeks before the start of the grass pollen season 2007 and continued throughout
the entire season. Symptomatic medication was provided as relief medication to
both groups in a stepwise fashion. Primary endpoints were rhinoconjunctivitis
symptom and medication scores. RESULTS: The rhinoconjunctivitis symptom and
medication scores and the asthma symptom score were all statistically
significantly different between the 2 treatment groups. The differences in
medians relative to placebo were 24%, 34%, and 64% in favor of active treatment. 
The immunologic response was similar to that observed in adults. The most common 
adverse reaction was oral pruritus, reported by 40 subjects (32%) in the active
and 3 (2%) in the placebo group. Six subjects withdrew because of adverse events.
No serious adverse events were assessed as treatment-related. CONCLUSION:
Immunotherapy with the grass tablet reduced grass pollen-induced
rhinoconjunctivitis and asthma symptoms in a pediatric population and introduced 
an immunomodulatory response, consistent with treatment of the underlying
allergic disease. The treatment was well tolerated.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 19130937 [PubMed - indexed for MEDLINE]

6: Am J Epidemiol. 2009 Mar 1;169(5):562-71. Epub 2009 Jan 6.

Cost-effectiveness of acupuncture in women and men with allergic rhinitis: a
randomized controlled study in usual care.

Witt CM, Reinhold T, Jena S, Brinkhaus B, Willich SN.

Social Medicine, Epidemiology, and Health Economics, Charité University Medical
Center, Berlin, Germany. claudia.witt@charite.de

To assess quality of life and cost-effectiveness of additional acupuncture
treatment for allergic rhinitis, patients were randomly allocated to 2 groups;
both received usual care, but one group received an additional 10 acupuncture
sessions. Quality of life (according to the SF-36 Health Survey), and direct and 
indirect costs, were assessed at baseline and after 3 months, and the incremental
cost-effectiveness ratio of acupuncture treatment was calculated. This German
study (December 2000-June 2004) involved 981 patients (64% women, mean age 40.9
years (standard deviation, 11.2); 36% men, mean age 43.2 years (standard
deviation, 13.0)). At 3 months, quality of life was higher in the acupuncture
group than in the control group (mean Physical Component Score 51.99 (standard
error (SE), 0.33) vs. 48.25 (SE, 0.33), P < 0.001; mean Mental Component Score
48.55 (SE, 0.42) vs. 45.35 (SE, 0.42), respectively, P < 0.001). Overall costs in
the acupuncture group were significantly higher than those in the control group
(Euro (euro; 1 euro = US $1.27) 763, 95% confidence interval: 683, 844 vs. 332
euro, 95% confidence interval: 252, 412; mean difference 432 euro, 95% confidence
interval: 318, 545). The incremental cost-effectiveness ratio was 17,377 euro per
quality-adjusted life year (women, 10,155 euro; men, 44,871 euro) and was robust 
in sensitivity analyses. Acupuncture, supplementary to routine care, was
beneficial and, according to international benchmarks, cost-effective. However,
because of the study design, it remains unclear whether the effects are
acupuncture specific.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 19126587 [PubMed - indexed for MEDLINE]

7: Mediators Inflamm. 2008;2008:496467. Epub 2008 Nov 30.

Citrus/Cydonia comp. can restore the immunological balance in seasonal allergic
rhinitis-related immunological parameters in vitro.

Baars EW, Savelkoul HF.

Department of Healthcare and Nutrition, Louis Bolk Instituut, 3972 LA Driebergen,
The Netherlands. e.baars@louisbolk.nl

In two in vitro studies, we examined the immunological (pathways of the) effects 
of Citrus/Cydonia comp. from, respectively, a healthy and an allergic donor;
peripheral blood mononuclear cells (PBMCs) were isolated out of peripheral blood 
and analyzed in vitro after polyclonal stimulation of T-cells. The
differentiation capacity and the influence with regard to Th1 (IFN-gamma) and Th2
(IL-5) cells were examined. Citrus/Cydonia comp. has a selective effect on the
differentiation of T-cells by producing relatively more IL-10 than IL-12. By
that, it also seems to have an effect on the induction of regulatory (IL-10
producing) T-cell subsets. It is in vitro capable of neutralizing (to some
extent) the changes, characteristic to allergic rhinitis, with regard to the
maturation, differentiation, and activity of the immune system. Thus,
Citrus/Cydonia comp. can potentially restore the disturbed immune state of
rhinitis patients, which essentially could be sufficient to make allergic
symptoms disappear permanently.

PMID: 19079587 [PubMed - indexed for MEDLINE]

8: Ann Allergy Asthma Immunol. 2008 Nov;101(5):535-43.

Acupuncture in patients with allergic rhinitis: a pragmatic randomized trial.

Brinkhaus B, Witt CM, Jena S, Liecker B, Wegscheider K, Willich SN.

Institute of Social Medicine, Epidemiology, and Health Economics, Charité
University Medical Center, Berlin, Germany. benno.brinkhaus@charite.de

BACKGROUND: Acupuncture is widely used in patients with allergic rhinitis, but
the available evidence of its effectiveness is insufficient. OBJECTIVE: To
evaluate the effectiveness of acupuncture in addition to routine care in patients
with allergic rhinitis compared with treatment with routine care alone. METHODS: 
In a randomized controlled trial, patients with allergic rhinitis were randomly
allocated to receive up to 15 acupuncture sessions during a period of 3 months or
to a control group receiving no acupuncture. Patients who did not consent to
random assignment received acupuncture treatment. All patients were allowed to
receive usual medical care. The Rhinitis Quality of Life Questionnaire (RQLQ) and
general health-related quality of life (36-Item Short-Form Health Survey) were
evaluated at baseline and after 3 and 6 months. RESULTS: Of 5,237 patients (mean 
[SD] age, 40 [12] years; 62% women), 487 were randomly assigned to acupuncture
and 494 to control, and 4,256 were included in the nonrandomized acupuncture
group. At 3 months, the RQLQ improved by a mean (SE) of 1.48 (0.06) in the
acupuncture group and by 0.50 (0.06) in the control group (3-month scores, 1.44
[0.06] and 2.42 [0.06], respectively; difference in improvement, 0.98 [0.08]; P <
.001). Similarly, quality-of-life improvements were more pronounced in the
acupuncture vs the control group (P < .001). Six-month improvements in both
acupuncture groups were lower than they had been at 3 months. CONCLUSIONS: The
results of this trial suggest that treating patients with allergic rhinitis in
routine care with additional acupuncture leads to clinically relevant and
persistent benefits. In addition, it seems that physician characteristics play a 
minor role in the effectiveness of acupuncture treatment, although this idea
needs further investigation.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 19055209 [PubMed - indexed for MEDLINE]

9: Asian Pac J Allergy Immunol. 2008 Jun-Sep;26(2-3):137-41.

Effects of lysed Enterococcus faecalis FK-23 on allergen-induced peritoneal
accumulation of eosinophils and serum total IgE concentration in inbred mice.

Shimada T, Zhu LP, Yin M, Motonaga C, Li HB, Shi HB, Enomoto K, Enomoto T, Cheng 
L.

Central Research Laboratories, Nichinichi Pharmaceutical Co. Ltd., Mie, Japan.

Recent clinical trials have shown the possibility of probiotics in prevention and
treatment of allergic diseases. The purpose of this experimental study was to
assess the influence of lysed Enterococcus faecalis FK-23 (LFK) on allergic
responses in different mouse strains. We performed a comparative study on the
effects of LFK for allergen-induced peritoneal accumulation of eosinophils and
serum total IgE concentration by using BALB/c, C57BL/6, C3H/HeN and C3H/HeJ mice.
There was no significant difference in total number of peritoneal accumulated
cells induced by cedar pollen allergen between the control and LFK groups in any 
strain of mice (p > 0.05); however, the ratio of eosinophils to total accumulated
cells was significantly decreased in LFK-treated mice of BALB/c (p = 0.016),
C3H/HeN (p = 0.010) and C3H/HeJ (p = 0.004), but not C57BL/6 (p > 0.05). No
significant difference in serum total IgE concentration was found between the
control and LFK groups of different mouse strains (p > 0.05). These results
reveal a different effect of LFK on suppressing allergen-induced local
eosinophila in inbred strains of mice, suggesting the effectiveness of probiotics
on limiting allergy might be under the influence of individual genetic
background.

Publication Types: 
    Comparative Study

PMID: 19054932 [PubMed - indexed for MEDLINE]

10: Asian Pac J Allergy Immunol. 2008 Jun-Sep;26(2-3):97-104.

A correlation between symptom severity and unbalanced reactive IgA production in 
Japanese cedar pollinosis patients.

Komatsu N, Harada M, Nakagawa M, Tanaka Y, Ono T, Gohara S, Ohkubo K, Itoh K.

Department of Immunology, Kurume University School of Medicine, Kurume, Japan.
kom@med.kurume-u.ac.jp

To better understand the unbalanced immunoglobulin production that occurs in
pollinosis, we measured the levels of IgG, IgA, and IgE reactive to either
Japanese cedar pollen, Cry j 1 protein, or Cry j 2 protein in the sera of
pollinosis patients. As expected, the levels of these immunoglobulins (Igs)
reactive to the three antigens were significantly higher in the patients than in 
the controls, and the RAST scores correlated with the levels of these Igs. Only
the levels of IgA reactive to the Cry j 2 protein and IgG reactive to the
Japanese cedar pollen antigen did not correlate with the RAST scores. We
classified the patients into mild and severe, based on the severity of their
allergic symptoms, and compared their levels of Igs. As expected, the levels of
IgE reactive to Japanese cedar pollen and Cry j 1 of the severe group were
significantly higher than those of the mild group. It is of note that the ratio
of anti-Cry j 1 IgE to anti-Japanese cedar pollen IgA was significantly higher in
the patients with severe symptoms suggesting that decreased IgA production could 
be responsible for the severity of pollinosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19054927 [PubMed - indexed for MEDLINE]

11: J Allergy Clin Immunol. 2009 Jan;123(1):160-166.e3. Epub 2008 Nov 29.

Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in
pediatric allergic rhinoconjunctivitis.

Wahn U, Tabar A, Kuna P, Halken S, Montagut A, de Beaumont O, Le Gall M; SLIT
Study Group.

Collaborators: Hansen LG, Hansen KS, Payot F, Levy J, Alt R, Mullard MR, Houssel 
JM, Seidenberg J, Nemat K, Rebien W, Folster-Hoelst, Bauer CP, Malaczynska T,
Kardas-Sobantka D, Hofman J, Baranovska R, Stelmach I, Springer E, Emeryk A,
Buczyłko K, Lebrero EA, Garcia MB, Toledano FL, Munoz MF, Munoz MT.

Berlin Children's Hospital, Charité/Campus Virchow-Klinikum, Augustenburger
Platz, Berlin, Germany. ulrich.wahn@charite.de

BACKGROUND: The efficacy and safety of the 300-index of reactivity (IR) dose of
5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergènes, Antony,
France) have been demonstrated for the treatment of hay fever in adults.
OBJECTIVE: We sought to assess the efficacy and safety of this tablet in children
and adolescents with grass pollen-related allergic rhinitis. METHODS: In this
multinational, randomized, double-blind, placebo-controlled study, 278 children
(5-17 years of age) with grass pollen-related rhinoconjunctivitis (confirmed by
means of a positive grass pollen skin prick test response and serum-specific IgE 
measurement) received once-daily SLIT tablets or placebo. Treatment was initiated
4 months before the estimated pollen season and continued throughout the season. 
The primary outcome was the rhinoconjunctivitis total symptom score (RTSS), a sum
of 6 individual symptom scores: sneezing, runny nose, itchy nose, nasal
congestion, watery eyes, and itchy eyes. Secondary end points included rescue
medication intake, individual scores, and safety. RESULTS: The intent-to-treat
population included 266 children (mean age, 10.9 +/- 3.22 years). The RTSS for
the 300-IR group was highly significantly different from that of the placebo
group (P = .001). The 300-IR group showed a mean improvement for the RTSS of
28.0% over that seen with placebo and a median improvement of 39.3%. Significant 
differences between the 300-IR and placebo groups were also observed regarding
rescue medication score and proportion of days using rescue medication during the
pollen season (P = .0064 and P = .0146, respectively). Adverse events were
generally mild or moderate in intensity and expected. No serious side effects
were reported. CONCLUSION: Five-grass-pollen SLIT tablets (300 IR) reduce both
symptom scores and rescue medication use in children and adolescents with grass
pollen-related rhinoconjunctivitis.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 19046761 [PubMed - indexed for MEDLINE]

12: J Physiol Biochem. 2008 Jun;64(2):143-8.

Monitoring antioxidant enzymes in red cells during allergen immunotherapy.

Lukan N, Racz O, Mocnejova I, Tkac I.

Department of Internal Medicine IV. Safarik University, Kosice, Slovakia.
norbertlukan@gmail.com

The aim of this report was to answer the question how specific immunotherapy
influences the antioxidant enzyme system in patients with respiratory allergy and
in longer perspective to find markers suitable to assess the efficacy of
treatment. In open prospective randomised study 28 patients (18 females and 10
males, age 14-48 years) with seasonal respiratory allergy were treated with
allergen immunotherapy. Subjects received subcutaneous therapy with allergens
absorbed on calcium phoshate or aluminium hydroxide and were analyzed by the
established protocol at the beginning, after three and 12 month of the treatment.
In all treatment group red cell superoxide dismutase and glutathione peroxidase
activities were in the normal range in allergic patients both before and during
the treatment. Catalase activity in the allergic patients was lower as compared
with controls and a significant increase of the enzyme activity occurred during
and at the end of the treatment. In patients treated with calcium phosphate
adsorbed allergen there was a continous increase of catalase activity from
beginning up to the end of observation. In the case of the aluminium hydroxide
treatment there was an increase from the baseline values up in the third month of
the treatment and a decrease on the 12th month. In summary, the present results
open the question that allergen immunotherapy may cause imbalance of oxidants and
antioxidants. To support our findings larger controlled field studies are needed.

Publication Types: 
    Randomized Controlled Trial

PMID: 19043984 [PubMed - indexed for MEDLINE]

13: Clin Exp Allergy. 2008 Dec;38(12):1875-81.

Association of serum interleukin-33 level and the interleukin-33 genetic variant 
with Japanese cedar pollinosis.

Sakashita M, Yoshimoto T, Hirota T, Harada M, Okubo K, Osawa Y, Fujieda S,
Nakamura Y, Yasuda K, Nakanishi K, Tamari M.

Laboratory for Genetics of Allergic Diseases, SNP Research Center, RIKEN,
Kanagawa, Japan.

BACKGROUND: IL-33, an IL-1-like cytokine, is a ligand for IL1RL1, which is an
important effector molecule of type 2 T helper responses. Although IL-33/IL1RL1
interaction has been suggested to be important in induction of allergic airway
inflammation, serum levels of IL-33 and the genetic influences of the
polymorphisms of IL-33 in human allergic diseases are unclear. OBJECTIVE: The aim
of this study was to examine whether the serum IL-33 level and polymorphisms in
IL-33 are associated with Japanese cedar (JC) pollinosis, the most common form of
allergic rhinitis, and a major public health problem, in Japan. METHODS: We
performed linkage disequilibrium (LD) mapping of the gene using the HapMap
database, and two selected tag single nucleotide polymorphisms were genotyped. We
conducted an association study of IL-33 (JC pollinosis, n=170; normal controls,
n=100) and measured the IL-33 levels in sera of the 270 subjects by ELISA.
RESULTS: Serum levels of IL-33 were significantly higher in patients with JC
pollinosis (P=0.0018) than in controls. In genetic association analysis, we found
a positive association between the polymorphism and JC pollinosis (P=0.048).
CONCLUSION: Our results support a role for IL-33 in the pathogenesis of JC
pollinosis.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 19037964 [PubMed - indexed for MEDLINE]

14: J Biol Regul Homeost Agents. 2008 Oct-Dec;22(4):267-70.

Bronchodilation test in allergic adolescents.

Marseglia GL, Marchi A, Caimmi D, Caimmi S, Di Gioacchino M, Ciprandi G.

This study highlights the close link between upper and lower airways and the
relevance of bronchodilation test in patients presenting with moderate-severe
persistent allergic rhinitis and mild persistent asthma.

Publication Types: 
    Letter

PMID: 19036230 [PubMed - indexed for MEDLINE]

15: Clin Exp Allergy. 2008 Dec;38(12):1891-900. Epub 2008 Oct 30.

Allergen-specific immunotherapy alters the expression of B and T lymphocyte
attenuator, a co-inhibitory molecule, in allergic rhinitis.

Okano M, Otsuki N, Azuma M, Fujiwara T, Kariya S, Sugata Y, Higaki T, Kino K,
Tanimoto Y, Okubo K, Nishizaki K.

Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
mokano@cc.okayama-u.ac.jp

BACKGROUND: B7/CD28 family co-signalling molecules play a key role in regulating 
T cell activation and tolerance. Allergen-specific immunotherapy (SIT) alters
allergen-specific T cell responses. However, the effect of SIT on the expression 
of various co-signalling molecules has not been clarified. OBJECTIVE: We sought
to determine whether SIT might affect the expression of three co-inhibitory
molecules, programmed death (PD)-1, B7-H1 and B and T lymphocyte attenuator
(BTLA), in Japanese cedar pollinosis (JCP). METHODS: Peripheral blood mononuclear
cells (PBMCs) were isolated from JCP patients who had or had not received SIT.
PBMC were cultured in the presence or absence of Cry j 1, after which the cell
surface expression of PD-1, B7-H1 and BTLA, as well as IL-5 production, were
determined. In addition, the effect of BTLA cross-linking on IL-5 production was 
examined. RESULTS: After Cry j 1 stimulation, no significant differences in PD-1 
and B7-H1 expression were observed between SIT-treated and SIT-untreated
patients. BTLA expression was down-regulated in untreated patients after Cry j 1 
stimulation and up-regulated in SIT-treated patients. Up-regulation of BTLA in
SIT-treated patients was particularly apparent in a CD4(+) T cell subset. IL-5
production was clearly reduced among SIT-treated patients, and the observed
changes in BTLA expression correlated negatively with IL-5 production. Moreover, 
immobilization of BTLA suppressed IL-5 production in JCP patients. CONCLUSION:
These results suggest that both IL-5 production and down-regulation of BTLA in
response to allergen are inhibited in SIT-treated patients with JCP.
BTLA-mediated co-inhibition of IL-5 production may contribute to the regulation
of allergen-specific T cell responses in patients receiving immunotherapy.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 19016801 [PubMed - indexed for MEDLINE]

16: J Allergy Clin Immunol. 2008 Nov;122(5):951-60.

Erratum in:
    J Allergy Clin Immunol. 2009 Jan;123(1):166. Valenta, Rudolph [corrected to
Valenta, Rudolf].

Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic 
rhinoconjunctivitis.

Pauli G, Larsen TH, Rak S, Horak F, Pastorello E, Valenta R, Purohit A, Arvidsson
M, Kavina A, Schroeder JW, Mothes N, Spitzauer S, Montagut A, Galvain S, Melac M,
André C, Poulsen LK, Malling HJ.

University Hospital, Strasbourg, France.

BACKGROUND: Recombinant DNA technology has the potential to produce
allergen-specific immunotherapy vaccines with defined composition. OBJECTIVE: To 
evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in 
patients with birch pollen allergy. METHODS: A multicenter, randomized,
double-blind, placebo-controlled trial was undertaken to compare the following 3 
vaccines in 134 adults with birch pollen allergy: recombinant birch pollen
allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified
birch pollen allergen (nBet v 1), and placebo. Patients received 12 weekly
injections followed by monthly injections of the maintenance dose containing 15
microg Bet v 1 for 2 years. RESULTS: Significant reductions (about 50%) in
rhinoconjunctivitis symptoms (rBet v 1, P = .0002; nBet v 1, P = .0006; birch
extract, P = .0024), rescue medication (rBet v 1, P = .0011; nBet v 1, P = .0025;
birch extract, P = .0063), and skin sensitivities (P < .0001) were observed in
the 3 actively treated groups compared with placebo during 2 consecutive pollen
seasons. Clinical improvement was accompanied by marked increases in Bet v
1-specific IgG levels, which were higher in the rBet v 1-treated group than in
the birch and nBet v 1-treated groups. New IgE specificities were induced in 3 of
29 patients treated with birch pollen extract, but in none of the 32 rBet v
1-treated or 29 nBet v 1-treated patients. No severe systemic adverse events were
observed in the rBet v 1-treated group. CONCLUSION: The rBet v 1-based vaccine
was safe and effective in treating birch pollen allergy, and induced a highly
specific immune response.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 19000581 [PubMed - indexed for MEDLINE]

17: J Asthma. 2008 Oct;45(8):710-4.

Risk factors for asthma and other allergic diseases in seasonal rhinitis.

Celikel S, Isik SR, Demir AU, Karakaya G, Kalyoncu AF.

Department of Chest Diseases, Adult Allergy Unit, Hacettepe University School of 
Medicine, Ankara, Turkey. scelikel@gmail.com

BACKGROUND: Rhinitis and asthma are common comorbidities. The aim of this study
was to determine the risk factors for asthma and other allergic diseases in
seasonal rhinitis (SR) patients. METHODS: Records of 922 patients diagnosed as SR
between 1991 and 2005 were evaluated retrospectively. Patients were grouped
according to the results of our standard skin prick tests as follows: I-No
sensitization: no sensitization to any allergen; II-Mono-pollen sensitization:
sensitization to only one pollen allergen; III-Poly-pollen sensitization:
sensitization to more than one pollen allergen; IV-Mite sensitization:
sensitization to mite with or without any other allergen sensitization. RESULTS: 
The mean age of the patients was 29.5 +/- 9.6 and 587 patients (63.2%) were
females. Age at onset of SR was median 21 years (16-29 years). Of the 922
patients, 99 had no sensitization, 335 had poly-pollen sensitization, 346 had
mono-pollen sensitization, and 142 had mite sensitization. The most prevalent
allergens were P. pratense (85.3%) and O. europae (31.5%). No sensitization group
as compared to poly-pollen sensitization group had significantly higher
prevalence of asthma as a single accompanying disease (14.1%, p < 0.05).
Mono-pollen sensitization was significantly associated with lower risk of any
accompanying allergic disease (OR: 0.7, 95% CI 0,5-0,9) while no sensitization
group (OR: 2.8, 95% CI 1.3-5.9) and mite sensitization were associated with
asthma (OR: 2.3, 95% CI 1.2-4.4). CONCLUSION: SR is a condition that presents
with different phenotypes. The group with no sensitization and mite sensitization
has the highest prevalence of asthma while SR patients with mono-pollen
sensitization are unlikely to have an accompanying allergic disease, including
asthma.

PMID: 18951265 [PubMed - indexed for MEDLINE]

18: J Pharmacol Sci. 2008 Oct;108(2):149-56.

Levocetirizine modulates lymphocyte activation in patients with allergic
rhinitis.

Mahmoud F, Arifhodzic N, Haines D, Novotney L.

Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences,
Kuwait University, Kuwait. fadia@hsc.edu.kw

Levocetirizine, a second generation non-sedating antihistamine that blocks the
H(1) histamine receptor, may exhibit immunoregulatory properties that augment its
primary pharmacological mechanism. To investigate this possibility, 13 Kuwaiti
seasonal allergic rhinitis (SAR) patients were treated with levocetirizine for
four weeks in comparison with a 7-member placebo-treated control group, followed 
by clinical evaluation and flow cytometric analysis of peripheral venous blood
for inflammatory cell and lymphocyte subpopulation profiles. Relative to the
controls, levocetirizine-treated patients exhibited an expected reduction in
early phase allergic symptoms, including sneezing (P<0.001), nasal itching
(P<0.01), nasal congestion, and running nose (P<0.001); reduced percentages of
eosinophils (P<0.05); and three subpopulations of activated T lymphocytes:
CD4+CD29+, CD4+CD212+, and CD4+CD54+ (P<0.05). Levocetirizine treatment also
correlated with a significant increase in the percentage of CD4+CD25+ T cells
(P<0.001). The ability of levocetirizine to reduce percentage representation of
cell phenotypes known to contribute to inflammatory tissue damage (eosinophils,
CD4+CD29+, CD4+CD212+, and CD4+CD54+) and expand percentages of CD4+CD25+, which 
may include protective immunoregulatory (Treg) cells, indicates that the drug has
pharmacological potential beyond the immediate effects of H(1) histamine-receptor
inhibition. Although the present data does not define a therapeutic mechanism,
the results reported here establish important trends that may be used to guide
future mechanistic examination of immunoregulatory capacity of H(1) inhibitors.

Publication Types: 
    Controlled Clinical Trial

PMID: 18946193 [PubMed - indexed for MEDLINE]

19: Curr Allergy Asthma Rep. 2008 Nov;8(6):465-74.

Subcutaneous and sublingual immunotherapy in children: complete update on
controversies, dosing, and efficacy.

Larenas-Linnemann D.

Hospital Médica Sur, Torre 2, cons. 602, Puente de Piedra 150, Col. Toriello
Guerra, Del. Tlalpan, 14050, Mexico D.F., Mexico. marlar1@prodigy.net.mx

For this review, articles on immunotherapy dosing in pediatric respiratory
allergy were identified via PubMed, through congressional abstracts for 2008, in 
reference lists of recent review articles, and via personal communication with
experts. In pediatric subcutaneous immunotherapy (SCIT), doses shown to be
effective, mostly in aluminium-adsorbed preparations administered every 6 weeks, 
contain 20 microg of group 5 major allergen, 12 microg Bet v 1, 15 microg Fel d
1, and 5 to 20 microg Der p 1. Evidence indicates that SCIT prevents new
sensitizations and asthma onset 7 years after discontinuation and reduces
symptoms 12 years after a 5-year SCIT course, even though skin reactivity
returns. Consistent evidence of effect exists for sublingual immunotherapy in
pediatric respiratory allergy with daily 15- to 25-microg grass group 5 major
allergen and 6 microg Bet v 1. Der p/f doses of 0.8/0.4 microg three times weekly
(up to 27/57 microg daily) demonstrate inconsistent findings. Evidence of effect 
exists for SCIT in pediatric allergic rhinitis and asthma as treatment and
preventive management. Evidence of effect exists for sublingual immunotherapy in 
pediatric allergic rhinoconjunctivitis and seasonal asthma. Similar results are
doubtful for perennial asthma.

Publication Types: 
    Review

PMID: 18940136 [PubMed - indexed for MEDLINE]

20: Mol Nutr Food Res. 2008 Nov;52 Suppl 2:S230-40.

Characterization of Bet v 1-related allergens from kiwifruit relevant for
patients with combined kiwifruit and birch pollen allergy.

Oberhuber C, Bulley SM, Ballmer-Weber BK, Bublin M, Gaier S, DeWitt AM, Briza P, 
Hofstetter G, Lidholm J, Vieths S, Hoffmann-Sommergruber K.

Biomay AG, Vienna, Austria.

Allergy to kiwifruit appears to have become more common in Europe and elsewhere
during the past several years. Seven allergens have been identified from
kiwifruit so far, with actinidin, kiwellin and the thaumatin-like protein as the 
most relevant ones. In contrast to other fruits, no Bet v 1 homologues were
characterized from kiwifruit so far. We cloned, purified, and characterized
recombinant Bet v 1-homologous allergens from green (Actinidia deliciosa, Act d
8) and gold (Actinidia chinensis, Act c 8) kiwifruit, and confirmed the presence 
of its natural counterpart by inhibition assays. Well-characterized recombinant
Act d 8 and Act c 8 were recognized by birch pollen/kiwifruit (confirmed by
double-blind placebo-controlled food challenge) allergic patients in IgE
immunoblots and ELISA experiments. The present data point out that Bet v 1
homologues are allergens in kiwifruit and of relevance for patients sensitized to
tree pollen and kiwifruit, and might have been neglected so far due to low
abundance in the conventional extracts used for diagnosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18925615 [PubMed - indexed for MEDLINE]

21: Scand J Work Environ Health. 2008 Oct;34(5):403-4. Epub 2008 Oct 14.

Occupational rhinitis caused by tolyltriazole in metalworking fluids.

Graff P, Elmsjö L, Björkander J, Flodin U.

Centre of Occupational and Environmental Medicine, University Hospital,
Linköping, Sweden. pal.graff@lio.se

OBJECTIVES: Exposure to metalworking fluids is known to cause mucous membrane
inflammation of the airways. In this case report, the authors attempted to
identify responsible components in the metalworking fluids for the rhinitis of an
exposed patient. METHODS: The patient underwent two provocation tests. The first 
provocation was performed with the different metalworking fluids used in the
factory, and the second was done double blind for some of the components in the
metalworking fluids. The patient was asked to quantify her symptoms before,
immediately after, 24 hours after, and finally 96 hours after the exposure.
RESULTS: The patient reacted to tolyltriazole with rhinitis and headache. These
symptoms started about 8 hours after the exposure and persisted for 24 hours.
CONCLUSION: The double-blind provocation exposure to the components of the
metalworking fluids showed that the patient reacted to the corrosion inhibitor
tolyltriazole. To the authors' knowledge, no such reaction to tolyltriazole in
the airways has previously been reported.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 18853069 [PubMed - indexed for MEDLINE]

22: Int J Immunopathol Pharmacol. 2008 Jul-Sep;21(3):761-5.

Consequences of long-lasting persistent allergic rhinitis in adolescents.

Marseglia GL, Grignani M, Civallero P, Colombo B, Di Gioacchino M, Marchi A,
Perrone A, Ciprandi G.

While it is well known that asthma is characterized by airway remodelling, only
few studies have investigated this issue in patients affected by allergic
rhinitis (AR). The aim of the present study is to investigate functional and
structural consequences of long-lasting persistent AR (PER) in a cohort of
adolescents. Eighty patients, forty with short-lasting and forty with
long-lasting PER were prospectively and consecutively evaluated both clinically
and by performing skin prick test, nasal cytology, and rhinomanometry.
Eosinophils were significantly higher in patients presenting with long-lasting
PER rather than in those with short-lasting PER (P < 0.0001). The degree of
inflammation was significantly associated with impaired nasal airflow (rs =
-0.81). This study provides evidence that adolescents with long-lasting PER may
show a progressive worsening of nasal function depending on the inflammation.

Publication Types: 
    Letter

PMID: 18831947 [PubMed - indexed for MEDLINE]

23: Ann Allergy Asthma Immunol. 2008 Sep;101(3):316-24.

Cost-effectiveness of specific subcutaneous immunotherapy in patients with
allergic rhinitis and allergic asthma.

Brüggenjürgen B, Reinhold T, Brehler R, Laake E, Wiese G, Machate U, Willich SN.

Institute for Social Medicine, Epidemiology and Health Economics,
Charité-University Medical Center, Berlin, Germany.

BACKGROUND: Specific immunotherapy is the only potentially curative treatment in 
patients with allergic rhinitis and allergic asthma. Health economic evaluations 
on this treatment, particularly in a German context, are sparse. OBJECTIVE: To
evaluate the cost-effectiveness of specific subcutaneous immunotherapy (SCIT) in 
addition to symptomatic treatment (ST) compared with ST alone in a German health 
care setting. METHODS: The analysis was performed as a health economic model
calculation based on Markov models. In addition, we performed a concomitant
expert board composed of allergy experts in pediatrics, dermatology, pneumology, 
and otolaryngology. The primary perspective of the study was societal. Additional
sensitivity analyses were performed to prove our results for robustness. RESULTS:
The SCIT and ST combination was associated with annual cost savings of Euro140
per patient. After 10 years of disease duration, SCIT and ST reach the breakeven 
point. The overall incremental cost-effectiveness ratio (ICER) was Euro-19,787
per quality-adjusted life-year (QALY), with a range that depended on patient age 
(adults, Euro-22,196; adolescents, Euro-14,747; children, Euro-12,750). From a
third-party payer's perspective, SCIT was associated with slightly additional
costs. Thus, the resulting ICER was Euro8,308 per QALY for all patients.
CONCLUSIONS: Additional SCIT was associated with improved medical outcomes and
cost savings compared with symptomatic treatment alone according to a societal
perspective. Taking a European accepted ICER threshold of up to Euro50,000 per
QALY into account, additional SCIT is considered clearly cost-effective compared 
with routine care in Germany. The degree of cost-effectiveness is strongly
affected by costs related to SCIT and the target population receiving such
treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18814456 [PubMed - indexed for MEDLINE]

24: Ann Allergy Asthma Immunol. 2008 Sep;101(3):304-10.

Frequency of acute systemic reactions in patients with allergic rhinitis and
asthma treated with sublingual immunotherapy.

Rodríguez-Pérez N, Ambriz-Moreno Mde J, Canonica GW, Penagos M.

Allergy Clinic, Autonomous State University of Tamaulipas, Matamoros, Tamaulipas,
Mexico. rnoel@prodigy.net.mx

BACKGROUND: Several studies have demonstrated the efficacy and safety of
sublingual immunotherapy in the treatment of respiratory allergy. OBJECTIVE: To
determine the frequency of systemic adverse reactions in patients treated with
standardized extracts of sublingual immunotherapy. METHODS: Allergic patients
with rhinitis with or without asthma and sensitized to at least 1 allergen were
included. Increasing doses of standardized allergens were administered until
reaching an average dose accumulated of 7,200 U after 26 weeks of treatment.
Adverse events were graded according to the European Academy of Allergy and
Clinical Immunology immunotherapy position paper. RESULTS: Forty-three patients
with a median age of 11 years (interquartile range, 8-20 years) were included.
All the patients had allergic rhinitis, and 63% had asthma; they were sensitized 
mostly to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Four
patients (9%) presented with an immediate and 1 (2%) with a late systemic
reaction. In total, 7 systemic reactions occurred in 23,154 doses, and all were
associated with wheezing or worsening of nasal symptoms (grade 2); in addition, 1
patient had angioedema and urticaria (grade 3). CONCLUSIONS: In this group,
systemic reaction frequency was 11.6%, and all were classified as grade 2 or 3.
Further assessments in larger samples of patients are required in the context of 
randomized controlled trials.

Publication Types: 
    Clinical Trial

PMID: 18814454 [PubMed - indexed for MEDLINE]

25: Ann Allergy Asthma Immunol. 2008 Sep;101(3):287-94.

Efficacy comparison of levocetirizine vs montelukast in ragweed sensitized
patients.

Patel P, Patel D.

Allied Research International, Cetero Research, Mississauga, Ontario, Canada.
ppatel@allied-research.com

BACKGROUND: To date, no adequate data are available on direct comparison of the
efficacy of levocetirizine, a recently approved histamine1-antihistamine, with
that of a leukotriene antagonist in the treatment of seasonal allergic rhinitis
(SAR) symptoms. OBJECTIVE: To compare the efficacy of therapeutic doses of 5 mg
of levocetirizine and 10 mg of montelukast in ragweed sensitized patients.
METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was
conducted between July and October 2006. Symptomatic patients with SAR were
exposed to ragweed pollen under controlled conditions in an environmental
exposure chamber for 4 to 5 hours after treatment with 5 mg of levocetirizine, 10
mg of montelukast, or matched placebo on 2 consecutive days. The mean change from
baseline in pollen-induced rhinitis symptoms, expressed as a major symptoms
complex (MSC) score (sum of scores for rhinorrhea, itchy nose, sniffles, nose
blows, sneezes, and watery eyes), in period 1 (first 5 hours after first drug
intake) was the primary efficacy outcome. RESULTS: A total of 611 patients were
screened, of whom 403 were randomized to receive treatment (102 placebo, 152
levocetirizine, and 149 montelukast). The MSC score in period 1 was progressively
decreased to a significantly greater extent in the levocetirizine group compared 
with the montelukast and placebo groups (adjusted mean differences, -2.18 [95%
confidence interval, -3.35 to -1.01; P < .001] and -2.22 [95% confidence
interval, -3.51 to -0.92; P < .001] for levocetirizine vs montelukast and vs
placebo, respectively). The effect of 10 mg of montelukast was not significantly 
different compared with placebo. Levocetirizine also achieved a significantly
faster onset of action within 2.5 hours of administration. Both products were
well tolerated. CONCLUSIONS: This study in an environmental exposure chamber
confirms the therapeutic efficacy of 5 mg of levocetirizine in improving symptoms
of SAR, which was superior to 10 mg of montelukast.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18814452 [PubMed - indexed for MEDLINE]

26: Expert Opin Pharmacother. 2008 Oct;9(15):2707-15.

Fluticasone furoate nasal spray consistently and significantly improves both the 
nasal and ocular symptoms of seasonal allergic rhinitis: a review of the clinical
data.

Scadding GK, Keith PK.

Royal National Throat, Nose and Ear Hospital, Rhinology Department, 330 Grey's
Inn Road, London WC1X 8DA, UK. g.scadding@ucl.ac.uk

BACKGROUND: Allergic rhinitis (AR) is a highly prevalent disorder, which often
manifests as both nasal (congestion, sneezing, itching and rhinorrhoea) and
ocular (redness, watery eyes, itching and burning) symptoms. Until recently,
efficacy against the ocular symptoms of AR has been inconsistent for any single
intranasal corticosteroid (INS). Fluticasone furoate is an enhanced-affinity
glucocorticoid with potent anti-inflammatory activity. OBJECTIVE: To assess
better the efficacy of an INS in the treatment of both the nasal and ocular
symptoms of seasonal AR (SAR). METHODS: Data from all four trials of fluticasone 
furoate nasal spray (FFNS) in the treatment of SAR are reviewed and critically
considered. RESULTS: FFNS consistently and significantly improved the nasal and
ocular symptoms of SAR in patients sensitised to several different seasonal
allergens (grass, ragweed and mountain cedar pollen) in all trials. An integrated
analysis of the results also confirmed improvements in both nasal and ocular
symptom scores in previously under-represented adolescent patients treated with
FFNS. CONCLUSION: FFNS is the first INS to show consistent nasal and ocular
efficacy across all SAR trials.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18803457 [PubMed - indexed for MEDLINE]

27: Appl Environ Microbiol. 2008 Nov;74(21):6814-7. Epub 2008 Sep 12.

Distribution of different species of the Bacteroides fragilis group in
individuals with Japanese cedar pollinosis.

Odamaki T, Xiao JZ, Sakamoto M, Kondo S, Yaeshima T, Iwatsuki K, Togashi H,
Enomoto T, Benno Y.

Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama,
Kanagawa 228-8583, Japan. t-odamak@morinagamilk.co.jp

We investigated associations of species of the Bacteroides fragilis group with
Japanese cedar pollinosis (JCPsis). Cell numbers of Bacteroides fragilis and
Bacteroides intestinalis were significantly higher in JCPsis subjects than in
non-JCPsis subjects before the pollen season. They correlated positively with
both symptom scores and JCPsis-specific immunoglobulin E levels.

PMID: 18791010 [PubMed - indexed for MEDLINE]

28: Clin Immunol. 2008 Nov;129(2):365-71. Epub 2008 Sep 11.

Role of the coagulation system in allergic inflammation in the upper airways.

Shimizu S, Shimizu T, Morser J, Kobayashi T, Yamaguchi A, Qin L, Toda M,
D'Alessandro-Gabazza C, Maruyama T, Takagi T, Yano Y, Sumida Y, Hayashi T, Takei 
Y, Taguchi O, Suzuki K, Gabazza EC.

Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu,
Shiga, Japan.

Thrombin has been detected and demonstrated to play a role in the airways of
patients with bronchial asthma, but its role in the upper airways including
during allergic rhinitis is unknown. This study was conducted to explore whether 
thrombin is presence in the upper airways and, if so, whether it affects mucin
secretion. Fifteen patients with allergic rhinitis were enrolled in the clinical 
study; primary nasal septum epithelial cells and normal bronchial epithelial
cells were used for in vitro evaluation, and rats as animal models. Significant
concentrations of thrombin were found in nasal secretion after allergic
provocation in allergic patients, and thrombin and its agonistic receptor peptide
induced significant secretion of mucin in primary nasal cells and normal
bronchial epithelial cells as compared to non-stimulated cells. Increased
mucosubstance secretion in septum epithelial cells was also induced after nasal
instillation of thrombin in rats. Further, the anticoagulant, activated protein
C, significantly inhibited thrombin-induced mucin secretion from septum
epithelial cells in rats. The results of this study suggest that activation of
the coagulation system occurs during the allergic response and that thrombin
plays a crucial role in the regulation of mucin production in the upper airways.

PMID: 18789772 [PubMed - indexed for MEDLINE]

29: Allergy. 2008 Oct;63(10):1352-8.

Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in
absence of systemic response.

Rondón C, Doña I, López S, Campo P, Romero JJ, Torres MJ, Mayorga C, Blanca M.

Allergy Service Carlos Haya Hospital, Malaga, Spain.

BACKGROUND: Patients with idiopathic rhinitis (IR) are considered to be
nonallergic because they have a negative skin prick test (SPT) and allergen
specific-IgE in serum. The concept of localized mucosal allergy in the absence of
atopy has recently been proposed. The immunological mechanisms involved in
seasonal IR have not been sufficiently studied. We examined nasal mucosa
inflammation, the presence of nasal specific-IgE and the response to nasal
allergen provocation test (NAPT) in patients with seasonal IR who presented
symptoms only in spring. METHODS: We evaluated 32 patients with seasonal IR and
35 with persistent allergic rhinitis to pollen (PAR-P) and compared these with
healthy controls and persons with PAR to house dust mite during the pollen
season, as well as by NAPT out-of-season with grass and Olea europea. We measured
the nasal leukocyte-lymphocyte phenotype (CD45, CD33, CD16, CD3, CD4 and CD8),
eosinophil-cationic-protein, and total and specific-IgE to grass and olive pollen
in serum and nasal lavage and performed NAPT. RESULTS: In the IR group, 62.5% had
a positive NAPT (IR-PosNAPT), 20/32 to grass, with four of these having a
positive NAPT to olive pollen as well. IR-PosNAPT patients showed a similar nasal
leukocyte-lymphocyte profile to the PAR-P patients and different to controls. We 
detected nasal specific-IgE in 35% of IR-PosNAPT patients. CONCLUSIONS: These
results support the hypothesis that a subgroup of patients with IR have seasonal 
symptoms with evidence of a nasal allergic immune reaction in the absence of a
positive SPT or serum specific IgE.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18782115 [PubMed - indexed for MEDLINE]

30: Allergy. 2008 Oct;63(10):1345-51.

Indices of lower airway inflammation in children monosensitized to house dust
mite after nasal allergen challenge.

Inal A, Kendirli SG, Yilmaz M, Altintas DU, Karakoc GB, Erdogan S.

Division of Pediatric Allergy and Immunology, Faculty of Medicine, University of 
Cukurova, Adana, Turkey.

BACKGROUND: There are few available data assessing the united airway disease and 
its systemic aspects in children. With this study, we aimed to investigate the
inflammation markers of upper and lower airways before and after nasal allergen
challenge in mite sensitive children with different clinical expression of the
allergic disease. METHODS: Four study groups were formed: rhinitis only, without 
bronchial hyper-responsiveness (R, n = 10), rhinitis with asthma (R + A, n = 22),
atopic asymptomatics (AA, n = 8) and nonallergic healthy controls (C, n = 10).
Blood eosinophils, nasal and sputum eosinophils, sputum eosinophil cationic
protein (ECP) and cys-LTs, and serum ECP levels were measured before and 24 h
after nasal allergen challenge. RESULTS: The groups were comparable in terms of
age and gender. Cumulative symptom scores recorded during and 1 h after nasal
challenge were not significantly different between patients with R, R + A and AA 
groups. At T(24), the children belonging to R, R + A and AA showed significant
increases in nasal eosinophils (P < 0.01, P < 0.001, and P = 0.01, respectively),
sputum eosinophils (P = 0.01, P < 0.001, and P < 0.05, respectively) and blood
eosinophils (P < 0.01, P < 0.001, and P < 0.05, respectively). Similarly,
increases in sputum ECP (P < 0.01, P < 0.001, and P = 0.07, respectively) and
sputum cys-LT levels (P = 0.07, P < 0.001, and P < 0.05, respectively) were
detected in children belonging to these three groups at T(24). Sputum eosinophils
significantly correlated with blood eosinophils (r = 0.54, P < 0.001) and sputum 
ECP (r = 0.58, P < 0.001) at T(24). CONCLUSIONS: This study showed that nasal
allergen challenge increased markers of eosinophilic inflammation in both upper
and lower airways of children monosensitized to mites, even before the onset of
clinical symptoms.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18782114 [PubMed - indexed for MEDLINE]

31: Allergy. 2008 Oct;63(10):1339-44.

Specific IgE serum concentration is associated with symptom severity in children 
with seasonal allergic rhinitis.

Rolinck-Werninghaus C, Keil T, Kopp M, Zielen S, Schauer U, von Berg A, Wahn U,
Hamelmann E; Omalizumab Rhinitis Study Group.

Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, 
Germany.

BACKGROUND: The impact of allergen-specific and total IgE serum levels before and
during the pollen season on symptom severity as well as efficacy of treatment
with anti-IgE requires further delineation. METHODS: Birch and grass pollen
allergic patients aged 6-17 years with seasonal allergic rhinitis (SAR) were
analyzed for the association of IgE serum concentration with symptom severity and
rescue medication use (combination: symptom load, SL) during the grass pollen
season. Reference group A (n = 53) received placebo, while group B (n = 54)
received Omalizumab (anti-IgE) monotherapy before and during the grass pollen
season. RESULTS: Patients on placebo with high baseline specific grass pollen IgE
(>50 kU/l) had a significantly higher SL compared with those with low IgE levels 
(< or =50 kU/l): SL 1.28 vs 0.61, P = 0.015. This association was nonexistent in 
patients treated with anti-IgE. In contrast, baseline total IgE levels did not
correlate with SL in any group. Patients with anti-IgE treatment and high free
total IgE levels (>16.7 ng/ml) had a significantly higher SL compared with those 
with low free total IgE levels (< or =16.7 ng/ml): SL 0.63 vs 0.23, P = 0.031.
CONCLUSIONS: Baseline specific IgE, but not total IgE, is associated with symptom
severity during the pollen season in children with SAR. Likewise, the symptom
load in SAR patients with anti-IgE correlates with free total IgE levels.
Although further research in larger populations is needed to confirm our
findings, our data suggest that specific IgE can be used as a parameter for
patient selection for this kind of treatment.

PMID: 18782113 [PubMed - indexed for MEDLINE]

32: Allergy. 2008 Oct;63(10):1335-8.

Soluble HLA-G and HLA-A,-B,-C serum levels in patients with allergic rhinitis.

Ciprandi G, Colombo BM, Contini P, Cagnati P, Pistorio A, Puppo F, Murdaca G.

DIMI, University of Genoa, Genoa, Italy.

BACKGROUND: Allergic rhinitis (AR) is characterized by Th2-polarized immune
response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. So far,
however, no study investigated them in AR. OBJECTIVE: The aim of this study was
to evaluate sHLA-G and sHLA-A,-B,-C serum levels in AR patients with pollen
allergy and in a group of healthy controls. METHODS: Forty-nine AR patients were 
enrolled. A group of healthy nonallergic subjects was considered as control.
sHLA-G and sHLA-A,-B,-C serum levels were determined by immunoenzymatic method.
The study was conducted during the winter, such as outside the pollen season.
RESULTS: Allergic patients had significantly higher levels of both sHLA-G (P <
0.0001) and sHLA-A,-B,-C (P = 0.011) molecules than normal controls. Moreover,
there was a significant relationship between these two soluble molecules (r =
0.69) in allergic patients. CONCLUSION: The present study provides the first
evidence that both sHLA-G and sHLA-A,-B,-C serum levels are significantly
increased in AR patients with pollen allergy.

Publication Types: 
    Comparative Study

PMID: 18782112 [PubMed - indexed for MEDLINE]

33: Curr Clin Pharmacol. 2008 Sep;3(3):185-97.

Combination therapeutic approach for asthma and allergic rhinitis.

Chauhan B, Patel M, Padhc H, Nivsarkar M.

Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education
and Research Development (PERD) Centre, Ahmedabad - 380 054, Gujarat, India.

BACKGROUND: Asthma and allergic rhinitis are symptomatically as well as
pathophysiologically overlapping conditions and their prevalence is increasing at
an alarming rate. Despite significant progress in pathophysiology of asthma and
allergic rhinitis and availability of several therapies in recent years, a true
and complete cure for asthma and allergic rhinitis so far seems out of reach.
OBJECTIVE: To review clinical efficacy & tolerability, pharmacoeconomics, quality
of life, outcomes of several clinical trails based on combination therapy for
asthma and allergic rhinitis. METHODS: DATA SOURCES: Computer-assisted MEDLINE
searches for articles on phathophysiology, clinical trials on combination therapy
for asthma and allergic rhinitis, treatment guidelines. SELECTION: Published
articles and pertinent abstracts (1981--2006) on the topics identified above were
selected. RESULTS: The pathophysiology of asthma and allergic rhinitis is a
complex cascade of events and mono therapy with drugs, which inhibits synthesis
and release of a mediator or blocks the receptors of respective mediators, does
not result in complete relief in the symptoms. From several clinical trials it
can be concluded that combination therapy with two or more drugs may provide
additive or synergistic benefits in blocking pathophysiological endpoints and
also complement each other by blocking a broad spectrum of inflammatory processes
than that provided by either drug alone. CONCLUSION: From the available
scientific data from clinical trials it can be concluded that combination
therapeutic approach may be a viable option for the treatment of asthma and
allergic rhinitis.

Publication Types: 
    Review

PMID: 18781905 [PubMed - indexed for MEDLINE]

34: Iran J Allergy Asthma Immunol. 2008 Sep;7(3):163-7.

A single center study of clinical and paraclinical aspects in Iranian patients
with allergic rhinitis.

Mohammadi K, Gharagozlou M, Movahedi M.

Department of Immunology and Allergy, Children Hospital Medical Center, Tehran
University of Medical Sciences, Tehran, Iran.

Allergic rhinitis (AR) is a common form of allergic disorder in Iran and rest of 
the world. This study was conducted to investigate the symptoms and paraclinical 
aspects of this allergy among Iranian patients. A total of 206 patients (51.5%:
male), with one of the specific symptoms of AR, from March 2005 to March 2007
were enrolled in the study. A written questionnaire was completed for each
patient. Furthermore, paraclinical evaluations including CBC, serum total IgE,
spirometry and skin prick test (SPT) with common allergens were done for the
patients. The ages of our patients ranged from 2 to 62 years of age (mean age of 
18 - /+11.8 years). Mean age of onset of symptoms was 11.6 -/+ 9.9 years. In 82% 
of cases histories of other allergic diseases were seen in patients or their
family members. Rhinorrhea was the most common symptom in our patients (77.9%).
Frequencies of mild persistent, moderate - severe persistent, mild intermittent
and moderate -severe intermittent types of AR were 20.5%, 41%, 21% and 17.5%,
respectively. Frequencies of positive SPTs in all cases, patients with persistent
and intermittent allergic rhinitis were 86.7%, 88.2% and 84.1%, respectively. The
most common allergens in positive SPTs, were trees, weeds, grasses and
Dermatophagoides pteronysinus. About 55.5 % of patients showed elevated total IgE
levels (> or = 100 IU/ML). Abnormal spirometry results were seen in 33.5% of
cases. The present study showed that among paraclinical investigations for AR,
positive SPTs with aeroallergens, are more consistent with clinical findings.
Regarding high ferequency of abnormal spirometry, we recommend that clinical
suspicion about hyperreactive airway disease in AR patients is mandatory and
performing spirometry for these cases is necessary whenever possible.

PMID: 18780951 [PubMed - indexed for MEDLINE]

35: J R Soc Med. 2008 Sep;101(9):466-72.

Trends in the epidemiology and prescribing of medication for allergic rhinitis in
England.

Ghouri N, Hippisley-Cox J, Newton J, Sheikh A.

Ayr Hospital, UK.

OBJECTIVE: To investigate recent trends in the recorded incidence, lifetime
prevalence and prescribing of symptom relief medication for allergic rhinitis in 
England. DESIGN: Analysis of primary healthcare datasets. SETTING: The UK
prevalence of allergic rhinitis has increased very significantly over recent
decades. Analysis of primary healthcare datasets offers the possibility to
advance understanding about the changing epidemiology and management of allergic 
rhinitis. QRESEARCH is one of the world's largest national aggregated health
databases containing the records of over nine million patients. We extracted data
on all patients with a recorded diagnosis of allergic rhinitis and calculated
annual age-sex standardized incidence and lifetime period prevalence rates for
each year from 2001-2005. We also analysed prescribing trends for antihistamines 
and drugs used in nasal allergy in those with a recorded diagnosis of allergic
rhinitis. MAIN OUTCOME MEASURES: Age-sex standardized incidence, lifetime
prevalence rates and prescribing trends for symptom relief medication for
allergic rhinitis in England. RESULTS: The age-sex standardized incidence of
allergic rhinitis was 5.57 per 1000 person-years in 2001 and increased by 33.0%
to 7.41 per 1000 person-years in 2005 (P<0.001). Lifetime age-sex standardized
prevalence of a recorded diagnosis of allergic rhinitis increased by 43.2% from
46.35 per 1000 in 2001 to 66.37 per 1000 in 2005 (P<0.001). Over this period a
41.7% overall increase in prescriptions for antihistamines and drugs used in
nasal allergy was observed (antihistamines 45.5%, drugs used in nasal allergies
35.5%). CONCLUSIONS: Recorded incidence and lifetime prevalence of allergic
rhinitis have increased substantially in recent years. A similar increase in
prescriptions for antihistamines and drugs used in nasal allergy in patients with
allergic rhinitis is also observed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18779249 [PubMed - indexed for MEDLINE]

36: Clin Exp Allergy. 2009 Jan;39(1):138-46. Epub 2008 Sep 4.

Important roles of tachykinins in the development of allergic nasal
hyperresponsiveness in guinea-pigs.

Nabe T, Tsuzuike N, Ohtani Y, Mizutani N, Watanabe S, Fujii M, Yoshimura M,
Nagasawa M, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, Kyoto, Japan.
nabe@mb.kyoto-phu.ac.jp

BACKGROUND: Although it has been suggested that the use of tachykinin receptor
antagonists might prove to be an effective treatment for allergic rhinitis (AR), 
they are not used clinically. Therefore, we decided to examine the effects of
tachykinin receptor antagonists on AR symptoms in an appropriate experimental
model. OBJECTIVE: To evaluate newly developed tachykinin receptor antagonists in 
a Japanese cedar pollen-induced AR model and to determine their effect on
allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR).
METHODS: Sensitized guinea-pigs were challenged by forced inhalation of pollen
once every week. Sneezing and nasal blockage were observed after pollen
challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4)
was assessed 2 days after an antigen challenge. We also evaluated whether
intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor
antagonists were administered before an intranasal treatment with antigen or
tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were
measured by an enzyme immunoassay. RESULTS: Although an NK(1) and NK(2) receptor 
dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal
blockage, it did completely suppress the development of NHR. Experiments using
specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor
activation was preferentially involved in the development of hyperresponsiveness.
Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal
tissue were noted 20 min-1 h after the challenge. Intranasal instillation of
either SP or NKA-induced NHR, which was almost completely inhibited by NK(2)
receptor antagonists and partially inhibited by NK(1) receptor antagonists.
CONCLUSIONS: SP and NKA, which are released early after the challenge, mediate
the development of NHR by preferentially activating NK(2) receptors. Therefore,
NK(2) receptor antagonists might prove to be effective treatment of AR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18778270 [PubMed - indexed for MEDLINE]

37: Nurs Stand. 2008 Jul 30-Aug 5;22(47):22-3.

Hay fever tightens its grip.

Wallis L.

The nature of hay fever is changing, with the season lasting longer and people in
their middle years being affected for the first time.

PMID: 18777818 [PubMed - indexed for MEDLINE]

38: J Asthma. 2008 Sep;45(7):548-51.

Effect of azelastine nasal spray on histamine-and allergen-induced skin wheal
response in patients with allergic rhinitis.

Agarwal MK, Vijayan VK, Vermani M.

Department of Respiratory Allergy & Applied Immunology, Vallabhbhai Patel Chest
Institute, University of Delhi, Delhi, India. agarwalmahendra@rediffmail.com

Effect of azelastine nasal spray on histamine-and allergen-induced skin test
response in patients suffering with allergic rhinitis was evaluated. Baseline
cutaneous response to histamine and 18 common allergen extracts were recorded by 
skin prick tests on 10 patients. The patients were then advised to take
azelastine nasal spray (1 spray per nostril, twice daily; 0.28 mg/dose). This
pediatric dose is reported to be effective also in adults (age > or = 12 years)
with improved tolerability as compared with usually recommended adult dose of 2
sprays per nostril twice daily. Skin tests were repeated 2 and 6 hours after
single dose, as well as after 6 days of continuous treatment. We did not find any
significant difference in skin wheal response with single dose and 6 days'
treatment of azelastine nasal spray (p > 0.05). It is concluded that diagnostic
allergen skin tests may be performed on patients undergoing azelastine nasal
spray treatment (0.28 mg/dose, twice a day) during their symptomatic period.

Publication Types: 
    Clinical Trial

PMID: 18773324 [PubMed - indexed for MEDLINE]

39: Curr Opin Allergy Clin Immunol. 2008 Oct;8(5):450-6.

Intranasal corticosteroids and allergic rhinoconjunctivitis.

Origlieri C, Bielory L.

UMDNJ - New Jersey Medical School, Newark, New Jersey 07103, USA.

PURPOSE OF REVIEW: To describe recent insight into the efficacy of intranasal
corticosteroids in treating ocular signs and symptoms of allergic
rhinoconjunctivitis. RECENT FINDINGS: The efficacy of intranasal corticosteroids 
in treating allergic nasal symptoms is well established, and recent evidence
indicates that this class of medication may be effective at alleviating ocular
symptoms as well. The present review reveals that the method of scoring ocular
symptoms in a clinical trial may influence whether statistically significant
improvements are detected among patients using intranasal corticosteroids.
Improvement is more likely to be detected if symptoms are scored individually
rather than pooled into a single ocular symptom score. Furthermore, the practice 
of allowing rescue medications likewise may preclude the ability to detect
statistically significant differences in allergic eye symptoms between intranasal
corticosteroids and controls. SUMMARY: Recent data show a promising effect of
intranasal corticosteroids on ocular symptoms of allergic rhinoconjunctivitis.
Additional trials should be conducted that require individuals to score ocular
symptoms individually and forbid the use of rescue medications.

Publication Types: 
    Review

PMID: 18769200 [PubMed - indexed for MEDLINE]

40: Int J Biometeorol. 2008 Nov;52(8):841-7. Epub 2008 Aug 27.

Trends in prevalence of allergic rhinitis and correlation with pollen counts in
Switzerland.

Frei T, Gassner E.

Federal Office of Meteorology and Climatology, Krähbühlstrasse 58, 8044, Zurich, 
Switzerland. thomas.frei@meteoswiss.ch

In recent decades, a large number of epidemiological studies investigating the
change of prevalence of hay fever showed an increase in the occurrence of this
disease. However, other studies carried out in the 1990s yielded contradictory
results. Many environmental factors have been hypothesized to contribute to the
increasing hay fever rate, including both indoor and ambient air pollution,
reduced exposure to microbial stimulation and changes in diets. However, the
observed increase has not convincingly been explained by any of these factors and
there is limited evidence of changes in exposure to these risk factors over time.
Additionally, recent studies show that no further increase in asthma, hay fever
and atopic sensitisation in adolescents and adults has been observed during the
1990s and the beginning of the new century. As the pattern of pollen counts has
changed over the years, partly due to the global warming but also as a
consequence of a change in the use of land, the changing prevalence of hay fever 
might partly be driven by this different pollen exposure. Epidemiological data
for hay fever in Switzerland are available from 1926 until 2000 (with large gaps 
between 1926 and 1958 and 1958 to 1986) whereas pollen data are available from
1969 until the present. This allows an investigation as to whether these data are
correlated provided the same time spans are compared. It would also be feasible
to correlate the pollen data with meteorological data which, however, is not the 
subject of our investigation. Our study focuses on analyzing time series of
pollen counts and of pollen season lengths in order to identify their trends, and
to ascertain whether there is a relationship between these trends and the changes
in the hay fever prevalence. It is shown in this paper that the pollen exposure
has been decreasing in Basel since the beginning of the 1990s whereas the rate of
the hay fever prevalence in Switzerland remained approximately unchanged in this 
period but with a slight tendency to decrease. In Locarno, most of the pollen
species also show a decreasing trend, while in Zurich, the development is
somewhat different as the pollen counts of most of the pollen types have been
increasing. It is interesting, however, that some of the pollen counts of this
station (grass, stinging nettle, mugwort and ragweed) have been decreasing in the
period 1982--2007.

PMID: 18751737 [PubMed - indexed for MEDLINE]

41: Allergol Int. 2008 Sep;57(3):205-9.

Anti-IgE antibody therapy for Japanese cedar pollinosis: omalizumab update.

Okubo K, Nagakura T.

Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.
ent-kimi@nms.ac.jp

Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a
substantial problem in Japan. Omalizumab, a novel humanized monoclonal
anti-immunoglobulin E (IgE) antibody, has already been proven to reduce symptoms 
associated with SAR. To investigate the safety and efficacy of omalizumab in the 
treatment of patients with Japanese cedar pollen-induced SAR compared to placebo 
or anti-allergic drug, two randomized, double-blind studies were conducted in
Japan. Omalizumab (150, 225, 300, or 375 mg) or placebo was administered
subcutaneously every 2 or 4 weeks based on serum total IgE and body weight at
baseline. IPD was administered 300 mg per day through the season. Primary and all
secondary efficacy variable scores were significantly lower in the omalizumab
group than in the placebo group (P < .01) and IPD, Th2 cytokine inhibitor group
(P < .01). Omalizumab was effective and safe in the treatment of SAR induced by
Japanese cedar pollens. And the methods of increasing effects by combining
omalizumab with antibody-specific immunotherapy are being considered. These
strategy is more effective than immune-therapy alone.

Publication Types: 
    Review

PMID: 18724074 [PubMed - indexed for MEDLINE]

42: Allergy. 2008 Oct;63(10):1280-91. Epub 2008 Aug 21.

Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis.
Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials.

Penagos M, Compalati E, Tarantini F, Baena-Cagnani CE, Passalacqua G, Canonica
GW.

Allergy and Respiratory Diseases Clinic, Department of Internal Medicine,
Università degli studi di Genova, Genoa, Italy.

RATIONALE: Several randomized, double-blind, placebo-controlled clinical trials
have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the
treatment of allergic rhinitis (AR) thus allowing for a meta-analysis to
determine the overall treatment effect. METHODS: A comprehensive search of the
MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October,
2007 was carried out. Randomized, double-blind, placebo-controlled, clinical
trials evaluating the efficacy of MFNS in patients with AR compared to placebo
were included. Total nasal symptom scores (TNSS), individual nasal symptoms,
total non-nasal symptom scores (TNNSS) and nasal airflow were analysed as the
standardized mean difference (SMD). Meta-analysis was performed with the random
or the fixed effect models depending on heterogeneity, by using revman 5
software. DATA SYNTHESIS: Sixteen of the 113 identified articles met the
inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed:
1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was
associated with a significant reduction in TNSS (SMD -0.49, 95% CI: -0.60 to
-0.38; P < 0.00001; I(2) = 50.1%). A significant effect on SMD for nasal
stuffiness/congestion (-0.41; 95% CI: -0.56 to -0.27), rhinorrhoea (-0.44; 95%
CI: -0.66 to -0.21), sneezing (-0.40; 95% CI: -0.57 to -0.23) and nasal itching
(-0.39; 95% CI: -0.53 to -0.25) was also demonstrated. Mometasone furoate nasal
spray treated subjects also showed a significant reduction in TNNSS (-0.30; 95%
CI: -0.43 to -0.18). The proportion of patients with adverse events was similar
for MFNS and placebo (0.99; 95% CI: 0.81-1.20; P = 0.91). CONCLUSIONS: This
meta-analysis provides a level Ia evidence for the efficacy of MFSN in the
treatment of AR vs placebo. Adverse events frequency was similar in both groups.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 18721246 [PubMed - indexed for MEDLINE]

43: J Natl Med Assoc. 2008 Aug;100(8):903-5.

The inner ear in patients with nasal allergy.

Lasisi AO, Abdullahi M.

Department of Otorhinolaryngology, College of Medicine, University of Ibadan,
Ibadan, Nigeria. akeemlasisi@gmail.com

BACKGROUND: The endolymphatic sac has been proposed as a target organ responsible
for inner-ear symptom in allergic subjects. This is a report of inner-ear
symptoms in patients with nasal allergy. METHOD: Retrospective review of record
charts of patients with known nasal allergy presenting to the otorhinolaryngology
out-patient department of the University College Hospital, Ibadan in 5 years.
RESULT: Ear symptoms were found in 95/144 (66%) subjects with nasal allergy. This
comprises of 41 males and 44 females (M: F = 1:1). Of these, itching of the
external ear canal, hearing loss and tinnitus accounted for 63 (66%), 55 (58%)
and 39 (41%), respectively, while vertigo was found in 12 (13%). Peripheral
vestibular signs of imbalance were seen in 11/95. The audiological assessment of 
73 subjects revealed normal pure-tone average in 43 (59%), and sensorineural
hearing loss (SHL) in 17 (23.3%). The severity of SHL was mild in 6/17, moderate 
in 7 and moderate-to-severe in 4. The erythrocyte sedimentation rate (ESR) and
C-reactive protein (CRP) were elevated in 10/15 (67%) and 6/15 (40%), while the
skin sensitivity test showed reactions to dust in 32, cold in 25, cockroach in 7,
perfume in 11, vegetable oil in 1 and insecticide in 2. The clinical diagnoses
were idiopathic tinnitus in 25 (26.3%), Idiopathic SHL in 17 (18%), cochlear
hydrop in 6 (6%) and autoimmune inner-ear disease in 6 (6%). CONCLUSION: This
report suggests some peculiar predisposition to inner-ear pathology in patients
with nasal allergy. However a longitudinal assessment of cochleovestibular
features of nasal allergy subjects will help in its validation.

PMID: 18717140 [PubMed - indexed for MEDLINE]

44: Int Arch Allergy Immunol. 2009;148(1):18-22. Epub 2008 Aug 21.

Correlation of quality of life with clinical parameters and eosinophilic cation
protein levels in children with allergic rhinoconjunctivitis.

Yuksel H, Yilmaz O, Sogut A, Ertan P, Onur E.

Department of Pediatric Allergy and Pulmonology, Celal Bayar University, Manisa, 
Turkey. hyukselefe@hotmail.com

BACKGROUND: Systemic and mucosal roles of eosinophils in the pathogenesis of
allergic rhinoconjunctivitis (AR) are known. The aim of this study was to
investigate the relationship of clinical parameters and quality of life with
eosinophilic cationic protein (ECP) in grass pollen-sensitive children with
seasonal AR. METHODS: This study included 31 children with AR and 18 healthy
controls aged between 5 and 15 years. ECP levels in nasal lavage fluid and serum 
were measured. AR symptom scores were calculated and the pediatric
rhinoconjunctivitis quality of life questionnaire (PRQLQ) was filled in for all
patients. RESULTS: Mean serum and nasal ECP levels (ng/ml) were significantly
higher in the patient group (p < 0.05 for both). In the AR group, the mean
clinical symptom score was 7.3 +/- 2.2, while the total PRQLQ score, activity
limitation, symptoms and emotional function domains were 2.5 +/- 0.9, 3.0 +/-
1.1, 2.5 +/- 1.2 and 2.6 +/- 1.1, respectively. The total clinical symptom score 
and disease duration showed a significant correlation with the total PRQLQ score 
(p = 0.00 and 0.003, respectively). However, neither nasal lavage nor serum ECP
levels were significantly correlated with symptom score, duration of disease,
PRQLQ total score or domains (p > 0.05 for all). CONCLUSION: These results may
indicate the absence of a correlation between clinical status and quality of life
and levels of ECP in tissues with allergic inflammation. (c) 2008 S. Karger AG,
Basel.

PMID: 18716399 [PubMed - indexed for MEDLINE]

45: Food Chem Toxicol. 2008 Oct;46 Suppl 10:S35-40. Epub 2008 Jul 30.

Molecular profiles: a new tool to substantiate serum banks for evaluation of
potential allergenicity of GMO.

Barber D, Rodríguez R, Salcedo G.

Departamento de I+D, ALK-Abelló S.A., C/Miguel Fleta 19, E-28037 Madrid, Spain.
domingo.barber@alk-abello.com

Assessment of the allergenicity of GMOs involves performing a test with a panel
of sera obtained from allergic donors. However, there is no clear indication of
how to characterize the above-mentioned panel. The patient selection criteria
should take into account the geographical location of patients, the intensity and
nature of the environmental allergens in the area and the potential
cross-reactivity among allergenic molecules. Sera for serum banks, obtained from 
patients with demonstrated food allergy, should be subjected to a further
characterization by screening with a panel of relevant allergenic molecules. A
representative panel of these sera should be used in the allergenicity
assessment. Finally, the "in vitro" methodologies should have the adequate
specificity and sensitivity, and the integrity of the molecules tested should be 
guaranteed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18706962 [PubMed - indexed for MEDLINE]

46: Allergy Asthma Proc. 2008 Jul-Aug;29(4):380-5.

Pharmacokinetics, safety and tolerability of an oral suspension of fexofenadine
for children with allergic rhinitis.

Segall N, Grubbe RE, Levy AL, Maloney MJ, Nayak AS, Kittner B, Quesada JT.

Clinical Research Atlanta, Stockbridge, Georgia 30342, USA.
nsegall@clinicalresearchatlanta.com

Allergic rhinitis (AR) is a common chronic condition in children and may impact a
child's quality of life. Increasing treatment compliance may improve quality of
life. An oral suspension of fexofenadine hydrochloride (HCl) has been developed
to ease administration to children and may, therefore, improve treatment
compliance. The purpose of this study was to assess the pharmacokinetic behavior,
safety, and tolerability of a single dose of fexofenadine HCl oral suspension
administered to children aged 2-5 years with allergic rhinitis. Children (aged
2-5 years) with AR were recruited in a multicenter, open-label, single-dose
study. Fexofenadine HCl (30 mg) was administered as a 6-mg/mL suspension (5 mL). 
Plasma samples were collected up to 24 hours postdose. Adverse events (AEs);
electrocardiograms (ECGs); vital signs; and clinical laboratory tests for
hematology, blood chemistry, and urinalysis were analyzed to evaluate safety and 
tolerability. Fifty subjects completed the study. Mean maximum plasma
concentration of fexofenadine was 224 ng/mL, and mean area under the plasma
concentration curve was 898 ng . hour/mL. Treatment-emergent AEs were mild in
intensity and reported in a total of seven subjects. No trends or clinically
meaningful changes in mean ECG, vital sign, or clinical laboratory test data
occurred during the study. In children aged 2-5 years, the exposure after a 30-mg
dose of fexofenadine HCl suspension was similar to the exposures previously seen 
after a 30- and 60-mg dose of fexofenadine HCl in children aged 6-11 years and in
adults, respectively. The suspension was also well tolerated.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18702885 [PubMed - indexed for MEDLINE]

47: Allergy Asthma Proc. 2008 Jul-Aug;29(4):349-57.

Managing rhinitis: Strategies for improved patient outcomes.

Carr WW, Nelson MR, Hadley JA.

Allergy and Asthma Associates of Southern California, Mission Viejo, California
92691, USA. warnercarr@hotmail.com

Allergic rhinitis affects more than 40 million Americans, with estimated costs
reaching $5.3 billion annually. The global impact includes negative effects on
quality of life (QOL), sleep, diminished work productivity, and exacerbation of
comorbid conditions. An accurate diagnosis of allergic or nonallergic rhinitis is
needed before selecting optimal treatment, which can include antihistamines,
decongestants, intranasal corticosteroids, immunotherapy, and anticholinergics.
It is also important to understand that pharmacologic properties of these
different interventions may affect patient satisfaction, compliance, and overall 
clinical response. This article reviews currently available therapies for
allergic rhinitis with a focus on improving patient outcomes.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18702880 [PubMed - indexed for MEDLINE]

48: Eur Ann Allergy Clin Immunol. 2008 May;40(1):14-21.

Forecasting the onset of an allergic risk to poaceae in Nancy and Strasbourg
(France) with different methods.

Cassagne E, Caillaud D, Besancenot JP, Thibaudon M.

Climat et Santé, Centre d'Epidémiologie de Population, Faculté de Médecine,
Dijon, France.

Pollens of Poaceae are among the most allergenic pollen in Europe with pollen of 
birch. It is therefore useful to elaborate models to help pollen allergy
sufferers. The objective of this study was to construct forecast models that
could predict the first day characterized by a certain level of allergic risk
called here the Starting Date of the Allergic Risk (SDAR). Models result from
four forecast methods (three summing and one multiple regression analysis) used
in the literature. They were applied on Nancy and Strasbourg from 1988 to 2005
and were tested on 2006. Mean Absolute Error and Actual forecast ability test are
the parameters used to choose best models, assess and compare their accuracy. It 
was found, on the whole, that all the models presented a good forecast accuracy
which was equivalent. They were all reliable and were used in order to forecast
the SDAR in 2006 with contrasting results in forecasting precision.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18700330 [PubMed - indexed for MEDLINE]

49: Int Immunopharmacol. 2008 Dec 10;8(12):1622-5. Epub 2008 Aug 8.

Carry-over effect on IFN-gamma production induced by allergen-specific
immunotherapy.

Ciprandi G, Sormani MP, Filaci G, Fenoglio D.

Department of Internal Medicine-CEBR, University of Genoa, Genoa, Italy.
gio.cip@libero.it

BACKGROUND: Allergic rhinitis is characterized by Th2 polarization and defective 
IFN-gamma production. Specific immunotherapy determines an allergen-specific
clinical improvement. AIM OF THE STUDY: It was to evaluate whether a course of
pre-seasonal SLIT with pollen allergen extract might affect the in vitro
IFN-gamma production using Dermatophagoides farinae (Df) allergen as stimulus, in
patients presenting with rhinitis due to pollen allergy. METHODS: Thirty-nine AR 
patients with pollen allergy were included in the study. They assumed
pre-seasonal SLIT for 3 months. IFN-gamma-specific producing cells were assessed 
by cytokine ELISPOT before and 3 months after the SLIT course end. RESULTS: SLIT 
provided a significant increase of both pollen-induced and Df-induced IFN-gamma
production (p<0.001). CONCLUSIONS: The present study provides evidence that
though the defective IFN-gamma production is allergen-specific in allergic
subjects, the SLIT increasing effects on IFN-gamma may be non-specific.

PMID: 18691675 [PubMed - indexed for MEDLINE]

50: Allergy. 2008 Aug;63(8):1008-14.

Physician and patient survey of allergic rhinitis in France: perceptions on
prevalence, severity of symptoms, care management and specific immunotherapy.

Demoly P, Didier A, Mathelier-Fusade P, Drouet M, David M, Bonnelye G, Blic J,
Klossek JM.

Unité d'Exploration des Allergies, INSERM U657 Hôpital Arnaud de Villeneuve,
Montpellier, France.

BACKGROUND: Specific immunotherapy (SIT) is the only aetiological treatment used 
in allergic rhinitis (AR). A telephone survey of patients and physicians in
France was carried out to understand better the real and perceived advantages and
inconveniences of this therapeutic approach. METHODS: A cohort of 453 individuals
with AR was selected using the Score For Allergic Rhinitis questionnaire. The
survey evaluated the level of understanding of allergic rhinitis and its
management, including both pharmacotherapy and SIT. A parallel survey was
conducted with 400 general practitioners, allergists and nonallergist
specialists. RESULTS: Approximately 50% of patients had heard about SIT as a
therapeutic option. Of these, 56% had a positive view of SIT and 14% a negative
image. A majority of patients and physicians with a positive opinion associated
SIT with improved well-being and quality of life, while those with a negative
opinion considered it to be a long and inconvenient treatment, with uncertain
results. Over 50% of patients who had been offered SIT had accepted it and
approximately 60% of these were satisfied with it. The future availability of SIT
as sublingual tablets was perceived positively by both patients and physicians.
CONCLUSIONS: Many patients with AR are unaware of their pathology and few seek
help from health professionals. When patients take medication, they are generally
satisfied with their treatment, even if it is only symptomatic. Patients and
physicians see the notion of definitive recovery as the main benefit of SIT,
whereas the main disadvantage is the duration of treatment.

PMID: 18691304 [PubMed - indexed for MEDLINE]

51: Allergy. 2008 Aug;63(8):990-6.

Allergic rhinitis management pocket reference 2008.

Bousquet J, Reid J, van Weel C, Baena Cagnani C, Canonica GW, Demoly P, Denburg
J, Fokkens WJ, Grouse L, Mullol K, Ohta K, Schermer T, Valovirta E, Zhong N,
Zuberbier T.

Allergic Rhinitis and its Impact on Asthma, Service des Maladies Respiratoires,
Hôpital Arnaud de Villeneuve, 34295 Montpellier Cédex 5, France.

Allergic rhinitis is a major chronic respiratory disease because of its
prevalence, impacts on quality of life and work/school performance, economic
burden, and links with asthma. Family doctors (also known as 'primary care
physicians' or 'general practitioners') play a major role in the management of
allergic rhinitis as they make the diagnosis, start the treatment, give the
relevant information, and monitor most of the patients. Disease management that
follows evidence-based practice guidelines yields better patient results, but
such guidelines are often complicated and may recommend the use of resources not 
available in the family practice setting. A joint expert panel of the World
Organization of Family Doctors (Wonca), the International Primary Care Airways
Group (IPAG) and the International Primary Care Respiratory Group (IPCRG), offers
support to family doctors worldwide by distilling the globally accepted,
evidence-based recommendations from the Allergic Rhinitis and its Impact on
Asthma (ARIA) initiative into this brief reference guide. This guide provides
tools intended to supplement a thorough history taking and the clinician's
professional judgment in order to provide the best possible care for patients
with allergic rhinitis. A diagnostic Questionnaire specifically focuses the
physician's attention on key symptoms and markers of the disease. When
questionnaire responses suggest a diagnosis of allergic rhinitis, a Diagnosis
Guide and a simple flowchart then lead the clinician through a series of
investigations commonly available in primary care to support the diagnosis. In
addition, key aspects of differential diagnosis are illuminated. According to
ARIA, allergic rhinitis may be classified as Intermittent or Persistent, and as
Mild or Moderate/Severe. The classification of rhinitis determines the treatment 
necessary, as set out in an ARIA flowchart included in this guide. The guide also
includes information about the strength of evidence for efficacy of certain
rhinitis treatments, a brief discussion of pediatric aspects, and a glossary of
allergic rhinitis medications to assist the clinician in making medication
choices for each individual patient. Finally, many patients with allergic
rhinitis also have concomitant asthma, and this must be checked. The World
Organization of Family Doctors has been delegated by WHO as the group that will
be taking primary responsibility for education about chronic respiratory diseases
among primary care physicians globally. This document will be a major resource in
this educational program.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18691301 [PubMed - indexed for MEDLINE]

52: Allergy. 2008 Aug;63(8):981-9.

Primary care: the cornerstone of diagnosis of allergic rhinitis.

Ryan D, van Weel C, Bousquet J, Toskala E, Ahlstedt S, Palkonen S, van den
Nieuwenhof L, Zuberbier T, Wickman M, Fokkens W.

Woodbrook Medical Centre, Loughborough, and University of Aberdeen, UK.

Allergic rhinitis (AR) is a very common disease with over 600 million people (200
million of them with concomitant asthma) worldwide suffering from it. The
majority of patients who seek medical advice are seen in primary care. Although
there is a selection of guidelines focused on the management of AR, there is a
paucity of guidance on how best to identify patients who would most benefit from 
treatment. The aim of this paper was to review the best practice for primary care
with respect to the diagnosis of AR within that clinical environment.

Publication Types: 
    Review

PMID: 18691300 [PubMed - indexed for MEDLINE]

53: Drugs. 2008;68(12):1723-39.

Mometasone furoate: a review of its intranasal use in allergic rhinitis.

Baldwin CM, Scott LJ.

Wolters Kluwer Health | Adis, Auckland, New Zealand. demail@adis.co.nz

Mometasone furoate (Nasonex) is a high-potency intranasal corticosteroid
available for the treatment and/or prophylaxis of the nasal symptoms of seasonal 
allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). In the EU, it is
approved for use in patients aged > or =6 years and, in the US, it is approved as
a treatment in patients aged > or =2 years and as prophylaxis in those > or =12
years of age.Extensive experience in both clinical trials and the clinical
practice setting has firmly established the efficacy and good tolerability
profile of intranasal mometasone furoate in children and adults with PAR or SAR. 
Thus, intranasal mometasone furoate is a useful first-line option for the
treatment and prophylactic management of these conditions, including in children 
as young as 2 years of age in some countries and 6 years of age in others.

Publication Types: 
    Review

PMID: 18681494 [PubMed - indexed for MEDLINE]

54: Ann Allergy Asthma Immunol. 2008 Jul;101(1):82-9.

The effects of the nasal antihistamines olopatadine and azelastine in nasal
allergen provocation.

Pipkorn P, Costantini C, Reynolds C, Wall M, Drake M, Sanico A, Proud D, Togias
A.

Division of Allergy and Clinical Immunology, Department of Medicine, Johns
Hopkins University, Baltimore, Maryland, USA.

BACKGROUND: Olopatadine, an antihistamine used in allergic conjunctivitis, is
under development as a nasal preparation for the treatment of allergic rhinitis. 
OBJECTIVES: To evaluate the efficacy of olopatadine in suppressing symptoms and
biomarkers of the immediate reaction induced by nasal allergen provocation and to
compare olopatadine with azelastine in the same model. METHODS: The study was
approved by the Johns Hopkins University institutional review board, and all
subjects gave written consent. We studied 20 asymptomatic subjects with seasonal 
allergic rhinitis. The study had 2 randomized, double-blind, placebo-controlled, 
crossover phases that evaluated 2 concentrations of olopatadine, 0.1% and 0.2%.
In a third exploratory phase, olopatadine, 0.1%, was compared with topical
azelastine, 0.1%, in a patient-masked design. Efficacy variables were the
allergen-induced sneezes, other clinical symptoms, and the levels of histamine,
tryptase, albumin, lysozyme, and cysteinyl-leukotrienes (third study only) in
nasal lavage fluids. RESULTS: Both concentrations of olopatadine produced
significant inhibition of all nasal symptoms, compared with placebo. Olopatadine,
0.1%, inhibited lysozyme levels, but olopatadine, 0.2%, inhibited histamine,
albumin, and lysozyme. The effects of olopatadine, 0.1%, were comparable to those
of azelastine, 0.1%. CONCLUSIONS: Olopatadine, at 0.1% and 0.2% concentrations,
was effective in suppressing allergen-induced nasal symptoms. At 0.2%,
olopatadine provided evidence suggestive of inhibition of mast cell
degranulation.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18681089 [PubMed - indexed for MEDLINE]

55: J Med Assoc Thai. 2008;91 Suppl 1:S68-72.

Factors associated with allergic rhinitis in Priest Hospital.

Pratyapipat S, Sinsakolwat J, Tantanawat A.

Department of Ear, Nose and Throat, Priest Hospital, Bangkok, Thailand.

OBJECTIVE: To study the prevalence and factors associated with allergic rhinitis 
(AR) in the priest and novices who came for treatment in Priest Hospital MATERIAL
AND METHOD: The retrospective study of 110 priests with allergic rhinitis was
conducted between January 2006 to June 2007. Questionnaire about allergic
history, eosinophile count, prick and intradermal skin test were done. RESULTS:
Most of the priests with the first manifestation of allergic rhinitis were in the
age between 14 to 66 years with mean of 28.93 years. Specific factors related to 
allergic rhinitis were house dust (87.3%), animal dandruff (40.9%), pollen
(35.5%) and insects (20%). Allergens that had positive skin test were house dust 
mite (54.4%), dog dandruff (50%), house dust (48.2%), Bermuda grass (44.5%),
Sedge (42.7%), and Para grass (39.1%). Non-specific factors which induced
rhinitis symptoms were joss stick (56.8%) and smoke (51.8%). CONCLUSION: All of
the factors both the specific and non specific were associated with AR. Future
clinical management guidelines for AR must take into account from the results of 
this study. Such guidelines must promote relief from allergen exposure, emotional
burden and the negative impact on daily activities. Health education to the
priests to eradicate allergen from their living place and maintain strong
partnership with healthcare professionals for sustainable result.

PMID: 18672596 [PubMed - indexed for MEDLINE]

56: Pediatr Allergy Immunol. 2008 Aug;19 Suppl 19:60-70.

New visions in specific immunotherapy in children: an iPAC summary and future
trends.

Halken S, Lau S, Valovirta E.

HC Andersen Childrens Hospital, Odense University Hospital, Odense, Denmark.
susanne.halken@ouh.regionsyddanmark.dk

Specific immunotherapy is indicated for confirmed immunoglobulin E-mediated
airway diseases using standardized allergen products with documented clinical
efficacy and safety. For decades the subcutaneous route of administration (SCIT) 
has been the gold standard. Recently, the sublingual immunotherapy (SLIT) has
also been investigated in children. SCIT, especially with grass and birch pollens
but also house dust mites, is an effective treatment in children with allergic
rhinitis and asthma when a significant part of their symptoms are caused by these
allergens. A long-term effect up to 12 yr after discontinuation of SCIT with
timothy allergen has been shown. Efficacy and safety of SLIT in pollen allergic
rhinoconjunctivitis have been demonstrated in adults. The evidence in children is
a little less convincing, and more data is needed. The clinical relevance,
long-term results and the size of the effect, as well as the dose, the treatment 
regimen and duration has not been sufficiently elaborated. It is demonstrated
that SCIT has the potential for preventing the development of asthma in children 
with allergic rhinoconjunctivitis. Also one randomized study indicates a
preventive effect of SLIT in children on the development of asthma. At present,
there are no studies who clearly demonstrates either a long-term effect or a
preventive effect on the development of asthma of SLIT in children. The areas
with lack of evidence should be addressed in well performed prospective,
randomized long-term studies both with SCIT and SLIT. This review was initiated
by iPAC (international Pediatric Allergy and Asthma Consortium) and aims to
review current knowledge related to specific immunotherapy in childhood, and to
identify needs for future research in this field.

Publication Types: 
    Review

PMID: 18665964 [PubMed - indexed for MEDLINE]

57: Pediatr Allergy Immunol. 2008 Aug;19 Suppl 19:51-9.

New visions in respiratory allergy (asthma and allergic rhinitis): an iPAC
summary and future trends.

Papadopoulos NG, Borres M, Gern J, Nieto A.

Department of Allergy, 2nd Pediatric Clinic, University of Athens, Athens,
Greece. ngp@allergy.gr

In many aspects, respiratory allergies, i.e., allergic asthma and rhinitis,
represent the hallmarks of allergy. Epidemiologic data highlight their large
prevalence of most parts of the world, socioeconomic analysis reveal their large 
impact on global health and the large number of scientific publications in this
field regularly brings to light many new aspects of these diseases. However, the 
current understanding of respiratory allergies, in particular in children remains
scarce. How can we efficiently prevent respiratory allergies in allergy-prone
infants? How can we prevent the progression of the disease? What therapeutic
strategies could efficiently address efficient immunomodulation? the
international Pediatric Allergy and Asthma Consortium, addressed these issues by 
a thorough review of the literature providing a state-of-the-art current
knowledge in respiratory allergy, and identified a series of needs to be
addressed in future studies.

PMID: 18665963 [PubMed - indexed for MEDLINE]

58: Postgrad Med. 2008 Jul;120(2):101-10.

Allergic rhinitis in family practice: the role of levocetirizine in clinical
care.

Bukstein DA, Lapine TJ.

University of Wisconsin-Madison, School of Medicine and Public Health, Health
Sciences Learning Center, Madison, WI 53705, USA. don.bukstein@deancare.com

Allergic rhinitis is one of the most common presentations of allergic disorders
in the United States, affecting more than 20% of the population. Chronic rhinitis
affects patients' quality of life and exacerbates comorbid conditions. Its
widespread burden affects society by substantially decreasing worker and
scholastic productivity. Allergic rhinitis is typically managed with
pharmacotherapy to alleviate symptoms and control comorbid conditions, yet many
of these agents carry their own burden due to bothersome and sometimes severe
side effects that can compromise patient safety. A new generation of non- or
less-sedating antihistamines has recently emerged. These agents offer the promise
of enhanced efficacy and tolerability. Of these agents, levocetirizine is the
latest antihistamine introduced in the United States. It appears to be safe and
effective for the treatment of allergic rhinitis. In addition to covering the
above topics, this article reviews the value of levocetirizine for the treatment 
of allergic rhinitis based on its pharmacologic and pharmacokinetic profile, its 
efficacy compared with placebo and other new-generation antihistamines, and its
safety and tolerability.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18654075 [PubMed - indexed for MEDLINE]

59: Clin Exp Allergy. 2008 Oct;38(10):1659-67. Epub 2008 Jul 2.

Sublingual immunotherapy in youngsters: adherence in a randomized clinical trial.

Röder E, Berger MY, de Groot H, Gerth van Wijk R.

Section of Allergology, Department of Internal Medicine, Erasmus MC-University
Medical Center Rotterdam, The Netherlands.

BACKGROUND: Adherence is essential for effective treatment. Although several
trials on the efficacy of sublingual immunotherapy (SLIT) in youngsters have been
published, few contain data on medication intake. OBJECTIVE: We aimed to quantify
adherence both to study protocol and medication intake as well as to identify
factors that may influence adherence to SLIT in youngsters with
rhinoconjunctivitis. METHODS: Two hundred and four youngsters (6-18 years) with
hayfever participated in a randomized controlled trial and used grass pollen
extract or placebo for 2 years. The primary outcome of the trial was the mean
daily total rhinoconjunctivitis symptom score in the second grass pollen season. 
Participants having completed the follow-up were considered adherent to the study
protocol. Adherence to medication intake was assessed by weighing the study
medication. Participants who completed the follow-up and used > or = 80% of the
prescribed medication were considered adherent to medication intake. Patient-,
disease- and treatment-related factors were analysed. RESULTS: One hundred and
fifty-four youngsters completed the study. The main reason for discontinuation
was the inability to take medication according to schedule. Drop-outs were older,
had more difficulty following the medication instructions and their overall
evaluation of the treatment effect was lower. The number and reasons for drop-out
did not differ between treatment groups. In total, 77% of the participants was
adherent to medication intake. Self-reported adherence was 99%. Non-adherent
participants experienced more severe symptoms before the trial. Symptom scores
did not differ between adherent and non-adherent participants. In adherent as
well as non-adherent participants, no difference was found between verum and
placebo group with respect to symptom scores. CONCLUSION: Adherence to both study
protocol and medication intake was good. Drop-out was affected by age, evaluation
of the treatment effect and medication instructions. Non-adherence to medication 
intake was influenced by the severity of the disease before the trial. The
ineffectiveness of SLIT could not be explained by non-adherence.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18631346 [PubMed - indexed for MEDLINE]

60: Mo Med. 2008 May-Jun;105(3):230-4.

Allergic rhinitis in children.

Sanford T.

Department of Otolaryngology-Head and Neck Surgery at Saint Louis University
School of Medicine, USA. tsanfor2@slu.edu

Allergic rhinitis (AR) is common in children. The prevalence has been reported to
be 20-40% in the pediatric population worldwide. The cause and risk factors for
the development of AR are incompletely defined but involve both genetic and
environmental elements. Although allergic rhinitis is seldom a severe or life
threatening disease, it can have profound effects on daily living and development
of a child. AR has multiple comorbidities and is closely related to asthma and
atopic dermatitis. Often the child's parents will concentrate on comorbid
diseases only and will not mention or be concerned by symptoms of their child's
allergic rhinitis. Diagnosis of AR is made by a combination of history and
physical exam. The causative allergens are identified by allergy testing. Allergy
testing is done in vivo (skin testing) or in vitro (Rast testing). Treatment ofAR
can include allergen avoidance, pharmacotherapy and immunotherapy. All three
therapies are effective and safe in children.

PMID: 18630302 [PubMed - indexed for MEDLINE]

61: Nutr J. 2008 Jul 14;7:20.

Clinical and biochemical effects of a combination botanical product (ClearGuard) 
for allergy: a pilot randomized double-blind placebo-controlled trial.

Corren J, Lemay M, Lin Y, Rozga L, Randolph RK.

Allergy Research Foundation, Los Angeles, USA. jcorren@ucla.edu

BACKGROUND: Botanical products are frequently used for treatment of nasal
allergy. Three of these substances, Cinnamomum zeylanicum, Malpighia glabra, and 
Bidens pilosa, have been shown to have a number of anti-allergic properties
in-vitro. The current study was conducted to determine the effects of these
combined ingredients upon the nasal response to allergen challenge in patients
with seasonal allergic rhinitis. METHODS: Twenty subjects were randomized to
receive the combination botanical product, (CBP) 2 tablets three times a day,
loratadine, 10 mg once a day in the morning, or placebo, using a randomized,
double-blinded crossover design. Following 2 days of each treatment and during
the third day of treatment, subjects underwent a nasal allergen challenge (NAC), 
in which nasal symptoms were assessed after each challenge dose and every 2 hours
for 8 hours. Nasal lavage fluid was assessed for tryptase, prostaglandin D2, and 
leukotriene E4 concentrations and inflammatory cells. RESULTS: Loratadine
significantly reduced the total nasal symptom score during the NAC compared with 
placebo (P = 0.04) while the CBP did not. During the 8 hour period following NAC,
loratadine and the CBP both reduced NSS compared with placebo (P = 0.034 and P = 
0.029, respectively). Analysis of nasal lavage fluid demonstrated that the CBP
prevented the increase in prostaglandin D2 release following NAC, while neither
loratadine nor placebo had this effect. None of the treatments significantly
affected tryptase or leukotriene E4 release or inflammatory cell infiltration.
CONCLUSION: The CBP significantly reduced NSS during the 8 hours following NAC
and marginally inhibited the release of prostaglandin D2 into nasal lavage fluid,
suggesting potential clinical utility in patients with allergic rhinitis.

Publication Types: 
    Randomized Controlled Trial

PMID: 18625073 [PubMed - indexed for MEDLINE]

62: Int Arch Allergy Immunol. 2008;147(4):323-30. Epub 2008 Jul 12.

Intranasal mometasone furoate alleviates the ocular symptoms associated with
seasonal allergic rhinitis: results of a post hoc analysis.

Anolik R, Nathan RA, Schenkel E, Danzig MR, Gates D, Varghese S.

Allergy and Asthma Specialists, PC470 Sentry Parkway EastBlue Bell, PA 19422,
USA. ranolik@allergypc.com

BACKGROUND: Burdensome symptoms of allergic rhinitis (AR) include nasal and
ocular symptoms such as itching, tearing and redness. Intranasal corticosteroids 
are efficacious in the treatment of nasal symptoms of AR. OBJECTIVE: It was the
aim of this study to determine the efficacy of the intranasal corticosteroid
mometasone furoate nasal spray (MFNS) in relieving ocular symptoms associated
with seasonal AR (SAR). METHODS: Ocular symptom data were analyzed for subjects
>or=12 years of age, randomized to MFNS 200 mug q.d. (n = 176) or placebo (n =
177) in a placebo-controlled, double-blind clinical trial. Post hoc efficacy
analysis assessed the mean change from baseline in subject-reported total ocular 
symptom scores (TOSS) averaged over the treatment period. RESULTS: Mean baseline 
TOSS was 4.91 for the MFNS group and comparable (5.05) for the placebo group -
combined average for individual symptoms such as itching, tearing and redness
ranged from 0 (no symptoms) to 9 (all symptoms, severe). Mean change from
baseline in TOSS averaged over days 1-15 was -1.42 for the MFNS group and -0.94
for the placebo group (p = 0.02), for an observed treatment difference of 0.49
(statistical data rounded to 2 decimal positions). Improvement in individual
symptoms (eye itching, tearing and redness) contributed to this treatment effect;
the greatest improvement occurred with tearing, which decreased -0.52 from the
baseline score 1.59 in the MFNS group and -0.31 from 1.67 in those receiving
placebo (p < 0.01), for an observed treatment difference of 0.21. Treatment with 
MFNS was safe and well tolerated. CONCLUSION: MFNS is effective in reducing
ocular symptoms of SAR, in addition to its established efficacy in reducing nasal
symptoms of SAR. 2008 S. Karger AG, Basel.

Publication Types: 
    Clinical Trial, Phase III
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18622139 [PubMed - indexed for MEDLINE]

63: Immunopharmacol Immunotoxicol. 2008;30(3):529-42.

Prevalence of legume sensitization in patients with naso-bronchial allergy.

Misra A, Prasad R, Das M, Dwivedi PD.

Food Toxicology Division, Indian Institute of Toxicology Research, Lucknow, Uttar
Pradesh, India.

Prevalence of legume allergy and concomitant sensitization to different allergens
was evaluated in patients of asthma and/ or rhinitis. Skin prick test with 27
common food allergens and 61 aeroallergens in 76 subjects was performed. Out of
76 subjects, 41 perceived allergenic problems with different food items as
contributing factor. Only six patients showed prick test positivity compatible
with their anamnesis. However, 35 subjects showed sensitization to different food
items, out of which thirty were sensitive to legumes. The common foods in
decreasing order of allergenicity were chickpea, followed by green gram, egg
white, and bean fresh/red gram. Concomitant sensitization to different legume
crops was found in patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18618316 [PubMed - indexed for MEDLINE]

64: Biomed Res. 2008 Jun;29(3):119-23.

A new murine model of allergic rhinitis by repeated intranasal Cry j 1 challenge.

Tsunematsu M, Yamaji T, Kozutsumi D, Murakami R, Nagai H, Kino K.

Research and Development Center, Division of Research and Development, Meiji
Dairies Corporation, Kanagawa, Japan. masako_tsunematsu@meiji-milk.com

To evaluate the long-lasting effects of new therapeutic approaches to allergies, 
we established a new model of allergic rhinitis by repeated challenges with
intranasal Cry j 1, a common Japanese cedar (Cryptomeria japonica) pollen
allergen, in B10.S mice. We sensitized B10.S mice subcutaneously with Cry j
1/alum three times at 1-week intervals. Five weeks after the final sensitization,
we challenged the mice by instilling Cry j 1 intranasally for 5 consecutive days 
starting 1 day after intranasal histamine pretreatment (challenge-1). We
challenged the mice by instilling histamine and Cry j 1 intranasally again 12
weeks later (challenge-2). There were significantly more sneezes after
challenge-2 than challenge-1. Cry j 1-specific IgE levels in serum were
significantly increased in both challenge-1 and 2 after continuous nasal antigen 
challenge. Serum levels of anti-Cry j 1 IgE in challenge-2 was 2.3 times higher
than after challenge-1. Thus, we have established a new model of seasonal
allergic rhinitis in B10.S mice by repeated intranasal antigen challenge, and
this model may help elucidate mechanisms of allergic rhinitis and the development
of new drugs.

PMID: 18614844 [PubMed - indexed for MEDLINE]

65: J Asthma. 2008 Aug;45(6):485-7.

Seasonal changes in platelet activity in pollen-induced seasonal allergic
rhinitis and asthma.

Kasperska-Zajac A, Brzoza Z, Rogala B.

Clinical Department of Internal Diseases, Allergology and Clinical Immunology,
Medical University of Silesia, Katowice, Poland. kasperska@plusnet.pl

BACKGROUND: Previously we reported that patients sensitized to pollen-allergens
who had seasonal allergic rhinitis and seasonal asthma may show increased plasma 
levels of platelet activation markers during grass pollen season. OBJECTIVE: To
find out whether the pattern of platelet activity measured by plasma PF-4 level
in the same group of patients changed off-season compared with the pollen season 
as well as in comparison with healthy control subjects. METHODS: Off-pollen
season, plasma PF-4 level was determined by enzyme-linked immunosorbent assay
(ELISA) in 16 grass pollen allergic patients who had seasonal allergic rhinitis
and seasonal asthmatic symptoms (none of them had any history of allergic
diseases outside the season) and in 29 healthy nonatopic subjects. RESULTS:
Plasma PF-4 level in the patients off-pollen season was significantly lower as
compared with the season and did not differ significantly as compared to the
healthy subjects. CONCLUSIONS: This observation taken along with our previous
results indicates that patients with seasonal allergic rhinitis and asthma
symptoms may have an increased circulating platelet activation, yet this
phenomenon disappears in the asymptomatic period of the disease. This might
indicate that platelet activation within the systemic circulation is an important
factor in the development of seasonal allergic airway inflammation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18612901 [PubMed - indexed for MEDLINE]

66: Urol Nurs. 2008 Jun;28(3):227-8.

Conventional, complementary, and alternative options for seasonal allergies.

Moyad MA.

University of Michigan Medical Center, Department of Urology, Ann Arbor, MI, USA.

Conventional and alternative medicine advice abounds in the area of seasonal
allergies. The number and cost of choices can be daunting to any health care
professional or patient. A quick overview is needed for consumers to review
simplistic lifestyle changes and non-prescription options for this year's allergy
season. For example, increasing laundry water temperature and using dehumidifiers
are evidenced in the literature, while using air purifiers or filters has minimal
to no research. Non-prescription generic antihistamines and prescription steroid 
nasal sprays are perhaps under-utilized and should receive more attention.
Several dietary supplements, such as butterbur and vitamin C, have some
preliminary evidence, whereas most other products lack clinical evidence.

PMID: 18605519 [PubMed - indexed for MEDLINE]

67: J Biol Regul Homeost Agents. 2008 Apr-Jun;22(2):117-23.

Serum IL-4 as a marker of immunological response to sublingual immunotherapy.

Ciprandi G, De Amici M, Murdaca G, Colombo BM, Quaglini S, Marseglia G, Di
Gioacchino M.

Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino,
Genoa University, Genoa, Italy. gio.cip@libero.it

Allergic rhinitis (AR) is characterized by a Th2 polarized immune response.
Specific Immunotherapy modifies this bias restoring a physiologic Th1 profile.
Sublingual immunotherapy (SLIT) is widely prescribed, but there is no early,
simple marker of response. This study was undertaken in order to determine
whether serum IL-4 might be a possible marker of SLIT immunological response in
order to quickly and easily detect responder patients. Thirty-nine AR patients
with a pollen allergy assumed preseasonal SLIT for 3 months. VAS for symptoms and
medication efficacy were evaluated. Serum IL-4 was assessed before and 3 and 6
months after SLIT initiation. Eighty-two percent of patients (32/39) showed a
clinical response to SLIT. Serum IL-4 significantly decreased at 6 months
post-therapy in responders, whereas it increased in non-responders. In
conclusion, these results may be considered clinically relevant proof that SLIT
treatment induces a quick reduction in Th2 polarization. Serum IL-4 appears to be
an early marker of immunological response to SLIT.

Publication Types: 
    Clinical Trial

PMID: 18597704 [PubMed - indexed for MEDLINE]

68: Ann Allergy Asthma Immunol. 2008 Jun;100(6):608-11.

Efficacy of nasal Staphylococcus aureus eradication by topical nasal mupirocin in
patients with perennial allergic rhinitis.

Zeldin Y, Weiler Z, Cohen A, Kalinin M, Schlesinger M, Kidon M, Magen E.

Allergy & Clinical Immunology Unit, Barzilai Medical Center, Ben Gurion
University of the Negev, Ashkelon, Israel.

BACKGROUND: Staphylococcus aureus (SA) colonization is frequent in patients with 
perennial allergic rhinitis (PAR). Mupirocin has well-recognized
antistaphylococcal activity, and its nasal formulation is approved for the
eradication of SA nasal colonization. OBJECTIVE: To investigate the frequency of 
SA nasal carriage, its possible influence on AR severity, and nasal mupirocin's
role on AR clinical severity. METHODS: Sixty patients, aged 5 to 60 years, with
AR were included, and 55 healthy individuals served as a control group. Nasal
smear specimens were drawn from both nares. A skin prick test to inhalational
allergens and a score-graded clinical evaluation of AR were performed. Carriers
of SA were treated with topical nasal mupirocin. RESULTS: The SA carrier (SAC)
state was found in 23 (38%) of the patients with AR and in 8 (15%) of the healthy
controls (P = .004). Comparing SACs with AR SA noncarriers, nasal symptom scores 
(SSs) tended to be higher in the SAC group (mean [SD], 11.09 [2.16] vs 8.86
[1.43]; P < .005). Treatment with topical nasal mupirocin diminished the SAC
state to 10% (P = .009) but did not change AR clinical severity, as assessed by
the SS. CONCLUSIONS: In patients with PAR, the SAC state is more prevalent
compared with the healthy population. Topical nasal mupirocin reduces the SAC
state but fails to clinically improve PAR, as assessed by the SS.

Publication Types: 
    Clinical Trial

PMID: 18592827 [PubMed - indexed for MEDLINE]

69: Ann Allergy Asthma Immunol. 2008 Jun;100(6):596-600.

Vine pollen allergy in areas with a high density of vineyards.

Brito FF, Gimeno PM, Bartolomé B, Alonso AM, Lara P, Fernández JA, Martínez A.

Allergy Section, General Hospital, Ciudad Real, Spain. feobrito@hotmail.com

BACKGROUND: In Castilla-La Mancha, Spain, the area with the highest density of
vineyards in the world, 2 cases of Vitis vinifera pollen allergy have been
previously reported. OBJECTIVE: To determine the clinical relevance and
biochemical characteristics of vine pollen in the Spanish province of Ciudad
Real. METHODS: We designed a prospective study of patients treated in the allergy
units from Puertollano and Ciudad Real for respiratory symptoms of 4 months'
duration in the year 2000. Skin prick tests with a standard aeroallergen battery 
and V vinifera pollen extract were performed on all patients. We also performed
conjunctival and bronchial provocation tests and serum specific IgE and sodium
dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting on the patients
who tested positive for V vinifera pollen. RESULTS: We included 200 patients, 98 
sensitized to any pollen and 9 to V vinifera pollen. We found 8 of 9 positive
conjunctival provocation test results and a positive bronchial provocation result
to vine pollen in a vine grower. Serum specific IgE against V vinifera pollen was
detected in 9 of 9 patients. Immunoblotting with V vinifera pollen extract showed
IgE-binding bands at 45 and 67 kDa. CONCLUSIONS: Vine pollen could be the cause
of pollinosis in exposed patients living in areas with a high density of
vineyards.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18592825 [PubMed - indexed for MEDLINE]

70: Am J Rhinol. 2008 May-Jun;22(3):246-52.

Diagnostic evaluation of inhalant allergies: a cost-effectiveness analysis.

Lewis AF, Franzese C, Stringer SP.

Department of Otolaryngology and Communicative Sciences, University of
Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi, USA.

BACKGROUND: The purpose of this study was to compare the cost-effectiveness of
modified quantitative testing (MQT), intradermal dilutional testing (IDT), and in
vitro allergy testing as diagnostic methods used in the management of patients
with suspected IgE-mediated inhalant allergies. METHODS: A systematic review was 
conducted to determine key statistics for analysis, such as prevalence of
disease, and sensitivity and specificity of each diagnostic modality. Costs were 
calculated based on charges from distribution companies to providers. A
deterministic cost-effectiveness analysis then was conducted using a decision
tree model to evaluate the various diagnostic strategies. After identifying
results at baseline, we performed a sensitivity and threshold analysis to assess 
the strength of recommendations. RESULTS: At an allergic rhinitis prevalence of
20%, MQT dominated IDT and in vitro testing, with 85 people correctly diagnosed
at a baseline total cost of $6630 for the 100 patients tested. Although in vitro 
testing had the highest effectiveness, it had an incremental cost-effectiveness
ratio of $3185. The results were sensitive to changes in the prevalence, costs,
and sensitivities and specificities of the different modalities. CONCLUSION: The 
prevalence of allergic rhinitis is high and rising according to many studies,
leading to a growing population of patients requiring allergy testing. Not only
does today's medical community want effective health interventions, but also
there is pressure to make health care cost efficient. This study looks at the
cost-effectiveness of various diagnostic allergy tests. In our model, we found
MQT to be the most cost-effective method of diagnosing allergic disease.

Publication Types: 
    Review

PMID: 18588756 [PubMed - indexed for MEDLINE]

71: Clin Immunol. 2008 Sep;128(3):358-65. Epub 2008 Jun 26.

Augmented Phl p 5-specific Th2 response after exposure of dendritic cells to
allergen in complex with specific IgE compared to IgG1 and IgG4.

Lundberg K, Lindstedt M, Larsson K, Dexlin L, Wingren C, Ohlin M, Greiff L,
Borrebaeck CA.

Department of Immunotechnology, Lund University, Lund, Sweden.

In this study we have elucidated the effects of allergen-specific antibodies on
human DCs and T-cells. Monocyte-derived DCs from allergic patients were exposed
to Phl p 5 alone or in complex with Phl p 5-specific human IgG1, IgG4 or IgE and 
further co-cultured with autologous memory CD4(+) T-cells. We demonstrate that
DCs treated with Phl p 5/IgE-complexes secrete higher levels of IL-1alpha, IL-6, 
VEGF and MCP-3 compared to Phl p 5 alone. Furthermore, we show that the ability
of DCs to present allergen to memory CD4(+) T-cells and induce a Th2 cytokine
profile is significantly augmented when the uptake is mediated by specific IgE
antibodies, whereas IgG1 and IgG4 have no such effect. The differences in
cytokine profiles depending on the antibody subtype could partly explain the
ability of allergic individuals to amplify allergen-specific immune response and 
could thus be involved in the etiology of allergic responses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18583195 [PubMed - indexed for MEDLINE]

72: Clin Exp Dermatol. 2008 Jul;33(4):383-9.

Food contact hypersensitivity syndrome: the mucosal contact urticaria paradigm.

Konstantinou GN, Grattan CE.

Dermatology Department, Norfolk and Norwich University Hospital, Norwich, UK.
georgenk@med.auth.gr

Oral allergy syndrome (OAS) or pollen-fruit allergy syndrome represents a mucosal
allergic contact urticaria in people sensitized to common pollens, due to IgE
cross-reactivity between homologous pollen allergens and various plant foods. It 
is the most prevalent food allergy, affecting millions of people with respiratory
allergies. Usually, symptoms are mild, self-limiting and localized to the
oropharyngeal mucosa, although they may sometimes become generalized and
life-threatening. Although patients usually recognize the offending foods,
diagnosis may sometimes be complicated. Several clinical syndromes and
association between pollens and plant-derived foods have been described.
Crossreactivity on the basis of stringent immunological and allergological
criteria can also occur in people without pollen sensitization or concomitant
respiratory allergies, as in latex-fruit syndrome. The term 'food contact
hypersensitivity syndrome' (FCHS) is proposed in this paper for the first time,
to include all mucosal hypersensitivity reactions presenting with contact to food
(both immunological and nonimmunological), whether due to crossreactivity with
homologous plant-derived allergens or not. At this time, prophylaxis and
treatment can only be attained by avoidance, even when symptoms are mild, with
consequent impairment in quality of life. A better understanding of the
pathophysiological mechanisms of FCHS and food allergy in general is essential
for deeper insights and future emergence of effective therapies.

Publication Types: 
    Review

PMID: 18582231 [PubMed - indexed for MEDLINE]

73: Ann Agric Environ Med. 2008 Jun;15(1):125-30.

Airborne ragweed (Ambrosia artemisiifolia L.) pollen content in the city of
Zagreb and implications on pollen allergy.

Peternel R, Music Milanovic S, Srnec L.

Polytechnic College Velika Gorica, Zagrebacka c. 5, HR-10 410 Velika Gorica,
Croatia. renata.peternel@vvg.hr

The increasing problem of sensitization to Ambrosia pollen in Europe has
stimulated studies on Ambrosia pollen occurrence and pollinosis in Croatia. The
aim of this study was to analyze the ragweed pollen pattern in Zagreb and to
determine the incidence of sensitization to this pollen types in patients with
seasonal respiratory allergy. The study was performed in the city of Zagreb
during the 2002-2005 seasons. Skin prick test were performed on a total of 750
patients aged 18-80 in Zagreb between 2 January - 31 December 2004. The mean
4-year rate of ragweed pollen in the Zagreb atmosphere was 14.8% of all plant
pollen. The highest rate of airborne ragweed pollen was recorded in August and
September. 365 patients were allergic to ragweed pollen; 20.3% of them
monosensitized; 10.9% allergic to Ambrosia and Artemisia pollen. Almost all study
patients suffered the most severe symptoms in August and September. The highest
proportion of allergic patients were recorded in the 31-50 age group and the
lowest proportion in the >50 age group. Forecasting of allergenic pollen season
in an area is a crucial pursuit for all developed countries, in order to minimize
clinical symptoms in patients suffering from respiratory allergy. This can be
achieved through public announcements by mass media (radio, television, internet,
etc.) aiming to protect allergic individuals.

PMID: 18581990 [PubMed - indexed for MEDLINE]

74: Rhinology. 2008 Jun;46(2):99-106.

The burden of allergic rhinitis as reported by UK patients compared with their
doctors.

Scadding GK, Williams A.

Royal National Throat, Nose and Ear Hospital, London, UK. g.scadding@ucl.ac.uk

This paper presents the results for the UK from a prospective, cross-sectional,
international survey to identify perceptions of symptoms and the impact of
disease in allergic rhinitis (AR). Data were recorded by 124 patients and matched
with data from their primary care physicians or specialists. According to the
physicians' assessments, a large proportion of patients presenting for routine
care had moderate or severe disease (56.5%), persistent disease (52.0%) and
comorbidities such as asthma (38.7%). Compared with the physicians' assessments, 
patients considered that their condition was more severe (p < 0.001). At the time
of the survey, 58.1% of patients reported suffering from nasal and ocular
symptoms, and these symptoms were moderate or severe in nature in 41.1% of
patients. Most patients (75.0%) reported some impact of the symptoms of AR on
daily activities, and health-related quality of life (HRQoL) was negatively
correlated with disease severity and the number of symptom-free days in the
previous 4 weeks. This survey highlights the unmet needs of many UK patients who 
suffer a high symptom burden and impaired health-related quality of life.
Overall, there was a poor correlation between patients and physicians in the
reporting of disease severity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18575009 [PubMed - indexed for MEDLINE]

75: Hum Immunol. 2008 Jul;69(7):409-13. Epub 2008 Jun 23.

Relationship between soluble HLA-G and HLA-A,-B,-C serum levels, and
interferon-gamma production after sublingual immunotherapy in patients with
allergic rhinitis.

Ciprandi G, Continia P, Fenoglio D, Sormani MP, Negrini S, Puppo F, Indiveri F.

Department of Internal Medicine, University of Genoa, Genoa, Italy.
gio.cip@libero.it

Allergic rhinitis (AR) is characterized by a T-helper (Th)-2 (Th2) polarized
immune response. Soluble human leukocyte antigen (sHLA) molecules play an
immunomodulatory role. Specific immunotherapy is the only causal treatment for AR
and is able to shift the immune response to Th1 polarization. The aim of this
study was to evaluate the relationship between sHLA-G and sHLA-A,-B,-C serum
levels and interferon-gamma (IFN-gamma) production in AR patients with pollen
allergy before and after a preseasonal course of sublingual immunotherapy (SLIT).
A total of 40 AR patients with pollen allergy were enrolled and given a course of
preseasonal SLIT for 3 months. Serum sHLA-G and sHLA-A,-B,-C levels were
determined by enzyme-linked immunoabsorbent assay, and cell production of
IFN-gamma was evaluated by enzyme-linked immunoabsorbent spot assay at baseline
and 3 months after the end of the SLIT course. There was a significant
relationship between sHLA-G serum level change and IFN-gamma increase as well as 
between sHLA-A,-B,-C level change and IFN-gamma increase after SLIT. The present 
study provides the first published evidence that the reduction of sHLA molecules 
serum levels and the increased IFN-gamma production after SLIT in AR patients
with pollen allergy are significantly related phenomena.

PMID: 18573288 [PubMed - indexed for MEDLINE]

76: Int Arch Allergy Immunol. 2008;146 Suppl 1:54-60. Epub 2008 May 27.

Blocking antibody is generated in allergic rhinitis patients during specific
immunotherapy using standardized Japanese cedar pollen extract.

Kawakami A, Koketsu R, Suzukawa M, Nagao M, Hiraguchi Y, Tokuda R, Fujisawa T,
Nagase H, Ohta K, Yamamoto K, Yamaguchi M.

Department of Allergy and Rheumatology, University of Tokyo Graduate School of
Medicine, Tokyo, Japan.

BACKGROUND: Japanese cedar pollen is by far the most important cause of allergic 
rhinitis in Japan. In this study, we assessed the induction of blocking antibody 
during specific immunotherapy (SIT) using a recently standardized allergen
extract from Japanese cedar pollen. METHODS: Basophils from nonallergic subjects 
were passively sensitized with serum samples prepared from pollinosis patients
before and after SIT; all patients showed good clinical efficacy. The cells were 
then stimulated with the standardized allergen, and histamine release was
measured. In most experiments, the basophil stimulation buffer contained 1%
serum. RESULTS: Pollinosis patients' sera obtained both before and after SIT
showed essentially similar sensitizing capacity for basophils. Basophil
degranulation in response to a relatively low concentration of pollen extract was
effectively suppressed by addition of post-SIT serum samples, indicating the
presence of blocking antibody. The blocking antibody was IgG, and its potency
varied widely among the donor patients. CONCLUSIONS: The standardized allergen
extract from Japanese cedar pollen is useful not only for clinical application in
SIT, but also for testing for induction of blocking antibody during SIT.
Copyright 2008 S. Karger AG, Basel.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18504408 [PubMed - indexed for MEDLINE]

77: Int Arch Allergy Immunol. 2008;146 Suppl 1:47-53. Epub 2008 May 27.

Allergen-induced basophil CD203c expression as a biomarker for rush immunotherapy
in patients with Japanese cedar pollinosis.

Nagao M, Hiraguchi Y, Hosoki K, Tokuda R, Usui T, Masuda S, Yamaguchi M, Fujisawa
T.

Institute for Clinical Research, Mie National Hospital, Mie, Japan.

BACKGROUND: Rush immunotherapy (RIT) can confer rapid clinical benefit on
patients with allergic rhinitis or asthma. However, biomarkers representing
mechanisms for the efficacy of RIT are still to be established. CD203c is a
basophil activation marker known to be upregulated by cross-linking of the
FcepsilonRIalpha receptor and may serve as a useful marker. OBJECTIVE: We sought 
to investigate the changes in allergen-induced CD203c expression in patients with
Japanese cedar pollen (JCP) pollinosis who received RIT. Methods: Nine patients
treated with RIT were enrolled in the study. Whole blood was incubated with
various concentrations of JCP extract. CD203c expression on basophils was
quantitated by means of flow cytometry. JCP-specific IgG4 levels in sera were
measured with ELISA. Basophil histamine release, CAP-RAST to JCP (JCP-IgE) and
total IgE were also examined. The biomarkers listed above were evaluated before
and sequentially after RIT. Symptom and quality of life scores were obtained
during pre- and posttreatment pollen seasons. RESULTS: All patients showed
significant improvement in symptom and quality of life scores after RIT. Serum
JCP-specific IgG4 titers were significantly elevated at 1 month and remained at
high levels 12 months after the treatment. Stimulation with JCP extract induced
enhancement of basophil CD203c expression in a concentration-dependent manner
except for 2 subjects in whom no increase in CD203c by an anti-IgE antibody was
observed (nonresponders). Significant reductions in the responses were observed
in 4 subjects after RIT (reduction in CD203c expression, RCE) whereas no changes 
were seen in 3 subjects (non-RCE). RCE subjects were older than non-RCE
counterparts, with mean ages of 20 and 12 years, respectively. No significant
changes in JCP-specific IgE and total IgE levels were seen before and after RIT. 
CONCLUSION: Allergen-induced CD203c expression in basophils may represent, at
least in part, the cellular mechanism for the therapeutic responses to RIT for
JCP pollinosis. However, further larger-scale studies to confirm the utility of
the test are necessary. Copyright 2008 S. Karger AG, Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18504407 [PubMed - indexed for MEDLINE]

78: J Allergy Clin Immunol. 2008 Aug;122(2):274-9. Epub 2008 Jun 20.

Birth by cesarean section, allergic rhinitis, and allergic sensitization among
children with a parental history of atopy.

Pistiner M, Gold DR, Abdulkerim H, Hoffman E, Celedón JC.

Division of Immunology, Children's Hospital Boston, Boston, Mass, USA.

BACKGROUND: Cesarean delivery can alter neonatal immune responses and increase
the risk of atopy. Studies of the relation between cesarean delivery and allergic
diseases in children not selected on the basis of a family history of atopy have 
yielded inconsistent findings. OBJECTIVE: We sought to examine the relation
between birth by cesarean delivery and atopy and allergic diseases in children at
risk for atopy. METHODS: We examined the relation between mode of delivery and
the development of atopy and allergic diseases among 432 children with a parental
history of atopy followed from birth to age 9 years. Asthma was defined as
physician-diagnosed asthma and wheeze in the previous year, and allergic rhinitis
was defined as physician-diagnosed allergic rhinitis and naso-ocular symptoms
apart from colds in the previous year. Atopy was considered present at school age
if there was 1 or more positive skin test response or specific IgE to common
allergens. Stepwise logistic regression was used to study the relation between
cesarean delivery and the outcomes of interest. RESULTS: After adjustment for
other covariates, children born by cesarean section had 2-fold higher odds of
atopy than those born by vaginal delivery (odds ratio, 2.1; 95% CI, 1.1-3.9). In 
multivariate analyses birth by cesarean section was significantly associated with
increased odds of allergic rhinitis (odds ratio, 1.8; 95% CI, 1.0-3.1) but not
with asthma. CONCLUSIONS: Our findings suggest that cesarean delivery is
associated with allergic rhinitis and atopy among children with a parental
history of asthma or allergies. This could be explained by lack of contact with
the maternal vaginal/fecal flora or reduced/absent labor during cesarean
delivery.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18571710 [PubMed - indexed for MEDLINE]

79: Acta Otolaryngol. 2008 Jun;128(6):666-9.

Nasal treatment with a microemulsion reduces allergen challenge-induced symptoms 
and signs of allergic rhinitis.

Andersson M, Greiff L, Wollmer P.

Department of Otorhinolaryngology, Head & Neck Surgery, Lund University Hospital,
Lund/Malm, Sweden. morgan.andersson@skane.se

CONCLUSIONS: Intranasal microemulsion treatment can attenuate allergen
challenge-induced nasal symptoms and plasma exudation in allergic rhinitis. We
hypothesize that the mechanism of action involves modification of the
allergen-mucosa interaction. The present observation suggests a novel principle
for prevention in allergic rhinitis. OBJECTIVE: To evaluate a specific
microemulsion as a treatment for allergic rhinitis in an acute allergen challenge
model. PATIENTS AND METHODS: Patients with allergic rhinitis were examined out of
the pollen season. Treatment with a single dose of a specific microemulsion was
given in a single-blind, placebo-controlled, and crossover design using a nasal
pool device. Nasal allergen challenges were carried out and symptoms of allergic 
rhinitis were scored. Furthermore, nasal lavages were performed and levels of the
plasma protein alpha 2-macroglobulin were measured as an index of exudative
inflammation. RESULTS: The allergen challenges produced significant increases in 
nasal symptoms (p=0.007) and in nasal lavage fluid levels of alpha
2-macroglobulin (p=0.008). The challenge-induced symptoms as well as the plasma
exudation were attenuated by treatment with the microemulsion (p=0.016 and 0.012,
respectively, compared with placebo).

Publication Types: 
    Randomized Controlled Trial

PMID: 18568502 [PubMed - indexed for MEDLINE]

80: J Nutr. 2008 Jul;138(7):1372-6.

Soy isoflavone intake is not associated with the development of cedar pollinosis 
in adults.

Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, Oba S, Shimizu H.

Department of Epidemiology and Preventive Medicine, Gifu University Graduate
School of Medicine, Gifu 501-1194, Japan. chisato@gifu-u.ac.jp

Although soy isoflavone has been suggested to have both immune-enhancing and
immune-suppressive effects, the effects of soy isoflavone intake on allergic
disorders are unclear. A cross-sectional study indicated that a high intake of
soy isoflavone is associated with a decreased risk of allergic rhinitis. We aimed
to prospectively examine the relationship between soy isoflavone intake and risk 
of cedar pollinosis, the most common seasonal allergic rhinitis in Japan. The
study was conducted in a population-based cohort of Japanese men and women. Each 
subject's usual diet, including soy isoflavone intake, was determined with the
use of a validated FFQ in 1992. In 2002, a total of 11,229 persons who were 35-69
y old and had no history of cancer or allergic diseases at the baseline responded
to a follow-up questionnaire asking about 4 symptoms related to cedar pollinosis.
Cox hazard regression model was used to determine the association between soy
isoflavone intake and the risk of cedar pollinosis. During the 10-y follow-up,
931 of these subjects reported that they had cedar pollinosis. There was no
significant association between soy isoflavone intake and risk of cedar
pollinosis in men and women after controlling for covariates. For the highest
compared with the lowest quartile of soy isoflavone intake, hazard ratios were
1.07 (95% CI: 0.81-1.42) in men and 0.89 (95% CI: 0.68-1.15) in women. These data
did not support an association between soy isoflavone intake and risk of cedar
pollinosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18567763 [PubMed - indexed for MEDLINE]

81: Allergol Int. 2008 Sep;57(3):265-75. Epub 2008 Jul 1.

A randomized double-blind comparative study of sublingual immunotherapy for cedar
pollinosis.

Okubo K, Gotoh M, Fujieda S, Okano M, Yoshida H, Morikawa H, Masuyama K, Okamoto 
Y, Kobayashi M.

Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.
ent-kimi@nms.ac.jp

BACKGROUND: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollen is 
a substantial problem in Japan. Sublingual immuno-therapy (SLIT) is safer than
conventional antigen-specific immunotherapy, the only treatment modality by which
complete cure of the disease can be expected. We investigated the safety and
efficacy of SLIT in the treatment of cedar pollinosis patients compared to
placebo. METHODS: A randomized, placebo-controlled, double-blind study was
conducted in 61 cedar pollinosis patients. Increasing doses of standardized
Japanese cedar extract or placebo were administered sublingually in intervals
ranging from daily to once a week after six weeks. The primary efficacy variable 
was the mean of the daily total symptom scores (TSS) during the pollen dispersing
period. Secondary efficacy variables included the QOL scores and related
variables. RESULTS: Primary efficacy variable scores were significantly lower for
some days in the SLIT group than in the placebo group (P < .01 or P < .05).
Secondary efficacy for the QOL score in SLIT group was almost of half of placebo 
group. There was no significant difference in the overall incidence of side
effects between the SLIT group and the placebo group. CONCLUSIONS: SLIT was
effective and safe in the treatment of cedar pollinosis.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18566549 [PubMed - indexed for MEDLINE]

82: Allergol Int. 2008 Sep;57(3):247-55. Epub 2008 Jul 1.

Therapeutic effect of montelukast, a cysteinyl leukotriene receptor 1 antagonist,
on Japanese patients with seasonal allergic rhinitis.

Okubo K, Baba K.

Department of Otorhinolaryngology, Nippon Medical School Hospital, Tokyo.
ent-kimi@nms.ac.jp

BACKGROUND: Secretion of nasal discharge was enhanced and airway-resistance in
the nasal cavity was augmented, resulting in nasal congestion, when leukotrienes 
were administered to the nasal mucosa. These results indicate that leukotrienes
play an important role in the pathogenesis of allergic rhinitis. METHODS: A
double-blind clinical study was carried out to evaluate the efficacy and the
safety of montelukast, a cysteinyl leukotriene receptor 1 antagonist, 5 mg, 10 mg
or placebo orally administered once daily at bedtime for 2 weeks, to Japanese
patients with seasonal allergic rhinitis. The composite nasal symptom scores
(average over the 2-week treatment period) were compared among the montelukast 5 
mg and 10 mg groups with the placebo group. RESULTS: The composite nasal symptom 
score significantly improved in the montelukast 5 mg and 10 mg groups compared
with the placebo group. The administration of montelukast 5 mg or 10 mg once
daily was well tolerated and the safety profiles were similar to those of the
placebo. There were no significant differences in the incidences of adverse
experience or drug-related adverse experience among the montelukast 5 mg, 10 mg
groups and the placebo group. CONCLUSIONS: Both montelukast 5 mg and 10 mg doses 
show clinically meaningful efficacy for the treatment of patients with seasonal
allergic rhinitis and the safety profiles of those are comparable to that of the 
placebo.

Publication Types: 
    Randomized Controlled Trial

PMID: 18566548 [PubMed - indexed for MEDLINE]

83: Ear Nose Throat J. 2008 Jun;87(6):340-53.

Onset of action of ciclesonide once daily in the treatment of seasonal allergic
rhinitis.

Patel P, Patel D, Kunjibettu S, Hall N, Wingertzahn MA.

Allied Research International, Mississauga, Ontario, Canada.
ppatel@allied-research.com

Ciclesonide is an intranasal corticosteroid approved for the treatment of
allergic rhinitis. We conducted a randomized, double-blind, parallel-group,
placebo-controlled study to evaluate the time to onset of action of ciclesonide
200 microg once daily in 502 adults with seasonal allergic rhinitis of at least 2
years' duration. To trigger immunologic priming, patients underwent between one
and five priming sessions with exposure to 3,500 grains/m(3) (+/-500) of ragweed 
pollen in an environmental exposure chamber. The criteria for a successful
priming session were a patient-assessed instantaneous total nasal symptom score
of at least 6 (of a possible 12) and a nasal congestion or rhinorrhea score of at
least 2 (of a possible 3) 90 minutes after allergen exposure during at least two 
consecutive priming sessions. Patients were then randomly assigned to receive
either a single dose of ciclesonide 200 microg (n = 251) or placebo (n = 251)
administered intranasally. The difference in the change from baseline total nasal
symptom scores in the two groups was assessed hourly for 12 hours after
administration. Onset of action was determined to have taken place the first time
that the effects of ciclesonide, as reflected in the total nasal symptom score,
were significantly greater than those of placebo at a particular hourly
assessment, provided that the subsequent hourly assessment also showed a
statistically significant difference. The onset of action of ciclesonide occurred
within 1 hour of administration (p = 0.01 vs. placebo), and the significant
difference in total nasal symptom scores between ciclesonide and placebo was
maintained through post-treatment hour 12 (p = 0.018).

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18561117 [PubMed - indexed for MEDLINE]

84: Curr Opin Allergy Clin Immunol. 2008 Jun;8(3):238-42.

How relevant is the impairment of smell for the quality of life in allergic
rhinitis?

Passàli GC, Ralli M, Galli J, Calò L, Paludetti G.

ENT Department, Catholic University of the Sacred Heart Medical School, Rome,
Italy. giulio.passali@rm.unicatt.it

PURPOSE OF REVIEW: In the present review, the authors try to evaluate how
relevant smell impairment is in patients suffering from allergic rhinitis and how
it affects their quality of life. Smell dysfunction has a significant impact on
the quality of life as it can lead to a wrong choice of food and intake, a
reduction in appetite and eventually to weight loss, malnutrition, immunity
reduction and worsening of medical illness. Patients with smell impairment are
reported to use larger quantities of sugar and salt to highlight flavours, thus
worsening their general health condition and increasing the risk of developing
diabetes and hypertension. RECENT FINDINGS: Recent studies estimate that a
complete loss of the sense of smell can be found in at least 1% of the US
population, and that an impairment in the olfactory function can be highlighted
in about 24% of individuals aged 53-97 years and 19% of individuals aged 20-92
years. Despite the high prevalence, subjective complaints do not accurately
reflect the real disturbance experienced by the patient, and usually go
unnoticed. SUMMARY: Current information in literature highlights the need for
additional studies that concentrate on the impact of olfactory dysfunction on the
quality of life of patients affected by allergic rhinitis.

Publication Types: 
    Review

PMID: 18560299 [PubMed - indexed for MEDLINE]

85: Biosci Biotechnol Biochem. 2008 Jun;72(6):1604-6. Epub 2008 Jun 7.

Impact of spermine on down-regulation of Th2 cytokines in peripheral blood
mononuclear cells from cedar pollinosis subjects in vitro.

Matsumoto M, Kimata H, Benno Y, Kamio S.

Dairy Science and Technology Institute, Kyodo Milk Industry Co., Ltd., Hinode,
Tokyo 190-0182, Japan. m-matumoto@meito.co.jp

The effects of spermine (SPM) on the production of Th1 and Th2 cytokines using
peripheral blood mononuclear cells (PBMCs) derived from cedar pollinosis subjects
were investigated. Th2 cytokines produced by PBMCs stimulated by 10 microM SPM
was significantly lower than that in the controls. These findings indicate that
blood SPM is an important factor in the Th1/Th2 balance.

PMID: 18540087 [PubMed - indexed for MEDLINE]

86: Drugs Today (Barc). 2008 Apr;44(4):251-60.

Fluticasone furoate nasal spray in allergic rhinitis.

Goyal N, Hochhaus G.

Department of Pharmaceutics, College of Pharmacy, University of Florida,
Gainesville, Florida 32610, USA. hochhaus@ufl.edu

Fluticasone furoate is a novel glucocorticoid developed for the treatment of
allergic rhinitis and other inflammatory diseases. Fluticasone furoate
demonstrates high systemic clearance, low oral bioavailability and low absolute
bioavailability after intranasal administration (<0.5%). The drug possesses a
high receptor affinity. Fluticasone furoate is given once daily at a dose of 110 
microg. Clinical studies tested the efficacy of fluticasone furoate in seasonal
allergic rhinitis and perennial allergic rhinitis. Patients randomized to the
drug experienced significant alleviation in their nasal and ocular symptoms as
well as clinically relevant improvement in quality of life. The drug is well
tolerated and has a good safety profile owing to reduced systemic exposure. Thus,
fluticasone furoate might represent a single treatment option for nasal and
ocular symptoms of allergic rhinitis. 2008 Prous Science, S.A.U. or its licensors

Publication Types: 
    Review

PMID: 18536783 [PubMed - indexed for MEDLINE]

87: Int Arch Allergy Immunol. 2008;147(2):117-24. Epub 2008 Jun 3.

Smoking and risk of cedar pollinosis in Japanese men and women.

Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, Oba S, Shimizu H.

Department of Epidemiology & Preventive Medicine, Gifu University Graduate School
of Medicine, Gifu, Japan. chisato@gifu-u.ac.jp

BACKGROUND: Pollinosis induced by the cedar pollen antigen is the most common
seasonal allergic reaction in Japan. We aimed to examine the relationship between
smoking and risk of cedar pollinosis in a population-based cohort of the
Japanese. METHODS: Study subjects were 12,221 men and women from the Takayama
Study cohort who were 35-69 years old at enrollment in 1992. A follow-up survey
in 2002 was used to obtain information about four symptoms related to cedar
pollinosis. RESULTS: A total of 1,000 subjects had cedar pollinosis during the
10-year follow-up. As compared with those who had never smoked, current smokers
at the baseline were at a significantly decreased risk of cedar pollinosis after 
controlling for covariates in men (hazard ratio [HR]: 0.64, 95% CI: 0.50-0.83) as
well as in women (HR: 0.64, 95% CI: 0.47-0.88). There was a significant
dose-response relationship between the risk of cedar pollinosis and the number of
cigarettes smoked each day as well as with the number of years an individual had 
smoked. A significant risk reduction was observed among men and women who had
continued to smoke cigarettes during the follow-up period in comparison with
those who had never smoked. There was no risk increase for former smokers at the 
baseline as well as for those who quit smoking during the follow-up. CONCLUSIONS:
Some components of tobacco may protect against cedar pollinosis. Our finding
could provide clues about therapeutic strategies for protection against cedar
pollinosis. (c) 2008 S. Karger AG, Basel.

PMID: 18520156 [PubMed - indexed for MEDLINE]

88: Expert Opin Pharmacother. 2008 Jun;9(9):1531-9.

Long-acting beta(2) agonists in asthma and allergic rhinitis.

Matera MG, Curradi G, Cazzola M.

2nd University of Naples, Department of Experimental Medicine, Naples, Italy.

BACKGROUND: Long-acting beta(2) agonists (LABAs) are effective second-line
bronchodilator controller agents in asthma, although they may also increase the
risk of hospitalization and asthma-related death in certain situations. Despite
the interesting findings obtained with short-acting beta(2) agonists (SABAs),
negative studies are available with LABAs in the treatment of allergic rhinitis. 
This is quite surprising given that there is now clear documentation of the link 
between asthma and allergic rhinitis. OBJECTIVE: The aim of this review is to
examine the role of beta(2) agonists in patients with asthma who also suffer from
allergic rhinitis and to try to explain the differences observed between SABAs
and LABAs in rhinitis. METHODS: SCOPUS, GOOGLE SCHOLAR and MEDLINE were searched 
for abstracts and papers; the search was completed in March 2008. No restriction 
was placed on language. CONCLUSION: The intriguing united airway concept led to
the hypothesis that common therapies may influence both and asthma and allergic
rhinitis. Consequently, better designed studies with LABAs in allergic rhinitis
are now mandatory. In particular, further studies are necessary to investigate
clinically relevant anti-inflammatory synergy between inhaled corticosteroids and
LABAs in upper airways. It will also be interesting to assess whether ultra-LABAs
(once-daily LABAs) are active in allergic rhinitis, although the information we
have seems to exclude a role for these agents.

Publication Types: 
    Review

PMID: 18518783 [PubMed - indexed for MEDLINE]

89: Ann Allergy Asthma Immunol. 2008 May;100(5):482-9.

Economic evaluation of sublingual vs subcutaneous allergen immunotherapy.

Pokladnikova J, Krcmova I, Vlcek J.

Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Charles
University in Prague, Hradec Kralove, Czech Republic.
jitka.pokladnikova@faf.cuni.cz

BACKGROUND: Sublingual allergen immunotherapy (SLIT) is a commonly used
alternative route of administration to standard subcutaneous immunotherapy (SCIT)
in Europe. Despite its wide use, the cost-effectiveness of SLIT vs SCIT has not
been well established. OBJECTIVE: To evaluate the cost and effectiveness of SLIT 
compared with SCIT in patients with allergic rhinoconjunctivitis during a 3-year 
specific allergen immunotherapy (SIT) from a third-party payer's, a patient's,
and society's perspectives. METHODS: We performed an open-label randomized
clinical trial of patients receiving SLIT (n = 19), patients receiving SCIT (n = 
23), and a control group (n = 22). The outcome measures were Rhinoconjunctivitis 
Quality of Life Questionnaire score, visual analog scale score, symptomatic
medication reduction, and direct and indirect costs. RESULTS: SLIT offered
clinical benefits to patients comparable to those provided by SCIT. From the
perspective of a third-party payer, the total average direct medical cost per
patient of 3-year SIT was estimated at Euro 416 vs Euro 482 in the SLIT and SCIT 
groups, respectively. A patient who received SLIT paid less than a patient who
received SCIT for all out-of-pocket costs (Euro176 for SLIT vs Euro 255 for SCIT)
but more for sole allergen extracts (Euro 72 for SLIT vs Euro 55 for SCIT). When 
both direct and indirect costs were considered, the 3-year SIT expenditures per
patient reached Euro 684 vs Euro 1,004 in the SLIT and SCIT groups, respectively.
CONCLUSIONS: SLIT represents a less expensive alternative relative to
subcutaneous administration from all perspectives. However, from a patient's
perspective, SCIT offers a less expensive alternative for patients who do not
experience loss of income and travel costs associated with treatment.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18517082 [PubMed - indexed for MEDLINE]

90: Ann Allergy Asthma Immunol. 2008 May;100(5):475-81.

Comment in:
    Ann Allergy Asthma Immunol. 2008 Oct;101(4):445; author reply 445-6.

Sublingual-oral administration of standardized allergenic extracts: phase 1
safety and dosing results.

Esch RE, Bush RK, Peden D, Lockey RF.

Research and Development, Greer Laboratories, Lenoir, North Carolina 28645, USA. 
esch@greerlabs.com

BACKGROUND: European studies provide a preponderance of evidence for sublingual
allergen immunotherapy (SLIT) safety and efficacy, but they use allergen products
that differ from those expected to be approved in the United States. OBJECTIVE:
To determine the safety and tolerability of 4 US-licensed standardized SLIT
allergenic extracts. METHODS: Adults 18 to 50 years old with allergic rhinitis
with or without asthma due to timothy grass pollen, short ragweed pollen, house
dust mite, or cat hair allergy completed a single-session dose escalation
followed by an 8-week, open-label daily course of SLIT. Participants documented
the presence and severity of adverse effects and adherence using a daily
electronic diary. RESULTS: Ninety-one participants initiated treatment, and 77
completed the phase 1 testing. Maximum tolerable doses ranged from 50 to 2,090
BAU for cat hair and dust mite extract, 31 to 91 Amb a 1 Units for short ragweed 
pollen extract, and 50 to 21,090 BAU for timothy grass pollen extract. During the
8-week treatment course, 98.9% of participants reported at least 1 mild, 70.4% at
least 1 moderate, and 13.6% at least 1 severe adverse effect. Most adverse
effects (94.6%) were rated as mild, 5.2% as moderate, and 0.1% as severe; nasal
and oral-mucosal adverse effects were most commonly reported. No life-threatening
adverse reactions occurred in more than 4,500 administered doses. CONCLUSIONS:
Daily sublingual-oral dosing of standardized allergenic extracts at maximum
tolerable doses was generally well tolerated. These results are a first step
toward establishing the safety of US-licensed SLIT extracts when appropriately
self-administered and monitored.

Publication Types: 
    Clinical Trial, Phase I
    Research Support, Non-U.S. Gov't

PMID: 18517081 [PubMed - indexed for MEDLINE]

91: Ann Allergy Asthma Immunol. 2008 May;100(5):463-8.

Association of polymorphisms of toll-like receptor 4 with a reduced prevalence of
hay fever and atopy.

Senthilselvan A, Rennie D, Chénard L, Burch LH, Babiuk L, Schwartz DA, Dosman JA.

Department of Public Health Sciences, School of Public Health, University of
Alberta, Edmonton, Alberta, Canada. sentil@ualberta.ca

BACKGROUND: The response to innate immune stimuli seems to be critical to
conditioning adaptive immunity. Early exposure to endotoxin initiates immune
responses that have been shown to alter the risk of asthma and allergic diseases.
The toll-like receptor 4 (TLR4) gene encodes the principal innate immunity
receptor in humans for bacterial endotoxin. Polymorphisms in the TLR4 gene may
regulate the effects of endotoxin exposure and could play a role in the
development of asthma and atopy-related phenotypes. OBJECTIVE: To investigate the
association between TLR4 polymorphisms and allergic phenotypes in nonsmokers.
METHODS: The data from 915 nonsmoking students were available for the study. The 
TLR4 299 and 399 polymorphisms were genotyped using mouthwash samples. The TLR4
299 and 399 polymorphisms were grouped together to define the TLR4 polymorphic
group. Skin prick tests were conducted in a subgroup of healthy participants. A
brief questionnaire was administered to determine demographic characteristics and
chronic health conditions. RESULTS: The prevalence of hay fever was 0% in the
TLR4 polymorphic group and 7.5% in the wild-type group (P = .01). After
controlling for age group and sex using logistic regression, the odds of having
hay fever were reduced by 88% (P = .009) in the TLR4 polymorphic group compared
with the wild-type group. In a subgroup analysis, the association between TLR4
polymorphisms and atopy was only observed among females. CONCLUSIONS: To our
knowledge, this study is the first to report an association between TLR4
polymorphisms and atopy-related phenotypes in a nonsmoking population. Further
investigation of the role of TLR4 polymorphisms in asthma and atopy-related
phenotypes is warranted.

Publication Types: 
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 18517079 [PubMed - indexed for MEDLINE]

92: Clin Exp Allergy. 2008 Aug;38(8):1290-301. Epub 2008 May 28.

Comment in:
    Clin Exp Allergy. 2008 Aug;38(8):1246-8.

A double-blind placebo-controlled birch allergy vaccination study II: correlation
between inhibition of IgE binding, histamine release and facilitated allergen
presentation.

Würtzen PA, Lund G, Lund K, Arvidsson M, Rak S, Ipsen H.

ALK-Abelló, Hørsholm, Denmark. paw@dk.alk-abello.com

BACKGROUND: The pathogenesis of IgE-mediated allergic disease is closely related 
to the production of T-helper type 2 (Th2) cytokines, which lead to IgE
production pivotal for activation of mast cells and basophils. Proliferating T
cells along with eosinophils expanded and attracted by Th2 cytokines are major
contributors to the late-phase reaction. The activation of these Th2 cells is
strongly enhanced by CD23-mediated IgE facilitated allergen presentation (FAP).
OBJECTIVE: The present study aims to investigate the effect of specific
immunotherapy (SIT)-induced allergen-specific non-IgE antibodies (blocking
antibodies) on IgE binding to allergen, histamine release (HR) and CD23-mediated 
allergen uptake in antigen-presenting cells. METHODS: Competition between IgE and
non-IgE for allergen binding was studied by Advia Centaur antibody measurements, 
passively sensitized basophils were used to study HR and IgE-facilitated binding 
of allergen to B cells (FAP) was studied by flow cytometry. FAP measurements were
performed both with and without the addition of a reference IgE serum, which was 
included to obtain optimal complex formation. The serum samples were obtained
from birch pollen immunotherapy (n=21) or placebo control patients (n=21) before 
and after 1 and 2 years of treatment. RESULTS: Statistically significant
reduction of all parameters investigated was observed after 1 year of treatment
and the effect was maintained during the second year of treatment. There was a
clear correlation between the two FAP measurements and between each of them and
the level of T cell activation reported upon previously. Moreover, strong
correlations were found between changes in FAP, IgE binding and HR. CONCLUSION:
The present study clearly demonstrates that SIT induces changes in the
composition of serum antibodies that inhibit IgE binding, HR and FAP to a similar
extent. This suggests that these measurements, individually or in combination,
may be used to monitor the immunological effect of SIT, even though direct
correlations to changes in clinical parameters could not be demonstrated.

Publication Types: 
    Randomized Controlled Trial

PMID: 18510696 [PubMed - indexed for MEDLINE]

93: Clin Exp Allergy. 2008 Aug;38(8):1282-9. Epub 2008 May 28.

Oral delivery of Lactobacillus casei Shirota modifies allergen-induced immune
responses in allergic rhinitis.

Ivory K, Chambers SJ, Pin C, Prieto E, Arqués JL, Nicoletti C.

Gastrointestinal Biology and Health Programme, Institute of Food Research,
Colney, Norwich, UK. kamal.ivory@bbsrc.ac.uk

BACKGROUND: Changes in the composition of the gut microbiota have been implicated
in the pathogenesis of allergic disorders, suggesting beneficial interactions
between the intestinal immune system and specific bacterial strains. Lactobacilli
are naturally present within the complex gastrointestinal microbiota of humans
and they are currently present in many probiotic supplements. OBJECTIVE: We
sought to investigate the role that Lactobacillus casei Shirota (LcS) may play in
modulating seasonal allergic rhinitis (SAR). METHODS: The study format was
double-blinded, placebo-controlled with 10 SAR sufferers in each group. We have
documented and compared changes in immune status arising through the daily
ingestion of a milk drink with or without live LcS, over a period of 5 months.
Pre-, peak- and post-grass pollen season blood samples were collected for
determination of plasma total IgE and grass pollen-specific IgG and IgE levels by
an enzyme immunoassay. At the same time, cytokine levels were determined by flow 
cytometric bead array technology following culture of peripheral blood
mononuclear cells for 6 days in the presence or absence of specific grass pollen 
antigens. RESULTS: Volunteers treated with LcS showed a significant reduction in 
levels of antigen-induced IL-5, IL-6 and IFN-gamma production compared with
volunteers supplemented with placebo. Meanwhile, levels of specific IgG increased
and IgE decreased in the probiotic group. CONCLUSION: Changes in antigen-induced 
production of cytokines were observed in patients treated with probiotics. These 
data show that probiotic supplementation modulates immune responses in allergic
rhinitis and may have the potential to alleviate the severity of symptoms.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18510694 [PubMed - indexed for MEDLINE]

94: Otolaryngol Head Neck Surg. 2008 Jun;138(6):725-9.

Relationship between rhinitis duration and worsening of nasal function.

Ciprandi G, Cirillo I, Pistorio A, La Grutta S.

Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino,
Genoa, Italy. gio.cip@libero.it

BACKGROUND: While it is well known that asthma is characterized by airway
remodeling, few studies instead have investigated this issue in patients with
allergic rhinitis (AR). OBJECTIVE: The aim of the study was to evaluate nasal
function, ie, nasal airflow, in a cohort of patients with persistent AR (PER).
METHODS: One hundred patients, 50 with short-term and 50 with long-term PER, were
prospectively and consecutively evaluated, clinically evaluated by visit, skin
prick test, and rhinomanometry. RESULTS: Nasal airflow values were significantly 
lower (median flow: 348 mL/sec) in patients with long-term rhinitis (median
duration nine years) as compared to patients with short-term (median duration one
year) rhinitis (median flow: 466 mL/sec) (P < 0.0001). CONCLUSION: This study
provides the first evidence that patients with PER may show a progressive
worsening of nasal airflow depending on the duration of the disorder.

PMID: 18503843 [PubMed - indexed for MEDLINE]

95: Curr Med Res Opin. 2008 Jun;24(6):1833-40. Epub 2008 May 21.

Fluticasone furoate versus placebo in symptoms of grass-pollen allergic rhinitis 
induced by exposure in the Vienna Challenge Chamber.

Zieglmayer P, Zieglmayer R, Bareille P, Rousell V, Salmon E, Horak F.

ENT University Clinic, Vienna, Austria. petra@zieglmayer.at

OBJECTIVE: The Vienna Challenge Chamber (VCC) offers a controlled and
controllable paradigm in which to reproducibly evaluate the efficacy of
anti-allergic treatment. The aim of this study was to assess the efficacy of the 
novel intranasal corticosteroid fluticasone furoate (FF) in the VCC. METHODS: The
single-centre, randomised, double-blind, placebo-controlled, two-period crossover
study was conducted in 59 adult males with grass pollen allergic rhinitis (AR).
Patients received either Fluticasone furoate 200 mcg once-daily, or placebo
intranasally for 8 days. AR symptoms were induced during 4-hour allergen
challenges with grass pollen in the VCC at the end of each 8-day treatment
period. A first challenge was conducted at 1-5 hours post-dose, followed by a
second challenge at 22-26 hours post-dose. The primary endpoint was total nasal
symptom score (TNSS; sum of itch, sneeze, rhinorrhoea, obstruction symptoms
assessed on a categorical scale of 0-3) weighted mean over 2-5 hours post-dose.
Secondary endpoints included: TNSS weighted mean over 23-26 hours post-dose and
global symptom score, eye symptom score, nasal secretions and nasal airflow
weighted means over 2-5 and 23-26 hours post-dose. RESULTS: Fluticasone furoate
showed consistent attenuation of AR symptoms in both the early and late
challenges. Compared with placebo, weighted mean of TNSS was reduced on average
by 4.14 point-scores at 2-5 hours post-dose and 3.63 point scores at 23-26 hours 
post-dose. These positive effects were also seen across all secondary endpoints. 
CONCLUSION: An 8-day treatment course of intranasal FF 200 mcg given once-daily
statistically significantly reduced symptoms of AR including associated eye
symptoms. Statistical significance was declared where the relevant two-sided 95% 
confidence interval did not contain zero. This positive effect was sustained over
24 hours suggesting that fluticasone furoate could be efficacious as a once daily
steroid.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18498678 [PubMed - indexed for MEDLINE]

96: Clin Exp Allergy. 2008 Jun;38(6):1033-7. Epub 2008 Apr 13.

Profilin sensitization detected in the office by skin prick test: a study of
prevalence and clinical relevance of profilin as a plant food allergen.

Asero R, Monsalve R, Barber D.

Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano (MI), Italy.
r.asero@libero.it

BACKGROUND: Profilin, a pan-allergen present in all eukaryotic cells, is one of
the main causes of cross-sensitization between pollen and plant-derived foods,
but its clinical relevance as a food allergen is still debated. OBJECTIVE: To
investigate the prevalence of profilin sensitization in a pollen-allergic
population and its clinical relevance as a food allergen. METHODS: Two hundred
consecutive patients with pollen allergy underwent skin prick tests (SPT) with
purified natural date palm profilin (Pho d 2; 50 microg/mL; Alk Abello, Madrid,
Spain). Those reporting adverse reactions to foods (confirmed by SPT with either 
commercial food extracts or fresh foods) underwent SPT with an apple extract
containing uniquely Mal d 1 (2 microg/mL; ALK-Abello), and with a commercial
peach extract containing uniquely lipid transfer protein (LTP 30 microg/mL;
ALK-Abello). RESULTS: Sixty patients (30%) showed skin reactivity to date palm
profilin, Pho d 2. All were sensitized to grass pollen, and most of them reacted 
to birch, mugwort, ragweed and plantain pollen as well. SPT with pellitory and
cypress scored negative in a high proportion of profilin reactors [26/60 (43%)
and 33/60 (55%), respectively]. More than one half (34/60 [57%]) of profilin
reactors had food allergy; 21 of these were monosensitized to profilin, 11 were
sensitized to both profilin and Bet v 1 homologous protein, one to both profilin 
and LTP, and one to all the three allergens. The large majority of
profilin-allergic patients reported oral allergy syndrome as the only
food-induced symptom and were able to tolerate the offending foods if they were
cooked or otherwise processed. Twenty-eight of 34 reported reactivity to two or
more plant-derived foods. Rosaceae, tree nuts, melon and watermelon, tomato,
pineapple, citrus fruits and banana were the more frequently offending foods.
CONCLUSION: Profilin should be considered a clinically relevant food allergen.
Allergy to melon, watermelon, tomato, banana, pineapple and orange may be
considered as a marker of profilin hypersensitivity. This study underlines the
clinical importance of being able to diagnose hypersensitivity to single food
allergenic proteins by SPT, particularly when the relevant food allergen sources 
contain several allergens that show different chemical/physical features and,
hence, completely different risk profiles.

PMID: 18489029 [PubMed - indexed for MEDLINE]

97: Clin Exp Allergy. 2008 Jun;38(6):1048-60. Epub 2008 Apr 13.

Allergenicity and cross-reactivity of Senecio pollen: identification of novel
allergens using the immunoproteomics approach.

Luengo O, Mollá R, Gámez C, Cardona V, López E, Sastre B, Waisel Y, Belmonte J,
Cadahia A, Lahoz C, del Pozo V.

Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron,
Universidad Autónoma de Barcelona, Barcelona, Spain.

BACKGROUND: The genus Senecio is the largest genus of the family Asteraceae
(Compositae). The allergenicity of Senecio has not been assessed previously.
OBJECTIVE: The aim of this study was to investigate the allergens of Senecio
jacobea pollen and to determine their immunological characteristics and clinical 
relevance. METHODS: Fifty patients with rhinoconjunctivitis and a positive skin
prick test (SPT) to Senecio were recruited. The clinical relevance of this pollen
was assessed by means of a nasal provocation test (NPT). Allergens were
characterized by one-dimensional electrophoresis (SDS-PAGE) and two-dimensional
gel electrophoresis and immunoblotting. Furthermore, characterization and
identification of the allergens were performed by mass spectrometry (MS). In
vitro inhibition tests were performed to evaluate cross-reactivity with other
pollen. RESULTS: Three predominant allergens, both in the intensity of reaction
and the frequency of recognition by human-allergic sera, were 59 (60%), 42 (50%) 
and 31 kDa (50%). The two-dimensional analysis allowed the identification of
several allergens. One spot around 42 kDa was identified as a protein homologous 
to pectate lyase and three other spots were homologous to malate dehydrogenase by
MS. S. jacobea proteins showed cross-reactivity with other proteins of the
Asteraceae family and also with Parietaria judaica. This was demonstrated by
immunoblotting and ELISA inhibition studies. CONCLUSION: S. jacobea constitute a 
newly discovered allergenic source. It shows cross-reactivity with other members 
of the Asteraceae plant family as well as with P. judaica.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18489028 [PubMed - indexed for MEDLINE]

98: Allergol Immunopathol (Madr). 2008 Mar-Apr;36(2):90-100.

Prevalence and associated factors of allergic rhinitis and atopic dermatitis in
children.

Torres-Borrego J, Molina-Terán AB, Montes-Mendoza C.

Pediatric Allergy and Pulmonology Unit, Department of Pediatrics, Reina Sofía
Children's Hospital, School of Medecine, Córdoba, Spain.
javier.torres.sspa@juntadeandalucia.es

Allergic disorders are the chronic diseases of greatest pediatric morbidity,
affecting over 25 % of the pediatric population. Indeed, this situation has been 
referred to as an "allergic epidemic". In comparison with asthma, atopic
dermatitis and allergic rhinitis have been less extensively investigated,
although this does not mean that they should be regarded as minor disorders but
rather as alterations that affect the quality of life of the patients and their
families, which generate considerable direct and indirect costs. Despite an
important research effort, the reason for this allergic epidemic is not well
known. These are multifactor disorders without a single causal agent, in which
the most important component is the genetic predisposition of the patient
(atopy), modulated by environmental factors, exposure to allergens, infections
and irritants, among others. A confounding element is the fact that the concept
of allergic diseases encompasses phenotypes of rhinitis, atopic dermatitis or
asthma in which no IgE-mediated atopic mechanism is demonstrated, and which can
manifest in a way similar to true allergic phenotypes. Differentiation between
the two is difficult to establish on the basis of self-administered
questionnaires alone, in the absence of a precise etiological diagnosis. The
present article reviews the numerous factors suggested to be responsible for the 
increase in allergic diseases recorded in the last few decades, and for the
differences in prevalence observed among centres. For most of these factors the
results published in the literature are contradictory, in some cases due to a
lack of control of the associated interacting or confounding factors. Consensus
exists for only some of these causal factors, such as the established parallelism
between the increase in allergic diseases and the reduction in infectious
processes on one hand, and the increase in particles generated by diesel fuel
combustion on the other. In addition, the implicated factors could act
differently (and in some cases even antagonically) upon atopy and on the
different disease phenotypes, thereby complicating the study of these
interactions even further.

Publication Types: 
    Review

PMID: 18479661 [PubMed - indexed for MEDLINE]

99: Allergol Immunopathol (Madr). 2008 Mar-Apr;36(2):79-84.

Parietaria sublingual allergoid immunotherapy with a co-seasonal treatment
schedule.

D'Anneo RW, Arena A, Gammeri E, Bruno ME, Falagiani P, Riva G, Leonardi S, La
Rosa M.

Respiratory Centre Disease, Papardo Hospital, Messina, Italy.

BACKGROUND: Sublingual immunotherapy (SLIT) with monomeric allergoid, given
according to the standard scheme, resulted effective and safe. However, the
achievement of a clinical benefit requires a long time. We thus performed this
study using an administration protocol starting in the co-seasonal period with a 
3-day build-up phase and lasting only 6 months, in order to obtain the above
benefit in a shorter time. METHODS AND RESULTS: The study, prospective,
randomised and controlled versus drug therapy, was conducted on 65 rhinitic
and/or asthmatic patients allergic to Parietaria with or without other
sensitisations. Twenty-four were allocated to 1,000 AU/week, 21 to 3,000 AU/week 
and 21 to drug therapy. They were treated from April to September 2006. At
baseline, 3 and 6 months a Visual Analogue Scale (VAS) was performed to assess
the patients' well-being. Drug consumption was evaluated by means of monthly
diary cards. Bronchial reactivity was investigated at baseline and 6 months by
methacholine challenge test. There was a greater VAS improvement in both the SLIT
groups than in the controls after 6 months (p<0.05). In patients taking 3,000
AU/week this was already evident after 3 months. There was a significant
reduction in rescue medication consumption between 3 and 6 months (p<0.05) in all
three groups. The bronchial reactivity was reduced only in the SLIT groups
(p<0.001). No adverse events were observed. CONCLUSIONS: At 6 months the
allergoid SLIT showed itself to be effective and safe. In addition the subjective
clinical benefit was obtained in a more rapid period, i.e. 3 instead of 6 months,
when a higher maintenance dose was administered.

Publication Types: 
    Randomized Controlled Trial

PMID: 18479659 [PubMed - indexed for MEDLINE]

100: J Am Board Fam Med. 2008 May-Jun;21(3):179-83.

Comment in:
    J Am Board Fam Med. 2008 Sep-Oct;21(5):477-8.

The association between hay fever and stroke in a cohort of middle aged and
elderly adults.

Matheson EM, Player MS, Mainous AG 3rd, King DE, Everett CJ.

Department of Family Medicine, Medical University of South Carolina, Charleston, 
SC 29425, USA. matheson@musc.edu

BACKGROUND: Asthma has been linked to stroke, but it is unknown if hay fever is
related to stroke. This study was designed to investigate if there is an
association between a reported history of hay fever and stroke during a 4.4-year 
study period. METHODS: Analysis was performed of the Atherosclerosis Risk in
Communities study, a cohort of middle aged and elderly adults. We examined the
association of a reported history of hay fever to the development of stroke.
RESULTS: There were 9272 participants meeting our criteria, of which 125 had
strokes. Of those with a history of hay fever, 2.2% had a stroke. Of those
without a history of hay fever, 1.25% had a stroke. Participants with a history
of hay fever had an unadjusted hazard ratio of 1.72 (95% CI, 1.08-2.27) for
stroke versus participants without hay fever. Risk of stroke remained significant
(hazard ratio, 1.87 [95% CI, 1.17-2.99]) after controlling for age, sex, race,
smoking status, body mass index, diabetes, hypertension, alcohol use, and
hyperlipidemia. CONCLUSION: A history of hay fever seems to be a risk factor for 
stroke, and this association may be an area for future research and intervention.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 18467528 [PubMed - indexed for MEDLINE]

101: Paediatr Drugs. 2008;10(3):151-62.

Optimal management of nasal congestion caused by allergic rhinitis in children:
safety and efficacy of medical treatments.

Scadding G.

Royal National Throat Nose & Ear Hospital, London, UK. g.scadding@ucl.ac.uk

Nasal congestion is such a frequent and multifactorial occurrence in young
children that parents and medical caregivers often overlook the need for medical 
intervention. However, children with congestion can suffer quality-of-life
detriments resulting from sleep disturbance, learning impairment, and fatigue.
Congestion also impairs the normal nasal breathing that is physiologically
important for the efficient cleaning and conditioning of inspired air. Further,
the most common cause of congestion, allergic rhinitis, is considered a potential
risk factor for asthma. Published guidelines on the treatment of allergic
rhinitis agree that management strategies in children should follow the same
principles as in adults, while recognizing the need for dosage adjustments and
being aware of unique safety issues. Intranasal corticosteroids, with robust
effects in reducing congestion and good tolerability, remain a treatment of
choice. Despite lingering concerns about the potential for growth suppression
with these drugs, clinical evidence suggests a very low risk at prescribed
dosages, especially with compounds that have a low systemic bioavailability.Oral 
antihistamines are commonly cited as first-line options for allergic rhinitis,
although their effect on nasal congestion is relatively modest. First-generation 
antihistamines should not be administered to children because of their sedative
properties, which can worsen learning problems associated with allergic rhinitis.
Second-generation oral antihistamines are preferred, although this class is not
completely devoid of adverse effects. Other treatments, such as a nasal
antihistamine, decongestants, and immunotherapy, present varying levels of safety
and tolerability issues in children.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18454568 [PubMed - indexed for MEDLINE]

102: Ann Allergy Asthma Immunol. 2008 Apr;100(4):343-50.

Effect of sublingual immunotherapy with grass monomeric allergoid on
allergen-specific T-cell proliferation and interleukin 10 production.

Burastero SE, Mistrello G, Falagiani P, Paolucci C, Breda D, Roncarolo D, Zanotta
S, Monasterolo G, Rossi RE.

Department of Biotechnology, San Raffaele Scientific Institute, Milan, Italy.
s.burastero@hsr.it

BACKGROUND: Sublingual immunotherapy (SLIT) is safe and efficacious in the
treatment of patients with allergic rhinitis. Although favorable clinical effects
have been observed with controlled trials as early as a few months since the
beginning of treatment, few biological changes induced by SLIT have been
demonstrated. OBJECTIVE: To investigate in grass-allergic patients the effect of 
a 2-month SLIT regimen, administered with a simplified protocol without
up-dosing, on proliferation and production of cytokines characteristic of the
regulatory T-cell phenotype (interleukin 10 [IL-10] and transforming growth
factor beta [TGF-beta]) by allergen-specific T cells. METHODS: Patients were
recruited to the study in January 2006. SLIT was performed by self-administration
and was continued for 60 days from February to April 2006. Eleven grass
pollen-allergic patients with seasonal rhinitis were treated daily before the
pollen season for 2 months with a modified allergen (monomeric allergoid) derived
from a 3-grass pollen extract. Allergen-specific proliferation and production of 
IL-10 and TGF-beta were measured on peripheral blood mononuclear cells at
baseline and treatment end. Tetanus toxoid served as the control antigen.
RESULTS: After SLIT, allergen-specific (P = .002) but not tetanus toxoid-specific
proliferation decreased, whereas IL-10 transcription increased (P < .001).
TGB-beta transcription was also increased after treatment, although not
statistically significantly (P = .06). Changes in proliferation to allergen and
in IL-10 transcription were correlated (r = -0.82, P = .003). CONCLUSIONS: A
short-term course of SLIT with modified allergen in grass-allergic patients is
associated with the reduction of allergen-specific proliferation and with the
up-regulation of the IL-10 regulatory cytokine.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18450120 [PubMed - indexed for MEDLINE]

103: Ann Allergy Asthma Immunol. 2008 Apr;100(4):338-42.

Effect of Lactobacillus rhamnosus GG on rBet v1 and rMal d1 specific IgA in the
saliva of patients with birch pollen allergy.

Piirainen L, Haahtela S, Helin T, Korpela R, Haahtela T, Vaarala O.

National Public Health Institute, Laboratory for Immunobiology, Helsinki,
Finland. laura.piirainen@helsinki.fi

BACKGROUND: Lactobacillus rhamnosus GG (LGG) has demonstrated promising results
in the treatment and prevention of atopic eczema. OBJECTIVE: To study the effects
of LGG on the oral immune response in adolescents and adults with birch pollen
allergy combined with oral allergy syndrome. METHODS: Patients received either
LGG (n = 19) or a placebo (n = 19) for 5.5 months (from February 8 to August 6,
1999), starting 2.5 months before the birch pollen season. An oral apple
challenge test was performed before, during, and after the pollen season. Saliva 
samples were collected before and after the challenges, and serum samples were
collected before the challenges. Total IgA, IgG, and IgM and rBet v1 and rMal dl 
specific IgA, IgG, IgG1, and IgG4 levels were measured from saliva with an
enzyme-linked immunosorbent assay (ELISA). Serum rBet v1 specific IgE ELISA and
birch radioallergosorbent testing were performed. RESULTS: After 5.5 months, rBet
v1 and rMal dl specific IgA levels had increased from baseline in the LGG
compared with the placebo group (delta rBet v1 IgA, 0.319 vs. -0.136 relative
units; P = .02; delta rMal d1 IgA, 0.097 vs -0.117, P = .02). rBet v1 specific
IgE serum levels did not differ between the groups. In the LGG group, rBet v1
specific IgE levels correlated positively with stimulated total IgA (P = .04) and
IgG (P = .003) in saliva. In the placebo group, rBet vl specific IgE levels
correlated negatively with stimulated rBet v1 and rMal d1 IgA levels (P = .009
for both) and IgG (P = .02 and P = .03, respectively). CONCLUSION: LGG showed
immunostimulating effects on oral mucosa seen as increased allergen specific IgA 
levels in saliva.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18450119 [PubMed - indexed for MEDLINE]

104: Eur Respir J. 2008 Sep;32(3):603-11. Epub 2008 Apr 30.

Farm exposure in utero may protect against asthma, hay fever and eczema.

Douwes J, Cheng S, Travier N, Cohet C, Niesink A, McKenzie J, Cunningham C, Le
Gros G, von Mutius E, Pearce N.

Centre for Public Health Research, Massey University, Wellington, New Zealand.
j.douwes@massey.ac.nz

The aim of the present study was to assess which factors contribute to the lower 
prevalence of allergic diseases in farmers' children, and the importance of
timing of exposure. In a cross-sectional questionnaire survey, asthma symptoms,
hay fever and eczema were assessed, as well as current, early and prenatal
farm-related exposures in 1,333 farmers' children and 566 reference children aged
5-17 yrs. Farmers' children had a lower incidence of asthma symptoms and eczema. 
Current and maternal exposure during pregnancy to animals and/or grain and hay
reduced the risk of asthma symptoms, hay fever and eczema. The exposure-response 
association for maternal exposure was nonlinear for most outcomes. After mutual
adjustment, the effects of prenatal exposure remained unchanged whereas current
exposure remained protective only for asthma medication, asthma ever and hay
fever. Exposure during the first 2 yrs was not associated with symptoms, after
controlling for prenatal exposure. A combination of prenatal and current exposure
was most strongly associated with wheeze (odds ratio (OR) 0.48, 95% confidence
interval (CI) 0.28-0.80), asthma medication (OR 0.50, 95% CI 0.30-0.82), asthma
ever (OR 0.50, 95% CI 0.33-0.76), hay fever (OR 0.47, 95% CI 0.30-0.73) and
eczema (OR 0.46, 95% CI 0.30-0.70). Prenatal exposure may contribute to the low
prevalence of asthma, hay fever and eczema in farmers' children, but continued
exposure may be required to maintain optimal protection.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18448493 [PubMed - indexed for MEDLINE]

105: Int Arch Allergy Immunol. 2008;147(1):35-40. Epub 2008 Apr 30.

High serum tryptophan concentration in pollinosis patients is associated with
unresponsiveness to pollen extract therapy.

Kositz C, Schroecksnadel K, Grander G, Schennach H, Kofler H, Fuchs D.

Division of Biological Chemistry, Biocenter, Innsbruck Medical University,
Innsbruck, Austria.

BACKGROUND/AIMS: The immunologic background of allergic asthma and rhinitis
includes a preponderance of Th2-type immunity. In parallel, Th1-type immune
response is suppressed by Th2-type cytokines. As a consequence, biochemical
pathways triggered by Th1-type cytokine interferon-gamma, such as tryptophan
degradation by indoleamine 2,3-dioxygenase and neopterin production, might be
altered. We examined whether they are related to the outcome of hyposensitization
therapy in atopic patients. METHODS: In serum specimens of 44 atopic patients (18
women, 26 men) before any specific immunotherapy, tryptophan and kynurenine
concentrations were measured by HPLC, and the kynurenine to tryptophan ratio
(kyn/trp) was calculated. Neopterin concentrations were measured by ELISA.
Results were compared with concentrations in 38 serum specimens from healthy
blood donors and with the outcome of specific subcutaneous immunotherapy in
atopics: on clinical grounds, 27 patients were classified as responders, and 17
patients as non-responders. RESULTS: Serum tryptophan concentrations were higher 
in atopics (84.3 +/- 24.4 microM) than in blood donors (57.9 +/- 7.46 microM; p <
0.001), kynurenine and kyn/trp were not different between the 2 groups. All of
the neopterin concentrations measured in patients were <8.7 nM, the upper limit
of the normal. Non-responders to subcutaneous immunotherapy had significantly
higher tryptophan concentrations (95.7 +/- 27.0 microM) than responders (77.1 +/-
19.9 microM; p = 0.01). No other marker concentrations differed between the
groups. CONCLUSIONS: The measurement of serum tryptophan may present an option to
predict the outcome of pollen extract therapy. Higher tryptophan levels may
result from lower indoleamine 2,3-dioxygenase activity in atopics. However, this 
possible relationship needs to be confirmed in further studies. Copyright 2008 S.
Karger AG, Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18446051 [PubMed - indexed for MEDLINE]

106: Allergy. 2008 Jun;63(6):660-9.

ARIA-suggested drugs for allergic rhinitis: what impact on quality of life? A
GA2LEN review.

Baiardini I, Braido F, Tarantini F, Porcu A, Bonini S, Bousquet PJ, Zuberbier T, 
Demoly P, Canonica GW; GA2LEN.

Allergy & Respiratory Diseases, DIMI - University of Genoa, Genoa, Italy.

Allergic diseases constitute a global health problem, as they have an increasing 
economic and social impact and, especially, they can deeply interfere with the
patients' daily life, being a cause of physical and emotional discomfort. This is
why the health-related quality-of-life (HRQoL) has become increasingly important 
in health care research; in fact, the assessment of the impact the disease and
its treatment have on patients, provides a more comprehensive approach in outcome
evaluation. Numerous validated questionnaires are available and many studies have
been performed evaluating HRQoL in people affected by allergic rhinitis (AR),
thus testifying a great interest in this topic. The aims of the present review
are: to examine the scientific literature of the last 3 years dealing with the
impact of AR treatments suggested by allergic rhinitis and its impact on asthma
guidelines on patients' QoL, and to identify the unexplored or
not-fully-investigated areas concerning this issue.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18445183 [PubMed - indexed for MEDLINE]

107: Clin Exp Allergy. 2008 Jun;38(6):987-94. Epub 2008 Apr 25.

Cluster immunotherapy with a glutaraldehyde-modified mixture of grasses results
in an improvement in specific nasal provocation tests in less than 2.5 months of 
treatment.

Subiza J, Feliú A, Subiza JL, Uhlig J, Fernández-Caldas E.

Centro de Asma y Alergia Subiza, Madrid, Spain. jsubiza@mi.madritel.es

BACKGROUND: Cluster immunotherapy is becoming increasingly used. It allows for a 
rapid build up phase and the administration of higher doses of allergen in a
shorter period of time. OBJECTIVES: To evaluate the effect of short-term
pre-seasonal immunotherapy using a glutaraldeyde-modified allergen vaccine in
reducing specific nasal hyperreactivity in nasal challenge tests. MATERIALS AND
METHODS: Thirty-three patients were selected. All patients had a positive history
of allergic rhinitis and skin tests to grass pollen, although most of them
(72.7%) were sensitized to other allergens as well. The study was conducted
outside of the pollen season and the patients did not receive any pharmacological
treatment during this period of time. Two randomized groups of patients were
established; Group A: 22 patients (13 females and nine males) and Group B, 11
control patients (seven females and four males). Patients in Group A received
immunotherapy with a vaccine containing 50% of the wild grasses Trisetum paniceum
and Dactylis glomerata. All patients underwent titrated nasal provocation tests
(NPT) before and after completion of the study (2.3 and 2.8 months for Groups A
and B, respectively). The administration schedule consisted of 0.1 and 0.2 mL at 
day 1, followed by 0.3 and 0.5 mL at day 7, 0.5 mL after 2 weeks followed by 0.5 
mL monthly. A single vial was used containing an allergen concentration of 10 000
TU/mL (105 microg of total protein and 24.6 microg of Group 1 plus 5
allergens/mL). A mean of 6.5 injections were administered to Group A patients
between NPTs. RESULTS: There were no significant differences between both groups 
at the beginning of the study (P=0.48). At the end, only Group A patients needed 
significant greater threshold concentrations for a positive NPT than at the
beginning (P=0.002). CONCLUSIONS: A short-term cluster pre-seasonal inmunotherapy
with a modified vaccine containing a mixture of grass pollen is effective as
determined by an objective measure after only a mean 2.3 months of treatment.

Publication Types: 
    Evaluation Studies
    Randomized Controlled Trial

PMID: 18445082 [PubMed - indexed for MEDLINE]

108: Int Immunopharmacol. 2008 Jun;8(6):945-9. Epub 2008 Mar 11.

Serum adiponectin levels in patients with pollen-induced allergic rhinitis.

Ciprandi G, Murdaca G, Marseglia G, Colombo BM, Quaglini S, De Amici M.

Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino - 
University of Genoa; Genoa, Italy. gio.cip@libero.it

BACKGROUND: Several studies have outlined a possible relationship between an
increased body mass index and respiratory allergic diseases, such as asthma and
rhinitis. OBJECTIVE: The aim of the study was to evaluate the serum adiponectin
levels in a cohort of patients with pollen-induced allergic rhinitis, enrolled
outside the pollen season, and in a group of healthy controls. METHODS: The study
included 41 patients with moderate-severe persistent allergic rhinitis due to a
pollen allergy and 34 normal subjects. All subjects were prospectively and
consecutively evaluated. A skin prick test and blood sampling for assessing serum
adiponectin levels were performed in all subjects. RESULTS: The comparison
between allergic patients and normal subjects, globally considered without gender
distinction, showed slightly higher values in the allergic population. After
analysing genders separately, allergic patients show significantly higher levels 
than normal males (p = 0.0134), whereas the comparison between allergic and
normal females was not significant (p = 0.1419). In addition, in normal males
adiponectin serum levels are significantly related with age (p = 0.0123).
CONCLUSION: This preliminary study provides the first evidence of significantly
higher adiponectin serum levels in male patients with pollen-induced allergic
rhinitis as compared to normal male subjects.

PMID: 18442802 [PubMed - indexed for MEDLINE]

109: Cytokine. 2008 Jun;42(3):325-9. Epub 2008 Apr 25.

Gender differences in inflammatory proteins and pathways in seasonal allergic
rhinitis.

Barrenäs F, Andersson B, Cardell LO, Langston M, Mobini R, Perkins A, Soini J,
Ståhl A, Benson M.

The Unit for Clinical Systems Biology, Department of Pediatrics, The Queen Silvia
Children's Hospital, SE 41685 Göteborg, Sweden. Fredrik.Barrenas@vgregion.se

In model organisms, thousands of genes differ in expression between females and
males. It is not known if differences on a similar scale are found in humans nor 
how this relates to disease. However, in allergic disease gender differences in
the levels of both inflammatory cells and proteins have been shown. In this
study, we found lower nasal fluid allergen-specific IgE in women than men with
seasonal allergic rhinitis (SAR). This led to genome-wide analyses of gene
expression in allergen-challenged CD4(+) cells from patients with SAR before and 
after treatment with cortisone. Before treatment, 975 genes differed in
expression between women and men: 337 were higher in women. After treatment only 
428 genes and one pathway differed in expression. The genes that differed in
expression between women and men were over-represented in 10 pathways. Five of
the pathways regulated chemotaxis. All five were less active in women. One of the
pathways was induced by the eosinophilic chemokine CCL4. Analysis of nasal fluid 
CCL4 protein confirmed lower levels in women with seasonal allergic rhinitis,
before and during the pollen season. By contrast, nasal fluid CCL3 levels did not
differ between the genders. In summary, this study shows gender differences in
specific inflammatory pathways and proteins in patients with seasonal allergic
rhinitis. Further studies are warranted to examine if such differences have
diagnostic and therapeutic implications in allergic diseases.

Publication Types: 
    Comparative Study

PMID: 18440239 [PubMed - indexed for MEDLINE]

110: Ann Allergy Asthma Immunol. 2008 Mar;100(3):272-9.

Comment in:
    Ann Allergy Asthma Immunol. 2008 Mar;100(3):193.

Ocular symptom reduction in patients with seasonal allergic rhinitis treated with
the intranasal corticosteroid mometasone furoate.

Bielory L.

Div. Allergy, Immunology, and Rheumatology, Clinical Research and Development,
Dept. of Medicine, Pediatrics, and Ophthalmology, University of Medicine and
Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA.
bielory@umdnj.edu

BACKGROUND: Allergic rhinitis (AR) is more appropriately termed allergic
rhinoconjunctivitis owing to the equally bothersome nasal and ocular symptoms.
Extensive evidence supports the ability of intranasal corticosteroids to reduce
nasal symptoms of AR, although less evidence is available to define clearly their
impact on allergic conjunctivitis. OBJECTIVE: To determine the effect of the
intranasal corticosteroid mometasone furoate nasal spray (NS) on the ocular
symptoms of seasonal AR. METHODS: This retrospective pooled analysis of 4
placebo-controlled clinical studies randomized patients 12 years and older with
symptomatic seasonal AR to receive mometasone furoate NS, 200 microg once daily
(n = 491), or placebo (n = 492). Ocular symptom (eye tearing [epiphora], itching 
[pruritus], and redness [erythema]) severity was rated by patients twice daily on
a 4-point scale (0 = none to 3 = severe) in the morning and evening, with scores 
averaged to obtain a daily mean score. Efficacy variables were the pooled mean
change from baseline in the averaged morning and evening total ocular symptom
score (TOSS) and the individual ocular symptom scores. RESULTS: The change in
mean TOSS from baseline to days 1 to 15 was -1.33 (-19.8%) with mometasone
furoate NS and -0.93 (-5.6%) with placebo (P < .001). Improvements in individual 
symptoms were significantly better with mometasone furoate NS than with placebo
on days 2 (tearing) and 4 (itching and redness). A slightly greater reduction in 
TOSS was seen with mometasone furoate NS treatment in the evening than in the
morning. CONCLUSIONS: This detailed analysis of an intranasal corticosteroid on
individual ocular symptoms supports the positive impact of mometasone furoate NS 
on ocular symptoms.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18434976 [PubMed - indexed for MEDLINE]

111: Allergy Asthma Proc. 2008 Mar-Apr;29(2):146-51.

Mediator measurements after daily instillation of allergen: Increased IL-5 and
decreased IFN-gamma.

McDermott RA, Nelson HS, Dreskin SC.

Division of Allergy and Clinical Immunology, Department of Medicine, University
of Colorado Health Sciences Center, Denver, CO, USA.

This study was designed to measure symptoms, IL-4, IL-5, IFN-gamma, and
eosinophilic cationic protein (ECP) in nasal secretions from subjects
experiencing an artificial allergy season and to look for evidence of priming.
Clinically relevant allergen was administered intranasally out of season to 12
asymptomatic individuals with seasonal allergic rhinitis. These individuals were 
then randomized to receive allergen or saline daily for the next 7 days. Nasal
secretions and scrapings of nasal epithelium were obtained at baseline (day 1),
24 hours after the initial allergen administration (day 2), and 24 hours after
the last instillation of allergen or saline (day 9). Nasal symptom scores (p <
0.0002), IL-5 mRNA (p = 0.03), and ECP (p < 0.02) increased after receiving the
first challenge (day 2 compared with day 1). In the six subjects randomized to
receive seven sequential daily challenges with allergen, symptom scores remained 
elevated (p < 0.02), IL-5 protein increased (p = 0.02), and IFN-gamma (p = 0.02) 
levels decreased (day 9 compared with day 1). In the six subjects randomized to
receive seven sequential daily challenges with placebo, symptom scores, IL-5, and
IFN-gamma levels were not significantly different (day 9 compared with day 1).
Compared with the findings at day 2 (n = 12), the treated subjects (n = 6) had no
further increase in symptoms but did show a further increase in IL-5 (p = 0.01)
and a decrease in IFN-gamma (p = 0.02) at day 9. Daily instillation of moderate
doses of allergen intranasally is characterized by persistent symptoms, elevation
of IL-5, and reduced levels of IFN-gamma.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18430311 [PubMed - indexed for MEDLINE]

112: BMC Complement Altern Med. 2008 Apr 22;8:13.

A systematic review of the clinical effectiveness of acupuncture for allergic
rhinitis.

Roberts J, Huissoon A, Dretzke J, Wang D, Hyde C.

West Midlands Health Technology Assessment Collaboration, Department of Public
Health and Epidemiology, University of Birmingham, UK.
jonathan.roberts@hpa.org.uk

BACKGROUND: Allergies cause a considerable burden to both sufferers and the
National Health Service. There is growing interest in acupuncture as a treatment 
for a range of conditions. Since acupuncture may modulate the immune system it
could be a useful treatment for allergic rhinitis (AR) sufferers. We therefore
assessed the evidence for the clinical effectiveness of acupuncture in patients
with AR by performing a systematic review of the literature. METHODS: Searches
(to 2007) were conducted in all major databases for randomised controlled trials 
(RCTs) evaluating the clinical effectiveness of acupuncture in the treatment of
AR. No limits were placed on language. Studies were included if they compared
acupuncture to a sham or inactive acupuncture treatment (placebo) with or without
standard care. Meta-analysis was performed where feasible. RESULTS: Seven
relevant RCTs were included after screening and application of inclusion and
exclusion criteria. The trials were generally of poor quality as assessed by a
modified Jadad scale, with the exception of two studies which scored highly. A
wide variety of outcomes was measured but most assessed symptom severity on a
visual analogue scale. A meta-analysis failed to show any summary benefits of
acupuncture treatment for symptom severity scores or serum IgE measures which
could not have been accounted for by chance alone. Acupuncture was not associated
with any additional adverse events in the trials. CONCLUSION: There is currently 
insufficient evidence to support or refute the use of acupuncture in patients
with AR. A large well conducted RCT, which overcomes identified methodological
problems in the existing RCTs, would be required to resolve this question.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18430229 [PubMed - indexed for MEDLINE]

113: Allergol Int. 2008 Jun;57(2):175-80.

A 13-year study of Japanese cedar pollinosis in Japanese schoolchildren.

Ozasa K, Hama T, Dejima K, Watanabe Y, Hyo S, Terada T, Araki N, Takenaka H.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural
University of Medicine, Kamigyo-ku, Kyoto, Japan. kozasa@koto.kpu-m.ac.jp

BACKGROUND: Japanese cedar pollen (JCP) sensitization and Japanese cedar
pollinosis (JCPS) appear to be increasingly prevalent in younger children. The
present study investigated factors affecting JCP sensitization and JCPS
development in school children. METHODS: In May or June each year from 1994 to
2006, 275-510 children were assessed for serum JCP-IgE and house dust mite
(HDM)-IgE levels, and surveyed regarding rhinoconjunctival symptoms. RESULTS:
Strong JCP sensitization (IgE > or = 17.5 U(A)/ml) was associated with age (odds 
ratio (OR) = 2.65), the amount of dispersed pollen in the observed year (OR =
2.03) and in the year following birth (OR = 1.51), the month of birth (OR =
2.18), and the recent birth cohort (OR = 1.96). Symptoms were negatively
correlated with the recent birth cohort (OR = 0.69) after adjusting for JCP-IgE
levels. Strong HDM sensitization was associated with gender (OR = 0.65 for girls)
and the recent birth cohort (OR = 1.76). CONCLUSIONS: JCP sensitization appeared 
to be associated with the recent birth cohort and to increases in dispersed
pollen just after birth and in the observed season. Although the recent birth
cohort was more easily sensitized, they were not more likely to develop symptoms.
In contrast to JCP sensitization, strong HDM sensitization appeared to develop
prior to commencement of primary school and was more likely to affect boys.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18427167 [PubMed - indexed for MEDLINE]

114: Ann Allergy Asthma Immunol. 2008 Mar;100(3):264-71.

Clinical benefits of combination treatment with mometasone furoate nasal spray
and loratadine vs monotherapy with mometasone furoate in the treatment of
seasonal allergic rhinitis.

Anolik R; Mometasone Furoate Nasal Spray With Loratadine Study Group.

Allergy & Asthma Specialists PC, East Blue Bell, Pennsylvania 19422, USA.
ranolik@allergypc.com

BACKGROUND: Intranasal corticosteroids and nonsedating antihistamines are the
drug classes most often prescribed to treat allergic rhinitis (AR). Treatment
guidelines recommend a combination of these agents for moderate-to-severe AR.
However, clinical studies have found that combining an antihistamine with an
intranasal corticosteroid provides few or no advantages over monotherapy with an 
intranasal corticosteroid. OBJECTIVE: To compare the efficacy of mometasone
furoate nasal spray (NS) plus loratadine with that of monotherapy with the
individual agents in patients 12 years and older with at least a 2-year history
of seasonal AR. METHODS: In a multicenter, randomized, double-blind,
parallel-group, placebo-controlled clinical study, 702 patients were randomized
to receive mometasone furoate NS, 200 microg, plus loratadine, 10 mg (n = 169);
mometasone furoate NS, 200 microg (n = 176); loratadine, 10 mg (n = 181); or
placebo (n = 176) once daily for 15 days. Primary efficacy variables were total
nasal symptom score (TNSS) and total symptom score (TSS) as recorded on diary
cards. RESULTS: No statistically significant differences were observed between
mometasone furoate NS plus loratadine and mometasone furoate NS monotherapy for
the primary efficacy variables. For TNSS and TSS, all 3 active drug therapies
were more effective than placebo (P < or = .02). Both mometasone furoate NS
treatment regimens were more effective than loratadine or placebo for TNSS (P <
.01 for both) and TSS (P < or = .03 for both), whereas loratadine was more
effective than placebo for TNSS only (P = .02). CONCLUSIONS: Combination therapy 
with mometasone furoate NS and loratadine provided benefits similar to
monotherapy with mometasone furoate NS for the symptoms of seasonal AR.
Therefore, mometasone furoate NS monotherapy was shown to be an effective
treatment for seasonal AR.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 18426147 [PubMed - indexed for MEDLINE]

115: Ann Allergy Asthma Immunol. 2008 Mar;100(3):256-63.

Efficacy and safety of specific immunotherapy with a high-dose sublingual grass
pollen preparation: a double-blind, placebo-controlled trial.

Pfaar O, Klimek L.

Rhinology and Allergology Center, Wiesbaden, Germany.
oliver.pfaar@hno-wiesbaden.de

BACKGROUND: Sublingual immunotherapy (SLIT) is increasingly being used for the
treatment of allergic rhinitis, but there are conflicting study results
demonstrating clinically relevant efficacy. OBJECTIVE: To show clinical efficacy 
and safety of a new high-dose grass pollen preparation for SLIT. METHODS: In a
2-year, double-blind, placebo-controlled trial, 185 subjects with rhinitis or
rhinoconjunctivitis, with or without asthma, were treated with a recently
developed, high-dose, 6-grass pollen mixture for SLIT once daily. RESULTS: The
primary end point, a combined symptom-medication score, showed almost no change
in the placebo group during a 42-day evaluation period in the grass pollen season
from 2003 to 2005, whereas active treatment was associated with a significant and
clinically relevant improvement (full analysis set, P = .01; main data set, P =
.002). The effect was irrespective of asthma diagnosis. Allergen-specific IgE
showed no difference in both groups, and specific IgG4 and IgG1 increased with
active treatment in the first and second study years compared with placebo,
clearly indicating the immunogenic effect of the active treatment. The SLIT was
well tolerated. No serious adverse drug reactions occurred. CONCLUSIONS:
High-dose, sublingual, specific immunotherapy with an extract of a 6-grass pollen
mixture showed a significant and clinically relevant improvement in subjects with
grass pollen-associated rhinitis or rhinoconjunctivitis, with or without asthma. 
The treatment with the sublingual solution was well tolerated.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18426146 [PubMed - indexed for MEDLINE]

116: Ann Allergy Asthma Immunol. 2008 Mar;100(3):194-9.

Nasal ocular reflexes and eye symptoms in patients with allergic rhinitis.

Baroody FM, Foster KA, Markaryan A, deTineo M, Naclerio RM.

Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The
University of Chicago, Chicago, Illinois 60637, USA.

BACKGROUND: Allergic patients often complain of eye symptoms during the allergy
season. A possible mechanism for these eye symptoms is a nasal ocular reflex.
OBJECTIVE: To demonstrate eye symptoms after nasal allergen challenge. METHODS:
In a double-blind, placebo-controlled, crossover, clinical trial, 20 patients
with seasonal allergic rhinitis were challenged in 1 nostril with antigen, and
the response was monitored in both nostrils and in both eyes. Symptoms were
recorded. Filter paper disks (intranasally) and Schirmer strips (intraocularly)
were used for collecting secretions, which were subsequently eluted for the
measurement of histamine and albumin levels. Patients were treated once topically
at the site of challenge with azelastine or placebo. RESULTS: After placebo
treatment, ipsilateral nasal challenge caused nasal symptoms and an increase in
secretion weights; both were blocked by treatment with azelastine. Histamine and 
albumin levels increased only at the site of nasal challenge. Azelastine
pretreatment inhibited the increase in albumin but not histamine levels. Symptoms
of itchy and watery eyes increased significantly compared with symptoms with sham
challenge after nasal allergen and were blocked by azelastine use. Ocular
secretion weights increased bilaterally after placebo use and were not inhibited 
by azelastine use. CONCLUSIONS: Nasal allergen challenge releases histamine at
the site of the challenge, which probably initiates a nasonasal and a nasal
ocular reflex. This reflex is reduced by an H1-receptor antagonist applied at the
site of the challenge. The eye symptoms associated with allergic rhinitis
probably arise, in part, from a naso-ocular reflex.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18426137 [PubMed - indexed for MEDLINE]

117: J Allergy Clin Immunol. 2008 Jun;121(6):1467-72, 1472.e1. Epub 2008 Apr 18.

Grass pollen immunotherapy induces Foxp3-expressing CD4+ CD25+ cells in the nasal
mucosa.

Radulovic S, Jacobson MR, Durham SR, Nouri-Aria KT.

Department of Upper Respiratory Medicine, Section of Allergy and Clinical
Immunology, National Heart and Lung Institute, Imperial College and Royal
Brompton Hospital London, London, United Kingdom.

BACKGROUND: Regulatory T (Treg) cells play an important role in controlling
allergic inflammation. The transcription factor Foxp3 regulates the development
and function of natural and adaptive CD4(+)CD25(+) Treg cells. OBJECTIVES: We
sought to examine the effect of grass pollen injection immunotherapy on the
numbers of Foxp3(+)CD4(+) and Foxp3(+)CD25(+) T cells in and out of season and
their expression of IL-10 in the nasal mucosa of patients with hay fever.
METHODS: Nasal biopsy specimens were obtained from untreated patients with hay
fever, participants with grass pollen allergy who had received 2 years of
immunotherapy, and healthy control subjects. Dual-immunofluorescence microscopy
was used to enumerate and colocalize Foxp3 expression to CD4(+) and CD25(+) T
cells in the nasal mucosa. Triple staining was performed to colocalize Foxp3(+)
cells to CD3(+)CD25(+) and CD3(+) IL-10-expressing cells. RESULTS: At peak
season, numbers of Foxp3(+)CD25(+) (P = .02) and Foxp3(+)CD4(+) (P = .03) cells
were significantly increased in the nasal mucosa of immunotherapy-treated
patients compared with numbers before treatment. Foxp3(+)CD25(+) (P = .03) and
Foxp3(+)CD4(+) (P = .04) cells were also greater in immunotherapy-treated
patients out of season compared with those in untreated patients with hay fever. 
Within the immunotherapy-treated group, 20% of CD3(+)CD25(+) cells expressed
Foxp3, and 18% of Foxp3(+)CD3(+) cells were IL-10 positive. CONCLUSION: The
presence of local Foxp3(+)CD25(+)CD3(+) cells in the nasal mucosa, their
increased numbers after immunotherapy, and their association with clinical
efficacy and suppression of seasonal allergic inflammation support a putative
role for Treg cells in the induction of allergen-specific tolerance in human
subjects.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18423565 [PubMed - indexed for MEDLINE]

118: Clin Exp Allergy. 2008 May;38(5):751-60.

Identification and management of undiagnosed and undertreated allergic rhinitis
in adults and children.

Stewart MG.

Department of Otorhinolaryngology, Weill Medical College of Cornell University,
New York, NY 10021, USA. mgs2002@med.cornell.edu

Allergic rhinitis (AR) is a common health problem that affects adults,
adolescents and children and is often undiagnosed or inadequately treated.
Because AR is not a life-threatening disease, many patients do not seek medical
treatment for their symptoms, and others self-medicate with over-the-counter
medications, often sedating antihistamines. However, untreated or inadequately
treated AR can substantially impair overall quality of life (QOL) by causing
fatigue, headache, cognitive impairment and other problems. The risk for comorbid
conditions, such as asthma, otitis media, and lymphoid hypertrophy with
obstructive sleep apnea, can increase, and the symptoms of AR can worsen if AR is
not adequately treated. Among the symptoms of AR, nasal congestion has been
described by patients as the most bothersome because it disrupts sleep, resulting
in diminished daytime performance. A new congestion screening tool, the
Congestion Quantifier, has been developed to aid in the diagnosis and treatment
of AR and to help guide treatment decisions. Intranasal corticosteroids (INSs)
are recommended as effective pharmaceutical treatments for controlling the
symptoms of AR. Randomized, controlled trials in children and adults have
demonstrated that INSs relieve rhinitis symptoms, thereby improving QOL in
individuals with seasonal or perennial AR. Most INSs are approved for use in
children >or=6 years of age, but mometasone furoate and fluticasone furoate are
approved for use in children as young as 2 years of age and fluticasone
propionate for children >or=4 years old. Long-term benefits have also been seen
with the use of immunotherapy, although some patients, especially children,
resist the injections used in subcutaneous immunotherapy. Recent studies with
sublingual immunotherapy have indicated that it might be an effective and
well-tolerated alternative to immunotherapy injections.

Publication Types: 
    Review

PMID: 18419620 [PubMed - indexed for MEDLINE]

119: Curr Allergy Asthma Rep. 2008 Apr;8(2):118-25.

Complementary therapy in allergic rhinitis.

Resnick ES, Bielory BP, Bielory L.

Division of Allergy, Immunology, and Rheumatology, UMDNJ-New Jersey Medical
School, Newark, NJ 07103, USA.

The term complementary/alternative medicine (CAM) refers to those therapeutic and
diagnostic approaches different from conventional allopathic medicine. CAM may
encompass homeopathy, acupuncture, phytotherapy, antioxidant therapy, and
numerous holistic or behavioral techniques. Allergists and physicians of all
disciplines are confronted with patients using CAM treatments, making it
imperative that they become familiar with the scientific literature surrounding
them. Given the high prevalence of allergic diseases and associated costs of CAM 
treatments, proof of CAM therapies is needed to establish appropriate guidelines 
for their use. Efficacy of CAM modalities should be established with randomized, 
double-blind, placebo-controlled trials, including adverse-effects monitoring. Of
all the CAM therapies examined to treat allergic rhinitis, some herbal therapies 
and antioxidants demonstrate a trend toward some clinical efficacy. Researchers
have yet to determine how to integrate these CAM modalities into the general
treatment paradigm of allergic rhinitis.

Publication Types: 
    Review

PMID: 18417053 [PubMed - indexed for MEDLINE]

120: Curr Allergy Asthma Rep. 2008 Apr;8(2):102-10.

Sublingual immunotherapy and allergic rhinitis.

Cox L.

Nova Southeastern University Osteopathic College of Medicine, Fort Lauderdale, FL
33334, USA. lindaswolfcox@msn.com

This paper reviews the safety and efficacy of sublingual immunotherapy (SLIT) in 
the treatment of allergic rhinitis. The literature from 1986 through 2007 shows
approximately a 6000-fold range in doses found to be effective with SLIT.
However, recent studies in large patient populations have demonstrated a clear
dose response with an effective dose range that appears to be equivalent to one
to two times the monthly subcutaneous immunotherapy dose administered daily or
weekly (ie, 15 to 30 microg of major allergen). Further study is needed to
establish the optimal dose and dosing schedule for each formulation. Local
reactions (eg, oral itchiness) are common, and serious adverse reactions,
although rare, have been reported. Cost-effective analysis cannot be made until
the effective dose is established. SLIT appears to be a promising treatment for
allergic rhinitis, but it is currently considered investigational in the United
States until a formulation approved by the US Food and Drug Administration is
available.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18417051 [PubMed - indexed for MEDLINE]

121: Am J Rhinol. 2008 Mar-Apr;22(2):135-8.

Expression of mammaglobins A and B in nasal polyps is similar in patients with
and without allergic rhinitis.

Chusakul S, Phannaso C, Tongkobpetch S, Aeumjaturapat S, Poovorawan Y,
Suphapeetiporn K, Shotelersuk V.

Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand.

BACKGROUND: The causes of nasal polyposis remain unclear. Mammaglobins have been 
implicated in its pathogenesis. However, their association with the occurrence of
nasal polyps in the presence of allergic rhinitis (AR) has not been explored. The
aim of this study was to compare the expression levels of mammaglobins A and B
with the nasal polyps of patients with and without AR. METHODS: Thirty-one
patients with bilateral nasal polyposis underwent skin-prick tests to specific
aeroallergens. Nasal polyp tissues were obtained from all patients and divided
into two groups as nasal polyps with and without AR depending on clinical history
and the skin-prick test results. All polyp tissues were analyzed for the levels
of mammaglobin A and mammaglobin B by using real-time quantitative polymerase
chain reaction technique. RESULTS: Of the 16 samples from patients having nasal
polyps with AR, only 1 sample expressed a detectable level of mammaglobin A
(1/16). There was no detectable expression of mammaglobin A in tissues from the
group of nasal polyps without AR (0/15). Expression of mammaglobin B was detected
in all nasal polyp tissues from both groups. The expression of mammaglobin B was 
not significantly different between nasal polyps with AR (median, 25th-75th
percentiles; 0.023, 0.013-0.046) and nasal polyps without AR (0.032, 0.007-0.16).
CONCLUSION: Expression levels of mammaglobins A and B in nasal polyps are not
different between patients with and without AR. Our findings suggest that
mammaglobins' implication in the pathogenesis of nasal polyps is independent of
an underlying AR.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18416968 [PubMed - indexed for MEDLINE]

122: Drugs. 2008;68(6):875-83.

Ciclesonide nasal spray: in allergic rhinitis.

Dhillon S, Wagstaff AJ.

Wolters Kluwer Health/Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, 
North Shore 0754, Auckland, New Zealand. demail@adis.co.nz

Ciclesonide nasal spray delivers the corticosteroid ciclesonide as a hypotonic
spray via a metered-dose manual pump. Systemic exposure to ciclesonide and its
active metabolite desisobutyryl-ciclesonide is low after intranasal
administration. High protein binding (approximately 99%) and rapid first-pass
clearance further reduce systemic exposure to the drug. In well designed trials, 
intranasal ciclesonide 200 microg once daily for 2-4 weeks was more effective
than placebo in terms of improving nasal symptoms in adolescents and adults with 
moderate to severe seasonal allergic rhinitis. Quality of life measures were
statistically significantly improved in ciclesonide relative to placebo
recipients during the first 2 weeks of therapy. Similarly, in adolescents and
adults with moderately severe perennial allergic rhinitis, ciclesonide 200 microg
once daily was more effective than placebo in terms of reducing nasal symptoms in
well designed trials of 6 weeks' and 1 year's duration. Improvements relative to 
placebo in quality of life measures were not considered clinically relevant.
Ciclesonide nasal spray was generally well tolerated in these clinical trials;
most adverse events were mild to moderate in intensity.

Publication Types: 
    Review

PMID: 18416590 [PubMed - indexed for MEDLINE]

123: Allergy. 2008 Apr;63 Suppl 87:5-28.

Rupatadine in allergic rhinitis and chronic urticaria.

Mullol J, Bousquet J, Bachert C, Canonica WG, Gimenez-Arnau A, Kowalski ML,
Martí-Guadaño E, Maurer M, Picado C, Scadding G, Van Cauwenberge P.

Unitat de Rinologia, Servei d'ORL, Hospital Clinic, IDIBAPS, Barcelona, Spain.

Histamine is the primary mediator involved the pathophysiology of allergic
rhinitis and chronic urticaria, and this explains the prominent role that
histamine H(1)-receptor antagonists have in the treatment of these disorders.
However, histamine is clearly not the only mediator involved in the inflammatory 
cascade. There is an emerging view that drugs which can inhibit a broader range
of inflammatory processes may prove to be more effective in providing symptomatic
relief in both allergic rhinitis and chronic urticaria. This is an important
consideration of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative
which provides a scientific basis for defining what are the desirable properties 
of an 'ideal' antihistamine. In this review of rupatadine, a newer dual inhibitor
of histamine H(1)- and PAF-receptors, we evaluate the evidence for a mechanism of
action which includes anti-inflammatory effects in addition to a powerful
inhibition of H(1)- and PAF-receptors. We assess this in relation to the clinical
efficacy (particularly the speed of onset of action) and safety of rupatadine,
and importantly its longer term utility in everyday life. In clinical trials,
rupatadine has been shown to be an effective and well-tolerated treatment for
allergic rhinitis and chronic idiopathic urticaria (CIU). It has a fast onset of 
action, producing rapid symptomatic relief, and it also has an extended duration 
of clinical activity which allows once-daily administration. In comparative
clinical trials rupatadine was shown to be at least as effective as drugs such as
loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms 
in adult/adolescent patients with seasonal, perennial or persistent allergic
rhinitis. Importantly, rupatadine demonstrated no adverse cardiovascular effects 
in preclinical or extensive clinical testing, nor negative significant effects on
cognition or psychomotor performance (including a practical driving study). It
improved the overall well-being of patients with allergic rhinitis or CIU based
on findings from quality of life questionnaires and patient global rating scores 
in clinical trials. Thus, rupatadine is a recently introduced dual inhibitor of
histamine H(1)- and PAF-receptors, which has been shown to be an effective and
generally well-tolerated treatment for allergic rhinitis and chronic urticaria.
It possesses a broader profile of anti-inflammatory properties inhibiting both
inflammatory cells and a range of mediators involved in the early- and late-phase
inflammatory response, but the clinical relevance of these effects remain to be
clarified.

Publication Types: 
    Review

PMID: 18339040 [PubMed - indexed for MEDLINE]

124: J Allergy Clin Immunol. 2008 May;121(5):1203-1209.e1. Epub 2008 Apr 8.

Filaggrin mutations, atopic eczema, hay fever, and asthma in children.

Weidinger S, O'Sullivan M, Illig T, Baurecht H, Depner M, Rodriguez E, Ruether A,
Klopp N, Vogelberg C, Weiland SK, McLean WH, von Mutius E, Irvine AD, Kabesch M.

Department of Dermatology and Allergy, Technical University Munich, Munich,
Germany. weidinger@lrz.tum.de

BACKGROUND: Mutations in the filaggrin gene (FLG) have been shown to play a
significant role in ichthyosis vulgaris and eczema, 2 common chronic skin
diseases. However, their role in the development of other atopic diseases such as
asthma and rhinitis has not yet been clarified in large population-based studies.
OBJECTIVES: To study the effect of FLG mutations at the population level and
their effect on other atopic phenotypes. METHODS: Association analysis of the 2
common FLG-null mutations R501X and 2282del4 and 3 recently identified rare FLG
variants (R2447X, S3247X, 3702delG) was performed on our cross-sectional
population of German children (n = 3099) recruited as part of the International
Study of Asthma and Allergies in Childhood II in Munich (n = 1159) and Dresden (n
= 1940). RESULTS: FLG variants increased the risk for eczema more than 3-fold
(odds ratio [OR], 3.12; 95% CI, 2.33-4.173; P = 2.5 x 10(-14);
population-attributable risk, 13.5%). Independent of eczema, FLG mutations
conferred a substantial risk for allergic rhinitis (OR, 2.64; 95% CI, 1.76-4.00; 
P = 2.5 x 10(-6); population-attributable risk, 10.8%). Nasal biopsies
demonstrated strong filaggrin expression in the cornified epithelium of the nasal
vestibular lining, but not the transitional and respiratory nasal epithelia. In
contrast, the association with asthma (OR, 1.79; 95% CI, 1.19-2.68; P = .0048)
was restricted to asthma occurring in the context of eczema, and there was a
strong association with the complex phenotype eczema plus asthma (OR, 3.49; 95%
CI, 2.00-6.08; P = 1.0 x 10(-5)). CONCLUSION: Our results suggest that FLG
mutations are key organ specific factors predominantly affecting the development 
of eczema and confer significant risks of allergic sensitization and allergic
rhinitis as well as asthma in the context of eczema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18396323 [PubMed - indexed for MEDLINE]

125: J Immunol. 2008 Apr 15;180(8):5680-8.

CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced
pollinosis in mice.

Nomiya R, Okano M, Fujiwara T, Maeda M, Kimura Y, Kino K, Yokoyama M, Hirai H,
Nagata K, Hara T, Nishizaki K, Nakamura M.

Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

PGD(2) is the major prostanoid produced during the acute phase of allergic
reactions. Two PGD(2) receptors have been isolated, DP and CRTH2 (chemoattractant
receptor-homologous molecule expressed on Th2 cells), but whether they
participate in the pathophysiology of allergic diseases remains unclear. We
investigated the role of CRTH2 in the initiation of allergic rhinitis in mice.
First, we developed a novel murine model of pollinosis, a type of seasonal
allergic rhinitis. Additionally, pathophysiological differences in the pollinosis
were compared between wild-type and CRTH2 gene-deficient mice. An effect of
treatment with ramatroban, a CRTH2/T-prostanoid receptor dual antagonist, was
also determined. Repeated intranasal sensitization with Cry j 1, the major
allergen of Cryptomeria japonica pollen, in the absence of adjuvants
significantly exacerbated nasal hyperresponsive symptoms, Cry j 1-specific IgE
and IgG1 production, nasal eosinophilia, and Cry j 1-induced in vitro production 
of IL-4 and IL-5 by submandibular lymph node cells. Additionally, CRTH2 mRNA in
nasal mucosa was significantly elevated in Cry j 1-sensitized mice. Following
repeated intranasal sensitization with Cry j 1, CRTH2 gene-deficient mice had
significantly weaker Cry j 1-specific IgE/IgG1 production, nasal eosinophilia,
and IL-4 production by submandibular lymph node cells than did wild-type mice.
Similar results were found in mice treated with ramatroban. These results suggest
that the PGD(2)-CRTH2 interaction is elevated following sensitization and plays a
proinflammatory role in the pathophysiology of allergic rhinitis, especially
pollinosis in mice.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18390753 [PubMed - indexed for MEDLINE]

126: Prescrire Int. 2008 Feb;17(93):28-32.

Seasonal allergic rhinitis: limited effectiveness of treatments.

[No authors listed]

(1) Seasonal allergic rhinitis, otherwise known as hayfever, is a harmless
condition, although it can cause major discomfort and interfere with activities
of daily living. We conducted a review of the literature, based on our in-house
methodology, to determine the risk-benefits of treatments used in this setting.
(2) Placebo-controlled trials show that sodium cromoglicate relieves symptoms,
especially if it is used before symptoms appear. Adverse effects are rare with
sodium cromoglicate nasal solutions and eye drops. (3) Nasal steroids have
well-documented efficacy. Beclometasone is the best choice. Adverse effects
include epistaxis, nasal irritation and, occasionally, systemic disorders. (4)
Oral antihistamines are less effective than nasal steroids. They also provoke
adverse effects, especially drowsiness. Nasal azelastine seems to have a similar 
efficacy as oral antihistamines. (5) The adverse effects of systemic steroids
must not be overlooked, especially with long-term use. Oral administration is an 
alternative for severe symptoms that do not respond to other treatments, although
this is rarely the case. Long-acting intramuscular steroids carry an increased
risk of adverse effects. (6) Despite evaluation in several randomised controlled 
trials, there is no firm evidence that homeopathic preparations have any specific
efficacy in allergic rhinitis. (7) Vasoconstrictors, ipratropium and montelukast,
have negative risk-benefit balances in hay fever. (8) When a single allergen is
responsible (grasses, ragweed, birch), clinical trials suggest that specific
desensitisation can provide a modest improvement. However, this treatment carries
a risk of local adverse effects, as well as a risk of rare but severe
anaphylactic reactions, especially in patients who also have unstable severe
asthma. (9) Sublingual desensitisation seems to be even less effective than
subcutaneous desensitisation in adults. Follow-up is too short to know whether
there is a risk of severe anaphylactic reactions. The results of paediatric
studies are even less convincing. (10) In practice, when drug therapy is needed
to relieve symptoms of seasonal allergic rhinitis, sodium cromoglicate is the
first-line treatment. If a nasal steroid solution is chosen, it should be used
for the shortest possible period.

PMID: 18383656 [PubMed - indexed for MEDLINE]

127: J Allergy Clin Immunol. 2008 May;121(5):1120-1125.e2. Epub 2008 Apr 18.

Grass pollen immunotherapy: IL-10 induction and suppression of late responses
precedes IgG4 inhibitory antibody activity.

Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, Till SJ.

Allergy and Clinical Immunology Section, National Heart and Lung Institute,
Imperial College London, London, United Kingdom.

BACKGROUND: Grass pollen immunotherapy is an effective treatment for seasonal
allergic rhinitis that provides the opportunity to study the induction and
maintenance of allergen-specific immune tolerance. OBJECTIVES: We investigated
the relationship between clinical responsiveness, regulatory cytokine production,
and antibody responses to allergen during 1 year of immunotherapy. METHODS:
Eighteen subjects with severe seasonal allergic rhinitis were randomized
double-blind to receive active or placebo injections of an alum-adsorbed grass
pollen vaccine (Alutard SQ). Subjects underwent repeated testing of early- and
late-phase skin responses to intradermal allergen, and cellular responses to
grass pollen allergen were tested. Sera were tested for allergen-specific IgG4,
IgA, and inhibitory activity in biologic assays of IgE responses. RESULTS: Grass 
pollen immunotherapy was effective in reducing overall symptom scores (P < .05)
and conjunctival reactivity (P < .05). In the active group significant IL-10
production occurred early at low allergen doses and at a similar time as
inhibition of late skin responses at 2 to 4 weeks. Serum allergen-specific IgG4, 
IgA, and inhibitory antibody activity for basophil histamine release and
IgE-facilitated allergen binding to B cells occurred later, at 6 to 12 weeks, at 
higher allergen doses and preceded inhibition of early skin responses.
CONCLUSION: IL-10 responses occur early but at immunotherapy doses that are not
clinically effective. Later induction of inhibitory antibodies, including IgG4
and IgA, might be required for efficacy through modulation of IgE-mediated
events.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18374405 [PubMed - indexed for MEDLINE]

128: Respir Res. 2008 Mar 28;9:29.

Comprehensive evaluation of genetic variation in S100A7 suggests an association
with the occurrence of allergic rhinitis.

Bryborn M, Halldén C, Säll T, Adner M, Cardell LO.

Laboratory of Clinical and Experimental Allergy Research, Department of
Otorhinolaryngology, Malmö University Hospital, LundUniversity, Malmö, Sweden.
malin.bryborn@med.lu.se

BACKGROUND: S100A7 is a calcium-binding protein with chemotactic and
antimicrobial properties. S100A7 protein levels are decreased in nasal lavage
fluid from individuals with ongoing allergic rhinitis, suggesting a role for
S100A7 in allergic airway inflammation. The aims of this study were to describe
genetic variation in S100A7 and search for associations between this variation
and allergic rhinitis. METHODS: Peripheral blood was collected from 184 atopic
patients with a history of pollen-induced allergic rhinitis and 378 non-atopic
individuals, all of Swedish origin. DNA was extracted and the S100A7 gene was
resequenced in a subset of 47 randomly selected atopic individuals. Nine
polymorphisms were genotyped in 184 atopic and 378 non-atopic individuals and
subsequently investigated for associations with allergic rhinitis as well as skin
prick test results. Haplotypes were estimated and compared in the two groups.
RESULTS: Thirteen polymorphisms were identified in S100A7, of which 7 were
previously undescribed. rs3014837 (G/C), which gives rise to an Asp --> Glu amino
acid shift, had significantly increased minor allele frequency in atopic
individuals. The major haplotype, containing the major allele at all sites, was
more common in non-atopic individuals, while the haplotype containing the minor
allele at rs3014837 was equally more common among the atopic individuals.
Additionally, heterozygotes at this site had significantly higher scores in skin 
prick tests for 9 out of 11 tested allergens, compared to homozygotes.
CONCLUSION: This is the first study describing genetic variation, associated with
allergy, in S100A7. The results indicate that rs3014837 is linked to allergic
rhinitis in our Swedish population and render S100A7 a strong candidate for
further investigations regarding its role in allergic inflammation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18373864 [PubMed - indexed for MEDLINE]

129: J Allergy Clin Immunol. 2008 May;121(5):1126-1132.e7. Epub 2008 Mar 26.

Nasal challenge with allergen leads to maxillary sinus inflammation.

Baroody FM, Mucha SM, Detineo M, Naclerio RM.

Section of Otolaryngology-Head and Neck Surgery, the Pritzker School of Medicine,
the University of Chicago, Chicago, IL 60637, USA.
fbaroody@surgery.bsd.uchicago.edu

BACKGROUND: Allergic rhinitis and chronic rhinosinusitis are both characterized
by chronic inflammation. OBJECTIVE: We sought to investigate the effect of nasal 
allergen challenge on the maxillary sinus and study the effect of premedication
with loratadine. METHODS: We performed a double blind, crossover, randomized,
placebo-controlled study in 20 allergic subjects out of season. After treatment
with either placebo or loratadine (10 mg PO daily) for 1 week, a catheter was
inserted into one maxillary sinus and used to lavage the cavity. The subjects
then underwent nasal challenge with diluent for the allergen extract, followed by
3 concentrations of grass or ragweed. Nasal and ipsilateral sinus lavages were
performed after each challenge and then hourly for 8 hours. Sneezes and symptoms 
were recorded, and the lavage specimens were evaluated for eosinophils and levels
of eosinophil cationic protein, albumin, and histamine. Eleven of the subjects
underwent a similar challenge with lactated Ringer's solution. RESULTS: Compared 
with the lactated Ringer's solution challenge, allergen challenge resulted in
significant increases in most early- and late-phase nasal parameters. Allergen
challenge of the nose also led to a significant increase compared with control
values in maxillary sinus eosinophils and the levels of albumin, eosinophil
cationic protein, and histamine during the late response. Loratadine resulted in 
significant inhibition of the nasal early response compared with that seen with
placebo (P < .05). CONCLUSION: These findings suggest that a neural reflex or
systemic allergic inflammation is responsible for the sinus inflammatory response
and that this inflammatory response might play a role in the development of
rhinosinusitis in allergic subjects.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18367240 [PubMed - indexed for MEDLINE]

130: Int Arch Allergy Immunol. 2008;146(4):338-42. Epub 2008 Mar 21.

Specific immunotherapy for common grass pollen allergies: pertinence of a five
grass pollen vaccine.

Moingeon P, Hrabina M, Bergmann KC, Jaeger S, Frati F, Bordas V, Peltre G.

Stallergènes SA, Antony, France.

Patients throughout Europe are concomitantly exposed to multiple pollens from
distinct Pooideae species. Given the overlap in pollination calendars and similar
grain morphology, it is not possible to identify which grass species are present 
in the environment from pollen counts. Furthermore, neither serum IgE reactivity 
nor skin prick testing allow the identification of which grass species are
involved in patient sensitisation. Due to their high level of amino acid sequence
homology (e.g., >90% for group 1, 55-80% for group 5), significant
cross-immunogenicity is observed between allergens from Pooideae pollens.
Nevertheless, pollen allergens also contain species-specific T or B cell
epitopes, and substantial quantitative differences exist in allergen (e.g.,
groups 1 and 5) composition between pollens from distinct grass species. In this 
context, a mixture of pollens from common and well-characterised Pooideae such as
Anthoxanthum odoratum, Dactylis glomerata, Lolium perenne, Phleum pratense and
Poa pratensis is suitable for immunotherapy purposes because (1) it has been
validated, both in terms of safety and efficacy, by established clinical
practice; (2) it reflects natural exposure and sensitisation conditions; (3) it
ensures a consistent and well-balanced composition of critical allergens, thus
extending the repertoire of T and B cell epitopes present in the vaccine.
Copyright 2008 S. Karger AG, Basel.

Publication Types: 
    Review

PMID: 18362477 [PubMed - indexed for MEDLINE]

131: Twin Res Hum Genet. 2008 Apr;11(2):121-31.

Heritability and shared genetic effects of asthma and hay fever: an Italian study
of young twins.

Fagnani C, Annesi-Maesano I, Brescianini S, D'Ippolito C, Medda E, Nisticò L,
Patriarca V, Rotondi D, Toccaceli V, Stazi MA.

National Centre for Epidemiology, Surveillance and Health Promotion, Istituto
Superiore di Sanità, Rome, Italy. corrado.fagnani@iss.it

A number of studies have provided evidence of a significant familial aggregation 
for both asthma and hay fever, and have reported a substantial comorbidity
between the two conditions. However, far fewer, especially in Italy, have aimed
at clarifying the origins of such comorbidity. The main aims of the present study
were (a) to estimate heritability of asthma and hay fever, (b) to measure the
association between asthma and hay fever at the individual level, and (c) to
assess the extent to which genetic and environmental factors, shared by the two
conditions, mediate this association. The twin method was used. The study sample 
was derived from the Italian Twin Registry, and included 392 twin pairs aged 8 to
17 years. Data collection was performed through parent self-administered
questionnaire. Bivariate structural equation twin modeling was applied to asthma 
and hay fever. Genetic factors accounted for 92% and 78% of the variance in
liability to asthma and hay fever, respectively, with the remaining contributions
due to unique environmental influences. The within-individual association between
asthma and hay fever was substantial. The genetic correlation between the two
conditions was .58, whereas no evidence of overlapping unique environmental
effects was found. In conclusion, this study showed a high heritability of asthma
and hay fever in the Italian child and adolescent population. It also indicated
that asthma and hay fever share, to a large extent, a common genetic background, 
and environmental factors are not relevant to explain the comorbidity.

Publication Types: 
    Twin Study

PMID: 18361712 [PubMed - indexed for MEDLINE]

132: J Investig Allergol Clin Immunol. 2008;18(1):31-5.

Prevalence and comorbidity of allergic eczema, rhinitis, and asthma in a city in 
western Turkey.

Yuksel H, Dinc G, Sakar A, Yilmaz O, Yorgancioglu A, Celik P, Ozcan C.

Department of Pediatric Allergy and Pulmonology, Celal Bayar University, Manisa, 
Turkey. hyukselefe@hotmail.com

BACKGROUND: Allergic diseases co-occur in many patients. There is no published
population-based epidemiologic study about allergic diseases in Turkey.
OBJECTIVE: The aim of this population-based study was to investigate the
prevalence of allergic eczema, allergic rhinitis, and asthma and their
co-occurence in Manisa. METHODS: The sample size was calculated using an
estimated prevalence of ever wheezing for the analyzed age group. Interviews were
conducted with 725 children. The survey instrument consisted of a set of
sociodemographic questions plus the questionnaire of the International Study of
Asthma and Allergies in Childhood. RESULTS: The mean (SD) age of the children
studied was 8.94 (5.16) years. The prevalence of ever having allergic eczema was 
4.7% whereas that of current allergic eczema was 3.2%. Current allergic rhinitis 
and allergic conjunctivitis were present in 14.5% and 13%, respectively. Asthma
was reported in 14.7% of the children older than 3 years of age while the
prevalence of physician-diagnosed asthma was 7.9%. The burden of allergy was
27.1%. The prevalence of concomitant eczema and rhinitis was 1.9%. Among children
aged between 3 and 17 years, 1.5% and 4.7% had asthma along with eczema and
rhinitis respectively. Asthma was significantly more common in children with
rhinitis (31.5% vs 11.8%; P < .01; odds ratio [OR], 3.45). Asthma was diagnosed
in 28.1% of children with eczema and 14% of children without eczema (P = .03; OR,
2.41). CONCLUSIONS: Atopic diseases seem to significantly increase the risk of
developing another atopic disease with ORs that range from 2.4 to 3.4.

PMID: 18361099 [PubMed - indexed for MEDLINE]

133: Clin Exp Allergy. 2008 Jun;38(6):968-76. Epub 2008 Mar 18.

Birth order, atopy, and symptoms of allergy and asthma among inner-city children 
attending Head Start in New York City.

Perzanowski MS, Canfield SM, Chew GL, Mellins RB, Hoepner LA, Jacobson JS,
Goldstein IF.

Department of Environmental Health Sciences, Mailman School of Public Health,
Columbia University, New York, NY 10032, USA. mp2217@columbia.edu

BACKGROUND: In past research, children with older siblings were more likely than 
others to wheeze at age 2 years, but less likely by age 6 years. Higher infection
transmission and a down-regulated allergic immune response as a result of these
infections, respectively, were suggested as the causes. However, in a study of
children aged 0-3 years in a low-income urban community in New York City, USA,
with high asthma prevalence, we observed no birth-order effect. OBJECTIVE: To
evaluate the association between birth order and atopy and respiratory symptoms
in 4-year-old children attending Head Start programs in NYC. METHODS: Respiratory
symptoms were assessed by questionnaire for 1005 children (mean age 4.0 years)
living in high asthma prevalence neighbourhoods. Serum was collected from a
subgroup of the children (n=494) and specific IgE responses to dust mite,
cockroach, mouse, and cat allergens were measured. RESULTS: Prevalence of
specific IgE (> or =0.35 IU/mL) did not differ significantly among first (35%),
second (35%), and later-born children (28%) (P=0.23). Increasing birth order was 
associated with increasing prevalence of respiratory symptoms in the prior year, 
including wheeze (first 20%, second 27%, third or later 35%; P<0.001), being
awakened at night by cough (28%, 33%, 38%; P=0.005), emergency department visits 
(14%, 17%, 21%; P=0.02) and hospitalizations for difficulty breathing (6.1%,
6.6%, 10%; P=0.04). The associations of birth order with respiratory symptoms
were statistically significant only for the non-seroatopic children and those
without an asthmatic parent. CONCLUSIONS: Non-seroatopic children with older
siblings were more likely than those without older siblings to have respiratory
symptoms at age 4 years. Although the stability of these associations over time
remains to be determined, the differences in findings between this study and our 
previous NYC birth cohort study suggest that patterns of asthma development may
vary even among low-income populations within the same city.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18355370 [PubMed - indexed for MEDLINE]

134: Can Respir J. 2008 Mar;15(2):91-8.

The link between allergic rhinitis and asthma: a role for antileukotrienes?

[Article in English, French]

Kim H, Bouchard J, Renzi PM.

McMaster University, Hamilton, Canada.

Allergic rhinitis and asthma are both chronic heterogeneous disorders, with an
overlapping epidemiology of prevalence, health care costs and social costs in
quality of life. Both are inflammatory disorders with a similar pathophysiology, 
and both share some treatment approaches. However, each disorder has an array of 
treatments used separately in controlling these atopic disorders, from inhaled
corticosteroids, beta(2)-agonists and antihistamines to newer monoclonal
antibody-based treatments. The present article reviews the shared components of
allergic rhinitis and asthma, and examines recent evidence supporting
antileukotrienes as effective agents in reducing the symptoms of both diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18354749 [PubMed - indexed for MEDLINE]

135: Allergol Int. 2008 Jun;57(2):157-64.

IgE profiles of Bermuda grass pollen sensitised patients evaluated by Phleum
pratense allergens Phl P 1, 2, 4, 5, 6 , 7, 11, 12.

Rossi RE, Monasterolo G, Prina P, Coco G, Operti D, Rossi L.

Allergy Unit, National Health Service, Rete di Allergologia, Regione Piemonte,
Ospedali di Fossano e Savigliano, Cuneo, Italy. immunoway@tin.it

BACKGROUND: Despite the difference in geographical dominance of certain grasses, 
a high degree of allergenic similarity or cross-reactivity between Bermuda grass 
pollen (BGP) and timothy grass pollen (TGP) has been previously demonstrated. The
aim of the present study was to ascertain the sensitisation to TGP in 411
patients known for their reactivity to BGP extracts by analysing their reactivity
to crude timothy pollen extract and timothy pollen purified allergens,
establishing their specific IgE-profiles. METHODS: Using the immunoenzymatic CAP 
method we evaluated IgE-specific antibodies for BGP- and TGP- extracts and the
timothy recombinant (r) and natural (n) allergens rPhl p 1, rPhl p 2, nPhl p 4,
rPhl p 5, rPhl p 6, rPhl p 7, rPhl p 11, and rPhl p 12. RESULTS: BGP-IgE positive
patients (median = 8.0 kUA/l, 2.8-22.2 kUA/l 25th-75th percentile) simultaneously
had IgE positive results for TGP (100% of subjects)(median = 48.9 kUA/l, 19.8- > 
100 kUA/l 25th-75th percentile) and high prevalence of sensitization to 6/8
Phleum pratense allergens (Phl p 1, 2, 4, 5, 6, 11, markers of genuine
sensitisation to TGP) other than profilin and calcium binding protein. More than 
72% of BGP allergic patients were co-sensitised to rPhl p 1, rPhl p 2, nPhl p 4, 
rPhl p 5, rPhl p 6. A decrease of total and specific IgE with patients' age was
observed. CONCLUSIONS: Our data show that all BGP-allergic patients
simultaneously exhibit higher IgE antibody levels to recombinant and natural P.
pratense allergens as well as to crude TGP extract. This suggests that when
choosing an immunotherapeutic regimen for BGP-sensitised patients (after
establishing their IgE profile via purified TGP-allergens), subcutaneous or
sublingual TGP-extract vaccines in appropriate doses, in order to influence T
epitope specificity, might be beneficial. Though extremely uncommon, in cases
where a patient is exclusively BGP allergen-sensitised, BGP-extract therapy is
the appropriate therapeutic response.

PMID: 18349590 [PubMed - indexed for MEDLINE]

136: Allergol Int. 2008 Jun;57(2):147-55.

Enhanced production of IgE anti-Japanese cedar pollen specific antibodies by
peripheral blood B cells from patients with Japanese cedar pollinosis.

Ohshima N, Hirohata S.

Department of Respiratory Medicine, National Hospital Organization, Tokyo
National Hospital, Tokyo, Japan.

BACKGROUND: IgE antibodies against Japanese cedar pollen (JCP) play an important 
role for the pathogenesis of the cedar pollinosis, but the mechanism of their
production has been unclear. We explored the capacity of peripheral blood B cells
from pollinosis patients to produce anti-JCP specific IgE. METHODS: Peripheral
blood B cells from 16 pollinosis patients and 9 normal subjects were cultured
with mitomycin-C treated T cells with immobilized anti-CD3 for 10 days. RESULTS: 
B cells from pollinosis patients produced higher amounts of anti-JCP specific IgE
than those from normal subjects upon stimulation with immobilized anti-CD3
activated autologous T cell, whereas the production of anti-JCP specific IgM were
comparable between normal subjects and patients. Exogenous IL-4/IL-5 or anti-CD3 
stimulated patients' T cells could not induce the production of anti-JCP specific
IgE from normal B cells. CONCLUSIONS: These results indicate that B cells from
normal individuals contain comparable numbers of precursors that are committed to
produce anti-JCP specific IgM to patients' B cells. Moreover, the data confirm
that the class switching of IgM to IgE within anti-JCP specific B cells
contributes to development of Japanese cedar pollinosis.

PMID: 18349589 [PubMed - indexed for MEDLINE]

137: Expert Opin Ther Targets. 2008 Apr;12(4):415-23.

Cysteinyl leukotriene receptor CysLT1 as a novel therapeutic target for allergic 
rhinitis treatment.

Shirasaki H.

Sapporo Medical University, Department of Otolaryngology, S-1 W-16, Chuo-ku,
Sapporo, 060-8543, Japan. shira@sapmed.ac.jp

Background: Cysteinyl leukotrienes (cys-LTs) play an important role in allergic
rhinitis because CysLT(1) receptor antagonists relieve the symptoms of allergic
rhinitis. Objective: I overview the clinical pharmacology of CysLT(1) receptor
antagonists and their potential role in patients with allergic rhinitis. Methods:
I review the evidence regarding the release of cys-LTs and localization of
CysLT(1) receptor on nasal mucosa, and evaluate the clinical efficacy of CysLT(1)
receptor antagonist in allergic rhinitis. Results/conclusion: Immunohistochemical
studies show that in allergic rhinitis, the major target of CysLT(1) receptor
antagonists are the vascular bed and infiltrated leukocytes such as mast cells,
eosinophils and macrophages. CysLT(1) receptor antagonists provide a new
opportunity for simultaneous management of allergic diseases of the upper and
lower respiratory tract.

Publication Types: 
    Review

PMID: 18348678 [PubMed - indexed for MEDLINE]

138: Clin Drug Investig. 2008;28(4):221-30.

Non-interventional study comparing treatment satisfaction in patients treated
with antihistamines.

De Vos C, Mitchev K, Pinelli ME, Derde MP, Boev R.

UCB SA, Brussels, Belgium. christine.devos@ucb-group.com

BACKGROUND AND OBJECTIVE: Allergic rhinitis and urticaria are common allergic
disorders that may affect approximately 15% of people at some time in their
lives. Antihistamines are the most widely used therapeutic interventions for
these disorders but the newer generation agents have differing pharmacokinetic
characteristics that may result in different patient satisfaction and
preferences. The objective of this study was to investigate patients' and
physicians' satisfaction with their current antihistamine treatment for allergic 
disease. METHODS: In an observational study, physicians in nine European
countries completed questionnaires evaluating 7,274 patients treated with an oral
antihistamine. The satisfaction of patients and physicians with the efficacy and 
tolerability of treatment was rated on a visual analogue scale. In addition, the 
proportion of patients satisfied with treatment (overall satisfaction) and
willing to continue treatment with the same antihistamine were assessed. Safety
and tolerability data were also gathered. RESULTS: The results of this study
indicate that modern antihistamines are generally considered effective and well
tolerated by patients. In general, levocetirizine scored significantly higher in 
terms of perception of efficacy, tolerability and overall satisfaction. In terms 
of tolerability, three-quarters of patients were 'very satisfied' and a further
fifth were moderately satisfied with levocetirizine and almost all (95%) were
happy to continue treatment. Overall, the most commonly reported adverse event in
this study was somnolence, a well known effect of antihistamines. The rate of
somnolence in the levocetirizine group (3.8%) was similar to that for
fexofenadine (both doses) and desloratadine, two products which are considered to
be nonsedating antihistamines, and significantly less than half the rate for
cetirizine. CONCLUSION: Levocetirizine is considered an effective and well
tolerated option for treating allergic disease by patients and physicians alike, 
particularly when the best available effectiveness and tolerability are required.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18345712 [PubMed - indexed for MEDLINE]

139: Clin Physiol Funct Imaging. 2008 Jul;28(4):240-50. Epub 2008 Jul 1.

Specific nasal symptoms and symptom-provoking factors may predict increased risk 
of developing COPD.

Nihlén U, Montnémery P, Andersson M, Persson CG, Nyberg P, Löfdahl CG, Greiff L.

Respiratory Medicine & Allergology, Lund University Hospital, Lund, Sweden.
ulf.nihlen@med.lu.se

In a 1992 questionnaire study, we found that certain nasal symptoms and
symptom-provoking factors were associated with prevalence of self-reported
chronic bronchitis/emphysema (CBE). In this follow-up study, we examined whether 
any nasal features could predict an increased incidence of self-reported
physician's diagnosis of CBE/chronic obstructive pulmonary disease (COPD). In
2000, a survey was performed similar to the one in 1992. Of a paired follow-up
group of 4933 participants aged 28-67 years, 4280 (86.8%) returned the
questionnaire. Odds ratios (ORs) for cumulative incidence (between 1992 and 2000)
of self-reported physician-diagnosed CBE/COPD and asthma, respectively, were
calculated by logistic regression with adjustment for age, gender and smoking
habits. Reports of thick, yellow nasal discharge and nasal blockage in 1992
predicted incidence of CBE/COPD: OR 2.3 (1.2-4.2) and 1.8 (1.1-2.8) respectively.
Moreover, nasal symptoms provoked by exposure to damp/cold air and tobacco smoke 
predicted CBE/COPD: OR 3.4 (1.9-6.0) and 2.5 (1.4-4.2). Nasal itching and nasal
symptoms provoked by exposure to grass pollen and furred animals predicted
incidence of asthma. These results suggest that certain nasal symptoms and nasal 
symptom-provoking exposures, different from those commonly associated with
asthma, may predict increased risk of developing CBE/COPD. This supports the
possibility of nasal co-morbidity in COPD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18331572 [PubMed - indexed for MEDLINE]

140: Allergy. 2008 Jun;63(6):695-702. Epub 2008 Mar 5.

A high-affinity monoclonal anti-IgE antibody for depletion of IgE and IgE-bearing
cells.

Laffer S, Lupinek C, Rauter I, Kneidinger M, Drescher A, Jordan JH, Krauth MT,
Valent P, Kricek F, Spitzauer S, Englund H, Valenta R.

Division of Immunopathology, Department of Pathophysiology, Center for Physiology
and Pathophysiology, Medical University of Vienna, Vienna, Austria.

BACKGROUND: We have identified a monoclonal anti-human immunoglobulin E (IgE)
antibody, which recognizes FcepsilonRI-bound IgE and prevents binding of IgE to
FcepsilonRI. In this study, we assessed the binding kinetics and affinity of
monoclonal antibody 12 (mAb12) for IgE and investigated whether mAb12 can be used
for depletion of IgE and isolation of IgE-bearing cells from peripheral blood.
METHODS: Binding kinetics and affinity for IgE were studied using Biacore surface
plasmon resonance technique experiments. IgE antibodies were depleted from serum 
using sepharose-coupled mAb12 and IgE-bearing cells were enriched from
heparinized blood samples with mAb12. The extent and biological relevance of IgE 
depletion were studied by quantitative IgE measurements and basophil histamine
release experiments. Specific binding of mAb12 to IgE-bearing cells (basophils,
mast cells, IgE-secreting plasma cells) was demonstrated by FACS. RESULTS:
Monoclonal antibody 12 shows rapid association (k(a) = 5.46e5/Ms) with IgE,
almost no dissociation (k(d) = 8.8e-5/s) and an affinity for IgE (K(D) = 1.61e-10
M), which is as high as that of FcepsilonRI. Immobilized mAb12 could be used to
deplete IgE antibodies and isolate IgE-bearing cells from peripheral blood in a
single-step procedure. CONCLUSIONS: Monoclonal antibody 12 is a high affinity
anti-human IgE antibody, which efficiently removes IgE and IgE-bearing cells from
peripheral blood and may thus be used for extracorporeal depletion of IgE and
IgE-bearing cells.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18325077 [PubMed - indexed for MEDLINE]

141: Clin Exp Allergy. 2008 May;38(5):761-6. Epub 2008 Feb 25.

Allergic rhinitis in children with asthma: a questionnaire-based study.

Hamouda S, Karila C, Connault T, Scheinmann P, de Blic J.

Université Paris Descartes, Assistance Publique des hôpitaux de Paris, Hôpital
Necker Enfants Malades, Service de Pneumologie et d'Allergologie Pédiatriques,
Paris, France.

BACKGROUND: Allergic rhinitis (AR) and asthma frequently coexist but has rarely
been evaluated in children. OBJECTIVE: This prospective study aimed to estimate
the prevalence of AR in asthmatic children, and ascertain whether AR is a risk
factor for the severity of asthma. METHODS: The questionnaire, modified from the 
adult form of the score for allergic rhinitis (SFAR), was completed by 404
asthmatic children aged 3-18 years seen in the outpatient clinic between June
2005 and July 2007. Each item was assigned a number of points with a final score 
ranging from 0 to 17. AR and asthma were classified according to ARIA and GINA
2004 recommendations, respectively. RESULTS: AR was diagnosed in 237 patients
(58.7%). It was intermittent in 57.8% of the patients and persistent in 42.2%. A 
total score >or=9 was discriminant for AR (sensitivity=91.1%, specificity=95.2%, 
positive predictive value=96.4%, negative predictive value=88.3%, Youden's
Index=0.86). The proportion of children having mild or moderate-to-severe asthma 
was independent of the presence of AR, 61.6% of moderate-to-severe asthmatic
children and 55.4% of intermittent and mild asthmatic children having AR.
CONCLUSION: AR and asthma are frequently associated (58.7%). The SFAR adapted for
children seems to be a simple and a reliable tool to detect AR in asthmatic
children.

PMID: 18307526 [PubMed - indexed for MEDLINE]

142: Allergy Asthma Proc. 2008 Jan-Feb;29(1):24-8.

Elucidating the mechanism underlying the ocular symptoms associated with allergic
rhinitis.

Naclerio RM, Pinto J, deTineo M, Baroody FM.

Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, The
University of Chicago, Chicago, Ilinois 60637, USA.
rnacleri@surgery.bsd.uchicago.edu

Ocular symptoms occur in approximately 40% of patients with allergic rhinitis.
The purpose of this study was to determine whether nasal challenge with antigen
induces a nasal-ocular reflex. We performed a double-blind crossover trial in 20 
subjects. A nasal challenge with antigen was performed in one nostril, and the
response was assessed in both nostrils and both eyes. Subjects were treated
before challenge with either placebo or azelastine, an H(1)-antihistamine. Nasal 
challenge with antigen led to a nasonasal reflex and a nasal-ocular reflex as
manifested by an increase in symptoms and secretion weights. Treatment with
azelastine reduced both reflexes. A nasal-ocular reflex follows nasal challenge
with antigen and probably contributes to the ocular symptoms associated with
allergic rhinitis.

Publication Types: 
    Randomized Controlled Trial

PMID: 18302834 [PubMed - indexed for MEDLINE]

143: Allergy Asthma Proc. 2008 Jan-Feb;29(1):14-23.

Pediatric allergic rhinitis: current and future state of the art.

Carr WW.

Allergy and Asthma Associates of Southern California, Viejo, California 92691,
USA. warnercarr@hotmail.com

Allergic rhinitis (AR) is the most common cause of allergic disease in the
pediatric population. This chronic condition impacts quality of life, exacerbates
comorbid conditions, and results in a significant economic burden. With an
accurate diagnosis, there are many available therapies to reduce the burden of
AR. Options include allergen avoidance, pharmacotherapy, and immune modulation.
This review provides a comprehensive discussion of the current and future state
of the art in the treatment of pediatric AR.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18302833 [PubMed - indexed for MEDLINE]

144: Allergy Asthma Proc. 2008 Jan-Feb;29(1):7-13.

Antihistamines in the pediatric population: achieving optimal outcomes when
treating seasonal allergic rhinitis and chronic urticaria.

Schad CA, Skoner DP.

Division of Allergy, Asthma and Immunology, Department of Pediatrics, Allegheny
General Hospital, Pittsburgh, PA 15212, USA.

Antihistamines are used frequently in adult and pediatric patients as first-line 
treatment for both allergic rhinitis and urticaria. There are several different
antihistamines on the market, generally divided into first- and second-generation
products. Although many of these show efficacy, there are significant differences
in the side effect profiles of these medications, with resultant differences in
their effect on quality of life and other outcomes. Although the most significant
differences are between generations, there are considerations even within
generations, especially regarding sedation and possible effects on learning.
Other than specific situations in which sedation may be a desired effect, the
second-generation antihistamines generally are preferred and the risks and
benefits of individual drugs within this group need to be considered for each
patient's specific circumstances.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18302832 [PubMed - indexed for MEDLINE]

145: Allergy Asthma Proc. 2008 Jan-Feb;29(1):1-6.

Pediatric allergic rhinitis: physical and mental complications.

Blaiss MS.

Department of Pediatrics, University of Tennessee Health Science Center, Memphis,
Tennessee, USA. wheezemd@gmail.com

Allergic rhinitis (AR) affects up to 40% of children in the United States and its
prevalence continues to increase. Most AR develops during the pediatric years and
it is the most common chronic allergic disorder seen in children. It is important
to note that AR is more than just sneezing and a nuisance for the children. There
are numerous complications that can lead to significant problems both physically 
and mentally in the child who suffers with AR. Under physical complications,
otitis media with effusion, recurrent and/or chronic sinusitis, asthma, and
snoring impact children with AR. Sleep disturbances, poor school performance, and
hyperactivity are all mental complications seen in many children related to their
nasal allergies. It is important for the clinician to take AR in the child
seriously to prevent or control complications that can have a detrimental effect 
on the child.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18302831 [PubMed - indexed for MEDLINE]

146: Clin Exp Allergy. 2008 Jul;38(7):1179-85. Epub 2008 Feb 20.

Comment in:
    Clin Exp Allergy. 2008 Jul;38(7):1071-3.

Alcohol consumption and the risk of self-reported perennial and seasonal allergic
rhinitis in young adult women in a population-based cohort study.

Bendtsen P, Grønbaek M, Kjaer SK, Munk C, Linneberg A, Tolstrup JS.

Centre for Alcohol Research, National Institute of Public Health, Øster
Farimagsgade Copenhagen, University of Southern Denmark, Denmark.

BACKGROUND: Alcohol consumption has been suggested to be associated with the
development of allergic rhinitis (AR), but there is limited data on the topic.
OBJECTIVES: The objective of this study was to investigate the association
between alcohol consumption and the risk of developing AR among young women.
METHODS: Five thousand eight hundred and seventy Danish women aged 20-29 years
participated in a prospective cohort study, and were free of seasonal and
perennial AR at baseline (1991-1993). Alcohol consumption was assessed by a food 
frequency questionnaire. The main outcome measures were self-reported information
on seasonal and perennial AR debuting during a mean follow-up period of 7.8
years. RESULTS: During follow-up, 831 women developed seasonal AR and 523 women
developed perennial AR, corresponding to 14% and 9%. Alcohol consumption was
positively associated with the risk of developing perennial AR. The adjusted odds
ratio (OR) for perennial AR was 1.78 (95% CI, 1.13-2.80) among women drinking
more than 14 drinks/week compared with women drinking <1 drink/week. There was no
association between alcohol consumption and seasonal AR. Having one or two
parents with asthma was, after adjustment, significantly associated with the risk
of developing seasonal (OR, 2.01; 95% CI, 1.65-2.45) and perennial AR (OR, 2.28; 
95% CI, 1.70-2.74). Smoking was not associated with an increased risk of
developing AR. CONCLUSION: In this population of young adult women, alcohol
consumption was associated with an increased risk of developing perennial AR.

PMID: 18294256 [PubMed - indexed for MEDLINE]

147: J Laryngol Otol. 2008 Jul;122(7):700-6. Epub 2008 Feb 19.

Expression of substance P, vasoactive intestinal peptide and heat shock protein
70 in nasal mucosal smears of patients with allergic rhinitis: investigation
using a liquid-based method.

Chalastras T, Nicolopoulou-Stamati P, Patsouris E, Eleftheriadou A, Kandiloros D,
Yiotakis I, Gonidi M, Athanassiadou P.

Department of Pathology Medical School, University of Athens, Athens, Greece.
chalastras@hotmail.com

OBJECTIVE: The aim of this study was to investigate expression of the
neuropeptides substance P, vasoactive intestinal peptide and heat shock protein
70 in the nasal mucosa cells of patients with seasonal allergic rhinitis, in
order to obtain more information on the pathophysiological and immunological role
of these markers in allergic rhinitis. MATERIAL AND METHODS: Nasal epithelium
specimens obtained from 42 patients with allergic rhinitis were studied, using
Shandon's Papspin liquid-based cytology method. Smears were immunostained with
antibodies against substance P, vasoactive intestinal peptide and heat shock
protein 70, and the results were correlated with the clinical features of
seasonal allergic rhinitis. RESULTS: A positive reaction for substance P,
vasoactive intestinal peptide and heat shock protein 70 was observed in 73.8,
66.7 and 69.0 per cent of the allergic rhinitis mucosal smears, respectively. The
Pearson chi-square test showed that 40.5 per cent of the immunostained smears had
a positive reaction for one or two of the markers studied (i.e. substance P,
vasoactive intestinal peptide or heat shock protein 70), and that 47.6 per cent
of the smears had a positive reaction for all the markers (p < 0.0001).
CONCLUSIONS: We found a high level of expression of substance P and vasoactive
intestinal peptide in the nasal mucosa smears of patients suffering from allergic
rhinitis. This indicates a role for these neuropeptides in the neuroregulation of
immunity and hypersensivity in this disease. Furthermore, expression of heat
shock protein 70 may contribute to the development of allergic rhinitis.

PMID: 18282334 [PubMed - indexed for MEDLINE]

148: Allergy. 2008 Mar;63(3):274-83.

Comment in:
    Allergy. 2008 May;63(5):506-8.

Infections presenting for clinical care in early life and later risk of hay fever
in two UK birth cohorts.

Bremner SA, Carey IM, DeWilde S, Richards N, Maier WC, Hilton SR, Strachan DP,
Cook DG.

Division of Community Health Sciences, St George's, University of London, London,
UK.

BACKGROUND: The 'hygiene hypothesis' proposes that infections in infancy protect 
against hay fever (HF). We investigated infections during infancy in relation to 
HF, including rarer ones not previously researched in this context, while
examining the role of potential confounding variables. METHODS: From birth
cohorts derived within the General Practice Research Database (GPRD) and Doctors 
Independent Network (DIN) database of computerized patient records from UK
general practice, we selected 3549 case-control pairs, matched for practice, age,
sex and control follow-up to case diagnosis. Conditional logistic regressions
were fitted for each of 30 infections; behavioural problems (BP) acted as a
control condition unrelated to HF. Odds ratios (OR), adjusted for consultation
frequency were pooled across the databases using fixed effect models. We also
adjusted for sibship size in GPRD and a socioeconomic marker in DIN. RESULTS:
Upper respiratory tract infections, diarrhoea and vomiting and acute otitis media
in infancy were each related with a moderately increased risk of HF in both
databases, as were BP. These associations were lost on adjustment for
consultation frequency. Only bronchiolitis was significantly associated with a
reduced pooled risk of HF after adjustment for consultations (OR = 0.8).
Adjustment for sibship size in GPRD and a socioeconomic marker in DIN had little 
impact on the OR. CONCLUSIONS: Of 30 infectious illnesses investigated, none had 
strong or consistent associations with HF after adjustment for consultation
frequency. Except for bronchiolitis, possibly a chance finding, none of the
clinically apparent infections considered appear to have an important role in
allergy prevention.

PMID: 18269673 [PubMed - indexed for MEDLINE]

149: Allergy. 2008 Apr;63(4):468-75. Epub 2008 Feb 11.

Modulation of neurotrophin and neurotrophin receptor expression in nasal mucosa
after nasal allergen provocation in allergic rhinitis.

Raap U, Fokkens W, Bruder M, Hoogsteden H, Kapp A, Braunstahl GJ.

Department of Dermatology and Allergology, Hannover Medical University, Hannover,
Germany.

BACKGROUND: Patients with allergic rhinitis (AR) feature both allergic airway
inflammation and a hyperresponsiveness to nonspecific stimuli which is partly
neuronally controlled. Still, it is unclear whether or not neurotrophins are
involved in airway pathophysiology of AR and in nasobronchial interaction.
METHODS: Nine AR patients with mono-allergy to grass pollen and nine healthy
controls underwent nasal allergen provocation (NP). Serum samples, nasal and
bronchial biopsies were taken before (T(0)) and 24 h after (T(24)) NP.
Pan-neurotrophin receptor p75(NTR), tyrosine kinase A (trkA), trkB, nerve growth 
factor (NGF), and brain-derived neurotrophic factor (BDNF) were assessed with
immunohistochemistry, and NGF and BDNF levels with ELISA. RESULTS: At T(24), BDNF
and NGF were upregulated in nasal mucosa (P < 0.05) and increased in the
peripheral blood of AR compared with T(0). The increase in nasal BDNF expression 
correlated positively with the maximum increase in total nasal symptom score in
AR (P = 0.02). p75(NTR) was expressed on peripheral nerves and epithelial layer, 
trkA on endothelial cells, and trkB on mast cells. trkB + mast cells
significantly decreased after NP in AR (P < 0.01). NP did not modulate p75(NTR)
and trkA expression in nasal mucosa and had no effect on the expression of
neurotrophins and receptors in bronchial mucosa. CONCLUSION: This study shows
that neurotrophins and their receptors are expressed in human airways. Allergic
rhinitis was characterized by a modulation of BDNF, NGF, and trkB in nasal mucosa
after NP and a correlation of nasal BDNF with the maximal increase of total nasal
symptom score. Therefore, our data suggest that neurotrophins participate in
upper-airway pathophysiology in AR, whereas their role in nasobronchial
interaction remains unclear.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18266897 [PubMed - indexed for MEDLINE]

150: Allergol Immunopathol (Madr). 2008 Jan-Feb;36(1):26-30.

Improving pollen immunotherapy: minor allergens and panallergens.

Moreno-Aguilar C.

Allergy Section, Reina Sofía Hospital, Córdoba, Spain.
cmoreno@sofia.hrs.sas.cica.es

Multiple sensitizations to pollens are common clinical situations in Spain, and
alter the efficacy of allergen-specific immunotherapy. We now know that
optimization of the diagnosis is required to define the best suited treatment for
each patient. All pollen allergens belong to 29 families of proteins - the most
abundant being the expansins, prophyllins and polcalcins. The ubiquitous nature
of proteins such as the prophyllins and polcalcins defines them as panallergens, 
and explains the cross-reactivity that is erroneously interpreted by clinicians
as constituting multi-sensitization. Other families of allergens, such as the
calcium transporting proteins (LTPs) are more restricted, but are associated to
severe types of allergic disease - this being particularly useful to decide upon 
the indication of immunotherapy. Although recombinant allergens can be produced
for in vitro diagnostic purposes, current legislation only allows the use of
natural proteins for immunotherapy. However, the same technology can be applied
to the study of extracts for vaccines, and it seems that allergen quantification 
by the manufacturers is a no return trip which clinicians are obliged to follow.

Publication Types: 
    Review

PMID: 18261430 [PubMed - indexed for MEDLINE]

151: Allergol Immunopathol (Madr). 2008 Jan-Feb;36(1):9-16.

Sensitisation to aeroallergens in Brazilian adolescents living at the periphery
of large subtropical urban centres.

Pastorino AC, Kuschnir FC, Arruda LK, Casagrande RR, de Souza RG, Dias GA,
Silveira HH, da Cunha AJ, Jacob CM, Solé D.

Department of Paediatrics, Children's Institute, São Paulo University School of
Medicine, São Paulo, Brazil. antoniocp@icr.hcnet.usp.br

OBJECTIVES: To evaluate the sensitization to aeroallergens determined by skin
prick test (SPT) in Brazilian adolescents, and to correlate its positivity with
the diagnosis of asthma and/or rhinitis based on the written questionnaire (WQ)
of ISAAC phase III study. PATIENTS AND METHODS: A total of 996 adolescents (387
boys) were selected by systematic samples. A standard allergen extracts panel
(positive/negative control, D pteronyssinus [Dpt], P americana [Pa], B germanica 
[Bg], dog, cat, fungal and grass mix) was used and its positivity compared with
positive responses to asthma, rhinitis or both. RESULTS: Positive SPT to at least
one allergen was observed in 466 adolescents (46.8 %), with sensitisation to Dpt 
in 79.1 %. Positivity to more than one allergen occurred in 232 students (49.8
%). The frequency of positive SPTs was significantly higher among adolescents
with asthma (OR = 2.16), rhinitis (OR = 1.69), and asthma and rhinitis (OR =
2.03). Positive SPT to four or more allergens were higher among asthmatics (OR = 
2.6) and among adolescents with asthma and rhinitis (OR = 3). CONCLUSIONS: A high
sensitisation rate to aeroallergens was observed, significantly higher among
those with asthma, rhinitis or a combination of both, especially in multiple
sensitisations.

Publication Types: 
    Multicenter Study

PMID: 18261427 [PubMed - indexed for MEDLINE]

152: J Asthma. 2008 Jan-Feb;45(1):73-8.

Childhood environment and atopic conditions, with emphasis on asthma in a Chilean
agricultural area.

Vargas C, Bustos P, Diaz PV, Amigo H, Rona RJ.

Department of Nutrition, Faculty of Medicine, University of Chile, Chile.

BACKGROUND: An explanation of the etiology of atopic conditions based on the
hygiene hypothesis remains controversial. OBJECTIVE: To analyze exposure
variables in childhood to assess their impact on hay fever, asthma, and
sensitization. METHODS: Data were collected on 1,232 young Chilean adults born
between 1974 and 1978. Information was available on consultations for infections 
early in life, number of siblings, sharing a bedroom, nursery school attendance, 
and contact with animals in the first 5 years of life. Information on asthma
symptoms and rhinitis were obtained from a standardized questionnaire.
Sensitization to eight allergens and bronchial hyper responsiveness (BHR) to
methacholine were assessed. The study design was non-concurrent longitudinal for 
infectious episodes and nutritional status in the first year and cross-sectional 
for the other outcomes. RESULTS: Number of siblings was associated with
sensitization only (p = 0.0048). Nursery school attendance was negatively
associated with positive BHR (odds ratio (OR) 0.54, 95% CI 0.30-0.95). A severe
respiratory infection early in life was protective of sensitization and wheeze
combined (OR 0.29, 95%CI 0.12-0.74). Contact with dogs in the first year was a
protective factor of rhinitis (OR 0.47, 95%CI 0.28-0.80), but contact with
poultry and cats early in life increased the risk of rhinitis (OR 1.42, 95%CI
1.06-1.88; 1.82, 95%CI 1.06-3.14). CONCLUSION: The pattern of associations
between environmental exposure in early life and atopic conditions was
inconsistent. The significant associations were evenly distributed as protective 
and risk factors of atopic conditions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18259999 [PubMed - indexed for MEDLINE]

153: Curr Med Res Opin. 2008 Mar;24(3):821-36. Epub 2008 Feb 6.

Evolving paradigm in the management of allergic rhinitis-associated ocular
symptoms: role of intranasal corticosteroids.

Blaiss MS.

University of Tennessee Health Sciences Center, Germantown, TN 38138, USA.
mblaiss@allergymemphis.com

BACKGROUND: Along with nasal symptoms, ocular symptoms such as itching, tearing, 
and redness are common, bothersome components of the allergic rhinitis (AR)
profile. Treatment of the patient with ocular allergy symptoms should take into
account a variety of factors, including severity of symptoms,
convenience/compliance issues, and patient preferences. OBJECTIVES: To review
from the primary care perspective the epidemiology, pathophysiology, and
management of ocular symptoms associated with AR, and to evaluate the emerging
role of intranasal corticosteroids (INSs). FINDINGS: A search of the PubMed
database identified clinical trials that assessed efficacy of agents in reducing 
ocular allergy symptoms. Internet searches identified further information
including data on over-the-counter agents for treatment of ocular symptoms.
Searches were conducted using search terms such as pathophysiology, epidemiology,
ocular allergy, quality of life, drug class, and drug names. Primary care
physicians are often the first point of contact for patients with seasonal AR
(SAR) or perennial AR (PAR) symptoms. Ocular allergy associated with SAR and PAR 
(seasonal and perennial allergic conjunctivitis, respectively) is characterized
by both early- and late-phase reactions, with symptoms often persisting long
after allergen exposure. Non-pharmacologic measures such as allergen avoidance,
use of artificial tears, and cool compresses are pertinent for all ocular allergy
sufferers, but may not afford adequate symptom control. Pharmacotherapy options
have traditionally included topical ophthalmic products for cases of isolated
ocular symptoms, and oral antihistamines for patients with both nasal and ocular 
symptoms. However, this paradigm is changing with new evidence regarding the
efficacy of INSs in reducing ocular symptoms. A number of meta-analyses and
individual studies, most of which studied ocular symptoms as secondary variables,
have demonstrated the ocular effects of INSs versus topical and oral
antihistamines. Additional prospective studies on this topic are encouraged to
provide further evidence for these findings. CONCLUSIONS: In light of their
well-established efficacy in reducing nasal allergy symptoms, INSs offer a
comprehensive treatment option in patients with nasal and ocular symptoms. Oral
antihistamines and/or topical eye drops may also be necessary depending on
symptom control.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18257976 [PubMed - indexed for MEDLINE]

154: Eur J Clin Invest. 2008 Mar;38(3):197-200.

Validation study of nasal nitric oxide measurements using a hand-held
electrochemical analyser.

Maniscalco M, de Laurentiis G, Weitzberg E, Lundberg JO, Sofia M.

Section of Respiratory Medicine, Hospital S. Maria della Pietà Casoria Naples,
Italy. mauromaniscalco@hotmail.com

BACKGROUND: Exhaled nitric oxide (NO) measurement is a simple and non-invasive
method for monitoring airway inflammation. Similarly, nasal NO has been proposed 
as a surrogate marker in inflammatory diseases of the upper airways, e.g.
allergic rhinitis. A new portable analyser using an electrochemical sensor has
been developed for measurements of exhaled NO, and its reproducibility and
comparison with other analysers has been tested recently in healthy subjects and 
in patients with lower airways disease. The application of this hand-held
analyser in nasal NO analysis was tested and compared to the gold standard
represented by a chemiluminescence analyser. MATERIALS AND METHODS: Thirty
subjects including 15 patients with allergic rhinitis (AR) and 15 healthy
subjects (HS) were studied. The intraindividual variability, calculated as the
difference in nasal NO levels between two measurements from a single nasally
exhaled breath manoeuvre, and the comparison between the electrochemical analyser
(NIOX MINO, Aerocrine) and a chemiluminescence analyser (NOA, Sievers) were
performed. RESULTS: In AR patients mean nasal NO was 59.0 +/- 16.3 p.p.b. with
the MINO and 58.3 +/- 15.6 p.p.b. with the NOA. In HS nasal NO was 49.1 +/- 10.8 
p.p.b. with the MINO and 49.8 +/- 8.2 p.p.b. with the NOA. The Bland-Altman
analysis showed bias values of 0.005 +/- 3.6 with the 95% limits of agreement
from -6.97 to 6.98 p.p.b. CONCLUSION: Measurements of nasal NO levels with a
hand-held electrochemical analyser are reproducible and the results are
comparable to a stationary chemiluminescence analyser.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18257783 [PubMed - indexed for MEDLINE]

155: Drug Ther Bull. 2008 Feb;46(2):9-10.

Grazax for hay fever?

BMJ Group.

Over 1 in 5 adults in the UK are estimated to have allergic rhinitis and around
half of these people are allergic to grass pollen. Despite optimal use of
intranasal corticosteroids and oral antihistamines, some patients continue to
have troublesome symptoms. For example, in one general practice survey, 62% of
patients taking both these treatments described control of their symptoms as
partial or poor. UK professional guidelines recommend the use of allergen
injection immunotherapy in patients with IgE-mediated seasonal pollen-induced
rhinitis and/or conjunctivitis "whose symptoms respond inadequately to usual
therapy". Such intervention by subcutaneous injection aims to modify the
underlying cause of allergic rhinitis and can reduce symptoms, but may result in 
severe bronchospasm and anaphylaxis requiring resuscitation. Sublingual
immunotherapy has been proposed as an alternative to the subcutaneous route.
Grazax (ALK-Abelló) is the first product licensed in the UK for sublingual
immunotherapy. Here we consider its role in the management of patients with hay
fever.

PMID: 18256175 [PubMed - indexed for MEDLINE]

156: Ann Allergy Asthma Immunol. 2008 Jan;100(1):74-81.

Comment in:
    Ann Allergy Asthma Immunol. 2008 Jul;101(1):111.

Combination therapy with azelastine hydrochloride nasal spray and fluticasone
propionate nasal spray in the treatment of patients with seasonal allergic
rhinitis.

Ratner PH, Hampel F, Van Bavel J, Amar NJ, Daftary P, Wheeler W, Sacks H.

Sylvana Research, San Antonio, Texas, USA.

BACKGROUND: To our knowledge, there are no published studies that evaluated the
efficacy of azelastine hydrochloride nasal spray in combination with an
intranasal corticosteroid, although anecdotal reports of the use of these agents 
in combination are common. OBJECTIVE: To determine if greater efficacy could be
achieved with the intranasal antihistamine azelastine and the intranasal
corticosteroid fluticasone propionate used concurrently compared with the
efficacy of each agent alone. METHODS: This randomized, 2-week, multicenter,
double-blind trial was conducted during the Texas mountain cedar season. After a 
5-day placebo lead-in period, 151 patients with moderate to severe nasal symptoms
were randomized to treatment with the following: (1) azelastine nasal spray, 2
sprays per nostril twice daily; (2) fluticasone nasal spray, 2 sprays per nostril
once daily; or (3) azelastine nasal spray, 2 sprays per nostril twice daily, plus
fluticasone nasal spray, 2 sprays per nostril once daily. The primary efficacy
variable was the change from baseline in the total nasal symptom score (TNSS),
consisting of sneezing, itchy nose, runny nose, and nasal congestion. RESULTS:
All 3 groups had statistically significant (P < .001) improvements from their
baseline TNSS after 2 weeks of treatment. The TNSS improved 27.1% with
fluticasone nasal spray, 24.8% with azelastine nasal spray, and 37.9% with the 2 
agents in combination (P < .05 vs either agent alone). All 3 treatments were well
tolerated. CONCLUSIONS: The significant improvement in the TNSS with combination 
therapy relative to the individual agents alone is in contrast to previously
published studies that found no advantage with an oral antihistamine and an
intranasal corticosteroid in combination. Azelastine nasal spray and fluticasone 
nasal spray in combination may provide a substantial therapeutic benefit for
patients with seasonal allergic rhinitis compared with therapy with either agent 
alone.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18254486 [PubMed - indexed for MEDLINE]

157: Ann Allergy Asthma Immunol. 2008 Jan;100(1):59-65.

Comment in:
    Ann Allergy Asthma Immunol. 2008 Jul;101(1):110.

Atopic disease and exhaled nitric oxide in an unselected population of young
adults.

van Asch CJ, Balemans WA, Rovers MM, Schilder AG, van der Ent CK.

Department of Paediatric Respiratory Medicine, Wilhelmina Children's Hospital,
University Medical Centre, Utrecht, the Netherlands.

BACKGROUND: Several studies have reported elevated levels of fractional exhaled
nitric oxide (FeNO) in atopic patients, particularly in asthmatic patients,
suggesting that FeNO is a marker of bronchial inflammation. However, the
independent influence of different atopic entities (eczema, allergic rhinitis,
and asthma) on FeNO has never been studied in the general population. OBJECTIVE: 
To study the influence of a questionnaire-based diagnosis of atopic diseases and 
IgE and lung function measurements on FeNO levels. METHODS: This study was part
of a follow-up on otitis media of a birth cohort of 1,328 children born in
Nijmegen, the Netherlands, between September 1, 1982, and August 31, 1983. Within
the birth cohort, the incidence of asthma, allergic rhinitis, and eczema was
determined, and off-line FeNO, spirometry, and IgE measurements were performed at
the age of 21 years. RESULTS: FeNO measurements were successfully performed in
361 participants. Median FeNO levels were significantly higher in those with vs
without eczema (23.6 vs 18.0 ppb; P < .0001), those with vs without allergic
rhinitis (20.7 vs 17.8 ppb; P = .0001), and those with vs without atopic asthma
(23.3 vs 18.1 ppb; P = .02) but not in those with vs without asthma (20.8 vs 18.3
ppb; P = .24). Eczema, allergic rhinitis, smoking, sex, and atopic sensitization 
appeared to be independently associated with log FeNO in this population sample, 
whereas (atopic) asthma was not. No effect on FeNO levels was observed for lung
function parameters. CONCLUSION: Eczema, allergic rhinitis, and atopic status
were all independently associated with elevated FeNO levels, whereas (atopic)
asthma was not. This finding implies that future studies into the role of FeNO in
asthma should consider the influence of atopic disease outside the lungs.

PMID: 18254484 [PubMed - indexed for MEDLINE]

158: Ann Allergy Asthma Immunol. 2008 Jan;100(1):12-6.

Nasal mucosal expression of nitric oxide synthases in patients with allergic
rhinitis and its relation to asthma.

Yuksel H, Kirmaz C, Yilmaz O, Pinar E, Vatansever S, Degirmenci PB, Ozbilgin K.

Department of Pediatric Allergy and Pulmonology, Celal Bayar University, Manisa, 
Turkey. hyukselefe@hotmail.com

BACKGROUND: Nitric oxide (NO) has contradictory roles in the pathophysiology of
allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of
NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large
amounts produced by inducible NOS (iNOS) are proinflammatory. OBJECTIVE: To
investigate the difference in constitutive endothelial NOS (eNOS) and iNOS
expression in nonallergic and allergic mucosa and the possible relation of this
to the coexistence of asthma in seasonal AR. METHODS: Seventeen patients (10
women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) 
with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy
specimens were obtained in all. Levels of eNOS and iNOS expressed as
immunohistochemical scores (HSCOREs) were determined immunohistochemically from
the specimens. RESULTS: The mean +/- SD HSCOREs for eNOS in patients with
seasonal AR were not significantly different from those of the nonallergic
controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P = .12). On the other hand, the mean
+/- SD HSCOREs for iNOS were significantly higher in patients with seasonal AR
(1.75 +/- 0.75 vs 0.71 +/- 0.6; P = .004). Furthermore, although eNOS expression 
was not different between seasonal AR patients with and without asthma, the mean 
+/- SD HSCOREs for iNOS were significantly higher in the patients with asthma
(1.93 +/- 0.78 vs 1.65 +/- 0.55; P = .01). CONCLUSION: Increased expression of
iNOS might have a role in the development of allergic inflammation in upper and
lower airways and in comorbidity of AR and asthma.

PMID: 18254476 [PubMed - indexed for MEDLINE]

159: Prim Care Respir J. 2008 Mar;17(1):7-18.

Allergic rhinitis-induced nasal congestion: its impact on sleep quality.

Storms W.

The Research Center, The William Storms Allergy Clinic, Colorado Springs, CO
80907, USA. sneezedoc@stormsallergy.com

Allergic rhinitis (AR) is an extremely common health problem affecting 20 to 40
million Americans and between 10-25% of the world's population. Patients with AR 
suffer from both nasal symptoms (congestion, rhinorrhea, itching, and sneezing)
and ocular symptoms (itching, redness, and tearing). The negative impact on sleep
quality and quantity, and consequently on various aspects of the patient's life, 
is an under-recognised and under-treated component of AR morbidity. Nasal
congestion, which is one of the most bothersome and prevalent symptoms of AR, is 
thought to be the leading symptom responsible for rhinitis-related sleep
problems. In addition to reducing clinical symptoms, pharmacologic therapies for 
AR that specifically reduce inflammatory cells and mediators - and therefore
nasal congestion and other symptoms - should also improve sleep quality and
overall quality of life (QOL). Intranasal corticosteroids (INS) are the current
mainstay of therapy for AR. Results of a number of clinical trials demonstrate
that INS effectively reduce nasal congestion and ocular symptoms, improve sleep
quality, and decrease daytime somnolence. Intranasal corticosteroids have also
proved to be effective in reducing symptoms of acute rhinosinusitis and nasal
polyposis, both of which also negatively impact on sleep quality. Intranasal
corticosteroids are considered safe due to their low systemic bioavailability.

Publication Types: 
    Review

PMID: 18253678 [PubMed - indexed for MEDLINE]

160: Ann Agric Environ Med. 2007 Dec;14(2):271-80.

Use of phenological and pollen-production data for interpreting atmospheric birch
pollen curves.

Jato V, Rodríguez-Rajo FJ, Aira MJ.

Department of Plant Biology and Soil Sciences, Campus As Lagoas Ourense,
University of Vigo, 32004 Ourense, Spain. vjato@uvigo.es

Although aerobiological data are frequently used as a flowering sign in
phenological research, airborne pollen counts are influenced by a number of
factors affecting pollen curves. A study was made about the reproductive biology 
of birch and environmental factors influencing its pollen release and transport, 
in order to achieve a reliable interpretation of Betula pollen curves.
Aerobiological data were recorded in 2002 and 2003 at two sites in NW Spain and
phenological observations were carried out on 20 trees from four Betula
populations (three Betula alba L. and one B. pendula Roth.). Pollen production
was calculated for six Betula alba trees. Chilling and heat requirements for
triggering development were calculated. Due to differences in the geographical
location, budbreak and flowering started first in Betula pendula. The flowering
period lasted from 8-13 days. Reduced pollen output per anther and catkin in
individual trees in 2003 prompted a marked decline in overall pollen production. 
Major differences observed in birch pollen curves were attributed to the
influence both of weather conditions and pollen transport from areas where the
flowering occurs at a different time. Heat requirements calculated using
phenological and aerobiological data were similar when the peak pollen-count date
was used.

PMID: 18247464 [PubMed - indexed for MEDLINE]

161: Ann Agric Environ Med. 2007 Dec;14(2):259-64.

Definition of main pollen season using a logistic model.

Ribeiro H, Cunha M, Abreu I.

Departamento de Botânica, Faculdade de Ciência, University of Porto, Rua do Campo
Alegre, 1191, 4150 Porto, Vairão, Portugal.

This paper proposes a method to unify the definition of the main pollen season
based on statistical analysis. For this, an aerobiological study was carried out 
in Porto region (Portugal), from 2003-2005 using a 7-day Hirst-type volumetric
spore trap. To define the main pollen season, a non-linear logistic regression
model was fitted to the values of the accumulated sum of the daily airborne
pollen concentration from several allergological species. An important feature of
this method is that the main pollen season will be characterized by the model
parameters calculated. These parameters are identifiable aspects of the flowering
phenology, and determine not only the beginning and end of the main pollen
season, but are also influenced by the meteorological conditions. The results
obtained with the proposed methodology were also compared with two of the most
used percentage methods. The logistic model fitted well with the sum of
accumulated pollen. The explained variance was always higher than 97%, and the
exponential part of the predicted curve was well adjusted to the time when higher
atmospheric pollen concentration was sampled. The comparison between the
different methods tested showed large divergence in the duration and end dates of
the main pollen season of the studied species.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18247462 [PubMed - indexed for MEDLINE]

162: Ann Agric Environ Med. 2007 Dec;14(2):233-6.

Estimation of pollen and seed production of common ragweed in France.

Fumanal B, Chauvel B, Bretagnolle F.

UMR 1210 Biologie et Gestion des Adventices, INRA, ENESAD, UB, 17 rue Sully - BP 
86510, 21000 Dijon, France. boris.fumanal@u-bourgogne.fr

Common ragweed (Ambrosia artemisiifolia L.) is an invasive weed of field crops
and human-disturbed habitats in Europe. As well as in its natural range (North
America), common ragweed is a threat to human health due to its abundant
allergenic pollen release. Most studies have been focused on airborne pollen
monitoring, but to date, no data have been available on precise individual plant 
pollen and seed production related to plant traits growing in natural environment
and on their corresponding source of variation. The aim of this study was to
evaluate pollen and seed production of common ragweed plants in several
populations in France. Seasonal pollen production per plant ranged from 100
million to 3 billion and seed production from 346 to 6,114, depending on plant
size and habitat. Common ragweed plants developing in field crops produced more
pollens and seeds than those growing in other habitats. Pollen and seed
production was closely related to plant volume and biomass, thus providing a
means of estimating potential pollen and seed production in given target areas.
Such biological data could be integrated into population management strategies or
into airborne pollen modelling.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18247457 [PubMed - indexed for MEDLINE]

163: Otolaryngol Head Neck Surg. 2008 Feb;138(2):129-39.

Intranasal corticosteroids reduce ocular symptoms associated with allergic
rhinitis.

Naclerio R.

University of Chicago Hopsitals, Chicago, IL 60637, USA.
rnacleri@surgery.bsd.uchicago.edu <rnacleri@surgery.bsd.uchicago.edu>

OBJECTIVE: Clinical data and recent guidelines support the positive effects of
intranasal corticosteroids on allergic rhinitis-associated ocular symptoms. This 
article reviews the epidemiology and pathophysiology of ocular allergy symptoms
and efficacy, tolerability, and potential mechanisms of action of intranasal
corticosteroids in the treatment of this condition. DATA SOURCES: MEDLINE
database. REVIEW METHODS: A search of pertinent literature identified in vitro,
preclinical, and clinical data that involve intranasal corticosteroids in
ocular-related studies. Searches that used epidemiology, pathophysiology, drug
class and specific agents, and other appropriate search terms were conducted.
RESULTS: Ocular symptoms, common in patients with allergic rhinitis, are
associated with reduced quality of life and substantial economic costs. In the
conjunctival epithelium, an early, type-1 hypersensitivity reaction occurs after 
direct allergen exposure. Progression to late-phase response, with recurrence of 
symptoms and infiltration of inflammatory cells, may occur 4 to 8 hours later and
appears to be dose-related. Alteration of nasal ocular reflex pathways may also
contribute to ocular symptoms in allergic rhinitis. Clinical data indicate that
intranasal corticosteroids significantly reduce total and individual ocular
symptoms in subjects with allergic rhinitis. Meta-analyses have found that
oral/topical antihistamines are not superior to intranasal corticosteroids in
reducing ocular allergy symptoms. Ocular adverse events from intranasal
corticosteroids are rare. CONCLUSION: Intranasal corticosteroids are effective
and well-tolerated in the treatment of ocular symptoms associated with allergic
rhinitis. Additional studies are needed to better understand the mechanisms
underlying the effects of intranasal corticosteroids on ocular symptoms.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 18241703 [PubMed - indexed for MEDLINE]

164: Respir Res. 2008 Jan 30;9:15.

Effects of intranasal TNFalpha on granulocyte recruitment and activity in healthy
subjects and patients with allergic rhinitis.

Widegren H, Erjefält J, Korsgren M, Andersson M, Greiff L.

Department of Otorhinolaryngology, Head & Neck Surgery, Lund University Hospital,
Lund, Sweden. henrik.widegren@skane.se

BACKGROUND: TNFalpha may contribute to the pathophysiology of airway
inflammation. For example, we have recently shown that nasal administration of
TNFalpha produces late phase co-appearance of granulocyte and plasma exudation
markers on the mucosal surface. The objective of the present study was to examine
indices of granulocyte presence and activity in response to intranasal TNFalpha
challenge. METHODS: Healthy subjects and patients with allergic rhinitis
(examined out of season) were subjected to nasal challenge with TNFalpha (10
microg) in a sham-controlled and crossover design. Nasal lavages were carried out
prior to and 24 hours post challenge. Nasal biopsies were obtained post
challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil
cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil
activity. Moreover, IL-8 and alpha2-macroglobulin were analyzed as markers of
pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers
of neutrophils and eosinophils were monitored. RESULTS: Nasal lavage fluid levels
of MPO recorded 24 hours post TNFalpha challenge were increased in healthy
subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (c.f.
sham challenge). Similarly, alpha2-macroglobulin was increased in healthy
subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage 
fluid levels of ECP and IL-8 were not affected by TNFalpha challenge. TNFalpha
increased the numbers of subepithelial neutrophils (p = 0.0021), but not the
numbers of eosinophils. CONCLUSION: TNFalpha produces a nasal inflammatory
response in humans that is characterised by late phase (i.e., 24 hours post
challenge) neutrophil activity and plasma exudation.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18234086 [PubMed - indexed for MEDLINE]

165: Adv Ther. 2008 Jan;25(1):29-36.

Long-term allergen-specific immunotherapy correlates with long-term
allergen-specific immunological tolerance.

Ali I, Goksal K, Ozan B, Gulsen D.

GATA, Department of Immunology, Ankara, Turkey. EDC85@Turk.net

INTRODUCTION: One method of treatment for allergic diseases is allergen-specific 
immunotherapy (SIT). The clinical efficacy of SIT in pollen-induced allergic
rhinitis has been demonstrated in several controlled clinical trials. There is no
consensus about the protective effect of SIT. In this study, we evaluated the
correlation between the duration of SIT and relapse of allergic
rhinoconjunctivitis. METHODS: We evaluated 148 patients who had received SIT
between 1998 and 2006. All of the patients had allergic rhinoconjunctivitis.
According to the data 116 had sensitivity to grass pollen and 32 to house dust.
SIT was performed on 87 patients for 4 y (Group A) and 61 patients for 6 y (Group
B). RESULTS: All of the 148 patients were monitored regularly with no medication 
for 2 y after SIT. Thirty-one patients in Group A relapsed (36%); 11 patients in 
Group B relapsed (18%). Mean duration until relapse was 11.1+/-1.99 mo in Group A
and 19.64+/-1.86 mo in Group B. During evaluation, symptom scores were
2.32+/-0.74 in Group A and 1.81+/-0.75 in Group B and serum total immunoglobulin 
E levels were 432.4+/-78.5 KU/lt in Group A and 288.6+/-55.3 KU/lt in Group B.
There was significant difference between the groups (P < 0.05). CONCLUSION:
According to these results, long-term SIT therapy correlates with long-term,
allergen-specific, acquired immunological tolerance.

PMID: 18224290 [PubMed - indexed for MEDLINE]

166: Pediatr Allergy Immunol. 2008 May;19(3):197-207. Epub 2008 Jan 24.

Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a
systematic review.

Röder E, Berger MY, de Groot H, van Wijk RG.

Allergen-specific immunotherapy is one of the cornerstones of allergic
rhinoconjunctivitis treatment. Since the development of non-invasive
administration forms with better safety profiles, there is an increasing tendency
to prescribe immunotherapy in youngsters. However, no overview is available on
the efficacy of immunotherapy in all its different administration forms in
youngsters. Therefore, we systematically reviewed randomized controlled trials
(RCTs) to evaluate the effect of immunotherapy with inhalant allergens on
symptoms and medication use in children and adolescents with allergic
rhinoconjunctivitis. Medline, EMBASE, the Cochrane Controlled Clinical Trials
Register and reference lists of recent reviews and published trials were
searched. RCTs including youngsters aged 0-18 yr with allergic
rhinoconjunctivitis and comparing immunotherapy with placebo, symptomatic
treatment or a different administration form of immunotherapy were included.
Primary outcome measures were rhinoconjunctivitis symptom and/or medication
scores. Methodological quality was assessed using the validated Delphi list. A
method of best evidence synthesis, a rating system with levels of evidence based 
on the overall quality and the outcome of the trials, was used to assess
efficacy. Six subcutaneous (SCIT), four nasal (LNIT), seven oral (OIT) and 11
sublingual (SLIT) immunotherapy trials, comprising 1619 youngsters, were
included. Only 39% of the trials were of high methodological quality. For the
SCIT and OIT subgroups the level of evidence for efficacy was conflicting.
Moderate evidence of effect was found for LNIT. Analysis of the SLIT subgroup
showed no evidence of effect. The evidence for the perennial and seasonal
allergen trials within the subgroups varied from moderate evidence of effect to
no evidence of effect. In conclusion, there is at present insufficient evidence
that immunotherapy in any administration form has a positive effect on symptoms
and/or medication use in children and adolescents with allergic
rhinoconjunctivitis.

Publication Types: 
    Editorial
    Review

PMID: 18221463 [PubMed - indexed for MEDLINE]

167: Ann Allergy Asthma Immunol. 2007 Dec;99(6):526-33.

Cross-allergenicity of pollens from the Compositae family: Artemisia vulgaris,
Dendranthema grandiflorum, and Taraxacum officinale.

Lee YW, Choi SY, Lee EK, Sohn JH, Park JW, Hong CS.

Division of Allergy and Immunology, Department of Internal Medicine, Yonsei
University College of Medicine, Seoul, Korea.

BACKGROUND: Chrysanthemum, dandelion, and mugwort belong to the Compositae
(Asteraceae) family. Their cross-allergenicity has not yet been completely
evaluated. OBJECTIVE: To investigate the sensitization and cross-allergenicity of
these 3 plants. METHODS: We reviewed 6,497 respiratory allergic patients who
underwent skin prick tests (SPTs) during the last 10 years (1995-2005) and
analyzed the sensitization rates of the 3 pollens. We sorted this population by
wheal size and selected the monosensitized or cosensitized patients. Their serum 
samples were used to evaluate specific IgE (sIgE) and cross-allergenicity of the 
3 pollens by CAP, immunoblotting, and inhibition enzyme-linked immunosorbent
assay (ELISA). RESULTS: On SPTs, mugwort, chrysanthemum, and dandelion sensitized
13.4%, 10.0%, and 8.5% of the enrolled population, respectively, and 5.2% of the 
population was cosensitized to all 3 pollens. Some patients were monosensitized
to 1 species (1.5% to chrysanthemum, 1.4% to dandelion, and 4.5% to mugwort). In 
inhibition ELISA that used a pooled serum sample cosensitized to all 3 pollens,
mugwort inhibited sIgE bindings to chrysanthemum, dandelion, and mugwort up to
95%, 86%, and 96%, respectively. The 50% inhibitory allergen concentrations for
sIgE to each of the 3 species were not different between solid-phase antigen and 
mugwort. The mugwort sIgE of this pooled serum was suppressed up to 74% and 27%
by chrysanthemum and dandelion, respectively. The 50% inhibitory allergen
concentrations of chrysanthemum and dandelion for mugwort sIgE were 0.3 and 57.0 
microg/mL, respectively, whereas that of mugwort was 0.05 microg/mL. We found a
patient who was truly monosensitized to dandelion. CONCLUSION: Chrysanthemum and 
dandelion were frequently cosensitized with mugwort in the general population
with respiratory allergic diseases. These 2 species also showed extensive
cross-allergenicity with mugwort. True monosensitization to these 2 species was
possible.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18219834 [PubMed - indexed for MEDLINE]

168: Ann Allergy Asthma Immunol. 2007 Dec;99(6):483-95.

Herbal medicines for the treatment of allergic rhinitis: a systematic review.

Guo R, Pittler MH, Ernst E.

Department of Complementary Medicine, Peninsula Medical School, University of
Exeter, England. ruoling.guo@pms.ac.uk

OBJECTIVE: To evaluate the efficacy of herbal medicines for the treatment of
allergic rhinitis (AR). DATA SOURCES: Five electronic databases until November 8,
2005; bibliographies of located articles; manufacturers of commercially available
preparations; and experts in the field. Study Selection: We only included
double-blind randomized clinical trials (RCTs), which tested a herbal medicine
against placebo or active comparator, in patients with AR, and evaluated
clinically relevant outcomes. Study selection, data extraction, and evaluation of
methodological quality were performed independently by 2 reviewers. Discrepancies
were resolved by discussion and by seeking the opinion of the third reviewer.
Meta-analysis was only performed if data were considered suitable for pooling.
RESULTS: Sixteen eligible RCTs, testing 10 different herbal products against
placebo or active comparator, were included. Six RCTs studied Petasites hybridus 
(butterbur) extract for AR and suggest that P hybridus is superior to placebo or 
similarly effective compared with nonsedative antihistamines for intermittent AR.
Two RCTs studied an Indian herbal combination, Aller-7, in patients with AR and
reported positive results. Single RCTs were identified for 8 other herbal
products as treatments for AR, reporting positive outcomes, except for grape seed
extract. The median methodological quality score was 4 of a possible maximum of
5. CONCLUSIONS: There is encouraging evidence suggesting that P hybridus may be
an effective herbal treatment for seasonal (intermittent) AR. However,
independent replication is required before a firm conclusion can be drawn because
of the financial support from the manufacturer of P hybridus extract to the 3
large trials. There are also promising results generated for other herbal
products, particularly Aller-7, Tinospora cordifolia, Perilla frutescens, and
several Chinese herbal medicines. Although these results are confined to the
paucity of data and the small sample size, confirmation in larger and more
rigorously designed clinical trials is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18219828 [PubMed - indexed for MEDLINE]

169: Am J Rhinol. 2008 May-Jun;22(3):253-7. Epub 2008 Jan 21.

Sublingual immunotherapy: a novel, albeit not so new, immunotherapy treatment
modality.

Saporta D.

Private practice, Elizabeth, New Jersey 07208, USA. allergydropsnj.com

BACKGROUND: Specific allergy immunotherapy traditionally has been thought of as
subcutaneous injection immunotherapy (SCIT). There also are noninjection routes
for the administration of immunotherapy. The best-known and studied of these
noninjection routes is the sublingual route, usually known as sublingual
immunotherapy (SLIT). SLIT has been in use for many decades; however, to this
date, it is not well known to the majority of allergy practitioners in this
country. The purpose of this study is to help change this perception so that SLIT
eventually can be considered one more tool in the allergist's armamentarium.
METHODS: A literature review was performed. It included articles from the early
American clinicians and present publications that are mostly of European origin. 
RESULTS: It will become clear to the reader that the key features of SLIT are its
efficacy, great safety, and simplicity of administration. CONCLUSION: SLIT is a
safe treatment modality that should be considered as a useful additional tool in 
the therapeutic armamentarium.

Publication Types: 
    Review

PMID: 18211743 [PubMed - indexed for MEDLINE]

170: Allergol Int. 2008 Mar;57(1):93-6. Epub 2008 Mar 1.

Detection of specific IgE antibodies in sera of Japanese birch-allergic patients 
using recombinant allergens Bet v 1, Bet v 2 and Bet v 4.

Shirasaki H, Yamamoto T, Koyanagi Y, Watanabe N, Himi T.

Department of Otolaryngology, Sapporo Medical University, School of Medicine,
Sapporo, Hokkaido, Japan. shira@sapmed.ac.jp

BACKGROUND: Birch pollen is the major allergen in pollinosis in northern Japan.
IgE reactivity to individual birch pollen allergens has been shown to differ
between populations of birch pollen-allergic patients living in different
countries. In this study, we examined the IgE profiles to recombinant birch
pollen allergens in birch-sensitive patients living in Sapporo. METHODS: This
study used the sera of 40 patients with specific IgE toward birch pollen extract.
Their sera were analyzed for specific IgE reactivity to individual birch pollen
allergens (recombinant Bet v 1, Bet v 2 and Bet v 4) and natural birch pollen
extract using Pharmacia CAP SystemTM. RESULTS: Of 40 sera with positive CAP
results for natural birch pollen extract, 39 (97.5%) had specific IgE towards Bet
v 1; 6 (15%) contained specific IgE against Bet v 2. Bet v 4 reactivity was
documented in only one subject (2.5%). CONCLUSIONS: The present data suggest that
the specific IgE reactivity profiles to birch pollen allergen in birch-sensitive 
patients in Sapporo correspond to those in Scandinavia, possibly due to the heavy
birch pollen exposure in this area. This observation provides useful information 
for future birch allergen-specific immunotherapy in Japan.

Publication Types: 
    Comparative Study

PMID: 18209509 [PubMed - indexed for MEDLINE]

171: Allergol Int. 2008 Mar;57(1):83-91. Epub 2008 Mar 1.

Protease activity of allergenic pollen of cedar, cypress, juniper, birch and
ragweed.

Gunawan H, Takai T, Ikeda S, Okumura K, Ogawa H.

Research Center, Juntendo University School of Medicine, Tokyo, Japan.

BACKGROUND: Pollen is an important trigger of allergic rhinitis, conjunctivitis, 
and/or asthma, and an exacerbating factor in atopic dermatitis. Although it is
proposed that protease activity from allergen sources, such as mites, enhances
allergenicity, little information is available on that from relevant allergenic
pollens such as Japanese cedar and Japanese cypress pollens, which are the major 
cause of pollinosis in Japan. METHODS: We analyzed the protease activities
derived from allergenic pollen of Japanese cedar, Japanese cypress, and Rocky
mountain juniper, which belong to the Cupressaceae/Taxodiaceae family, and white 
birch and short ragweed, using synthetic substrates and class-specific
inhibitors. RESULTS: We found that the pollen of the three members of the
Cupressaceae/Taxodiaceae family contained serine protease activity, that the
pollen of white birch and short ragweed contained not only serine protease
activity but also cysteine protease activity, that all five types of pollen
tested contained at least one other type of serine protease, whose sensitivity to
a serine protease-specific inhibitor was relatively low, and that the content and
releasability of the pollen-derived proteases differed according to the plant
families. CONCLUSIONS: Clinically relevant allergenic pollens tested in the
present study can release serine and/or cysteine endopeptidases. Information on
the spectrum of the endopeptidase activities from these allergenic pollen grains 
will be useful for investigating their contribution to the pathogenesis of
allergies.

Publication Types: 
    Comparative Study

PMID: 18209508 [PubMed - indexed for MEDLINE]

172: Prim Care. 2008 Mar;35(1):1-10, v.

Allergic rhinitis.

Weber RW.

National Jewish Medical and Research Center, The University of Colorado Health
Sciences Center, 1400 Jackson Street, Room J326, Denver, CO 80206, USA.
weberr@njc.org

Allergic rhinitis is common malady with a significant impact on quality of life. 
It can affect 25% to 35% of people, depending on the population studied. Costs
for physicians' visits and medications, and indirect costs of missed school and
work and lost productivity, are estimated to be $2 billion annually in the United
States. Pharmacotherapy is the most used therapeutic modality. Topical
corticosteroids are the preferred method of treatment for seasonal and perennial 
allergic rhinitis. Antihistamines and antileukotrienes may be beneficial add-ons 
to topical steroids. Allergen avoidance is recommended, but may be difficult.
Allergen immunotherapy is effective and should be considered with poor response
to pharmacotherapy and avoidance.

Publication Types: 
    Review

PMID: 18206714 [PubMed - indexed for MEDLINE]

173: J Allergy Clin Immunol. 2008 Jan;121(1):227-32.

Allergy immunotherapy among Medicaid-enrolled children with allergic rhinitis:
patterns of care, resource use, and costs.

Hankin CS, Cox L, Lang D, Levin A, Gross G, Eavy G, Meltzer E, Burgoyne D,
Bronstone A, Wang Z.

BioMedEcon, LLC, PO Box 129, Moss Beach, CA 94038, USA.
cherylhankin@biomedecon.com

BACKGROUND: Although research demonstrates that allergy immunotherapy (IT)
improves allergic rhinitis (AR) outcomes, little is known about IT patterns of
care and associated resource use and costs among US children with diagnoses of
AR. OBJECTIVE: We sought to examine characteristics associated with receiving IT,
patterns of IT care, and health care use and costs incurred in the 6 months
before versus after IT. METHODS: We performed retrospective Florida Medicaid
claims data (1997-2004) analysis of children (<18 years of age) given new
diagnoses of AR. RESULTS: Of 102,390 patients with new diagnoses of AR, 3048
(3.0%) received IT. Male patients, Hispanic patients, and those with concomitant 
asthma were significantly more likely to receive IT. Approximately 53% completed 
less than 1 year and 84% completed less than 3 years of IT. Patients who received
IT used significantly less pharmacy (12.1 vs 8.9 claims, P < .0001), outpatient
(30.7 vs 22.9 visits, P < .0001), and inpatient (1.2 vs 0.4 admissions, P = .02) 
resources in the 6 months after versus before IT. Pharmacy ($330 vs $60, P <
.0001), outpatient ($735 vs $270, P < .0001), and inpatient ($2441 vs $1, P <
.0001) costs (including costs for IT care) were significantly reduced after IT.
CONCLUSION: Despite suboptimal treatment persistence (only 16% of patients
completed 3 years of IT), resource use and costs after treatment were
significantly reduced from pre-IT levels.

PMID: 18206509 [PubMed - indexed for MEDLINE]

174: Acta Dermatovenerol Alp Panonica Adriat. 2007 Dec;16(4):143-8.

Sublingual immunotherapy in pollen-induced seasonal rhinitis and conjunctivitis: 
a randomized controlled trial.

Mösges R, Brüning H, Hessler HJ, Götz G, Knaussmann HG.

IMSIE - Klinikum der Universität zu Köln, D-50924 Cologne, Germany.
ralph@moesges.de

BACKGROUND: Sublingual immunotherapy (SLIT) is a recognized and safe treatment
for allergic rhinitis and conjunctivitis. The aim was to evaluate the efficacy
and safety of tablets for grass and rye pollen- induced rhinitis and
conjunctivitis. METHODS: A double-blind, randomized, placebo-controlled trial was
carried out over 9 months. 105 patients received a standardized grass/rye mix
extract or a placebo using sublingual drops during the build-up phase. Drops were
replaced by sublingual tablets during the maintenance phase (300 IR/daily).
RESULTS: In patients that received active treatment, a significantly lower total 
symptom score (rhinitis and conjunctivitis) compared to the placebo group was
observed (p = 0.038). The investigators' assessment revealed a significant
improvement in favor of the active treatment group (p = 0.018). Skin reactivity
to grass and rye pollen was significantly reduced in the active treatment group
(p < 0.05). No statistical difference was observed between the two groups for
serum-specific IgG4 levels. Side effects were local and mild, and no severe
systemic reactions were reported. CONCLUSION: This study indicates that
tablet-based sublingual immunotherapy was safe and significantly improved
grass/rye pollen-induced rhinoconjunctivitis symptoms. It was also associated
with a significant inhibition of the immediate skin response.

Publication Types: 
    Randomized Controlled Trial

PMID: 18204744 [PubMed - indexed for MEDLINE]

175: Allergy Asthma Proc. 2007 Nov-Dec;28(6):724-34.

Levocetirizine: The latest treatment option for allergic rhinitis and chronic
idiopathic urticaria.

Dubuske LM.

Immunology Research Institute of New England, Gardner, MA 01440, USA.
ldubuske@aol.com

Levocetirizine is the most recent antihistamine available in the United States
and is indicated for the symptomatic treatment of allergic rhinitis (AR; seasonal
[SAR] and perennial [PAR]) and chronic idiopathic urticaria (CIU). The purpose of
this study was to review the current literature on pharmacologic properties of
levocetirizine, its safety, tolerability, and effectiveness in AR and CIU.
Relevant articles in English or with English abstracts were identified from
systematic Medline searches using combinations of the terms antihistamine/s, CIU,
H(1)-receptor antagonist/s, levocetirizine, PAR and persistent AR (PER),
pharmacodynamic, pharmacokinetic, and SAR. Levocetirizine is the active
enantiomer of cetirizine. Pharmacologic and clinical studies indicate that
levocetirizine has a fast onset and long duration of action, with a
well-tolerated adverse effect profile. These favorable features may be caused by 
levocetirizine's pharmacokinetic and pharmacodynamic properties including high
bioavailability, low apparent volume of distribution, low degree of metabolism,
and high in vivo potency and H(1)-receptor occupancy. Several large
well-controlled clinical trials in adults and children aged 6-12 years have shown
levocetirizine to be consistently efficacious and well tolerated in relieving the
symptoms of SAR, PAR, and PER and CIU. Levocetirizine is a welcome new treatment 
option in the United States for symptomatic treatment of AR and CIU.

Publication Types: 
    Review

PMID: 18201439 [PubMed - indexed for MEDLINE]

176: Allergy Asthma Proc. 2007 Nov-Dec;28(6):716-23.

Comprehensive report of the efficacy, safety, quality of life, and work impact of
Olopatadine 0.6% and Olopatadine 0.4% treatment in patients with seasonal
allergic rhinitis.

Fairchild CJ, Meltzer EO, Roland PS, Wells D, Drake M, Wall GM.

Alcon Laboratories, Inc., 6201 South Freeway, Fort Worth, Texas 76134, USA.
Carol.Fairchild@alconlabs.com

Seasonal allergic rhinitis (SAR) treatment should reduce symptoms and help
patients resume normal function. This study was performed to determine the effect
of olopatadine (Olo) nasal spray on symptoms, quality of life (QoL), work, and
activities of SAR patients. A pooled analysis was conducted of two Institutional 
Review Board-approved, randomized, double-blind clinical trials that compared
2-week treatment with Olo 0.6% and Olo 0.4% to placebo. Symptoms were assessed
with the Total Nasal Symptom Score (TNSS) from daily diaries. Health outcomes
were measured by the Work Productivity and Activity Impairment
Questionnaire-Allergy Specific (WPAI-AS) and Rhinoconjunctivitis Quality of Life 
Questionnaire (RQLQ). The studies included 1240 SAR patients with a mean age of
37 years; 64% were women. TNSS and RQLQ improvements were significantly different
from placebo: TNSS, Olo 0.6% (p < 0.0001) and Olo 0.4% (p < 0.0037); RQLQ, Olo
0.6% (p < 0.001) and Olo 0.4% (p < 0.05). WPAI-AS improvements also were
significant for overall work impact and activity impairment in the Olo 0.6% (p < 
0.001) and Olo 0.4% (p < 0.05). Correlations between Olo 0.6% TNSS scores and
work impact were r = 0.45 (p < 0.0001); activities, r = 0.55 (p < 0.0001); and
RQLQ score, r = 0.61 (p < 0.0001), indicating that symptom reduction with Olo
therapy was associated with improvements in function and QoL. Adverse events were
nonserious and infrequent in all treatment groups. The most frequent adverse
events were unpleasant taste and headache. This analysis indicates that Olo is a 
safe and effective intranasal treatment and is associated with significant
improvement in QoL and ability to perform work and conduct usual activities of
SAR patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18201438 [PubMed - indexed for MEDLINE]

177: Pediatr Allergy Immunol. 2008 Feb;19(1):20-4.

FcgammaRIIIa-V/F 158 polymorphism in Turkish children with asthma bronchiale and 
allergic rhinitis.

Zeyrek D, Tanac R, Altinoz S, Berdeli A, Gulen F, Koksoy H, Demir E.

Department of Pediatric Allergy and Pulmonology, Aegean University, Izmir,
Turkey. dost.zeyrek@ege.edu.tr

Fc receptors (FcR) play an important role in immune regulation. This might be
linked to the variability in immune response, therefore relating to the
pathogenesis of atopic diseases. The aim of the present study was to evaluate the
FcgammaRIIIa gene polymorphism in Turkish children with asthma and allergic
rhinitis. The study included 364 atopic children (184 bronchial asthma, 180
allergic rhinitis) and 234 healthy subjects as the control group, aged between 5 
to 16 years. Patients were recruited from outpatient clinics of allergy and
general pediatric care. Plasma IgE concentrations were measured by immunoassays
and skin prick test was done in children with atopic diseases. The FcgammaRIIIa
gene polymorphism was determined using the polymerase chain reaction method.
Distribution of V158V genotype was significantly different among patient groups
compared to controls (for asthmatic children OR: 5.33, 95% CI: 2.80-10.23, p <
0.001; for allergic rhinitis OR: 3.25, 95% CI: 1.75-6.07, p = 0.001).
Distribution of 158 V allele was significantly different among asthmatic children
(OR: 2.20, 95% CI: 1.65-2.92, p < 0.001) and allergic rhinitis patients (OR:
1.77, 95% CI: 1.32-2.35, p < 0.001) compared to healthy controls. Our study shows
that the V158V genotype in FcgammaRIIIa gene polymorphism may be a genetic risk
factor for the development of atopic diseases.

PMID: 18199088 [PubMed - indexed for MEDLINE]

178: Eur J Pharmacol. 2008 Mar 17;582(1-3):139-44. Epub 2008 Jan 14.

Involvement of peroxynitrite in pollen-induced nasal blockage in guinea pigs.

Mizutani N, Nabe T, Fujii M, Yoshino S, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, Yamashina, Kyoto
607-8414, Japan.

Nitric oxide (NO) has been implicated in early and late phase nasal blockage in a
Japanese cedar pollen-induced experimental allergic rhinitis guinea pig model. In
this study, we investigated the role of peroxynitrite, which is formed by a rapid
reaction of NO with superoxide anion, in the antigen-induced biphasic nasal
blockage. Sensitized guinea pigs were repeatedly challenged by pollen inhalation 
once every week. The peroxynitrite scavenger, ebselen (30 mg/kg), or the xanthine
oxidase inhibitor, allopurinol (50 mg/kg), was intraperitoneally administered 30 
min before the antigen challenge. The late phase nasal blockage induced 4 h after
the challenge was largely suppressed by ebselen (57% inhibition; P<0.05) and
allopurinol (47% inhibition; P<0.05), but neither ebselen nor allopurinol
influenced the early phase response. On the other hand, the intranasal
instillation of peroxynitrite (10(-3) and 10(-2) M, 10 microl/nostril) caused a
remarkable dose-dependent nasal blockage in the sensitized guinea pig. These
results suggest that peroxynitrite plays a major role in the late phase nasal
blockage induced by the antigen challenge in sensitized guinea pigs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18191833 [PubMed - indexed for MEDLINE]

179: Curr Opin Allergy Clin Immunol. 2008 Feb;8(1):1-9.

The voice of the patients: allergic rhinitis is not a trivial disease.

Valovirta E, Myrseth SE, Palkonen S.

Turku Allergy Center, Turku, Finland. erkka.valovirta@allergiakeskus.fi

PURPOSE OF REVIEW: Patient and physician perspectives on the impact of allergic
rhinitis have previously been studied in the general population. We evaluated the
burden of allergic rhinitis among patients from the members of European allergy
patient organizations. The Patient Voice Allergy Survey was a quantitative,
self-completion survey of 3562 patients with allergic rhinitis (16 years and
older). Background information on allergic rhinitis, severity of allergic
rhinitis symptoms and their impact on lives, nonmedical measures for relieving of
symptoms, types of medications, and concomitant conditions were evaluated. RECENT
FINDINGS: Almost 50% of the responders reported symptoms lasting for more than a 
season. Preventive household adjustments are expensive with little perceived
benefit. Sleep and emotional life are affected by allergic rhinitis. Most
patients are satisfied with the current allergic rhinitis medications; at least
one-fifth report dissatisfaction. Patients perceive that allergic rhinitis
worsens other concomitant allergic diseases. SUMMARY: Future management
guidelines for allergic rhinitis must take into account the results of this
survey. Such guidelines must promote relief from the emotional burden of allergic
rhinitis and from the negative impact on daily activities, encourage patient
education, and maintain and build on the strong partnership between patients and 
healthcare professionals.

Publication Types: 
    Review

PMID: 18188010 [PubMed - indexed for MEDLINE]

180: Drugs Today (Barc). 2007 Dec;43(12):841-8.

An extract of Timothy-grass pollen used as sublingual immunotherapy for summer
hay fever.

Kay AB.

Allergy and Clinical Immunology, National Heart & Lung Institute, Imperial
College, London, UK. a.b.kay@imperial.ac.uk

Grazax is a lyophilisate of an extract of Timothy-grass pollen (Phleum pratense) 
administered by the sublingual route to induce desensitization (or
hyposensitization) to grass pollen in subjects with hay fever. Since allergen
avoidance measures are limited in hay fever sufferers, present treatment, at
least in the United Kingdom, is almost always by symptomatic medication. The
effectiveness of symptomatic treatment in hay fever is variable and depends on
patient compliance and the judicious prescribing of antihistamines and
anti-inflammatory preparations either alone or in combination. Desensitization
(hyposensitization or specific immunotherapy) by subcutaneous injection has been 
shown to be very efficacious and is used for patients who do not adequately
respond to drug treatment. A rare side effect of desensitizing injections is
anaphylaxis, and so use is limited to specialized centers. For these reasons
there has been considerable interest in specific immunotherapy by the sublingual 
route. Grazax has recently been approved in the United Kingdom. It is commenced
at least four months prior to the expected start of the grass pollen season and
in line with injection immunotherapy treatment will be recommended for a period
of three years with annual reviews to assess patient outcomes. Grazax grass
allergen tablets are well tolerated in patients with grass pollen allergy with
most adverse events being mild local reactions. There have been no instances of
anaphylaxis. In randomized double-blind placebo controlled trials Grazax reduces 
symptoms and medication scores in adults with hay fever. The long-term effects of
Grazax are currently being investigated.

Publication Types: 
    Review

PMID: 18174969 [PubMed - indexed for MEDLINE]

181: ScientificWorldJournal. 2007 Dec 17;7:1968-77.

Changes in allergy symptoms and depression scores are positively correlated in
patients with recurrent mood disorders exposed to seasonal peaks in
aeroallergens.

Postolache TT, Lapidus M, Sander ER, Langenberg P, Hamilton RG, Soriano JJ,
McDonald JS, Furst N, Bai J, Scrandis DA, Cabassa JA, Stiller JW, Balis T, Guzman
A, Togias A, Tonelli LH.

Mood and Anxiety Program, Department of Psychiatry, University of Maryland School
of Medicine, Baltimore, MD, USA. tpostolache@psych.umaryland.edu

Although growing evidence supports an association between allergy, allergens and 
depression, it remains unknown if this relationship is between "states" (possible
triggers) or "traits" (possible vulnerabilities). We hypothesized that patients
with recurrent mood disorders who are sensitized to tree pollen (as determined by
allergen specific IgE antibodies), in comparison to those who are not sensitized,
would report larger negative changes in mood during exposure to tree pollen in
spring. We also hypothesized that differences between high and low tree pollen
periods in self reported allergy symptoms would correlate positively with
differences in self reported depression scores. We present 1-year preliminary
data on the first 51 patients with unipolar or bipolar disorder (age: 19-63
years, 65% female, twelve patients were tree-pollen IgE positive). Ratings of
mood and allergic disease status were performed once during the peak airborne
pollen counts and once during the period of low airborne pollen counts, as
reported by two local pollen counting stations. Linear regression models were
developed to examine associations of changes in depression scores (dependent
variable) with tree pollen sensitization, changes in the allergy symptom severity
score, adjusted for gender and order of testing. We did not confirm the
hypothesized relationship between a specific tree pollen sensitization and
changes in mood during tree pollen exposure. We did confirm the hypothesized
positive relationship between the changes in allergy symptoms and changes in
subjects' depression scores (adjusted p<0.05). This result is consistent with
previous epidemiological evidence connecting allergy with depression, as well as 
our recent reports of increased expression of cytokines in the prefrontal cortex 
in victims of suicide and in experimental animals sensitized and exposed to tree 
pollen. A relationship between changes in allergy symptom scores and changes in
depression scores supports a state-level rather than only trait-level
relationship, and thus lends optimism to future causality-testing interventional 
studies, which might then lead to novel preventative environmental interventions 
in mood disorders.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18167612 [PubMed - indexed for MEDLINE]

182: Br J Nutr. 2008 Jul;100(1):112-9. Epub 2008 Jan 2.

Immunological and metabolic effects of cis-9, trans-11-conjugated linoleic acid
in subjects with birch pollen allergy.

Turpeinen AM, Ylönen N, von Willebrand E, Basu S, Aro A.

Department of Applied Chemistry and Microbiology (Nutrition), University of
Helsinki, PO Box 66, Helsinki 00014, Finland. anu.turpeinen@helsinki.fi

Animal studies suggest that conjugated linoleic acid (CLA) may modulate the
immune response, while studies in healthy human subjects have shown little effect
and results are controversial. However, the effects of CLA may be more prominent 
in situations of immune imbalance, such as allergy. We studied the effects of the
natural CLA isomer, cis-9, trans-11-CLA, on allergy symptoms and immunological
parameters in subjects with birch pollen allergy. In a randomised,
placebo-controlled study, forty subjects (20-46 years) with diagnosed birch
pollen allergy received 2 g CLA/d in capsules, which contained 65.3 % cis-9,
trans-11-CLA and 8.5 % trans-10, cis-12-CLA (n 20), or placebo (high-oleic acid
sunflower-seed oil) (n 20) for 12 weeks. The supplementation began 8 weeks before
the birch pollen season and continued throughout the season. Allergy symptoms and
use of medication were recorded daily. Lymphocyte subsets, cytokine production,
immunoglobulins, C-reactive protein, lipid and glucose metabolism and lipid
peroxidation were assessed before and after supplementation. The CLA group
reported a better overall feeling of wellbeing (P < 0.05) and less sneezing (P < 
0.05) during the pollen season. CLA supplementation decreased the in vitro
production of TNF-alpha (P < 0.01), interferon-gamma (P < 0.05) and IL-5 (P <
0.05). Total plasma IgE and birch-specific IgE concentrations did not differ
between groups, whereas plasma IgA (P < 0.05), granulocyte macrophage
colony-stimulating factor (P < 0.05) and eosinophil-derived neurotoxin (P < 0.05)
concentrations were lower after CLA supplementation. Urinary excretion of
8-iso-PGF2alpha, a major F2-isoprostane (P < 0.01), and
15-keto-dihydro-PGF2alpha, a primary PGF2alpha metabolite (P < 0.05), increased
in the CLA group. The results suggest that cis-9, trans-11-CLA has modest
anti-inflammatory effects in allergic subjects.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18167173 [PubMed - indexed for MEDLINE]

183: MedGenMed. 2007 Aug 15;9(3):35.

Treating the ocular component of allergic rhinoconjunctivitis and related eye
disorders.

Bielory L, Katelaris CH, Lightman S, Naclerio RM.

UMDNJ, New Jersey Medical School, Newark, New Jersey, USA. bielory@umdnj.edu

CONTEXT: Allergy symptoms that affect the eyes are common in adults and children 
worldwide, and are often associated with nasal allergy symptoms, prompting the
term 'rhinoconjunctivitis' to describe the condition. However, this condition has
not always been recognized, and earlier literature reported allergic
conjunctivitis only within a subset of nasal allergy patients. EVIDENCE
ACQUISITION: To assess the current state of ocular allergy epidemiology,
pathophysiology, and currently available treatment options, we performed a
MEDLINE search for articles regarding ocular allergy, rhinoconjunctivitis, vernal
keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant
papillary conjunctivitis (GPC). EVIDENCE SYNTHESIS: The more severe forms of
ocular allergy are not only distressing, but can also threaten a patient's
vision. Each type of ocular allergy is associated with ocular redness, itching,
and tearing; however, AKC and VKC can threaten the cornea, and research has
revealed that involvement of different immune cell populations (mast cells,
eosinophils, and lymphocytes) may cause these more severe symptoms. A variety of 
treatment options exist to control ocular allergy symptoms. Nonpharmacologic
options include allergen avoidance and lubrication with saline, and if these fail
to be sufficiently effective, symptom relief may be provided by medicinal agents 
that are either applied topically to the eye or taken orally. Recent evidence
suggests that nasal allergy treatments applied topically to the nose may also
positively affect ocular allergy symptoms, which raises the interesting
possibility that a parasympathetic nasal-ocular neural reflex pathway may be
involved in the stimulation of allergic responses in the eye. CONCLUSIONS: Ocular
allergy is underdiagnosed and has a significant impact on the life of the
patient. It is vital to reach a better understanding of ocular allergic
mechanisms and inflammation, which may lead to improved treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18092041 [PubMed - indexed for MEDLINE]

184: Laryngoscope. 2008 Mar;118(3):385-8.

Persistent allergic rhinitis includes different pathophysiologic types.

Ciprandi G, Cirillo I, Pistorio A.

Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino,
Genoa, Italy. gio.cip@libero.it

BACKGROUND: Allergy rhinitis is typically classified as seasonal allergy rhinitis
(SAR) and perennial allergy rhinitis (PAR). More recently, the Allergic Rhinitis 
and its Impact on Asthma document proposed the intermittent (ITR) and persistent 
forms (PER). However, it has been previously reported that each single allergen
may induce different clinical and pathophysiologic features. OBJECTIVE: The aim
of the study was to test the hypothesis that the type of causal allergen might
characterize pathophysiologic differences in a cohort of patients with PER.
METHODS: Three hundred nineteen patients, sailors of the Italian Navy, with
moderate-severe PER were prospectively and consecutively evaluated with clinical 
evaluation, skin prick test, rhinomanometry, and nasal decongestion test.
RESULTS: Patients with pollen allergy showed significantly more severe symptoms, 
lower nasal airflow, and higher response to decongestion test than patients with 
allergy to perennial allergens (P < .0001). CONCLUSION: This study provides
evidence that patients with PER may show different pathophysiologic patterns
depending on the type of causal allergen.

PMID: 18091329 [PubMed - indexed for MEDLINE]

185: Allergol Int. 2008 Mar;57(1):79-81. Epub 2008 Mar 1.

Correlations between alder specific IgE and alder-related tree pollen specific
IgE by RAST method.

Maeda Y, Ono E, Fukutomi Y, Taniguchi M, Akiyama K.

Clinical Center of National Hospital Organization Sagamihara Hospital, Kanagawa, 
Japan. y-maeda@sagamihara-hospital.gr.jp

BACKGROUND: Wild birch trees grow in limited areas in Japan and are not a common 
aero-allergen. However, many patients who do not live in the area show positive
birch pollen Radioallergosorbent Test (RAST). Therefore, being sensitized by
another tree pollen which is closely related to birch may result in showing a
specific IgE antibody to birch. Alder is a one of these trees and in the past it 
grew widely in Japan. However, there is no available RAST data as to the
correlations between alder and alder-related trees. METHODS: We measured the
alder specific IgE (CAP-RAST, Phadea) in stored sera which was positive in birch 
RAST (228 samples), beech RAST (36 samples), oak RAST (152 samples) and cedar
RAST (411 samples) and examined correlations between the RAST of alder and other 
trees. RESULTS: The correlation coefficient value of birch was very high (0.971).
The other coefficient values of beech and oak were high (0.884 in beech and 0.895
in oak) but were slightly lower than that of the birch. This means that in terms 
of allergenicities, birch pollen is almost the same as alder and beech and oak
are partly different from the alder. CONCLUSIONS: The Japanese respond to alder
pollen just same as they do to birch pollen in forming specific IgE antibody. In 
clinical practice, positive alder RAST has the same meaning as positive birch
RAST.

Publication Types: 
    Comparative Study

PMID: 18089941 [PubMed - indexed for MEDLINE]

186: J Investig Allergol Clin Immunol. 2007;17(6):399-405.

Efficacy and quality of life with once-daily sublingual immunotherapy with
grasses plus olive pollen extract without updosing.

Moreno-Ancillo A, Moreno C, Ojeda P, Domínguez C, Barasona MJ, García-Cubillana
A, Martín S.

Hospital Virgen del Puerto, Plasencia, Spain.

OBJECTIVE: The purpose of this randomized, double-blind, placebo-controlled study
was to evaluate the clinical efficacy and tolerance of once-daily sublingual
immunotherapy without updosing. Reduction in symptoms and medication use was the 
primary endpoint. METHODS: One hundred five patients with rhinitis and/or asthma 
due to grass and olive sensitization were randomized to be treated with placebo
or active sublingual immunotherapy with the SLITone grass mix plus olive pollen
extract for 6 months before the 2005 pollen season. Patients recorded symptoms
and medication intake for 8 weeks during the pollen seasons in 2004 (n=37) and
2005 (n=85). RESULTS: Allergic symptoms were significantly decreased in the
active immunotherapy group (P = .004) but not in the placebo group. There were no
differences in scores between groups during the 2005 pollen season. Subjective
assessments on a visual analog scale and a quality-of-life questionnaire
indicated an improvement in actively treated patients with significant
differences in both symptoms and medication use (P = .006). The rate of systemic 
adverse reactions was comparable in the 2 groups. No anaphylactic or severe
adverse reactions were reported. Local adverse reactions, which were more common 
in the active immunotherapy group, were mostly immediate, were limited to the
lips and mouth, and did not require treatment. CONCLUSION: Once-daily sublingual 
immunotherapy without updosing was well tolerated. The actively treated patients 
showed a significant reduction in symptom and medication scores and an
improvement in their quality of life although there were no significant
differences between the groups probably due to the low allergen season in which
the study was evaluated.

Publication Types: 
    Randomized Controlled Trial

PMID: 18088023 [PubMed - indexed for MEDLINE]

187: Int Arch Allergy Immunol. 2008;146(1):76-84. Epub 2007 Dec 14.

A randomized controlled trial of sublingual immunotherapy for Japanese cedar
pollinosis.

Horiguchi S, Okamoto Y, Yonekura S, Okawa T, Yamamoto H, Kunii N, Sakurai D,
Fujimura T, Nakazawa K, Yasueda H.

Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine,
Chiba University, Chiba, Japan.

BACKGROUND: Japanese cedar pollen represents an important and unique allergen.
Sublingual immunotherapy (SLIT) has been suggested to be a highly effective route
of desensitization against a variety of allergens. However, little information is
available about its use in cedar pollen allergy. METHODS: A blinded randomized,
placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a
period of 6 months. Sixty-seven subjects were enrolled and the symptom scores
during the pollen season were evaluated by a symptom diary, measurement of
cedar-specific IgE and IgG4, and determination of Cry j-specific Th2 clones
before SLIT and before and after the pollen season. RESULTS: No major adverse
effects were observed in either group. The serum-specific IgG4 activity increased
significantly after SLIT in the active group. The active group also exhibited
significantly lower symptom scores compared to the placebo. The specific Th2
clone sizes were not significantly different between the groups before the pollen
season. However, an increase in the clone size was observed after the pollen
season in the placebo group, but not in the active group. CONCLUSION: Use of SLIT
for Japanese cedar pollinosis was found to be safe and associated with an
increase in cedar-specific IgG4 levels. Such therapy inhibited the increase in
Cry j-specific Th2 clone size induced by pollen exposure. Finally, use of SLIT
resulted in significant improvement of the clinical symptoms of cedar pollinosis 
in this patient population. These observations suggest that SLIT may offer
another safe approach to the management of cedar pollinosis. Copyright 2007 S.
Karger AG, Basel.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18087165 [PubMed - indexed for MEDLINE]

188: Ann Epidemiol. 2008 Apr;18(4):283-9. Epub 2008 Feb 20.

Obesity and adult asthma: potential effect modification by gender, but not by hay
fever.

Loerbroks A, Apfelbacher CJ, Amelang M, Stürmer T.

Institute of Psychology, University of Heidelberg, Germany.
adrian.loerbroks@psychologie.uni-heidelberg.de

PURPOSE: First, we sought to estimate the magnitude of the cross-sectional
associations between overweight/obesity and asthma stratified by gender and by
self-reported hay fever and second we sought to assess both directions of
causality in longitudinal analyses. METHODS: We used cross-sectional and
longitudinal data from a population-based cohort study (n=5114, ages 40-65 at
baseline). After 8.5 years, 4010 adults were followed-up by questionnaires.
Self-reported height and weight were used to calculate body mass index
categories. Multivariate adjusted prevalence ratios (PRs), relative risks (RRs), 
and 95% confidence intervals (95% CI) were calculated using Poisson regression.
RESULTS: In cross-sectional analyses, adjusted PRs were comparable for overweight
women and men but differed between obese women and men (PR 1.93, 95% CI 1.19-3.14
and PR 0.98, 95% CI 0.56-1.72). PRs were similar when stratified by hay fever.
Longitudinal analyses suggested that overweight/obesity did not increase asthma
risk substantially (RR 1.02, 95% CI 0.50-2.06), but a relation between asthma and
subsequent weight gain could not be excluded (RR 1.34, 95% CI 1.01-1.77).
CONCLUSIONS: The prevalence of asthma is almost twice as high in obese versus
normal weight women, but not in obese men. The association between
overweight/obesity and asthma does not vary by hay fever. A causal relationship
between asthma and incident weight gain cannot be excluded.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18083546 [PubMed - indexed for MEDLINE]

189: Biosci Biotechnol Biochem. 2007 Dec;71(12):3019-25. Epub 2007 Dec 7.

Effects of polysaccharide derived from black currant on relieving clinical
symptoms of Japanese cedar pollinosis: a randomized double-blind,
placebo-controlled trial.

Dejima K, Ohshima A, Yanai T, Yamamoto R, Takata R, Yoshikawa T.

Department of Otolaryngology, Kyoto Second Red Cross Hospital, Kyoto, Japan.
kdejima2002@yahoo.co.jp

We investigated the efficacy of the polysaccharide derived from black currant,
named cassis polysaccharide (CAPS), for inhibiting Japanese cedar pollinosis
symptoms and improving quality of life by a randomized double-blind,
placebo-controlled trial in 2006. A total of 28 subjects were enrolled in the
study, and 10 subjects in each group completed the trial. Although there was no
significant difference between the CAPS and placebo group in the weekly mean
value of any symptom in the daily symptom diary at any time, a smaller degree of 
final symptom aggravation was found in the CAPS group. Significant aggravation of
the score was finally observed in the placebo group with inferior conch swelling 
and with sneezing, itchy nose, itchy eye and watery eye in the Japan
rhino-conjunctivitis quality of life questionnaire assessment, while the changes 
observed in the CAPS group were not significant. In conclusion, our findings
clearly indicate that CAPS would be useful as a food supplement in assisting the 
treatment of Japanese cedar pollinosis.

Publication Types: 
    Randomized Controlled Trial

PMID: 18071252 [PubMed - indexed for MEDLINE]

190: Clin Exp Allergy. 2008 Feb;38(2):329-37. Epub 2007 Dec 7.

Omalizumab is more effective than suplatast tosilate in the treatment of Japanese
cedar pollen-induced seasonal allergic rhinitis.

Nagakura T, Ogino S, Okubo K, Sato N, Takahashi M, Ishikawa T.

The Allergy and Internal Medicine, Yoga Allergy Clinic, Tokyo, Japan.
nagakura@yg-allergy.com

BACKGROUND: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is
a major problem in Japan. Omalizumab, a humanized monoclonal anti-IgE antibody,
improves symptoms associated with SAR, but a comparative study with an
anti-allergy drug has not yet been conducted. OBJECTIVE: To compare the efficacy 
and safety of omalizumab with suplatast tosilate, a selective T-helper type 2
(Th2) cytokine inhibitor, in patients with Japanese cedar pollen-induced SAR.
METHODS: A randomized, double-blind, double-dummy study was conducted in 308
Japanese patients with a history of moderate-to-severe SAR who showed a CAP-RAST 
value (> or =2+) specifically to Japanese cedar pollens. Patients were treated
for 12 weeks with omalizumab plus placebo of suplatast tosilate or suplatast
tosilate plus placebo of omalizumab. RESULTS: The mean daily nasal symptom
medication scores (sum of the daily nasal symptom severity score and daily nasal 
rescue medication score) were significantly lower in the omalizumab group than in
the suplatast tosilate group during three evaluation periods (P<0.001). The
omalizumab group also had significantly lower mean daily nasal severity scores,
each of the mean daily nasal and ocular symptom severity scores (sneezing, runny 
nose, stuffy nose, itchy nose, itchy eyes, watery eyes, and red eyes). Omalizumab
reduced rescue medication requirements, and the proportion of days with any
rescue medication use in the omalizumab group was significantly lower. Serum-free
IgE levels markedly decreased in the omalizumab group and it was associated with 
clinical efficacy. The adverse reaction profiles were similar between the two
groups. The overall incidence of injection site reactions was higher in the
omalizumab group than in the suplatast tosilate group, but all these events were 
of mild degree. No anti-omalizumab antibodies were detected. CONCLUSION:
Omalizumab showed significantly greater improvements than suplatast tosilate in
the treatment of SAR induced by Japanese cedar pollens.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18070163 [PubMed - indexed for MEDLINE]

191: Clin Exp Allergy. 2008 Mar;38(3):405-12. Epub 2007 Dec 7.

Seasonal changes in antigen-specific T-helper clone sizes in patients with
Japanese cedar pollinosis: a 2-year study.

Horiguchi S, Tanaka Y, Uchida T, Chazono H, Ookawa T, Sakurai D, Okamoto Y.

Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine,
Chiba University, Chiba, Japan.

BACKGROUND: Allergic rhinitis (AR) is a typical type I allergic disease that
occurs through the induction of allergen-specific effector T cells. Once
established, new effector T cells derive mostly from memory T cells that are
capable of surviving for extended periods, although the mechanisms by which these
memory functions are maintained have not yet been clarified. In particular, the
exact life-span of memory T cells is still not well understood. OBJECTIVE:
Pollinosis patients seemed to be suitable subjects to investigate because such
patients are exposed to antigens strongly for only a limited period once a year. 
We compared the seasonal changes in memory T-helper type 2 (Th2) between
pollinosis and perennial allergic subjects. METHODS: The clone sizes of the
Japanese cedar pollen-specific memory Th cells were measured by an ELISPOT assay 
using specific peptides from the patients with cedar pollinosis, and the seasonal
changes were noted. This study was performed for 2 years. The cedar-specific IgE 
levels in the peripheral blood were also studied. Mite allergy patients were also
enrolled in the study. RESULTS: The Japanese cedar-specific IL-4-producing Th2
cells were detected in all patients examined, although the number of cells was
low. These Th memory cells increased during the pollen season and decreased
during the off-season. However, more than 60% of the cedar-specific memory Th2
cells survived up to 8 months after the pollen season. The cedar-specific IgE
levels exhibited changes similar to the cedar-specific Th cells. On the other
hand, there was no drifting of Th memory clone size with the mite allergics, and 
the IgE levels also did not change. CONCLUSIONS: While pollen-specific Th cells
decreased after pollen exposure, their memory functions continued. Memory clone
size maintenance therefore requires repetitive antigen irritation.

Publication Types: 
    Comparative Study

PMID: 18070160 [PubMed - indexed for MEDLINE]

192: Drugs. 2007;67(18):2717-26.

Histamine and leukotriene receptor antagonism in the treatment of allergic
rhinitis: an update.

Van Hoecke H, Vandenbulcke L, Van Cauwenberge P.

Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
helen.vanhoecke@ugent.be

Allergic rhinitis represents a global health burden. The disease can seriously
affect quality of life and is associated with multiple co-morbidities. Histamine 
and leukotrienes are important pro-inflammatory mediators in nasal allergic
inflammation. Their actions on target cells are mediated through specific
receptors and, consequently, molecules that block the binding of histamine and
leukotrienes to their receptors have been important areas of pharmacological
research. The published literature of the pathophysiology of histamine and
leukotrienes, and the effects of histamine H(1)-receptor antagonists (H(1)
antihistamines) and leukotriene antagonists in monotherapy or in combination
therapy in the treatment of allergic rhinitis was reviewed. The presented results
are based on the best available evidence. The efficacy of H(1) antihistamines and
leukotriene antagonists (montelukast in particular) in allergic rhinitis has been
established in numerous randomised placebo-controlled trials. Results from
meta-analyses indicate that H(1) antihistamines and leukotriene antagonists are
equally effective in improving symptoms of allergic rhinitis and quality of life,
but that both drugs are less effective than intranasal corticosteroids. Data on
the combination of H(1) antihistamines and leukotriene antagonists in allergic
rhinitis are limited. The available evidence shows that a combined mediator
inhibition has additional benefits over the use of each agent alone, but is still
inferior to intranasal corticosteroids. More well designed studies are needed to 
fully understand the benefits of a concomitant use of these agents.

Publication Types: 
    Review

PMID: 18062720 [PubMed - indexed for MEDLINE]

193: Vaccine. 2007 Dec 21;26(1):77-81. Epub 2007 Nov 20.

Allergen immunotherapy in intermittent allergic rhinitis reduces the
intracellular expression of IL-4 by CD8+ T cells.

Glück J, Rogala B, Rogala E, Oleś E.

Medical University of Silesia, Zabrze, Poland. joagluck@mp.pl

BACKGROUND: T helper subset dysregulation is evident in allergic disorders. The
role of T cytotoxic subsets is less understood. We investigated whether allergen 
immunotherapy in intermittent allergic rhinitis influences the intracellular
expression of IL-4 and IFN-gamma by CD3+CD8(-) and CD3+CD8+ cells. METHODS:
Nineteen adult patients with intermittent allergic rhinitis were evaluated before
the pollen season, and then after one preseasonal course of subcutaneous allergen
immunotherapy. Twelve healthy nonatopic patients matched for age and sex served
as controls. Intracellular expression of IFN-gamma and IL-4 by CD3+CD8(-) (Th1
and Th2, respectively) and CD3+CD8+ (Tc1 and Tc2, respectively) was estimated by 
flow cytometry in peripheral blood cells after stimulation with PMA and
ionomycin. RESULTS: Before immunotherapy the percentages of Th1, Th2, Tc1 and Tc2
did not significantly differ between the patients and the controls. After
immunotherapy the percentage of Tc2 was lower in the rhinitic patients than in
the controls (0.38% vs. 0.45%, p=0.04). The percentage of Tc2 cells decreased
significantly after immunotherapy in the intermittent allergic rhinitis group
(0.64% vs. 0.38%, p=0.02) with tendency to decrease in ratios of Tc2/Tc1
(p=0.059) and with no changes in ratios of Th2/Th1. The percentages of Th1, Th2
and Tc1 were comparable before and after immunotherapy within the rhinitic
patient group. CONCLUSIONS: The preseasonal allergen subcutaneous immunotherapy
applied to intermittent allergic rhinitis patients suppressed the percentage of
IL-4 producing CD3+CD8+ cells. Decreased number of CD3+CD8+IL-4+ cells may
participate in the regulatory mechanisms of immunotherapy.

PMID: 18054415 [PubMed - indexed for MEDLINE]

194: Curr Med Res Opin. 2008 Jan;24(1):261-6.

Comparison of costs of sublingual immunotherapy and drug treatment in
grass-pollen induced allergy: results from the SIMAP database study.

Berto P, Frati F, Incorvaia C, Cadario G, Contiguglia R, Di Gioacchino M,
Puccinelli P, Senna GE, Valle C.

School of Pharmacy, University of Padova, Italy; PBE Consulting, Verona, Italy.

OBJECTIVES: This analysis is focused on the comparison of costs of allergic
rhinitis (R) alone or with allergic asthma (R + A) in grass pollen allergy, for
subjects treated with sublingual immunotherapy (SLIT) and symptomatic drugs,
versus standard care controls. METHODS: The SIMAP (Sublingual IMmunotherapy in
Allergic Patients) study is a longitudinal observational database operated by a
network of Allergy centers. Patients suffering from grass pollen allergy were
included in this analysis and assigned to SLIT (plus drugs as needed) or to
treatment with drugs alone. Outcome measures included use of medications, SLIT,
visits and tests. Costs were assessed from the perspective of the Italian
National Health Service; unit costs were obtained from published sources to
produce an average cost/patient for the first year after enrolment. RESULTS: One 
hundred and two patients were analyzed. Demographics were comparable in the two
groups. Overall per patient yearly cost of treatment was higher in SLIT patients,
both in the whole sample (euro311 vs. euro180/patient), in the R (euro288 vs.
euro116) and R + A (euro362 vs. euro230) subpopulations, with R + A patients
generating more costs than R patients in both groups. Nevertheless considerable
savings were obtained in the cost of symptomatic drugs (-22% for R; -34% for R + 
A) in SLIT patients. CONCLUSIONS: Other studies have shown that SLIT can reduce
the use of drugs for asthma and rhinitis, but this is the first time this outcome
has been demonstrated in a routine care population (in the medical practice
environment of an observational study) within the first year of treatment.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 18053319 [PubMed - indexed for MEDLINE]

195: Ann Allergy Asthma Immunol. 2007 Nov;99(5):453-61.

Sublingual-swallow immunotherapy with standardized 3-grass pollen extract: a
double-blind, placebo-controlled study.

de Blay F, Barnig C, Kanny G, Purohit A, Leynadier F, Tunon de Lara JM, Chabane
H, Guérin L; SUBLIM Group.

Département de Pneumologie, Hôpital Lyautey, Hôpitaux Universitaires de
Strasbourg, Strasbourg, France. frederic.deblay@chru-strasbourg.fr

BACKGROUND: Sublingual immunotherapy (SLIT) is accepted as a safe and effective
route for the treatment of grass pollen allergy, but clarification of its
clinical and biological efficacy requires more study. OBJECTIVE: To evaluate the 
efficacy, safety, and compliance of SLIT with a standardized 3-grass pollen
extract in patients with grass pollen seasonal allergic rhinoconjunctivitis, with
or without mild asthma. METHODS: This multicenter, randomized, double-blind study
included 127 patients (aged 12-41 years; mean age, 24.9 years) with grass pollen 
seasonal allergic rhinoconjunctivitis, with or without mild asthma. They received
either SLIT with a high-dose, standardized, 3-grass pollen extract or placebo for
10 months before and during the grass pollen season. The efficacy evaluation
compared weekly clinical scores (defined as the sum of the symptom score and
rescue medication score) to measure rhinoconjunctivitis and asthma for the first 
8 weeks of the pollen season. We also evaluated safety and compliance and
measured changes in anti-Dactylis specific IgG4 antibody levels. RESULTS: There
was a trend in favor of the study group in the mean adjusted clinical score. The 
groups were not comparable on inclusion (P = .02): the SLIT group included more
subjects with asthma and had a higher mean IgG4 serum level. Additional
exploration according to subgroups with and without asthma found that among the
patients without asthma, the SLIT group had a significantly better clinical score
(P = .045). Anti-Dactylis specific IgG4 levels increased significantly in the
SLIT group. CONCLUSION: SLIT with a standardized, high-dose, 3-grass pollen
extract is safe and significantly improves the clinical score in patients with
hay fever and without asthma during the pollen season.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18051216 [PubMed - indexed for MEDLINE]

196: J Investig Allergol Clin Immunol. 2007;17 Suppl 1:36-40.

Component-resolved diagnosis to optimize allergen-specific immunotherapy in the
Mediterranean area.

Valenta R, Twaroch T, Swoboda I.

Christian Doppler Laboratory for Allergy Research, Division of Immunopathology,
Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical
University of Vienna, Austria. rudolf.valenta@meduniwien.ac.at

Allergen-specific immunotherapy (SIT) is the only allergen-specific treatment for
allergy. It can prevent progression of the disease and has a long-lasting
therapeutic effect. Since SIT is allergen-specific, the identification of the
disease-eliciting allergen is an essential prerequisite for the accurate
prescription of treatment. Diagnostic tests based on allergen extracts consist of
mixtures of various allergens of which some are specific for the allergen source 
and others occur as cross-reactive allergens in various unrelated allergen
sources. It may therefore be difficult and sometimes impossible to identify the
disease-causing allergen with such tests, particularly in patients who are
sensitized to more than one allergen source. Sensitization to pollens from olive,
grasses, and Parietaria in the Mediterranean area is frequently treated with SIT.
Here, we describe allergen molecules from these sources that can be used for
component-resolved diagnosis of allergy to facilitate the selection of patients
for SIT and monitor the immunological effects of treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18050570 [PubMed - indexed for MEDLINE]

197: J Investig Allergol Clin Immunol. 2007;17 Suppl 1:31-5.

Modulation of allergic response by gene-environment interaction: olive pollen
allergy.

Cárdaba B, Llanes E, Chacártegui M, Sastre B, López E, Mollá R, del Pozo V,
Florido F, Quiralte J, Palomino P, Lahoz C.

Immunology Department, Jiménez Díaz-CAPIO Foundation, CIBERES (ISCIII), Madrid,
Spain. bcardaba@fjd.es

This article summarizes the most important advances of recent years in the field 
of gene-environment interaction in allergic response. It specifically examines
sensitization to olive pollen as an example of one of the main causes of allergic
disease in the Mediterranean area. The presence of at least 20 proteins with
allergic activity has been demonstrated in olive pollen, and 10 of these have
been characterized (Ole e 1 to Ole e 10). Ole e 1, which is considered to be the 
majority allergen (causing sensitization in more than 70% of patients), has been 
the subject of many studies looking for risk factors and ways to protect against 
sensitization. Markers of the major histocompatibility complex and other genetic 
loci associated with the allergic response have been analyzed using
population-based, family-based, and functional approaches, which have revealed
the involvement of genetic regulation in this type of response. Furthermore,
evaluation of environmental factors and their relationship with genetic factors
is essential when attempting to understand this type of disease. In this review, 
we provide examples of how exposure to high doses of olive pollen allergen in a
specific genetic context can trigger different allergic conditions (from asthma
to nonresponse). We stress the importance of evaluating these factors in order to
modulate this response correctly.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18050569 [PubMed - indexed for MEDLINE]

198: J Investig Allergol Clin Immunol. 2007;17 Suppl 1:24-30.

Modelling diseases: the allergens of Olea europaea pollen.

Quiralte J, Palacios L, Rodríguez R, Cárdaba B, Arias de Saavedra JM, Villalba M,
Florido JF, Lahoz C.

Allergology Section, Jaén Hospital Complex, Jaén, Spain. jqe01j@saludalia.com

This study analyzes the influence of the IgE response to certain olive pollen
allergens in the modulation of the different clinical phenotypes of allergic
disease and their relationship with the level of exposure to pollen and genetic
factors. Patients from high-exposure areas had a complex IgE antibody response to
allergens of Olea euroapea, which included 3 or more allergens in 75% of cases.
The majority allergens were Ole e 1, Ole e 2 (profilin), Ole e 7 (lipid
transporting protein), Ole e 9 (glucanase), and Ole e 10. The existence of the
antigen HLA-DR2 (15) led to a higher risk of sensitization to Ole e 10 and a
greater trend towards the development of severe asthma, which increased in the
presence of an anti-profilin IgE. Thirty percent of patients suffering from
pollinosis simultaneously presented allergy to vegetable foods. Anti-Ole e 7 IgE 
was significantly associated with fruit anaphylaxis and anti-profilin IgE was
detected in 90% of patients with oral syndrome. Finally, we analyzed the role of 
glucanase and Ole e 10 as causes of the pollen-latex-fruit syndrome.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18050568 [PubMed - indexed for MEDLINE]

199: J Investig Allergol Clin Immunol. 2007;17 Suppl 1:11-6.

Degree of olive pollen exposure and sensitization patterns. Clinical
implications.

Barber D, Moreno C, Ledesma A, Serrano P, Galán A, Villalba M, Guerra F,
Lombardero M, Rodríguez R.

Department of Research and Development, ALK-Abelló, SA, Madrid, Spain.
domingo.barber@alk-abello.com

BACKGROUND: Very high levels of exposure to olive pollen in the south of Spain
lead to differential allergen sensitization profiles. Therefore, new approaches
to allergen standardization, diagnosis, and vaccination are necessary. METHODS:
Quantification of minor allergens in extracts, component-resolved patient
diagnosis, and IgG4 individual allergen responses were used to evaluate new
strategies in the management of olive pollen allergy. RESULTS: Allergen
variability observed between different olive cultivars can be used to identify
suitable allergen sources that can be combined to yield consistent allergen
extracts for diagnosis and immunotherapy. Component-resolved diagnosis can
provide a better patient classification. IgG4 levels to major allergens increase 
significantly, whereas specific IgG4 to minor allergens does not seem to
increase, at least during the early phases of immunotherapy. CONCLUSION: Patients
exposed to extreme olive pollen levels display a different severity of allergy
from those exposed to normal levels, which makes it necessary to follow a
different clinical approach. The use of component-resolved diagnosis, better
standardized allergen extracts, and new efficacy monitoring techniques will lead 
to a significant improvement in the management of olive allergy disease.

PMID: 18050566 [PubMed - indexed for MEDLINE]

200: J Investig Allergol Clin Immunol. 2007;17 Suppl 1:4-10.

Olive pollen recombinant allergens: value in diagnosis and immunotherapy.

Rodríguez R, Villalba M, Batanero E, Palomares O, Quiralte J, Salamanca G,
Sirvent S, Castro L, Prado N.

Department of Biochemistry and Molecular Biology, Faculty of Chemistry,
Complutense University of Madrid, Madrid, Spain. rrg@bbm1.ucm.es

Olive pollen has a complex allergenic profile, from which more than 10 allergens 
have been identified and characterized. Some of these belong to well-known
protein families and others cannot be included in reported biochemical types.
Most of these allergens have been produced by recombinant technology, mainly in
Escherichia coli or in Pichia pastoris, and they are good candidates for
diagnostic and therapeutic purposes. Diagnosis and immunotherapy of allergy
currently use extracts prepared from homogenates of natural sources, which only
allow us to detect sensitivity to the complete source. These extracts can be
successfully replaced by mixtures with controlled amounts of specific allergenic 
proteins obtained by recombinant technology in order to define the sensitization 
profile of individual patients. Recombinant Ole e 1 can be used as a marker for
sensitization to Oleaceae. Recombinants Ole e 2 (profilin) and Ole e 3
(polcalcin) can serve as markers of polysensitivity. Finally, recombinant forms
of Ole e 6, Ole e 10, and the carboxy-terminal and amino-terminal domains of Ole 
e 9 would help to detect sensitization to these minority allergens that could be 
overlooked in the complete olive pollen extract. These recombinant molecules can 
help provide an accurate diagnosis of sensitivity to individual allergens and,
therefore, improve the design of more efficacious allergen-based immunotherapy
strategies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18050565 [PubMed - indexed for MEDLINE]

201: Allergy. 2007;62 Suppl 85:17-25.

A survey of the burden of allergic rhinitis in Europe.

Canonica GW, Bousquet J, Mullol J, Scadding GK, Virchow JC.

Facoltà di Medicina e Chirurgia, Dipartimento di Medicina Interna e Specialità
Mediche (DIMI), University of Genova, Genova, Italy.

BACKGROUND: The perceptions of patients and physicians regarding the symptoms and
impact of allergic rhinitis (AR) were assessed in a prospective, cross-sectional,
international survey. This paper presents the combined survey results from five
European countries (Germany, France, Italy, Spain and the UK). METHODS: Data were
recorded by 1,482 patients and matched with records from 415 primary care
physicians and specialists. Diagnostic tests to confirm AR had been performed on 
1,279 (86.3%) patients. Both physicians and patients recorded the presence,
severity and impact of symptoms at the time of consultation in addition to those 
symptoms frequently, but not currently, present. Health-related quality of life
(HRQoL) was assessed using the Mini Rhinoconjunctivitis Quality of Life
Questionnaire. RESULTS: A large proportion of patients had moderate-severe
disease (67.2%; n = 996), persistent disease (42.5%; n = 630) and comorbidities
such as asthma (31.5%; n = 467). Overall, patients rated their disease as more
severe than did physicians (P < 0.001). At the time of the consultation,
one-third of all patients reported that their current nasal and ocular symptoms
were moderate or severe in nature. According to the physicians' assessment, good 
control of nasal and ocular symptoms was achieved in 45.4% (n = 673) and 51.3% (n
= 760) of patients, respectively, and poor symptom control in 18.0% (n = 267) and
12.1% (n = 179). Overall, 43.3% (n = 641) of those surveyed were using two or
more medicines for their AR. Health-related quality of life was correlated with
disease severity and with the number of days without symptoms in the previous 4
weeks. Allergic rhinitis had a significantly greater impact in patients with more
persistent disease than in those with intermittent disease (2.3 +/- 1.3 vs 1.9
+/- 1.2; P < 0.001). Nonetheless, 81.8% (n = 601) of patients with intermittent
disease reported some impairment of their daily life as a result of their AR.
CONCLUSIONS: Allergic rhinitis remains a significant health problem because of
the high burden of symptoms and its impact on general well being and HRQoL among 
patients consulting for this condition. Overall, there was a poor correlation
between patients and physicians in the reporting of disease severity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17927674 [PubMed - indexed for MEDLINE]

202: Allergy. 2007;62 Suppl 85:9-16.

A survey of the burden of allergic rhinitis in the USA.

Schatz M.

Department of Allergy, Kaiser Permanente Medical Center, San Diego, CA 92111,
USA.

BACKGROUND: A prospective, cross-sectional, international survey was conducted
among patients and physicians to identify symptom perception and the impact of
allergic rhinitis (AR) on health-related quality of life (HRQoL). This paper
presents the results from the USA. METHODS: Data were recorded by 447 patients
and matched with data collected on these patients by primary care physicians or
specialists. Tests to confirm a diagnosis of AR had been performed on 345 (77.2%)
patients. Because of the intermittent nature of the disease, both physicians and 
patients recorded the presence, severity and impact of symptoms at the time of
consultation, in addition to symptoms frequently, but not currently, present.
Health-related quality of life was assessed using the Mini Rhinoconjunctivitis
Quality of Life Questionnaire. RESULTS: According to the physicians' assessment, 
a large proportion of patients had moderate or severe disease (62.6%; n = 280),
persistent disease (47.0%; n = 213) and comorbidities such as asthma (28.4%; n = 
127). Comparison of the physicians' and patients' assessment of disease severity 
found that patients rated their disease as more severe than physicians across all
three types of AR (P < 0.001). At the time of the consultation, 44.0% (n = 197)
of patients were suffering from nasal and ocular symptoms, and 23.7% (n = 106) of
all patients reported that their current nasal and ocular symptoms were moderate 
or severe in nature. More than 50% of the patients surveyed (56.4%; n = 252) were
using two or more medications for their AR. Health-related quality of life
correlated negatively with the number of symptom-free days in the previous 4
weeks. Allergic rhinitis had a significantly greater impact on patients with more
persistent disease compared with those with intermittent disease (2.3 +/- 1.3 vs 
1.4 +/- 1.1; P < 0.001); nevertheless, approximately two-thirds of patients with 
intermittent disease reported some impairment of their professional or daily life
as a result of AR. CONCLUSIONS: The results of this survey highlight the unmet
needs of the many patients in the USA who present during routine care with
moderate or severe and/or persistent disease and an associated high symptom
burden and impaired HRQoL.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17927673 [PubMed - indexed for MEDLINE]

203: Allergy. 2007;62 Suppl 85:6-8.

Physician and patient survey of allergic rhinitis: methodology.

Higgins V, Kay S, Small M.

Adelphi Group Products, Adelphi Mill, Bollington, Cheshire, UK.

Methodology for Disease Specific Programme (DSP) surveys designed by Adelphi
Group Products is used each year to survey patients and physicians on their
perceptions of treatment effectiveness, symptoms and impact of diseases. These
point-in-time surveys, conducted in the USA and Europe (France, Germany, Italy,
Spain and UK), provide useful information on the real-world management and
treatment of diseases. This paper describes the methodology for the DSP survey in
allergic rhinitis, detailing the preparation of materials, recruitment of
physicians, data collection and data management.

PMID: 17927672 [PubMed - indexed for MEDLINE]

204: Otolaryngol Head Neck Surg. 2007 Dec;137(6):918-24.

Erratum in:
    Otolaryngol Head Neck Surg. 2008 Feb;138(2):258. Beezley, Susan F [corrected to
Beezley, Sally F].

An assessment of the onset and duration of action of olopatadine nasal spray.

Patel P, Roland PS, Marple BF, Benninger PJ, Margalias H, Brubaker M, Beezley SF,
Drake M, Potts SL, Wall GM.

Allied Research International, Mississauga, ON, Canada.
ppatel@allied-research.com

OBJECTIVE: Seasonal allergic rhinitis (SAR) is a highly prevalent disease. This
study was conducted to evaluate the onset and duration of action of three
concentrations of olopatadine nasal spray. METHODS: This was a randomized,
double-blind, single-dose, placebo-controlled study, conducted in an
environmental exposure chamber in patients with SAR. A total of 320 patients were
exposed to ragweed allergen in the chamber and randomized to olopatadine nasal
spray 0.2%, 0.4%, 0.6%, or placebo nasal spray. Symptoms (sneezing, runny, itchy,
and stuffy nose) were self-assessed during a 12-hour study period. RESULTS: All
concentrations of olopatadine nasal spray provided clinically meaningful
reductions in total nasal symptom scores at 30 minutes compared to the placebo.
Olopatadine nasal spray 0.6% was significantly more effective (P < 0.05) than
placebo nasal spray at all time-points starting at 90 minutes post-dose and
continuing over 12 hours. CONCLUSIONS: Olopatadine nasal spray 0.6% demonstrated 
a fast onset of action and maintained an effect for at least 12 hours after
dosing.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18036421 [PubMed - indexed for MEDLINE]

205: Asian Pac J Allergy Immunol. 2007 Jun-Sep;25(2-3):121-6.

Is pulmonary arterial pressure affected by allergic rhinitis with nasal
obstruction?

Bayrak P, Kirmaz C, Sekuri C, Yuksel H.

Division of Immunology and Allergy, Department of Internal Medicine, Celal Bayar 
University, Medical Faculty, Turkey.

Obstructive pathologies of the pulmonary tract may cause various levels of
hypoxia. To compensate for the hypoxia, pulmonary arterial pressure and pulmonary
arterial flow may increase. We investigated 35 patients with seasonal allergic
rhinitis (AR) whether hypoxia caused by AR with a high level of obstruction in
the airways may lead to an increased pulmonary arterial pressure. An
echocardiographical evaluation was made following the determination of the
symptomatic and non-symptomatic symptom scores. We found a positive correlation
between the symptom scores both in the symptomatic and non-symptomatic periods,
nasal obstruction scores and the mean pulmonary arterial pressures during these
periods. Further studies with more cases are needed in order to determine the
cardiac effects of hypoxia in AR, mainly pulmonary arterial hypertension.

PMID: 18035798 [PubMed - indexed for MEDLINE]

206: Clin Ther. 2007 Sep;29(9):1795-802.

Desloratadine treatment for intermittent and persistent allergic rhinitis: a
review.

Bachert C, van Cauwenberge P.

Department of Otorhinolaryngology, University Hospital Ghent, Ghent, Belgium.
claus.bachert@ugent.be

BACKGROUND: Allergic rhinitis (AR) has a high prevalence and substantial impact
on quality of life (QoL). The traditional classification of AR as either seasonal
or perennial is being superseded in many countries by the ARIA (Allergic Rhinitis
and its Impact on Asthma) definitions, in which the term intermittent AR denotes 
the presence of symptoms for <4 days a week or <4 weeks, and the term persistent 
AR denotes the presence of symptoms for >4 days a week for >4 weeks. These
definitions, particularly that of persistent AR, may better reflect the true
pattern of AR as it is experienced by patients. Desloratadine has been approved
by the European Medicines Evaluation Agency for the treatment of intermittent and
persistent AR, as defined by the ARIA classification. OBJECTIVE: The purpose of
this review was to assess data concerning desloratadine in relation to the ARIA
definitions of intermittent and persistent AR. METHODS: Relevant clinical studies
and information on treatment guidelines were identified through searches of the
English-language literature indexed on MEDLINE through May 2007. Search terms
included intermittent AR, persistent AR, seasonal AR, perennial AR, and
desloratadine. Results: Desloratadine has been found to be effective and well
tolerated in studies in subjects with symptoms of AR analogous to/consistent with
the ARIA definitions of intermittent and persistent disease. In a 2-week,
randomized, double-blind, placebo-controlled study in subjects with a > or
=2-year history of intermittent AR, desloratadine was associated with greater
reductions relative to placebo in congestion scores (P < 0.05) and total symptom 
scores (TSS) (P <0.01). In a 4-week, multicenter, randomized, double-blind,
placebo-controlled study in subjects with a > or =2-year history of perennial AR,
desloratadine had greater efficacy than placebo in terms of reductions in TSS as 
early as day 2 (P > or = 0.02), as well as reductions in nasal and nonnasal
symptom scores (P > or =0.04). A 4-week, randomized, double-blind,
placebo-controlled study assessing QoL found that desloratadine improved QoL
scores to a greater extent than placebo in subjects with a > or =2-year history
of perennial AR (P = 0.009). Conclusions: According to the ARIA guidelines,
second-generation antihistamines are a cornerstone of pharmacologic therapy for
AR. Desloratadine is effective in the treatment of AR across all classifications 
of disease, either seasonal/perennial or intermittent/persistent.

Publication Types: 
    Review

PMID: 18035184 [PubMed - indexed for MEDLINE]

207: Allergy Asthma Proc. 2007 Sep-Oct;28(5):592-9.

Onset and duration of action of nasal sprays in seasonal allergic rhinitis
patients: olopatadine hydrochloride versus mometasone furoate monohydrate.

Patel D, Garadi R, Brubaker M, Conroy JP, Kaji Y, Crenshaw K, Whitling A, Wall
GM.

Allied Research International, Inc., Mississauga, Ontario, Canada.

Rapid relief of symptoms should be one of the primary goals of treatment for
allergic rhinitis (AR). The onset and duration of action of olopatadine
hydrochloride nasal spray, 665 mcg (OLO; Patanese), for seasonal AR (SAR) was
evaluated in this study. This study was performed to determine the onset and
duration of action of OLO compared with placebo spray, with mometasone furoate
monohydrate, 50 mcg (MM; Nasonex), as a reference standard. This was a single
center, single-dose, randomized, double-blinded parallel-group environmental
exposure chamber study. Patients were primed at two 2-hour priming visits.
Eligible patients were randomized to OLO, placebo spray, or MM, 2 sprays/nostril.
Allergy symptoms (sneezing, runny, itchy, and stuffy nose) were rated by patients
at 16 time points during 12 hours after dosing and patient satisfaction was
assessed at 4 and 12 hours postdose. Safety was assessed by a review of adverse
events, cardiovascular and nasal examination parameters. Four hundred twenty-five
adult patients were randomized. OLO was superior to placebo spray in reducing
total nasal symptoms (TNSS) within 30 minutes after dosing and maintained
superiority for at least 12 hours (p < 0.05). The onset of MM was not observed
until 150 minutes postdose and was smaller in magnitude compared with OLO. OLO
was superior to both placebo spray (p < 0.0001) and MM (p < 0.05) in patient
satisfaction. Treatment was well-tolerated with no safety concerns. OLO is
superior to placebo spray and MM in reducing allergy symptoms; OLO has a rapid
onset of action and a duration of effect of at least 12 hours.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18034980 [PubMed - indexed for MEDLINE]

208: Clin Physiol Funct Imaging. 2008 Mar;28(2):81-5. Epub 2007 Nov 22.

Allergic rhinitis with hyper-responsiveness differ from asthma in degree of
peripheral obstruction during metacholine challenge test.

Aronsson D, Tufvesson E, Ankerst J, Bjermer L.

Department of Respiratory Medicine and Allergology, Institution of Clinical
Medicine and Science, University Hospital, Lund, Sweden. david.aronsson@med.lu.se

Allergic rhinitis (AR) is a risk factor for developing clinical asthma. Moreover,
AR is often associated with bronchial hyper-responsiveness (BHR). The aim of this
study was to compare the degree of involvement of the peripheral airways during
metacholine (MCh) challenge test in asthmatics and patients with AR with or
without BHR by using the impulse oscillometry (IOS) technique. Fifty-three
patients with seasonal AR were investigated with MCh challenge test and IOS.
Thirteen healthy non-reactive subjects served as controls. MCh challenge test was
performed, cut-off value FEV1PD20 2000 microg. Linear regression analysis was
used to calculate a MCh/FEV1 slope (Slope-FEV1MCh), which was used as an index of
BHR. IOS was performed, measuring respiratory resistance and reactance during the
MCh challenge test. Twenty-six subjects had both AR and asthma symptoms, 27
patients reported AR only, without asthma symptoms, 17 (63%) manifested BHR by
spirometric criteria. Patients with AR and symptoms of asthma manifested greater 
peripheral airway obstruction compared to those with AR only with BHR. Increased 
peripheral obstruction in the asthmatic group compared to patients with AR and
BHR may explain previous findings that asthmatics perceive greater airway
obstruction during MCh challenge tests.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18034849 [PubMed - indexed for MEDLINE]

209: J Allergy Clin Immunol. 2008 Jan;121(1):105-9. Epub 2007 Oct 29.

Intranasal noninhaled carbon dioxide for the symptomatic treatment of seasonal
allergic rhinitis.

Casale TB, Romero FA, Spierings EL.

Division of Allergy and Immunology, Department of Medicine, Creighton University,
Omaha, NE 68131, USA. tbcasale@creighton.edu

BACKGROUND: Noninhaled intranasal carbon dioxide (CO2) has been shown to be
effective in the abortive treatment of migraine headache. Migraine headache is
associated with trigeminal neuronal activation and release of calcitonin
gene-related peptide, events also implicated in allergic rhinitis. Intranasal CO2
might inhibit trigeminal neuronal activation and suppress the release of
calcitonin gene-related peptide. OBJECTIVE: We studied whether noninhaled
intranasal CO2 would be effective in the treatment of seasonal allergic rhinitis.
METHODS: We conducted a single-center, randomized, double-blind,
placebo-controlled, parallel-group study. Treatment consisted of either CO2
(verum) or air (placebo) at a 2:1 ratio administered in each nostril for 60
seconds per nostril at a flow rate of 10 mL/s. The primary efficacy end point was
the change from baseline in total nasal symptom score (TNSS), the sum of
congestion, rhinorrhea, itching, and sneezing scored on a 0- to 5-point scale, at
30 minutes. RESULTS: Eighty-nine subjects received treatment, 60 with CO2 and 29 
with placebo, and all subjects completed the study. CO2 resulted in a
statistically significant improvement in TNSS at 30 minutes over placebo
(absolute changes of 5.0 for CO2 and 2.2 for placebo, P = .00019). Improvement
from baseline in TNSS (CO2 vs placebo) was statistically significant at 10
minutes and remained so for 24 hours. CONCLUSION: Two 60-second intranasal CO2
treatments resulted in rapid (10 minutes) and sustained (24 hours) relief of
seasonal allergic rhinitis symptoms.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18028997 [PubMed - indexed for MEDLINE]

210: Allergy. 2008 Mar;63(3):292-8. Epub 2007 Nov 20.

Frequency and impact of allergic rhinitis in asthma patients in everyday general 
medical practice: a French observational cross-sectional study.

Magnan A, Meunier JP, Saugnac C, Gasteau J, Neukirch F.

INSERM, Nantes; Université de Nantes, Faculté de Médecine, Nantes and CHU Nantes,
l'Institut du Thorax, Service de Pneumologie, Nantes, France.

BACKGROUND: Allergic rhinitis (AR) and asthma are inflammatory conditions of the 
airways that often occur concomitantly. This observational, cross-sectional,
national study was undertaken to describe the frequency and severity of AR in
asthmatic patients. The impact of AR on the quality of life and the therapeutic
management of patients in everyday general medical practice were also assessed.
METHODS: From April to October 2005, 1906 French general practitioners (GP)
participated in the study. Each physician had to fill out a questionnaire
(including the Juniper Asthma Control Questionnaire and a Rhinitis Questionnaire)
for up to 10 consecutive adult asthmatic patients. The first three patients with 
a confirmed diagnosis of AR (Allergic Rhinitis and its Impact on Asthma
classification) were asked to complete the Juniper Rhinoconjunctivitis Quality of
Life Questionnaire (RQLQ). RESULTS: A total of 14,703 patient questionnaires and 
4335 auto-questionnaires were analysed. Patients presented with intermittent
(45%), mild (25%), moderate (25%) and severe (4%) persistent asthma. The
frequency of AR in asthmatic patients was 55.2% (CI: 95%, 54.4-56.0%). Allergic
rhinitis was mild for 54% and moderate/severe for 46% of patients. The frequency 
and severity of AR increased with the severity of asthma (P < 0.001). Moreover,
AR was associated with worse asthma control whatever be the severity of asthma (P
< 0.001). The global RQLQ scores of AR patients worsened with the severity of
asthma (P < 0.001). Prescription of anti-asthma treatments significantly
increased with the severity of AR. The majority of AR patients (81%) were treated
for rhinitis. CONCLUSIONS: This survey suggested that AR was associated with more
severe asthma, more difficulty to control asthma and substantial impairment of
quality of life. The high frequency of AR in asthma patients requires that these 
conditions should be recognized and managed by GP.

PMID: 18028246 [PubMed - indexed for MEDLINE]

211: BioDrugs. 2007;21(6):403-10.

The role of anti-IgE therapy in combination with allergen specific immunotherapy 
for seasonal allergic rhinitis.

Stock P, Rolinck-Werninghaus C, Wahn U, Hamelmann E.

Department of Pediatric Pneumology and Immunology, Charité University Medicine,
Berlin, Germany.

Novel therapies that interfere specifically with immunologic mechanisms
underlying allergen-induced pathology are currently in clinical evaluation. Among
these is anti-IgE, which directly targets IgE serum antibodies, thus inhibiting
the central mechanism of immediate-type hypersensitivity reactions. Application
of anti-IgE antibodies effectively reduces IgE serum levels regardless of
allergen specificity. Anti-IgE therapy has been successfully tested in patients
with allergic rhinitis, asthma, and food allergy, showing significant efficacy in
reducing symptom scores and the use of rescue medications. However, such therapy 
is limited by high costs and the requirements for permanent or every-season
treatment. The advantage of specific immunotherapy (SIT) is the potential to
alter the course of the disease, which has been demonstrated in patients with
allergic rhinitis, insect venom allergy and, to a lesser degree, asthma. The
broader application of SIT is restricted by sometimes life-threatening adverse
effects. The combination of anti-IgE with SIT was suggested to be superior to
each single treatment protocol in children and adolescents with allergic
rhinitis. In a randomized, double-blind trial to assess the efficacy and safety
of anti-IgE (omalizumab) or placebo in combination with SIT (birch pollen or
grass pollen), the combination therapy reduced symptom load, the sum of daily
symptom severity score plus rescue medication use, over the birch and grass
pollen seasons by nearly 50% over SIT alone. These data show that the combination
of anti-IgE plus SIT may be beneficial for the treatment of allergic diseases,
offering improved efficacy, limited adverse effects, and potential
immune-modifying effects.

Publication Types: 
    Review

PMID: 18020623 [PubMed - indexed for MEDLINE]

212: Conf Proc IEEE Eng Med Biol Soc. 2007;2007:1479-82.

Clinical effects of far-infrared therapy in patients with allergic rhinitis.

Hu KH, Li WT.

Department of Biomedical Engineering, Chung-Yuan Christian University, Chung-Li, 
32023 Taiwan, ROC. drhook@ms68.hinet.net

Allergic rhinitis (AR) is the sixth most common chronic illness worldwide, which 
has a significant impact on patients' quality of life. The actual cost of AR is
staggering, approximately $5.6 billion being spent annually in direct medical
costs and other indirect costs. Therefore, it should be taken seriously upon its 
evaluation and treatment. AR is an IgE-mediated inflammation, which symptoms are 
likely due to increased vascular permeability. Current therapeutic options such
as avoidance of allergen, medication and immunotherapy are unsatisfactory.
Far-infrared (FIR) is an invisible electromagnetic wave with a wavelength longer 
than that of visible light. It has been used to treat vascular diseases as a
result of an increase in blood flow. The objective of this study was to evaluate 
the clinical effects of FIR therapy in patients with AR. Thirty-one patients with
AR were enrolled in this study. A WS TY101 FIR emitter was placed to face the
patient's nasal region at a distance of 30 cm. The treatment was performed for 40
min every morning for 7 days. Every day, patients recorded their symptoms in a
diary before and during treatment. Each symptom of rhinitis was rated on a
4-point scale (0-3) according to severity. During the period of FIR therapy, the 
symptoms of eye itching, nasal itching, nasal stuffiness, rhinorrhea and sneezing
were all significantly improved. Smell impairment was not improved until after
the last treatment. No obvious adverse effect was observed in the patients during
treatment and follow-up. We concluded that FIR therapy could improve the symptoms
of AR and might serve as a novel treatment modality for AR.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18002246 [PubMed - indexed for MEDLINE]

213: Am J Rhinol. 2007 Sep-Oct;21(5):556-9.

Fungus culture of the nasal secretion of chronic rhinosinusitis patients:
seasonal variations in Daegu, Korea.

Shin SH, Ye MK, Lee YH.

Department of Otorhinolaryngology, School of Medicine, Catholic University of
Daegu, Daegu, Korea. hsseung@cu.ac.kr

BACKGROUND: The role of fungi in the pathogenesis of chronic rhinosinusitis (CRS)
is being increasingly recognized. The presences of fungal spores are a necessary 
condition for fungal sinusitis, and fungal spore counts vary widely, both
geographically and seasonally. The aim of this study was to characterize fungal
seasonal variation in the nasal cavity of CRS patients and to compare it with
histologic types of nasal polyps. METHODS: One hundred eight patients with a
clinical diagnosis of CRS with polyps were enrolled in this study for 1 year.
Nasal secretions were obtained by aspiration and cultured to identify fungi.
Nasal polyps were divided into four histologic types: eosinophilic,
fibroinflammatory, seromucinous, and atypical. RESULTS: Positive cultures for
fungi were obtained in 60 of 108 (63.0%) CRS patients, and 28 of 45 (62.2%)
normal volunteers. Fungus culture rates were higher during summer and fall.
Cladosporium, Aspergillus, Alternaria, and Penicilium were frequently isolated
from CRS patients and normal volunteers. The most common histologic type was the 
fibroinflammatory type (60.2%), although in the summer and fall the proportion of
the eosinophilic type increased. CONCLUSION: Fungi were commonly cultured during 
a hot and humid environment, during summer and fall, and cultured organism types 
were found to be seasonal dependent. Histologic types of nasal polyps appear to
be associated with fungal culture rate, organism type, and seasonal variations.

PMID: 17999789 [PubMed - indexed for MEDLINE]

214: J Photochem Photobiol B. 2007 Dec 14;89(2-3):163-9. Epub 2007 Oct 5.

Effects of intranasal phototherapy on nasal mucosa in patients with allergic
rhinitis.

Koreck A, Szechenyi A, Morocz M, Cimpean A, Bella Z, Garaczi E, Raica M, Olariu
TR, Rasko I, Kemeny L.

Department of Dermatology and Allergology, University of Szeged, P.O. Box 427,
H-6701 Szeged, Hungary.

RATIONALE: Rhinophototherapy has been shown to be effective in the treatment of
allergic rhinitis. Considering that phototherapy with ultraviolet light (UV)
induces DNA damage, it is of outstanding importance to evaluate the damage and
repair process in human nasal mucosa. METHODS: We have investigated eight
patients undergoing intranasal phototherapy using a modified Comet assay
technique and by staining nasal cytology samples for cyclobutane pyrimidine
dimers (CPDs), which are UV specific photoproducts. RESULTS: Immediately after
last treatment Comet assay of nasal cytology samples showed a significant
increase in DNA damage compared to baseline. Ten days after the last irradiation 
a significant decrease in DNA damage was observed compared to data obtained
immediately after finishing the treatment protocol. Difference between baseline
and 10 days after last treatment was not statistically significant. Two months
after ending therapy, DNA damage detected by Comet assay in patients treated with
intranasal phototherapy was similar with that of healthy individuals. None of the
samples collected before starting intranasal phototherapy stained positive for
CPDs. In all samples collected immediately after last treatment strong positive
staining for CPDs was detected. The number of positive cells significantly
decreased 10 days after last treatment, but residual positive staining was
present in all the examined samples. This finding is consistent with data
reported in skin samples after UV irradiation. Cytology samples examined two
months after ending therapy contained no CPD positive cells. CONCLUSION: Our
results suggest that UV damage induced by intranasal phototherapy is efficiently 
repaired in nasal mucosa.

PMID: 17997323 [PubMed - indexed for MEDLINE]

215: Patient Educ Couns. 2008 Jan;70(1):111-7. Epub 2007 Nov 7.

Healthcare professional versus patient goal setting in intermittent allergic
rhinitis.

O'Connor J, Seeto C, Saini B, Bosnic-Anticevich S, Krass I, Armour C, Smith L.

The University of Sydney, Sydney, Australia.

OBJECTIVE: To examine the impact of healthcare professional versus patient goal
setting for the self-management of intermittent allergic rhinitis (AR) on symptom
severity and quality of life. METHODS: This was a 6 week, parallel group study.
Group A participants, with pharmacist facilitation, nominated personally relevant
goals and strategies relating to their AR. Group B participants had their goals
and strategies set by the pharmacist. The main outcome measures used included
perceived symptom severity and quality of life. In addition, goals and strategies
data from participants of both groups were collected and analysed. RESULTS: Both 
groups demonstrated significant improvements in symptom severity and quality of
life scores however Group B symptom severity scores improved more. Group B set a 
greater number of goals and strategies which were better structured and more task
specific. CONCLUSION: This is the first study to investigate the impact of goal
setting on patient behaviour in a chronic yet episodic illness. Our results
suggest that self-management goals set by the healthcare professional which are
clinically indicated but tailored to the patient's nominated symptoms yields
better outcomes than goals nominated by the patient. PRACTICE IMPLICATIONS: A
brief, structured intervention, tailored to patient symptoms, can enhance
self-management of intermittent allergic rhinitis.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17997261 [PubMed - indexed for MEDLINE]

216: Curr Opin Allergy Clin Immunol. 2007 Dec;7(6):556-60.

How strong is the evidence that immunotherapy in children prevents the
progression of allergy and asthma?

Jacobsen L, Valovirta E.

Allergy Learning and Consulting, Copenhagen, Denmark. info@allergylearning.dk

PURPOSE OF REVIEW: The purpose of this review is to describe the scientific
evidence that specific immunotherapy can prevent the development of asthma in
patients suffering from rhinoconjunctivitis as well as reduce the number of new
allergies developing. RECENT FINDINGS: Proposed strategies for the prevention of 
the development of allergic rhinoconjunctivitis and asthma include allergen
avoidance, pharmacological treatment (antihistamines and steroids) and specific
immunotherapy. Long-term follow-up on immunotherapy studies demonstrates that
specific immunotherapy for 3 years shows persistent long-term effects on clinical
symptoms after termination of treatment and long-term, preventive effects on
later development of asthma in children with seasonal rhinoconjunctivitis. It is 
so far the only treatment for allergic diseases that has been shown to be able to
prevent worsening of disease and development of asthma. Also, specific
immunotherapy seems to reduce the development of new allergic sensitivities as
measured by the skin prick test as well as specific IgE measurements. SUMMARY:
Specific immunotherapy is the only treatment that interferes with the basic
pathophysiological mechanisms of the allergic disease and thereby carries the
potential for changes in the long-term prognosis of respiratory allergy. Specific
immunotherapy should be recognized not only as first-line therapeutic treatment
for allergic rhinoconjunctivitis, but also as secondary preventive treatment for 
respiratory allergic diseases.

Publication Types: 
    Review

PMID: 17989534 [PubMed - indexed for MEDLINE]

217: J Pharmacol Sci. 2007 Nov;105(3):291-7. Epub 2007 Nov 6.

Polycyclic aromatic hydrocarbons aggravate antigen-induced nasal blockage in
experimental allergic rhinitis.

Mizutani N, Nabe T, Ohtani Y, Han HY, Fujii M, Yoshino S, Hirayama T, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi,
Misasagi, Yamashina, Kyoto 607-8414, Japan.

It has been hypothesized that air pollution has played a role in the increase in 
allergy prevalence. However, it remains unclear what exact roles are played by
polycyclic aromatic hydrocarbons (PAHs), which are encountered in the environment
in the form of air pollution, in allergic rhinitis. Thus, we examined whether
benzo(a)pyrene (BaP) and 1-nitropyrene (1-NP), representative PAHs, aggravate
allergic rhinitis symptoms, using a guinea-pig model. Sensitized animals were
repeatedly challenged by inhalation of Japanese cedar pollen once a week. BaP or 
1-NP was daily and intranasally administered for 2 weeks (short-term treatment)
or for 22 weeks from the time before the sensitization period (long-term
treatment). The short-term treatment affected neither nasal blockage nor sneezing
induced by antigen. In contrast, the long-term treatment aggravated the
antigen-induced nasal blockage that was induced 7 weeks after the start of the
treatment with BaP or 1-NP. This aggravation continued during the intranasal
treatment with PAH. However, neither sneezing nor Cry j 1-specific IgE antibody
production was affected even by the long-term treatment. In conclusion, the
long-term treatment with BaP and 1-NP can aggravate allergic rhinitis. The
mechanisms underlying this aggravation are not associated with production of Cry 
j 1-specific IgE.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17986815 [PubMed - indexed for MEDLINE]

218: Biosci Biotechnol Biochem. 2007 Nov;71(11):2852-5. Epub 2007 Nov 7.

Effects of Citrus unshiu powder on the cytokine balance in peripheral blood
mononuclear cells of patients with seasonal allergic rhinitis to pollen.

Tanabe S, Kinuta Y, Yasumatsu H, Takayanagi M, Kobayashi S, Takido N, Sugiyama M.

Graduate School of Biosphere Science, Hiroshima University, Japan.
stanabe@hiroshima-u.ac.jp

We evaluated the effects of a 50% methanol extract of Citrus unshiu powder (MEC) 
on cytokines in peripheral blood mononuclear cells (PBMCs) obtained from patients
with seasonal allergic rhinitis to cedar pollen. The levels of cytokines, such as
TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, IL-10, IL-12 (p70), IL-13, and GM-CSF,
produced by pollen-stimulated PBMC were measured. We found that MEC suppressed
pollen-induced TNF-alpha release and increased IFN-gamma release from PBMCs. The 
results suggest that Citrus unshiu powder has an immunomodulatory effect in vitro
and that its use could improve seasonal allergic rhinitis symptoms.

PMID: 17986783 [PubMed - indexed for MEDLINE]

219: Curr Allergy Asthma Rep. 2007 Nov;7(6):410-20.

Sublingual immunotherapy in pediatric allergic rhinitis and asthma: efficacy,
safety, and practical considerations.

Cox L.

Nova Southeastern University College of Osteopathic Medicine, 5333 North Dixie
Highway, Suite 210, Fort Lauderdale, FL 33334, USA. lindaswolfcox@msn.com

Specific allergen immunotherapy (SIT) is the only disease-modifying treatment for
allergic rhinitis and asthma. Subcutaneous immunotherapy (SCIT) is the only
method with a US Food and Drug Administration (FDA)-approved formulation, but
safety concerns limit administration to medical facilities. Sublingual
immunotherapy (SLIT), under investigation in the United States, appears to have a
more favorable safety profile, which may expand its use to populations generally 
not treated with SIT (eg, young children). This paper reviews SLIT studies that
were specifically limited to the pediatric population. Most demonstrated evidence
of clinical efficacy, but approximately 29% failed to demonstrate efficacy in
symptom and medication scores in the first treatment year. Efficacy was seen in a
broad range of allergen doses, but optimal dose range has not been established.
SLIT appeared to be well tolerated in children as young as 2 years, but serious
adverse reactions, including anaphylaxis, were reported. SLIT is a promising
immunotherapy that may expand the population receiving SIT because of the
convenience of home administration due to its favorable safety profile. However, 
questions remain unanswered, including optimal therapeutic dose.

Publication Types: 
    Review

PMID: 17986370 [PubMed - indexed for MEDLINE]

220: Eur J Epidemiol. 2008;23(1):17-22. Epub 2007 Nov 6.

A prospective study on the association between hay fever among children and
incidence of asthma in East Germany.

Rzehak P, Schoefer Y, Wichmann HE, Heinrich J.

GSF-National Research Center for Environment and Health, Institute of
Epidemiology, Ingolstaedter Landstrasse 1, Neuherberg, Germany.
peter.rzehak@gsf.de

BACKGROUND: Aim of this study was to examine the effect of hay fever in childhood
for asthma onset from childhood to adulthood in a prospective cohort of 3,199
asthma-free children, initially aged 5-13 years, which were followed for up to 12
years in East-Germany. METHODS: Crude and adjusted incidence rate ratios (IRR) of
asthma onset due to hay fever at baseline were calculated by a generalized
estimation equation approach accounting for person years at risk, age at study
entry, parental asthma, and gender. RESULTS: Overall 142 incident cases of asthma
were observed. Prevalence of hay fever at baseline was 4%. Crude and adjusted IRR
were essentially the same and showed overall and in each age group a substantial 
higher risk of asthma onset due to hay fever. The adjusted IRR was 4 overall and 
ranged between 3 and 5 within the three age groups. Restricting the analysis to
those participants, who were 17-25 years of age at the end of follow-up resulted 
in similar IRR. CONCLUSION: Hay fever in childhood is a strong predictor of
asthma onset later in life up to adulthood. The preventive potential of early and
efficient treatment of allergic rhinitis to avoid asthma development needs to be 
investigated.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17985197 [PubMed - indexed for MEDLINE]

221: Allergy. 2007 Dec;62(12):1372-8.

Health-related quality of life in allergic rhinitis: comparing the short form
ESPRINT-15 and MiniRQLQ questionnaires.

Valero A, Alonso J, Antépara I, Baró E, Colás C, del Cuvillo A, Ferrer M, Herdman
M, Marti-Guadaño E, Monclús L, Navarro-Pulido AM, Sastre J, Izquierdo I, Mullol
J.

Unidad de Alergia, Servicio de Neumologia y Alergia Respiratoria, Hospital
Clinic, Barcelona, Spain.

BACKGROUND: We compared the psychometric properties of the ESPRINT-15, the short 
form of a new Spanish instrument to measure health-related quality of life in
allergic rhinitis (AR) patients, with those of the Mini-Rhinoconjunctivitis
Quality of Life Questionnaire (MiniRQLQ). METHODS: The questionnaires were
compared in Spanish patients with intermittent allergic rhinitis (IAR) or
persistent AR in a prospective, observational study. Floor and ceiling effects,
internal consistency (Cronbach's alpha), test-retest reliability (intraclass
correlation coefficient; ICC), convergent and known groups validity, and
sensitivity to change (standardized response means; SRMs) were compared. RESULTS:
In terms of content, while the MiniRQLQ has a dimension covering practical
problems and places more emphasis on symptoms, the ESPRINT-15 has two dimensions 
(Sleep and Psychological impact) which are not included in the MiniRQLQ. In the
validation study, 400 patients were included and 59% of the sample had persistent
AR. There were no significant floor or ceiling effects on any dimension on either
questionnaire. Cronbach's alpha values for the ESPRINT-15 and MiniRQLQ overall
scores were 0.92 and 0.90, respectively. In 48 clinically stable patients, ICCs
were 0.80 and 0.77, respectively. Both instruments discriminated between patients
with IAR and persistent AR. Correlations with symptom scores and generic measures
were moderate to strong. SRMs for overall scores and individual dimensions on the
two questionnaires in the 197 patients reporting a change in health status ranged
from 0.7 to 1.3. CONCLUSIONS: Both questionnaires performed well in psychometric 
terms. The ESPRINT-15 is particularly recommended for use in Spanish-speaking
populations.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17983372 [PubMed - indexed for MEDLINE]

222: Int J Immunopathol Pharmacol. 2007 Apr-Jun;20(2 Suppl 2):65-7.

Allergenic pollens and spores in the working environment of Japanese pear
farmers.

Teranishi H, Uchida M, Hayashi S, Yamada N.

Department of Public Health, Faculty of Medicine, University of Toyama, Toyama,
Japan. hiterani@med.u-toyama.ac.jp

Occupational allergies such as pollinosis are reported in several agricultural
works in Japan. Many pollens and spores were observed in Japanese pear orchard
during the artificial pollination season. By the study on daily symptoms in an
allergic farmer, we confirmed that the pollinosis symptoms were most common and
most severe during the artificial pollination. These results suggest that the
exposure to allergenic pollens and spores induces allergic symptoms. Thus,
caution should be paid for the avoidance of the exposure to these allergenic
pollens and spores to prevent the allergy.

PMID: 17903360 [PubMed - indexed for MEDLINE]

223: Int J Immunopathol Pharmacol. 2007 Apr-Jun;20(2 Suppl 2):27-9.

High prevalence of pollinosis symptoms among the farmers cultivating Japanese
pears.

Hayashi S, Teranishi H, Shimooka Y, Yamada N.

Department of Environmental Systems Engineering, Toyama Prefectural University,
Toyama, Japan. setsuo@pu-toyama.ac.jp

In a district of Japanese pear cultivators, a questionnaire survey and an IgE
antibody survey were conducted on the pollinosis. A high prevalence of 36.3
percent of the farmers complained of pollinosis symptoms. By the IgE antibody
survey, the symptoms were found to be related to the airborne pollens in the
orchard.

PMID: 17903353 [PubMed - indexed for MEDLINE]

224: J Immunol. 2007 Nov 15;179(10):7157-65.

IL-21 administration into the nostril alleviates murine allergic rhinitis.

Hiromura Y, Kishida T, Nakano H, Hama T, Imanishi J, Hisa Y, Mazda O.

Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University 
of Medicine, Kyoto, Japan.

Type I allergic diseases such as allergic rhinitis are caused by IgE-mediated
humoral immune responses, while eosinophils also fulfill important roles in the
etiology of IgE-mediated allergy. IL-21 regulates growth, differentiation, and
function of T, B, and NK cells, while the production of IgE is also influenced by
IL-21. In this study we examined whether IL-21 is capable of controlling
IgE-mediated allergic reactions in vivo by using the allergic rhinitis mouse
model that was established by repetitive sensitization and intranasal challenge
with OVA. Intranasal administration with recombinant mouse IL-21 (rmIL-21)
significantly reduced the number of sneezes, as well as the serum concentration
of OVA-specific IgE, in comparison with that of untreated allergic mice. The
rmIL-21 treatment also suppressed germline Cepsilon transcription in the
nasal-associated lymphoid tissues, which may have, at least partly, resulted from
the up-regulation of Bcl-6 mRNA caused by IL-21. Local expression of IL-4, IL-5, 
and IL-13 was also inhibited by the intranasal cytokine therapy whereas, in
contrast, the expression of endogenous IL-21 mRNA was induced by exogenous
rmIL-21. Moreover, IL-21 acted on nasal fibroblasts to inhibit production of
eotaxin. This novel function of IL-21 may be associated with the attenuation of
eosinophil infiltration into nasal mucosa that was revealed by histopathological 
observation. These results indicated that IL-21 nasal administration effectively 
ameliorated allergic rhinitis through pleiotropic activities, i.e., the
prevention of IgE production by B cells and eotaxin production by fibroblasts.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17982108 [PubMed - indexed for MEDLINE]

225: Value Health. 2007 Nov-Dec;10(6):466-77.

Development and validation of a new Spanish instrument to measure health-related 
quality of life in patients with allergic rhinitis: the ESPRINT questionnaire.

ESPRINT Study Group and Investigators, Valero A, Alonso J, Antepara I, Baró E,
Colas C, del Cuvillo A, Ferrer M, Herdman M, Martí-Guadaño E, Monclús L, Mullol
J, Navarro-Pulido AM, Navas C, Sastre J, Baltasar M, Bartra J, Serrano C, Cardona
V, Castillo JA, Cerda MT, Cistero A, Conejero A, Davila I, Escudero C, Hernandez 
E, Vereda A, Fernandez B, Mencia J, Fernández J, Florido J, Quiralte J, Guardia
P, Malek T, Montoro J, Orta JC, Oehling A, Pascual MJ, de la Parte B, Raga E,
Rubira N, Ranea S, Rivas P, Serra J, Tabar A.

Unidad de Alergia, Servicio de Neumologia y Alergia Respiratoria, Hospital Clínic
i Provincial, C. Villarroel, 170, 08036 Barcelona, Spain. valero@clinic.ub.es

OBJECTIVES: To develop and validate an instrument to measure health-related
quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and
primarily for use in Spanish and Spanish-speaking populations. METHODS: An
initial item pool was generated from literature review, focus groups with AR
patients, and consultations with clinical experts. Item reduction was performed
using clinimetric and psychometric approaches after administration of the item
pool to 400 AR patients. The resulting instrument's internal consistency,
test-retest (2-4 weeks) reliability, known groups and convergent validity, and
sensitivity to change were tested in a longitudinal, observational, multicenter
study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of
Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1
(5.4) minutes to answer. Floor and ceiling effects were less than 15% on all
dimensions. Cronbach's alpha values and intraclass correlation coefficient values
for six of the sevendimensions and the overall score exceeded 0.70. Statistically
significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and
the overall score between patients with mild (mean overall score 1.97, SD 0.99), 
moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score
3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all
dimensions than patients with intermittent AR. Correlations between the
ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score
changes between the two study visits ranged from 0.96 to 1.76 for individual
dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed
instrument to measure HRQOL in AR patients has shown good reliability, validity, 
and sensitivity to change. It has also proved easy to use and administer.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17970929 [PubMed - indexed for MEDLINE]

226: Allergol Int. 2007 Dec;56(4):465-72. Epub 2007 Nov 1.

Effect of Cry-consensus peptide, a novel recombinant peptide for immunotherapy of
Japanese cedar pollinosis, on an experimental allergic rhinitis model in B10.S
mice.

Tsunematsu M, Yamaji T, Kozutsumi D, Murakami R, Kimura S, Kino K.

Research and Development Center, Division of Research and Development, Meiji
Dailies Corporation, Odawara, Kanagawa, Japan. MASAKO_TSUNEMATSU@MEIJI-MILK.COM

BACKGROUND: We are developing an immunotherapeutic peptide, Cry-consensus
peptide, for Japanese cedar pollinosis. Cry-consensus peptide is a recombinant
polypeptide containing six major human T-cell epitopes derived from both Cry j 1 
and Cry j 2, two major allergens of Japanese cedar pollen. We examined the effect
of Cry-consensus peptide on an allergic rhinitis model in B10.S mice, which have 
one common T-cell epitope in the Cry-consensus peptide. METHODS: B10.S mice were 
sensitized with Cry j 1/alum, then the Cry-consensus peptide was administered
subcutaneously once a week for 5 weeks from the last sensitization. Histamine was
dropped in both nostrils (10 microL per nostril) of each mouse on the day before 
continuous intranasal instillation of Cry j 1. Soon after the final challenge
with Cry j 1, the mice were observed for 5 minutes for the resulting number of
sneezes. In addition, serum levels of Cry j 1-specific IgE and IgG2a antibody,
eosinophil infiltration in nasal tissue, and Cry j 1-specific cytokine production
from splenocytes were evaluated. RESULTS: Cry-consensus peptide markedly
inhibited Cry j 1-induced sneezes, eosinophil infiltration, and eosinophil
peroxidase (EPO) activity in nasal tissue. Cry-consensus peptide inhibited the
production of anti-Cry j 1 IgE (Th2-mediated) and significantly enhanced anti-Cry
j 1 IgG2a (Th1-mediated). In cytokine production from splenocytes, Cry-consensus 
peptide significantly decreased in IL-4/IFN-gamma and IL-5/IFN-gamma ratios.
CONCLUSIONS: It was concluded that Cry-consensus peptide effectively controlled
allergic responses, which results from shifting from a Th2-dominated to a
Th1-dominated immune response.

PMID: 17965586 [PubMed - indexed for MEDLINE]

227: Allergol Int. 2007 Dec;56(4):427-31. Epub 2007 Nov 1.

Impact of nasal condition on self-assessed disease control and treatment
satisfaction in patients with asthma complicated by allergic rhinitis.

Koga T, Matsuse H, Kohrogi H, Kohno S, Aizawa H.

Department of Medicine, Division of Respirology, Neurology and Rheumatology,
Kurume University School of Medicine, Kurume, Fukoka, Japan.
kogat@med.kurume-u.ac.jp

BACKGROUND: Bodies of evidences have suggested that upper and lower airways are
intricately interconnected with each other in patients with allergic airways
diseases, however, few data are available concerning the impact of allergic
rhinitis on self-assessed asthma condition and treatment satisfaction. The
present study was conducted to clarify the association between nasal condition
and self-assessment of asthma control and treatment satisfaction. METHODS: Adult 
patients with asthma were consecutively recruited for a systematic
self-administered questionnaire to obtain information on nasal condition,
self-perceived condition of asthma, and asthma treatment satisfaction. RESULTS:
3,140 adult patients with asthma completed the questionnaire, and of these 634
patients (mean age:53.1, 389 female) had physician-diagnosed allergic rhinitis.
There were significant correlations between nasal symptoms (sneeze, rhinorrhea,
nasal obstruction) and self-perceived asthma condition (limited daily activity,
wheeze, dyspnea/chest tightness, cough, sputum, sleep disturbance, overall asthma
condition). Patients who considered their overall nasal condition as unfavorable 
or bad were more likely than those who considered their condition as good or
favorable to be dissatisfied with asthma treatment (p<0.01). CONCLUSIONS: Nasal
condition is closely associated with self-assessed asthma condition and asthma
treatment satisfaction. Controlling allergic rhinitis is critical to attain
optimal management of asthma in patients complicated by allergic rhinitis.

Publication Types: 
    Comparative Study

PMID: 17965581 [PubMed - indexed for MEDLINE]

228: J Pharmacol Sci. 2007 Nov;105(3):251-7. Epub 2007 Oct 27.

Nasal blockage induced by oral administration of non-steroidal anti-inflammatory 
drugs in a guinea-pig model of allergic rhinitis.

Han HY, Nabe T, Mizutani N, Fujii M, Terada T, Takenaka H, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi.
Misasagi, Yamashina, Kyoto 607-8414, Japan.

To elucidate the mechanisms underlying nasal symptoms in patients with aspirin
hypersensitivity, we evaluated the effects of orally administered non-steroidal
anti-inflammatory drugs (NSAIDs) on the nasal patency of guinea pigs with cedar
pollen-induced chronic allergic rhinitis. Indomethacin (10 mg/kg) administered 1 
h before a pollen challenge amplified the antigen-induced nasal blockage. More
interestingly, even in the absence of the pollen challenge, indomethacin induced 
nasal blockage at 30 min at 4 h after administration. However,
indomethacin-induced nasal blockage was not provoked in non-sensitized animals.
Another NSAID, diclofenac (30 mg/kg), also evoked nasal blockage, but
unexpectedly, aspirin (500 mg/kg) did not affect nasal patency.
Indomethacin-induced nasal blockage was unaffected by a cysteinyl leukotriene
receptor (CysLT(1) receptor) antagonist, pranlukast (30 mg/kg, p.o.), or by
prostaglandin E2 (10(-3) M, intranasal), suggesting that the nasal blockage may
not be due to hyperproduction of cysteinyl leukotrienes or inhibition of
prostaglandin E2 production. These results indicate that the indomethacin-induced
nasal blockage may not be an identical phenomena to airway symptoms in aspirin
hypersensitivity patients. However, because chronic nasal inflammation is
indispensable for the development of nasal blockage, indomethacin-induced nasal
blockage may become a clue to elucidate new mechanisms underlying
hypersensitivity to NSAIDs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17965537 [PubMed - indexed for MEDLINE]

229: Respir Med. 2008 Feb;102(2):256-65. Epub 2007 Oct 26.

Changes in airway hyperresponsiveness following smoking cessation: comparisons
between Mch and AMP.

Piccillo G, Caponnetto P, Barton S, Russo C, Origlio A, Bonaccorsi A, Di Maria A,
Oliveri C, Polosa R.

Smoking Cessation Research Centre, Department of Internal and Specialistic
Medicine, University of Catania, Ascoli-Tomaselli Hospitals, 95125 Catania,
Italy.

BACKGROUND: Given the observed association between smoking, inflammation and
airway hyperresponsiveness (AHR) one may predict that smoking cessation may
improve AHR. However, only a few studies have investigated the effect of smoking 
on AHR and their results appear to be conflicting depending on the stimulus used 
in their bronchoprovocation protocol. The aim of the current study was to compare
changes in AHR between direct (methacholine (Mch)) and indirect (adenosine
5'monophosphate (AMP)) stimuli before and at different time points after smoking 
cessation in smokers with allergic rhinitis (+/-asthma). METHODS: We have
prospectively studied changes in AHR to inhaled Mch and AMP in smokers with
allergic rhinitis (+/-asthma), before and at 6 and 12 months after smoking
cessation. RESULTS: It was found that 28% (16/57) of the participants had quit
smoking by the end of the study. No significant change in AHR was observed in
smoking cessation failures. A significant improvement in AHR to AMP but not Mch
was observed 6 months after smoking cessation in quitters; a 1.2 doubling
concentrations change in PC20 AMP was measured whereas only a 0.4 doubling
concentrations change was observed for PC20 Mch. However, after 12 months smoking
cessation the improvement in AHR became significant for both AMP and Mch, their
dose-response curves being displaced to the right to a similar extent (1.4 and
1.1 doubling concentrations for AMP and Mch, respectively). CONCLUSION: Smoking
cessation can improve AHR in smokers who quit with a 6 months improvement being
reported for the airways response to AMP but not Mch. AMP challenge may detect
earlier changes in AHR in smokers during smoking cessation.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17964770 [PubMed - indexed for MEDLINE]

230: Allergy. 2008 Mar;63(3):255-60. Epub 2007 Oct 18.

Impact of allergic rhinitis on asthma: effects on spirometric parameters.

Ciprandi G, Cirillo I, Pistorio A.

Department of Internal Medicine, Azienda Ospedaliera Universitaria San Martino,
Genoa, Italy.

BACKGROUND: Close association exists between allergic rhinitis and asthma.
Moreover, allergic rhinitis is a strong risk factor for the onset of asthma in
adults. This study was aimed at evaluating a large group of patients with
moderate-to-severe and persistent allergic rhinitis alone for investigating the
presence of spirometric abnormalities and possible risk factors related to it.
METHODS: A total of 392 patients with persistent allergic rhinitis were
prospectively and consecutively evaluated. Clinical examination, skin prick test 
and spirometry were performed in all patients. RESULTS: There were 24 (6.1%)
patients with forced vital capacity (FVC < 80%) of predicted, 50 (12.8%) with
forced expiratory volume in the first second (FEV(1) < 80%) of predicted and 341 
(87.0%) with forced expiratory flow at 25% and 75% of the pulmonary volume
(FEF(25-75)) < 80% of predicted. The logistic regression analysis evidenced that 
rhinitis duration (OR(Adj): 1.9/year) and sensitization to house dust mites
(OR(Adj): 8.2) were significantly associated with impaired values of 2 or 3
spirometric parameters. CONCLUSION: This study highlights the close link between 
upper and lower airways and the role of some risk factors, such as duration and
mites sensitization, as early prognostic markers of bronchial involvement in
patients with moderate-to-severe and persistent allergic rhinitis alone.

PMID: 17944984 [PubMed - indexed for MEDLINE]

231: Clin Exp Allergy. 2007 Dec;37(12):1773-80. Epub 2007 Oct 17.

Lipopolysaccharide administration to the allergic nose contributes to lower
airway inflammation.

Bachar O, Gustafsson J, Jansson L, Adner M, Cardell LO.

Laboratory of Clinical Experimental Allergy Research, Department of
Otorhinolaryngology, Malmö University Hospital, Malmö, Sweden.

BACKGROUND: Allergic rhinitis (AR) is an inflammatory reaction not confined to a 
single local compartment, but rather involving the whole airway system. Allergens
known to induce AR are not always the sole trigger of the inflammatory reaction
as infections and organic dust might also cause exacerbations of rhinitis and
associated conditions. OBJECTIVE: To examine the effects of intranasal
lipopolysaccharide (LPS) exposure, as a surrogate for upper airway bacterial
infections, in patients with symptomatic AR. METHODS: Fourteen patients with a
history of moderate to severe pollen-induced AR were challenged intranasally with
LPS. After 3-6 weeks, the same patients were challenged again, first with
allergen and 24 h later with LPS. Nasal symptom scores, nasal lavage leucocyte
counts and nasal airway resistance were assessed at 6-24 h after each provocation
along with measurements of nitric oxide (NO) levels in the nose and lung.
RESULTS: Six hours after the LPS challenge, an increased level of leucocytes
could be obtained in the lavage fluid, but no symptoms were experienced and no
increase in nasal resistance could be recorded. The NO production in the upper
and lower airways was similar before and 6 h after the provocation. In contrast, 
in patients exposed to pollen before the LPS challenge, both the nasal and the
pulmonary NO levels were enhanced. This was accompanied by an increase in
leucocytes. CONCLUSION: The present study demonstrates a priming effect of
allergen on the nasal response to LPS as well as the presence of a systemic link 
between airway mucosal sites in the upper and lower airways. This suggests that
exogenously derived signals, like upper airway infections, can interfere with the
initiation, maintenance and progression of asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17941911 [PubMed - indexed for MEDLINE]

232: Ann Allergy Asthma Immunol. 2007 Oct;99(4):358-63.

Safety and tolerability of fexofenadine for the treatment of allergic rhinitis in
children 2 to 5 years old.

Milgrom H, Kittner B, Lanier R, Hampel FC.

Department of Pediatrics, University of Colorado Health Sciences Center, National
Jewish Medical and Research Center, Denver 80206, USA. milgromh@njc.org

BACKGROUND: The safety of fexofenadine has been examined extensively in adults
and school-age children. However, the safety of fexofenadine in children younger 
than 6 years has not been reported to date. OBJECTIVE: To compare the safety and 
tolerability of twice-daily fexofenadine hydrochloride, 30 mg, and placebo in
preschool children aged 2 to 5 years with allergic rhinitis. METHODS: This was a 
multicenter, double-blind, randomized, placebo-controlled, parallel-group study, 
conducted between February 29, 2000, and June 14, 2001. Participants were
randomized to either fexofenadine hydrochloride, 30 mg, or placebo twice daily
for a 2-week period. To facilitate dosing, capsule content was mixed with
applesauce (approximately 10 mL). Safety assessments depended on date of entry
into the study because of an amendment to the protocol. Before the amendment,
assessments included physical examination, vital signs reporting (oral
temperature, heart rate, and respiratory rate), and adverse event (AE) reporting.
After the amendment, safety assessments included laboratory testing (blood
chemistry and hematology profiles), physical examination, 12-lead
electrocardiography, and vital signs (oral temperature, blood pressure, heart
rate, and respiratory rate) and AE reporting. RESULTS: Treatment-emergent AEs
were observed in 116 of 231 participants receiving placebo and 111 of 222
receiving fexofenadine. These AEs were possibly related to study medication in 19
(8.2%) and 21 (9.5%) of the participants receiving placebo and fexofenadine,
respectively, and most frequently involved the digestive system. No clinically
relevant differences in laboratory measures, vital signs, and physical
examinations were observed. CONCLUSIONS: The findings show that fexofenadine
hydrochloride, 30 mg, is well tolerated and has a good safety profile in children
aged 2 to 5 years with allergic rhinitis.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17941284 [PubMed - indexed for MEDLINE]

233: J Allergy Clin Immunol. 2007 Dec;120(6):1338-45. Epub 2007 Nov 1.

Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 
5-grass pollen tablet for seasonal allergic rhinitis.

Didier A, Malling HJ, Worm M, Horak F, Jäger S, Montagut A, André C, de Beaumont 
O, Melac M.

Department of Pneumology, Larrey Hospital, Toulouse, France.
Didier.a@chu-toulouse.fr

BACKGROUND: Sublingual immunotherapy is well tolerated and data suggest its
effectiveness for the treatment of allergic rhinitis in adults, but it lacks
optimum dose definition. OBJECTIVE: To assess the efficacy, safety, and optimal
dose of grass pollen tablets for immunotherapy of patients with allergic
rhinoconjunctivitis. METHODS: In this multinational, randomized, double-blind,
placebo-controlled study, 628 adults with grass pollen rhinoconjunctivitis
(confirmed by positive skin prick test and serum-specific IgE) received 1 of 3
doses of a standardized 5-grass pollen extract, or placebo, administered
sublingually using a once-daily tablet formulation. The treatment was initiated 4
months before the estimated pollen season and continued throughout the season.
The primary outcome was Rhinoconjunctivitis Total Symptom Score; secondary
outcomes included 6 individual symptom scores, rescue medication use, quality of 
life, and safety assessments. RESULTS: Both the 300-index of reactivity (IR) and 
500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score
(3.58 +/- 3.0, P = .0001; and 3.74 +/- 3.1, P = .0006, respectively) compared
with placebo (4.93 +/- 3.2) in the intent-to-treat and per-protocol analyses. The
100-IR group (4.70 +/- 3.1) score was not significantly different from placebo.
Analysis of all secondary efficacy variables (sneezing, runny nose, itchy nose,
nasal congestion, watery eyes, itchy eyes, rescue medication usage, and quality
of life) confirmed the efficacy of the 300-IR and 500-IR doses. No serious side
effects were reported. CONCLUSION: In the first pollen season, the efficacy and
safety of sublingual immunotherapy with grass tablets was confirmed. The 300-IR
and 500-IR doses both demonstrated significant efficacy compared with placebo.
CLINICAL IMPLICATIONS: The risk-benefit ratio favors the use of 300-IR tablets
for clinical practice.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17935764 [PubMed - indexed for MEDLINE]

234: Prim Care Respir J. 2007 Oct;16(5):299-303.

Concerns of patients with allergic rhinitis: the Allergic Rhinitis Care Programme
in South Africa.

Green RJ, Davis G, Price D.

Department of Paediatrics, University of Pretoria, South Africa.

BACKGROUND: The major reason for treating chronic rhinitis is to improve quality 
of life. Although primary symptoms cause morbidity in their own right, these
symptoms are significantly aggravated by the impact of cognitive dysfunction and 
quality of life. OBJECTIVE: The Allergic Rhinitis Care Programme was initiated by
the South African Allergic Rhinitis Working Group. An important task of this
programme was to document health-related quality of life impairment amongst
allergic rhinitis patients in South Africa. METHODS: A questionnaire, appropriate
to South Africa, was distributed to patients. The questionnaire inquired about
symptoms, quality of life, complications, trigger factors, associated allergic
conditions, medication preference, medication adherence and concerns about the
condition. RESULTS: 1181 people completed the questionnaire and returned the
survey. Nasal congestion was identified as a common and frequent problem, while
seasonality of symptoms was uncommon. Symptoms affected sleep in 76.6% of
sufferers, and in at least a third this was every night. Over 1000 respondents
felt miserable due to allergic rhinitis (85.2%). 63.1% indicated that they always
followed instructions for taking rhinitis medication. A variety of perceived
concerns around having and being treated for allergic rhinitis were identified,
suggesting multiple reasons for non-adherence. CONCLUSIONS: We report symptom
frequency and quality of life impairment for respondents who identify themselves 
as having allergic rhinitis. Since allergic rhinitis is, in the main, a
doctor-diagnosed condition, this would suggest a significant problem with
inappropriate, insufficient or incorrect therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17934676 [PubMed - indexed for MEDLINE]

235: Biosci Biotechnol Biochem. 2007 Oct;71(10):2551-6. Epub 2007 Oct 7.

Dietary pulverized konjac glucomannan prevents the development of allergic
rhinitis-like symptoms and IgE response in mice.

Onishi N, Kawamoto S, Ueda K, Yamanaka Y, Katayama A, Suzuki H, Aki T, Hashimoto 
K, Hide M, Ono K.

Department of Molecular Biotechnology, Graduate School of Advanced Sciences of
Matter, Hiroshima University, Japan.

Konjac is a traditional Japanese food with a peculiar texture, and it has been
suggested that its main ingredient, konjac glucomannan (KGM), ameliorates
metabolic disorders such as diabetes and hypercholesteremia. We have found that
feeding with pulverized KGM (PKGM) prevents skin inflammation in a murine model
of atopic dermatitis. Here, we show that dietary PKGM suppresses allergic
rhinitis-like symptoms in mice upon immunization and nasal sensitization with
ovalbumin (OVA). The PKGM-fed mice showed a much lower frequency of sneezing than
in control animals. We also found that PKGM supplementation exclusively
suppressed OVA-specific IgE response without affecting IgG1/IgG2a responses as
well as systemic Th1/Th2 cytokine production. These results suggest that PKGM can
be a beneficial foodstuff in preventing nasal allergy such as seasonal
pollinosis.

Publication Types: 
    Comparative Study

PMID: 17928709 [PubMed - indexed for MEDLINE]

236: Allergy. 2007;62 Suppl 84:1-41.

Common characteristics of upper and lower airways in rhinitis and asthma: ARIA
update, in collaboration with GA(2)LEN.

Cruz AA, Popov T, Pawankar R, Annesi-Maesano I, Fokkens W, Kemp J, Ohta K, Price 
D, Bousquet J; ARIA Initiative Scientific Committee.

ProAR, Programme for Control of Asthma and Allergic Rhinitis in Bahia, Federal
University of Bahia School of Medicine, and CNPq, Salvador, Brazil.

This update aimed to review the new evidence available to support or refute prior
Allergic Rhinitis and its Impact on Asthma (ARIA) statements. A Medline search of
publications between 2000 and 2005 was conducted, with articles selected by
experts. New evidence supports previous ARIA statements, such as: (i) allergic
rhinitis (AR) is a risk factor for asthma; (ii) patients with persistent rhinitis
should be evaluated for asthma; (iii) most patients with asthma have rhinitis;
(iv) a combined strategy should be used to treat the airways and (v) in low- to
middle-income countries, a different strategy may be needed. The increased risk
of asthma has also been found among sufferers from non-AR. Recent reports show AR
is a global problem. Many studies demonstrated parallel increasing prevalence of 
asthma and rhinitis, but in regions of highest prevalence, it may be reaching a
plateau. Factors associated with a reduced risk of asthma and AR have been
identified, confirming previous findings of protection related to exposure to
infections. Treatment of rhinitis with intranasal glucocorticosteroids,
antihistamines, leukotriene antagonists or immunotherapy may reduce morbidity
because of asthma. To take advantage of the paradigm of unified airways, there is
a need to rationalize diagnosis and treatment to optimize management.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17924930 [PubMed - indexed for MEDLINE]

237: Clin Ther. 2007 Aug;29(8):1738-47.

A 2-week, crossover study to investigate the effect of fluticasone furoate nasal 
spray on short-term growth in children with allergic rhinitis.

Gradman J, Caldwell MF, Wolthers OD.

Asthma and Allergy Clinic, Children's Clinic Randers, Randers, Denmark.
j.gradman@dadlnet.dk

BACKGROUND: It is essential to assess potential growth effects of any newly
developed corticosteroid. Fluticasone furoate is a recently approved, enhanced-
affinity intranasal corticosteroid with low systemic bioavailability and proven
efficacy in treating allergic rhinitis. OBJECTIVE: The aim of the current study
was to assess whether treatment with fluticasone furoate nasal spray affected the
short-term lower-leg growth rate in children with allergic rhinitis. METHODS:
Prepubertal children with seasonal or perennial allergic rhinitis of at least 1
year's duration were included in this single-center, randomized, double-blind,
placebo-controlled, crossover study. The study consisted of 4 periods, each of 2 
weeks' duration screening, then 2 treatment periods separated by a washout).
Study medications were fluticasone furoate nasal spray 110 microg and placebo
nasal spray, both administered QD in the morning. The primary end point,
lower-leg growth rate (measured in millimeters per week), was assessed by
knemometry. Adverse events were also assessed. RESULTS: Fifty-eight patients were
randomized to the study and comprised the intent-to-treat (ITT) population (mean 
[SD] age, 9.1 [1.4] years; 39 males, 19 females). Five patients were excluded
from the ITT group due to protocol violations; thus, 53 patients (mean [SD] age, 
9.0 [1.4] years; 35 males, 18 females) comprised the growth population (a de
facto per-protocol group). In the growth population, the adjusted mean lower-leg 
growth rate was 0.40 and 0.42 mm/wk with fluticasone furoate and placebo,
respectively. The difference in adjusted mean lower-leg growth rate between
fluticasone furoate and placebo was -0.016 mm/wk (95% CI, -0.13 to 0.10).
Fluticasone furoate was noninferior to placebo, as the lower boundary of the 95% 
CI was above the prespecified noninferiority margin of -0.20 mm/wk. These results
were supported by the ITT analysis. Fluticasone furoate nasal spray was well
tolerated and had an adverse-event profile similar to that of placebo nasal
spray. Nasopharyngitis (placebo, 4; fluticasone furoate, 1) and headache
(placebo, 3; fluticasone furoate, 1) were the most frequent adverse events during
the treatment periods. CONCLUSION: In this study, fluticasone furoate nasal spray
110 microg QD for 2 weeks had no effect on lower-leg growth rate in these
prepubertal children with allergic rhinitis. Copyright 2007 Excerpta Medica, Inc.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17919555 [PubMed - indexed for MEDLINE]

238: Allergy. 2007 Nov;62(11):1282-7.

Allergic sensitization to cat in childhood as major predictor of incident
respiratory allergy in young adults.

Schäfer T, Wölke G, Ring J, Wichmann HE, Heinrich J.

Institute of Social Medicine, Medical University Lübeck, Lübeck, Germany.

BACKGROUND: Little is known on the predictive value of sensitization to specific 
aeroallergens in children with respect to asthma and hay fever incidence in young
adulthood. We followed the incidence of asthma and hay fever in children (mean
age 11 years) over 9 years, and analyzed the predictive value of sensitization to
five common aeroallergens. METHODS: Three consecutive surveys were conducted in
East German school children. Specific IgE antibodies to birch and timothy grass
pollen, house dust mite, cat, and cladosporium were measured. In 1207 out of the 
2453 children, the 9-year incidence of asthma and hay fever was assessed by
reported doctors' diagnoses. For sensitization, diagnostic parameters were
determined and logistic regression analyses controlled for relevant confounders. 
RESULTS: A total of 176/78 incident hay fever/asthma cases occurred equaling a
cumulative incidence of 1.93/0.86% per year. Incident asthma was associated with 
previous sensitization to cat [risk ratio (RR) 3.49, 1.57-7.74] and grass pollen 
(RR 1.79, 1.01-3.19), whereas incident hay fever was associated with each
allergen, with grass pollen (RR 6.00, 4.04-8.90) and cat (RR 5.36, 2.87-9.99)
exhibiting the strongest associations. When mutually adjusting for all allergens,
sensitization to cat remained significantly associated with asthma and hay fever.
The latter was also associated with sensitization to grass pollen. The highest
positive predictive values for asthma and hay fever were obtained for cat
sensitization (10/49 = 20.4% and 23/49 = 46.9%). CONCLUSIONS: Childhood
sensitization to cat and grass pollen predicts the incidence of asthma and hay
fever in young adulthood. The predictive capacity differs by allergen and
manifestation of atopy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17919143 [PubMed - indexed for MEDLINE]

239: Wien Med Wochenschr. 2007;157(11-12):243-7.

Subjective health and impaired quality of life due to allergies in a
representative population survey.

Dorner T, Müller KH, Schmidl H, Freidl W, Stronegger WJ, Lawrence K, Kunze M,
Rieder A.

Institute of Social Medicine, Centre for Public Health, Medical University of
Vienna, Vienna, Austria. thomas.dorner@univie.ac.at

OBJECTIVES: To examine the quality of life among patients with different allergic
diseases and to assess the health perception of patients with allergies compared 
to patients without allergies. METHODS: The source of data was the Vienna Health 
and Social Survey, a representative cross-sectional survey, commissioned by the
City of Vienna. RESULTS: 18.7% of those suffering from allergies in the year
before questioning reported that they had felt "very impaired", 30.0% felt "quite
impaired", 42.4% "a little impaired" and 8.9% "not impaired at all". Women felt
"very impaired" as a consequence of allergy more often than men (21.8% vs. 15.2%,
p < 0.05). On a scale of 0 to 100 (0 = worst possible; 100 = best possible state 
of health) patients with allergies rated their state of health as distinctly
worse than those people without allergies (71.7 vs. 74.1 points, p < 0.001). Of
the various allergic illnesses patients suffering from asthma or allergy-related 
intestinal problems experienced the greatest impairment in quality of life. For
these two diseases physical ability and feeling fit enough to do what one would
like to do was also significantly reduced, when compared with subjects without
allergies. CONCLUSION: Compared to people without allergies, patients with
allergies have a significantly more impaired quality of life. It is important to 
take this into account when deciding upon a treatment regime.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 17915436 [PubMed - indexed for MEDLINE]

240: Clin Immunol. 2007 Dec;125(3):291-8. Epub 2007 Oct 29.

The role of CCL22/macrophage-derived chemokine in allergic rhinitis.

Yanai M, Sato K, Aoki N, Takiyama Y, Oikawa K, Kobayashi H, Kimura S, Harabuchi
Y, Tateno M.

Department of Pathology, Asahikawa Medical College, Hokkaido, Japan.
mitsuru@asahikawa-med.ac.jp

Dendritic cells (DCs) are considered to be the most powerful antigen-presenting
cells (APCs). DCs are thought to be associated with Th1 or Th2 polarization and
with polarization-induced disease such as atopic dermatitis, asthma and allergic 
rhinitis, but its mechanism is not well known. In this study, we analyzed the
mRNA expression of DCs between birch pollen allergic rhinitis and healthy
controls by using cDNA array. We found that the expressions of
CCL22/macrophage-derived chemokine (MDC) differed significantly. We also revealed
that CCL22/MDC production was higher in patients than in healthy donors. By
chemotaxis assay, CCL22/MDC can enhance the migration of patient's T cells rather
than those of healthy controls. Surface marker analysis of migrated cells
revealed that the most of migrated cells expressed CCR4, which were considered to
be Th2 cells. Furthermore, CD1a(+) CD83(+) cells located in the nasal mucosa
expressed CCL22/MDC in vivo. To the best of our knowledge, this is the first
report clearly indicating the role of CCL22/MDC in allergic rhinitis.

PMID: 17911044 [PubMed - indexed for MEDLINE]

241: Ann Allergy Asthma Immunol. 2007 Sep;99(3):267-72.

Efficacy and safety of azelastine nasal spray at a dose of 1 spray per nostril
twice daily.

Lumry W, Prenner B, Corren J, Wheeler W.

AARA Research Center, Dallas, Texas 75231, USA. lumrymd@sbcglobal.net

BACKGROUND: Azelastine hydrochloride nasal spray is available worldwide for the
treatment of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis.
One spray per nostril twice daily is the most commonly recommended dose.
OBJECTIVE: To determine the efficacy and safety of azelastine nasal spray, 1
spray per nostril twice daily, in patients with SAR. METHODS: In 2 studies
conducted in the United States we assessed 554 patients with moderate-to-severe
SAR who were still symptomatic after a 1-week placebo lead-in period. Patients
were randomized to 2 weeks of double-blind treatment with azelastine nasal spray,
1 spray per nostril twice daily, or placebo nasal spray. The primary efficacy
variable was change from baseline in total nasal symptom score, consisting of
sneezing, itchy nose, runny nose, and nasal congestion. RESULTS: Mean differences
in total nasal symptom score between the azelastine and placebo groups were
significant in both studies: 2.69 vs 1.31 (P = .01) in study 1 and 3.68 vs 2.50
(P = .02) in study 2. Bitter taste was reported by 8.3% of patients treated with 
1 spray per nostril twice daily compared with the labeled incidence of 19.7% with
2 sprays per nostril twice daily. Somnolence was reported by 1 patient (0.4%)
using the 1-spray regimen compared with the labeled incidence of 11.5% using the 
2-spray regimen. CONCLUSIONS: Azelastine nasal spray at a dose of 1 spray per
nostril twice daily is effective and has improved tolerability compared with 2
sprays per nostril twice daily in patients with SAR.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17910331 [PubMed - indexed for MEDLINE]

242: Ann Allergy Asthma Immunol. 2007 Sep;99(3):203-11; quiz 212-3, 231.

Cross-reactivity of pollen allergens: impact on allergen immunotherapy.

Weber RW.

National Jewish Medical & Research Center, University of Colorado Health Sciences
Center, Denver, Colorado, USA. weberr@njc.org

OBJECTIVE: To provide guidelines for the rational formulation of allergen
immunotherapy extracts based on knowledge of pollen allergen and epitope
cross-reactivity. DATA SOURCES: A PubMed search was performed for articles
published from 1966 to 2007 using the keywords pollen, allergen, and
cross-reactivity. Older literature was found through cross-referencing of older
articles and older reviews on pollen cross-reactivity. Study Selection: Articles 
that dealt with crude pollen extracts and characterized allergens that addressed 
cross-reactivity were selected for inclusion in this review. RESULTS: In addition
to unique allergens, several families of botanic proteins have similarities that 
allow them to act as pan-allergens. Although frequently these are minor
allergens, in some circumstances they may also be major allergens. Recent studies
have investigated nonspecific lipid transfer proteins, calcium-binding proteins, 
pathogenesis-related protein families, and profilins. Calcium-binding proteins
and nonspecific lipid transfer proteins are responsible for pollen-fruit
interactions and pollen cross-reactivity. Clarification of pollen allergen
enzymatic activity helps explain the ubiquitous nature of these proteins.
CONCLUSION: Characterization of specific pollen allergens and their protein
families has provided insight into cross-reactivity. Clarification of these
relationships allows for consolidation or substitution in formulation of inhalant
extracts.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17910323 [PubMed - indexed for MEDLINE]

243: Arch Pediatr Adolesc Med. 2007 Oct;161(10):972-7.

Infections in child day care centers and later development of asthma, allergic
rhinitis, and atopic dermatitis: prospective follow-up survey 12 years after
controlled randomized hygiene intervention.

Dunder T, Tapiainen T, Pokka T, Uhari M.

Department of Pediatrics, University of Oulu, PO Box 5000, FIN-90014 Oulu,
Finland. teija.dunder@oulu.fi

OBJECTIVE: To evaluate the effect of successful prevention of common infections
in child day care centers on the later development of allergic diseases. DESIGN: 
Prospective follow-up survey with a questionnaire administered 12 years after a
controlled randomized hygiene intervention. SETTING: Twenty municipal child day
care centers in Oulu, Finland. PARTICIPANTS: A questionnaire was sent to 1354
prior participants (98%) in the intervention trial. The response rate was 68%
(928 of 1354 participants). MAIN INTERVENTION: Hygiene intervention from March 1,
1991, to May 31, 1992. MAIN OUTCOME MEASURES: The number of respondents who had a
diagnosis of asthma, allergic rhinitis, and/or atopic dermatitis made by a
physician, and the number of those who reported symptoms of atopic diseases.
RESULTS: Asthma was diagnosed by a physician in 48 of the 481 respondents (10%)
from the intervention child day care centers, with markedly fewer infections, and
in 46 of the 447 controls (10%) (relative risk, 1.0; 95% confidence interval,
0.7-1.4). Similarly, no differences were found in the numbers of children who had
a diagnosis of other atopic diseases or who had reported such symptoms.
CONCLUSION: The prevention of common respiratory tract and enteric infections
during early childhood does not change later allergic morbidity.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17909141 [PubMed - indexed for MEDLINE]

244: Pulm Pharmacol Ther. 2008;21(2):340-8. Epub 2007 Aug 30.

Differential responses to various classes of drugs in a model of allergic
rhinitis in guinea pigs.

Al Suleimani YM, Dong Y, Walker MJ.

Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health 
Sciences, Sultan Qaboos University, Oman. rsdaa@interchange.ubc.ca

Different drugs from various pharmacological classes were compared for their
ability to protect against the nasal effects of acute allergen challenge in a
guinea pig model. In the model, sneezing and nose rubbing were recorded after an 
initial allergen challenge in guinea pigs previously sensitized to egg albumin.
Four days later the same guinea pigs were re-challenged a second time when
anesthetised. In these anaesthetized animals, nasal airway pressure, pulmonary
inflation pressure and cellular infiltration into nasal lavage fluid were
measured. The drug tested were autacoid antagonists (mepyramine--3mg/kg,
cetirizine--3mg/kg and montelukast--10mg/kg), L-NAME (10 or 20mg/kg), heparin
(20mg/kg) and dexamethasone (20mg/kg) given either intraperitoneally or
intravenously; all were given shortly before challenge. Sneezing induced by
allergen challenge was statistically significantly reduced by mepyramine,
cetirizine and dexamethasone whereas only cetirizine reduced nose rubbing.
Changes in nasal airway pressure due to allergen exposure were reduced by
cetirizine, montelukast, L-NAME, and heparin, but not by mepyramine, nor
dexamethasone. In the presence of L-NAME, nasal airway pressure actually changed 
in the opposite direction. Cellular infiltration, as assessed by cytometry in
nasal lavage fluid 60min after acute allergen challenge, was reduced by
montelukast and heparin but not by antihistamines, L-NAME nor dexamethasone. This
pattern of effects of the drugs, given by doses and routes previously described
in the literature as being effective was not completely consistent with expected 
responses. The lack of effect of dexamethasone probably reflects the fact that it
was given acutely whereas in the clinic chronic administration is used. The two
antihistamines were not identical in their actions, presumably reflecting the
fact that cetirizine has therapeutic actions not entirely confined to blockade of
H1 receptors. Montelukast has not been reported to have major effects on sneezing
and itching in the clinic but reduces nasal obstruction (lower nasal airway
pressure or nasal patency). Montelukast's effects on cellular infiltration
indicate the possible involvement of leukotrienes. Heparin has actions on
inflammatory cell infiltration. This could explain its profile of reducing both
cellular infiltration, and increased nasal airway pressure.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17905620 [PubMed - indexed for MEDLINE]

245: Adv Drug Deliv Rev. 2007 Aug 31;59(9-10):852-82. Epub 2007 Aug 17.

Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma.

Smolensky MH, Lemmer B, Reinberg AE.

School of Public Health, RAS-Rm. W606, University of Texas Health Science Center 
at Houston, 1200 Herman Pressler, Houston, Texas 77030, USA.
Michael.H.Smolensky@uth.tmc.edu

Study of the chronobiology of allergic rhinitis (AR) and bronchial asthma (BA)
and the chronopharmacology and chronotherapy of the medications used in their
treatment began five decades ago. AR is an inflammatory disease of the upper
airway tissue with hypersensitivity to specific environmental antigens, resulting
in further local inflammation, vasomotor changes, and mucus hypersecretion.
Symptoms include sneezing, nasal congestion, and runny and itchy nose.
Approximately 25% of children and 40% of adults in USA are affected by AR during 
one or more seasons of the year. The manifestation and severity of AR symptoms
exhibit prominent 24-h variation; in most persons they are worse overnight or
early in the morning and often comprise nighttime sleep, resulting in poor
daytime quality of life, compromised school and work performance, and
irritability and moodiness. BA is also an inflammatory medical condition of the
lower airways characterized by hypersensitivity to specific environmental
antigens, resulting in greater local inflammation as well as bronchoconstriction,
vasomotor change, and mucus hypersecretion. In USA an estimated 6.5 million
children and 15.7 million adults have BA. The onset and worsening of BA are
signaled by chest wheeze and/or croupy cough and difficult and labored breathing.
Like AR, BA is primarily a nighttime medical condition. AR is treated with
H1-antagonist, decongestant, and anti-inflammatory (glucocorticoid and
leukotriene receptor antagonist and modifier) medications. Only H1-antagonist AR 
medications have been studied for their chronopharmacology and potential
chronotherapy. BA is treated with some of the same medications and also
theophylline and beta2-agonists. The chronopharmacology and chronotherapy of many
classes of BA medications have been explored. This article reviews the rather
extensive knowledge of the chronobiology of AR and BA and the chronopharmacology 
and chronotherapy of the various medications used in their treatment.

Publication Types: 
    Review

PMID: 17900748 [PubMed - indexed for MEDLINE]

246: Iran J Allergy Asthma Immunol. 2007 Sep;6(3):143-9.

Acetaminophen intake and risk of asthma, hay fever and eczema in early
adolescence.

Vlaski E, Stavric K, Isjanovska R, Seckova L, Kimovska M.

Department of Pulmonology and Allergology, University Children's Hospital,
Skopje, Republic of Macedonia. vlaskie@sonet.com.mk

A positive association between acetaminophen intake and allergic diseases has
recently been reported in developed countries with impaired oxidant/antioxidant
balance and promotion of atopy as proposed underlying mechanisms. The aim of the 
study was to explore the relationship between acetaminophen intake and asthma,
hay fever, and eczema in The Republic of Macedonia as a country with
acetaminophen intake not physician-controlled, high passive smoke exposure and
dietary antioxidant intake, and moderately low prevalence of allergic diseases.
Self-reported data obtained through the standardized International Study of
Asthma and Allergies in Childhood Phase Three written questionnaires of 3026
adolescents aged 13/14 years from randomly selected schools in Skopje, the
capital of Macedonia, were used. The frequency of current acetaminophen
intake--both unadjusted and adjusted for confounding factors--was correlated to
current and ever-diagnosed asthma, hay fever and eczema by odds ratios (OR, 95%
CI) in binary logistic regression. Use of acetaminophen at least once monthly
increased the risk of current wheeze (adjusted OR 2.04, 1.31-3.20 p = 0.002),
asthma 'ever' (adjusted OR 2.77, 1.06-7.26 p=0.039), current allergic
rhinoconjunctivitis (adjusted OR 2.95, 1.79-4.88 p=0.000) and hay fever 'ever'
(adjusted OR 2.25, 1.36-3.70 p=0.002). A significant association between frequent
acetaminophen intake and atopic eczema and also between infrequent acetaminophen 
intake and investigated allergic diseases was not established.The findings
suggest an increased risk of asthma and hay fever, but not atopic eczema
associated with frequent acetaminophen use in a developing country.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17893435 [PubMed - indexed for MEDLINE]

247: J Med Microbiol. 2007 Oct;56(Pt 10):1301-8.

Influence of Bifidobacterium longum BB536 intake on faecal microbiota in
individuals with Japanese cedar pollinosis during the pollen season.

Odamaki T, Xiao JZ, Iwabuchi N, Sakamoto M, Takahashi N, Kondo S, Miyaji K,
Iwatsuki K, Togashi H, Enomoto T, Benno Y.

Food Research and Development Laboratory Morinaga Milk Industry Co. Ltd, Zama,
Kanagawa 228-8583, Japan. t-odamak@morinagamilk.co.jp

It has been reported that intake of yogurt or powder supplemented with the
Bifidobacterium longum BB536 probiotic strain alleviated subjective symptoms and 
affected blood markers of allergy in individuals with Japanese cedar pollinosis
(JCPsis) during the pollen seasons of 2004 and 2005, based on randomized,
double-blind, placebo-controlled trials. Furthermore, the 2004 study found that
intestinal bacteria such as the Bacteroides fragilis group significantly
fluctuated during the pollen season in JCPsis individuals and intake of BB536
yogurt tended to suppress these fluctuations. The present study investigated
faecal microbiota to examine whether any changes occurred during the pollen
season and whether any influence was exerted by intake of BB536 powder in the
2005 pollen season, which happened to be a heavy season, to confirm the 2004
findings and to evaluate the relationship of microbiota with symptom development.
In a randomized, double-blind, placebo-controlled trial, 44 JCPsis subjects
received BB536 or a placebo for 13 weeks during the pollen season. Another 14
Japanese cedar pollen (JCP)-specific IgE negative healthy subjects received
placebo for the same period. Faecal samples were collected before (week 0),
during (weeks 4, 8 and 13) and after (week 17) intervention, and out of JCP
season (week 28). Faecal microbiota were analysed using terminal-RFLP (T-RFLP)
and real-time PCR methods. Principal component analysis based on T-RFLP indicated
distinct patterns of microbiota between healthy subjects and JCPsis subjects in
the placebo group, but an intermediate pattern in the BB536 group at week 13, the
last stage of the pollen season. The coordinate of principal component 1 at week 
13 correlated with composite scores of JCPsis symptoms recorded during the pollen
season. Faecalibacterium prausnitzii and the Bacteroides fragilis group were
identified as the main contributors to microbiotal fluctuations. Real-time PCR
indicated that BB536 intake suppressed increases in the Bacteroides fragilis
group compared with the placebo group (P <0.05). These results suggest that
faecal microbiota in JCPsis subjects, but not healthy subjects, fluctuate at the 
end of the pollen season and that BB536 intake plays a role in maintaining normal
microbiota.

Publication Types: 
    Randomized Controlled Trial

PMID: 17893165 [PubMed - indexed for MEDLINE]

248: Asian Pac J Allergy Immunol. 2007 Mar;25(1):1-5.

Prevalence and severity of symptoms of asthma, allergic rhinitis, and eczema in
10- to 15-year-old schoolchildren in central Taiwan.

Chiang LC, Chen YH, Hsueh KC, Huang JL.

School of Nursing, China Medical University, Taichung, Taiwan.

The International Study of Asthma and Allergies in Childhood (ISAAC)
questionnaire was distributed through 14 schools and was completed by 11,874
students out of which are parents of 4,167 children aged between 10 and 12 years 
old and 7,677 older children aged between 13 and 15 years in central Taiwan. The 
overall cumulative and 12-month prevalence of wheezing, rhinitis, and eczema were
7.4%, 43.0%, and 7.2%, respectively. It was shown that boys had significantly
higher prevalence of wheezing and rhinitis (p < 0.001 and p = 0.001) when
compared to girls in central Taiwan. The study also found that prevalence rates
among younger children with symptoms of wheezing, rhinitis, and recurrent itchy
rash in the past 12-month (8.2%, 44.4%, and 8.8%) were higher than that among
older children (6.9%, 42.2%, and 6.3%, respectively). In conclusion, boys had
significantly higher prevalence of wheezing and rhinitis than girls while younger
children tend to have higher prevalence of the disorders than those that are
older in age.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17891915 [PubMed - indexed for MEDLINE]

249: Allergy Asthma Proc. 2007 Jul-Aug;28(4):404-9.

Therapy in allergic rhinoconjunctivitis: new horizons.

Mahr TA.

Department of Allergy/Immunology, Gundersen Lutheran Medical Center, University
of Wisconsin School of Medicine and Public Health, La Crosse, Wisconsin 54601,
USA. tamahr@gundluth.org

Allergic Rhinitis (AR) is a common disease that impacts productivity and has
significant patient morbidity. We have a variety of agents available for the
treatment of AR, but numerous patients still lack good control of symptoms and
some are tolerating undesired side effects. Surveys have shown 1/5 of patients
with AR are not fully satisfied with their AR medications and almost 1/2 feel
they receive insufficient attention from their physicians. Newer agents for the
treatment of AR are in development, and an overview of some of these are
presented here.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17883907 [PubMed - indexed for MEDLINE]

250: Allergy Asthma Proc. 2007 Jul-Aug;28(4):398-403.

The pathophysiology of allergic rhinoconjunctivitis.

Broide DH.

Department of Medicine, University of California San Diego, San Diego,
California, USA. dbroide@ucsd.edu

Allergic rhinitis and conjunctivitis are very common manifestations of allergy
affecting approximately 10-30% of adults and up to 40% of children. An improved
understanding of the immune and inflammatory mechanisms underlying the
pathogenesis of these allergic disorders has provided important insight into the 
pathogenesis of allergic symptoms related to rhinitis and conjunctivitis, as well
as identified potential novel therapeutic targets to interrupt the
proinflammatory pathways that contribute to ongoing rhinitis and conjunctivitis
symptoms.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17883906 [PubMed - indexed for MEDLINE]

251: Am J Rhinol. 2007 Jul-Aug;21(4):499-503.

Onset of action of azelastine nasal spray compared with mometasone nasal spray
and placebo in subjects with seasonal allergic rhinitis evaluated in an
environmental exposure chamber.

Patel P, D'Andrea C, Sacks HJ.

Allied Research International, Inc., Mississauga, Ontario, Canada.

BACKGROUND: The objective of this study was to determine the onset of action of
azelastine hydrochloride nasal spray compared with placebo and an intranasal
steroid, mometasone furoate, in subjects with seasonal allergic rhinitis (SAR).
METHODS: Subjects with a history of SAR and symptomatic while exposed to ragweed 
pollen in an environmental exposure chamber (EEC) were randomized to azelastine
nasal spray (n=150), mometasone nasal spray (n=150), or placebo (n=150) and
recorded total nasal symptom scores (TNSS), consisting of sneezing, nasal
pruritus, rhinorrhea, and congestion, during an 8-hour study period. RESULTS:
Azelastine nasal spray showed a statistically significant improvement in the TNSS
at 15 minutes compared with placebo. The effect was durable at each time point
during the 8-hour study. Azelastine nasal spray also was significantly more
effective than mometasone at each time point. CONCLUSION: Azelastine nasal spray 
has a rapid (15 minute) onset of action. Azelastine nasal spray was superior to
both placebo and imometasone nasal spray in reducing nasal symptoms of SAR
occurring within 8 hours after an allergen challenge.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17882923 [PubMed - indexed for MEDLINE]

252: Clin Exp Allergy. 2007 Nov;37(11):1624-31. Epub 2007 Sep 17.

Erratum in:
    Clin Exp Allergy. 2007 Dec;37(12):1895.

Skin prick test can identify eczematous infants at risk of asthma and allergic
rhinitis.

Lowe AJ, Hosking CS, Bennett CM, Carlin JB, Abramson MJ, Hill DJ, Dharmage SC.

Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Faculty
of Medicine, Dentistry & Health Sciences, The University of Melbourne, Melbourne,
Australia. lowe.adrian@gmail.com

BACKGROUND: Assessment of allergic sensitization is not routinely performed in
infants and young children with eczema. OBJECTIVE: To determine whether infants
who have atopic eczema (with sensitization) are at a greater risk of developing
asthma and allergic rhinitis (AR) than those with non-atopic eczema (without
concurrent sensitization). METHODS: The presence of eczema was prospectively
documented until 2 years of age in a birth cohort of 620 infants with a family
history of atopic disease. Sensitization status was determined by skin prick
tests (SPTs) at 6, 12, and 24 months using six common allergens. Interviews were 
conducted at 6 and 7 years to determine the presence of asthma and AR. RESULTS:
Within the first 2 years of life, 28.7% of the 443 children who could be
classified had atopic eczema: 20.5% had non-atopic eczema, 19.0% were
asymptomatic but sensitized and 31.8% were asymptomatic and not sensitized. When 
compared with children with non-atopic eczema in the first 2 years of life,
children with atopic eczema had a substantially greater risk of asthma [odds
ratio (OR)=3.52, 95% confidence interval=1.88-6.59] and AR (OR=2.91, 1.48-5.71). 
The increased risk of asthma was even greater if the infant had a large SPT
(OR=4.61, 2.34-9.09) indicative of food allergy. There was no strong evidence
that children with non-atopic eczema had an increased risk of asthma or AR
compared with asymptomatic children. CONCLUSION: In children with eczema within
the first 2 years of life, SPT can provide valuable information on the risk of
childhood asthma and AR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17877754 [PubMed - indexed for MEDLINE]

253: Auris Nasus Larynx. 2008 Mar;35(1):61-6. Epub 2007 Sep 7.

Efficacy of nasal corticosteroids alone or combined with antihistamines or
montelukast in treatment of allergic rhinitis.

Pinar E, Eryigit O, Oncel S, Calli C, Yilmaz O, Yuksel H.

ENT Department, Izmir Ataturk Training and Research Hospital, Izmir, Turkey.
epinar66@yahoo.com

OBJECTIVE: Topical corticosteroids are recommended as initial therapy in allergic
rhinitis (AR) patients. We investigated clinical efficacy of monotherapy with
topical steroid and combined therapy in AR patients. METHODS: Ninety-five AR
patients sensitive to grass pollens according to skin prick test results were
enrolled in this placebo-controlled and open study. Patients were divided to four
groups. Group-1 received only intranasal mometasone furoate (MF) 200microg
(n=25), group-2 received intranasal MF and oral desloratadine (DLR) 5mg (n=25),
group-3 received intranasal MF and oral montelukast (MSK) 10mg (n=25), group-4
received only placebo (n=20). Efficacy was assessed on the basis of total nasal
symptom scores, rhinoconjunctivitis quality of life questionnaire scores and
nasal inspiratory peak flow rates. RESULTS: All groups that received treatment
had better results when compared to the placebo group. Significant improvement in
total nasal symptom scores was first evident at the end of the 2nd week in
group-2. Group-3 had better results than those of the other groups at the end of 
the 1st month (p<0.05). Quality of life scores were significantly better in
group-2 and -3 when compared to those in group-1 (p<0.05). CONCLUSION: Although
corticosteroids are the mainstay of treatment in allergic rhinitis, montelukast
may be considered as an additional agent especially in treatment of patients with
impaired quality of life and it may be used to reduce nasal symptom scores.

Publication Types: 
    Comparative Study

PMID: 17826020 [PubMed - indexed for MEDLINE]

254: J Allergy Clin Immunol. 2007 Oct;120(4):863-9. Epub 2007 Sep 7.

Childhood allergic rhinitis predicts asthma incidence and persistence to middle
age: a longitudinal study.

Burgess JA, Walters EH, Byrnes GB, Matheson MC, Jenkins MA, Wharton CL, Johns DP,
Abramson MJ, Hopper JL, Dharmage SC.

Centre for Molecular, Environmental, Genetic and Analytic Epidemiology,
University of Melbourne, Melbourne, Victoria, Australia.
j.burgess@pgrad.unimelb.edu.au

BACKGROUND: The association between allergic rhinitis and asthma is well
documented, but the temporal sequence of this association has not been closely
examined. OBJECTIVE: We sought to assess the associations between childhood
allergic rhinitis and (1) asthma incidence from preadolescence to middle age and 
(2) asthma persistence to middle age. METHODS: Data were gathered from the 1968, 
1974, and 2004 surveys of the Tasmanian Asthma Study. Cox regression was used to 
examine the association between childhood allergic rhinitis and asthma incidence 
in preadolescence, adolescence, and adult life. Binomial regression was used to
examine the association between childhood allergic rhinitis and asthma beginning 
before the age of 7 years and persisting at age 44 years. RESULTS: Childhood
allergic rhinitis was associated with a significant 2- to 7-fold increased risk
of incident asthma in preadolescence, adolescence, or adult life. Childhood
allergic rhinitis was associated with a 3-fold increased risk of childhood asthma
persisting compared with remitting by middle age. CONCLUSIONS: Childhood allergic
rhinitis increased the likelihood of new-onset asthma after childhood and the
likelihood of having persisting asthma from childhood into middle age. CLINICAL
IMPLICATIONS: Asthma burden in later life might be reduced by more aggressive
treatment of allergic rhinitis in early life.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17825896 [PubMed - indexed for MEDLINE]

255: Clin Ther. 2007 Jul;29(7):1428-40.

Allergic rhinitis: the impact of discordant perspectives of patient and physician
on treatment decisions.

Meltzer EO.

Allergy & Asthma Medical Group and Research Center, San Diego, California 92123, 
USA. eomeltzer@aol.com

BACKGROUND: A wealth of literature is available that documents the effects of
inadequately controlled allergic rhinitis (AR) on patients' daily activities,
including impaired sleep, reduced cognitive functioning, and interference with
sport and leisure activities. However, despite its high prevalence and
significant impact on health-related quality of life (HRQOL) and productivity, AR
may be undertreated. This might arise, in part, from the low priority given to
the disease by physicians. OBJECTIVE: This article aims to assess the existence
of disparities between the attitudes of patients and physicians to AR, and to
comment on the impact these disparities may have on treatment choices. METHODS: A
search was conducted of MEDLINE (1990-2006) and data presented at recent
congresses (The 25th Congress of the European Academy of Allergology and Clinical
Immunology, June 10-14, 2006, Vienna, Austria, and the 62nd Annual American
Academy of Allergy, Asthma and Immunology Meeting, March 3-7, 2006, Miami Beach, 
Florida) for articles that contained combinations of the terms allergic rhinitis,
patient, physician, perspective, attitude, opinion, experience, or burden.
Appropriate articles were selected for review in combination with data from a
recent Adelphi Group Products (New York, New York) survey. RESULTS: A study of
the impact of seasonal AR on HRQOL found that adolescent patients (n = 83) scored
practical problems higher in terms of importance. AR was found to affect the home
and social life of > or =33% of patients in a study from the United Kingdom. A
European survey of 1494 patients with AR found that nasal congestion was the most
common moderate or severe nasal symptom (55%) and that 44% of patients suffered
moderate or severe ocular symptoms. A Danish study of adults and adolescents
found that AR was undiagnosed in 32% of patients. In a study of 100 physicians in
the United States, approximately 30% of physicians under-estimated the severity
of AR and its impact on patients' work or school activities. Furthermore, 1 study
indicated that approximately 99% of physicians did not issue adequate treatment, 
although no study was found that directly linked physicians' perspectives of AR
and their treatment decisions to date. CONCLUSIONS: In a review of the existing
literature, evidence of disparities between patients' and physicians'
perspectives of AR were found, although no studies linked perspectives to
prescribing behavior; therefore, research into the impact on treatment decisions 
might be warranted. In the future, the patient-physician dialogue might be
improved by a standardized questionnaire designed to identify the most bothersome
symptoms of a patient's disease, so that the most appropriate treatments can be
selected to maximize quality of life.

PMID: 17825694 [PubMed - indexed for MEDLINE]

256: Int Arch Allergy Immunol. 2008;145(2):94-101. Epub 2007 Sep 7.

Prevalence of IgE-binding to Art v 1, Art v 4 and Amb a 1 in mugwort-allergic
patients.

Oberhuber C, Ma Y, Wopfner N, Gadermaier G, Dedic A, Niggemann B, Maderegger B,
Gruber P, Ferreira F, Scheiner O, Hoffmann-Sommergruber K.

Department of Pathophysiology, Center of Physiology and Pathophysiology, Medical 
University of Vienna, Vienna, Austria.

BACKGROUND: Mugwort (Artemisia vulgaris) represents an important source of weed
pollen allergens. The objectives of the present study were (i) to analyze the IgE
binding profiles in a group of mugwort-allergic patients, (ii) to identify
individual marker allergens crucial for the diagnosis of mugwort allergy and
(iii) to identify potential crossreactive allergens present in ragweed (Ambrosia 
artemisiifolia) pollen extract. METHODS: Sera from 100 pediatric mugwort-allergic
patients were analyzed for their IgE binding pattern to natural mugwort and
ragweed pollen proteins, purified natural and recombinant Art v 1, recombinant
Art v 4 and recombinant Amb a 1 using immunoblots and ELISA. RESULTS: 91% of the 
patients' sera tested displayed IgE binding to one or more mugwort pollen
allergens in ELISA and 88% were positive in immunoblot. Purified natural Art v 1 
was recognized by 79%, the recombinant protein by 39% of the patients tested and 
purified recombinant Art v 4 by 34% of the patients' sera. 67% of the sera
displayed crossreactive IgE to one or more ragweed pollen allergens. Recombinant 
Amb a 1 was noted in only 14% of the mugwort-allergic sera. CONCLUSIONS:
Allergen-specific in vitro diagnosis was performed in 100 pediatric
mugwort-allergic serum samples. Using two allergens (Art v 1 and Art v 4), 91% of
the patients could be identified as mugwort pollen-sensitized patients by IgE in 
vitro tests. Crossreactivity to ragweed pollen allergens was demonstrated by in
vitro experiments, suggesting a new important and potent allergen source
expanding across Europe. 2007 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17823540 [PubMed - indexed for MEDLINE]

257: Allergy. 2007 Dec;62(12):1379-86. Epub 2007 Sep 5.

Quantification of atopy and the probability of rhinitis in preschool children: a 
population-based birth cohort study.

Marinho S, Simpson A, Söderström L, Woodcock A, Ahlstedt S, Custovic A.

Academic Division of Medicine and Surgery, University of Manchester, Manchester, 
UK.

BACKGROUND: Atopy quantification using IgE levels/skin test diameter (SPT-MWD)
may better predict the expression of rhinitis than using atopy as a dichotomous
variable. OBJECTIVE: To investigate the association between the presence,
temporal pattern and severity of rhinitis in preschool children and specific IgE 
levels/SPT-MWDs. METHODS: Children were followed prospectively to age 5 years in 
a whole-population birth cohort study. We administered questionnaires (n = 815), 
skin prick tested children (n = 717) and measured specific serum IgE (n = 478) to
inhalant and food allergens. Main outcomes were current rhinitis (CR) and current
rhinoconjunctivitis (CRC). RESULTS: The prevalence of CR and CRC was 26.1% and
12.1%, respectively. The risk of CR and CRC increased significantly with
increasing IgE to grass, mite and cat; CRC was also associated with increasing
IgE to dog and peanut. Similarly, increasing SPT-MWDs to inhalant allergens were 
significantly associated with CR and CRC. This association was also shown for
grass within the group of atopic children. Perennial and seasonal rhinitis were
associated with increasing IgE/SPT-MWD to mite and grass, respectively.
Moderate/severe rhinitis was associated with increasing IgE/SPT-MWD to grass. In 
a multivariate analysis, increasing levels of IgE/SPT-MWD to grass were the
strongest independent predictors of both CR (for IgE: OR 1.42, 95% CI 1.23-1.64, 
P < 0.001) and CRC (for IgE: 1.51, 1.30-1.76, P < 0.001). CONCLUSION: The
probability of CR/CRC increases with increasing specific IgE levels or SPT-MWD.
With respect to allergic rhinitis, the absolute levels of specific IgE antibody
or the size of SPT wheal offer more information than just the presence/absence of
sensitization.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17822449 [PubMed - indexed for MEDLINE]

258: Laryngoscope. 2007 Aug;117(8):1323-8.

Effects of dexamethasone on the expression of transforming growth factor-beta in 
the mouse model of allergic rhinitis.

Lee SS, Won TB, Kim JW, Rhee CS, Lee CH, Hong SC, Min YG.

Department of Otorhinolaryngology-Head and Neck Surgery, Ewha Womans University
College of Medicine, Seoul, Korea.

OBJECTIVES/HYPOTHESIS: This study aimed to evaluate the effect of dexamethasone
on the expression of transforming growth factor (TGF)-beta in the mouse model of 
allergic rhinitis. STUDY DESIGN: Female BALB/c mice were randomly assigned to
four groups, including two control groups and two treatment groups. METHODS:
General sensitization and local challenge were performed with ovalbumin (OVA). In
the treatment groups, dexamethasone was injected intraperitoneally 3 hours before
general sensitization or local challenge. Symptom score, eosinophil infiltration,
and immunostaining for TGF-beta1 and CD4 in nasal mucosa, and TGF-beta1 and
OVA-specific immunoglobulin E (IgE) in sera were analyzed. RESULTS: Dexamethasone
administration before general sensitization reduced the symptom score,
OVA-specific IgE, and eosinophil infiltration and increased the serum level of
TGF-beta1 significantly. Dexamethasone administration before local challenge
reduced only the eosinophil infiltration significantly. Immunoreactivity of
TGF-beta1 and CD4 was lower in both treatment groups. CONCLUSION: These results
suggest that dexamethasone may play an important role in the regulation of
allergic reactions by at least two mechanisms; one by suppressing allergic
sensitization through decrease of CD4+ T cells and increase of TGF-beta, and the 
other by suppressing late allergic reactions through the inhibition of
proliferation and chemotaxis of inflammatory cells such as eosinophils.

PMID: 17762268 [PubMed - indexed for MEDLINE]

259: Prescrire Int. 2007 Aug;16(90):149.

Nasal azelastine for self-medication: modest symptomatic relief from rhinitis.

[No authors listed]

Azelastine nasal solution is another drug to be marketed for allergic rhinitis,
backed by a direct-to-consumer advertising campaign, similar to previous
promotional campaigns for oral cetirizine and nasal beclometasone.
Self-medication with azelastine via the nasal route is acceptable, as it does not
seem to provoke serious adverse effects. In contrast, its effectiveness in terms 
of symptomatic relief from rhinitis is limited.

PMID: 17724840 [PubMed - indexed for MEDLINE]

260: Curr Med Res Opin. 2007 Oct;23(10):2441-52.

Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical
efficacy and tolerability.

Bernstein JA.

Bernstein Clinical Research Center, Cincinnati, OH, USA.
jonathan.bernstein@uc.edu

INTRODUCTION: Azelastine hydrochloride (Astelin) nasal spray 0.1% solution is a
second-generation intranasal antihistamine available in the US for treatment of
both seasonal allergic rhinitis (SAR) and nonallergic vasomotor rhinitis (VMR).
SCOPE: Searches of journal articles including the title word 'azelastine' from
1979 through the present were conducted by the product manufacturer primarily
through Medline and EMBASE but also included, at various times, Dialog, Biosis,
Toxline, and Diogenes (an adverse-event database). One limitation of the present 
review is that it could not exclude the possibility of publication bias, whereby 
findings from smaller studies and/or trials with negative findings may not have
been published. FINDINGS: Azelastine is a phthalazinone derivative with
H(1)-receptor binding approximately tenfold greater than chlorpheniramine on a
milligram-per-milligram basis. Azelastine has demonstrated a wide range of
pharmacologic effects on chemical mediators of inflammation including
leukotrienes, kinins, and platelet activating factor in vitro and in vivo. The
molecule also has been shown to downregulate intercellular adhesion molecule-1
expression and to reduce inflammatory cell migration in patients with rhinitis.
Well-controlled studies in SAR and VMR demonstrated that azelastine nasal spray
improves nasal symptoms of rhinitis, including congestion and postnasal drip, and
has a rapid onset of action that appears likely due to topical activity.
Azelastine nasal spray has demonstrated greater efficacy when used in combination
with fluticasone propionate nasal spray when compared to either agent alone, and 
this combination may provide benefit for patients with moderate-to-severe
rhinitis. Bitter taste is the most common side effect associated with azelastine 
nasal spray and this problem can be mitigated by the dosing technique recommended
by the manufacturer in the product labeling. The incidence of somnolence also may
be reduced with the recommended administration technique. CONCLUSIONS: Azelastine
is an effective, rapid-acting, and well-tolerated second-generation antihistamine
that improves nasal symptoms associated with SAR and VMR. Clinical studies
demonstrated that azelastine nasal spray can improve symptoms of SAR in patients 
who remained symptomatic after treatment with oral antihistamines and that
azelastine nasal spray in combination with fluticasone nasal spray provided
significantly (p < 0.05) greater relief than either agent alone in patients with 
SAR.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17723160 [PubMed - indexed for MEDLINE]

261: Drugs. 2007;67(13):1905-15.

Fluticasone furoate: intranasal use in allergic rhinitis.

McCormack PL, Scott LJ.

Wolters Kluwer Health | Adis, Auckland, New Zealand. demail@adis.co.nz

Fluticasone furoate nasal spray is a new topical intranasal corticosteroid with
enhanced affinity for the glucocorticoid receptor and low systemic exposure,
which was recently approved in the US for the treatment of seasonal or perennial 
allergic rhinitis in adults and in children aged >or=2 years. Fluticasone furoate
nasal spray employs a novel delivery device with a unique side-actuated design, a
short nozzle and a new trigger mechanism designed for ease of use. In well
controlled clinical trials, intranasal fluticasone furoate 110microg once daily
for 2 weeks in adults and adolescents with seasonal allergic rhinitis reduced
nasal and ocular symptoms, and improved health-related quality of life to a
significantly greater extent than placebo. Similarly, treatment with intranasal
fluticasone furoate 110microg once daily for 4-6 weeks in adults and adolescents 
with perennial allergic rhinitis was superior to placebo in reducing nasal
symptoms and with respect to overall response to therapy. In children aged 6-11
years, fluticasone furoate nasal spray was shown to be effective in reducing the 
nasal symptoms of seasonal and perennial allergic rhinitis following treatment
for 2 and 4 weeks, respectively. Fluticasone furoate nasal spray was well
tolerated in adults, adolescents and children aged 2-11 years, with an overall
incidence of adverse events similar to that with placebo.

Publication Types: 
    Review

PMID: 17722960 [PubMed - indexed for MEDLINE]

262: Allergy. 2007 Nov;62(11):1335-8. Epub 2007 Aug 21.

Effect of grass pollen immunotherapy with Alutard SQ on quality of life in
seasonal allergic rhinoconjunctivitis.

Powell RJ, Frew AJ, Corrigan CJ, Durham SR.

Clinical Immunology Unit, University Hospital, Queens Medical Centre, Nottingham,
UK.

BACKGROUND: Treatment of allergic rhinitis with subcutaneous allergen
immunotherapy is effective in terms of reductions in symptoms and seasonal use of
reliever medication. Its effect on quality of life (QoL), reflecting the impact
of symptoms on work/school performance and leisure activities is, however,
important and often overlooked. AIMS OF THE STUDY: To assess effect on QoL of
specific immunotherapy with two doses of Alutard SQ Phleum pratense in patients
with moderately to severe seasonal allergic rhinoconjunctivitis inadequately
controlled by standard drug therapy. METHODS: Double-blind, randomized,
placebo-controlled study of 410 patients with seasonal allergic
rhinoconjunctivitis. Participants were randomized (2 : 1 : 1) to receive Alutard 
SQ P. pratense (ALK-Abelló) at maintenance doses of 100,000 SQ-U (203 subjects), 
10,000 SQ-U (104 subjects) or placebo (103 subjects) given by subcutaneous
injections. The groups were well matched for demographics and baseline symptoms. 
Quality of life was assessed using the Rhinoconjunctivitis Quality of Life
Questionnaire which covers seven domains of health before and in the peak of the 
pollen season. RESULTS: While all domain scores were significantly improved when 
comparing 100,000 SQ-U with placebo, two domain scores were significantly
improved when comparing 10,000 SQ-U with placebo. When comparing 100,000 SQ-U
with 10,000 SQ-U, four domain scores were significantly improved. CONCLUSION:
Treatment with Alutard SQ significantly improved the seasonal QoL of patients
suffering from allergic rhinoconjunctivitis. The improvement was more pronounced 
and wider ranging in patients who received the higher 100,000 SQ-U maintenance
dose.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17714551 [PubMed - indexed for MEDLINE]

263: Expert Opin Pharmacother. 2007 Sep;8(13):2173-87.

Update on montelukast and its role in the treatment of asthma, allergic rhinitis 
and exercise-induced bronchoconstriction.

Storms W.

The William Storms Allergy Clinic, Colorado Springs, CO 80907, USA.
sneezedoc@stormsallergy.com

Montelukast sodium (Singulair, Merck and Co., Inc., Whitehouse Station, NJ) is a 
selective and orally-active leukotriene receptor antagonist with demonstrated
effectiveness for treating allergic asthma and allergic rhinitis in adults and
children as young as 12 months of age for allergic asthma and 6 months of age for
allergic rhinitis. It was recently approved in the US for prevention of
exercise-induced bronchoconstriction in patients who are > or = 15 years of age. 
This paper updates a prior review of the data on the clinical efficacy of
montelukast published in this journal.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17714069 [PubMed - indexed for MEDLINE]

264: Allergol Int. 2007 Dec;56(4):411-7. Epub 2007 Sep 1.

Symptoms of allergic rhinitis in women during early pregnancy are associated with
higher prevalence of allergic rhinitis in their offspring.

Shinohara M, Wakiguchi H, Saito H, Matsumoto K.

Department of Pediatrics, Kochi Medical School, Kochi, Japan.

BACKGROUND: Epigenetic control of gene expression profiles is a ubiquitous
mechanism during cell differentiation, organogenesis and chronic inflammatory
reactions. Recent studies have shown that allergen exposure during very early
pregnancy increases bronchial hypersensitivity in offspring in a murine model of 
bronchial asthma. However, no such phenomena were reported in humans. In the
present study, the role of epigenetic control in the onset of allergic diseases
was investigated. METHODS: A total of 400 pairs of mothers with
physician-diagnosed allergic rhinitis (AR) and their offspring (age 7-18 months) 
who participated in a large-scale medical check-up were enrolled in this
retrospective cohort study. Family history of allergic diseases and the presence 
or absence of AR symptoms during pregnancy were inquired about using a
self-answered questionnaire. A logistic regression model adjusted for age,
gender, birth month and father's history of allergic diseases was statistically
analyzed. RESULTS: Offspring whose mothers had any AR symptoms during early
pregnancy showed a significantly higher adjusted odds ratio for the onset of AR
in offspring than those whose mothers had no symptoms during pregnancy (adjusted 
Odds Ratio: 6.26, p = 0.036). However, the symptoms of AR during late pregnancy
showed no effects on the odds ratio. In contrast, the presence or absence of AR
symptoms during early or late pregnancy showed no association with the prevalence
of food allergy, atopic dermatitis or asthma in offspring. CONCLUSIONS: Our
results suggest the presence of possible epigenetic mechanisms regulating the
onset of AR in humans presumably through increased organ-specific
hypersensitivity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17713362 [PubMed - indexed for MEDLINE]

265: Neuroimmunomodulation. 2007;14(2):78-83. Epub 2007 Aug 21.

Botulinum toxin therapy in the ovalbumin-sensitized rat.

Wen WD, Yuan F, Wang JL, Hou YP.

School of Life Science, Lanzhou University, Lanzhou, PR China.

OBJECTIVE: The aim of this study was to determine whether intranasal
administration of botulinum toxin type A (BTX-A) could relieve the typical
symptoms of allergic rhinitis (AR) and alter substance P (SP)- and vasoactive
intestinal peptide (VIP)-immunoreactive (IR) expression in nasal mucosa of AR
animals sensitized with ovalbumin (OVA). METHODS: AR was induced by
intraperitoneal injection of OVA followed by its repeated intranasal instillation
in female Wistar rats. Some AR animals were intranasally treated with a cotton
strip containing BTX-A (10 U per nostril) for 1 h. After BTX-A treatment, OVA was
repeatedly instilled in AR and AR + BTX-A groups every 2 days for 10 days.
Subsequently, nasal symptoms were evaluated, and nasal secretions collected.
Finally, the nasal mucosae of all animals were prepared for histological and
immunohistochemical assessment. RESULTS: BTX-A administration alleviated typical 
AR symptoms including rhinorrhea, nasal itching and sneezing, and subsequent
intranasal repeated challenge with OVA did not trigger AR symptoms. After BTX-A
treatment, inflammatory histological characteristics within the nasal mucosa of
AR animals were absent, but atrophy of serous glands was observed. BTX-A
decreased dense SP-IR and VIP-IR cells and fibers within and beneath the
epithelium, around blood vessels and close to serous glands in AR animals.
CONCLUSION: Local BTX-A treatment is an effective method to reduce AR symptoms.
BTX-A decreased the excessive SP-IR and VIP-IR expression induced by OVA.
Therefore, BTX-A may affect the nasal mucosa via the suppression of
neuropeptides, playing a major role in autonomous mucosal innervation in the
pathophysiology of AR. Copyright (c) 2007 S. Karger AG, Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17713354 [PubMed - indexed for MEDLINE]

266: Eur Ann Allergy Clin Immunol. 2007 Jun;39(6):200-1.

Drug allergy and pollinosis. A short report.

Palma-Carlos AG, Clode MH, Ferreira AM, Palma-Carlos ML.

Clinical Allergy Immunology Center, CAIC, Lisbon, Portugal.
a-g-palma-carlos@clix.pt

2 series of patients with pollinosis and drug allergy studied 10 years apart and 
comprising 115 cases are presented. In both series grass pollens and parietaria
are as usual the most common cause of pollinosis but Parietaria was more common
in the first series. Beta-lactams were the major cause of drug allergy in the
first group, supersed by NSAID in the second group. Rhinitis was the more
frequent symptom on pollinosis and urticaria/angioedema on drug allergy.

PMID: 17713173 [PubMed - indexed for MEDLINE]

267: Rhinology. 2007 Jun;45(2):134-9.

Side-effects of injective allergen immunotherapy administered to intermittent or 
persistent allergic rhinitis patients.

Rogala B, Markiewicz-Bendkowska IB, Brzoza Z, Glück J, Oleś E.

Chair and Clinical Department of Internal Diseases, Allergology and Clinical
Immunology, Silesian University School of Medicine, Zabrze, Poland.
b_rogala@pro.onet.pl

AIM: Evaluation of the side-effects of conventional subcutaneous allergen
immunotherapy in inhalant allergy. MATERIAL AND METHODS: Retrospective analysis
of early and late, local and systemic, short-term and long-term side-effects of
4723 injections given to 224 patients suffering from intermittent or persistent
allergic rhinitis. RESULTS: There were 65 systemic reactions in 48 patients (21%)
after 61 injections (1.29%). Most of them were late, and included dyspnoea,
rhinorrhoea, fever, fatigue and urticaria. Incidence of systemic reactions did
not correlate to age or sex, but was higher in grass pollen than in house dust
mite allergy and during the up-dosing phase of treatment. Late intense local
reactions were observed after 1.6% of injections. CONCLUSIONS: Allergen
immunotherapy in inhalant allergy is a safe method of treatment.

PMID: 17708460 [PubMed - indexed for MEDLINE]

268: BMC Genomics. 2007 Aug 17;8:282.

Optimization of candidate-gene SNP-genotyping by flexible oligonucleotide
microarrays; analyzing variations in immune regulator genes of hay-fever samples.

Pullat J, Fleischer R, Becker N, Beier M, Metspalu A, Hoheisel JD.

Division of Functional Genome Analysis, Deutsches Krebsforschungszentrum, Im
Neuenheimer Feld 580, 69120 Heidelberg, Germany. janne@ut.ee

BACKGROUND: Genetic variants in immune regulator genes have been associated with 
numerous diseases, including allergies and cancer. Increasing evidence suggests a
substantially elevated disease risk in individuals who carry a combination of
disease-relevant single nucleotide polymorphisms (SNPs). For the genotyping of
immune regulator genes, such as cytokines, chemokines and transcription factors, 
an oligonucleotide microarray for the analysis of 99 relevant SNPs was
established. Since the microarray design was based on a platform that permits
flexible in situ oligonucleotide synthesis, a set of optimally performing probes 
could be defined by a selection approach that combined computational and
experimental aspects. RESULTS: While the in silico process eliminated 9% of the
initial probe set, which had been picked purely on the basis of potential
association with disease, the subsequent experimental validation excluded more
than twice as many. The performance of the optimized microarray was demonstrated 
in a pilot study. The genotypes of 19 hay-fever patients (aged 40-44) with high
IgE levels against inhalant antigens were compared to the results obtained with
19 age- and sex-matched controls. For several variants, allele-frequency
differences of more than 10% were identified. CONCLUSION: Based on the ability to
improve empirically a chip design, the application of candidate-SNP typing
represents a viable approach in the context of molecular epidemiological studies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17705862 [PubMed - indexed for MEDLINE]

269: J Med Virol. 2007 Oct;79(10):1600-5.

Respiratory syncytial virus protects against the subsequent development of
Japanese cedar pollen-induced allergic responses.

Liu B, Kimura Y.

Department of Microbiology, Fukui University School of Medicine, Fukui, Japan.

Respiratory syncytial virus (RSV) infection has been hypothesized to be a risk
factor for the development of allergy and asthma, but epidemiologic studies in
humans still remain inconclusive. The association between RSV infection and
allergic diseases may be dependent on atopic background and previous history of
RSV infection. In this study, the influence of the timing of RSV infection on the
development of Japanese cedar pollen (JCP)-induced allergic responses was
examined. BALB/c mice were intranasally infected with RSV before or after
sensitization to JCP. Production of cytokines in the culture fluid of lung
parenchyma cells and the level of antigen-specific antibodies in the serum were
determined. It became clear that JCP was a strong inducer for the elicitation of 
Th2-type responses, characterized by production of interleukin (IL)-4 and IL-5 in
the lung and JCP-specific IgE antibody in the serum. RSV infection, however,
suppressed JCP-induced allergic responses by decreasing the production of
Th2-like cytokines and Th2-type antibodies. This phenomenon was observed more
clearly in the groups that were infected with RSV, 2 weeks or 2 days before
sensitization to JCP. The inhibitory mechanism of RSV infection seems to be due
to RSV-induced Th1 type dominant environment, which down-regulated the Th2-type
responses subsequently induced by allergen sensitization. On the other hand,
JCP-inoculation altered RSV-induced immune responses to shift from Th1- to
Th2-type dominance, by inhibiting RSV-induced Th1-like cytokine production. These
data provide evidence that under a certain condition, RSV infection may play a
protective role in JCP-induced allergic responses. (c) 2007 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17705182 [PubMed - indexed for MEDLINE]

270: J Investig Allergol Clin Immunol. 2007;17(4):211-5.

Peak expiratory flow monitoring to screen for asthma in patients with allergic
rhinitis.

Baser S, Ozkurt S, Topuz B, Kiter G, Karabulut H, Akdag B, Evyapan F.

Pamukkale University Medical Faculty, Department of Pulmonary Diseases, Denizli, 
Turkey. basersevin@yahoo.com

AIM: To investigate the benefit of using peak expiratory flow (PEF) monitoring to
screen for asthma in allergic rhinitis patients. METHODS: Eighty-nine consecutive
patients with allergic rhinitis but never assessed for asthma were included in
this prospective study.Their allergic status was determined by skin prick tests. 
All of the subjects filled in a questionnaire on asthma-like symptoms. If they
reported such symptoms, pulmonary function tests were carried out. Then, PEF was 
checked twice daily for 3 weeks. RESULTS: Thirty-six percent of our study group
were male and 64% were female patients with a mean (SD) age of 36.3 (14.0) years.
Skin prick tests were positive to grass mixture in 71 (79.8%) patients, to tree
mixture in 51 (57.3%), to mite in 46 (51.7%), and to epidermal mix in 26 (29.2%) 
patients. Thirty-six patients (41%) reported 3 or more asthma symptoms. Lung
function test results for these 36 patients showed obstruction for 11.1% (4
patients); the remaining patients (88.9%) had normal function parameters. The
subjects who reported 3 or more asthma symptoms but had normal lung function
monitored their PEF for 3 weeks. Sixteen (50%) patients from this group and the 4
patients with demonstrated airway obstruction had more than 20% diurnal variation
in PEF. These 20 patients' asthma symptoms disappeared after they received 3
months of low-dose inhaled corticosteroid therapy. CONCLUSION: It is necessary to
look for asthma in patients suffering from allergic rhinitis. PEF monitoring is a
low-cost, objective approach to asthma diagnosis that can be performed by a
patient with allergic rhinitis even if spirometry is normal. Knowledge of this
technique is of utmost importance because delay in diagnosis will result in the
unsatisfactory treatment of the disease.

Publication Types: 
    Clinical Trial

PMID: 17694692 [PubMed - indexed for MEDLINE]

271: ORL Head Neck Nurs. 2007 Spring;25(2):9-14.

Diagnostic testing for inhalant allergies.

Krouse HJ.

Wayne State University, College of Nursing Detroit, MI, USA.

Allergic rhinitis is one of the most commonly treated disorders seen in
otolaryngology office settings. It is often difficult to distinguish the symptoms
associated with allergic rhinitis from other causes of rhinitis. Many times these
nasal symptoms can be effectively treated using nonspecific pharmacotherapeutic
agents in conjunction with general information on ways to reduce exposure to
allergens or irritants in the environment. When allergic rhinitis is suspected
and a targeted treatment approach is needed, allergy testing can confirm the
diagnosis and guide effective treatment for the condition. This paper discusses
various methods for diagnosing inhalant allergies with a special focus on a newer
approach to skin testing, known as modified quantitative testing or MQT. This
paper also presents an overview of the immune response as it occurs in allergic
rhinitis, along with a discussion of common inhalant allergens. Finally, this
paper offers a general approach to allergy testing and patient preparation.

Publication Types: 
    Review

PMID: 17691597 [PubMed - indexed for MEDLINE]

272: Biosci Biotechnol Biochem. 2007 Aug;71(8):1955-62. Epub 2007 Aug 7.

Clinical effects of a hop water extract on Japanese cedar pollinosis during the
pollen season: a double-blind, placebo-controlled trial.

Segawa S, Takata Y, Wakita Y, Kaneko T, Kaneda H, Watari J, Enomoto T, Enomoto T.

Frontier Laboratories of Value Creation, Sapporo Breweries Ltd., Yaizu, Shizuoka,
Japan. shuuichi.segawa@sapporobeer.co.jp

The clinical effects of an oral administration of a hop water extract (HWE) on
the improvement of Japanese cedar pollinosis (JCPsis) symptoms were investigated.
In a double-blind, placebo-controlled trial, 39 subjects took a drink containing 
either 100 mg of HWE or a placebo for 12 weeks during the pollen season. Nasal
symptoms (sneezing attacks, nasal discharge, and nasal obstruction) were assessed
from the subjects' diaries. A clinical examination and blood sampling were
carried out before and 4, 8 and 12 weeks after the initiation of treatment. As a 
result, a significant difference was observed in the symptom score and in the
symptom-medication score 10 weeks after the intervention in comparison with the
placebo group. Improvements were observed in nasal swelling, nasal color, amount 
of nasal discharge, and characteristics of nasal discharge in the intervention
group 12 weeks after the treatment. No significant eosinophil infiltration into
the nasal discharge was apparent in the intervention group throughout the study
period, although it was observed in the placebo group. These findings indicate
that an oral administration of HWE may be effective in alleviating the allergic
symptoms related to JCPsis.

Publication Types: 
    Controlled Clinical Trial

PMID: 17690485 [PubMed - indexed for MEDLINE]

273: Respir Med. 2007 Nov;101(11):2321-6. Epub 2007 Aug 7.

Peripheral nitric oxide is increased in rhinitic patients with asthma compared to
bronchial hyperresponsiveness.

Tufvesson E, Aronsson D, Ankerst J, George SC, Bjermer L.

Respiratory Medicine and Allergology, Department of Clinical Sciences, Lund
University, 221 85 Lund, Sweden. Ellen.Tufvesson@med.lu.se

Allergic rhinitis is a predisposing factor for developing clinical asthma.
Moreover, allergic rhinitis is often associated with bronchial
hyperresponsiveness (BHR). We hypothesise that patients with asthma have more
small airway involvement than those with allergic rhinitis and BHR alone. The aim
of this study was to assess peripheral and proximal NO concentration in rhinitic 
subjects, and to correlate the peripheral NO concentration to the peripheral
obstruction in response to methacholine. Patients with allergic rhinitis with or 
without BHR, or clinical asthma were investigated in and out of the allergy
season. Healthy subjects served as controls. Fractional exhaled NO was performed,
and peripheral NO concentration and proximal flux of NO was calculated.
Methacholine test was performed including impulse oscillometry. Rhinitic patients
with asthma demonstrate an increase in both proximal and peripheral NO compared
to those with rhinitis alone or those with BHR. There is a trend of increased
peripheral NO from patients with rhinitis only, rhinitis and BHR, to rhinitis
with asthma. The increase in peripheral NO correlated with an increased
peripheral obstruction in response to methacholine. Patients with seasonal
allergic rhinitis demonstrated a decrease in both proximal and peripheral NO in
the off-season. The results support our hypothesis that rhinitic patients with
asthma have more peripheral lung inflammation and small airway involvement
compared to rhinitic patients with BHR alone.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17686621 [PubMed - indexed for MEDLINE]

274: Allergy. 2007 Sep;62(9):1085-6.

Vitamin D serum levels and allergic rhinitis.

Wjst M, Hyppönen E.

Molecular Epidemiology Group, GSF National Research for Environment and Health,
Ingolstaedter Landstrasse 1, Munich-Neuherberg, Germany.

In addition to its role in the regulation of calcium metabolism, vitamin D has a 
number of immunological effects. Several studies in children found an effect of
oral supplementation on allergic sensitization but so far there are no
population-based studies of vitamin D serum levels. We therefore examined
25(OH)-D(3) status in 18,224 adults of the Third National Health and Nutrition
Examination Survey. There was no effect on sensitization to a single allergen
while the prevalence of allergic rhinitis increased across quartile groups of
current vitamin D serum levels. The association could be due to unrecognized
confounding, however, could also point towards an altered metabolism or an
increased sensitivity to vitamin D in allergic patients.

PMID: 17686112 [PubMed - indexed for MEDLINE]

275: Allergy. 2007 Sep;62(9):1078-84.

Once daily fluticasone furoate nasal spray is effective in seasonal allergic
rhinitis caused by grass pollen.

Fokkens WJ, Jogi R, Reinartz S, Sidorenko I, Sitkauskiene B, van Oene C, Faris
MA, Ellsworth A, Caldwell MF.

Academisch Medisch Centrum, Divisie Neurozintuigspecialismen, Polikliniek KNO,
Amsterdam, The Netherlands.

BACKGROUND: Fluticasone furoate is a new enhanced-affinity glucocorticoid with a 
unique combination of pharmacodynamic and physicochemical properties suitable for
topical activity. METHODS: In this multicentre, randomized, double-blind,
placebo-controlled, parallel-group study, patients [adults and adolescents >or=12
years of age with seasonal allergic rhinitis (SAR)] received once-daily (od)
treatment for 2 weeks with either fluticasone furoate nasal spray 110 microg (n =
141) or placebo nasal spray (n = 144) administered in a unique, side-actuated
device. Efficacy measures included total nasal symptom score (TNSS) and total
ocular symptom score (TOSS). Patients also reported their overall response to
therapy and rated their quality of life using the Rhinoconjunctivitis Quality of 
Life Questionnaire (RQLQ). RESULTS: Fluticasone furoate significantly improved
the mean change from baseline in daily reflective TNSS compared with placebo
(treatment difference of -1.757; P < 0.001). Fluticasone furoate was also
significantly more effective in improving the morning predose instantaneous TNSS 
(treatment difference of -1.898; P < 0.001) and daily reflective TOSS (treatment 
difference of -0.741; P = 0.001). A significant treatment effect was observed as 
early as day 1. Compared with placebo-treated patients, fluticasone
furoate-treated patients showed significantly greater improvements in overall
evaluation of response to therapy (P < 0.001), as well as in overall RQLQ score
(P < 0.001). Fluticasone furoate was well tolerated. CONCLUSION: Fluticasone
furoate nasal spray 110 mug od was effective in improving the nasal symptoms of
SAR. It also produced significant improvements in ocular symptoms.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17686111 [PubMed - indexed for MEDLINE]

276: Allergy. 2007 Sep;62(9):1064-70.

Relationship between ARIA classification and drug treatment in allergic rhinitis 
and asthma.

Antonicelli L, Micucci C, Voltolini S, Senna GE, Di Blasi P, Visonà G, De Marco
R, Bonifazi F.

Allergy Unit, Department of Internal Medicine, Immuno-Allergic and Respiratory
Diseases, Ospedali Riuniti di Ancona, Ancona, Italy.

INTRODUCTION: The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines
provide a stepwise treatment to rhinitis, which classifies the disease according 
to its duration and severity. OBJECTIVES: The aim of the study was to verify
whether these variables influence drug prescriptions for rhinitis and asthma.
METHODS: A multi-centre cross-sectional pharmaco-epidemiological survey was
carried out on 1,610 allergic rhinitis patients and the relationship between the 
clinical features of rhinitis and drug therapy for rhinitis and asthma was
evaluated. RESULTS: A total of 1,321 adult patients were enrolled. Mild
intermittent rhinitis was diagnosed in 7.7%of the patients, moderate/severe
intermittent in 17.1%, mild persistent in 11.6%, and moderate/severe persistent
in 63.6%. A high level of rhinitis-asthma comorbidity (616/1,321 = 46.6%) was
found. The majority of patients [1,060 (80.24%)] were treated. Significant
associations between the severity of rhinitis and the presence of therapy (P =
0.008), the use of oral antihistamines (P < 0.001), topical nasal steroids (P =
0.020) and systemic steroids (P = 0.005) were found. A weak association was found
between the features of rhinitis and the therapy for asthma, and vice versa the
comorbidity with asthma increases the prescription of inhalant (P < 0.001) and
oral steroids (P = 0.015) to treat rhinitis. CONCLUSION: The severity of rhinitis
influences patient request for rhinitis therapy and the type of medication more
than the duration. These features of rhinitis seem to poorly influence asthma
therapy. As the ARIA classification is able to reveal a relevant impairment
notwithstanding therapy, its role in treated patients merits further study.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17686109 [PubMed - indexed for MEDLINE]

277: Allergy. 2007 Sep;62(9):1038-43.

Epidemiology of rhinitis in Portugal: evaluation of the intermittent and the
persistent types.

Todo-Bom A, Loureiro C, Almeida MM, Nunes C, Delgado L, Castel-Branco G, Bousquet
J.

SPAIC- Portuguese Society of Allergology and Clinical Immunology, Portugal.

BACKGROUND: The prevalence of rhinitis is rapidly increasing in recent years and 
has become a major public health problem in developed countries. A new
classification of allergic rhinitis has been proposed by the allergic rhinitis
and its impact on asthma group. In this study we aimed to evaluate the prevalence
of rhinitis, including different rhinitis subtypes and to describe the severity, 
rate of diagnosis and use of medication in this pathology. METHODS: A
cross-sectional, population-based study including 6,859 questionnaire responses
was performed. RESULTS: The estimated prevalence of rhinitis was 26.1% (48% for
intermittent vs 52% for persistent rhinitis). Only about one-third of the
rhinitis cases (31.9%) had done skin prick tests (35.3% for persistent rhinitis
vs 21.5% for intermittent rhinitis: P < 0.001) or had medication prescribed in
the last year (34%), (35.6% for persistent rhinitis vs 20.1% for intermittent
rhinitis : P < 0.001). The prevalence of rhinitis was higher in women (28.2 vs
22.2%; P < 0.001). Intermittent/persistent rhinitis showed the following
percentages : <or=25 years (65.6 vs 34.5, P = 0.001); 25-65 years (50.2 vs 49.5) 
>or= 65 years (52.1 vs 47.9). The estimated prevalence of rhino conjunctivitis
was 18.4%. In a severity scale from 0 to 10, the mean value was 6.1 points (6.4
for persistent rhinitis vs 4.8 for intermittent rhinitis: P < 0.001). CONCLUSION:
A significant prevalence of rhinitis and rhino conjunctivitis was identified in
all age groups. The severity, the frequency and duration of the symptoms which
classify the persistent type should be considered to establish a more effective
treatment and improve the quality of life of the patients with rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17686106 [PubMed - indexed for MEDLINE]

278: Allergy. 2007 Sep;62(9):1023-8.

Assessment of combined symptom and medication scores for rhinoconjunctivitis
immunotherapy clinical trials.

Clark J, Schall R.

Biostatistics, Quintiles South Africa, Centurion, South Africa.

BACKGROUND: In randomized, double-blind, placebo-controlled clinical trials the
efficacy of immunotherapy for allergic rhinoconjunctivitis is evaluated using the
Average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is
associated with lower ARTSS relative to placebo. For ethical reasons patients are
provided with registered rescue medication, which may alleviate symptoms and thus
reduce symptom scores. This effect biases the mean difference in ARTSS between
effective treatment and placebo towards zero. Therefore, when rescue medication
is taken by a patient, the ARTSS needs to be adjusted appropriately. METHODS: We 
considered five outcome measures: ARTSS, Average Rescue Medication Score (ARMS), 
and three combined symptom and RMSs. To assess the different outcome measures
regarding their power to discriminate between effective treatment and placebo, we
calculated their effect size when applied to data from a clinical trial of
immunotherapy for allergic rhinoconjunctivitis. RESULTS: Of the five outcome
measures considered, the average of the ARTSS and ARMS was associated with the
largest effect size, and thus with the highest power to show treatment efficacy. 
Discriminant and multivariate analyses suggest that this average is approximately
optimal among all weighted sums of ARTSS and ARMS. CONCLUSION: Our findings
support recommendations made in a World Allergy Organisation document on
methodological aspects of immunotherapy trials. The average of the ARTSS and ARMS
should be considered as a primary efficacy variable in clinical trials of
immunotherapy for allergic rhinoconjunctivitis.

Publication Types: 
    Randomized Controlled Trial

PMID: 17686105 [PubMed - indexed for MEDLINE]

279: Allergy. 2007 Sep;62(9):1007-13.

Effects of pollen and nasal glucocorticoid on FOXP3+, GATA-3+ and T-bet+ cells in
allergic rhinitis.

Malmhäll C, Bossios A, Pullerits T, Lötvall J.

Lung Pharmacology Group, Department of Internal Medicine/Respiratory Medicine and
Allergology, The Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden.

BACKGROUND: T-regulatory cells (Treg) affect the balance of T(H)2 and T(H)1
cells. Treg, T(H)2 and T(H)1 cells are regulated by the FOXP3, GATA-3 and T-bet
transcription factors respectively. Our aim was to determine the number of
FOXP3(+), GATA-3(+) and T-bet(+) cells in nasal mucosa in symptom-free allergic
rhinitis (AR) patients vs healthy controls, as well as the effects of natural
pollen exposure and concomitant nasal glucocorticoid treatment on these cells.
METHODS: Nasal biopsies were taken from healthy controls and patients with
grass-pollen AR preseason. The AR patients were randomized to receive treatment
with either fluticasone propionate (FP) or a placebo, and additional biopsies
were taken during the pollen season. FOXP3(+), GATA-3(+) and T-bet(+) cells in
nasal mucosa were quantified by immunohistochemistry. RESULTS: The number of
FOXP3(+) and GATA-3(+) cells, but not T-bet(+) cells, was significantly higher in
AR patients vs controls preseason. The number of FOXP3(+) cells remained
unchanged in the former group after the pollen season but decreased significantly
in the nasal mucosa as a result of FP treatment. The pollen season substantially 
increased the number of GATA-3(+) cells, which was inhibited by FP. The number of
T-bet(+) cells was not affected by pollen or FP. CONCLUSION: These data suggest
that nasal glucocorticoids attenuate the allergic inflammation partly by reducing
the number of T(H)2 cells, but not by means of local upregulation of Treg cells. 
The local relationship between T(H)1 and T(H)2 cells as well as between Treg and 
T(H)2 is maintained by nasal glucocorticoid treatment.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17686103 [PubMed - indexed for MEDLINE]

280: Pediatr Allergy Immunol. 2007 Sep;18(6):523-7.

Omalizumab (Xolair) in children with seasonal allergic rhinitis: leukotriene
release as a potential in vitro parameter to monitor therapeutic effects.

Kopp MV, Stenglein S, Kamin W, Friedrichs F, von Berg A, Zielen S, Hamelmann E,
Wahn U, Kuehr J.

University Children's Hospital, Freiburg, Germany.
matthias.kopp@uniklinkik-freiburg.de

To investigate the effect of omalizumab, a humanized monoclonal antibody, in
addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release
(SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with
omalizumab. Children and adolescents (6.3-17.6 yr) with sensitization to birch
and grass pollens and suffering from seasonal allergic rhinitis were included in 
a Phase III, placebo-controlled, multicenter clinical study. Within the four-arm 
study, patients were randomly chosen to receive SIT for either birch or grass
pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen 
season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy
continued. Blood samples were collected from 92 (A, B) and 78 children (C),
respectively. Leukocytes were isolated and stimulated with grass and birch pollen
allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA 
[cellular allergen stimulation test, DPC-Biermann, Germany]. At the end of
treatment the combination of omalizumab + SIT-grass [median SLT-release: 2125
(before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as
omalizumab + SIT-birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly 
lower SLT release after stimulation with the corresponding allergen compared to
placebo + SIT-grass [2231 and 2490 ng/ml] or placebo + SIT-birch [1324 and 2489
ng/ml]. One year after omalizumab or placebo treatment, there was no significant 
difference in SLT release between the 4 groups (omalizumab + SIT-grass: 2855;
SIT-grass + placebo: 2543; omalizumab + SIT-birch: 2417; SIT-birch + placebo:
2573 ng/ml). These results strongly suggest that the observed effects of
decreased SLT release after omalizumab treatment were attributable to the
treatment with omalizumab, rather than to SIT therapy.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17680911 [PubMed - indexed for MEDLINE]

281: Pediatr Allergy Immunol. 2007 Sep;18(6):516-22.

Safety of specific sublingual immunotherapy with SQ standardized grass allergen
tablets in children.

Ibañez MD, Kaiser F, Knecht R, Armentia A, Schöpfer H, Tholstrup B, Bufe A.

Servicio de Alergia, Hospital Universitario Niño Jesús, Madrid, Spain.
dibanezs@medynet.com

The aim of the study was to confirm the safety of an orodispersible grass
allergen tablet 75,000 SQ-T (Grazax, ALK-Abelló A/S, Hørsholm, Denmark) in
children aged 5-12 yr. The study was randomized, double-blinded and
placebo-controlled. Sixty children aged 5-12 yr suffering from grass
pollen-induced rhinoconjunctivitis (with or without asthma) from five centres in 
two countries (three in Germany and two in Spain) participated in the study. They
were randomized at the ratio of 3:1 as receiving either Grazax or placebo tablet 
given sublingually once daily for 28 days outside the grass pollen season. A
total of 810 treatment-related adverse events were reported in the Grazax group. 
The majority of these were local reactions in the mouth or throat and were mostly
mild (71%) to moderate (27%) in severity and resolved within days. Thirty-five
(78%) subjects treated with Grazax and five (33%) treated with placebo reported
at least one treatment-related adverse event. Oral pruritus, throat irritation,
mouth oedema and ear pruritus appeared as the most frequently reported
treatment-related adverse events. 62% (28 of 45) of the actively treated subjects
reported oral pruritus, 36% (16 of 45) throat irritation, 31% (14 of 45) mouth
oedema and 22% (10 of 45) ear pruritus. Two actively treated subjects withdrew
from the study: one subject due to four adverse events (moderate eye pruritus,
moderate pharyngolaryngeal pain, moderate non-cardiac chest pain and moderate
dysphagia) and one subject due to a serious adverse event (asthmatic attack). The
subjects recovered completely from the events. In conclusion, in the present
study, Grazax was in general tolerated in a paediatric population and considered 
suitable for further clinical investigations in children.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17680910 [PubMed - indexed for MEDLINE]

282: Pulm Pharmacol Ther. 2008;21(3):461-7. Epub 2007 Jun 28.

Syk inhibitors as treatment for allergic rhinitis.

Masuda ES, Schmitz J.

Rigel Inc., 1180 Veterans Boulevard, South San Francisco, CA 94080, USA.
emasuda@rigel.com <emasuda@rigel.com>

Allergic rhinitis is characterized by a hypersensitive immune response in the
upper airways to seasonal or perennial allergens leading to episodes of sneezing,
itching, runny nose and nasal congestion. These symptoms are mainly the
manifestations of a large number of mediators released by mast cells and
basophils localized in the nasal mucosa, following their activation via
allergen-specific immunoglobulin E (IgE) receptors. Current medications
antagonize the action of distinct mediators such as histamine and leukotrienes
for symptom relief, or block the production of pro-inflammatory cytokines to
suppress allergic inflammation. Notably, rather than neutralizing individual
mediators, Syk kinase inhibitors can block the allergen-induced release of all
mast cell mediators and the production of most eicosanoids and cytokines. Thus,
Syk kinase represents an attractive therapeutic target for acute and chronic
allergic inflammation. Syk kinase inhibitors are now entering clinical trials.
Using cell-based structure-activity relationships with primary human mast cells, 
a series of 2,4-diaminopyrimidine Syk kinase inhibitors was developed. One of
these compounds, referred to as R112, exhibited suitable characteristics for
intranasal delivery and was tested for safety and efficacy in allergic rhinitis
patients. In a park environment, R112 showed remarkable amelioration of acute
allergic rhinitis symptoms with rapid onset of action. These results demonstrate 
the clinical significance of inhibiting Syk in allergic upper airway disorders.

Publication Types: 
    Review

PMID: 17669674 [PubMed - indexed for MEDLINE]

283: Ann Agric Environ Med. 2007;14(1):123-8.

Regional importance of Alnus pollen as an aeroallergen: a comparative study of
Alnus pollen counts from Worcester (UK) and Poznań (Poland).

Smith M, Emberlin J, Stach A, Czarnecka-Operacz M, Jenerowicz D, Silny W.

National Pollen and Aerobiology Research Unit, University of Worcester, Henwick
Road, Worcester, WR2 6AJ, United Kingdom. m.smith@worc.ac.uk

Daily average Alnus pollen counts (1996-2005) from Worcester (UK) and Poznan
(Poland) were examined with the aim of assessing the regional importance of Alnus
pollen as an aeroallergen. The average number of Alnus pollen grains recorded
annually at Poznan was more than 2.5 times that of Worcester. Furthermore, daily 
average Alnus pollen counts exceeded the thresholds of 100, 500 and 1,000
grains/m3 more times at Poznan than Worcester. Skin prick test results
(1996-2005) and allergen-specific IgE (asIgE) measurements using the CAP
(Pharmacia) system (2002-2005), were supplied by the Allergic Diseases Diagnostic
Centre in Poznan. The annual number of positive skin prick tests to Alnus pollen 
allergens was significantly related (p<0.05) to seasonal variations in the
magnitude of the Alnus pollen catch recorded at Poznan (r=0.70). The symptoms of 
patients with positive skin prick tests to Alnus pollen allergens were: 51%
pollinosis, 43% atopic dermatitis, 4% asthma, 1% chronic urticaria and 1% eczema.
On a scale of 0-6, 20.5% of patients examined for serum asIgE in relation to
Alnus pollen allergens had asIgE measurements in classes 5 and 6. Alnus pollen is
generally considered to be mildly allergenic. However, the amount of Alnus pollen
released into the atmosphere in places such as Poznan may increase its impact on 
the population and make it one of the more important aeroallergens present.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17655189 [PubMed - indexed for MEDLINE]

284: Ann Agric Environ Med. 2007;14(1):87-91.

Incidence of Betulaceae pollen and pollinosis in Zagreb, Croatia, 2002-2005.

Peternel R, Milanović SM, Hrga I, Mileta T, Culig J.

Polytechnic College Velika Gorica, Zagrebacka 5, HR-10410 Velika Gorica, Croatia.
renata.peternel@zg.t-com.hr

Pollen allergy is characterized by seasonal allergic manifestations affecting
patients during the plant pollen season. The aim of this study was to analyze the
Betulaceae pollen pattern in Zagreb (2002-2005) and to determine the incidence of
sensitization to these pollen types in patients with seasonal respiratory
allergy. Twenty-four-hour pollen counts were carried out using volumetric
procedure. Skin prick test were performed on a total of 864 patients aged 18-80< 
in Zagreb between 2 January-31 December 2004. Pollen of the representatives of
the family Betulaceae accounted for a significant proportion of total pollen (34%
on an average), predominated by Betula pollen and considerably lower proportion
of Alnus sp. and Corylus sp. pollen. Alder and hazel pollen first occurred in the
air in February throughout the study period. The highest airborne pollen
concentration of these taxa was recorded in February and March. The birch pollen 
season generally peaked in April. Only 2.67% of patients showed birch pollen
monosensitization. The proportion of patients with polysensitization to
Betulaceae pollen was considerably greater (12.88%), whereas polysensitization to
Betulaceae, Poaceae and Ambrosia pollen was recorded in the highest proportion of
patients (26.23%). According to age, the highest and lowest rate of allergy was
recorded in the 31-50 and >51 age groups, respectively (46.22% vs 23.12%). Female
predominance was observed across all age groups. The patients with
monosensitization to birch pollen had the most severe symptoms in April. In the
patients with poylsensitization to alder, hazel and birch pollen who developed
cross-reaction, initial symptoms occurred as early as February, with abrupt
exacerbation in March and April. The most severe condition was observed in the
patients allergic to birch, hazel, alder, grass and ragweed pollen, with symptoms
present throughout the year and exacerbation in spring and late summer months.

PMID: 17655183 [PubMed - indexed for MEDLINE]

285: Ann Agric Environ Med. 2007;14(1):63-9.

Airborne allergenic pollen in natural areas: Hornachuelos Natural Park, Cordoba, 
southern Spain.

Garcia-Mozo H, Dominguez-Vilches E, Galan C.

Department of Botany, Ecology and Plant Physiology, Campus Universitario de
Rabanales, Universidad de Cordoba, Cordoba, Spain. bv2gamoh@uco.es

The present study shows the results of monitoring the atmospheric pollen in the
atmosphere of an area of natural vegetation, the Hornachuelos Natural Park,
Cordoba, southern Spain, during a six years (1998-2003). Special attention was
paid in the seasonal and intra-diurnal characteristics of airborne allergenic
pollen. During this period, 31 pollen types were described, some of them rare in 
aerobiological analysis. High concentrations of allergenic pollen from
entomophilous species and from areas at a long distance were found. Significant
differences between pollen spectrum and pollen concentration of the natural study
area and the surrounding cities were detected. Intra-diurnal pattern from trees
surrounding the trap presented a clear peak at midday/afternoon. Pollen from taxa
comprising many species and from species at far locations showed a smoother
intra-diurnal pattern. The correlation with meteorological parameters was
positive with maximum and mean temperatures, and negative with humidity and
rainfall.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17655179 [PubMed - indexed for MEDLINE]

286: Ann Agric Environ Med. 2007;14(1):39-43.

Allergy to periwinkle pollen (Catharanthus roseus G. Don.).

Ghosh D, Roy I, Chanda S, Gupta-Bhattacharya S.

Department of Botany, Bose Institute, 93/1 Acharya Prafulla Chandra Road,
Calcutta - 700 009, India.

Catharanthus roseus G. Don. (CR) or periwinkle plants are widely grown/
cultivated as garden plants in the tropics and subtropics. In spite of its
predominantly entomophilous nature, CR pollen had been reported to be airborne
and allergenic. The objective of this study was to discover the seasonal changes 
of CR pollen concentration in air, to determine its potential to cause
respiratory allergy and to analyze its allergenic components. A 2-year
aerobiological survey was conducted with a Burkard 7-day sampler in an
agricultural farm in the suburban zone of Calcutta city where CR pollen was found
to be almost perennial with 3.6-5.4% contribution to the aeropollen load. Skin
prick test was conducted on 282 respiratory allergic individuals living within a 
15 km radius of the study area. 29.8% of them were positive to CR pollen. Among
them, 80.9% were directly involved in gardening. The whole pollen extract was
subjected to gel filtration in a Sephacryl S-200 column. Among 5 eluted
fractions, fraction I showed optimum IgE-reactivity in ELISA-inhibition. The
fraction I shows 4 protein components in SDS-PAGE, within which 3 (40-66 kD
molecular mass) were found to be IgE-reactive in immunoblotting using patient
sera. It can be concluded that CR pollen can trigger IgEmediated respiratory
allergy in the people living in close proximity.

PMID: 17655175 [PubMed - indexed for MEDLINE]

287: Pediatr Allergy Immunol. 2008 Mar;19(2):110-24. Epub 2007 Jul 25.

Worldwide time trends for symptoms of rhinitis and conjunctivitis: Phase III of
the International Study of Asthma and Allergies in Childhood.

Björkstén B, Clayton T, Ellwood P, Stewart A, Strachan D; ISAAC Phase III Study
Group.

Collaborators: Ait-Khaled N, Anderson HR, Asher MI, Beasley R, Bjorkstén B,
Cookson W, Crane J, Ellwood P, Foliaki S, Keil U, Lai CK, Mallol J, Robertson C, 
Mitchell EA, Montefort S, Odhiambo J, Pearce J, Stewart AW, Strachan DP, von
Mutius E, Weiland SK, Williams H.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
bengt.bjorksten@ki.se

In Phase III of the International Study of Asthma and Allergies in Childhood
(ISAAC) time trends in the prevalence of rhinoconjunctivitis symptoms were
analysed. Cross-sectional questionnaire surveys with identical protocols and
questionnaires were completed a mean of 7 yr apart in two age groups comprising
498,083 children. In the 13- to 14-yr age group 106 centres in 56 countries
participated, and in the 6- to 7-yr age group 66 centres in 37 countries
participated. A slight worldwide increase in rhinoconjunctivitis prevalence was
observed, but the variations were large among the centres and there was no
consistent regional pattern. Prevalence increases in the older children exceeding
1% per year were recorded in 13 centres, including 3 of 9 centres in Africa, 2 of
15 in Asia-Pacific, 1 of 8 in India, 3 of 15 in Latin America, 3 of 9 in Eastern 
Europe and 1 of 34 in Western and Northern Europe. Decreasing
rhinoconjunctivititis prevalence of similar magnitude was only seen in four
centres. The changes were less pronounced in the 6- to 7-yr-old children and only
in one centre did any change exceed 1% per year. The decrease in highest
prevalence rates in ISAAC Phase I suggests that the prevalence has peaked in
those regions. An increase was recorded in several centres, mostly in low and
mid-income countries. The increases were more pronounced in the older age group, 
suggesting that environmental influences on the development of allergy may not be
limited to early childhood.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17651373 [PubMed - indexed for MEDLINE]

288: Clin Exp Allergy. 2007 Aug;37(8):1204-12.

The long-range transport of birch (Betula) pollen from Poland and Germany causes 
significant pre-season concentrations in Denmark.

Skjøth CA, Sommer J, Stach A, Smith M, Brandt J.

Department of Atmospheric Environment, National Environmental Research Institute,
Roskilde, Denmark. cas@dmu.dk

BACKGROUND: Birch pollen is highly allergic and has the potential for
episodically long-range transport. Such episodes will in general occur out of the
main pollen season. During this time, allergy patients are unprotected and high
pollen concentrations will therefore have a full allergenic impact. OBJECTIVE: To
show that Denmark obtains significant quantities of birch pollen from Poland or
Germany before the local trees start to flower. METHODS: Simultaneous
observations of pollen concentrations and phenology in the potential source area 
in Poland as well as in Denmark were performed in 2006. The Danish pollen records
from 2000 to 2006 were analysed for possible long-range transport episodes and
analysed with trajectories in combination with a birch tree source map. RESULTS: 
In 2006, high pollen concentrations were observed in Denmark with bi-hourly
concentrations above 500 grains/m(3) before the local trees began to flower.
Poland was identified as a source region. The analysis of the historical pollen
record from Copenhagen shows significant pre-seasonal pollen episodes almost
every year from 2000 to 2006. In all episodes, trajectory analysis identified
Germany or Poland as source regions. CONCLUSION: Denmark obtains significant
pre-seasonal quantities of birch pollen from either Poland or Germany almost
every year. Forecasting of birch pollen quantities relevant to allergy patients
must therefore, take into account long-range transport. This cannot be based on
measured concentrations in Denmark. The most effective way to improve the current
Danish pollen forecasts is to extend the current forecasts with atmospheric
transport models that take into account pollen emission and transport from
countries such as Germany and Poland. Unless long-range transport is taken into
account, pre-seasonal pollen episodes will have a full allergic impact, as the
allergy patients in general will be unprotected during that time.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17651151 [PubMed - indexed for MEDLINE]

289: Clin Exp Allergy. 2007 Aug;37(8):1183-8.

Increased expression of tissue vascular endothelial growth factor and foetal
liver kinase-1 receptor in seasonal allergic rhinitis and relevance to asthma
component.

Yuksel H, Kose C, Yilmaz O, Ozbilgin K, Degirmenci PB, Pinar E, Kirmaz C.

Department of Pediatric Allergy and Pulmonology, Celal Bayar University, Manisa, 
Turkey. hyukselefe@hotmail.com

BACKGROUND: There is a difference in the extent of remodelling in allergic
rhinitis (AR) and asthma. This may be attributed to the difference in local
tissue response to these mediators. OBJECTIVES: The aim of this study was to
compare vascular endothelial growth factor (VEGF) and its receptor foetal liver
kinase (Flk)-1 expression between seasonal AR patients with or without asthma and
non-allergic controls as well as that between AR patients with and without
asthma. METHODS: Thirteen subjects with seasonal AR and six non-allergic controls
were included in the study. Allergic sensitization was demonstrated by a skin
prick test. Inferior turbinate thiny biopsies were obtained from both groups.
Monoclonal mouse antibodies were used to demonstrate VEGF and Flk-1. Nasal
mucosal endothelial cells' staining intensity was graded semi-quantitatively and 
the histochemical score (HSCORE) was calculated. In all samples, VEGF- and
Flk-1-labelled vessels were counted for the assessment of vascular surface
density (VSD). RESULTS: The mean HSCORE for VEGF and anti-VEGF-based VSD were
significantly higher in the patient group (P=0.001 and 0.002, respectively). The 
mean HSCORE for Flk-1 and anti-Flk-1-based VSD in the patient group were
significantly higher than those in the control group (P=0.016 and 0.028,
respectively). Differences between the mean HSCORE for VEGF and anti-VEGF-based
VSD in patients with pure AR and AR and asthma were insignificant (P=0.16 and
0.39, respectively). The mean HSCORE for Flk-1 and anti-Flk-1-based VSD in
patients with pure AR were significantly lower than those in patients with AR and
asthma (P=0.004 and 0.018, respectively). CONCLUSION: Angiogenic factor VEGF and 
its receptor Flk-1 is increased in AR. A similar increase in VEGF in AR with and 
without asthma despite a higher Flk-1 in AR patients with asthma may be a
possible explanation for the presence of angiogenesis in the airway wall in
patients with asthma but not in those with pure AR.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17651148 [PubMed - indexed for MEDLINE]

290: Pharmacoeconomics. 2007;25(8):665-76.

Healthcare utilisation and costs associated with adding montelukast to current
therapy in patients with mild to moderate asthma and co-morbid allergic rhinitis:
PRAACTICAL study.

Dal Negro R, Piskorz P, Vives R, Guilera M, Sazonov Kocevar V, Badia X.

Lung Department, Bussolengo General Hospital, Verona, Italy.

OBJECTIVE: To evaluate the healthcare resource use and costs associated with
adding montelukast to therapy in patients with mild to moderate persistent asthma
and co-morbid seasonal allergic rhinitis whose asthma is inadequately controlled 
by their current asthma therapy. METHODS: A multicentre, pre-post retrospective
cohort study was conducted in three European countries (Italy, Poland and Spain).
Consecutive patients who were receiving inhaled corticosteroid therapy
(monotherapy or combination therapy with long-acting beta(2)-adrenoceptor
agonists) and who started concomitant treatment with montelukast between January 
1999 and December 2002 were identified from clinical charts. Asthma/seasonal
allergic rhinitis-related concomitant medications and asthma-related outpatient
care, ED visits and hospitalisations for the periods 12 months before and 12
months after montelukast initiation were recorded from patient charts and
combined with country-specific published unit costs (adjusted to 2004 values).
The analysis was performed from a third-party-payer perspective and thus direct
healthcare resource utilisation due to asthma/seasonal allergic rhinitis and
associated costs for each country were estimated. RESULTS: A total of 98
physicians provided data for 696 asthmatic patients with seasonal allergic
rhinitis (Italy: n = 158; Poland: n = 334; and Spain: n = 204). The mean age of
patients was 32.7 years, 57.5% were female and patients had asthma that was
considered either mild-persistent (54.5%) or moderate-persistent (45.5%)
according to the Global Initiative for Asthma classifications. The introduction
of montelukast (10 mg/day daily cost range euro0.8-1.68) was associated with
increases in the total annual mean healthcare cost per patient of 11.9%, 60.4%
and 5.5% for Italy, Poland and Spain, respectively. However, mean annual costs
for asthma-related outpatient care, ED visits and hospitalisations dropped
significantly in all three countries (Italy: from euro805.00 to euro281.60 [p <
0.01]; Poland: from euro127.10 to euro99.00 [p < 0.01]; and Spain: from
euro463.40 to euro119.70 [p < 0.01]). CONCLUSIONS: The addition of montelukast to
therapy in patients with mild to moderate asthma and concomitant seasonal
allergic rhinitis whose asthma was inadequately controlled by current asthma
therapy significantly reduced the use of concomitant asthma-allergy medications, 
ED visits, outpatient care visits and hospitalisation. The total direct
healthcare cost obtained after the addition of montelukast increased only as a
result of the montelukast treatment cost.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17640108 [PubMed - indexed for MEDLINE]

291: J Allergy Clin Immunol. 2007 Sep;120(3):688-95. Epub 2007 Jul 12.

Combination treatment with omalizumab and rush immunotherapy for ragweed-induced 
allergic rhinitis: Inhibition of IgE-facilitated allergen binding.

Klunker S, Saggar LR, Seyfert-Margolis V, Asare AL, Casale TB, Durham SR, Francis
JN; Immune Tolerance Network Group.

Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, National 
Heart and Lung Institute, Imperial College London, United Kingdom.

BACKGROUND: The combination of anti-IgE (omalizumab) therapy with ragweed
injection immunotherapy for seasonal allergic rhinitis results in a significant
reduction in systemic side effects and enhanced efficacy compared with
immunotherapy alone. One proposed mechanism of immunotherapy is to induce
regulatory antibodies that inhibit facilitated antigen presentation. OBJECTIVES: 
We sought to determine whether the combination protocol has a cumulative effect
on inhibition of facilitated antigen presentation both during and after
discontinuation of treatment. METHODS: Ragweed allergen immunotherapy with and
without omalizumab therapy was tested in a 4-arm, double-blind,
placebo-controlled study. Flow cytometry was used to detect serum inhibitory
activity for IgE-facilitated CD23-dependent allergen binding to B cells as a
surrogate marker for facilitated antigen presentation. Serum ragweed-specific
IgG4 was measured by means of ELISA. RESULTS: Immunotherapy alone resulted in
partial inhibition of allergen-IgE binding after 5 to 19 weeks of treatment
compared with baseline (P < .01). Complete inhibition of allergen-specific IgE
binding was observed in both treatment groups receiving omalizumab (P < .001).
Allergen-specific IgG4 levels were only increased after immunotherapy (P < .05), 
both in the presence and absence of anti-IgE treatment. Combined treatment
resulted in the induction of long-lasting inhibitory antibody function for up to 
42 weeks compared with either treatment alone. CONCLUSION: Ragweed immunotherapy 
induced serum regulatory antibodies that partially blocked binding of
allergen-IgE complexes to B cells. Additional treatment with anti-IgE, by
directly blocking IgE binding to CD23, completely inhibited allergen-IgE binding.
CLINICAL IMPLICATIONS: The combination of ragweed immunotherapy and anti-IgE
resulted in prolonged inhibition of allergen-IgE binding compared with either
treatment alone, events that might contribute to enhanced efficacy.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17631952 [PubMed - indexed for MEDLINE]

292: Eur Ann Allergy Clin Immunol. 2007 May;39(5):148-56.

Pharmacoeconomic assessment of specific immunotherapy versus current symptomatic 
treatment for allergic rhinitis and asthma in France.

Omnes LF, Bousquet J, Scheinmann P, Neukirch F, Jasso-Mosqueda G, Chicoye A,
Champion L, Fadel R.

AREMIS, Neuilly sur Seine, France.

OBJECTIVES: The therapeutic benefit of specific immunotherapy (SIT) in allergic
rhinitis and asthma has been endorsed by expert consensus. This study compared
the cost/efficacy (C/E) of SIT with current symptomatic treatments (CST) for
allergic rhinitis and asthma. METHODS: A C/E analysis was performed using a
decision tree model. The decision tree and medical and economic hypotheses were
defined by a panel of experts. The perspective adopted was that of the French
Social Security. The costs and efficacy of SIT and CST were compared for
dust-mite and pollen allergies, in adults and children. Direct medical costs
included diagnosis and follow-up, consultations, CST and SIT. End-point economic 
criteria were cost per stabilised patient and cost per asthma case avoided. A
sensitivity analysis was performed for each model. RESULTS: In adults, the
incremental costs per asthma case avoided with injectable SIT were 393 Euro and
1327 Euro for dust-mite and pollen allergy, respectively, over a 6-year period.
For sublingual SIT, the costs per asthma case avoided were 3158 Euro and 1708
Euro, respectively. In children, over a 7-year period, the incremental costs per 
asthma case avoided with injectable SIT were 583 Euro and 597 Euro for dust-mite 
and pollen allergy, respectively. For sublingual SIT the incremental costs were
3938 Euro and 824 Euro. CONCLUSION: Compared to CST, SIT is a cost-effective
treatment in pollen and dust-mite-induced allergic rhinitis and asthma.
Sublingual SIT is an attractive option in pollen-induced rhinitis, particularly
in children. SIT appears to be an economically relevant strategy compared to CST.

PMID: 17626329 [PubMed - indexed for MEDLINE]

293: Int J Immunopathol Pharmacol. 2007 Apr-Jun;20(2):267-78.

Interleukin-3 promotes the expression of E-NPP3/CD203C on human blood basophils
in healthy subjects and in patients with birch pollen allergy.

Hauswirth AW, Sonneck K, Florian S, Krauth MT, Bohm A, Sperr WR, Valenta R,
Schernthaner GH, Printz D, Fritsch G, Buhring HJ, Valent P.

Department of Internal Medicine I, Division of Hematology and Hemostaseology,
Medical University of Vienna, Austria.

We recently identified the ectoenzyme CD203c as a novel basophil activation
antigen that is upregulated in response to FcepsilonRI cross-linkage. We
investigated the effects of various interleukins (ILs) on expression of CD203c on
blood basophils using an antibody against CD203c and flow cytometry. Of all
cytokines tested, only IL-3 was found to upregulate expression of CD203c on
basophils above baseline levels. The effects of IL-3 were dose- and
time-dependent (EC(50): 0.1-1 ng/ml) without differences observed between healthy
and allergic donors. Whereas anti-IgE induced maximum upregulation of CD203c
within 15 minutes, the IL-3-induced upregulation showed a maximum after 180
minutes. IgE-receptor cross-linking resulted in enhanced expression of both CD63 
and CD203c, whereas IL-3 enhanced the levels of CD203c without promoting
expression of CD63. The IL-3-induced upregulation of CD203c was also observed in 
highly enriched basophils and was counteracted by a blocking antibody against the
alpha chain of the IL-3 receptor (CD123). The IL-3-induced upregulation of CD203c
was also found to depend on the presence of calcium. To analyze signaling
pathways involved in IL-3-induced upregulation of CD203c, pharmacologic
inhibitors were applied. The PI3-kinase inhibitors, wortmannin and LY294002
counteracted the IL-3-induced expression of CD203c, whereas MEK- and PKC
inhibitors showed no effects. In conclusion, IL-3 upregulates expression of
CD203c on basophils through a specific receptor and via a PI3-kinase-dependent
signaling-pathway. Compared to FcepsilonRI-mediated cell activation, IL-3-induced
upregulation of CD203c is a late(r) event and is not accompanied by upregulation 
of CD63.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17624239 [PubMed - indexed for MEDLINE]

294: Curr Opin Otolaryngol Head Neck Surg. 2007 Aug;15(4):268-73.

Neural aspects of allergic rhinitis.

Kim D, Baraniuk JN.

Division of Rheumatology, Immunology and Allergy, Georgetown University,
Washington, District of Columbia 20007-2197, USA.

PURPOSE OF REVIEW: Recent advances have helped to clarify the role of nerves in
allergic rhinitis. RECENT FINDINGS: Mast cell histamine release activates
histamine H1 receptors on a subset of nonmyelinated Type C afferent trigeminal
neurons to convey the sensation of itch. The itch nerves may be distinct from
those responsible for burning pain and the dull ache of congestion. Activation of
brain stem centers leads to cognition of nasal pruritus, generation of the
systemic sneeze reflex and recruitment of local nasal parasympathetic reflexes.
These cholinergic reflexes stimulate M3 muscarinic receptors on the submucosal
glands to cause exocytosis and the thick mucous discharge of allergic rhinitis.
The importance of these neural pathways is demonstrated by the benefits of
antihistamines to block itch and sneeze, and anticholinergic drugs to block
glandular secretion. One open question remains the role of mediators of allergic 
inflammation on the sensitivity and reactivity of afferent neurons and these
secretory reflexes. SUMMARY: The neurology of the nose helps to explain the
sensations encountered in allergic rhinitis and opens new frontiers for drug
discovery.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 17620902 [PubMed - indexed for MEDLINE]

295: Allergy. 2007 Aug;62(8):958-61.

Prolonged preseasonal treatment phase with Grazax sublingual immunotherapy
increases clinical efficacy.

Calderon MA, Birk AO, Andersen JS, Durham SR.

Imperial College, National Heart and Lung Institute, London, UK.

BACKGROUND: Sublingual immunotherapy treatment with grass allergen tablets
(Grazax) is initiated preseasonally without up-dosing and treatment is continued 
throughout the entire grass pollen season. Aims of the study: The influence of
the duration of preseasonal treatment on clinical efficacy obtained within the
grass pollen season was investigated. METHODS: Data from three randomized,
double-blind, placebo-controlled, multi-centre trials with varying preseasonal
treatment periods were analysed. In the grass pollen season, symptom and
medication score reductions relative to placebo were calculated and correlated
with the duration of the preseasonal treatment period. RESULTS: The analysis was 
based on data from 934 patients. A significant reduction in seasonal daily
rhinoconjunctivitis symptom and medication scores (17%, CI: 1-33% and 23%, CI:
1-47%, P < 0.05) was observed for patients treated with Grazax compared with
placebo after approximately 8 weeks of pretreatment. The magnitude of the
reductions in rhinoconjunctivitis symptom and medication scores increased with
longer duration of preseasonal treatment (P < 0.0001). CONCLUSIONS: Sublingual
immunotherapy with Grazax) must be initiated at least 8 weeks prior to the grass 
pollen season to provide a significant clinical efficacy. A longer preseasonal
treatment period (>8 weeks) improves the clinical efficacy (relative to placebo) 
during the grass pollen season.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17620076 [PubMed - indexed for MEDLINE]

296: Allergy. 2007 Aug;62(8):954-7.

Grass allergen tablet immunotherapy relieves individual seasonal eye and nasal
symptoms, including nasal blockage.

Durham SR, Riis B.

National Heart and Lung Institute, Imperial College and Royal Brompton Hospital, 
London, UK.

BACKGROUND: Symptoms of allergic rhinitis have a considerable impact on the
quality of life of the sufferer. Sneezing, runny nose, blocked nose and headache 
are some of the most common symptoms of allergic rhinitis, which affects work,
home and social life for many patients. Sublingual immunotherapy has shown to
induce a protective immune response and provide sustained symptom prevention for 
allergic patients. AIMS OF THE TRIAL: The overall aims were to investigate the
efficacy and safety of a sublingual grass allergen tablet (Grazax) 75 000 SQ-T;
ALK-Abelló A/S, Denmark). Reported here are the effects of Grazax on individual
eye and nasal symptoms. METHODS: The trial was a double-blind placebo-controlled 
trial including 634 participants with significant rhinoconjunctivitis because of 
grass pollen. Participants were randomized 1 : 1 to Grazax (a fast dissolving,
once daily immunotherapy tablet for home administration) or placebo and received 
treatment for at least 16 weeks prior to and continuing during the grass pollen
season of 2005. Four nasal symptoms and two eye symptoms were scored on a scale
from 0 (no symptoms) to 3 (severe symptoms) every day during the entire grass
pollen season. Nasal symptoms included runny nose, blocked nose, sneezing and
itchy nose; eye symptoms included gritty feeling/red/itchy eyes and watery eyes. 
RESULTS: Consistent and highly significant reductions in individual eye and nasal
symptoms (from 22 to 44%) were observed following treatment with Grazax as
compared with placebo (P < 0.0001). CONCLUSIONS: Grazax has effects on multiple
allergic symptoms, including nasal blockage, and is an effective treatment of
rhinoconjunctivitis, thereby reducing the need for topical anti-allergic drugs.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17620075 [PubMed - indexed for MEDLINE]

297: Allergy. 2007 Aug;62(8):949-53.

Allergen-induced in vitro expression of IL-18, SLAM and GATA-3 mRNA in PBMC
during sublingual immunotherapy.

Savolainen J, Nieminen K, Laaksonen K, Laiho T, Jacobsen L, Lahesmaa R, Terho EO,
Valovirta E.

Department of Pulmonary Diseases and Clinical Allergology, University of Turku,
Turku, Finland.

BACKGROUND: Signalling lymphocytic activation molecule (SLAM) and interleukin
(IL)-18 induce interferon (IFN)-gamma production from Th1 cells. The
allergen-induced SLAM and IL-18 mRNA expressions are increased during
subcutaneous immunotherapy (SCIT), but nothing is known about their role during
sublingual immunotherapy (SLIT). Transcription factor GATA-3 is associated with
Th2 cells but its role in SCIT and SLIT is yet unexplored. This study was
undertaken to analyse the allergen induced in vitro mRNA expression of IL-18,
SLAM and GATA-3 in peripheral blood mononuclear cells (PBMC) of children with
allergic rhinitis (AR) during SLIT. METHODS: Ten patients with AR undergoing
pollen SLIT with a weekly dose of 200,000 SQ-U, 10 with 24,000 SQ-U of mixture of
Betula verrucosa, Corylus avellana and Alnus glutinosa and 10 with placebo were
included. Peripheral blood mononuclear cell were stimulated with birch extract
prior to, after 1 and 2 years of the treatment. The mRNA expression was assessed 
using kinetic real-time RT-PCR (TaqMan); Applied Biosystems, Foster City, CA,
USA). RESULTS: The expression of IL-18 mRNA was increased in the high-dose group 
in comparison to the placebo group after 1 year of therapy (P = 0.028) and had an
inverse correlation with the late phase skin reaction after the second study year
(r = -0.41, P = 0.041). SLAM mRNA expression increased in the high-dose group
from baseline to 1 year (P = 0.028) and correlated with IL-10 (r = 0.96, P <
0.0001) and transforming growth factor-beta (r = 0.80, P = 0.0037) mRNA
expression. No significant changes were seen in GATA-3 mRNA expression.
CONCLUSIONS: During SLIT, IL-18 and SLAM are upregulated, suggesting that the Th2
type inflammatory response is downregulated during SLIT by increased Th1 type
response.

Publication Types: 
    Randomized Controlled Trial

PMID: 17620074 [PubMed - indexed for MEDLINE]

298: Allergy. 2007 Aug;62(8):943-8.

Specific immunotherapy has long-term preventive effect of seasonal and perennial 
asthma: 10-year follow-up on the PAT study.

Jacobsen L, Niggemann B, Dreborg S, Ferdousi HA, Halken S, Høst A, Koivikko A,
Norberg LA, Valovirta E, Wahn U, Möller C; (The PAT investigator group).

ALK-Abelló, Hørsholm, Denmark.

BACKGROUND: 3-year subcutaneous specific immunotherapy (SIT) in children with
seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma
during treatment and 2 years after discontinuation of SIT (5-year follow-up)
indicating long-term preventive effect of SIT. OBJECTIVE: We evaluated the
long-term clinical effect and the preventive effect of developing asthma 7-years 
after termination of SIT. METHODS: One hundred and forty-seven subjects, aged
16-25 years with grass and/or birch pollen allergy was investigated 10 years
after initiation of a 3-year course of SIT with standardized allergen extracts of
grass and/or birch or no SIT respectively. Conjunctival provocations were
performed outside the season and methacholine bronchial provocations were
performed during the season and winter. Asthma was assessed by clinical
evaluation. RESULTS: The significant improvements in rhinoconjunctivitis and
conjunctival sensitivity persisted at the 10-year follow-up. Significantly less
actively treated subjects had developed asthma at 10-year follow-up as evaluated 
by clinical symptoms [odds ratio 2.5 (1.1-5.9)]. Patients who developed asthma
among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment 
effect when adjusted for bronchial hyper-responsiveness and asthma status at
baseline including all observations at 3, 5 and 10 years follow-up (children with
or without asthma at baseline, n = 189; 511 observations) was statistically
significant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5-13.7) 
in favor of SIT. CONCLUSION: A 3-year course of SIT with standardized allergen
extracts has shown long-term clinical effects and the potential of preventing
development of asthma in children with allergic rhinoconjunctivitis up to 7 years
after treatment. CLINICAL IMPLICATION: Specific immunotherapy has long-term
clinical effects and the potential of preventing development of asthma in
children with allergic rhino conjunctivitis up to 7 years after treatment
termination.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17620073 [PubMed - indexed for MEDLINE]

299: Am J Respir Crit Care Med. 2007 Oct 1;176(7):659-66. Epub 2007 Jul 5.

Allergic rhinitis and onset of bronchial hyperresponsiveness: a population-based 
study.

Shaaban R, Zureik M, Soussan D, Antó JM, Heinrich J, Janson C, Künzli N, Sunyer
J, Wjst M, Burney PG, Neukirch F, Leynaert B.

INSERM U700, Epidémiologie des Maladies Respiratoires Faculté Xavier Bichat, BP
416, Paris, France. shaaban@bichat.inserm.fr

RATIONALE: Patients with allergic rhinitis have more frequent bronchial
hyperresponsiveness (BHR) in cross-sectional studies. OBJECTIVES: To estimate the
changes in BHR in nonasthmatic subjects with and without allergic rhinitis during
a 9-year period. METHODS: BHR onset was studied in 3,719 subjects without BHR at 
baseline, who participated in the follow-up of the European Community Respiratory
Health Survey. MEASUREMENTS AND MAIN RESULTS: BHR was defined as a >or=20%
decrease in FEV(1) for a maximum dose of 1 mg of methacholine. Allergic rhinitis 
was defined as having a history of nasal allergy and positive specific IgE
(>or=0.35 IU/ml) to pollen, cat, mites, or Cladosporium. The cumulative incidence
of BHR was 9.7% in subjects with allergic rhinitis and 7.0% in subjects with
atopy but no rhinitis, compared with 5.5% in subjects without allergic rhinitis
and atopy (respective odds ratios [OR] and their 95% confidence intervals [95%
CI] for BHR onset, 2.44 [1.73-3.45]; and 1.35 [0.86-2.11], after adjustment for
potential confounders including sex, smoking, body mass index and FEV(1)).
Subjects with rhinitis sensitized exclusively to cat or to mites were
particularly at increased risk of developing BHR (ORs [95% CI], 7.90 [3.48-17.93]
and 2.84 [1.36-5.93], respectively). Conversely, in subjects with BHR at baseline
(n = 372), 35.3% of those with allergic rhinitis, compared with 51.8% of those
without rhinitis had no more BHR at follow-up (OR [95% CI], 0.51 [0.33-0.78]).
BHR "remission" was more frequent in patients with rhinitis treated by nasal
steroids than in those not treated (OR [95% CI], 0.33 [0.14-0.75]). CONCLUSIONS: 
Allergic rhinitis was associated with increased onset of BHR, and less chance for
remission except in those treated for rhinitis.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17615387 [PubMed - indexed for MEDLINE]

300: Respir Med. 2007 Sep;101(9):1885-94. Epub 2007 Jul 3.

Cost-effectiveness of GRAZAX for prevention of grass pollen induced
rhinoconjunctivitis in Southern Europe.

Canonica GW, Poulsen PB, Vestenbaek U.

Allergy and Respiratory Diseases Clinic, DIMI, University of Genova,
Pad.Maragliano, L.go R.Benzi 10, 16132 Genoa, Italy.

BACKGROUND: Allergic rhinoconjunctivitis is a global health problem. Around 14
million people in Spain, France, Italy, and Austria suffer from grass pollen
induced allergic rhinitis. Standard care only provides symptoms relief, while
allergen specific immunotherapy (SIT) treats the underlying cause of the disease.
Grazax from ALK-Abelló is a new, tablet-based, effective route of SIT for home
treatment. The objective was to assess the cost-effectiveness of Grazax in four
Southern European countries. METHODS: A prospective pharmacoeconomic analyses was
carried out alongside a multinational, clinical trial measuring the efficacy of
Grazax. Pooled data on resource use and health outcomes were collected. A
societal perspective was adopted, and the analysis had a nine-year time horizon. 
The primary outcome measure was quality adjusted life years (QALYs). RESULTS:
Grazax was superior to standard care for all efficacy endpoints, including QALYs 
gained, and resulted in significantly less use of rescue medication and fewer
hours missed from work. Grazax was cost-effective for all countries for an annual
price in the range of 1500 euros - 1900 euros. The result was improved by
inclusion of future costs of asthma and exclusion of Spanish trial centers which 
experienced an exceptionally low pollen season. CONCLUSION: The analysis
illustrates that allergen SIT with Grazax for grass pollen induced
rhinoconjunctivitis is a cost-effective intervention in Southern Europe.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17611095 [PubMed - indexed for MEDLINE]

301: Ann Allergy Asthma Immunol. 2007 Jun;98(6):524-32.

Lower respiratory tract complications during nasal provocation: nonspecific
stimulant or specific allergen?

Kirmaz C, Degirmenci PB, Tunali D, Yuksel H.

Division of Allergy and Immunology, Department of Internal Medicine, Celal Bayar 
University Medical Faculty, Manisa, Turkey. ckirmaz@yahoo.com

BACKGROUND: Allergic rhinitis (AR) is an allergic inflammatory disease in which
allergen exposure leads to the appearance of symptoms in sensitized individuals
because of histamine liberation from nasal mucosal mast cells. Comorbidity of
this disease with allergic asthma is common. Therefore, the one airway one
disease theory has been put forward. Lower respiratory tract provocation tests
with both nonspecific (methacholine) and specific stimulants (allergen) have
yielded positive results in nonasthmatic patients with AR. However, not enough
research is available to demonstrate whether there is a response in the lower
respiratory tract during nasal provocation tests (NPTs) performed to evaluate
only nasal airway in these patients. OBJECTIVES: To determine if the lower
respiratory tract was affected as a result of NPTs with nonspecific and specific 
stimulants in nonasthmatic patients with AR and to determine the frequency of
lower respiratory tract obstruction due to NPT with nonspecific and specific
stimulants. METHODS: Thirty-six participants were enrolled in the study between
November 2005 and January 2006 (18 AR patients and 18 healthy control subjects). 
Patients underwent 2 sessions of NPT. The first session was performed with nasal 
methacholine as a nonspecific stimulant, and the second session was performed
with nasal Olea europaea extract as a specific stimulant. The control group
underwent only nonspecific nasal provocation with methacholine. Basal nasal
opening and nasal pressures were evaluated spirometrically by rhinomanometric
measurements and basal respiratory function tests in both groups before
methacholine nasal provocation. Whether or not nasal provocation was achieved,
spirometric measurements were performed in all patients and controls after NPTs. 
RESULTS: NPTs with methacholine resulted in a similar frequency of nasal
provocation in the patient and control groups (P = .63). However, the mean
methacholine dose was lower in patients with AR (P = .049). There was a decrease 
in parameters of asthma, including the ratio of forced expiratory volume in 1
second to forced vital capacity (P = .04), peak expiratory flow (P = .01), and
forced expiratory flow between 25% and 75% (P = .004), as a result of NPTs with
methacholine in the patient group. However, NPTs with allergen did not cause a
change in lower respiratory tract obstruction criteria. CONCLUSIONS: Lower
respiratory tract obstruction can occur after NPTs with nonspecific stimulants;
therefore, tests performed with specific allergens can be regarded as safer.

PMID: 17601264 [PubMed - indexed for MEDLINE]

302: Acta Derm Venereol. 2007;87(4):305-11.

Differential immunomodulating effects of inactivated probiotic bacteria on the
allergic immune response.

Rasche C, Wolfram C, Wahls M, Worm M.

Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin,
Berlin, Germany. margitta.worm@charite.de

Bacterial stimulation plays an important role in modulating the allergic immune
response. The aim of this study was to investigate the effects of inactivated
probiotic Lactobacillus acidophilus and non-pathogenic Escherichia coli strain
Nissle on the phenotype and function of T- and B-cells. Peripheral blood
mononuclear cells from patients with grass-pollen allergy (n=10) and non-allergic
patients (n=19) were co-stimulated with inactivated bacteria and grass-pollen
allergen. Expression of CD23, CD80, CD86 and CD69 were analysed, and the
intracellular production of interleukin-4 and interferon-gamma was measured by
direct ex vivo flow cytometry after stimulation. Both bacteria induced a
significant up-regulation of CD69 expression on T-lymphocytes (p=0.001). CD23
expression was significantly increased following stimulation with allergen
(p=0.008), but reduced after stimulation with Lactobacillus and significantly
reduced with E. coli plus allergen (p=0.029). CD80 expression was reduced after
stimulation with Lactobacillus in the allergic group only (p=0.021). By contrast,
CD86 expression was significantly increased after stimulation with Lactobacillus 
(p=0.049) and distinctly increased with E. coli in both groups (p=0.001). The
cytokine patterns of CD69-positive T-lymphocytes from allergic patients showed a 
TH2-dominated response after allergen stimulation
(interferon-gamma/interleukin-4-ratio 0.2), directed into a T-helper1-like
response by stimulation with both types of bacteria
(interferon-gamma/interleukin-4-ratios 1.5-2.0 in both groups). These data show
that both types of bacteria modulate the allergic immune response by the
alteration of CD23 and co-stimulatory molecule expression. Regarding cytokine
production, the data suggest a differential response to both bacteria depending
on the atopic state, but a clear promotion of T-helper1-dominated response in
allergic donors.

PMID: 17598032 [PubMed - indexed for MEDLINE]

303: Pediatr Pulmonol. 2007 Aug;42(8):693-8.

Exhaled nitric oxide: interactions between asthma, hayfever, and atopic
dermatitis in school children.

Welsh L, Lercher P, Horak E.

Medical University Innsbruck, Department of Hygiene, Microbiology and Social
Medicine, Austria. l.welsh@ich.ucl.ac.uk

BACKGROUND: Clinicians frequently rely on reported symptoms and basic pulmonary
function testing to assess asthma prevalence in the community. However, given
that spirometry results are often normal for asthmatic children and the fact that
there is no equivalent word for 'wheeze' in languages other than English, the
assessment of asthma prevalence can be troublesome. OBJECTIVE: To evaluate in a
population based setting, whether FeNO as a non-invasive marker, contributes to
the detection of asthma. METHODS: This cross-sectional study was carried out on
primary school children from Northern and Southern Tyrol. FeNO measurements were 
made using the online single breath technique prior to spirometry. Symptom status
including asthma, hayfever and atopic dermatitis was determined by the ISAAC
questionnaire. RESULTS: Six hundred and forty-four Tyrolean children aged 8-10
years participated. In terms of FEV1 % predicted, the asthma and hayfever group
had significantly lower values compared to the asymptomatic group, the hayfever
only, and the atopic dermatitis only groups. For FeNO, participants with asthma
and hayfever, asthma and atopic dermatitis, and hayfever only recorded
significantly greater FeNO values when compared to the asymptomatic group.
Moreover, the asthma and atopic dermatitis group recorded significantly greater
FeNO when compared to the asthma only group. Multivariate regression revealed
that asthma had a small significant inverse association with FEV1 % predicted for
the individual model and when combined with hayfever. For FeNO, each of the
individual and combined model analyses achieved significance. CONCLUSION:
Although FeNO appears to be influenced by asthma, the presence of other atopic
conditions confounds the relationship. Elevated levels of FeNO do not distinguish
between asthma and other atopic conditions. Therefore, FeNO does not contribute
to the detection of asthma in the community. CLINICAL IMPLICATION: FeNO is not a 
valuable tool for the detection of asthma in the community as it is confounded by
other atopic conditions. 2007 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17588251 [PubMed - indexed for MEDLINE]

304: Allergol Int. 2007 Sep;56(3):277-83. Epub 2007 Jul 1.

Relationship between airborne Cry j 1 and the onset time of the symptoms of
Japanese cedar pollinosis patients.

Takahashi Y, Aoyama M, Yoshitake M, Abe E, Ohta N, Sakaguchi M.

The Yamagata Prefectural Institute of Public Health, Yamagata City, Yamagata,
Japan. takahashiyui@pref.yamagata.jp

BACKGROUND: Some patients with Japanese cedar (JC) pollinosis already show
pollinosis symptoms before the first day of the pollen season as determined by
microscopic pollen counts. METHODS: Airborne pollen allergen (Cry j 1) levels
were measured by electron spin resonance radical immunoassay, a highly-sensitive 
method for Cry j 1 with a sensitivity 10-100-fold higher than conventional
enzyme-linked immunosorbent assay. The symptom data from patients with JC
pollinosis were collected from a mobile phone site, "pollen check sheet", and the
onset times of the patients' symptoms were analyzed. RESULTS: The relationship
between airborne Cry j 1 levels and the onset time of pollinosis symptoms was
investigated. The symptoms of some patients began at the time airborne Cry j 1
levels fluctuated at 1 to 3 pg/m3 and symptom scores increased at the time of
sudden increase in Cry j 1 levels. About 40% of patients began to show symptoms
until the first day of the pollen season and the time nearly corresponds to the
time of sudden increase in Cry j 1 levels. CONCLUSIONS: Pollinosis symptoms of
some patients began at the time airborne Cry j 1 levels fluctuated at 1 to 3
pg/m3 and symptom scores increased at the time of sudden increase in Cry j 1
levels. The latter time nearly corresponds to the first day of the pollen season.

PMID: 17582210 [PubMed - indexed for MEDLINE]

305: Allergy. 2007 Sep;62(9):1057-63. Epub 2007 Jun 20.

Undertreatment of rhinitis symptoms in Europe: findings from a cross-sectional
questionnaire survey.

Maurer M, Zuberbier T.

Allergie-Centrum-Charité Department of Dermatology and Allergy, Charité-
Universitätsmedizin Berlin, Member of GA(2)LEN Berlin, Germany.

BACKGROUND: Allergic rhinitis is a frequent disease affecting one in five
Europeans with a significant impact on patient quality of life, health-care
costs, and economic productivity. Although effective treatments exist, the
disease often remains undiagnosed and not correctly treated, despite clear
diagnostic and therapeutic guidelines from WHO, EAACI (European Academy of
Allergology and Clinical Immunology), and GA(2)LEN (Global Allergy and Asthma
European Network). This study elucidates the reasons for this discrepancy from
the patients' point of view. METHODS: An internet and telephone survey was
conducted with 2,966 randomly selected adults with allergies from the general
population in the five major EU countries: UK, France, Germany, Italy, and Spain.
RESULTS: The main reason that the majority of respondents first visited a medical
professional for their rhinitis symptoms was because these symptoms became
intolerable. The respondents had not seen a medical professional in the past year
for their rhinitis symptoms in 52.6% of the cases, and 30.2% of the respondents
preferred nonprescription medication because it did not require visiting a
doctor. 'Nontreaters' and 'homeopathic treaters' together made up 26.2% of the
respondents, and 40.2% of them gave the cost of medication as a reason they do
not use allergy medications. CONCLUSIONS: Allergic rhinitis remains widely
undertreated in Europe with avoidable socioeconomic consequences. Effective
treatment exists, but patients wait too long to seek medical advice, and health
providers neglect to actively screen early for allergies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17581263 [PubMed - indexed for MEDLINE]

306: Clin Exp Allergy. 2007 Jul;37(7):1111-9.

A pectin methylesterase as an allergenic marker for the sensitization to Russian 
thistle (Salsola kali) pollen.

Barderas R, García-Sellés J, Salamanca G, Colás C, Barber D, Rodríguez R,
Villalba M.

Dpto. Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad
Complutense, Madrid, Spain.

BACKGROUND: Chenopodiaceae pollen is considered the main cause of pollen allergy 
in desert countries and its incidence is world-wide increasing by the
desertization of extensive zones. Although the correlation between the
sensitization to Chenopodium album and Salsola kali pollens of patients suffering
from allergy to Chenopodiaceae pollens is high, a significant number of patients 
exhibited IgE sensitivity exclusively towards S. kali. OBJECTIVE: To analyse this
differential reactivity and to purify, clone and characterize the putative
responsible allergen. METHODS: Immunoblotting was used to analyse the IgE binding
to pollen extract for S. kali and C. album. The protein was isolated by two
chromatographic steps and characterized by Edman degradation, mass spectrometry, 
finger print analysis and Concanavalin A lectin staining. Specific cDNA was
amplified by polymerase chain reaction, cloned in Escherichia coli and sequenced.
Immunologic characterization was performed by immunoblotting, enzyme-linked
immunoassay detection and inhibition experiments using sera from 11 patients
allergic to S. kali pollen. RESULTS: cDNA codifies for a mature protein of 339
amino acids plus a putative signal peptide of 23 residues and it belongs to the
plant pectin methylesterase (PME) family. It is a mildly basic and polymorphic
protein and was recognized by the IgE from all the patients allergic to S. kali
included in the study, and was called Sal k 1. The protein was not recognized in 
the C. album pollen extract using the sera of these patients. CONCLUSION: Sal k 1
is a protein from the PME family with a high allergenic relevance. Considering
this allergen as responsible for the different sensitization between S. kali and 
C. album pollen, it may be a useful marker to classify patients allergic to
Chenopodiaceae allowing a safer and more specific immunotherapy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17581207 [PubMed - indexed for MEDLINE]

307: Clin Exp Allergy. 2007 Jul;37(7):1067-73.

Cysteinyl-leukotriene levels in sputum differentiate asthma from rhinitis
patients with or without bronchial hyperresponsiveness.

Tufvesson E, Aronsson D, Bjermer L.

Department of Respiratory Medicine and Allergology, University Hospital, Lund,
Sweden. Ellen.Tufvesson@med.lu.se

BACKGROUND: We have previously reported that asthma differs from rhinitis with or
without bronchial hyperresponsiveness in the perception and degree of lower
airway inflammation. OBJECTIVE: The aim of the present study was to investigate
whether sputum levels of inflammatory markers could further distinguish these
patient groups. METHODS: Patients with seasonal allergic rhinitis with or without
asthma or bronchial hyperresponsiveness to methacholine were investigated.
Induced sputum was performed during as well as off season, and analysed for
cysteinyl-leukotrienes, hyaluronan, eosinophilic cationic protein (ECP) and other
inflammatory markers. RESULTS: Asthmatic patients differentiated from those with 
rhinitis with or without bronchial hyperresponsiveness in levels of
cysteinyl-leukotrienes [geometric mean: 3.3 (lower 95%-upper 95% confidence
interval (CI) of geometric mean: 1.9-5.1) vs. 1.4 (0.9-2.2) and 0.7 (0.3-1.6)
pg/microg total protein] and hyaluronan [0.30 (0.22-0.43) vs. 0.15 (0.10-0.20)
and 0.20 (0.12-0.35) ng/microg total protein] in sputum. The levels of
cysteinyl-leukotrienes decreased in sputum from the asthmatic patients, while the
levels of hyaluronan remained elevated off-season. Furthermore, elevated levels
of ECP were noticed among both the asthmatic and rhinitis patients with
hyperresponsiveness compared with controls [0.022 (0.014-0.033) and 0.015
(0.011-0.021) compared with 0.010 (0.007-0.014) ng/microg total protein]. The
level of ECP remained elevated off season. CONCLUSION: Cysteinyl-leukotrienes are
possibly more related to mast cell-mediated inflammation and remodelling, also
indicated by increased levels of hyaluronan during and off season. This
inflammation may be partly different from the eosinophil-driven inflammation.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17581201 [PubMed - indexed for MEDLINE]

308: Clin Ther. 2007 Mar;29(3):419-26.

Effectiveness of desloratadine 5 mg once daily in patients with symptoms of
seasonal allergic rhinitis: results of a Canadian multicenter, open-label trial.

Keith PK, Luciuk G.

McMaster University, Hamilton, Ontario, Canada. keithp@mcmaster.ca

BACKGROUND: Seasonal allergic rhinitis (SAR) is an inflammatory response to
seasonal allergens. Desloratadine, a once-daily selective histamine H(1)-receptor
antagonist, has been reported to be efficacious in relieving symptoms of SAR in
controlled clinical trials. However, to assess the actual effectiveness of a
drug, it is important to examine information about its use in routine clinical
practice. OBJECTIVE: The Partners in Allergy Control and Therapy (PACT) study
examined the effectiveness of desloratadine in patients with SAR symptoms
receiving treatment in a community setting of primary care physicians in Canada. 
METHODS: Patients with symptoms of SAR received desloratadine 5 mg once daily for
7 days during the spring-summer allergy season (April-July 2002). Patients rated 
their SAR symptoms along with their physicians by completing a questionnaire at
baseline and day 7. Nasal, ocular, respiratory, and overall symptoms were rated
on a scale of 0 (no symptoms evident) to 3 (severe/interfere with activities of
daily living and/or sleeping). Physicians were asked to keep a record of adverse 
events reported by patients. The Wilcoxon signed-rank test was used to evaluate
symptom severity scores. A 2-way (time x treatment), repeated measures, mixed
analysis of variance (ANOVA) model was constructed to assess differences in
variables over time. RESULTS: A total of 6829 patients participated in the study.
Patients reported nasal stuffiness/congestion as their most severe symptom. Just 
over half (50.1%) of patients were receiving another medication for SAR at study 
entry; 29.7% were receiving an intranasal corticosteroid. After 7 days of
treatment with desloratadine, individual symptom scores and overall symptom
scores were significantly reduced compared with baseline (all scores, P<0.001).
An improvement in nasal/stuffiness/ congestion was reported by 88.0% of patients.
The ANOVA detected a statistically significant incremental benefit with
desloratadine and an intranasal corticosteroid compared with desloratadine
monotherapy (P<0.001). No severe adverse events were reported. CONCLUSION:
Desloratadine 5 mg once daily was associated with significant improvement in
symptoms of SAR, and appeared to provide additional benefit in relieving moderate
to severe nasal stuffiness/congestion in 6786 patients receiving 7-day treatment 
in an actual practice setting of primary care physicians in Canada.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17577463 [PubMed - indexed for MEDLINE]

309: J Allergy Clin Immunol. 2007 Aug;120(2):381-7. Epub 2007 Jun 8.

Seasonal allergic rhinitis is associated with a detrimental effect on examination
performance in United Kingdom teenagers: case-control study.

Walker S, Khan-Wasti S, Fletcher M, Cullinan P, Harris J, Sheikh A.

Education for Health, Warwick, United Kingdom. s.walker@educationforhealth.org.uk

BACKGROUND: Seasonal allergic rhinitis is common globally, and symptoms have been
shown to impair learning ability in children in laboratory conditions. Critical
examinations in children are often held in the summer during the peak grass
pollen season. OBJECTIVE: To investigate whether seasonal allergic rhinitis
adversely impacts examination performance in United Kingdom teenagers. METHODS:
Case-control analysis of 1,834 students (age 15-17 years; 50% girls) sitting for 
national examinations. Cases were those who dropped 1 or more grades in any of 3 
core subjects (mathematics, English, and science) between practice (winter) and
final (summer) examinations; controls were those whose grades were either
unchanged or improved. Associations between allergic rhinitis symptoms,
clinician-diagnosed allergic rhinitis, and allergic rhinitis-related medication
use, recorded on examination days immediately before the examination, were
assessed using multilevel regression models. RESULTS: Between 38% and 43% of
students reported symptoms of seasonal allergic rhinitis on any 1 of the
examination days. There were 662 cases (36% of students) and 1,172 controls.
After adjustment, cases were significantly more likely than controls to have had 
allergic rhinitis symptoms during the examination period (odds ratio [OR], 1.4;
95% CI, 1.1-1.8; P = .002), to have taken any allergic rhinitis medication (OR,
1.4; 95% CI, 1.1-1.7; P = .01), or to have taken sedating antihistamines (OR,
1.7; 95% CI, 1.1-2.8; P = .03). CONCLUSION: Current symptomatic allergic rhinitis
and rhinitis medication use are associated with a significantly increased risk of
unexpectedly dropping a grade in summer examinations. CLINICAL IMPLICATIONS: This
is the first time the relationship between symptomatic allergic rhinitis and poor
examination performance has been demonstrated, which has significant implications
for clinical practice.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17560637 [PubMed - indexed for MEDLINE]

310: Eur J Pharmacol. 2007 Jul 19;567(3):245-51. Epub 2007 Feb 8.

Involvement of chemical mediators in nasal allergic responses of HDC-KO mice.

Rahman MA, Inoue T, Ishikawa T, Yatsuzuka R, Ohtsu H, Kamei C.

Department of Medicinal Pharmacology, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.

The present study was undertaken to investigate the involvement of chemical
mediators in nasal allergic responses using histidine decarboxylase knockout
(HDC-KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type
mice by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and
pertussis toxin. Five days later, they were boosted by a subcutaneous injection
of ovalbumin into the back. From day 18 after the first immunization to day 39,
intranasal sensitization with ovalbumin was performed every day and the severity 
of allergic rhinitis was observed by measuring nasal allergic responses and total
IgE levels. It was found that the intranasal administration of antigen caused a
significant increase of nasal sneezing and rubbing from day 25 to day 39 both in 
sensitized HDC-KO and wild-type mice. In addition, a significant elevation of
total IgE levels in serum was also found both in sensitized HDC-KO and wild-type 
mice from day 18 to day 39 after the first immunization. L-733,060, a tachykinin 
NK(1) receptor antagonist at a dose of 10 mg/kg (s.c.), resulted in the
dose-dependent inhibition of nasal allergic responses induced by antigen in both 
HDC-KO and wild-type mice. In addition, both chlorpheniramine at doses of 3 and
10 mg/kg (p.o.) and BW A868C at doses of 0.3 and 1 mg/kg (i.v.) also showed a
dose-related reduction of the nasal allergic responses induced by antigen in
sensitized wild-type mice. On the other hand, they had no effects on the nasal
signs induced by antigen in HDC-KO mice. From these results, it was revealed that
substance P induces nasal allergic responses in the mouse model of chronic
allergic rhinitis through the activation of tachykinin NK(1) receptors.
Therefore, it can be concluded that not only histamine, but also substance P and 
prostaglandin D(2), participated in the nasal allergic responses induced by
antigen in mice.

PMID: 17543300 [PubMed - indexed for MEDLINE]

311: Pharmacotherapy. 2007 Jun;27(6):852-9.

Meta-analysis of azelastine nasal spray for the treatment of allergic rhinitis.

Lee TA, Pickard AS.

Midwest Center for Health Services and Policy Research, Hines Veterans Affairs
Hospital, Hines, Illinois, USA.

STUDY OBJECTIVE: To systematically review the efficacy of azelastine nasal spray 
for the treatment of allergic rhinitis. DESIGN: Meta-analysis of published
randomized controlled trials reported in English. DATA SOURCE: Published
literature from the PubMed-MEDLINE database. PATIENTS: Patients aged at least 12 
(United States) or 16 years (Europe) with allergic rhinitis or nonallergic
vasomotor rhinitis. MEASUREMENTS AND MAIN RESULTS: A global assessment of
efficacy was used to estimate the number needed to treat for azelastine nasal
spray compared with placebo or active comparators. The total symptom score was
used to compare the effect size between azelastine and placebo. In five
comparisons of azelastine and placebo, azelastine was most efficacious, with a
summary number needed to treat of 5.0 (95% confidence interval [CI] 3.3-10.0). In
reviewing 11 studies of azelastine versus active comparators, we found no
significant difference between azelastine and active comparators (number needed
to treat 66.7, 95% CI 14.3 to infinity to 25). Azelastine was more efficacious
than placebo in terms of total symptom score (effect size of 0.36, 95% CI
0.26-0.46). CONCLUSION: Azelastine nasal spray was more efficacious than placebo 
in the treatment of allergic rhinitis. No significant differences were observed
between azelastine and active comparators for the treatment of allergic rhinitis;
however, when azelastine was compared with oral antihistamines as monotherapy,
the trend favored azelastine. Because azelastine appears to be as efficacious as 
oral antihistamines, the choice of treatment for seasonal allergic rhinitis
should depend on the patient's preference regarding the route of administration, 
adverse effects, and the cost of the drug.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 17542768 [PubMed - indexed for MEDLINE]

312: Int Arch Allergy Immunol. 2007;144(2):123-7. Epub 2007 May 24.

Changes in plasma TARC levels during Japanese cedar pollen season and
relationships with symptom development.

Xiao JZ, Kondo S, Takahashi N, Odamaki T, Iwabuchi N, Miyaji K, Iwatsuki K,
Enomoto T.

Food Research and Development Laboratory, Morinaga Milk Industry, Zama, Japan.
j_xiao@morinagamilk.co.jp

BACKGROUND: Japanese cedar pollinosis (JCPsis) is an immunoglobulin E-mediated
type I allergy caused by exposure to Japanese cedar pollen (JCP). Blood thymus
and activation-regulated chemokine (TARC) levels are well known as an objective
parameter for disease severity for several allergic disorders. The present study 
aims to evaluate the relationship between TARC levels and disease symptoms during
the pollen season. METHODS: Analysis was performed of results of symptom scores
and blood parameters obtained from 42 JCPsis patients who participated in a
probiotic (Bifidobacterium longum BB536) intake trial in the JCP season of 2005
(January to April), using a randomized, double-blind, placebo-controlled design. 
RESULTS: Significant increases in plasma TARC levels were observed in subjects
receiving placebo (p < 0.05 in February and p < 0.01 in March), but not in
subjects receiving BB536. Increased plasma TARC levels were markedly greater in
subjects who experienced severe symptoms and were thus excluded early from the
intervention (placebo group: n = 8; BB536 group: n = 2). Significant differences 
were found in changes from baseline TARC levels in February and March between the
subjects where treatment was terminated early and the remaining ones. Among the
remaining subjects, significant positive correlations were found as regards
changed values of TARC compared to baseline in March and April with symptom
scores recorded in the pollen season. CONCLUSION: Changed values of blood TARC in
the pollen season may offer promising parameters for assessing disease severity
and monitoring treatment. 2007 S. Karger AG, Basel

PMID: 17536220 [PubMed - indexed for MEDLINE]

313: Int Arch Allergy Immunol. 2007;144(2):162-70. Epub 2007 May 29.

Links between pollen, atopy and the asthma epidemic.

Taylor PE, Jacobson KW, House JM, Glovsky MM.

School of Botany, University of Melbourne, Parkville, Australia.
taylor@caltech.edu

Pollen allergy has been found in 80-90% of childhood asthmatics and 40-50% of
adult-onset asthmatics. Despite the high prevalence of atopy in asthmatics, a
causal relationship between the allergic response and asthma has not been clearly
established. Pollen grains are too large to penetrate the small airways where
asthma occurs. Yet pollen cytoplasmic fragments are respirable and are likely
correlated with the asthmatic response in allergic asthmatics. In this review, we
outline the mechanism of pollen fragmentation and possible pathophysiology of
pollen fragment-induced asthma. Pollen grains rupture within the male flowers and
emit cytoplasmic debris when winds or other disturbances disperse the pollen.
Peak levels of grass and birch pollen allergens in the atmosphere correlated with
the occurrence of moist weather conditions during the flowering period.
Thunderstorm asthma epidemics may be triggered by grass pollen rupture in the
atmosphere and the entrainment of respirable-sized particles in the outflows of
air masses at ground level. Pollen contains nicotinamide adenine dinucleotide
phosphate (reduced) oxidases and bioactive lipid mediators which likely
contribute to the inflammatory response. Several studies have examined
synergistic effects and enhanced immune response from interaction in the
atmosphere, or from co-deposition in the airways, of pollen allergens, endogenous
pro-inflammatory agents, and the particulate and gaseous fraction of combustion
products. Pollen and fungal fragments also contain compounds that can suppress
reactive oxidants and quench free radicals. It is important to know more about
how these substances interact to potentially enhance, or even ameliorate,
allergic asthma. 2007 S. Karger AG, Basel

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17536216 [PubMed - indexed for MEDLINE]

314: J Am Acad Nurse Pract. 2007 Jun;19(6):290-8.

Caring for patients with allergic rhinitis.

Hayden ML, Womack CR.

Virginia Adult/Pediatric Allergy and Asthma, Virginia, USA.
mlhayden@vaallergy.com

PURPOSE: Allergic rhinitis (AR) affects up to 40 million Americans, with an
estimated cost of $2.7 billion per annum. This review discusses several
therapeutic options that reduce the symptoms of AR, including allergen avoidance,
antihistamines, intranasal corticosteroids (INS), leukotriene receptor
antagonists, and immunotherapy. DATA SOURCES: The articles included in this
review were retrieved by a search of Medline literature on the subjects of AR,
antihistamines, INS, leukotriene antagonists, and immunotherapy, as well as
current published guidelines for the treatment of AR. CONCLUSIONS: Allergen
avoidance is recommended for all patients prior to pharmacologic therapy. Oral
and nasal H(1)-antihistamines are recommended to alleviate the mild and
intermittent symptoms of AR, and INS are recommended as the first-line treatment 
choice for mild persistent and more moderate-to-severe persistent AR.
IMPLICATIONS FOR PRACTICE: There are a number of different types of therapy for
the management of AR; with so many options available, successful tailoring of
treatment to suit individual requirements is realistically achievable.

Publication Types: 
    Review

PMID: 17535338 [PubMed - indexed for MEDLINE]

315: Respir Med. 2007 Sep;101(9):1982-7. Epub 2007 May 25.

Effects of TNFalpha on the human nasal mucosa in vivo.

Widegren H, Korsgren M, Andersson M, Greiff L.

Department of Otorhinolaryngology, Head & Neck Surgery, Lund University Hospital,
Lund, Sweden.

BACKGROUND: TNFalpha is a cytokine that may contribute to the pathophysiology of 
airway inflammation. Inhalation of TNFalpha produces granulocyte recruitment and 
airway hyperresponsiveness in man. Anti-TNFalpha treatment may inhibit
allergen-induced plasma exudation in guinea-pig airways. Increased nasal mucosal 
output of TNFalpha has been demonstrated in allergic rhinitis, but the effect of 
TNFalpha on the human nasal mucosa has not been examined in vivo. OBJECTIVE: To
examine effects of topical TNFalpha on the human nasal mucosa in vivo. METHODS:
In a dose-finding study, healthy subjects received intranasal TNFalpha (0-7.5
microg). Nasal lavages were carried out before as well as 10 min and 24 h post
challenge and alpha(2)-macroglobulin was measured as an index of plasma
exudation. In a second study, involving patients with allergic rhinitis examined 
out of season, a sham-controlled nasal challenge with TNFalpha (10 microg) was
performed and followed 24 h later by an allergen challenge. Lavages were
performed before the TNFalpha challenge, 24 h thereafter, and 10 min post
allergen challenge. alpha(2)-Macroglobulin, eosinophil cationic protein (ECP),
myeloperoxidase (MPO), and IL-8 were analyzed as indices of plasma exudation,
eosinophil activity, neutrophil activity, and pro-inflammatory cytokine
production, respectively. RESULTS: In the dose-finding study, TNFalpha produced
significant increases in alpha(2)-macroglobulin 24h post challenge (p<0.01). In
allergic rhinitis, 10 microg of TNFalpha also produced this effect (p<0.01) as
well as increases in ECP and IL-8 (p<0.01). MPO was increased 24 h post
challenge, but this change did not reach statistical significance. TNFalpha did
not produce any acute effects and did not affect the responsiveness to allergen. 
CONCLUSION: The present study demonstrates that topical TNFalpha produces a human
nasal inflammatory response. These data suggest a role of TNFalpha in nasal
conditions characterized by mucosal inflammation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17532197 [PubMed - indexed for MEDLINE]

316: Am J Med. 2007 Jun;120(6):498-502.

Allergic respiratory disease in the elderly.

Busse PJ.

Mount Sinai School of Medicine, Department of Medicine, Division of Clinical
Immunology, New York, NY 10129, USA. paula.busse@mssm.edu

Allergic asthma and allergic rhinosinusitis are typically considered disorders of
children and young adults. As a result, these diseases are frequently not
considered in the differential diagnosis of nasal obstruction, cough, wheeze, and
dyspnea in older individuals. However, many older adults have long-standing
allergic disorders or develop them later in life. This article addresses the
complexities of diagnosis and treatment of allergic respiratory diseases in
seniors.

PMID: 17524748 [PubMed - indexed for MEDLINE]

317: Eur Ann Allergy Clin Immunol. 2007 Apr;39(4):123-6.

Additional benefit of a third year of specific grass pollen allergoid
immunotherapy in patients with seasonal allergic rhinitis.

Williams A, Henzgen M, Rajakulasingam K.

Homerton University Hospital NHS Foundation Trust, Homerton Row, London, UK.

BACKGROUND: Aluminium-adsorbed six grass pollen allergoid therapy for 2 years was
found to be efficacious and safe in patients with hay fever and seasonal asthma. 
Using high-dose, hypoallergenic allergen products (allergoids) enables a
short-term pre-seasonal treatment regimen. However, it is not known whether
further treatment beyond 2 yrs had any additional benefit. METHODS: Following an 
initial 2-year randomized, double-blind, multi-centre, placebo-controlled
clinical trial in 154 grass pollen-allergic patients, an additional short course 
of specific immunotherapy with the high-dose, hypoallergenic grass pollen
preparation Allergovit was performed in 61 patients of the active treatment group
during the 3rd open-label treatment year. RESULTS: Further treatment of patients 
with the Allergovit 6-grass pollen preparation resulted in a further reduction of
symptom medication score and improved quality of life in comparison to the first 
and second treatment year. Changes in allergen-specific IgG4 levels supported
these results. CONCLUSIONS: Pre-seasonal short-term immunotherapy with the
high-dose, hypoallergenic allergen preparation Allergovit has been shown to be
efficacious and safe. A course of three years of 6-grass pollen SIT further
improves allergic symptoms, quality of life and reduces the need for
anti-allergic medication.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17523386 [PubMed - indexed for MEDLINE]

318: Eur Ann Allergy Clin Immunol. 2007 Apr;39(4):119-22.

Comparison of efficacy, safety and immunologic effects of subcutaneous and
sublingual immunotherapy in birch pollinosis: a randomized study.

Mauro M, Russello M, Incorvaia C, Gazzola GB, Di Cara G, Frati F.

Allergy Unit, Sant'Anna Hospital, Como, Italy.

BACKGROUND: Sublingual immunotherapy (SLIT) is currently considered a valid
option to subcutaneous immunotherapy (SCIT), but only a few studies made a direct
comparison of their effectiveness. The aim of this study was to compare the
clinical and immunological effects of SCIT and SLIT in pollinosis induced by
Betulaceae. METHODS: Forty-seven adult patients were randomized to receive SCIT
or SLIT, performed by Betulaceae (alder, birch, and hazel) extracts from
Stallergenes (Antony, France) standardized in index of reactivity (IR) with the
treatment schedules proposed by the producer. The clinical effects were
established by symptom-medication scores recorded during the month of March. Side
effects were reported directly by the physicians for SCIT and were registered in 
diary cards by the patients for SLIT. Immunologic evaluation was done by
measuring specific IgE and IgG4 to Bet v 1. RESULTS: Thirty-four patients (19 for
SCIT and 15 for SLIT) completed the registration of symptoms and drug consumption
during pollen period of Betulaceae. Mean cumulative doses of respectively 50.65
IR by SCIT and 4653.1 IR by SLIT were administered, with a SLIT/SCIT ratio of 92.
There was no significant difference in mean symptom-medication score between SCIT
and SLIT. Systemic reactions occurred in 16% of SCIT treated but in none of SLIT 
treated. As to immunologic evaluation, Bet v 1 specific IgE did not rise after
the pollen season in SCIT treated, while increased non significantly in SLIT
treated. Bet v 1 specific IgG4 increased in both treatment, buy only the increase
with SCIT was significant (p = 0.001). CONCLUSION: SLIT and SCIT with a ratio of 
about 100 are equally effective in controlling rhinoconjunctivitis caused by tree
pollen allergy. SLIT is safer than SCIT, but does not show the same immunologic
effects on serum specific IgE and lgG4 antibodies.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17523385 [PubMed - indexed for MEDLINE]

319: Allergy. 2007 Nov;62(11):1331-4. Epub 2007 May 23.

Desloratadine improves quality of life and symptom severity in patients with
allergic rhinitis.

Pradalier A, Neukirch C, Dreyfus I, Devillier P.

Department of Internal Medicine, Hôpital Louis Mourier, Colombes Cedex, France.

BACKGROUND: Desloratadine is associated with decreased signs and symptoms and
improved nasal airflow in multiple clinical trials in patients with allergic
rhinitis (AR). The effect of desloratadine on quality of life (QOL) in AR has not
been widely reported to date. We compared the effects of desloratadine and
placebo on QOL in seasonal AR using validated, disease-specific measures.
METHODS: This was a multicenter, double-blind, randomized, parallel-group study
of desloratadine 5 mg or placebo daily for 2 weeks in patients with symptomatic
seasonal AR. QOL was assessed at baseline and at day 14 using the
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). AR signs/symptoms and
the global response to therapy were measured at baseline and at day 14;
signs/symptoms were also rated AM/PM in patient diaries. Adverse events (AE) were
recorded. RESULTS: Overall 234 patients received desloratadine and 249 received
placebo. At day 14 desloratadine was associated with a significantly larger
improvement from baseline in the mean total RQLQ score vs placebo (P = 0.0003).
Desloratadine also led to significant improvements from baseline in all RQLQ
sub-domains (P < or = 0.043). At day 14 significant decreases from baseline were 
noted in the desloratadine group for total nasal (P = 0.0003), total non-nasal (P
= 0.001) and total symptoms scores (P = 0.0001). Morning AR symptoms were
significantly decreased in the desloratadine group after 1 day of treatment.
Desloratadine was well tolerated, with an AE rate similar to placebo. CONCLUSION:
Significant reductions in signs and symptoms of AR with desloratadine treatment
were accompanied by improved disease-specific QOL measures.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17521311 [PubMed - indexed for MEDLINE]

320: Ann Allergy Asthma Immunol. 2007 May;98(5):495-7.

Allergen immunotherapy in a patient with human immunodeficiency virus: effect on 
T-cell activation and viral replication.

Randhawa IS, Junaid I, Klaustermeyer WB.

UCLA West Los Angeles VA Medical Center, Los Angeles, California 90073, USA.
docrandhawa@yahoo.com

BACKGROUND: Allergen immunotherapy is a major therapeutic modality in the
treatment of allergic rhinitis. However, with T-cell activation potential, its
role in patients with human immunodeficiency virus (HIV) was theoretically
limited. OBJECTIVE: To report the results of allergen immunotherapy in a patient 
with HIV treated with highly active antiretroviral therapy (HAART). METHODS: A
44-year-old man with a history of HIV did not respond to medical therapy for
allergic rhinitis. His HIV status was well controlled with HAART. Owing to the
severity of his allergic rhinitis symptoms, he accepted the risk of allergy
immunotherapy despite the unknown effect of immunotherapy in patients with HIV.
RESULTS: After 6 weeks of weekly immunotherapy injections, his viral load
remained undetectable and his CD4 cell count changed from 540 to 570
cells/microL. After 16 weeks of weekly immunotherapy, his viral load increased to
10,900 copies/mL, and his CD4 cell count increased to 665 cells/microL. After 24 
weeks of weekly immunotherapy, his viral load returned to an undetectable level, 
and his CD4 cell count stabilized at 356 cells/microL. Despite his notable change
in HIV status, he continues to receive the same HAART. He currently continues en 
route to maintenance immunotherapy. CONCLUSIONS: The effect of allergen
immunotherapy on HIV infection has not been previously reported. A concern
remains that any form of immunotherapy may negatively affect HIV disease
progression. This case illustrates that weekly allergen immunotherapy may have
induced limited T-cell proliferation and a modest increase in RNA viral load,
which resolved with continuation of HAART.

Publication Types: 
    Case Reports

PMID: 17521037 [PubMed - indexed for MEDLINE]

321: Curr Med Res Opin. 2007 May;23(5):1113-20.

A cost-effectiveness analysis of immunotherapy with SQ allergen extract for
patients with seasonal allergic rhinoconjunctivitis in selected European
countries.

Keiding H, Jørgensen KP.

Department of Economics, University of Copenhagen, Copenhagen, Denmark.
hans.keiding@pop.oko.ku.dk

BACKGROUND: Seasonal allergic rhinoconjunctivitis can, for some people, reduce
quality of life and the ability to cope with everyday tasks. SCOPE: In this paper
we investigate the cost-effectiveness of immunization therapy with Alutard SQ
(ASQ) and compare the cost-effectiveness in countries where the therapy has been 
in use in order to assess the impact of national therapeutic practices on the
results of health economic assessments. Data are obtained from a clinical trial
carried out in 2001-2002. To evaluate the cost-effectiveness of immunization we
have added data on resource use in Austria, Denmark, Finland, Germany, The
Netherlands, and Sweden. FINDINGS: The computations result in cost-effectiveness 
ratios for allergen immunization between 10,000 euros and 20,000 euros per QALY
even without provision for indirect costs, and achieving dominance in most
countries where indirect costs have also been taken into account. The country
comparisons show that the direct cost of administrating the up-dosing and
maintenance differs considerably between countries, and that the cost of medical 
staff is substantial, constituting in most cases more than half of the direct
costs of the immunization therapy. CONCLUSION: The study shows that immunotherapy
with SQ allergen extract is cost-effective in a wide range of national
environments, and that cost-effectiveness differences by country are largely a
result of different practices in the up-dosing phase.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17519078 [PubMed - indexed for MEDLINE]

322: Clin Exp Allergy. 2007 Jun;37(6):954-60.

Allergic rhinitis and asthma comorbidity: ARIA classification of rhinitis does
not correlate with the prevalence of asthma.

Antonicelli L, Micucci C, Voltolini S, Feliziani V, Senna GE, Di Blasi P, Visonà 
G, De Marco R, Bonifazi F.

Allergy Unit, Department of Internal Medicine, Immuno-Allergic and Respiratory
Diseases, Ospedali Riuniti di Ancona, Ancona, Italy.
l.antonicelli@ao-umbertoprimo.marche.it

BACKGROUND: Allergic rhinitis and asthma comorbidity is supported by both the
similar underlying pathogenesis and immunologic mechanisms. The aim of this study
was to verify whether the characteristics of rhinitis classified according to the
new Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines correlate with
the prevalence of asthma. METHODS: From 1 March to 30 June 2002, a multi-centre
cross-sectional study was conducted by 154 allergists chosen from throughout
Italy. Duration, severity of rhinitis (according to the ARIA classification) and 
the type of allergic sensitizations were compared with the prevalence of asthma. 
RESULTS: One thousand three hundred and twenty-one consecutive rhinitis-allergic 
patients aged 18 years or older were enrolled for the study. The majority of
patients, 1060 (80.24%), were on medication at the time of their specialist
visit. Mild intermittent rhinitis was diagnosed in 7.7% of patients,
moderate/severe intermittent in 17.1%, mild persistent in 11.6%, and
moderate/severe persistent in 63.6%. The prevalence of asthma was 48% in patients
with mild intermittent rhinitis, 49.6% in moderate-severe intermittent rhinitis, 
36.6% in mild persistent rhinitis and 47.5% in moderate severe persistent
patients. No correlation between the ARIA categories of rhinitis and the
prevalence of asthma was found. A multivariate analysis, after adjustment for
age, sex, type of sensitization, level of severity and duration of rhinitis
classified according to the ARIA guidelines, demonstrated that age, over 41 years
[risk ratio (RR) 1.260, 95% confidence interval (CI) 1.072-1.482] and especially 
over 51 years (RR 1.460, 95% CI 1.237-1.723), sensitization to indoor allergens
(mite and cat), (RR 1.203, 95% CI 1.060-1.366), and polysensitization (RR 1.178, 
95% CI 1.004-1.383) are significant risk factors for asthma. CONCLUSION: In
allergic rhinitis (AR) patients referred to a specialist, the features of AR as
defined by the ARIA classification are not able to predict the presence of
asthma, therefore all such patients should be assessed for asthma.

Publication Types: 
    Multicenter Study

PMID: 17517110 [PubMed - indexed for MEDLINE]

323: Clin Exp Allergy. 2007 Jun;37(6):901-8.

Immunoreactivity profile of peripheral blood mononuclear cells from patients with
ragweed-induced allergic rhinitis.

Sun J, Wong B, Cundall M, Goncharova S, Conway M, Dalrymple A, Coyle AJ, Waserman
S, Jordana M.

Department of Pathology and Molecular Medicine and Division of Respiratory
Diseases and Allergy, Centre for Gene Therapeutics, McMaster University,
Hamilton, Ontario, Canada.

BACKGROUND: Seasonal rhinitis is manifested by a series of nasal symptoms in
response to exposure to seasonal allergens including ragweed pollen.
Understanding its immunological mechanisms may help to better manage the disease.
OBJECTIVE: We sought to determine comprehensively ragweed-induced cytokine and
chemokine production by peripheral blood mononuclear cells from normal
individuals and patients with seasonal rhinitis sensitized to ragweed pollen, and
to assess its regulation by exogenous IL-10. METHODS: Cells were cultured in the 
presence or absence of a purified ragweed pollen extract with or without
exogenous IL-10. Cytokines and chemokines were measured in the supernatant. Gene 
expression was evaluated using real-time quantitative reverse transcription PCR. 
RESULTS: Ragweed stimulation significantly increased the production of the
Th2-associated cytokines IL-5, IL-9 and IL-13, the chemokines CCL17 and CCL22 and
the regulatory cytokine IL-10 in allergic patients, whereas transforming growth
factor-beta (TGF-beta) production was increased only in normal individuals. No
difference was detected between groups in the production of the Th1 cytokine
IFN-gamma or the Th1-affiliated chemokines CXCL10 and CXCL11. Exogenous IL-10
significantly suppressed spontaneous and induced production of both Th1- and
Th2-associated cytokines and chemokines. CONCLUSION: Our work demonstrated that
locally manifested allergic rhinitis is underlined by a systemic Th2 immune
response specific to allergens. The molecular pathogenesis of allergic rhinitis
may be linked to a compromised allergen-specific immune regulation, e.g., reduced
spontaneous and allergen-induced TGF-beta production in patients compared with
healthy controls. Our data also show that IL-10 inhibits both the effector and
directional mechanisms of allergen-specific immune response, further supporting
its potential therapeutic benefit in preventing and treating allergic diseases.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17517104 [PubMed - indexed for MEDLINE]

324: Otolaryngol Head Neck Surg. 2007 Jun;136(6 Suppl):S107-24.

Keys to successful management of patients with allergic rhinitis: focus on
patient confidence, compliance, and satisfaction.

Marple BF, Fornadley JA, Patel AA, Fineman SM, Fromer L, Krouse JH, Lanier BQ,
Penna P; American Academy of Otolaryngic Allergy Working Group on Allergic
Rhinitis.

University of Texas Southwestern Medical School, Dallas, TX 75390-7208, USA.
Bradley.marple@utsouthwestern.edu

OBJECTIVE: The American Academy of Otolaryngic Allergy (AAOA) convened an expert,
multidisciplinary Working Group on Allergic Rhinitis to discuss patients'
self-treatment behaviors and how health care providers approach and treat the
condition. PROCEDURES AND DATA SOURCES: Co-moderators, who were chosen by the
AAOA Board of Directors, were responsible for initial agenda development and
selection of presenters and participants, based on their expertise in diagnosis
and treatment of allergic rhinitis. Each presenter performed a literature search 
from which a presentation was developed, portions of which were utilized in
developing this review article. SUMMARY OF FINDINGS: Allergic rhinitis is a
common chronic condition that has a significant negative impact on general
health, co-morbid illnesses, productivity, and quality of life. Treatment of
allergic rhinitis includes avoidance of allergens, immunotherapy, and/or
pharmacotherapy (ie, antihistamines, decongestants, corticosteroids, mast cell
stabilizers, anti-leukotriene agents, anticholinergics). Despite abundant
treatment options, 60% of all allergic rhinitis patients in an Asthma and Allergy
Foundation of America survey responded that they are "very interested" in finding
a new medication and 25% are "constantly" trying different medications to find
one that "works." Those who were dissatisfied also said their health care
provider does not understand their allergy treatment needs and does not take
their allergy symptoms seriously. Dissatisfaction leads to decreased compliance
and an increased reliance on multiple agents and over-the-counter products.
Furthermore, a lack of effective communication between health care provider and
patient leads to poor disease control, noncompliance, and unhappiness in a
significant portion of patients. CONCLUSIONS: Health care providers must gain a
greater understanding of patient expectations to increase medication compliance
and patient satisfaction and confidence.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17512862 [PubMed - indexed for MEDLINE]

325: J Voice. 2008 Jul;22(4):512-5. Epub 2007 May 18.

Voice change in seasonal allergic rhinitis.

Millqvist E, Bende M, Brynnel M, Johansson I, Kappel S, Ohlsson AC.

Department of Otorhinolaryngology and Allergy Centre, Central Hospital, Skövde,
Sweden.

Voice problems are seldom reported in pollen allergy, although the allergic
reaction involves the entire airways. The objective of this study was to
investigate voice dysfunction during the pollen season in patients with allergic 
rhinitis. Thirty patients with verified birch pollen allergy and 30 controls were
investigated twice, during the pollen season and outside the pollen season. Both 
times they scored respiratory and voice symptoms, the latter with the validated
questionnaire Voice Handicap Index (VHI), and performed standardized voice
recordings. These recordings were analyzed in a controlled manner by a
professional voice therapist. During the allergy season, patients reported more
respiratory and voice symptoms compared with controls. Those with blinded scored 
voice dysfunction scored their voice quality during springtime as 31 mm (95%
confidence interval [CI] 20-42 mm), compared with 13 mm (95% CI 6-21 mm for
participants without voice dysfunction (P<0.01). Furthermore, the group with
experienced voice dysfunction scored significantly higher on the VHI in the
functional and physical domains and in the total VHI score. Although voice
problems during the pollen season are rarely discussed, in allergic rhinitis the 
larynx may also be involved. These findings support that some patients experience
voice change, an experience which can be objectively confirmed.

PMID: 17512169 [PubMed - indexed for MEDLINE]

326: Am J Otolaryngol. 2007 May-Jun;28(3):148-52.

The role of allergic rhinitis in the development of otitis media with effusion:
effect on eustachian tube function.

Yeo SG, Park DC, Eun YG, Cha CI.

Department of Otolaryngology, College of Medicine, KyungHee University, Seoul,
South Korea. yeo2park@yahoo.co.kr <yeo2park@yahoo.co.kr>

PURPOSE: The pathogenesis of otitis media with effusion (OME) is considered
multifactorial, with viral upper respiratory tract infection and eustachian tube 
dysfunction. Allergy may be related to the pathogenesis of OME or to another
etiological factor. We investigated the role of allergic rhinitis (AR) in
children with OME and evaluated eustachian tube function in patients with AR.
MATERIALS AND METHODS: We prospectively analyzed the prevalence of AR, serum
eosinophil count, and serum total IgE concentrations in 123 children with OME and
in 141 controls. IgE concentration in middle ear effusion was compared in
children with OME with and without AR, and eustachian tube function after a nasal
provocation test was compared between patients with AR and controls. RESULTS: The
prevalence of AR in children with OME (28.4%) and control subjects (24.1%) did
not differ significantly. These 2 groups also showed no differences in total
eosinophil count and serum and middle ear effusion IgE concentration.
Abnormalities in eustachian tube function were the same in patients with AR and
controls. CONCLUSIONS: Allergic rhinitis may not be related to the development of
OME in children.

PMID: 17499128 [PubMed - indexed for MEDLINE]

327: Curr Opin Allergy Clin Immunol. 2007 Jun;7(3):249-56.

Assessing outcomes from the sleep disturbance associated with rhinitis.

Pratt EL, Craig TJ.

Section of Allergy, Asthma, and Immunology, Penn State Milton S. Hershey Medical 
Center, 500 University Drive, Hershey, PA 17033, USA.

PURPOSE OF REVIEW: The purpose of this review is to identify which aspects of
allergic rhinitis limit the quality of life in patients, to present information
on how rhinitis affects sleep, and to review instruments available to assess the 
impact that rhinitis has on sleep. RECENT FINDINGS: Subjective and objective
instruments reveal patients with allergic rhinitis frequently suffer from
sleep-disordered breathing, poor sleep quality, daytime somnolence, and fatigue. 
Sleep disturbances associated with allergic rhinitis can lead to decreased
cognitive and psychomotor abilities, impaired work performance, decreased
productivity, impaired learning, difficulty concentrating, and memory deficits.
SUMMARY: Objective and subjective instruments are available to measure the extent
of compromise in quality of life in affected patients. Subjective measurements
available to evaluate allergic rhinitis include general and disease specific
quality of life questionnaires, including rhinitis specific and sleep specific
questionnaires. Objective measurements available include evaluation of nasal
patency and physiology in rhinitis, nasal inspiratory peak flow, acoustic
rhinometry, rhinomanometry, polysomnography, the Multiple Sleep Latency Test, the
Maintenance of Wakefulness Test, and learning and performance testing. The
continued utilization of these and other available instruments is vital for
further assessment on the effect of allergic rhinitis on sleep.

Publication Types: 
    Review

PMID: 17489043 [PubMed - indexed for MEDLINE]

328: Int J Pediatr Otorhinolaryngol. 2007 Jul;71(7):1017-23. Epub 2007 May 4.

The influence of birch pollination on the adenoid size in children with
intermittent allergic rhinitis.

Modrzynski M, Zawisza E.

The Regional Allergology Outpatient Euromedica, 86-300 Grudziadz, Legionow 71,
Poland. euromedica@lekarz.net

INTRODUCTION: Allergic sensitization of the airways occurs not only in the mucosa
of the shock organ, but also in the lymphatic stations draining these structures.
The lymphatic structure closest to the nasal mucosa in humans is the adenoid.
Many researches show that in part of children allergic rhinitis can be a risk
factor for adenoid hypertrophy. MATERIALS AND METHODS: We used acoustic
rhinometry and endoscopy to evaluate the influence of the birch pollination on
the adenoid size in 67 children between 5 and 12 years old. Four separate groups 
of children were examined. The study group consisted of 28 children
hypersensitive to tree pollen with seasonal allergic rhinitis (interview,
positive skin prick test results, presence of sIgE in the serum and positive
nasal provocation test with birch pollen allergens). The first control group
consisted of 14 atopic children hypersensitive to motherwort pollen. The second
control group consisted of 15 non-atopic children. The third control group
consisted of 10 children hypersensitive to tree pollen, they have got
anti-allergic treatment (topical nasal steroid and antihistaminic) a week before 
birch pollination. In all of the groups the adenoid size was examined before,
during and after birch pollination. In the study group, we examined the influence
of specific nasal provocation test on the adenoid size too. RESULTS: In most
children from the study group (71.4%) we observed the significant increase of
adenoid size in endoscopic examination and decrease of nasopharyngeal cavity
volume in acoustics rhinometry (92.9%) during the birch pollination. The changes 
returned after pollination period in most children (90%). In the first and the
second control group there were almost no changes observed (p>0.05). The medical 
treatment used in the third control group avoided the increase of adenoid size
during birch pollination season. In the study group there was no statistically
significant correlation between the changes in nasopharyngeal volume during the
pollination period and the results of nasal provocation test (r=0.18).
CONCLUSION: The result of our study suggests that in children with seasonal
allergic rhinitis the exposure on the allergenic factor can influence the adenoid
size. Properly administered nasal glucocorticoid together with antihistaminic in 
standard doses can probably avoid this effect.

PMID: 17482282 [PubMed - indexed for MEDLINE]

329: Allergy Asthma Proc. 2007 Mar-Apr;28(2):226-9.

Daytime sleepiness and cognitive performance improve in seasonal allergic
rhinitis treated with intranasal fluticasone propionate.

Mansfield LE, Posey CR.

Western Sky Medical Research, El Paso, Texas 79902, USA.

Patients with symptomatic allergic rhinitis often complain of daytime drowsiness 
and impairment in their speed of thinking responses. In this study, we compared
subjects with allergic rhinitis treated with intranasal fluticasone propionate or
placebo. We measured nasal symptoms, daytime sleepiness, and cognitive
performance. Total nasal symptoms (p = 0.002) and nasal congestion (p = 0.003)
improved in the intranasal fluticasone propionate group. Concomitantly, daytime
sleepiness decreased (p = 0.001) and cognitive performance improved (p = 0.02).
The placebo-treated subjects did not show any significant changes. Effective
therapy of allergic rhinitis ameliorates the symptoms of daytime sleepiness and
decreased cognitive performance.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17479609 [PubMed - indexed for MEDLINE]

330: Allergy Asthma Proc. 2007 Mar-Apr;28(2):216-25.

Optimal dose selection of fluticasone furoate nasal spray for the treatment of
seasonal allergic rhinitis in adults and adolescents.

Martin BG, Ratner PH, Hampel FC, Andrews CP, Toler T, Wu W, Faris MA, Philpot EE.

Southwest Allergy and Asthma Research, San Antonio, Texas 78229, USA.

Efficacy and safety of fluticasone furoate nasal spray, administered using a
unique side-actuated device, were evaluated in patients > or =12 years of age
with seasonal allergic rhinitis to determine the optimal dose. A randomized,
double-blind, parallel-group, placebo-controlled, dose-ranging study was
performed on 641 patients who received placebo (n=128) or fluticasone furoate, 55
microg (n=127), 110 microg (n=127), 220 microg (n=129), or 440 microg (n=130),
once daily for 2 weeks. Fluticasone furoate was significantly more effective than
placebo for mean changes from baseline over the 2-week treatment period in daily 
reflective total nasal symptom score (primary end point; p < 0.001 each dose vs. 
placebo), morning predose instantaneous total nasal symptom score (p < 0.001 each
dose versus placebo), daily reflective total ocular symptom score (p < or = 0.013
each dose versus placebo), and morning predose instantaneous total ocular symptom
score (p < or = 0.019 for three highest doses versus placebo). The onset of
action for fluticasone furoate nasal spray versus placebo was observed 8 hours
after the first. dose of study medication in the 110 and 440 microg treatment
groups (p < or = 0.032). The incidence of adverse events, results of clinical
laboratory tests, and changes in 24-hour urinary cortisol values were similar
between active treatment groups and placebo. The preliminary profile of
fluticasone furoate is that of a rapidly effective therapy that confers 24-hour
efficacy for both nasal and ocular symptoms with once-daily dosing. The
110-microg dose was chosen for phase III development because it achieved
statistically significant and clinically meaningful results for all efficacy end 
points and provided the optimal risk-benefit ratio.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17479608 [PubMed - indexed for MEDLINE]

331: Allergy Asthma Proc. 2007 Mar-Apr;28(2):183-9.

Risk factors for asthma symptoms at school age: an 8-year prospective study.

Morais-Almeida M, Gaspar A, Pires G, Prates S, Rosado-Pinto J.

Immunoallergy Department, Dona Estefânia Hospital, Lisbon, Portugal.
mmoraisalmeida@netcabo.pt

Childhood recurrent wheezing is a very prevalent heterogeneous clinical entity.
An 8-year prospective study was performed to correlate the clinical outcome of
recurrent wheezing in the first years of life with prognostic risk factors. A
cohort of 308 children with recurrent wheezing, aged <7 years, were enrolled in
1993, studied using a questionnaire, skin-prick tests, and serum total IgE.
According to the study protocol, in 1996 and 2001, the cohort was assessed. In
2001, 81% of the initial sample was reevaluated (n=249); 61% remained
symptomatic. Prevalence of atopy was 48% in 1993, 65% in 1996, and 75% in 2001.
By logistic regression analysis, we identified the following as independent risk 
factors for asthma symptoms in the last year of the follow-up: personal history
of rhinitis (odds ratio [OR] = 15.8, 95% confidence interval [CI], 6.1-40.8; p < 
0.001), paternal asthma (OR =, 7.2; 95% CI = 1.7-29.7; p = 0.007), personal
history of atopic dermatitis (OR = 5.9, 95% CI = 2.2-15.7; p < 0.001), maternal
asthma (OR = 5.4, 95% CI = 1.7-17.1; p = 0.004), allergen sensitization (OR =
3.4, 95% CI = 1.2-10.4; p = 0.03), and onset of symptoms in the 2nd year or later
in preschool-aged children (OR = 2.1, 95% CI = 1.1-4.8; p = 0.04). Kindergarten
attendance before 12 months was identified as a protective factor (OR = 0.4, 95% 
CI = 0.2-0.9; p = 0.04). Among the 128 nonatopic children in 1993, 52% developed 
allergen sensitization. We identified as prognostic risk factors for asthma
symptoms personal history of allergic disease, parental asthma, atopy, and late
onset of symptoms. In a significant number of children clinical symptoms can
occur years before allergen sensitization.

Publication Types: 
    Evaluation Studies

PMID: 17479602 [PubMed - indexed for MEDLINE]

332: Allergy Asthma Proc. 2007 Mar-Apr;28(2):145-52.

Safety considerations of intranasal corticosteroids for the treatment of allergic
rhinitis.

Blaiss MS.

Department of Pediatrics and Medicine, University of Tennessee Health Sciences
Center, Memphis, Tennessee, USA. wheezemd@gmail.com

Allergic rhinitis (AR) is a major chronic inflammatory disease of the upper
airways. AR is increasing in prevalence and causes negative effects on quality of
life, impairs performance and productivity, and imposes a serious economic
burden. More than 20% of the American population suffers from AR. Intranasal
corticosteroids (INS) are an effective and safe first-line treatment for AR, with
potent anti-inflammatory properties and a high therapeutic ratio. The systemic
bioavailability of the majority of INS is relatively low; however, the
pharmacokinetics of absorption, first-pass metabolism, volume of distribution,
half-life, and clearance of INS varies considerably, depending on lipophilicity, 
receptor affinity, and lipid conjugation in the nasal tissue. The short-term
(e.g., effect on linear lower-leg growth rate) and long-term (e.g., effect on
height) systemic side effects of INS in patients with AR are determined by these 
important characteristics. AR is present in up to 75% of patients with asthma,
and patients with AR are three times more likely to develop asthma compared with 
patients without AR. Therefore, the overall increased systemic steroid burden
resulting from concomitant use of inhaled corticosteroids (ICS) and INS in adult 
and pediatric patients with comorbid AR and asthma warrants critical monitoring
of systemic side effects. This review evaluates the overall safety of INS in AR
and the importance of systemic safety considerations of INS, particularly when
coadministered with ICS.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17479597 [PubMed - indexed for MEDLINE]

333: J Am Board Fam Med. 2007 May-Jun;20(3):289-98.

Comment in:
    J Am Board Fam Med. 2008 May-Jun;21(3):251; author reply 251-2.

Treating asthma and comorbid allergic rhinitis in pregnancy.

Yawn B, Knudtson M.

Olmsted Medical Center, University of Minnesota, Rochester, MN 55904, USA.
yawnx002@umn.edu

Women with severe or uncontrolled asthma are at higher risk for pregnancy
complications and adverse fetal outcomes than women with well-controlled asthma. 
Recent evidence-based guidelines have concluded that it is safer for pregnant
women with asthma to be treated pharmacologically than to continue to have asthma
symptoms and exacerbations. According to the Asthma and Pregnancy Working Group
(APWG) of the National Asthma Education and Prevention Program, optimal treatment
of asthma during pregnancy includes treatment of comorbid allergic rhinitis (AR),
which can trigger or aggravate asthma symptoms. In general, treatment of both
asthma and AR during pregnancy should follow the same stepwise approach that is
used in the general population. This article presents the specific
recommendations from the most recent APWG report and from other systematic
reviews about which asthma and allergic rhinitis drugs should be preferred during
pregnancy. Of the corticosteroids, budesonide has the most data and is listed as 
Pregnancy Category B (no evidence of risk in humans). Other inhaled and
intranasal corticosteroids have less data and are listed as Pregnancy Category C 
but may be continued during pregnancy if the patient's asthma was well controlled
with the medication before pregnancy. Family physicians should help their
patients control allergic rhinitis and asthma during pregnancy, encouraging
adherence to needed medications.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17478662 [PubMed - indexed for MEDLINE]

334: Otolaryngol Head Neck Surg. 2007 May;136(5):720-5.

The effect of Bacillus Calmette-Guerin in a mouse model of allergic rhinitis.

Kim SW, Yeo SW.

Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The
Catholic University of Korea, Seoul, South Korea.

OBJECTIVE: To develop an allergic rhinitis model via local sensitization of mice 
with Dermatophagoides pteronyssinus and to use the model to investigate the
antiallergic effect of Bacillus Calmette-Guerin (BCG). METHODS: BALB/c mice were 
randomized to the allergic rhinitis group, the BCG group sensitized with D
pteronyssinus via local sensitization for 7 weeks, or the control group. The BCG 
group received 1 x 10(5) colony-forming unit/mL of BCG seven times. We evaluated 
symptoms, nasal mucosa eosinophilia, serum total IgE, cytokines, and eosinophilia
in bronchoalveolar lavage fluid. RESULTS: In the allergic rhinitis group, allergy
symptoms (P < 0.001), eosinophil count (P < 0.001), total IgE (P < 0.001),
inflammatory cells (P < 0.01), and IL-13 (P = 0.046) increased and interferon
gamma (IFN-gamma) (P < 0.001) decreased compared with the control group. In the
BCG group, allergy symptoms (P < 0.001), eosinophil count (P < 0.001), and
inflammatory cells (P < 0.01) decreased and IFN-gamma (P = 0.031) increased
compared with the allergic rhinitis group. CONCLUSION: In an allergic rhinitis
animal model developed via local sensitization of mice with D pteronyssinus, BCG 
was shown to exhibit an antiallergic effect.

PMID: 17478204 [PubMed - indexed for MEDLINE]

335: Otolaryngol Head Neck Surg. 2007 May;136(5):707-13.

Microarray analysis of allergic fungal sinusitis and eosinophilic mucin
rhinosinusitis.

Orlandi RR, Thibeault SL, Ferguson BJ.

Division of Otolaryngology-Head and Neck Surgery, University of Utah, Salt Lake
City, UT 84132, USA. Richard.Orlandi@hsc.utah.edu

OBJECTIVE: Our goal was to determine and compare the differential gene expression
in allergic fungal sinusitis (AFS) and eosinophilic mucin rhinosinusitis (EMRS). 
STUDY DESIGN AND SETTING: We conducted a complementary DNA microarray analysis of
prospectively gathered tissue from a tertiary rhinology practice. RESULTS:
Compared to normal subjects, 38 genes or potential genes were differentially
expressed in AFS patients, while 10 genes were differentially expressed in EMRS
patients. Four genes differentially expressed in EMRS were not differentially
expressed in AFS: cathepsin B, sialyltransferase 1, GM2 ganglioside activator
protein, and S100 calcium binding protein. These genes mediate lysosomal activity
and are known to have differential expression in inflammatory and neoplastic
states. CONCLUSIONS: EMRS and AFS show some similarities in gene expression
profiles using microarray analysis. Significant differences in gene expression in
both EMRS and AFS patients compared with normal subjects provide early clues to
the pathophysiology of EMRS and AFS. SIGNIFICANCE: This study demonstrates that
complementary DNA microarray analysis is a feasible tool for studying different
disease subclassifications and is the first to study these subclasses in chronic 
rhinosinusitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17478202 [PubMed - indexed for MEDLINE]

336: Clin Ther. 2007 Feb;29(2):342-51.

Findings from a 1000-patient internet-based survey assessing the impact of
morning symptoms on individuals with allergic rhinitis.

Long AA.

Division of Rheumatology, Department of Medicine, Massachusetts General Hospital,
Boston, Massachusetts 02114, USA. aalong@partners.org

BACKGROUND: Although the severity of allergic rhinitis symptoms might depend on
the degree of exposure to the triggering allergen, it has also been noted that
symptom severity varies over the course of the day. OBJECTIVES: The aims of this 
study were to investigate the reported impact (influence on behavior and/or
feelings) of morning symptoms on individuals with allergic rhinitis and determine
their perception of the effectiveness of allergy treatment. METHODS: In January
2005, online interviews based on a 16-item questionnaire were presented to adults
(aged >or=18 years) with physician-diagnosed allergic rhinitis in the United
States. Participants were recruited from the Roper Public Affairs and Media US
national online panel. The survey sample was balanced to reflect the US
population by Census Division, ethnicity, sex, and presence of children living at
home. Data were weighted by sex (65% female, 35% male) based on previous research
of the adult population suffering from allergies. RESULTS: The first 1000
respondents (sex, female,550 [55%]; age, >or=55 years, 378 [38%], race, white,
883 [88%]) that met all inclusion/exclusion criteria were included in the study
results. There was no significant difference in the regional distribution of
participants: South (34%), Midwest (25%), West (22%), and Northeast (19%). The
majority of the sample (83%) reported experiencing morning symptoms of allergic
rhinitis; 49% reported that their symptoms were most severe during the morning
hours. The most common symptom on awakening was nasal congestion, reported by 85%
of those with symptoms when they first woke tip. Of those with symptoms on
awakening, the majority reported that these affected their feelings (96;/0) or
behavior (87%). Among respondents who experienced symptoms on awakening, the
majority reported that their symptoms affected the rest of their day "somewhat"
or "a great deal" (51% and 24%, respectively). Of those respondents using allergy
medication, 33% reported that its effectiveness wore off before the next dose
most or all of the time. A majority of respondents reported feeling that it was
very important for an allergy medication to maintain effectiveness until the next
dose (68%), provide relief all day and into the next morning (62%), and enable
them to wake tip with their symptoms render control (63%). CONCLUSIONS: Based on 
the results from this large Internet-based survey, the morning symptoms of
allergic rhinitis have a negative impact on individuals, both emotionally and in 
terms of disruption of daily activities. Medication used for treating allergic
rhinitis was reported as not always effective for the whole time interval between
doses. This suggests that it might be important, when considering management
options in allergic rhinitis, to select medications that offer sustained
effectiveness throughout the 24-hour period.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17472826 [PubMed - indexed for MEDLINE]

337: J Investig Allergol Clin Immunol. 2007;17(2):92-100.

Fluctuation of fecal microbiota in individuals with Japanese cedar pollinosis
during the pollen season and influence of probiotic intake.

Odamaki T, Xiao JZ, Iwabuchi N, Sakamoto M, Takahashi N, Kondo S, Iwatsuki K,
Kokubo S, Togashi H, Enomoto T, Benno Y.

Food Research and Development Laboratory Morinaga Milk Industry Co, Ltd, Zama,
Kanagawa, Japan. t-odamak@morinagamilk.co.jp

BACKGROUND: We have previously reported the results of a randomized,
double-blind, placebo-controlled trial that found the intake of yogurt
supplemented with a probiotic strain, Bifidobacterium longum BB536, alleviates
symptoms and affects blood parameters in individuals with Japanese cedar
pollinosis (JCPsis) during the pollen season. OBJECTIVE: In the present study,
fecal microbiota were investigated to examine whether any changes occur during
the pollen season and whether any influence is exerted by probiotic intake.
METHODS: Yogurt either with BB536 (BB536 yogurt) or without BB536 (placebo
yogurt) was administered for 14 weeks at 2 x 100 g per day to 40 subjects (17
men, 23 women) with a clinical history of JCPsis. Fecal samples were obtained
from 23 subjects (placebo group, n=13; BB536 group, n=10) before and during the
intervention (weeks 4, 9 and 13) and fecal microbiota were analyzed using
terminal-restriction fragment length polymorphism and real-time polymerase chain 
reaction (PCR) methods. RESULTS: From the fluctuation patterns of
terminal-restriction fragments, the Bacteroides fragilis group and bifidobacteria
were among the species that changed most with pollen dispersion. Real-time PCR
analyses indicated that the cell numbers of the B fragilis group increased
significantly along with pollen dispersion in both BB536 and placebo groups. Cell
numbers of bifidobacteria were significantly higher in the BB536 group compared
with the placebo group (P < .05 at weeks 4 and 9). The ratio of cell numbers of
the B fragilis group to bifidobacteria increased significantly during the pollen 
season in the placebo group (P < .01 at weeks 9 and 14), but not in the BB536
group. An in vitro study using peripheral blood mononuclear cells from JCPsis
subjects indicated that strains of the B fragilis group induced significantly
more helper T cell (T(H)) type2 cytokines (interleukin [IL]-6) but fewer T(H)1
cytokines (IL-12 and interferon) compared with those of bifidobacteria.
CONCLUSIONS: These results suggest a relationship between fluctuation in
intestinal microbiota and pollinosis allergy. Furthermore, intake of BB536 yogurt
appears to exert positive ihfluences on the formation of anti-allergic
microbiota.

Publication Types: 
    Randomized Controlled Trial

PMID: 17460947 [PubMed - indexed for MEDLINE]

338: J Investig Allergol Clin Immunol. 2007;17(2):70-6.

Effect of lysed Enterococcus faecalis FK-23 on allergen-induced immune responses 
and intestinal microflora in antibiotic-treated weaning mice.

Shimada T, Cheng L, Shi HB, Hayashi A, Motonaga C, Tang J, Enomoto K, Enomoto T.

Central Research Laboratories, Nichinichi Pharmaceutical Co Ltd, Mie, Japan.

BACKGROUND: Recent epidemiological studies have indicated that early life receipt
of antibiotics may be associated with an increased risk of developing atopic
disorder. Lysed Enterococcus faecalis FK-23 (LFK), a probiotic product of E
faecalis, has been shown to have inhibitory effects on allergen-induced immune
responses in mice. OBJECTIVE: The purpose of this study was to evaluate the
effects of LFK on immune responses and intestinal microflora in
antibiotic-treated, and allergen-sensitized weaning mice. METHODS: Three-week-old
BALB/c mice were sensitized with cedar pollen allergen to establish the
experimental model. The allergen-induced peritoneal accumulation of eosinophils, 
serum levels of total and allergen-specific immunoglobulin (Ig) E and IgG2a, and 
the intestinal bacterial flora were determined in the control, antibiotic, LFK
and antibiotic-LFK groups (n = 7 in all groups). Orally administered
erythromycin, one kind of macrolide antibiotic, was used for the experiments.
RESULTS: There was no significant difference in the allergen-induced peritoneal
accumulation of eosinophils and serum specific IgE and IgG2a levels in
erythromycin-treated mice compared to a control group. However, the ratio of
serum total IgE to IgG2a levels was significantly increased in
erythromycin-treated mice relative to that found either in LFK-treated mice or in
erythromycin-treated mice with LFK supplementation. The total aerobes, total
anaerobes and Enterococcus species of intestinal microflora were not
significantly different among all groups. Lactobacillus species were distinctly
eliminated in the mice exposed to erythromycin on day 7 and totally recovered in 
erythromycin-treated mice with LFK intervention on day 28, but could not be
recovered in the erythromycin-treated mice without LFK intervention. CONCLUSIONS:
Our results suggest that LFK may improve the intestinal ecosystem disturbed by
antibiotic use, and thereby prevent subsequent development of atopy. However,
whether different antibiotics have different effects on immune responses needs to
be addressed further.

PMID: 17460944 [PubMed - indexed for MEDLINE]

339: Laryngoscope. 2007 Jun;117(6):960-4.

Inverse association between T-cell immunoglobulin and mucin domain-1 and T-bet in
a mouse model of allergic rhinitis.

Xu G, Cheng L, Wen W, Oh Y, Mou Z, Shi J, Xu R, Li H.

Otorhinolaryngology Hospital of The First Affiliated Hospital of Sun Yat-sen
University and the Otorhinolaryngology Institute of Sun Yat-sen University,
Guangzhou, China.

BACKGROUND: It has been suggested that human hepatitis A virus cellular receptor,
also known as T-cell immunoglobulin and mucin domain-1 (TIM-1), plays an
important role in the development of allergic diseases on the basis of
epidemiologic data, but the molecular mechanism has been unclear. In a murine
model of ovalbumin (OVA)-sensitized allergic rhinitis (AR), we examined the
expression of TIM-1 and its correlation with T helper1-associated transcription
factor, T-bet, as a potential mediator of T-cell immunoglobulin expression.
METHODS: Mice were challenged intranasally with OVA to elicit AR. The expression 
of TIM-1 in nasal tissues was examined by real-time reverse-transcription
polymerase chain reaction (RT-PCR), and the surface expression of TIM-1 in
peripheral blood mononuclear cells was evaluated by means of flow cytometry. In
addition, the expression of TIM-1 as well as T-bet in splenic lymphocytes was
examined by Western blotting. RESULTS: TIM-1 mRNA was increased significantly in 
nasal tissues (P < .05) as seen by real-time RT-PCR. Flow cytometry indicated a
differential TIM-1 expression of 135.5 +/- 34.2 in the AR group versus 51.1 +/-
10.9 in the control group (P < .05). The mean values of normalized TIM-1 were
0.43 +/- 0.18 and 0.21 +/- 0.10 in AR and control groups, respectively, whereas
the mean values of normalized T-bet were 0.22 +/- 0.13 and 0.67 +/- 0.17 in the
AR and control groups, respectively. There was a significant difference in the
production of TIM-1 as well as T-bet in AR mice versus control mice (P < .05).
The increased production of TIM-1 correlated significantly with the decreased
T-bet in spleen tissue of AR mice (r = -0.52, P < .05). CONCLUSION: Our
experimental model recapitulates an increase in lymphocyte TIM-1 expression seen 
in AR both locally and systemically. Our results also demonstrate an inverse
relationship between lymphocyte TIM-1 and T-bet expression, suggesting a possible
mechanism that TIM-1 influences the development of AR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17460580 [PubMed - indexed for MEDLINE]

340: Ann Allergy Asthma Immunol. 2007 Apr;98(4):316-21.

Clinical efficacy and pharmacokinetic profiles of intranasal and oral cetirizine 
in a repeated allergen challenge model of allergic rhinitis.

Korsgren M, Andersson M, Borgå O, Larsson L, Aldén-Raboisson M, Malmqvist U,
Greiff L.

Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
Magnus.Korsgren@med.lu.se

BACKGROUND: Intranasal and oral antihistamines are effective in treating allergic
rhinitis. Studies comparing these routes of administration of an antihistamine
regarding efficacy and pharmacokinetic profile are lacking. OBJECTIVE: To compare
topical and oral routes of administration of cetirizine regarding efficacy,
plasma exudation, and systemic drug levels in a repeated allergen challenge model
of allergic rhinitis. METHODS: Oral cetirizine dihydrochloride, 10 mg once daily,
and topical cetirizine dinitrate in a dose corresponding to 4.4 mg of the
dihydrochloride salt twice daily were given to grass pollen-sensitive individuals
for 12 days in a double-blind, placebo-controlled, crossover design. Timothy
grass pollen allergen challenges were given once daily for 7 days using a nasal
spray device. Nasal symptoms and peak inspiratory flow were recorded in the
morning, 10 minutes after allergen challenge, and in the evening. The
pharmacokinetics of the treatments was monitored in 8 patients. The remaining 28 
patients were challenged topically with histamine 12 and 24 hours after the final
topical and oral cetirizine doses, respectively. Nasal lavage levels of
alpha2-macroglobulin were determined to evaluate histamine-induced mucosal plasma
exudation. RESULTS: During the last 3 days of the repeated allergen challenge
model, chronic symptoms were established. Both treatments reduced symptoms 10
minutes after allergen challenge (P < .001 vs placebo). Neither treatment reduced
morning and evening symptoms or nasal peak inspiratory flow. Topical, but not
oral, cetirizine reduced histamine-induced plasma exudation (P < .01 vs placebo) 
when systemic drug levels were similar in the 2 treatment regimens. CONCLUSIONS: 
Topical and oral cetirizine reduced acute nasal symptoms produced by allergen
challenges in patients with established chronic symptoms. There were also
antihistaminic effects of topical cetirizine not related to systemic drug levels.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17458426 [PubMed - indexed for MEDLINE]

341: Curr Opin Mol Ther. 2007 Apr;9(2):160-7.

Specific immunotherapy in pollen allergy.

Wallner M, Briza P, Thalhamer J, Ferreira F.

Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of
Molecular Biology, University of Salzburg, Hellbrunnerstralle 34, A-5020
Salzburg, Austria.

Pollen allergy affects at least 10% of the global population, and up to one-third
of the affected individuals displaying hay fever symptoms will later develop
allergic asthma. The efficacy of allergen-specific immunotherapy (SIT) in
seasonal allergic rhinitis has been confirmed in many clinical studies using
grass, ragweed, and birch pollen extracts. SIT prevents the onset of new
sensitizations to different allergens, and reduces the development of asthma in
patients with allergic rhinitis caused by inhaled allergens, including pollen.
Several rational approaches are being developed to improve the efficacy of SIT by
reducing immunoglobulin (Ig)E-mediated adverse reactions. The use of chemically
modified, recombinant or genetically engineered allergens is being explored, in
addition to the investigation of novel adjuvants and alternative routes of
administration. The first clinical trials using recombinant allergens provided
encouraging results, suggesting that allergen extracts can be successfully
substituted by molecule-based formulations. These new formulations, for use in
the routine management of pollen allergies, should become available in the near
future.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17458170 [PubMed - indexed for MEDLINE]

342: Clin Exp Allergy. 2007 May;37(5):772-9.

Cost-effectiveness of grass allergen tablet (GRAZAX) for the prevention of
seasonal grass pollen induced rhinoconjunctivitis - a Northern European
perspective.

Bachert C, Vestenbaek U, Christensen J, Griffiths UK, Poulsen PB.

Upper Airway Research Laboratory (URL), ENT Department, University Hospital,
Ghent, Belgium.

BACKGROUND: The prevalence of allergic rhinoconjunctivitis has increased
dramatically. Seventeen million people in the United Kingdom, Germany, the
Netherlands, Sweden, Denmark, Norway and Finland suffer from grass pollen induced
allergic rhinitis. Symptomatic therapy with antihistamines and topical steroids
is partially effective but allergen-specific immunotherapy by injection or
sublingual routes is superior. The grass allergen tablet (GRAZAX) is a new
allergen-specific immunotherapy for home administration. OBJECTIVE: To assess the
cost-effectiveness of the grass allergen tablet compared with symptomatic
medication in seven Northern European countries. METHODS: A prospective
pharmacoeconomic analysis was carried out alongside a multinational clinical
trial. Pooled data on resource use and health outcomes were collected. A societal
perspective was adopted, and the analysis had a 9-year time horizon. The outcome 
measure was Quality Adjusted Life Years (QALYs). RESULTS: The grass allergen
tablet was clinically superior to symptomatic treatment, producing statistically 
significant differences for all efficacy end-points, including the number of
QALYs gained - 0.976 vs. 0.947 QALYs gained. There was a significantly higher
usage of the rescue medications loratadine and budesonide, and more hours missed 
from work (production loss), in the symptomatic treatment group. The cost per
QALY gained in the grass allergen tablet group was similar in the seven countries
(euro 12,930 to euro 18,263 for an annual cost of the grass allergen tablet of
euro 1500). The analysis showed that the grass allergen tablet was cost-effective
for all countries for an annual treatment cost below euro 2200. CONCLUSION: The
pharmacoeconomic analysis illustrated that allergen-specific immunotherapy with
the grass allergen tablet is a cost-effective intervention for the prevention of 
grass pollen induced rhinoconjunctivitis in Northern European countries, for a
tablet price below euro 6. In Germany for example the price of the tablet is euro
2.95 corresponding to a yearly treatment cost of euro 358 - based on a 9-year
time horizon.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17456225 [PubMed - indexed for MEDLINE]

343: Curr Allergy Asthma Rep. 2007 May;7(2):134-40.

Rodent models of allergic rhinitis: relevance to human pathophysiology.

Wagner JG, Harkema JR.

211 Food Safety and Toxicology Building, Michigan State University, East Lansing,
MI 48824, USA. wagnerja@msu.edu

Rodent models of allergic airways disease employ a wide range of test allergens, 
sensitization and provocation protocols, animal strains, and experimental
endpoints. Studies of experimental asthma, especially the use of murine models,
have contributed significantly to the understanding of the genetics and
immune-mediated pathophysiology of pulmonary airways during allergy. By
comparison, rodent models of allergic rhinitis are less well developed. Recent
interest in the potential mechanistic links between asthma and allergic rhinitis 
has increased the need for relevant animal studies directed at upper airways
responses. Specifically, the nature of nasal airway remodeling in response to
chronic activation of allergic pathways and its relationship to airway occlusion 
is not well described. This cursory review discusses current approaches to
assessing nasal obstruction in rodent models, and how the histopathologic
analysis might be improved to facilitate understanding of the pathogenesis of
allergic rhinitis in humans.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Review

PMID: 17437684 [PubMed - indexed for MEDLINE]

344: Clin Exp Allergy. 2007 Apr;37(4):564-71.

Comment in:
    Clin Exp Allergy. 2007 Oct;37(10):1576; author reply 1576-7.

Comparison of allergenicity and immunogenicity of an intact allergen vaccine and 
commercially available allergoid products for birch pollen immunotherapy.

Lund L, Henmar H, Würtzen PA, Lund G, Hjortskov N, Larsen JN.

ALK-Abelló A/S, Research Department, Hørsholm, Denmark.

BACKGROUND: Specific immunotherapy with intact allergen vaccine is a
well-documented treatment for allergic diseases. Different vaccine formulations
are currently commercially available, the active ingredient either being intact
allergens or chemically modified allergoids. The rationale behind allergoids is
to decrease allergenicity while maintaining immunogenicity. However, data from
the German health authorities based on reporting of adverse events over a 10-year
period did not indicate increased safety of allergoids over intact allergens.
OBJECTIVE: The objective of this study was to investigate the effect of chemical 
modification on allergenicity and immunogenicity comparing four commercial
allergoid products for birch pollen immunotherapy with an intact allergen
vaccine. METHODS: Solid-phase IgE inhibition and histamine release assays were
selected as model systems for allergenicity, and a combination of human T cell
proliferation and IgG titres following mouse immunizations were used to address
the immunogenicity of the intact allergen vaccine and the four allergoids. In all
assays, the products were normalized with respect to the manufacturer's
recommended maintenance dose. RESULTS: IgE inhibition experiments showed a change
in epitope composition comparing intact allergen vaccine with allergoid. One
allergoid product induced enhanced histamine release compared to the intact
allergens, while the other three allergoids showed reduced release. Standard T
cell stimulation assays using lines from allergic patients showed a reduced
response for all allergoids compared with the intact allergen vaccine regardless 
of the cell type used for antigen presentation. All allergoids showed reduced
capacity to induce allergen-specific IgG responses in mice. CONCLUSION: While
some allergoids were associated with reduced allergenicity, a clear reduction in 
immunogenicity was observed for all allergoid products compared with the intact
allergen vaccine, and the commercial allergoids tested therefore do not fulfil
the allergoid concept.

Publication Types: 
    Comparative Study

PMID: 17430354 [PubMed - indexed for MEDLINE]

345: Clin Exp Allergy. 2007 Apr;37(4):512-7.

Vaccinations, infections and antibacterials in the first grass pollen season of
life and risk of later hayfever.

Bremner SA, Carey IM, DeWilde S, Richards N, Maier WC, Hilton SR, Strachan DP,
Cook DG.

Division of Community Health Sciences, St George's, University of London, London,
UK.

BACKGROUND: It has been hypothesized that early-life exposure to vaccinations,
infections or antibacterials influence allergic disease development. Concurrent
exposure to grass pollens may alter any effect. OBJECTIVE: To test the hypothesis
that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections
during the first grass pollen seasons of life influences the risk of hayfever
more than at any other time of the year. METHODS: Nested case-control studies
were based on birth cohorts within two large databases of computerized patient
records from UK general practices: the General Practice Research Database (GPRD) 
and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever
cases, diagnosed after age 2, were matched to controls for practice, age, sex and
follow-up of control to case ascertainment date. Conditional logistic regression 
was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the
grass pollen season (May, June, July). Odds ratios (ORs) were pooled across
databases. RESULTS: There were no associations in either database between MMR
during vs. outside the grass pollen season and later hayfever. Of 23 infections
studied, none were statistically significant; although analyses for the less
common conditions were limited by low statistical power. The pooled OR for
hayfever comparing exposure to antibacterials only in the grass pollen season
with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI
0.72-0.98). CONCLUSION: Although an interaction between early exposure to
microbial agents and concurrent grass pollen exposure on hayfever risk seemed
plausible, there was little evidence to support it across a range of analyses.
However, the effect of DTP though weak deserves further study.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17430347 [PubMed - indexed for MEDLINE]

346: Allergol Immunopathol (Madr). 2007 Mar-Apr;35(2):44-51.

Specific immunotherapy is effective in the prevention of new sensitivities.

Reha CM, Ebru A.

Department of Allergy, Ministry of Health, Ankara Diskapi Children's Diseases
Training and Research Hospital, Ankara, Turkey.

BACKGROUND: Allergen specific immunotherapy is the only specific and curative
approach in the treatment of IgE-mediated allergic diseases such as bronchial
asthma and allergic rhinitis. The safety and clinical efficacy of this treatment 
are well documented but data on the prevention of new sensitizations remain
scarce. OBJECTIVE: To demonstrate the efficacy of specific immunotherapy in
allergic respiratory diseases in childhood and to determine whether this
treatment prevents the development of new sensitizations in children sensitized
to house dust mite or pollen species. METHODS: Fifty-six patients received
specific immunotherapy (43 sensitive to house dust mite and 13 sensitive to
pollen). Fifty-one patients not receiving immunotherapy but treated with
pharmacotherapy were enrolled in the control group. The patients were followed-up
for at least 4 years and treatment efficacy and the development of new
sensitizations were compared between the two groups. RESULTS: The number of
patients with symptoms was significantly decreased in both groups at the end of
the treatment period. No new sensitizations were found in 35 of the 43 (81.39 %) 
patients in the house dust mite immunotherapy group and in 10 of 13 (76.92 %)
patients in the pollen immunotherapy group. In contrast, 20 of 51 (39.21 %)
patients in the control group showed new sensitizations. The difference between
the house dust mite and pollen immunotherapy groups and the control group in this
parameter was statistically significant (p = 0.033). CONCLUSION: Our data
demonstrate that administration of specific immunotherapy in allergic patients
significantly reduced symptoms and the development of new sensitivities.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial

PMID: 17428399 [PubMed - indexed for MEDLINE]

347: Drugs. 2007;67(6):887-901.

Montelukast in the treatment of allergic rhinitis: an evidence-based review.

Nayak A, Langdon RB.

Sneeze, Wheeze & Itch Associates, Normal, Illinois 61761, USA.
drnayak@asthma2.com

Cysteinyl-leukotrienes (CysLTs) are endogenous mediators of inflammation and play
an important role in allergic airway disease by stimulating bronchoconstriction, 
mucus production, mucosal oedema and inflammation, airway infiltration by
eosinophils, and dendritic cell maturation that prepares for future allergic
response. Montelukast inhibits these actions by blocking type 1 CysLT receptors
found on immunocytes, smooth muscle and endothelium in the respiratory mucosa.
Initially developed as a treatment for asthma, montelukast has more recently
found use in the treatment of allergic rhinitis (AR). We conducted a systematic
review of studies that have evaluated montelukast in the treatment of seasonal AR
(SAR) and perennial AR (PAR), with and without concomitant asthma. Primary
consideration was given to large, randomised, placebo-controlled, double-blind
clinical trials in which AR endpoints were assessed and the use of concurrent
treatments for AR was excluded. Eight such studies were found in the literature. 
The primary endpoint in these was daytime nasal symptom severity represented by a
composite score derived from individual self-ratings of nasal congestion,
rhinorrhoea, nasal pruritus and sneezing. Secondary endpoints have included these
individual nasal symptom scores, additional scores for eye, ear and throat
symptoms, the impact of rhinitis on quality of sleep, global evaluations of
outcome by patients and physicians, and measures of the severity of concomitant
asthma. A general outcome was that patients treated with montelukast had
significantly greater improvements in their symptoms of SAR and PAR than did
patients who were given a placebo. As monotherapy, montelukast exhibited efficacy
similar to that of loratadine, but less than that of the intranasally
administered corticosteroid fluticasone propionate. The use of montelukast in
combination with antihistamines such as loratadine or cetirizine has generally
resulted in greater efficacy than when these agents were used alone, and in some 
studies has produced results comparable with intranasally applied
corticosteroids. In patients with AR comorbid with asthma, montelukast treatment 
has resulted in significant improvements in both, compared with placebo.
Montelukast is well tolerated and has a favourable safety profile; adverse events
have occurred at similar frequencies in patients taking either montelukast or
placebo. Montelukast provides an effective and well tolerated oral treatment for 
allergic airway inflammation in patients with SAR or PAR without asthma, and in
patients in whom AR is comorbid with asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17428106 [PubMed - indexed for MEDLINE]

348: Am J Rhinol. 2007 Mar-Apr;21(2):236-40.

Assessment for microsatellite DNA instability in nasal cytology samples of
patients with allergic rhinitis.

Karatzanis AD, Samara KD, Zervou M, Tzortzaki E, Helidonis ES, Siafakas N,
Velegrakis GA.

Departments of Otorhinolaryngology, Head and Neck Surgery, Medical School,
University of Crete, Heraklion, Crete, Greece. akaratzanis@yahoo.com

BACKGROUND: Genetic alterations, including microsatellite instability (MSI) and
loss of heterozygosity (LOH), have been described in both malignant and benign
diseases. Previous studies have successfully detected such alterations in sputum 
samples of patients with bronchial asthma (BA). The aim of this study was to
assess the presence of MSI and/or LOH in nasal cytology samples of patients with 
allergic rhinitis (AR). METHODS: Nasal brush samples and peripheral blood from 20
patients with AR were analyzed. DNA was extracted and analyzed for MSI and LOH
using the following microsatellite markers: D16S289, D4S2394, D4S1651, DXS8039,
D3S3606, and D2S2113, harboring potential susceptibility genes for AR and atopy. 
Microsatellite analysis was performed also in eight control subjects. RESULTS: No
MSI and/or LOH were noted in either the AR or the control group. CONCLUSION:
Although MSI and LOH are detectable phenomena in sputum samples of patients with 
BA, this seems not to be the case for nasal cytology samples of patients with AR.
Additional studies are needed, using a larger number of polymorphic markers, to
assess if such a difference exists among two diseases otherwise very closely
related.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17424887 [PubMed - indexed for MEDLINE]

349: J Allergy Clin Immunol. 2007 Apr;119(4):881-91.

Comment in:
    J Allergy Clin Immunol. 2008 Feb;121(2):536; author reply 536.

Allergic rhinitis and its impact on asthma update: allergen immunotherapy.

Passalacqua G, Durham SR; Global Allergy and Asthma European Network.

Allergy and Respiratory Diseases, Department of Internal Medicine, University of 
Genoa, Genoa, Italy. passalacqua@unige.it

The Allergic Rhinitis and its Impact on Asthma document was first published in
2001. Since then, new data on specific immunotherapy have appeared. This review
is intended as an update to the original document. MedLine (2001 to June 2006)
was searched with appropriate key words, and panelists were asked to identify
further relevant articles. Randomized controlled trials were considered for the
evaluation of efficacy. For the evaluation of safety and additional effects,
studies with lower grades of evidence were included. The clinical efficacy of
injection immunotherapy in rhinitis and asthma was confirmed, as well as the
safety, provided that recommendations are followed. Studies have demonstrated the
long-term efficacy and the preventive effect of immunotherapy in reducing the
onset of new sensitizations. One randomized open trial demonstrated that in
children with allergic rhinitis, injection immunotherapy may reduce the risk of
developing asthma. There is strong evidence that sublingual immunotherapy is
effective in allergic rhinitis in adults. Recent meta-analyses demonstrated its
efficacy in allergic rhinitis in children and in asthma, although more definitive
trials are required. Current data indicate that sublingual immunotherapy is safe 
and the rate of adverse reactions is not greater below 5 years of age. One
randomized open trial showed that in children with allergic rhinitis, sublingual 
immunotherapy reduced the onset of asthma. Further studies are needed to identify
the optimal maintenance dose and to elucidate the mechanism of action. Novel
approaches for immunotherapy are currently under evaluation, including the use of
adjuvants, peptides, and DNA-conjugated and recombinant allergens.

Publication Types: 
    Comparative Study
    Review

PMID: 17418661 [PubMed - indexed for MEDLINE]

350: J Allergy Clin Immunol. 2007 Jun;119(6):1430-7. Epub 2007 Apr 5.

Comment in:
    J Allergy Clin Immunol. 2007 Dec;120(6):1473-4; author reply 1474.    J Allergy Clin Immunol. 2008 Feb;121(2):538-9.    J Allergy Clin Immunol. 2008 Jan;121(1):265; author reply 265.

Fluticasone furoate nasal spray: a single treatment option for the symptoms of
seasonal allergic rhinitis.

Kaiser HB, Naclerio RM, Given J, Toler TN, Ellsworth A, Philpot EE.

Clinical Research Institute, Minneapolis, MN 55402, USA.
hbk@allergy-asthma-docs.com

BACKGROUND: Fluticasone furoate (USAN-approved name) is a novel,
enhanced-affinity glucocorticoid administered in a unique side-actuated device
for the management of seasonal allergic rhinitis (SAR). OBJECTIVE: We sought to
evaluate the efficacy and safety of once-daily fluticasone furoate nasal spray,
110 microg, in patients aged 12 years or older with fall SAR. METHODS: Patients
(n = 299) received fluticasone furoate or placebo for 2 weeks in this
double-blind, parallel-group randomized study. Patients evaluated nasal and
ocular symptoms using a 4-point categoric scale. Efficacy was assessed on the
basis of the mean change from baseline in reflective and instantaneous total
nasal symptom scores and reflective total ocular symptom scores. RESULTS:
Fluticasone furoate produced significantly greater improvements than placebo in
daily reflective total nasal symptom score (-1.473, P < .001; primary end point),
morning predose instantaneous total nasal symptom score (-1.375, P < .001), daily
reflective total ocular symptom score (-0.600, P = .004), and patient-rated
overall response to therapy (P < .001). The onset of therapeutic effect occurred 
at 8 hours after initial administration. Fluticasone furoate was well tolerated. 
CONCLUSION: Fluticasone furoate, 110 microg once daily, was effective and well
tolerated for the treatment of nasal symptoms of SAR in patients aged 12 years
and older. Treatment also produced significant improvements in ocular symptoms.
Fluticasone furoate was fast acting, as indicated by an 8-hour onset of action,
and provided 24-hour symptom control. CLINICAL IMPLICATIONS: New treatments for
the bothersome symptoms of SAR are needed. One such treatment, fluticasone
furoate nasal spray, provides effective relief of the symptom profile of SAR.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17418384 [PubMed - indexed for MEDLINE]

351: J Allergy Clin Immunol. 2007 May;119(5):1099-104. Epub 2007 Apr 9.

The relationship between seroatopy and symptoms of either allergic rhinitis or
asthma.

Abraham CM, Ownby DR, Peterson EL, Wegienka G, Zoratti EM, Williams LK, Joseph
CL, Johnson CC.

Section of Allergy and Immunology, Medical College of Georgia, Augusta, GA 30912,
USA.

BACKGROUND: Epidemiologic data on allergic rhinitis and asthma are frequently
based on self-reported symptoms. OBJECTIVE: This cross-sectional study examined
the relationship between self-reported symptoms and histories of allergic
rhinitis or asthma and a marker of allergic sensitization, allergen-specific IgE.
METHODS: We surveyed 702 pregnant women in Michigan. Blood samples were analyzed 
for specific IgE to 9 allergens: dust mites (Dermatophagoides farinae and
Dermatophagoides pteronyssinus), cat, dog, cockroach, ragweed, timothy grass,
egg, and Alternaria alternata. Seratopy was defined as a specific IgE greater
than or equal to 0.35 kU/L to any allergen. RESULTS: Seroatopy was found in 66.7%
of those with hay fever symptoms, 68.3% with a physician's diagnosis of asthma,
and 72.1% of those with both conditions. These results differed significantly
from asymptomatic subjects, where 49.8% of patients without hay fever and 50.4%
without asthma were seroatopic. Race and education did not modify the
relationships. Symptoms related to specific exposures were modest predictors of
positive specific IgE to related allergens (positive predictive values from 26.5%
to 50.3%). CONCLUSION: Self-reported symptoms of allergic rhinitis or asthma were
significantly associated with allergic sensitization, but the odds ratios were of
relatively low magnitude for this historical information to be considered
evidence of current allergic sensitization. A 66% to 68% probability existed that
those with symptoms of allergic rhinitis or asthma would have a positive specific
IgE test. CLINICAL IMPLICATIONS: Self-reported histories of hay fever or asthma
alone are only modest predictors of allergic sensitization. When knowledge of
allergic sensitization is important, information beyond self-reported symptoms is
necessary.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17416408 [PubMed - indexed for MEDLINE]

352: Drug Saf. 2007;30(4):317-26.

Mometasone furoate nasal spray: a review of safety and systemic effects.

Zitt M, Kosoglou T, Hubbell J.

State University of New York, Stony Brook, New York, NY, USA.
myron.zitt@gmail.com

The development of corticosteroids that are delivered directly to the nasal
mucosa has alleviated much of the concern about the systemic adverse effects
associated with oral corticosteroid therapy. However, given the high potency of
these drugs and their widespread use in the treatment of allergic rhinitis, it is
important to ensure that intranasal corticosteroids have a favourable
benefit-risk ratio. One agent that typifies the systemic safety found in the
majority of intranasal corticosteroids is mometasone furoate nasal spray, a
potent and effective treatment for seasonal and perennial allergic rhinitis and
nasal polyposis. Mometasone furoate does not reach high systemic concentrations
or cause clinically significant adverse effects. Results from pharmacokinetic
studies in adults and children suggest that systemic exposure to mometasone
furoate after intranasal administration is negligible. This is probably because
of the inherently low aqueous solubility of mometasone furoate, which allows only
a small fraction of the drug to cross the nasal mucosa and enter the bloodstream,
and because a large amount of the administered drug is swallowed and undergoes
extensive first-pass metabolism. There is no clinical evidence that mometasone
furoate nasal spray suppresses the function of the hypothalamus-pituitary-adrenal
axis when the drug is administered at clinically relevant doses (100-200
microg/day); consequently, mometasone furoate nasal spray has not been associated
with growth inhibition in children. The safety and tolerability of mometasone
furoate nasal spray have been rigorously assessed in clinical trials involving
approximately 4,500 patients, with epistaxis, headache and pharyngitis being the 
most common adverse effects associated with treatment in adolescents and
adults.The clinical effectiveness of mometasone furoate nasal spray, coupled with
its agreeable safety and tolerability profile, confirms its favourable
benefit-risk ratio.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17408308 [PubMed - indexed for MEDLINE]

353: Curr Med Res Opin. 2007 Apr;23(4):721-30.

Asthma control in patients with asthma and allergic rhinitis receiving add-on
montelukast therapy for 12 months: a retrospective observational study.

Borderias L, Mincewicz G, Paggiaro PL, Guilera M, Sazonov Kocevar V, Taylor SD,
Badia X.

Pneumology Department, San Jorge Hospital, Huesca, Spain.

BACKGROUND: Montelukast, a potent leukotriene receptor antagonist, is approved
for treatment of both asthma and allergic rhinitis (AR). No studies to date have 
examined whether montelukast can improve asthma control over a long period of
time in patients with seasonal AR and asthma. OBJECTIVE: To evaluate asthma
control and use of asthma-related medical resources by patients with inadequately
controlled mild to moderate persistent asthma and seasonal AR who required
addition of montelukast as part of routine care. METHODS: This multicenter,
24-month, pre-post retrospective observational study included patients receiving 
current inhaled corticosteroid (ICS) therapy (alone or in combination with
long-acting beta-agonist [LABA]), who received add-on treatment with montelukast 
for 12 consecutive months. The incidence of asthma attacks, defined as emergency 
department visit, hospitalization, or oral corticosteroid use for asthma, was
compared for the year before and the year after addition of montelukast to
therapy. RESULTS: For the 696 patients from Italy, Poland, and Spain who were
included in the analyses, the proportion of patients experiencing an asthma
attack declined from 31.5% in the year before to 10.1% (p < 0.001) the year after
addition of montelukast to therapy. Proportions of patients with an
asthma-related emergency room visit, hospitalization, and oral corticosteroid use
declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p <
0.01), respectively. The incidence of these outcomes declined in all three
countries, regardless of baseline asthma severity or asthma therapy (ICS alone or
ICS + LABA). Important study limitations include the possibility of selection
bias or missing medical chart data in this retrospective study design. Also
noteworthy is the inclusion of only those patients who remained persistent with
montelukast therapy. Therefore, the results of the study are relevant for
patients who remain persistent with montelukast therapy. CONCLUSIONS: Addition of
montelukast to current ICS therapy improved long-term asthma control and resulted
in substantial reductions in asthma-related resource use by patients with mild or
moderate persistent asthma and concomitant seasonal AR who were persistent with
montelukast therapy in this retrospective observational study.

Publication Types: 
    Evaluation Studies
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17407628 [PubMed - indexed for MEDLINE]

354: Prim Care Respir J. 2007 Apr;16(2):98-105.

Erratum in:
    Prim Care Respir J. 2007 Aug;16(4):257.

The impact of allergic rhinitis on work productivity.

Szeinbach SL, Seoane-Vazquez EC, Beyer A, Williams PB.

College of Pharmacy, Ohio State University, Columbus, Ohio 43210, USA.
Szeinbach.1@osu.edu

AIM: Patients with allergic rhinitis experience a multitude of symptoms that
usually compromise some aspect of lifestyle. However, few data are available that
specifically address the impact of allergic rhinitis on work productivity.
METHODS: A questionnaire was developed and mailed to 2,065 patients enrolled in a
500,000-member managed care organisation. Patients were identified by diagnostic 
codes for allergic rhinitis as determined by a retrospective examination of
medical and prescription claims records from January 1 2000 to December 31 2000. 
Patients were divided into three different care groups according to whether they 
were managed by family physicians, by allergists, or were self-managed. RESULTS: 
Chi-square and analysis of variance tests revealed significant differences among 
the three care groups (p<0.05) for years with allergies, symptoms, family
history, testing, immunotherapy, test value, and prescribed antihistamine use.
Multiple linear regression analysis revealed that sleep, health, certain allergy 
symptoms and prescribed antihistamines were significantly related to work
productivity. CONCLUSIONS: The results of this study revealed that the ability of
individuals with allergic rhinitis to engage in productive work is influenced by 
sleep, health-related quality of life (HRQoL), specific symptoms, and prescribed 
antihistamine use.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17404676 [PubMed - indexed for MEDLINE]

355: Allergy Asthma Proc. 2007 Jan-Feb;28(1):74-8.

Role of forced expiratory flow at 25-75% as an early marker of small airways
impairment in subjects with allergic rhinitis.

Marseglia GL, Cirillo I, Vizzaccaro A, Klersy C, Tosca MA, La Rosa M, Marseglia
A, Licari A, Leone M, Ciprandi G.

Department of Pediatrics, IRCCS Policlinico San Matteo, University of Pavia,
Italy. gl.marseglia@smatteo.pv.it

A close link exists between allergic rhinitis and asthma. Small airway disease
(SAD), defined by a reduction in forced expiratory flow at 25-75% of the
pulmonary volume (FEF25-75) and normal spirometry (normal forced expiratory
volume at 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC ratio), may 
be a marker for early allergic or inflammatory involvement of the small airways
in subjects with allergic diseases and no asthma. The aim of this study was to
determine if there is a relationship between SAD, the outcome variable, and
several allergic predictors in patients without asthma but with allergic
rhinitis. A cross-sectional study was performed. Two hundred eleven midshipmen
attending the third and fifth course of the Navy Academy of Livorno were
screened. Fifty-eight midshipmen showed slight spirometric anomalies. Thus, they 
were referred to the Navy Hospital of La Spezia for standardized tests:
skin-prick test, nasal cytology, spirometry, and methacholine bronchial
challenge. A reduced FEF(25-75) was arbitrarily defined as < 80% of predicted.
All 58 subjects had a normal FEV1, FVC, and FEV1/FVC ratio. Twenty subjects had a
reduced FEF(25-75), consistent with the definition of SAD. A mean value of
FEF(25-75) of 70.3 (SD, 8.5) was measured in patients with a reduced FEF, and it 
was 108.0 (SD, 14.3) in patients with preserved FEF(25-75). All the candidate
allergic predictors appeared to be strongly associated with a reduced FEF(25-75).
The proportion of subjects with reduced FEF(25-75) appeared to increase with
increasing severity of the allergic predictors, and, correspondingly, the mean
value of FEF(25-75) appeared to decrease. This study provides evidence that there
is a relationship between SAD and allergic parameters such as nasal symptoms and 
eosinophils.

PMID: 17390762 [PubMed - indexed for MEDLINE]

356: Allergy Asthma Proc. 2007 Jan-Feb;28(1):16-9.

Allergic rhinitis: selective comparisons of the pharmaceutical options for
management.

Lanier B.

Department of Pediatrics/Immunology, University of North Texas, Fort Worth, USA. 
boblaniermd@askdrbob.com

The depth and variety of pharmaceuticals available to manage the syndrome of
allergic rhinitis is unparalleled. To arrive at a personal formulary, a physician
would be well advised to understand what patients want and what they are willing 
to accept in terms of expense and adverse events. Patients want medications that 
are nonsteroidal, non habituating, produce no drowsiness, and could be used
intermittently on demand only. This review is intended as an aid in comparing
classes and formats of medications affecting nasal allergy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17390751 [PubMed - indexed for MEDLINE]

357: Allergy Asthma Proc. 2007 Jan-Feb;28(1):10-5.

New insights into the pathophysiology of allergic rhinitis.

Rosenwasser L.

Department of Medicine, and Basic Science, University of Missouri-Kansas City
School of Medicine 64108, USA. lrosenwasser@cmh.edu

The immune response to an allergen is dependent on an initial sensitization
process, with future exposures triggering a two-part allergic response including 
an early and a late phase. The process by which an allergen is recognized as
such, including which cell types and cytokines are involved in the sensitization 
process, has become clearer over the last several years. Similarly, the roles of 
the different preformed mediators responsible for many of the signs and symptoms 
of the early phase response have been elucidated. Recent work also has shed some 
light on the multitude of cells and mediators involved in the late-phase
reactions, which can lead to priming and long-term inflammation. This article
will discuss some of this recent work as well as review the basics behind all of 
the stages of the allergic response, especially as they apply to the nose and
upper airway.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17390750 [PubMed - indexed for MEDLINE]

358: Allergy Asthma Proc. 2007 Jan-Feb;28(1):3-9.

The burden of allergic rhinitis.

Nathan RA.

University of Colorado Health Sciences Center, Denver, Colorado, USA.
DrRNathan@aol.com

Although formerly regarded as a nuisance disease, allergic rhinitis (AR) has a
considerable effect on quality of life and can have significant consequences if
left untreated. The total burden of this disease lies not only in impaired
physical and social functioning but also in a financial burden made greater when 
considering evidence that AR is a possible causal factor in comorbid diseases
such as asthma or sinusitis. Compared with matched controls, patients with AR
have an approximate twofold increase in medication costs and 1.8-fold the number 
of visits to health practitioners. Hidden direct costs include the treatment of
comorbid asthma, chronic sinusitis, otitis media, upper respiratory infection,
and nasal polyposis. Nasal congestion, the most prominent symptom in AR, is
associated with sleep-disordered breathing, a condition that can have a profound 
effect on mental health, including increased psychiatric disorders, depression,
anxiety, and alcohol abuse. Furthermore, sleep-disordered breathing in childhood 
and adolescence is associated with increased disorders of learning performance,
behavior, and attention. In the United States, AR results in 3.5 million lost
workdays and 2 million lost schooldays annually. Patients struggle to alleviate
their misery, frequently self-adjusting their treatment regimen of
over-the-counter and prescription medications because of lack of efficacy,
deterioration of efficacy, lack of 24-hour relief, and bothersome side effects.
Ironically, health care providers overestimate patient satisfaction with therapy.
Therefore, improvement in patient-practitioner communication may enhance patient 
adherence with prescribed regimens.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17390749 [PubMed - indexed for MEDLINE]

359: Allergol Int. 2007 Jun;56(2):125-30. Epub 2007 Mar 1.

Preliminary study on Japanese cedar pollinosis in an artificial exposure chamber 
(OHIO Chamber).

Hashiguchi K, Tang H, Fujita T, Tsubaki S, Fujita M, Suematsu K, Gotoh M, Okubo
K.

Department of Otolaryngology, Kitasato Institute Hospital, Minatoku, Tokyo,
Japan. hashiguchi-k@kitasato.or.jp

BACKGROUND: A pollen exposure chamber (OHIO Chamber) was built in central Tokyo, 
Japan, in order to study seasonal allergic rhinitis (SAR). Since satisfactory
outcomes were obtained from the controlled pollen exposure at the chamber, we
conducted preliminary studies in volunteers with SAR. METHODS: Ten volunteers
with SAR sensitive to Japanese cedar (JC) pollen were enrolled in this study. In 
order to investigate the intranasal and intraocular pollen number, volunteers
were initially exposed to a low concentration of JC (2500 grains/m3) for at most 
1 hour in this chamber. Before and after the exposure, nasal cavities and eyes
were washed with 100ml and 25 ml of saline, respectively. Nasal and eye washing
solutions were collected and the number of JC pollen was counted. After 3 hours
the volunteers were subsequently exposed to a moderate concentration of JC (4500 
grains/m3) for 2 hours. Subjective nasal and ocular symptoms were recorded and
the amount of nasal secretion was measured during the allergen exposure periods. 
RESULTS: During the initial exposure, all volunteers except one stayed in the
chamber for 1 hour without any nasal or ocular symptoms. The number of pollen in 
the nose and eyes was 249.2 +/- 120.9 and 13.6 +/- 13.6 grains, respectively.
During the subsequent 2-hour exposure to JC pollen, nasal and ocular symptoms
developed gradually in a time dependent manner in all the volunteers except one. 
CONCLUSIONS: This is the first clinical study using Japanese cedar pollen under
well-controlled conditions in the OHIO chamber in which the induction of allergic
symptoms was observed. The OHIO chamber will be useful for studying allergic
rhinitis in Japan.

PMID: 17384532 [PubMed - indexed for MEDLINE]

360: J Allergy Clin Immunol. 2007 May;119(5):1119-26. Epub 2007 Mar 26.

Alleviation of seasonal allergic symptoms with superfine beta-1,3-glucan: a
randomized study.

Yamada J, Hamuro J, Hatanaka H, Hamabata K, Kinoshita S.

Department of Ophthalmology, Meiji University of Oriental Medicine.
jyamada@ophth.kpu-m.ac.jp

BACKGROUND: The incidence of allergic symptoms to cedar pollen has reached
epidemic proportions in Japan. Intravenous injection of beta-1,3-glucan in human 
subjects is known to induce a T(H)1 response, whereas oral uptake does not.
OBJECTIVE: It was examined whether orally ingested, superfine dispersed
beta-1,3-glucan (SDG), easily absorbed by intestinal mucosa, would alleviate
allergic symptoms. METHODS: Allergic patients were orally administrated either
SDG (n = 30) or nondispersed beta-1,3-glucan (n = 30), and allergic symptoms were
assessed clinically in a double-blind, placebo-controlled randomized study.
RESULTS: SDG alleviated ongoing symptoms of Japanese cedar pollen-induced
rhinorrhea, sneezing, nasal congestion, and itchy watery eyes, and its oral
uptake before symptom onset exhibited preventive effects. Alleviation of allergic
symptoms was evident not only for seasonal allergy to cedar pollen but also for
perennial allergy. Oral ingestion of beta-1,3-glucan in individuals with allergic
tropism could reduce the spontaneous increase in both allergen-specific and total
IgE titers. The clinical responses to treatment were well correlated with the
capacity of monocytes to bind to beta-1,3-glucan. Although SDG reduced allergic
symptoms, the oral uptake of nondispersed beta-1,3-glucan produced no clinical
effects, despite the identical amount of beta-1,3-glucan in both preparations.
CONCLUSION: We postulate that orally taken beta-1,3-glucan prepared in a form
easily absorbed by intestinal mucosa is able to alleviate cedar pollen-induced
allergic symptoms. CLINICAL IMPLICATIONS: Orally effective SDG might greatly
contribute to the resolution of epidemic medical problems of seasonal cedar
pollen-induced allergy.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17379290 [PubMed - indexed for MEDLINE]

361: Ann Allergy Asthma Immunol. 2007 Mar;98(3):269-73.

Nasal provocation of patients with allergic rhinitis and the
hypothalamic-pituitary-adrenal axis.

Kalogeromitros D, Syrigou EK, Makris M, Kempuraj D, Stavrianeas NG, Vasiadi M,
Theoharides TC.

Allergy Clinical Research Center, Allergy Section, Attikon Hospital, University
of Athens Medical School, Athens, Greece.

BACKGROUND: Allergic rhinitis is a common problem involving activation of nasal
mast cells and irritability. The hypothalamic-pituitary-adrenal (HPA) axis is
stimulated in cases of emotional or environmental stress, and mast cells have
been implicated in stress-induced immune responses. OBJECTIVE: To investigate
whether intranasal challenge of patients allergic to a single antigen would
stimulate the HPA axis. METHODS: Plasma corticotropin and cortisol levels were
measured 20, 40, 60, 80, 100, and 120 minutes after intranasal antigen
administration in healthy volunteers (n=3) and in patients with rhinitis who are 
allergic to Parietaria (n=10). RESULTS: Mean +/- SD corticotropin levels were
24.43 +/- 14.38 pg/mL in patients compared with 8.83 + 5.02 pg/mL in controls,
and this increase was statistically significant (P = .049). Patient cortisol
levels also increased to a mean +/- SD of 8.87 +/- 4.90 pg/mL (at 40 minutes)
compared with 4.36 +/- 1.72 pg/mL in controls (P = .11 due to 1 outlier).
Compared with individual patient prechallenge levels, corticotropin levels
increased in 7 patients and cortisol levels increased in 5 at 40 minutes.
CONCLUSION: These results suggest that allergic rhinitis may activate the HPA
axis. A larger study with additional controls is required for definitive
conclusions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17378259 [PubMed - indexed for MEDLINE]

362: J Immunol. 2007 Apr 1;178(7):4658-66.

Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response
associated with mucosal TGF-beta expression.

Pilette C, Nouri-Aria KT, Jacobson MR, Wilcock LK, Detry B, Walker SM, Francis
JN, Durham SR.

Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, National 
Heart and Lung Institute, Imperial College, Dovehouse Street, London, U.K.

Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic
rhinitis and asthma. IT has been shown to modify lymphocyte responses to
allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for
IgA and local TGF-beta-producing cells remains to be determined. In 44 patients
with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J
chain-containing) Abs to the major allergen Phl p 5 were determined by ELISA
before and after a 2-year double-blind trial of grass pollen (Phleum pratense)
injection IT. Nasal TGF-beta expression was assessed by in situ hybridization.
Sera from five IT patients were fractionated for functional analysis of the
effects of IgA and IgG Abs on IL-10 production by blood monocytes and
allergen-IgE binding to B cells. Serum Phl p 5-specific IgA2 Abs increased after 
a 2-year treatment (approximately 8-fold increase, p = 0.002) in contrast to
IgA1. Increases in polymeric Abs to Phl p 5 (approximately 2-fold increase, p =
0.02) and in nasal TGF-beta mRNA (p = 0.05) were also observed, and TGF-beta mRNA
correlated with serum Phl p 5 IgA2 (r = 0.61, p = 0.009). Post-IT IgA fractions
triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding 
to B cells as observed with IgG fractions. This study shows for the first time
that the IgA response to IT is selective for IgA2, correlates with increased
local TGF-beta expression, and induces monocyte IL-10 expression, suggesting that
IgA Abs could thereby contribute to the tolerance developed in IT-treated
allergic patients.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17372025 [PubMed - indexed for MEDLINE]

363: Allergy. 2007 Apr;62(4):423-8.

Polymorphisms in eosinophil pathway genes, asthma and atopy.

Kabesch M, Depner M, Dahmen I, Weiland SK, Vogelberg C, Niggemann B, Lau S, Illig
T, Klopp N, Wahn U, Reinhardt D, von Mutius E, Nickel R.

University Children's Hospital, Ludwig Maximilians University Munich, Munich,
Germany.

BACKGROUND: Eosinophilic inflammation is considered to play an important role in 
the development as well as in the perpetuation of asthma. As eosinophil
production and survival is under genetic control we investigated whether
polymorphisms in eosinophil regulation pathway genes (IL-3, IL-5, GM-CSF and
their respective enhancers and receptors) may influence the development of atopic
diseases. METHODS: In two large study populations of children, the German part of
the International Study of Asthma and Allergy in Childhood (ISAAC II) and the
German Multicentre Atopy Study (MAS), 3099 and 824 children, seven polymorphisms 
previously associated with the development of atopic diseases were genotyped: two
in and around the GM-CSF gene (Ile117Thr and T3085G), one in IL-3 (Pro27Ser), in 
IL-5 (C-746T), and in the IL-5 high affinity receptor chain IL-5R (G-80A) and two
in the common receptor chain CSFR2b for IL-3, IL-5, and GM-CSF (Asp312Asn and
Glu249Gln). Statistical analyses were performed using chi-squared tests and
variance analyses. Gene by gene interactions were evaluated in logistic
regression models. RESULTS: The T allele at position -746 in the IL-5 gene was
significantly protective for atopy in the ISAAC II population (P = 0.006).
Furthermore, the risk for atopic asthma was decreased in carriers of the T allele
(P = 0.036) and evidence for interaction with the enhancer polymorphism 3085 bp
3' of GM-CSF was detected. CONCLUSIONS: IL-5 C-746T influenced atopic outcomes
and showed evidence for gene by gene interaction. No significant associations
were found with all other tested polymorphisms in the eosinophil regulation
pathway after correction for multiple testing.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17362254 [PubMed - indexed for MEDLINE]

364: Allergy. 2007 Apr;62(4):378-84.

Nasal nitric oxide: longitudinal reproducibility and the effects of a nasal
allergen challenge in patients with allergic rhinitis.

Boot JD, de Kam ML, Mascelli MA, Miller B, van Wijk RG, de Groot H, Cohen AF,
Diamant Z.

Centre for Human Drug Research, Leiden, The Netherlands.

BACKGROUND: Exhaled nitric oxide (eNO) is a validated noninvasive marker of
airway inflammation in asthma. In patients with allergic rhinitis (AR), increased
levels of nasal nitric oxide (nNO) have also been measured. However, the
applicability of nNO as a marker of upper airway inflammation awaits validation. 
AIM: To test the longitudinal reproducibility of standardized nNO measurements in
patients with AR and the effects of nasal allergen challenge. METHODS: Twenty
patients with clinically stable, untreated AR participated in a combined study
design. First, reproducibility of nNO was tested over 1, 7, and 14-21 days.
Subsequently, the effect of nasal allergen challenge on nNO was studied in a
placebo-controlled, parallel design. Nasal NO was measured with a
chemoluminescence analyzer. Ten subjects randomly underwent a standardized nasal 
allergen challenge; 10 subjects received placebo. Response to nasal challenge was
monitored by composite symptom scores. RESULTS: There was a good reproducibility 
of nNO up to 7 days [coefficient of variation (CV) over 1 (16.45%) and 7 days
(21.5%)], decreasing over time [CV (14-21 days): 38.3%]. As compared with
placebo, allergen challenge caused a significant increase in symptom scores (P < 
0.001), accompanied by a decrease in nNO at 20 min postchallenge (P = 0.001).
Furthermore, there was a gradual increase in nNO at 7 h, reaching significance at
24-h postallergen (P = 0.04). CONCLUSIONS: Similar to eNO in asthma, nNO is a
noninvasive marker, potentially suitable to monitor upper airway inflammation
following allergen-induced late response. Present data show a good
reproducibility of nNO measurements, decreasing over time, probably because of
subclinical seasonal influences.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17362248 [PubMed - indexed for MEDLINE]

365: Allergy. 2007 Apr;62(4):373-7.

Grass pollen symptoms interfere with the recollection of birch pollen symptoms - 
a prospective study of suspected, asymptomatic skin sensitization.

Assing K, Bodtger U, Poulsen LK, Malling HJ.

Allergy Clinic, National University Hospital, Copenhagen, Denmark.

BACKGROUND: Asymptomatic skin sensitization (AS) is a risk factor for the
development of allergic symptoms. A meticulous definition of this condition
requires a systematic assessment of clinical symptoms before inclusion.
OBJECTIVE: To examine the concordance between retrospective assessment of
seasonal allergic symptoms and prospective seasonal symptom registration among
subjects with AS. METHODS: On the basis of a population survey, autumn 2002,
including skin prick tests (positive if > or =3 mm) and a screening
questionnaire, 87 subjects with AS to birch and/or grass pollen, birch and/or
grass pollen allergic symptomatic subjects (n = 63) and healthy controls (n = 40)
were included in January to March 2003, completed diary cards on symptom and
medication use during the relevant seasons 2003, and were examined at follow up
in autumn 2003. Allergy: positive SPT and symptoms > or = seven diary days.
RESULTS: Eleven AS subjects (birch: n = 10) subsequently developed allergic
symptoms, yet nine admitted, at follow up, to have had symptoms before inclusion,
or even denied pollen-related symptoms despite a significant diary. Compared with
AS subjects sensitized to grass pollen, AS subjects sensitized to birch pollen
had significantly larger skin prick reactions and more often and severe pollen
symptoms. CONCLUSION: In the context of double-sensitization, retrospective
symptom assessment is not a reliable method for ensuring that subjects
classified, as asymptomatically skin sensitized, are truly, asymptomatic. This
matter should be considered in studies on allergy development.

PMID: 17362247 [PubMed - indexed for MEDLINE]

366: Clin Exp Allergy. 2007 Mar;37(3):441-50.

Generation of a low immunoglobulin E-binding mutant of the timothy grass pollen
major allergen Phl p 5a.

Wald M, Kahlert H, Weber B, Jankovic M, Keller W, Cromwell O, Nandy A, Fiebig H.

Allergopharma J. Ganzer KG, Research & Development, Reinbek, Germany.
marin.wald@allergopharma.de

BACKGROUND: Immunotherapy of grass pollen allergy is currently based on the
administration of pollen extracts containing natural allergens. Specifically
designed recombinant allergens with reduced IgE reactivity could be used in safer
and more efficacious future therapy concepts. OBJECTIVES: This study aimed to
generate hypoallergenic variants of the timothy grass major allergen Phl p 5a as 
candidates for allergen-specific immunotherapy. METHODS: Three deletion mutants
were produced in Escherichia coli and subsequently purified. The overall
IgE-binding capacity of the mutants was compared with the recombinant wild-type
allergen by membrane blot and IgE-inhibition assays. The capacity for effector
cell activation was determined in basophil activation assays. T cell
proliferation assays with allergen-specific T cell lines were performed to
confirm the retention of T cell reactivity. Structural properties were
characterized by circular dichroism analysis and homogeneity by native
isoelectric focusing. The deletion sites were mapped on homology models
comprising the N- and C-terminal halves of Phl p 5a, respectively. RESULTS: The
double-deletion mutant rPhl p 5a Delta(94-113, 175-198) showed strongly
diminished IgE binding in membrane blot and IgE-inhibition assays. Both deletions
affect predominantly alpha-helical regions located in the N- and C-terminal
halves of Phl p 5a, respectively. Whereas deletion of Delta175-198 alone was
sufficient to cause a large reduction of the IgE reactivity in a subgroup of
allergic sera, only the combination of both deletions was highly effective for
all the sera tested. rPhl p 5a Delta(94-113, 175-198) consistently showed at
least an 11.5-fold reduced capacity to activate basophils compared with the
recombinant wild-type molecule, and the T cell proliferation assays demonstrated 
retention of T cell reactivity. CONCLUSION: The mutant rPhl p 5a Delta(94-113,
175-198) fulfils the basic requirements for a hypoallergenic molecule suitable
for a future immunotherapy of grass pollen allergy; it offers substantially
reduced IgE binding and maintained T cell reactivity.

PMID: 17359394 [PubMed - indexed for MEDLINE]

367: Clin Exp Allergy. 2007 Mar;37(3):400-14.

Inhibition of the histamine-induced weal and flare response: a valid surrogate
measure for antihistamine clinical efficacy?

Devillier P, Bousquet J.

Hôpital Foch, Suresnes, France. p.devillier@hopital-foch.org

Histamine plays a central role in allergic responses. Inhibition of the weal and 
flare response to histamine is a traditional pharmacodynamic tool to measure the 
activity of H(1)-receptor antagonists. The time course and duration of cutaneous 
weal and flare inhibition are often used as surrogate measures of clinical
efficacy. Pharmacodynamic differences among antihistamines are often interpreted 
to indicate differences in clinical efficacy. A systematic review of literature
from 1980 to 2006 regarding the histamine induced weal and flare was undertaken. 
Search terms included 'histamine', 'skin test', 'weal', 'flare', and
'antihistamine'; retrieved articles were searched for relevant studies not
identified initially. Data from human studies on the inhibition of the weal and
flare by second-generation antihistamines were extracted and assessed. A
literature search from 1980 to 2006 was undertaken for comparative studies of
second-generation antihistamines in the clinical settings of allergic rhinitis
(AR) and chronic idiopathic urticaria; data extracted from these studies
underwent systematic review. Differences were noted among second-generation
antihistamines in terms of their ability to inhibit the histamine-induced weal
and flare. Corresponding differences in terms of clinical efficacy in AR and
chronic urticaria were not identified following a systematic review. The reasons 
for the disconnect between pharmacodynamic effects and clinical efficacy may
include differences between the route and concentration of histamine, the
involvement of mediators other than histamine in the allergic response, and the
short time course of pharmacodynamic studies. The histamine-induced weal and
flare response is a pharmacodynamic test that should not be used to compare the
clinical efficacy of different antihistamines, and is not an adequate alternative
to clinical end-point assessments in AR or chronic idiopathic urticaria.

Publication Types: 
    Review

PMID: 17359390 [PubMed - indexed for MEDLINE]

368: Int Arch Allergy Immunol. 2007;143(4):269-75. Epub 2007 Mar 12.

Analysis of the relationship between pollinosis and date of birth in Switzerland.

Graf N, Johansen P, Schindler C, Wuthrich B, Ackermann-Liebrich U, Gassner M,
Kundig TM, Senti G.

Unit for Experimental Immunotherapy, Department of Dermatology, University
Hospital of Zurich, Zurich, Switzerland.

BACKGROUND: The first months of life may represent a vulnerable period in the
development of atopic diseases. The objective of this study was to examine the
relationship between the month of birth and the development of birch and grass
pollen allergy in the Swiss population. METHODS: Data from the Swiss Study on Air
Pollution and Lung Diseases in Adults(SAPALDIA) as well as the Swiss Study on
Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution and
Climate (SCARPOL) were used. A logistic regression was calculated with grass and 
birch pollen sensitisation (positive skin prick test) or allergy (positive skin
prick test and allergic symptoms) as outcome variables and the season of birth as
predictor variable. The contribution of the season of birth on pollinosis was
further adjusted for well-known risk factors and potential confounding variables.
RESULTS: The logistic regression revealed a significant effect of the season of
birth on birch pollen sensitisation and an effect of borderline significance on
birch pollen allergy, i.e. subjects born in the pollen season (March to April)
showed an increased risk of being sensitised/allergic to birch pollen. The
results also indicated a tendency towards an increased risk for subjects born in 
the grass pollen season (May to June) to develop grass pollen allergy.
CONCLUSION: Our results support the hypothesis that the first few months of life 
constitute a sensitive period, during which inhalative exposure to certain
allergens may predispose to the subsequent development of atopic respiratory
disease. Copyright 2007 S. Karger AG, Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17351326 [PubMed - indexed for MEDLINE]

369: Biochim Biophys Acta. 2007 Jun;1771(6):781-91. Epub 2007 Jan 8.

Plant non-specific lipid transfer proteins: an interface between plant defence
and human allergy.

Salcedo G, Sánchez-Monge R, Barber D, Díaz-Perales A.

Unidad de Bioquímica, Departamento de Biotecnología, E.T.S. Ingenieros Agrónomos,
UPM, Ciudad Universitaria, 28040-Madrid, Spain. gabriel.salcedo@upm.es

Plant non-specific LTPs (lipid transfer proteins) form a protein family of basic 
polypeptides of 9 kDa ubiquitously distributed throughout the plant kingdom. The 
members of this family are located extracellularly, usually associated with plant
cell walls, and possess a broad lipid-binding specificity closely related to
their three-dimensional structure. The nsLTP fold is characterized by a compact
domain composed of 4 alpha-helices, firmly held by a network of 4 conserved
disulphide bridges. This fold presents a large internal tunnel-like cavity, which
can accommodate different types of lipids. nsLTPs are involved in plant defence
mechanisms against phytopathogenic bacteria and fungi, and, possibly, in the
assembly of hydrophobic protective layers of surface polymers, such as cutin. In 
addition, several members of the nsLTP family have been identified as relevant
allergens in plant foods and pollens. Their high resistance to both heat
treatment and digestive proteolytic attack has been related with the induction by
these allergens of severe symptoms in many patients. Therefore, they are probably
primary sensitizers by the oral route. nsLTP sensitization shows an unexpected
pattern throughout Europe, with a high prevalence in the Mediterranean area, but 
a low incidence in Northern and Central European countries.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17349819 [PubMed - indexed for MEDLINE]

370: Int J Pediatr Otorhinolaryngol. 2007 Jun;71(6):843-9. Epub 2007 Mar 7.

The effect of regular versus on-demand desloratadine treatment in children with
allergic rhinitis.

Dizdar EA, Sekerel BE, Keskin O, Kalayci O, Adalioglu G, Dogan C, Tuncer A.

Hacettepe University School of Medicine, Pediatric Allergy and Asthma Unit, 06100
Ankara, Turkey. drevrim@yahoo.com

OBJECTIVE: Desloratadine is a potent antihistamine. Whether regular or on-demand 
use of desloratadine influences its therapeutic efficacy in allergic rhinitis is 
unknown. The aim of the study was to compare the clinical efficacy and the
anti-inflammatory activity of regularly administered desloratadine to its
on-demand use in children with allergic rhinitis due to pollen allergy. METHODS: 
Thirty-seven patients with allergic rhinitis with or without mild intermittent
asthma were enrolled in a prospective parallel group study. Patients were treated
with desloratadine regularly or on-demand during pollen season. Rescue
medications and symptom scores were recorded on a diary card. Nasal flow rate and
inflammatory markers were recorded, and methacholine (Mch) challenge test was
administered before and within the pollen season. RESULTS: Though symptoms were
lower in the evening than in the morning (p<0.001), there was no difference
between the two groups. There was no difference between the groups with respect
to medication score except that the salbutamol use was lower in the regular
treatment group during the fourth week (p=0.032) in the pollen season. Nasal flow
rate and inflammatory markers failed to show any difference between the groups. A
significant reduction in PC20 values (provocative concentration of Mch causing a 
20% fall in FEV(1)) was observed in regular (p=0.016) and on-demand (p=0.005)
treatment groups compared to the pre-season measurements. The number of children 
with a PC20 below 8 mg/ml increased significantly in the on-demand group.
CONCLUSION: Our study demonstrates that on-demand use of desloratadine during the
pollen season is clinically as effective as regular treatment. However, regular
treatment may provide better control of lower airway symptoms and airway
reactivity.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17346807 [PubMed - indexed for MEDLINE]

371: J Photochem Photobiol B. 2007 Apr 2;87(1):58-65. Epub 2007 Jan 19.

Ultraviolet light phototherapy for allergic rhinitis.

Kemény L, Koreck A.

Department of Dermatology and Allergology, University of Szeged, Koranyi fasor 6,
6720 Szeged, Hungary. kl@mail.derma.szote.u-szeged.hu

Phototherapy has a profound immunosuppressive effect and is widely used for the
treatment of immune mediated skin diseases. Phototherapy is able to inhibit
immediate type hypersensitivity reaction in the skin. Intranasal phototherapy is 
a new approach for treatment of allergic rhinitis. In two open studies, 308 nm
excimer laser and topical PUVA therapy efficiently inhibited clinical symptoms of
allergic rhinitis. In a randomized, double-blind study combined low dose UVB, low
dose UVA and visible light proved to be effective in reducing symptom scores for 
sneezing, rhinorrhea, nasal itching and the total nasal score in ragweed allergic
patients. Mechanism of action of phototherapy is complex, it reduces the antigen 
presenting capacity of dendritic cells, induces apoptosis of immune cells and
inhibits synthesis and release of pro-inflammatory mediator from several cell
types. Therefore, intranasal phototherapy may represent an alternative treatment 
of allergic rhinitis and other inflammatory and immune mediated mucosal diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17329119 [PubMed - indexed for MEDLINE]

372: Respir Res. 2007 Feb 28;8:17.

Expression of Toll-like receptor 9 in nose, peripheral blood and bone marrow
during symptomatic allergic rhinitis.

Fransson M, Benson M, Erjefält JS, Jansson L, Uddman R, Björnsson S, Cardell LO, 
Adner M.

Laboratory of Clinical and Experimental Allergy Research, Department of
Oto-Rhino-Laryngology, Malmö University Hospital, Lund University, Malmö, Sweden.
Mattias.Fransson@med.lu.se

BACKGROUND: Allergic rhinitis is an inflammatory disease of the upper airway
mucosa that also affects leukocytes in bone marrow and peripheral blood.
Toll-like receptor 9 (TLR9) is a receptor for unmethylated CpG dinucleotides
found in bacterial and viral DNA. The present study was designed to examine the
expression of TLR9 in the nasal mucosa and in leukocytes derived from different
cellular compartments during symptomatic allergic rhinitis. METHODS: The study
was based on 32 patients with seasonal allergic rhinitis and 18 healthy subjects,
serving as controls. Nasal biopsies were obtained before and after allergen
challenge. Bone marrow, peripheral blood and nasal lavage fluid were sampled
outside and during pollen season. The expression of TLR9 in tissues and cells was
analyzed using immunohistochemistry and flow cytometry, respectively. RESULTS:
TLR9 was found in several cell types in the nasal mucosa and in different
leukocyte subpopulations derived from bone marrow, peripheral blood and nasal
lavage fluid. The leukocyte expression was generally higher in bone marrow than
in peripheral blood, and not affected by symptomatic allergic rhinitis.
CONCLUSION: The widespread expression of TLR9 in the nasal mucosa along with its 
rich representation in leukocytes in different compartments, demonstrate the
possibility for cells involved in allergic airway inflammation to directly
interact with bacterial and viral DNA.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17328813 [PubMed - indexed for MEDLINE]

373: J Investig Allergol Clin Immunol. 2007;17(1):39-47.

Prevalence of Artemisia species pollinosis in western Poland: impact of climate
change on aerobiological trends, 1995-2004.

Stach A, García-Mozo H, Prieto-Baena JC, Czarnecka-Operacz M, Jenerowicz D, Silny
W, Galán C.

Laboratory of Aeropalynology, Adam Mickiewicz University, Poznan, Poland.

BACKGROUND: Artemisia species pollen represents a major cause of allergy in
Central Europe. Variations in the pollen season, the influence of climate
variables and the prevalence of pollinosis to it were analyzed in Poznan, in
western Poland between 1995 and 2004. METHODS: A Hirst volumetric spore trap was 
used for atmospheric sampling. Pollination date trend analysis and Spearman
correlation tests were performed. Skin prick tests (SPT) and allergen specific
immunoglobulin (lg)E antibody measurements were performed in 676 and 524
patients, respectively. RESULTS: The Artemisia species pollen season grew longer 
due to a clear advance in the starting day and only a slightly earlier end point;
the peak day also came slightly earlier. Rainfall in the first fortnight of July 
highly influenced pollen season severity. Temperature was directly correlated
with daily Artemisia species pollen levels; relative humidity was inversely
correlated. Twelve percent of patients had a positive SPT reaction to Artemisia
species. Their symptoms were rhinitis and conjunctivitis (15%), atopic dermatitis
(15%), chronic urticaria (14.3%), bronchial asthma (2.4%), and facial and
disseminated dermatitis (1.3%). Elevated specific IgE concentrations were
detected in the sera of 10.1% of patients. CONCLUSIONS: Artemisia species pollen 
is an important cause of pollinosis in western Poland. Pollen season intensity is
highly influenced by rainfall in the previous weeks. Trends towards earlier
season starts and longer duration, possibly caused by climate change, may have an
impact on the allergic population.

Publication Types: 
    Historical Article

PMID: 17323862 [PubMed - indexed for MEDLINE]

374: J Allergy Clin Immunol. 2007 Apr;119(4):892-8. Epub 2007 Feb 23.

Sublingual immunotherapy with grass pollen is not effective in symptomatic
youngsters in primary care.

Röder E, Berger MY, Hop WC, Bernsen RM, de Groot H, Gerth van Wijk R.

Section of Allergology, Department of Internal Medicine, Erasmus MC Rotterdam,
The Netherlands.

BACKGROUND: Sublingual immunotherapy (SLIT) is considered safer and more
convenient than subcutaneous therapy and therefore has been proposed as
especially suitable for children and in primary care. Most efficacy studies in
children lack power to be conclusive, and all have been performed in referral
centers. OBJECTIVE: To investigate the efficacy of SLIT with grass pollen
allergen in children and adolescents with rhinoconjunctivitis in a primary care
setting. METHODS: Youngsters aged 6-18 years with hay fever were enrolled from
general practices and randomly assigned to receive placebo or grass pollen mix
for 2 years. The primary outcome was the mean daily total symptom score (scale
0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and
itching eyes during the months May-August of the second treatment year. RESULTS: 
Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91
verum, 77 placebo). The mean daily total symptom score did not differ between
participants allocated to verum and those allocated to placebo (difference for
verum minus placebo: -0.08, 95%CI, -0.66-0.50; P = .78). No differences were
found for rescue medication-free days, disease-specific quality of life, and
overall evaluation of the treatment effect. Local side effects were more frequent
in the verum group (39% vs 17% of participants; P = .001). CONCLUSION: Sublingual
immunotherapy with grass pollen in a primary care setting is not effective in
children and adolescents. CLINICAL IMPLICATIONS: Currently, SLIT cannot be
recommended for general practitioners as a therapeutic modality in youngsters
with grass pollen allergy.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17321581 [PubMed - indexed for MEDLINE]

375: Croat Med J. 2007 Feb;48(1):68-75.

Allergic rhinitis and asthma in southern Croatia: impact of sensitization to
Ambrosia elatior.

Cvitanović S, Znaor L, Kanceljak-Macan B, Macan J, Gudelj I, Grbić D.

Department of Pulmonary Diseases, Split University Hospital, Split, Croatia.

AIM: To identify pollen types in southern Croatia and investigate the impact of
sensitization to Ambrosia elatior (A. elatior) on symptoms and treatment of
patients with seasonal allergic rhinitis and/or asthma. METHODS: The study
recruited 120 patients from Split-Dalmatian County with seasonal rhinitis and
asthma symptoms and positive skin prick test to one or more common inhaled
allergens. Patients with positive skin prick test and increased specific IgE to
A. elatior (n=56) were included in the follow-up study during the A. elatior
pollen season. Rhinitis and asthma symptoms were scored and drug treatment
recorded using standardized questionnaires. Also, forced vital capacity (FVC),
forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and
eosinophil count in peripheral blood were measured. Type and pollen concentration
of A. elatior in the air over the nine-week pollen season were determined on the 
glass slides using the gravimetric method. The results were expressed as the
proportion of A. elatior pollen in the total pollen. RESULTS: Fifty-six of 120
patients (46.7%) were sensitized to A. elatior. Its proportion in total pollen
peaked to 12% in the first week of September. Forty-one patients who completed
the follow-up study showed a significantly higher score of symptoms during this
peak period than in the beginning of the pollen season for seasonal allergic
rhinitis (median +/-interquartile range, 50+/-11 vs 7+/-4; P<.001) and for
seasonal allergic asthma (12+/-2 vs 0+/-0; P<.001). CONCLUSION: A. elatior is an 
important cause of seasonal allergic rhinitis and asthma and must be included in 
the routine diagnostic procedures in southern Croatia.

PMID: 17309141 [PubMed - indexed for MEDLINE]

376: Ann Allergy Asthma Immunol. 2007 Feb;98(2):134-8.

Evaluation of visual analog scales for the assessment of symptom severity in
allergic rhinoconjunctivitis.

Senti G, Vavricka BM, Graf N, Johansen P, Wüthrich B, Kündig TM.

Unit for Experimental Immunotherapy, Department of Dermatology, University of
Zurich, Zurich, Switzerland. gabriela.senti@usz.ch

BACKGROUND: The severity of rhinoconjunctivitis is typically monitored by means
of nasal provocation tests (NPTs), where the nasally applied allergens trigger
symptoms that are recorded using a scoring system. However, NPTs are
time-consuming and stressful for patients; therefore, recording of symptoms
during natural allergen exposure on visual analog scales (VASs) is increasingly
being used in clinical trials. OBJECTIVES: To evaluate (1) the correlation
between VAS symptom recording by patients during natural allergen exposure and
symptom scoring by the physician during the NPT and (2) the possibility of
replacing the more laborious and distressing allergen provocation tests with the 
more patient-friendly VAS. METHODS: A total of 119 patients with allergic
rhinitis due to grass pollen were enrolled in the study between June 20, 2001,
and January 31, 2002. Patients reported the severity of different seasonal
symptoms on a VAS and underwent a NPT. RESULTS: No significant correlations
between VAS and NPT scores were found. However, all the correlation coefficients 
between the symptom scores from the NPT and the corresponding symptom scores from
the VAS were much higher for the female than the male subgroup. CONCLUSIONS: The 
VAS does not correlate with the NPT and, therefore, cannot replace the NPT.
However, the result may suggest it worthwhile to explore the role of sex in the
perception of allergy symptoms.

Publication Types: 
    Clinical Trial, Phase I
    Comparative Study

PMID: 17304879 [PubMed - indexed for MEDLINE]

377: Iran J Allergy Asthma Immunol. 2007 Mar;6(1):27-31.

The evaluation of new classification of Allergic Rhinitis in patients referred to
a clinic in the city of Shiraz.

Alyasin S, Amin R.

Department of Clinical Immunology and Allergy, Clinical Immunology and Allergy
Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran.
alyasins@sums.ac.ir

Allergic rhinitis is the most common cause of allergic diseases. The recent
guidelines of Allergic Rhinitis and its Impact on Asthma (ARIA) group, classified
it to intermittent (less than 4 days per week and for less than 4 weeks) and
persistent (more than 4 days per week or lasting more than 4 weeks regardless of 
the number of days per week). The present study evaluates the patients with ARIA 
classification. The patients referred to Motahhari Clinic (Shiraz, Iran) were
evaluated. Age, sex, seasonal or perennial, intermittent or persistent type,
duration, sneezer or blocker, diurnal change and presence of allergic
conjunctivitis were recorded. The patients who had one or more symptoms of;
impairment of sleep, daily activity or work in school or troublesome symptoms had
moderate to severe disease and those who did not have these problems have mild
disease. The information of 96 patients (46 male and 50 female) were analysed
(mean age+/-SD: 24.45+/-10.37 years). The mean duration of disease was
4.26+/-4.12 years, was more in female (P<0.05). Seasonal allergic rhinitis was
present in 49 (52%) patients; 30 male, 19 female (P=0.007), perennial in 15
(16%), 1 male, 14 female and mixed type in 29 (30%); 11 male, 18 female. Mild
intermittent rhinitis was diagnosed in only 2 (2%) patients, 1 male and 1 female,
mild persistent rhinitis in 23 (24%); male 11, female 12; moderate/severe
intermittent rhinitis in 4 (4%); 3 male, 1 female; and moderate/severe persistent
rhinitis in 56 (58%); 22 male, 34 female (P<0.05). Fifty-seven percent were more 
sneezer and 36% were more blocker type, sneezers suffered more in days and others
more at nights. Others were both sneezer and blocker. Sixty percent had allergic 
conjunctivitis too, 76% of them were moderate/severe persistent, and 85% were in 
seasonal or mixed groups. Eleven patients (12%), in persistent group, had history
of asthma. Family history of allergic rhinitis and asthma was found in 53% and in
25% of patients, respectively. According to new guidelines for classification of 
allergic rhinitis, most of the patients are moderate to severe types. The
classification of allergic rhinitis to seasonal and perennial disease is not
proportional to intermittent and persistent types of classification. .

PMID: 17303926 [PubMed - indexed for MEDLINE]

378: Clin Exp Immunol. 2007 Mar;147(3):491-6.

Tolerance and immunological changes of chemically modified allergen vaccine of
Parietaria judaica in accelerated schedules.

Asturias JA, Ferrer A, Arilla MC, Andreu C, Madariaga B, Martínez A.

Research & Development Department, Bial-Arístegui, Bilbao, Spain.
juan.asturias@bial.com

The physicochemical modification of allergen vaccines provides a chance for
administering higher doses in a shorter period of time. We sought to assess the
safety and immunological changes of using a biologically standardized and
modified Parietaria judaica pollen extract in accelerated schedules. Two
accelerated schedules were tested in 45 P. judaica-allergic patients: 20 patients
reached the maximum dose after two visits using two different concentrations and 
25 patients reached the maximum dose after only one visit with two injections of 
the maximum concentration vial. The tolerance was assessed by recording all side 
effects related with immunotherapy. Specific antibody levels against native
extract and rPar j 2 allergen were evaluated at the beginning and the end of the 
study. Allergenic potency determined by enzyme allergosorbent test (EAST)
inhibition and skin prick test showed that modified P. judaica pollen had a 99.9%
less allergenicity than native extract. After 650 doses administered, two
clinically irrelevant local reactions (diameter<0 x 5 cm) and no systemic
reactions were registered. Significant increases in allergen-specific IgG4 and
IgG against P. judaica extract and rPar j 2 and significant decrease of specific 
IgE against Par j 2 were observed. The modified extract of P. judaica is safe to 
treat sensitive patients, even at accelerated regimens, and induces significant
immunological changes.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17302898 [PubMed - indexed for MEDLINE]

379: Life Sci. 2007 Mar 20;80(15):1388-94. Epub 2007 Jan 23.

Establishment of an allergic rhinitis model in mice for the evaluation of nasal
symptoms.

Tsunematsu M, Yamaji T, Kozutsumi D, Murakami R, Kimura S, Kino K.

Research and Development Center, Division of Research and Development, Meiji
Dailies Corporation, 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
MASAKO_TSUNEMATSU@MEIJI-MILK.COM

The purpose of our study was to establish a new model of allergic rhinitis in
mice, eliciting symptoms such as sneezing, infiltration of eosinophils into the
nasal mucosa, and antigen-specific IgE production. One of the major human T-cell 
epitopes in Cry j 1, an allergen of Japanese cedar pollen, is also a major murine
T-cell epitope in B10.S mice. Thus we tried to establish an allergic rhinitis
model in B10.S mice with Cry j 1 as the antigen. We sensitized B10.S mice
subcutaneously with Cry j 1/alum three times at intervals of 1 week. Five weeks
after the final sensitization, we challenged the mice by instilling Cry j 1
intranasally from the day after intranasal histamine pretreatment. Soon after, we
counted the number of sneezes. We then evaluated the infiltration of eosinophils 
into the nasal tissues and also measured the serum levels of antigen-specific IgE
antibody. In addition, we confirmed the effects of ketotifen fumarate and
dexamethasone hydrochloride on these animals. In Cry j 1-sensitized B10.S mice,
sneezes, eosinophil peroxidase (EPO) activity in nasal tissues, and Cry j
1-specific IgE clearly increased after intranasal histamine pretreatment and 5
days of continuous intranasal Cry j 1 challenge. Both ketotifen and dexamethasone
inhibited the increase in sneezing, and dexamethasone also inhibited EPO activity
and Cry j 1-specific IgE. Thus we succeeded in establishing a new model of
allergic rhinitis in Cry j 1-sensitized B10.S mice, which exhibited sneezing,
eosinophil infiltration into the nasal mucosa, and Cry j 1-specific IgE
production.

PMID: 17300813 [PubMed - indexed for MEDLINE]

380: Headache. 2007 Feb;47(2):204-12.

Is headache related to asthma, hay fever, and chronic bronchitis? The Head-HUNT
Study.

Aamodt AH, Stovner LJ, Langhammer A, Hagen K, Zwart JA.

Norwegian National Headache Centre, Trondheim University Hospital, Norway.

OBJECTIVES: To examine the relationship between migraine and nonmigrainous
headache and asthma, hay fever, and chronic bronchitis in a large cross-sectional
population-based study. BACKGROUND: Associations between prevalence of migraine
and asthma or allergy have been demonstrated in clinic-based and epidemiologic
studies whereas studies on chronic bronchitis are scarce. METHODS: A total of
51,383 subjects completed a headache questionnaire and constituted the
"Head-HUNT" Study. Of these 50,401 (98.1%) answered the questions about asthma
and chronic bronchitis, and 47,029 (91.5%) answered the question about hay fever.
Associations were assessed in multivariate analyses, estimating prevalence odds
ratios (ORs) with 95% confidence intervals (CI). RESULTS: Both migraine and
nonmigrainous headache were approximately 1.5 times more likely among those with 
current asthma, asthma related symptoms, hay fever, and chronic bronchitis than
those without. The association increased with increasing headache frequency.
CONCLUSIONS: This large questionnaire-based study confirms that migraine and
other headaches are associated with respiratory and allergic disorders. The
magnitude of the association between headache and asthma, hay fever, and chronic 
bronchitis tended to be in the same order. Headache frequency seems to have a
greater impact on the association with respiratory or allergic conditions than
headache diagnoses. Whether it is a causal relationship is uncertain, but the
results underline the importance of considering comorbid disorders among patients
with frequent headache.

PMID: 17300360 [PubMed - indexed for MEDLINE]

381: J Appl Toxicol. 2007 Jul-Aug;27(4):399-409.

Pollinex Quattro Ragweed: safety evaluation of a new allergy vaccine adjuvanted
with monophosphoryl lipid A (MPL) for the treatment of ragweed pollen allergy.

Baldrick P, Richardson D, Woroniecki SR, Lees B.

Scientific and Regulatory Consulting, Covance Laboratories Ltd, Otley Road,
Harrogate HG3 1PY, UK.

A novel allergy vaccine (Pollinex Quattro Ragweed) has been developed for the
prevention or relief of allergic symptoms caused by pollen from Ambrosia spp.
(ragweed). An extract from the pollen (chemically modified by glutaraldehyde) is 
adsorbed onto l-tyrosine with addition of the immunostimulatory adjuvant,
monophosphoryl lipid A (MPL). A specific preclinical safety testing strategy was 
developed to support clinical use and comprised reference to preclinical data
available for the marketed non-MPL adjuvanted form of the ragweed vaccine
(Pollinex R) and a new repeat dose toxicity study in the rat. Studies with
Pollinex R comprised single dose subcutaneous toxicity studies in mice and rats, 
repeat dose (10 injections over 20 days) parenteral toxicity studies in rats and 
dogs, an in vitro gene mutation assay along with single and multiple injection
local tolerance studies in rats and dogs. The repeat dose subcutaneous toxicity
study with Pollinex Quattro Ragweed involved seven injections over 3 weeks (which
was more aggressive than the four weekly doses used in the clinic) with dose
levels of up to 0.5 ml per animal used. Overall, the product showed no
toxicological findings of significance at levels greatly in excess of those
proposed for clinical use. As is a feature with vaccination, some dose site
irritation was seen. Copyright (c) 2007 John Wiley & Sons, Ltd.

PMID: 17299813 [PubMed - indexed for MEDLINE]

382: Allergy. 2007 Feb;62(2):178-83.

Inverse relation between nasal fluid Clara Cell Protein 16 levels and symptoms
and signs of rhinitis in allergen-challenged patients with intermittent allergic 
rhinitis.

Benson M, Fransson M, Martinsson T, Naluai AT, Uddman R, Cardell LO.

Queen Silvia Children's Hospital, Gothenburg, Sweden.

BACKGROUND: Decreased levels of the anti-inflammatory Clara Cell Protein 16
(CC16) are found in intermittent allergic rhinitis (IAR) and asthma. In asthma
this decrease has been associated with hyperreactivity and the A38G single
nucleotide polymorphism (SNP). The aim of this study was to examine if IAR is
associated with signs and symptoms of rhinitis and the A38G SNP. METHODS: Nasal
fluid CC16 was analyzed in 20 patients with IAR before allergen challenge and 1
and 6 h after challenge, and from 28 healthy controls. The A38G SNP was analyzed 
in 80 patients with IAR and 106 controls. Nasal biopsies were obtained from three
subjects in each group for immunohistochemical analysis of CC16. RESULTS: In the 
allergen-challenged patients symptoms and rhinoscopic signs of rhinitis increased
after 1 h and normalized after 6 h. In contrast, nasal fluid CC16 decreased 1 h
after allergen challenge and returned to baseline after 6 h. Nasal fluid CC16
levels did not differ from controls before and 6 h after challenge.
Immunohistochemical investigation showed intense CC16 staining in the nasal
epithelium of both patients before season and healthy controls, but weak staining
in symptomatic patients during season. No significant association between the
A38G SNP and IAR was found. CONCLUSION: There was an inverse relation between
nasal fluid CC16 levels and symptoms and signs of rhinitis in allergen-challenged
patients with IAR. However, there was no association between IAR and the A38G
SNP.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17298427 [PubMed - indexed for MEDLINE]

383: Arch Environ Occup Health. 2005 Sep-Oct;60(5):243-7.

Major lymphocyte populations and T-cell expression of ICAM-1 and L-selectin
adhesion molecules in Kuwaitis with asthma and rhinitis.

Arifhodzic NA, Mahmoud FF, Abul HT, Haines DD, Al-Dowaisan AR, Ammar IM, Novotny 
L, Wise JA.

Al-Rashed Allergy Center, Sabah Hospital, Kuwait.

The authors evaluate major immunologic features of asthma and allergies in a
Kuwaiti population. They analyzed peripheral venous blood from 17 asthmatic and
17 healthy long-term residents of Kuwait by using two-color flow cytometry for
major lymphocyte subpopulations; they also evaluated 10 healthy individuals who
had recently arrived in Kuwait. Relative to healthy subjects, asthmatics
exhibited increased percentages of T+ NK cells (p < .01), T-helper cells (p <
.05), T-cytotoxic and NK cells for both total numbers (p < .01-.001) and
percentages (p < .05-.01), and increased percentages of T cells expressing CD54
(ICAM-1; p < .001) and CD62 (L-selectin; p < .01). However, B cells were present 
at significantly lower levels in asthmatics, both in total numbers (p < .05) and 
percentages (p < .01). In comparison with healthy individuals who had recently
arrived in Kuwait, healthy long-term residents exhibited elevated numbers of
pan-T cells (p < .01) and T-helper cells (p < .05). These results help establish 
immunological parameters for asthma and allergies in Kuwaiti populations.

Publication Types: 
    Comparative Study

PMID: 17290844 [PubMed - indexed for MEDLINE]

384: Int Arch Allergy Immunol. 2007;143(3):185-9. Epub 2007 Feb 6.

An observational study on outgrowing food allergy during non-birch
pollen-specific, subcutaneous immunotherapy.

Alonso R, Enrique E, Pineda F, Basagaña M, San Miguel-Moncín MM, Bartra J,
Palacios R, Cisteró-Bahíma A.

Allergy Department, Institut Universitari Dexeus, Universitat Autònoma de
Barcelona, Barcelona, Spain.

BACKGROUND: Birch pollen-specific immunotherapy (SIT) decreases allergy to foods 
containing birch pollen-homologous allergens. Cross-reactivity was also observed 
between plane tree pollen and some vegetable foods. OBJECTIVE: The aim of this
study was to evaluate the outgrowing of food allergy by patients suffering from
vegetable food allergy associated with plane tree pollinosis (rhinoconjunctivitis
and/or asthma) during plane tree pollen SIT. METHODS: An observational and
prospective study was conducted in 16 adult patients suffering from vegetable
food allergy (hazelnut, walnut, lettuce, peach and cherry) and from plane tree
pollinosis receiving plane tree pollen SIT for 1 year. Open oral challenges with 
the implicated food were performed before and after SIT. Blood samples were drawn
for measurement of pollen- and food-specific IgE and IgG4 before and after
treatment. RESULTS: Plane tree SIT resulted in a significant decrease in food
allergy, since the mean food quantity provoking objective symptoms increased from
2.19 to 13.74 g (p < 0.05), and 6 of the 11 patients tolerated the highest level 
(25 g) of the challenged food after plane tree SIT. Laboratory data also showed a
decrease in IgE levels and an increase in IgG4 levels after immunotherapy.
CONCLUSION: SIT with plane tree pollen has a positive impact on food allergy in
plane tree pollen-allergic subjects.

PMID: 17284927 [PubMed - indexed for MEDLINE]

385: Int Arch Allergy Immunol. 2007;143(3):163-9. Epub 2007 Feb 5.

ARIA (Allergic Rhinitis and Its Impact on Asthma) classification of allergic
rhinitis severity in clinical practice in France.

Bousquet PJ, Bousquet-Rouanet L, Co Minh HB, Urbinelli R, Allaert FA, Demoly P.

Exploration des Allergies, Maladies Respiratoires, INSERM U454-IFR3, Hôpital
Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France.

BACKGROUND: The Allergic Rhinitis and Its Impact on Asthma (ARIA) workshop
proposes a classification of allergic rhinitis severity. It does not take into
account impairment in quality of life and treatment should be adapted
accordingly. METHODS: Two cross-sectional surveys were designed:a spring survey, 
for which 1,321 practitioners enrolled 3,026 patients consulting for seasonal
allergic rhinitis and an autumn-winter survey, for which 1,346 practitioners
enrolled 3,507 patients consulting for perennial allergic rhinitis. Simple
quality of life parameters were included and logistic regressions were performed 
in order to assess the impairment of quality of life. RESULTS: The majority of
the patients were experiencing an impairment on their quality of life (92.2%).
Except for cough, these patients had significantly more nasal, lung and ocular
symptoms. In a multivariate analysis, rhinorrhea, nasal itching, red eyes,
dyspnea, change in voice, fatigue and headache were correlated to impairment of
quality of life. Persistent rhinitis was associated only with subjects who
expressed difficulties in reading, and intermittent rhinitis with those who had
to blow their nose and who expressed an impact on their professional activities. 
CONCLUSIONS: The proposal of the ARIA expert panel defining the severity of
allergic rhinitis based on quality of life parameters is likely to simplify daily
physician practice.

PMID: 17284924 [PubMed - indexed for MEDLINE]

386: Int J Pediatr Otorhinolaryngol. 2007 May;71(5):713-9. Epub 2007 Feb 5.

An analysis of the incidence of adenoid hypertrophy in allergic children.

Modrzynski M, Zawisza E.

The Regional Allergology Outpatient Euromedica, 86-300 Grudziadz, Legionow 71,
Poland. mmodrzynski@interia.pl

INTRODUCTION: The adenoidectomy is the most often made operation in small
children but the reasons of adenoid hypertrophy are not completely explained.
Some researches show that in part of children, allergy can be a risk factor for
adenoid hypertrophy. The main aim of this study was the analysis of adenoid
hypertrophy in children with different allergic diseases. MATERIAL AND METHODS:
Two separate groups of children were examined. The study group consisted of 436
children between 4 and 9 years old with allergic rhinitis and/or bronchial asthma
and/or atopic dermatitis hypersensitive to house dust mites (interview, positive 
skin-prick test results). The control group consisted of 229 non-atopic children 
(negative interview and skin-prick tests) in the similar age. In the both groups 
we examined the incidence of adenoid hypertrophy and its dependence of the kind
of allergic disease, age, sex, infections, results of skin-prick test and other
sensitization. RESULTS: The probability of adenoid hypertrophy was statistically 
more significant (logistic regression analysis) only in children from the study
group with allergic rhinitis. There were no differences in adenoid hypertrophy
incidence between children with other allergic diseases and the control group.
The children from the study group with adenoid hypertrophy were more often
hypersensitive to pollen and moulds allergens than the children without adenoid
hypertrophy (chi square test). But there were no differences in the incidence of 
infection, age, sex and results of skin-prick tests. CONCLUSION: The result of
our study suggests that the chance of adenoid hypertrophy in allergic children
hypersensitive to dust mites is greater only in them with allergic rhinitis.

PMID: 17280719 [PubMed - indexed for MEDLINE]

387: Int Immunopharmacol. 2007 Mar;7(3):372-4. Epub 2006 Dec 19.

Nasal decongestion test in allergic rhinitis: definition of responder.

Ciprandi G, Cirillo I, Klersy C, Castellazzi AM, Barberi S, Marseglia GL.

Dipartimento Medicina Interna, Semeiotica Medica I- Padiglione 3, Azienda
Ospedaliera Universitaria San Martino, Largo R. Benzi 10, 16132 Genoa, Italy.

BACKGROUND: Nasal airflow, as measured by rhinomanometry, is frequently impaired 
in allergic rhinitis (AR). The decongestion test evaluates whether the
application of an intranasal vasoconstrictor drug increases nasal airflow.
OBJECTIVE: The aim of this study was to define the characteristics of
decongestion test responders. METHODS: 123 subjects (112 males and 11 females,
mean age 22.9+/-5.7 years) with AR were studied. Nasal eosinophils,
rhinomanometry, and decongestion test were assessed in all subjects. RESULTS: The
optimal cut-off for % variation of nasal airflow and nasal eosinophils >5 was =
34.4, with sensibility = 82.7% (95%CI 73.7-89.6) and specificity = 80% (95%CI
59.3-93.1). CONCLUSIONS: The clinical relevance of this study is that
non-responders may have a likely moderate-severe allergic inflammation that
should be adequately evaluated and treated.

PMID: 17276895 [PubMed - indexed for MEDLINE]

388: Immunol Allergy Clin North Am. 2007 Feb;27(1):129-39.

A rice-based edible vaccine expressing multiple T-cell epitopes to induce oral
tolerance and inhibit allergy.

Takaiwa F.

Transgenic Crop Research and Development Center, National Institute of
Agrobiological Sciences, Kannondai 2-1-2, Tsukuba, Ibaraki 305-8602, Japan.
takaiwa@nias.affrc.go.jp

Plant pollens are the most common cause of seasonal allergic disease. The number 
of patients undergoing treatment for allergies to the pollen of Japanese cedar
(major antigens, Cry j 1 and Cry j 2) has increased steadily each year. A rice
seed-based edible vaccine has been shown to be effective for treating Japanese
cedar pollinosis. Rice seeds containing the major T-cell epitopes derived from
cedar pollen allergens were orally administrated to mice before systemic
challenge with total pollen protein. Mucosal immune tolerance leading to a
reduction of allergen-specific IgE, T-cell proliferative reactions, and histamine
were induced, resulting in suppression of allergy-specific symptoms such as
sneezing. Oral seed-based peptide immunotherapy offers a safe, simple, and
cost-effective alternative to conventional allergen-specific immunotherapy using 
crude allergen extracts for treating allergic disease. A human version of rice
seed-based edible vaccine containing seven T-cell epitopes from the Cry j 1 and
Cry j 2 allergens was recently developed and is undergoing safety assessments.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17276883 [PubMed - indexed for MEDLINE]

389: Eur Ann Allergy Clin Immunol. 2006 Dec;38(10):355-60.

Efficacy and tolerability of high dose sublingual immunotherapy in patients with 
rhinoconjunctivitis.

Worm M.

Allergie-Centrum Charité, Klinik für Dermatologie und Allergologie
Universitätsmedizin Berlin, Universitätsklinikum Charité, Charite-Platz 1,
D-10117 Berlin.

In a multi-centre, randomized, double-blind, placebo-controlled clinical trial
over 3 years high dose sublingual specific immunotherapy with an extract of a
6-grass-pollen mixture showed a highly significant and clinically relevant
improvement in patients with grass pollen rhinitis/-conjunctivitis with or
without asthma and an increase in allergen specific antibodies (IgG1, IgG4)
indicating immunological efficacy. A difference of 46% in mean symptom medication
score between active and placebo group was seen. The treatment with the
sublingual solution was well tolerated. High dose sublingual immunotherapy can
therefore be considered as an efficient therapeutic option in the management of
IgE-mediated allergic airway diseases.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 17274520 [PubMed - indexed for MEDLINE]

390: Eur Ann Allergy Clin Immunol. 2006 Dec;38(10):347-50.

Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune
diabetes: focus on the choice of anti-H1 drugs.

Moneret-Vautrin DA, de Chillou C, Codreanu A.

Department of Internal Medicine - Clinical Immunology and Allergology, University
Hospital, 29 avenue du Maréchal de Lattre de Tassigny, 54035 Nancy Cedex, France.

The long QT syndrome is a rare disease. The prevalence is estimated at 1/5 000 to
1/20,000. Numerous drugs are contra-indicated because they can lengthen the QT
interval. A case of pollen allergy in an adolescent with LQTS is described. The
possibility to prescribe anti-H1 drugs is reviewed since cases of torsades de
pointe and even deaths have been reported for terfenadine and astemizole.
Diphenhydramine, orphenadrine and hydroxyzine are contra-indicated. No accidents 
and no effects on the QT interval have been published for ebastine, fexofenadine,
desloratadine and levocetirizine. These anti-H1 drugs could be used with great
care, without any association with drugs resulting in low serum potassium level. 
Azelastine eye drops have been authorized and a routine protection by inhaled
corticosteroids during the pollinic period has been advised in this adolescent
treated by betablockers.

Publication Types: 
    Case Reports

PMID: 17274518 [PubMed - indexed for MEDLINE]

391: Curr Med Res Opin. 2006 Dec;22(12):2541-8.

Identifying and managing rhinitis and its subtypes: allergic and nonallergic
components--a consensus report and materials from the Respiratory and Allergic
Disease Foundation.

Nassef M, Shapiro G, Casale TB; Respiratory and Allergic Disease Foundation.

Columbia University and New York-Presbyterian Hospital, New York, NY, USA.
mn9@columbia.edu

BACKGROUND: Rhinitis is one of the most common chronic disorders presenting to an
internal medicine, pediatric, or family practice clinician. It can greatly impact
a patient's quality of life and exerts a tremendous societal burden in terms of
both its direct and indirect costs. In practice, in treatment guidelines, and in 
the literature, discussions of rhinitis as an inflammatory (allergic) disease
often eclipse discussions of the nonallergic components, which often contribute
to, or are responsible for, a patient's disease. Recommendations for specific
diagnostic criteria and treatment options for nonallergic rhinitis are often
lacking compared with those addressing allergic rhinitis. Previous guidelines
primarily focus on allergic rhinitis and do not provide easy-to-use tools to help
primary care practitioners differentiate between, and appropriately treat, the
different types of rhinitis. Although it is often difficult and time-consuming
clinically to differentiate between the various rhinitis subtypes, this must be
done in order to select an appropriate treatment and achieve desirable outcomes. 
OBJECTIVE: We sought to develop a useful diagnostic worksheet and treatment
algorithm to help clinicians correctly identify rhinitis subtypes and provide the
appropriate therapy. METHODS: An expert multidisciplinary consensus panel,
comprising five allergy and immunology specialists and three ear, nose, and
throat specialists with expertise in the diagnosis and treatment of rhinitis, was
assembled by the Respiratory & Allergic Disease Foundation (RAD) to discuss a
practical clinical approach to rhinitis that considers both inflammatory and
noninflammatory elements of the disease. During this meeting, the panel discussed
current data and treatment recommendations as well as clinical experiences and
challenges in treating rhinitis. Materials to help simplify the diagnosis and
management of rhinitis were developed as tools to aid the healthcare
practitioner. RESULTS: A rhinitis diagnostic worksheet and treatment algorithm
were developed by the authors following the meeting, based on transcripts of the 
consensus panel's discussions. The diagnostic worksheet can be used to quickly
categorize patients as having allergic, nonallergic, or 'mixed' rhinitis using
descriptive criteria. Using the treatment algorithm as a guide, the appropriate
treatment can then be selected based on the suspected rhinitis subtype.
CONCLUSION: The use of these clinical practice tools may improve the management
of rhinitis by helping clinicians to identify both the allergic and nonallergic
components of a patient's disease and choose an appropriate treatment.

Publication Types: 
    Consensus Development Conference
    Research Support, Non-U.S. Gov't

PMID: 17265594 [PubMed - indexed for MEDLINE]

392: Am J Epidemiol. 2007 May 1;165(9):1023-30. Epub 2007 Jan 25.

Fertility rates in women with asthma, eczema, and hay fever: a general
population-based cohort study.

Tata LJ, Hubbard RB, McKeever TM, Smith CJ, Doyle P, Smeeth L, West J, Lewis SA.

Division of Epidemiology and Public Health, School of Community Health Sciences, 
University of Nottingham, Nottingham, United Kingdom. laila.tata@nottingham.ac.uk

The protective association between having older siblings and the risk of
subsequent allergic disease may be due to decreased fertility among women with
allergic disease. In this study, the authors compared fertility rates among women
with asthma, eczema, or hay fever with those in the general female population.
Computerized primary-care data from the United Kingdom were used to conduct a
cohort analysis of 491,516 women. General fertility rates and age-specific
fertility rates for 1994-2004 were estimated. Using Poisson regression, the
authors compared fertility rates among women with asthma, eczema, or hay fever
with rates in women without these diagnoses. Fertility rates were 53.0 and 52.3
livebirths per 1,000 person-years in women with and without asthma, respectively.
The fertility rate ratio for women with asthma compared with women without asthma
was 1.02 (95% confidence interval (CI): 1.00, 1.04) after adjustment for age,
smoking, body mass index, and socioeconomic status. Equivalent fertility rate
ratios for eczema and hay fever were 1.15 (95% CI: 1.13, 1.17) and 1.08 (95% CI: 
1.06, 1.10), respectively. The authors found no evidence that the fertility rates
of women with asthma, eczema, or hay fever are lower than those of women in the
general population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17255115 [PubMed - indexed for MEDLINE]

393: Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001936.

Comment in:
    Otolaryngol Head Neck Surg. 2007 Apr;136(4):511-4.

Allergen injection immunotherapy for seasonal allergic rhinitis.

Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S.

Royal Brompton Hospital, Department of Allergy and Respiratory Medicine, Imperial
College School of Medicine at the National Heart and Lung Institute, London, UK, 
SW3 6LY. m.calderon@imperial.ac.uk

BACKGROUND: Allergic rhinitis is the most common of the allergic diseases.
Despite improved understanding of the pathophysiology of allergic rhinitis and
advances in its pharmacological treatment, its prevalence has increased
worldwide. For patients whose symptoms remain uncontrolled despite medical
treatment, allergen injection immunotherapy is advised. An allergen-based
treatment may reduce symptoms, the need for medication and modify the natural
course of this disease. OBJECTIVES: To evaluate the efficacy and safety of
subcutaneous specific allergen immunotherapy, compared with placebo, for reducing
symptoms and medication requirements in seasonal allergic rhinitis patients.
SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group
Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL)
(The Cochrane Library, Issue 1 2006), MEDLINE (1950 to 2006), EMBASE (1974 to
2006), Pre-MEDLINE, KOREAMED, INDMED, LILACS, PAKMEDINET, Scisearch, mRCT and the
National Research Register. The date of the last search was February 2006.
SELECTION CRITERIA: All studies identified by the searches were assessed to
identify randomised controlled trials involving participants with symptoms of
seasonal allergic rhinitis and proven allergen sensitivity, treated with
subcutaneous allergen specific immunotherapy or corresponding placebo. DATA
COLLECTION AND ANALYSIS: Two independent authors identified all studies reporting
double-blind, placebo controlled randomised trials of specific immunotherapy in
patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Two 
authors independently performed quality assessment of studies. Data from
identified studies were abstracted onto a standard extraction sheet and
subsequently entered into RevMan 4.2.8. Analysis was performed using the
Standardised Mean Difference (SMD) method and a random-effects model; P values < 
0.05 were considered statistically significant. The primary outcome measures were
symptom scores, medication use, quality of life and adverse events. MAIN RESULTS:
We retrieved 1111 publications of which 51 satisfied our inclusion criteria. In
total there were 2871 participants (1645 active, 1226 placebo), each receiving on
average 18 injections. Duration of immunotherapy varied from three days to three 
years. Symptom score data from 15 trials were suitable for meta-analysis and
showed an overall reduction in the immunotherapy group (SMD -0.73 (95% CI -0.97
to -0.50, P < 0.00001)). Medication score data from 13 trials showed an overall
reduction in the immunotherapy group (SMD of -0.57 (95% CI -0.82 to -0.33,
p<0.00001)). Clinical interpretation of the effect size is difficult. Adrenaline 
was given in 0.13% (19 of 14085 injections) of those on active treatment and in
0.01% (1 of 8278 injections) of the placebo group for treatment of adverse
events. There were no fatalities. AUTHORS' CONCLUSIONS: This review has shown
that specific allergen injection immunotherapy in suitably selected patients with
seasonal allergic rhinitis results in a significant reduction in symptom scores
and medication use. Injection immunotherapy has a known and relatively low risk
of severe adverse events. We found no long-term consequences from adverse events.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17253469 [PubMed - indexed for MEDLINE]

394: J Hum Genet. 2007;52(2):152-8. Epub 2007 Jan 25.

Interleukin-18 and its three gene polymorphisms relating to allergic rhinitis.

Sebelova S, Izakovicova-Holla L, Stejskalova A, Schüller M, Znojil V, Vasku A.

Department of Pathophysiology, Masaryk University, 662 43 Brno, Czech Republic.
ssebelova@chello.cz

The study aimed to examine an association of three different single nucleotide
polymorphisms (SNPs) of the IL-18 gene (-607 C/A, -137 G/C and -133 C/G) on
chromosome 11q22 with allergic rhinitis (AR). Genotyping for the SNPs was
performed using 539 patients with AR and 312 healthy control volunteers.
Positivity to the skin prick test for the fungus Alternaria sp. in patients with 
AR, and IgE levels according to particular genotypes of selected SNPs, were also 
determined. There were no significant differences in the distribution of single
IL-18 alleles or genotypes between controls and AR patients. However, frequencies
of combined IL-18 genotypes arising from combinations of the three common
polymorphisms (-607, -137 and -133) were significantly different between both
groups (P = 0.009, P (corr) < 0.05, OR = 5.35, 95% CI: 1.9-15.2). There was a
marginally significant association of the IL-18-607 variant with IgE levels (P = 
0.05) in patients, but not in the case of the other SNPs. Patients allergic to
Alternaria, but not those allergic to other antigens, showed a significant
association with the IL-18-607 polymorphism (P = 0.0037, P (corr) < 0.05).
Results suggest that IL-18 gene variants may be one of the factors participating 
in the pathogenesis of AR or its intermediary phenotypes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17252172 [PubMed - indexed for MEDLINE]

395: Clin Exp Allergy. 2007 Feb;37(2):261-9.

Identification of a plane pollen lipid transfer protein (Pla a 3) and its
immunological relation to the peach lipid-transfer protein, Pru p 3.

Lauer I, Miguel-Moncin MS, Abel T, Foetisch K, Hartz C, Fortunato D,
Cistero-Bahima A, Vieths S, Scheurer S.

Department of Allergology, Paul-Ehrlich-Institut, Langen, Germany. lauir@pei.de

BACKGROUND: An association between plane tree pollen allergy and plant food
allergy has been described, but the cross-reacting allergens have not yet been
identified. The aim of this study was the identification of homologous
non-specific lipid-transfer proteins (nsLTPs) in plane pollen, and to investigate
its immunological relationship with the peach LTP, Pru p 3. METHODS: Three
different patient groups were recruited in Spain: 22 plane pollen-allergic
patients without food allergy (A), 36 plane pollen-allergic patients with peach
allergy (B) and 10 peach-allergic patients without plane pollen allergy (C).
Proteins from plane pollen extract were fractionated by ion-exchange and
reversed-phase chromatography. Further methods applied were N-terminal amino acid
sequence analysis, immunoblotting, enzyme allergosorbent test, CAP and basophil
histamine release assays. RESULTS: A 10 kDa IgE-reactive protein was purified
from plane pollen and identified as nsLTP. Pla a 3 was characterized as a minor
allergen (27.3%) in plane pollen-allergic patients without food allergy (A) and
as a major allergen in plane pollen-allergic patients with peach allergy (B)
showing a prevalence of IgE-reactivity of 63.8%. Group B contained patients
sensitized to Pru p 3 without IgE-reactivity to plane-LTP (16.6%). By contrast,
Pla a 3 IgE-reactive patients without sensitization to Pru p 3 could be found
(16.6%). The sera of patients sensitized to both LTPs (50%), Pla a 3 and Pru p 3,
showed different biological activity in histamine release assay: depending on
individual patient's sera tested, Pla a 3 showed a similar, a stronger or a
weaker allergenic potency in comparison with Pru p 3. CONCLUSIONS: Plane LTP is a
major allergen in plane pollen-allergic patients with peach allergy recruited in 
the Mediterranean area. The results of histamine release tests and different
IgE-binding profiles pointed towards the existence of species-specific IgE
epitopes. Likewise, no general conclusion on the sensitizer could be made.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17250699 [PubMed - indexed for MEDLINE]

396: Clin Exp Allergy. 2007 Feb;37(2):251-60.

Hypoallergenic mutants of Ole e 1, the major olive pollen allergen, as candidates
for allergy vaccines.

Marazuela EG, Rodríguez R, Barber D, Villalba M, Batanero E.

Departamento de Bioquímica y Biología Molecular, Facultad de Química, Universidad
Complutense, Madrid, Spain.

BACKGROUND: The C-terminal region of Ole e 1, a major allergen from olive pollen,
is a dominant IgE-reactive site and offers a target for site-directed mutagenesis
to produce variants with reduced IgE-binding capability. OBJECTIVE: To evaluate
in vitro and in vivo the immunogenic properties of three engineered derivatives
of Ole e 1. METHODS: One point (Y141A) and two deletion (135Delta10 and
140Delta5) mutants were generated by site-directed mutagenesis of Ole e
1-specific cDNA and produced in Pichia pastoris. Ole e 1 mutants were analysed
for IgE reactivity by ELISA using sera from olive pollen-allergic patients. Their
allergenicity was also investigated in both a mouse model of allergic
sensitization and in basophil activation assays. IgG1 response was assayed by
immunoblotting and competitive ELISA. T cell reactivity was evaluated by
proliferation assays and cytokine production in splenocyte cultures. RESULTS: The
135Delta10 mutant showed the strongest reduction in the IgE-binding capability of
sera from olive pollen-allergic patients. Rat basophil leukaemia assays
identified the deletion mutant 135Delta10 as the variant with the lowest
beta-hexosaminidase-releasing capacity. Furthermore, the same 135Delta10 mutant
induced the lowest IgE levels in a BALB/c mouse model of sensitization. All Ole e
1 mutants retained their allergen-specific T cell reactivity. Immunization of
mice with the mutants induced IgG1 antibodies, which cross-reacted with Ole e 1
and Ole e 1-like allergens from ash, lilac and privet pollens. The ability of the
human IgE to block the binding of anti-Ole e 1 mutant-specific mouse IgG1
antibodies to natural Ole e 1 demonstrated that Ole e 1 mutants are able to
induce in vivo antibodies reactive to the natural allergen. CONCLUSION: The
135Delta10 mutant with reduced allergenicity, intact T cell reactivity and
capacity to induce blocking antibodies could provide a suitable candidate vaccine
for efficient and safer therapy of olive pollen allergy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17250698 [PubMed - indexed for MEDLINE]

397: Clin Exp Allergy. 2007 Feb;37(2):243-50.

Diagnosis of Parietaria judaica pollen allergy using natural and recombinant Par 
j 1 and Par j 2 allergens.

González-Rioja R, Ferrer A, Arilla MC, Ibarrola I, Viguera AR, Andreu C, Martínez
A, Asturias JA.

Research & Development Department, Bial-Arístegui, Bilbao, Spain.

BACKGROUND: Parietaria judaica pollen is one of the main causes of allergic
diseases in the Mediterranean area and contains two major allergens, called Par j
1 and Par j 2. OBJECTIVE: To evaluate the diagnostic potential of natural and
recombinant forms of Par j 1 and Par j 2 in comparison with standardized P.
judaica pollen extract. METHODS: Thirty patients allergic to P. judaica pollen
and 15 control patients were investigated. Skin prick tests and determination of 
specific IgE levels were performed with commercial P. judaica extract, natural
Par j 1 and Par j 2, and recombinant forms of both allergens expressed in P.
pastoris. RESULTS: The whole group of patients with allergy to P. judaica had a
positive skin test reaction to purified nPar j 1-Par j 2 and rPar j 2 at 5
microg/mL, and no false-positive reactions were detected. Natural and recombinant
Par j 1 and Par j 2 showed no significantly different responses in skin tests
compared with P. judaica extract. A high correlation was found between the
serum-specific IgE levels to P. judaica extract vs. natural (R=0.996; P<0.001)
and recombinant allergens (R=0.887 and 0.982 for rPar j 1 and rPar j 2,
respectively; P<0.001). rPar j 2 displayed a 100% sensitivity and specificity
among P. judaica-allergic patients. CONCLUSIONS: In vivo and in vitro diagnosis
of P. judaica pollen allergy could be simplified using rPar j 2. This protein
showed comparable IgE response and skin prick reactivity with those produced by
P. judaica pollen extract.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17250697 [PubMed - indexed for MEDLINE]

398: Clin Exp Allergy. 2007 Feb;37(2):188-96.

Skin prick-test reactivity to aeroallergens and allergic symptoms in an urban
population of central Italy: a longitudinal study.

Dottorini ML, Bruni B, Peccini F, Bottini P, Pini L, Donato F, Casucci G,
Tantucci C.

Dipartimento di Medicina Interna e Scienze Endocrino Metaboliche (DiMISEM),
Università di Perugia, Perugia, Italy. marcodottorini@qubisoft.it

BACKGROUND: Cross-sectional studies report an increasing prevalence of allergic
diseases, such as rhinitis and asthma. Not thoroughly known, instead, is the
natural history of allergic sensitization and the progress of the allergic
disease-related symptoms. AIM: The purpose of this study was to evaluate
longitudinally the skin reactivity for the most common aeroallergens and the
allergic symptoms in an urban population living in Perugia, a town of central
Italy with a low-level of air pollution exposure. METHODS: In the 1998-1999
period 788 subjects were tested for skin reactivity to a panel of aeroallergens
and underwent the administration of a questionnaire. These same subjects were
part of a cohort of 1200 subjects who participated in a previous epidemiological 
study performed in 1984-1985 using the same tools. Subjects were aged between 14 
and 64 years at the time of the first survey. RESULTS: In the present survey 196 
subjects (24.9%) had skin reactivity to at least one aeroallergen, while in the
previous survey 143 subjects (18.1%) had skin prick-test reactivity. The increase
of the skin reactivity between the two observations was highly significant
(P<0.001) and was mainly observed in subjects <40-years old. The greatest
increment in skin reactivity was seen to Dermatophagoides pteronyssinus (house
dust mite) allergen. Data obtained from questionnaires showed that subjects who
declared allergic symptoms increased from 341 (43.3%) to 380 (48.2%). However,
the increase was significant (P<0.01) only in subjects who had a positive
association between allergic symptoms and prick-test reactivity and was greater
for rhino-conjunctivitis than for asthma-related symptoms. CONCLUSIONS: In a
cohort of urban population of the centre of Italy, exposed to a low and stable
level of air pollution, the sensitization to common aeroallergens increased with 
time, mostly in people <40-years of age. The greatest increment was found for
indoor allergens such as Dermatophagoides pteronysimus. A significant increase in
allergic symptoms, mainly related to rhino-conjunctivitis, was observed only in
the presence of positive prick test.

PMID: 17250691 [PubMed - indexed for MEDLINE]

399: Pediatr Int. 2007 Feb;49(1):64-9.

Efficacy of pollen immunotherapy in seasonal allergic rhinitis.

Can D, Tanaç R, Demir E, Gülen F, Veral A.

Division of Pediatric Allergy and Pulmonology, Behcet Uz Children Hospital,
Izmir, Turkey. ddcam15@hotmail.com

BACKGROUND: The efficacy of subcutaneous pollen immunotherapy has been documented
in published double-blind, placebo-controlled studies related to treatment of
seasonal allergic rhinitis. In the present study, subjective (symptom scores) and
objective (nasal peak inspiratory flow, nasal smear, nasal biopsy) parameters
were used to study the efficacy of pollen immunotherapy. METHODS: Forty-eight
patients (32 male), mean +/- SE age 13.6 +/- 2.8 years allergic to grass-pollen
participated in the present study. Patients were divided into three groups: group
I, 24 patients who did not receive pollen immunotherapy; group II, 12 patients
who received the build-up phase of pollen immunotherapy; and group III, 12
patients who had just finished pollen immunotherapy. With regard to objective and
subjective parameters these three groups were compared. RESULTS: When group I was
compared to groups II and III, the patients who had not received any
immunotherapy were found to have a high daytime nasal symptoms score (P < 0.01), 
high daytime eye symptoms score(P < 0.01) and high night-time symptoms score (P <
0.01). In objective parameters, it was found that group I had low nasal peak
inspiratory flow (P < 0.05), and a high eosinophil count in nasal smears (P <
0.05) and peripheral blood (P < 0.05). It was also demonstrated that there was an
increased eosinophil infiltration (P < 0.01) and mast cell infiltration (P <
0.05) in nasal biopsy in group I. There was no significant difference between
group II and group III according to these results (P > 0.05). CONCLUSIONS:
Immunotherapy leads to a better clinical and histopathological prognosis in
children with seasonal allergic rhinitis.

PMID: 17250508 [PubMed - indexed for MEDLINE]

400: Iran J Allergy Asthma Immunol. 2006 Mar;5(1):29-31.

Evaluation of six years allergen immunotherapy in allergic rhinitis and allergic 
asthma.

Farid R, Ghasemi R, Baradaran-Rahimi M, Jabbari F, Ghaffari J, Rafatpanah H.

Immunology Research Centre, Buali Research Institute, Mashhad University of
Medical Sciences, Mashhad, Iran.

Allergen immunotherapy involves the administration of gradually increasing
quantities of specific allergens to patients with IgE-mediated conditions until a
dose is reached that is effective in reducing disease severity from natural
exposure. In the present study we evaluated a period of six years immunotherapy
allergic rhinitis and allergic asthma patients with positive skin prick test of
common aeroallergen. The immunotherapy was performed on 156 patients. One hundred
twenty of the cases were allergic rhinitis (80%), 29 cases had allergic asthma
and 7 cases were mixed (4.5%). 70% in allergic rhinitis group, 75% in allergic
asthma group and 42.8% in mixed group completely improved. Immunotherapy, an
older therapeutic method, has now been updated, and with appropriate indications,
precautions and methods, has been clearly shown to be effective in the treatment 
of allergic rhinitis and in some cases of asthma and insect hypersensitivity.

Publication Types: 
    Evaluation Studies

PMID: 17242501 [PubMed - indexed for MEDLINE]

401: Iran J Allergy Asthma Immunol. 2006 Jun;5(2):63-7.

Acetaminophen use and the symptoms of asthma, allergic rhinitis and eczema in
children.

Karimi M, Mirzaei M, Ahmadieh MH.

Department of Pediatrics, School of Medicine, Shahid Sadoughi University Of
Medical Sciences and Health Services, Yazd, Iran. mehrankarimi1@hotmail.com

Allergic diseases are frequent in children and their prevalence and severity
differ in the different regions of the world. A number of studies have been
performed to determine the factors which are effective in the incidence of these 
diseases. One of the drugs that might have a role in incidence or intensity of
the symptoms of allergic diseases is Acetaminophen. In our survey conducted with 
standardized method (International Study of Asthma and Allergies in Childhood),
3000 children 6-7 years old and 3000 teenagers 13-14 years old were questioned
regarding asthma, allergic rhinitis and eczema. The prevalence of ever wheezing
in the children of 6-7 years old who took acetaminophen in the first year of
their life was 11.3%, which is more than other group (Odds Ratio=1.54, 95%
Confidence Interval: 1-2.38, P=0.049) and the prevalence of ever wheezing in
older age group who have taken acetaminophen at least once in a month was 25.1%
which is more than those taken less acetaminophen (OR=1.7, 95%CI=1.43-2.04,
P=0.000). Moreover taking more acetaminophen during past 12 months led to more
prevalence of night dry coughs and the symptoms of rhinitis in children 6-7 years
old and eczema and rhinitis symptoms in the 13-14 years old. Our findings suggest
that taking more acetaminophen may be associated with increasing allergic
symptoms in children.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17237578 [PubMed - indexed for MEDLINE]

402: Int Arch Allergy Immunol. 2007;143(2):83-91. Epub 2007 Jan 15.

Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen 
extract in seasonal indigenous cypress pollen rhinoconjunctivitis. A
double-blind, placebo-controlled study.

Charpin D, Gouitaa M, Dron-Gonzalvez M, Fardeau MF, Massabie-Bouchat YP, Hugues
B, Fabre C, Vivinus S, Pegliasco H, André C.

Service de Pneumologie, Hôpital Nord, Marseille, France.

BACKGROUND: The efficacy of standardized Juniperus ashei extract was assessed in 
patients with allergic rhinoconjunctivitis due to European cypress pollens.
METHODS: Forty adults with European cypress-allergic rhinoconjunctivitis were
randomized to receive immunotherapy or a matched placebo. Specific immunotherapy 
was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract
with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of 
Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in
October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per
month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point
score. RESULTS: Seventeen patients from the treated group and 15 patients from
the placebo group completed year 2001; 14 in each group completed year 2002. A
statistically significant improvement (41%, p < 0.02) in the conjunctivitis
symptom score was observed in actively treated patients compared to the placebo
group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was
not significant. This significant improvement was greater at the peak of the 2002
pollen season (63%, p < 0.01). CONCLUSIONS: This study therefore indirectly
validates the concept of treatment by major allergen because J. ashei is absent
from the region in which this study was conducted.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17228169 [PubMed - indexed for MEDLINE]

403: J Affect Disord. 2007 Aug;101(1-3):269-74. Epub 2007 Jan 12.

Mood-worsening with high-pollen-counts and seasonality: a preliminary report.

Guzman A, Tonelli LH, Roberts D, Stiller JW, Jackson MA, Soriano JJ, Yousufi S,
Rohan KJ, Komarow H, Postolache TT.

Mood and Anxiety Program, Department of Psychiatry, University of Maryland School
of Medicine, Baltimore, MD, USA. aguzman@psych.umaryland.edu

BACKGROUND: Because aeroallergens produce inflammation in the respiratory
airways, and inflammation triggers depression in vulnerable individuals, we
hypothesized that mood sensitivity to pollen, the most seasonal aeroallergen,
will be associated with a greater seasonality of mood. Since pollen is absent
during winter, we specifically predicted that mood sensitivity to tree pollen
will predict non-winter SAD but not winter SAD. METHODS: A convenience sample of 
African and African American college students who lived in the Washington DC
metropolitan area for at least the past 3 years completed the Seasonal Pattern
Assessment Questionnaire (SPAQ), from which the Global Seasonality Score (GSS)
was calculated, a diagnosis of cumulative SAD (syndromal or subsyndromal SAD) was
derived, a seasonal pattern (winter vs non-winter) identified, and self-reported 
mood changes during high pollen counts obtained. A Mann-Whitney test was used to 
compare GSS between participants with vs without mood worsening during high
pollen counts. The capability of mood worsening with high pollen counts, gender, 
ethnicity, and age to predict non-winter SAD was analyzed with logistic
regressions. RESULTS: GSS was greater (z=5.232, p<0.001) in those who reported
mood worsening with high pollen counts. Mood sensitivity to pollen predicted
non-winter SAD (p=0.017), but not winter SAD. LIMITATIONS: The SPAQ is not a
definitive tool to assess seasonality, and self-reported mood worsening with high
pollen counts relies on recollection. No direct measures of depression scores or 
pollen counts were collected. The non-winter SAD concept has not been previously 
established. CONCLUSIONS: Our study, which should be considered preliminary in
light of its limitations, suggests that self-reported mood-worsening with high
pollen count is associated with a greater seasonality of mood, and predicts SAD
of non-winter type.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 17222915 [PubMed - indexed for MEDLINE]

404: Rhinology. 2006 Dec;44(4):283-7.

The prevalence of allergic rhinitis in adults in Aydin, Turkey.

Başak O, Başak S, Gültekin B, Tekin N, Söylemez A.

Adnan Menderes University Medical Faculty, (Tip Fakültesi), Department of Family 
Medicine, Aydin, Turkey. obasak@superonline.com

BACKGROUND: Allergic rhinitis is the most common allergic disease in Turkey. Our 
objective was to determine the prevalence of allergic rhinitis among adults
living in Aydin, Turkey. METHODS: A population-based survey was undertaken among 
adults aged 16-64 years. Allergic rhinitis was confirmed in the subjects screened
positive by the clinical examination and specific immunoglobulin E testing.
RESULTS: A total of 465 interviews were conducted in spring 2005. The prevalence 
of allergic rhinitis in the past 12 months was 14.0%. The prevalence rate of
clinically confirmable AR was computed as 11.4%. The prevalence was significantly
higher among females and in urban areas. Specific IgE were detected for at least 
one of tested aeroallergens in 34.8% of the subjects with self-reported AR.
CONCLUSION: Our study revealed that the prevalence of allergic rhinitis among
adults living in the city of Aydin was as high as the prevalence in other regions
of Turkey but less than in Europe.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17216747 [PubMed - indexed for MEDLINE]

405: Respir Med. 2007 Jun;101(6):1106-12. Epub 2007 Jan 9.

Effects of topical formoterol alone and in combination with budesonide in a
pollen season model of allergic rhinitis.

Ahlström Emanuelsson C, Andersson M, Persson CG, Thorsson L, Greiff L.

Department of Otorhinolaryngology, Lund University Hospital, SE-221 85 Lund,
Sweden. cecilia-ahlstrom-emanuelsson@skane.se

BACKGROUND: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma
exudation effects. While available data suggest no or only marginal effects of
beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether 
these drugs may add to the efficacy of anti-rhinitis drugs. OBJECTIVE: To examine
effects of a beta(2)-agonist, alone and in combination with an intranasal
glucocorticosteroid, on symptoms and signs of allergic rhinitis. METHODS:
Patients were examined in a pollen season model. Budesonide 64 microg, alone and 
in combination with formoterol 9 microg, as well as formoterol 9 microg alone was
given in a placebo-controlled and crossover design. After 7 days of treatment,
the patients received allergen challenges for 7 days. Symptoms and nasal peak
inspiratory flow (PIF) were recorded. Nasal lavages with and without histamine
were carried out at the end of each challenge series. These lavages were analysed
for tryptase, eosinophil cationic protein (ECP), and alpha(2)-macroglobulin as
indices of mast cell activity, eosinophil activity, and plasma exudation,
respectively. RESULTS: Budesonide reduced symptoms of allergic rhinitis and
improved nasal PIF in the morning, in the evening as well as post allergen
challenge. Formoterol alone did not affect symptoms or nasal PIF and did not
affect the efficacy of budesonide. Tryptase, ECP, and alpha(2)-macroglobulin were
significantly reduced by budesonide. Formoterol alone did not affect these
indices and did not affect the anti-inflammatory effect of budesonide.
CONCLUSION: The present dose of formoterol does not affect symptoms and
inflammatory signs of allergic rhinitis and does not add to the efficacy of
topical budesonide.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17215115 [PubMed - indexed for MEDLINE]

406: Ann Allergy Asthma Immunol. 2006 Dec;97(6):767-74.

Effect of montelukast on symptoms and exhaled nitric oxide levels in 7- to
14-year-old children with seasonal allergic rhinitis.

Razi C, Bakirtas A, Harmanci K, Turktas I, Erbas D.

Department of Pediatric Allergy and Asthma, Gazi University Faculty of Medicine, 
Ankara, Turkey. cemrazi2@superonline.com

BACKGROUND: Cysteinyl leukotrienes have been found to exert potent inflammatory
effects in the upper airways and play a fundamental role in the pathogenesis of
allergic rhinitis. Previous studies have reported increased levels of exhaled
nitric oxide (eNO) in patients with allergic rhinitis without asthma symptoms.
OBJECTIVE: To investigate the role of treatment with montelukast on symptoms, eNO
levels, and peripheral eosinophil counts of children with seasonal allergic
rhinitis during pollen season. METHODS: A randomized, double-blind,
parallel-group study performed between April and June 2005 in 57 children aged 7 
to 14 years with seasonal allergic rhinitis was performed. The study comprised a 
1-week screening period, a 1-week run-in period, and a 2-week treatment period
with once daily montelukast, 5 mg, or matching placebo. RESULTS: No significant
difference at baseline was found in symptom scores, eNO levels, and blood
eosinophil counts between the treatment and placebo groups. After 2 weeks of
montelukast treatment, improvements from the baseline in the daytime nasal,
composite, and daytime eye symptoms scores were significantly greater in the
montelukast group compared with the placebo group (P < .001, P < .001, and P <
.01, respectively). A significant decrease was also found in eosinophil counts (P
< .001) in the montelukast group compared with the placebo group after treatment.
Montelukast treatment did not produce a significant effect on eNO levels compared
with placebo (P = .96). CONCLUSION: Montelukast treatment provided significant
improvement in symptoms and peripheral eosinophil counts of school-age children
with seasonal allergic rhinitis; however, it did not show a significant effect on
eNO levels.

Publication Types: 
    Randomized Controlled Trial

PMID: 17201236 [PubMed - indexed for MEDLINE]

407: Eur J Clin Pharmacol. 2007 Feb;63(2):135-41. Epub 2007 Jan 3.

The effect of MK-0524, a prostaglandin D(2) receptor antagonist, on prostaglandin
D (2)-induced nasal airway obstruction in healthy volunteers.

Van Hecken A, Depré M, De Lepeleire I, Thach C, Oeyen M, Van Effen J, Laethem T, 
Mazina K, Crumley T, Wenning L, Gottesdiener KM, Deutsch P, Clement P, Lai E, de 
Hoon JN.

Center for Clinical Pharmacology, UZ Gasthuisberg, (K.U.Leuven), Herestraat 49,
3000 Leuven, Belgium. Anne.VanHecken@uz.kuleuven.ac.be

INTRODUCTION: Nasal congestion in allergic rhinitis results from tissue edema and
vasodilatation in the nasal mucosa. Of the mediators released by mast cells in
response to allergens, prostaglandin (PG) D(2) is regarded as the most potent
inducer of nasal congestion. Intranasal administration of PGD(2) reproduces the
nasal blockade experienced by patients with seasonal allergic rhinitis (SAR) via 
its action on the PGD(2) (DP) receptor to induce nasal vasodilatation. Intranasal
challenge with PGD(2) can be a useful tool for evaluating DP-receptor
antagonists. OBJECTIVE: The main purpose of this study was to examine the ability
of MK-0524, a DP receptor antagonist in development for the treatment of SAR, to 
block PGD(2) induced nasal congestion in healthy volunteers. METHODS: To this
end, a double-blind, placebo-controlled, randomized, 3-period study was performed
in 15 healthy subjects. During each period, subjects received MK-0524 25 mg,
MK-0524 100 mg or placebo qd for 3 days. Twenty-four hours following the last
dose, nasal provocations with PGD(2) were performed to determine the PD(75),
which is the intranasal dose of PGD(2) that provokes a 75% increase in baseline
total nasal airway resistance as performed by active anterior rhinomanometry.
RESULTS: Following treatment with MK-0524, the PD(75) (mean+/-SD) was
significantly shifted from 15.8 +/- 18.3 mug/nostril during the placebo period to
more than 512 mug/nostril both following the 25- and 100-mg (maximum challenge
dose tested) dose regimen. CONCLUSION: Whether this >45 fold increase in PD(75)
will induce a clinically meaningful effect of MK-0524 will require clinical study
in participants with SAR.

Publication Types: 
    Randomized Controlled Trial

PMID: 17200838 [PubMed - indexed for MEDLINE]

408: Int Arch Allergy Immunol. 2007;143(1):75-82. Epub 2006 Dec 29.

Effects of probiotics on allergic rhinitis induced by Japanese cedar pollen:
randomized double-blind, placebo-controlled clinical trial.

Tamura M, Shikina T, Morihana T, Hayama M, Kajimoto O, Sakamoto A, Kajimoto Y,
Watanabe O, Nonaka C, Shida K, Nanno M.

Department of Otolaryngology and Sensory Organ Surgery, Osaka University School
of Medicine, Osaka, Japan. mtamua@ent.osaka-u.ac.jp

BACKGROUND: Lactobacillus casei strain Shirota (LcS) has been found to exert
antiallergic effects in animal experiments, but there is little information about
its clinical effects in human patients with allergy. METHODS: We performed a
randomized double-blind, placebo-controlled study to investigate the effects of
LcS in patients with allergic rhinitis triggered by Japanese cedar pollen (JCP). 
Participants were asked to drink fermented milk containing LcS (LcS group) or
placebo (control group) for 8 weeks. Clinical symptoms and immunological
parameters were compared between the two groups. RESULTS: Symptom-medication
scores (SMS) worsened in accordance with the increase in the amount of scattered 
JCP. In terms of the nasal and ocular SMS, there was no significant difference
between the LcS group and the placebo group during the ingestion period. In the
subgroup of patients with moderate-to-severe nasal symptom scores before starting
the ingestion of test samples, supplementation with LcS tended to reduce nasal
SMS. CONCLUSION: These results indicate that fermented milk containing LcS does
not prevent allergic symptoms in patients sensitive to JCP, but may delay the
occurrence of allergic symptoms in patients with moderate-to-severe nasal symptom
scores. (c) 2007 S. Karger AG, Basel.

Publication Types: 
    Randomized Controlled Trial

PMID: 17199093 [PubMed - indexed for MEDLINE]

409: Eur Ann Allergy Clin Immunol. 2006 Nov;38(9):310-2.

Safety, tolerability and efficacy of sublingual allergoid immunotherapy with a
4-day shortened build-up phase.

Giordano T, Quarta C, Bruno ME, Falagiani P, Riva G.

Allergology and Clinical Immunology Service, Vito Fazzi Hospital, AUSL Lecce 1,
Lecce, Italy.

BACKGROUND: Sublingual specific immunotherapy (SLIT) with monomeric allergoid has
shown to be safe and effective the studies performed so far. The build-up phase, 
however, is rather time consuming mainly if performed with the conventional
schedule of 14 weeks. AIMS OF STUDY: We evaluated the possibility of shortening
and simplifying this phase, through a new build-up scheme of only 4 days, as well
as the persistence of the allergoid SLIT efficacy after 12 months. METHODS:
Thirty-nine patients (26 M, 13 F, mean age 20.5 years, range 6-49) with a history
of moderate/severe rhinitis with or without mild asthma due to perennial and/or
seasonal allergens entered the study. The posological schedule, adopting only
1,000 AU tablets, was the following: 1/2 tablet the 1st day; 1/2 table twice the 
second day; 1/2 table plus 1 table the 3rd day, 1 tablet twice the 4th day; 1
tablet twice weekly from the 5th to the 365th day (maintenance therapy). RESULTS:
Only two mild adverse reactions occurred during the initial phase which
disappeared with the prosecution of the treatment. During the maintenance therapy
no adverse event was observed. Symptoms improved consistently and drug
consumption was reduced in most of the patients. CONCLUSIONS: The 4-day shortened
build-up phase resulted to be safe, well tolerated and effective, already after
one year of treatment.

Publication Types: 
    Evaluation Studies

PMID: 17191751 [PubMed - indexed for MEDLINE]

410: Biomed Pharmacother. 2007 Jan;61(1):29-33. Epub 2006 Dec 5.

Mechanisms of immunotherapy in allergic rhinitis.

Jayasekera NP, Toma TP, Williams A, Rajakulasingam K.

Department of Respiratory Medicine/Allergy, Homerton University Hospital NHS
Foundation Trust, Homerton Row, London E9 6SR, UK.

Allergic rhinitis is a common condition, but many people still experience
suboptimal control of symptoms despite measures such as allergen avoidance,
intra-nasal steroids and antihistamines. Specific immunotherapy (SIT) has been
used for many years, but though many studies show clinical efficacy, its
mechanism of action is still not clearly understood. Earlier studies showed
changes in antibodies and it may be that SIT works through mechanisms that alter 
the ratio of 'protective' IgG4 to 'pro-allergenic' IgE. Other studies have shown 
a reduction in eosinophil migration to nasal mucosa as well as a reduction in
inflammatory mediator release including basophil histamine release. More recent
studies have proposed that SIT works through inhibition of T-helper 2 lymphocytes
(Th2) which preferentially produce cytokines that promote allergic responses. SIT
may cause a deviation from Th2 to Th1 (T-helper 1 lymphocytes) or may induce
T-regulatory cells (T-regs) which inhibit Th2 responses directly or through
inhibitory cytokines.

Publication Types: 
    Review

PMID: 17189678 [PubMed - indexed for MEDLINE]

411: Expert Rev Vaccines. 2006 Oct;5(5):617-29.

Pollinex Quattro: a novel and well-tolerated, ultra short-course allergy vaccine.

Patel P, Salapatek AM.

Allied Research International Inc., 4540 Dixie Road, Mississauga, ON L4W1N2,
Canada. ppatel@allied-research.com

Pollinex Quattro is a novel, ultra short-course vaccine for treatment of seasonal
allergic rhinitis from grass, tree or ragweed pollen allergy. Its unique
formulation combines chemically modified allergens adsorbed onto a L-tyrosine
depot to enhance tolerability with the novel adjuvant, monophosphoryl lipid A, to
improve efficacy. Controlled clinical studies indicate that four preseasonal
injections with grass or tree formulations significantly reduce
rhinoconjunctivitis symptoms and medication use, as well as elevate
allergen-specific immunoglobulin G and blunt elevation of immunoglobulin E upon
allergen exposure. Postmarketing surveillance studies indicate similar clinical
outcomes. In all cases, the allergy vaccine was well tolerated with minimal local
reactions, while systemic reactions were rare and mild. Results from recent
investigational trials with grass and ragweed formulations are consistent with
previous efficacy and safety outcomes, and will be used toward product
registration in North America.

Publication Types: 
    Review

PMID: 17181436 [PubMed - indexed for MEDLINE]

412: Drugs. 2006;66(18):2309-19.

Selecting the optimal oral antihistamine for patients with allergic rhinitis.

Lehman JM, Blaiss MS.

Department of Pediatrics, Division of Clinical Allergy and Immunology, University
of Tennessee Health Science Center, Memphis, Tennessee, USA.

Allergic rhinitis (AR) is now recognised as a global health problem that affects 
10-30% of adults and up to 40% of children. Each year, millions of patients seek 
treatment from their healthcare provider. However, the prevalence of AR maybe
significantly underestimated because of misdiagnosis, under diagnosis and failure
of patients to seek medical attention. In addition to the classical symptoms such
as sneezing, nasal pruritus, congestion and rhinorrhoea, it is now recognised
that AR has a significant impact on quality of life (QOL). This condition can
lead to sleep disturbance as a result of nasal congestion, which leads to
significant impairment in daily activities such as work and school.
Traditionally, AR has been subdivided into seasonal AR (SAR) or perennial AR
(PAR). SAR symptoms usually appear during a specific season in which
aeroallergens are present in the outdoor air such as tree and grass pollen in the
spring and summer and weed pollens in the autumn (fall); and PAR symptoms are
present year-round and are triggered by dust mite, animal dander, indoor molds
and cockroaches. Oral histamine H(1)-receptor antagonists (H(1) antihistamines)
are one of the most commonly prescribed medications for the treatment of AR.
There are several oral H(1) antihistamines available and it is important to know 
the pharmacology, such as administration interval, onset of action, metabolism
and conditions that require administration adjustments. When prescribing oral
H(1) antihistamines, the healthcare provider must take into account the clinical 
efficacy and weigh this against the risk of adverse effects from the agent. In
addition to the clinical efficacy, potential for improvement in QOL with a
particular treatment should also be considered.

Publication Types: 
    Review

PMID: 17181374 [PubMed - indexed for MEDLINE]

413: Am J Rhinol. 2006 Nov-Dec;20(6):641-7.

Role of FEF25-75 as an early marker of bronchial impairment in patients with
seasonal allergic rhinitis.

Ciprandi G, Cirillo I, Klersy C, Marseglia GL, Vizzaccaro A, Pallestrini E, Tosca
M.

Azienda Ospedaliera Universitaria San Martino, Genoa, Italy. gio.cip@libero.it

BACKGROUND: Allergic rhinitis may be associated with asthma. Forced expiratory
flow between 25 and 75% of vital capacity (FEF2575) is a measure of small airways
narrowing. The aim of this study was to evaluate whether patients with seasonal
allergic rhinitis (SAR) without symptoms of asthma might, nevertheless, have
airways obstruction both in and out of the pollen season. METHODS: Fifty patients
(mean age, 23.7+/-4.9 years) with SAR were evaluated both during and outside the 
pollen season. All of them had moderate-severe grade of nasal obstruction. Total 
symptom score, rhinomanometry, nasal lavage, nasal scraping, spirometry, and
methacholine (MCH) bronchial challenge were assessed in all subjects. RESULTS:
Although data on forced vital capacity and response to MCH were similar in and
out of the pollen season, all other parameters were markedly different. The major
finding of the study was that FEF25-75 was significantly associated with nearly
all of the parameters considered, including bronchial hyperreactivity, with
Pearson R ranging from 31 to 75% and differences in mean FEF25-75 ranging between
14.5 and 16.5% of predicted. The more significant association was with nasal
airflow in the pollen season (R = 82.8%; p < 0.001). A significant association
persisted for all parameters while controlling for season. CONCLUSION: This study
highlights the link between upper and lower airways and the role of FEF25-75 as
an early marker of bronchial impairment in those patients with SAR alone.

PMID: 17181110 [PubMed - indexed for MEDLINE]

414: Clin Exp Allergy. 2006 Dec;36(12):1505-12.

Comment in:
    Clin Exp Allergy. 2006 Dec;36(12):1483-6.

Purified allergens vs. complete extract in the diagnosis of plane tree pollen
allergy.

Asturias JA, Ibarrola I, Amat P, Tella R, Malet A, Cisteró-Bahíma A, Enrique E,
Malek T, Martínez A.

Bial-Arístegui, R&D Department, Bilbao, Spain. juan.asturias@bial.com

BACKGROUND: Plane tree pollen allergy is a clinical disorder affecting human
population in cities of Europe, North America, South Africa, and Australia.
OBJECTIVE: To compare IgE-reactivity of the natural and recombinant forms of two 
major plane allergens, Pla a 1 and Pla a 2, with the reactivity of Platanus
acerifolia pollen extract. METHODS: Forty-seven patients with P. acerifolia
allergy, 15 of them monosensitized, and 24 control subjects were included in the 
study. Natural Pla a 1 and Pla a 2 were purified by standard chromatographic
methods and recombinant proteins were expressed in Escherichia coli. Skin prick
test and determination of specific IgE were performed with commercial P.
acerifolia extract and natural and recombinant purified allergens. RESULTS: Pla a
1 and Pla a 2 were responsible for 79% of the IgE-binding capacity against P.
acerifolia pollen extract. A high correlation has been found between the IgE
response to nPla a 1 (R = 0.80; P < 0.001) or nPla a 2 (R = 0.79; P < 0.001) vs. 
P. acerifolia extract as well as between natural and recombinant Pla a 1 (R =
0.89; P < 0.001). Skin testing showed no significant differences between extract 
and nPla a 2, whereas a higher reactivity was found with nPla a 1. In contrast,
rPla a 1 revealed markedly reduced sensitivity in comparison with extract by skin
prick test and specific IgE. The sensitivity of the mix Pla a 1+Pla a 2 was 100% 
and 87.5% for monosensitized and polysensitized patients, respectively, with no
false-positive reactions detected. Conclusion Pla a 1 and Pla 2 are sufficient
for a reliable diagnosis of P. acerifolia in most patients and induce comparable 
skin test reactivity as a whole extract.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17177673 [PubMed - indexed for MEDLINE]

415: Clin Exp Allergy. 2006 Dec;36(12):1488-93.

Do skin prick and conjunctival provocation tests predict symptom severity in
seasonal allergic rhinoconjunctivitis?

Radcliffe MJ, Lewith GT, Prescott P, Church MK, Holgate ST.

Infection Inflammation and Repair Research Division, School of Medicine,
Southampton General Hospital, University of Southampton, Southampton, UK.
mjr3@soton.ac.uk

BACKGROUND: In the investigation of seasonal allergic rhinoconjunctivitis (SAR), 
quantitative skin and conjunctival allergen challenge tests are used to measure
individual allergen sensitivity. These tests are reproducible and relate well to 
prevalence but their relationship to symptom severity is less well established.
OBJECTIVE: We wished to determine if quantitative skin prick tests (QSPT) and
conjunctival provocation tests (CPTs) using a single grass pollen allergen
extract are reproducible and predict symptom severity in SAR. METHODS: We
retrospectively analysed data from 91 participants in a previously published
randomized placebo controlled study of low dosage allergen immunotherapy who were
randomized to receive placebo treatment. We examined the relationship between
pre-seasonal QSPT, CPT and SAR symptoms. RESULTS: We found a high level of
reproducibility when repeated measures were compared for both the QSPT (P <
0.001) and the CPT (P < 0.001) and moderate correlation (0.49) between the
standard skin prick test (SPT) and the QSPT (P < 0.001). We found weak negative
correlation (-0.27) between the QSPT and the CPT (P < 0.001). We found no
correlation between seasonal symptom, use of rescue medication or quality of life
(QOL) scores and pre-seasonal QSPT or CPT. Conclusion In the assessment of
seasonal rhinoconjunctivitis, quantitative skin and conjunctival allergen
challenge tests are strongly reproducible, although there is no correlation
between these tests and seasonal symptom, use of rescue medication or QOL scores.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17177671 [PubMed - indexed for MEDLINE]

416: Allergy Asthma Proc. 2006 Nov-Dec;27(6):465-72.

Effect of desloratadine on the control of morning symptoms in patients with
seasonal and perennial allergic rhinitis.

Schenkel EJ.

Valley Allergy and Asthma Treatment Center/Valley Clinical Research Center, 3729 
Easton-Nazareth Highway, Suite 202, Easton, PA 18045, USA. eschenkelm@aol.com

The symptoms of allergic rhinitis vary in severity over the course of the day and
often are worse in the morning. This review focuses on data from clinical studies
of the antihistamine desloratadine to establish whether it effectively controls
the morning symptoms of allergic rhinitis. Studies of desloratadine in patients
with allergic rhinitis that used instantaneous scoring to assess the severity of 
morning symptoms were selected for inclusion from published literature
(peer-reviewed articles and abstracts presented at professional meetings). When
administered once daily, desloratadine is effective in alleviating the morning
symptoms of allergic rhinitis, including nasal congestion. Its action is
sustained over the 24-hour dosing interval. A comparison of morning and evening
dosing of desloratadine revealed equivalent relief of morning symptoms,
illustrating that the effect of desloratadine is independent of the time of
dosing. Clinical studies indicate that desloratadine is nonsedating and well
tolerated, with no evidence of adverse cardiac effects. For many patients with
allergic rhinitis, symptoms are most severe in the morning. To maximize the
benefits for patients, pharmacologic agents used in the management of allergic
rhinitis should be effective in controlling these peak morning symptoms. The
sustained 24-hour action of desloratadine and its effective control of morning
symptoms make it a valuable tool for improving the quality of life of patients
with allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17176780 [PubMed - indexed for MEDLINE]

417: Allergol Immunopathol (Madr). 2006 Nov-Dec;34(6):257-62.

The natural course of atopy determined by skin prick tests in patients with
bronchial asthma and/or rhinitis.

Karakaya G, Kalyoncu AF.

School of Medicine, Department of Chest Diseases, Adult Allergy Unit, Hacettepe
University, 06100 Sihhiye, Ankara, Turkey. gkarakay@hacettepe.edu.tr

BACKGROUND: The skin prick test (SPT) is the cheapest, most widely used and
practical method for the diagnosis of allergic diseases. The results of repeat
test might show variations due to aging. OBJECTIVE: To perform repeat SPTs to
determine possible changes in the atopy rate in general as well as changes in the
allergen spectrum of atopic patients occurring over time and to identify the
factors that could affect this change. METHODS: A total of 222 patients who
received a diagnosis of bronchial asthma and/or persistent rhinitis in our Adult 
Allergy Unit and who attended follow-up visits in the outpatient unit over a
2-year period were enrolled. SPT with 10 visit common aeroallergens were
performed at the first and the second test was performed after an interval of at 
least 2 years. RESULTS: The mean age was 36.4 +/- 11.4 years and 77.5 % of the
patients were women. The mean interval between the two tests was 43.4 +/- 20.0
(minimum = 24-maximum = 105) months. Repeat tests showed that the atopy rate
decreased from 58.6 % to 47.7 %; sensitivity rates to 10 allergens also
decreased. These differences were statistically significant (p <0.05).
CONCLUSION: The atopy rate determined by SPTs tends to decrease over time. The
most important factor affecting this decrease is time itself.

PMID: 17173843 [PubMed - indexed for MEDLINE]

418: Ann Allergy Asthma Immunol. 2006 Nov;97(5):703-6.

Bee pollen sensitivity in airborne pollen allergic individuals.

Pitsios C, Chliva C, Mikos N, Kompoti E, Nowak-Wegrzyn A, Kontou-Fili K.

Department of Allergology and Clinical Immunology, "Laikon" General Hospital,
Athens, Greece. pitsios@yahoo.com

BACKGROUND: Physicians who practice alternative medicine often prescribe bee
pollen as a food supplement and a treatment for various ailments. OBJECTIVES: To 
determine the qualitative and quantitative composition of bee pollen and to
investigate the cutaneous reactivity of atopic patients to bee pollen extracts.
METHODS: The absolute number of pollen grains per gram of bee pollen was
calculated, and morphologic identification of the botanical family was performed.
Five extracts of bee pollen were prepared for skin prick testing, according to
standard methods. Two hundred two volunteers participated in the study; 145 were 
atopic patients with respiratory allergy. The remaining 57 were healthy
volunteers or nonatopic patients and served as a control group. All participants 
underwent skin prick testing with a standard battery of 6 aeroallergens (olive,
grasses mix, Parietaria, mugwort, Dermatophagoides pteronyssinus, and
Dermatophagoides farinae) and with all homemade bee pollen extracts. RESULTS: All
samples of bee pollen contained Oleaceae pollen in high concentrations. Small
amounts of anemophilous pollen (Compositeae, Chenopodiaceae) were detected in
various samples. A strong positive correlation was observed between cutaneous
reactivity to bee pollen extracts and olive, grasses, and mugwort. CONCLUSIONS:
Bee pollen contains a large amount of pollen, which belongs to various allergenic
families of plants. Bee pollen retains its allergenic potential as demonstrated
by strong cutaneous responses to bee pollen extracts observed in atopic patients 
in contrast to nonatopic subjects. Regarding pollen allergic individuals, further
studies are needed to evaluate the safety of ingesting large amounts of bee
pollen.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17165283 [PubMed - indexed for MEDLINE]

419: Ann Allergy Asthma Immunol. 2006 Nov;97(5):657-63.

Effectiveness of ciclesonide nasal spray in the treatment of seasonal allergic
rhinitis.

Ratner PH, Wingertzahn MA, van Bavel JH, Hampel F, Darken PF, Hellbardt S,
Brookman S, Shah T.

Sylvana Research, San Antonio, Texas 78229, USA. phratner@swbell.net

BACKGROUND: Ciclesonide is an investigational corticosteroid under development
for treatment of allergic rhinitis. Ciclesonide is converted to active
metabolite, desisobutyryl-ciclesonide (des-CIC), by upper and lower airway
esterases. In vitro studies in human nasal epithelial cells and bronchial
epithelial cells have demonstrated a long duration of anti-inflammatory activity 
of des-CIC. OBJECTIVE: To evaluate the dose-dependent efficacy and safety of a
hypotonic intranasal formulation of ciclesonide in patients with seasonal
allergic rhinitis (SAR). METHODS: This was a phase 2, randomized, parallel-group,
double-blind, placebo-controlled study. Adults (n = approximately 145 per
treatment group) with a minimum 2-year history of SAR received placebo or
ciclesonide (25, 50, 100, or 200 microg/d) for 14 days. The primary end point was
change in the sum of morning and evening reflective total nasal symptom scores
(TNSSs) over 2 weeks. Safety was monitored throughout the study. RESULTS:
Ciclesonide, 100 microg/d (P = .04) and 200 microg/d (P = .003), significantly
improved the sum of morning and evening reflective TNSS vs placebo at more than 2
weeks of treatment. Baseline values for morning and evening reflective TNSS
ranged from 17.80 to 18.82 across treatment groups. The average change from
baseline in reflective TNSS was -4.2 for placebo and -4.8, -4.8, -5.3, and -5.8
for ciclesonide, 25, 50, 100, and 200 microg/d, respectively. There were no
dose-related differences in the incidence of adverse events among treatment
groups. CONCLUSIONS: Results from this study indicate that 100-microg and
200-microg daily doses of ciclesonide are effective in the treatment of SAR.
Ciclesonide, 200 microg/d, appears to be the optimal dose studied for reducing
the symptoms of SAR while maintaining an acceptable safety profile.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17165276 [PubMed - indexed for MEDLINE]

420: Ann Allergy Asthma Immunol. 2006 Nov;97(5):615-21.

Economic evaluation of sublingual immunotherapy vs symptomatic treatment in
adults with pollen-induced respiratory allergy: the Sublingual Immunotherapy
Pollen Allergy Italy (SPAI) study.

Berto P, Passalacqua G, Crimi N, Frati F, Ortolani C, Senna G, Canonica GW;
Italian SPAI Study Group.

School of Pharmacy, University of Padova, and PBE Consulting, Verona, Italy.

BACKGROUND: Few data are available on the pharmacoeconomic aspects of
immunotherapy. OBJECTIVE: To evaluate, from the health care system and societal
perspectives, the costs and consequences of sublingual immunotherapy (SLIT) added
to pharmacotherapy compared with drugs alone for respiratory allergy. METHODS:
This study compared costs, clinical outcomes, and cost-effectiveness ratios of 2 
strategies in the management of allergic rhinitis and asthma, namely, SLIT
associated with pharmacotherapy and pharmacotherapy alone (no SLIT). A decision
tree was developed and populated with epidemiologic and resource utilization data
concerning approximately 2,200 patients. Direct costs included visits, tests,
pharmacotherapy, immunotherapy, and hospitalizations. Indirect costs and
out-of-pocket drugs were also included. Outcome was calculated as the number of
improved patients and asthma cases avoided at 6 years. Sensitivity analysis was
performed by varying costs and epidemiologic data. RESULTS: SLIT improved the
symptoms of 399 of 1,000 patients and prevented asthma in 229 of 1,000 patients
compared with drugs alone. For SLIT added to pharmacotherapy and pharmacotherapy 
alone, the direct cost per patient at more than 6 years was Euro2,400 and
Euro3,026, whereas the indirect cost was Euro1,913 and Euro3,400. CONCLUSION:
From both perspectives and for both effectiveness end points, SLIT is less
expensive and more effective than pharmacotherapy alone.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17165269 [PubMed - indexed for MEDLINE]

421: Ann Allergy Asthma Immunol. 2006 Nov;97(5):579-86; quiz 586-9, 671.

Allergic rhinitis and its effect on sleep, fatigue, and daytime somnolence.

Santos CB, Pratt EL, Hanks C, McCann J, Craig TJ.

Allergy Research, Hershey Medical Center, Penn State University, Hershey,
Pennsylvania 17033-0850, USA.

OBJECTIVE: To examine the adverse effects of sleep impairment on the quality of
life of patients with the disorder and how these effects can be treated with
therapies targeted at the underlying problems that influence sleep. DATA SOURCES:
Medline and Ovid search for sleep and rhinitis. STUDY SELECTION: All literature
on this topic were reviewed, and, if significant, were incorporated into this
review. RESULTS: Intranasal corticosteroids used as treatment for allergic
rhinitis have been shown to reduce the nasal congestion characteristic of the
disorder. Data on sleep-related end points from clinical trials on intranasal
corticosteroids also reveal that the treatment's effectiveness in alleviating
nasal congestion leads to better sleep, reduced daytime somnolence, and improved 
quality of life. CONCLUSION: Further research, specifically using sleep
measurements as primary end points, is needed to definitively show that
intranasal corticosteroids reduce nasal congestion, thereby improving sleep and, 
consequently, quality of life in patients with allergic rhinitis. These future
trials will serve to identify the most effective therapies that target the
adverse effects of sleep impairment in this disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17165263 [PubMed - indexed for MEDLINE]

422: Int Immunopharmacol. 2007 Jan;7(1):46-54. Epub 2006 Sep 8.

Immunotherapy with CpG DNA conjugated with T-cell epitope peptide of an
allergenic Cry j 2 protein is useful for control of allergic conditions in mice.

Suzuki M, Ohta N, Min WP, Matsumoto T, Min R, Zhang X, Toida K, Murakami S.

Department of Surgery and Microbiology and Immunology, University of Western
Ontario 339 Windermere Road, London, Canada N6A5A5. msuzuki5@uwo.ca

Immunotherapy using T-cell epitope peptides or CpG DNA conjugated with allergenic
protein is useful, although the mechanisms of these therapies differ. However,
the combination of CpG DNA and peptide, but not protein, had not been documented.
Therefore, we investigated CpG DNA conjugated with peptide to obtain positive
synergistic effects. In the first experiment, mice were vaccinated with a
conjugate of CpG DNA and Cry j 2 T-cell epitope peptide p246-259 (CpG-peptide); a
mixture of CpG DNA and peptide (CpG+peptide); peptide alone, or PBS alone, and
immunized with Cry j 2. In the second experiment, mice were immunized with Cry j 
2 and injected with CpG-peptide, CpG+peptide, peptide only, or PBS only. In both 
experiments, Cry j 2-specific IgE, IL-4, and IL-5 were significantly lower in
mice given CpG-peptide, versus those given CpG+peptide, peptide alone, or PBS
alone. However, IgG2a, IgG2b and IFN-gamma did not increase in mice injected with
CpG-peptide. In the third experiment, CpG-peptide significantly attenuated nasal 
symptoms (sneezing and nasal rubbing) compared to CpG+peptide, peptide alone, or 
PBS alone. Mice were also injected with a conjugate of CpG DNA and Cry j 2
protein (CpG-Cry j 2) or CpG-peptide to compare prime responses. Mice vaccinated 
with CpG-Cry j 2 generated Cry j 2-specific IgG1, whereas those vaccinated with
CpG-peptide did not produce IgG1. This study demonstrated, for the first time,
that immunotherapy with CpG DNA conjugated with a T-cell peptide is useful in
preventing and treating allergic conditions.

PMID: 17161816 [PubMed - indexed for MEDLINE]

423: Clin Ther. 2006 Oct;28(10):1658-69.

Onset of action of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride
120 mg in subjects aged 12 years with moderate to severe seasonal allergic
rhinitis: a pooled analysis of two single-dose, randomized, double-blind,
placebo-controlled allergen exposure unit studies.

Berkowitz RB, McCafferty F, Lutz C, Bazelmans D, Godfrey P, Meeves S, Liao Y,
Georges G.

Rx Research, Woodstock, Georgia 30188, USA. bberkowitz@atlantaallergy.com

BACKGROUND: The onset of action of antihistamine-decongestant combinations is an 
important factor in the treatment of subjects with seasonal allergic rhinitis
(SAR). OBJECTIVE: This was a pooled analysis of 2 published studies with
identical designs investigating the onset of action of the combination of
fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg
(FEX60/PSE120) in subjects with moderate to severe SAR. METHODS: Subjects aged 12
years received single doses of FEX60/PSE120 or placebo in 2 randomized,
double-blind, placebo-controlled, parallel-group, allergen exposure unit studies 
and recorded their SAR symptoms on diary cards before dosing, at 15-minute
intervals for 2 hours after dosing, and at 30-minute intervals for the next 4
hours. The primary efficacy end point was onset of action, assessed in terms of
absolute change in the major symptom complex (MSC) score, which was the sum of
scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery
eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included 
the absolute and percent change in the total symptom complex (TSC) score (the sum
of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and 
cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs)
were recorded. Analyses were performed on the modified intention-to-treat (mITT) 
population, which included all subjects who were randomized to treatment and took
the single dose of study medication according to the protocol. RESULTS: A total
of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in 
study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT
population consisted of 784 subjects. Subjects' mean age was 33.4 years, and
64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least 
squares mean (SD) treatment difference in the change from baseline in absolute
MSC score was 0.8 (0.31) (95% CI, 0.2-1.4; P = 0.008). All subsequent changes
from baseline in MSC scores were statistically significant for FEX60/PSE120
compared with placebo (P < 0.001). The absolute and percent change in TSC score
and the percent change in MSC score were significantly decreased at all time
points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, 
P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly
improved with FEX60/PSE120 compared with placebo (all, P < 0.05). TEAEs were
reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and
placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and
placebo groups was somnolence (n = 4 and n = 6, respectively). CONCLUSION: In
this pooled analysis of 2 allergen exposure unit studies, FEX60/PSE120 had an
onset of action of 45 minutes and a sustained effect throughout the 6-hour study 
period in subjects with moderate to severe SAR.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17157121 [PubMed - indexed for MEDLINE]

424: Allergy. 2007 Jan;62(1):11-6.

Thunderstorm-asthma and pollen allergy.

D'Amato G, Liccardi G, Frenguelli G.

Division of Pneumology and Allergology, Department of Respiratory Diseases, High 
Speciality Hospital A. Cardarelli, Napoli, Italy.

Thunderstorms have been linked to asthma epidemics, especially during the pollen 
seasons, and there are descriptions of asthma outbreaks associated with
thunderstorms, which occurred in several cities, prevalently in Europe
(Birmingham and London in the UK and Napoli in Italy) and Australia (Melbourne
and Wagga Wagga). Pollen grains can be carried by thunderstorm at ground level,
where pollen rupture would be increased with release of allergenic biological
aerosols of paucimicronic size, derived from the cytoplasm and which can
penetrate deep into lower airways. In other words, there is evidence that under
wet conditions or during thunderstorms, pollen grains may, after rupture by
osmotic shock, release into the atmosphere part of their content, including
respirable, allergen-carrying cytoplasmic starch granules (0.5-2.5 microm) or
other paucimicronic components that can reach lower airways inducing asthma
reactions in pollinosis patients. The thunderstorm-asthma outbreaks are
characterized, at the beginning of thunderstorms by a rapid increase of visits
for asthma in general practitioner or hospital emergency departments. Subjects
without asthma symptoms, but affected by seasonal rhinitis can experience an
asthma attack. No unusual levels of air pollution were noted at the time of the
epidemics, but there was a strong association with high atmospheric
concentrations of pollen grains such as grasses or other allergenic plant
species. However, subjects affected by pollen allergy should be informed about a 
possible risk of asthma attack at the beginning of a thunderstorm during pollen
season.

Publication Types: 
    Review

PMID: 17156336 [PubMed - indexed for MEDLINE]

425: Allergy. 2007 Jan;62(1):3-10.

The impact of pollen-related food allergens on pollen allergy.

Bohle B.

Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical
University of Vienna, Vienna, Austria.

Patients with birch pollen allergy frequently develop hypersensitivity reactions 
to certain foods, e.g. apples, celery, carrots and hazelnuts. These reactions are
mainly caused by IgE-antibodies specific for the major birch pollen allergen, Bet
v 1, which cross-react with homologous proteins in these foods. Analyzing the
T-cell response to Bet v 1-related food allergens revealed that these dietary
proteins contain several distinct T-cell epitopes and activate Bet v 1-specific T
cells to proliferate and produce cytokines. Several of these cross-reactive
T-cell epitopes were not destroyed by simulated gastrointestinal digestion of
food allergens and stimulated Bet v 1-specific T cells despite nonreactivity with
IgE antibodies. Similarly, cooked food allergens did not elicit IgE-mediated
symptoms (oral allergy syndromes) but caused T-cell-mediated late-phase reactions
(deterioration of atopic eczema) in birch pollen-allergic patients with atopic
dermatitis because thermal processing affected their conformational structure and
not the primary amino acid sequence. Thus, T-cell cross-reactivity between Bet v 
1 and related food allergens occurs independently of IgE-cross-reactivity in
vitro and in vivo. We speculate that symptom-free consumption of pollen-related
food allergens may have implications for the pollen-specific immune response of
allergic individuals.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17156335 [PubMed - indexed for MEDLINE]

426: J Investig Allergol Clin Immunol. 2006;16(6):377-84.

Phoenix sylvestris Roxb pollen allergy: a 2-year randomized controlled trial and 
follow-up study of immunotherapy in patients with seasonal allergy in an
agricultural area of West Bengal, India.

Chakraborty P, Roy I, Chatterjee S, Chanda S, Gupta-Bharracharya S.

Department of Botany, Sree Chaitanya College, Habra, West Bengal, India.

BACKGROUND: Although the efficacy of allergen immunotherapy has been demonstrated
in seasonal pollen allergy, there is no report of a double-blind
placebo-controlled trial with standardized pollen extract in seasonal respiratory
allergy from India. In the agricultural area of eastern India, Phoenix sylvestris
Roxb or date sugar palm is grown or cultivated and seasonal allergic rhinitis is 
common during the pollen season. OBJECTIVE: The objective of the present study
was to observe the clinical and immunological changes during a 2-year
double-blind placebo-controlled trial of immunotherapy with standardized P
sylvestris pollen extract in respiratory patients sensitive to pollen from this
wild date palm. Thirty-five subjects with typical seasonal allergic rhinitis with
or without bronchial asthma were selected. A symptom-medication score (based on a
questionnaire and diary) was correlated with pollen counts as recorded in a
Burkard sampler. Eighteen subjects were randomized to a specific immunotherapy
(SIT) group receiving regular injections containing standardized allergen extract
and 17 to a placebo control group. Changes in the level of specific
immunoglobulin (Ig) E, IgG1, and IgG4 were recorded at 3-month intervals.
Measurement of wheal diameter, total IgE level and forced expiratory volume in 1 
second (FEV1) were performed before starting and a month after finishing therapy.
RESULTS: The SIT group showed decreases of 33.5% and 57% from the baseline
symptom-medication scores during the first and second treatment season,
respectively. This group showed significant decreases in skin-reactivity to P
sylvestris pollen extract and in specific IgE levels, and significant increases
in FEV,, specific IgGI (1.95-3.2 times higher) and IgG4 (21.24-30.83 times
higher). There were no significant changes in total IgE levels. The control group
showed no significant changes for any parameter except the development of new
sensitization in 2 cases (to Saccharum officinarum pollen grain and Alternaria
species spores). The rate of local adverse reactions was 0.024%. CONCLUSION:
After a 2-year study, allergen immunotherapy with standardized P sylvestris
pollen extract was found to be effective in seasonal respiratory allergic
subjects susceptible to P sylvestris pollen with a narrow range of sensitization.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17153886 [PubMed - indexed for MEDLINE]

427: J Investig Allergol Clin Immunol. 2006;16(6):338-44.

Specific immunotherapy with high dose SO standardized grass allergen tablets was 
safe and well tolerated.

Calderón M, Essendrop M.

Upper Respiratory Medicine, Royal Brompton Hospital, Imperial College, London,
United Kingdom m.calderon@imperial.ac.uk

BACKGROUND: Sublingual immunotherapy with grass allergen tablets may be the
future treatment for grass pollen allergy because it reduces symptoms and
medication use, improves quality of life and is easy to use. Rhinoconjunctivitis 
and asthma co-exist and we aimed to find a safe dose range of a self-administered
grass allergen tablet (ALK Abello A/S) in patients suffering from
rhinoconjunctivitis and asthma. METHODS: Four doses were investigated in a
randomised, double-blind, placebo-controlled, dose escalation trial. Outside the 
pollen season 4 groups of 12 patients commenced treatment in a staggered manner, 
at intervals of 1 week. For 28 days doses of 75000 (approximately 15microg Phleum
pratense protein 5), 150,000, 300,000, 500,000 standardised quality tablet (SQ-T)
units or placebo were given once daily as sublingual tablets. RESULTS: Fourty
three patients were randomised to receive either active treatment or placebo
(3:1). Each dose group consisted of 12 patients except the 500000 SQ-T group (5
active, 2 placebo). No asthma exacerbations were seen and no serious or severe
adverse events were reported. The majority of adverse events were local
reactions. The number of adverse events was dose related. No patients withdrew
from the study. CONCLUSIONS: Treatment with grass allergen tablets in doses up to
500000 SQ-T in patients with asthma and rhinoconjunctivitis was safe and well
tolerated.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17153880 [PubMed - indexed for MEDLINE]

428: Arch Environ Occup Health. 2005 May-Jun;60(3):170-6.

Short-term effects of airborne pollen on the risk of allergic
rhinoconjunctivitis.

Zeghnoun A, Ravault C, Fabres B, Lecadet J, Quénel P, Thibaudon M, Caillaud D.

Département Santé Environnement Institut de Veille Sanitaire, Saint-Maurice ,
France. a.zeghnoun@invs.sante.fr

The authors carried out a pilot study in Clermont-Ferrand (France) over the
period from 2000 to 2001 to analyze the short-term relationship between daily
variations in rhinitis and allergic conjunctivitis and daily variations in pollen
counts. Data from the ERASME database made it possible to identify all the
individuals for whom at least one drug was prescribed to treat rhinitis or
allergic conjunctivitis. Ten allergenic pollens were studied, and a Poisson
regression model with penalized spline functions was used. A positive and
significant association was found for pollens of Betula, Cupressaceae, Quercus,
Fraxinus, and Poaceae. The relative risks varied between 1.3 (95% confidence
interval [CI] = 1.0-1.5) and 1.2 (95% CI = 1.1-1.5) for an interquartile range
increase of daily pollen counts of Cupressaceae (13 grains/m3) and of Betula (45 
grains/m3), respectively. Further analyses, in particular, those using longer
time series, are necessary to confirm these results.

PMID: 17153090 [PubMed - indexed for MEDLINE]

429: Clin Allergy Immunol. 2007;19:23-34.

Epidemiology of rhinitis: allergic and nonallergic.

Settipane RA, Charnock DR.

Department of Medicine, Brown Medical School, Providence, Rhode Island, USA.

In summary, the epidemiological data and characterization of allergic and
nonallergic rhinitis has been reviewed. Chronic rhinitis symptoms are among the
most common problems presenting to physicians. When approaching this problem the 
diagnostic challenge is to determine the etiology, specifically whether it is
allergic, nonallergic, or perhaps an overlap of both conditions. Estimates of the
prevalence of allergic rhinitis range from as low as 9% to as high as 42%.
Although the prevalence of nonallergic rhinitis has not been studied
definitively, it appears to be very common with an estimated prevalence in the
United States of approximately 19 million. In comparison, the prevalence of mixed
rhinitis is approximately 26 million, and allergic rhinitis ("pure" and "mixed"
combined) 58 million. Challenges in the differential diagnosis of rhinitis result
from two major factors. Not only are presenting symptoms of allergic,
nonallergic, and mixed rhinitis often indistinguishable from one another, but
also the differential diagnosis of nonallergic rhinitis is extensive. Nonallergic
rhinitis is often characterized by onset after age 20, female predominance, nasal
hyperactivity, perennial symptoms, and nasal eosinophilia in approximately
one-third of the population. Positive tests for relevant specific IgE sensitivity
in the setting of rhinitis do not rule out "mixed rhinitis" and may not rule out 
nonallergic rhinitis. The significance of symptom exacerbation by nonallergic
triggers in the setting of allergic rhinitis remains to be determined. Goals for 
the future include reaching a consensus on the definitions of rhinitis and
rhinitis subtypes including the establishment of mixed rhinitis, updating
guidelines for the interpretation of nonrelevant positive tests for specific IgE 
sensitivity, and reaching agreement on the nonallergic triggers that best define 
VMR or VMR subtypes. Only then can the most applicable research results be
obtained. The desired result is the delivery of the most appropriate treatment,
specifically tailored to the accurate diagnosis of patients with rhinitis.

Publication Types: 
    Review

PMID: 17153005 [PubMed - indexed for MEDLINE]

430: Braz J Otorhinolaryngol. 2006 Jul-Aug;72(4):562-7.

Pollen allergic disease: pollens and its major allergens.

Taketomi EA, Sopelete MC, de Sousa Moreira PF, de Assis Machado Vieira F.

Universidade Federal de Uberlândia, Brazil.

Patients with grass pollen allergy, commonly called pollinosis, often present
reactivity to pollen allergens from a number of grass species due to
cross-reactivity of IgE antibodies to pollen proteins present in pollen grasses. 
In this context, Italian rye grass (Lolium multiflorum) pollen of the Poaceae
family cultivated in Southern Brazil has been considered a major sensitizing
agent in patients with pollinosis. In this region, Italian rye grass is capable
of producing a great amount of pollen. In addition to L. multiflorum, other
Poaceae grasses are naturally grown as weed in Southern Brazil, but with no
clinical relevance. Pollen extracts derived from homologous or heterologous
grasses are often used for both diagnosis and treatment of seasonal allergy.
However, no standardized L. multiflorum pollen extract is commercially available 
in Brazil and mixed grass extracts are commonly used for diagnosis and
immunotherapy of grass pollen allergy. Further studies are required to better
characterize the cross-reactivity between L. multiflorum and other grass pollen
allergens for improving the diagnosis and immunotherapy to L. multiflorum pollen 
allergy.

Publication Types: 
    Review

PMID: 17143438 [PubMed - indexed for MEDLINE]

431: Biol Pharm Bull. 2006 Dec;29(12):2506-9.

Cry-consensus peptide, a novel peptide for immunotherapy of Japanese cedar
pollinosis, induces Th1-predominant response in Cry j 1-sensitized B10.S mice.

Kozutsumi D, Tsunematsu M, Yamaji T, Murakami R, Yokoyama M, Kino K.

Research and Development Section, Pharmaceuticals Development Department, Meiji
Dairies Corporation, Kanagawa, Japan. daisuke_kozutsumi@meiji-milk.com

Cry-consensus peptide (CCP) is a newly designed peptide for peptide-based
immunotherapy of Japanese cedar pollinosis but its mechanism of efficacy is
unknown. We investigated the effect of CCP on Cry j 1-specific Th1/Th2 response
in a mice model. Subcutaneous injection of CCP decreased Cry j 1-specific IgE and
IgG1 in blood slightly, but the IgG2a level was increased significantly in a dose
dependent manner. Splenocytes from these mice were stimulated with Cry j 1 in
vitro. This inhibited IL-4, IL-5 and IL-10 secretion significantly, but IFN-gamma
secretion was increased. In vitro CCP stimulation of splenocytes from Cry j
1-sensitized mice induced more marked Th1-predominancy of cytokine production
than native allergen stimulation. Taken together, these data suggest that one of 
the mechanisms of CCP is dependent on the modulation of the antigen-specific
Th1/Th2 response.

PMID: 17142991 [PubMed - indexed for MEDLINE]

432: BMC Pulm Med. 2006 Nov 30;6 Suppl 1:S5.

Allergic rhinitis and asthma: inflammation in a one-airway condition.

Jeffery PK, Haahtela T.

Lung Pathology, Imperial College at the Royal Brompton Hospital, London, SW3 6NP,
UK. p.jeffery@imperial.ac.uk

BACKGROUND: Allergic rhinitis and asthma are conditions of airway inflammation
that often coexist. DISCUSSION: In susceptible individuals, exposure of the nose 
and lungs to allergen elicits early phase and late phase responses. Contact with 
antigen by mast cells results in their degranulation, the release of selected
mediators, and the subsequent recruitment of other inflammatory cell phenotypes. 
Additional proinflammatory mediators are released, including histamine,
prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines,
chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate
accumulations of mast cells, eosinophils, and basophils in the epithelium and
accumulations of eosinophils in the deeper subepithelium (that is, lamina
propria). Examination of bronchial tissue, even in mild asthma, shows lymphocytic
inflammation enriched by eosinophils. In severe asthma, the predominant pattern
of inflammation changes, with increases in the numbers of neutrophils and, in
many, an extension of the changes to involve smaller airways (that is,
bronchioli). Structural alterations (that is, remodeling) of bronchi in mild
asthma include epithelial fragility and thickening of its reticular basement
membrane. With increasing severity of asthma there may be increases in airway
smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting
glands. Remodeling in the nose is less extensive than that of the lower airways, 
but the epithelial reticular basement membrane may be slightly but significantly 
thickened. CONCLUSION: Inflammation is a key feature of both allergic rhinitis
and asthma. There are therefore potential benefits for application of
anti-inflammatory strategies that target both these anatomic sites.

Publication Types: 
    Review

PMID: 17140423 [PubMed - indexed for MEDLINE]

433: BMC Pulm Med. 2006 Nov 30;6 Suppl 1:S4.

Allergic rhinitis: evidence for impact on asthma.

Thomas M.

Department of General Practice and Primary Care, University of Aberdeen,
Foresterhill Health Centre, Westburn Road, Aberdeen AB25 2AY, UK.
drmike.thomas@btinternet.com

BACKGROUND: This paper reviews the current evidence indicating that comorbid
allergic rhinitis may have clinically relevant effects on asthma. DISCUSSION:
Allergic rhinitis is very common in patients with asthma, with a reported
prevalence of up to 100% in those with allergic asthma. While the temporal
relation of allergic rhinitis and asthma diagnoses can be variable, the diagnosis
of allergic rhinitis often precedes that of asthma. Rhinitis is an independent
risk factor for the subsequent development of asthma in both atopic and nonatopic
individuals. Controlled studies have provided conflicting results regarding the
benefits for asthma symptoms of treating comorbid allergic rhinitis with
intranasal corticosteroids. Effects of other treatments for comorbid allergic
rhinitis, including antihistamines, allergen immunotherapy, systemic anti-IgE
therapy, and antileukotriene agents, have been examined in a limited number of
studies; anti-IgE therapy and antileukotriene agents such as the leukotriene
receptor antagonists have benefits for treating both allergic rhinitis and
asthma. Results of observational studies indicate that treating comorbid allergic
rhinitis results in a lowered risk of asthma-related hospitalizations and
emergency visits. Results of several retrospective database studies in the United
States and in Europe indicate that, for patients with asthma, the presence of
comorbid allergic rhinitis is associated with higher total annual medical costs, 
greater prescribing frequency of asthma-related medications, as well as increased
likelihood of asthma-related hospital admissions and emergency visits. There is
therefore evidence suggesting that comorbid allergic rhinitis is a marker for
more difficult to control asthma and worsened asthma outcomes. CONCLUSION: These 
findings highlight the potential for improving asthma outcomes by following a
combined therapeutic approach to comorbid allergic rhinitis and asthma rather
than targeting each condition separately.

Publication Types: 
    Review

PMID: 17140422 [PubMed - indexed for MEDLINE]

434: BMC Pulm Med. 2006 Nov 30;6 Suppl 1:S3.

Survey on the impact of comorbid allergic rhinitis in patients with asthma.

Valovirta E, Pawankar R.

Turku Allergy Centre, 20610 Turku, Finland. erkka.valovirta@allergiakeskus.fi

BACKGROUND: Allergic rhinitis (AR) and asthma are inflammatory conditions of the 
airways that often occur concomitantly. This global survey was undertaken to
understand patient perspectives regarding symptoms, treatments, and the impact on
their well-being of comorbid AR and asthma. METHODS: Survey participants were
adults with asthma (n = 813) and parents of children with asthma (n = 806) from
four countries each in the Asia-Pacific region and Europe. Patients included in
the survey also had self-reported, concomitant AR symptoms. Patients and parents 
were recruited by telephone interview or by direct interview. RESULTS: Most
patients (73%) had pre-existing symptoms of AR when their asthma was first
diagnosed. Shortness of breath (21%) was the most troublesome symptom for adults,
and wheezing (17%) and coughing (17%) the most troublesome for children. Patients
used different medications for treating asthma (most commonly short-acting
beta-agonists and inhaled corticosteroids) and for treating AR (most commonly
oral antihistamines). The concomitant presence of AR and asthma disrupted the
ability to get a good night's sleep (79%), to participate in leisure and sports
activities (75%), to concentrate at work or school (69% of adults, 73% of
children), and to enjoy social activities (57% of adults, 51% of children). Most 
patients (79%) reported worsening asthma symptoms when AR symptoms flared up.
Many (56%) avoided the outdoors during the allergy season because of worsening
asthma symptoms. Many (60%) indicated difficulty in effectively treating both
conditions, and 72% were concerned about using excessive medication. In general, 
respondents from the Asia-Pacific region reported more disruption of activities
caused by symptoms and more concerns and difficulties with medications than did
those from Europe. Differences between the two regions in medication use included
more common use of inhaled corticosteroids in Europe and more common use of
Chinese herbal remedies in the Asia-Pacific region. CONCLUSION: Results of this
survey suggest that comorbid asthma and AR substantially impact patient
well-being and that the worsening of AR symptoms in patients with asthma can be
associated with worsening asthma symptoms. These findings underscore the need for
physicians who treat patients with asthma to evaluate treatment options for
improving symptoms of both AR and asthma when present concomitantly.

PMID: 17140421 [PubMed - indexed for MEDLINE]

435: Int Arch Allergy Immunol. 2007;142(4):329-34. Epub 2006 Nov 28.

Genotypes and haplotypes of CCR2 and CCR3 genes in Japanese cedar pollinosis.

Nakamura H, Higashikawa F, Nobukuni Y, Miyagawa K, Endo T, Imai T, Hatta K, Ozasa
K, Motohashi Y, Matsuzaki I, Sasahara S, Ogino K, Akimaru K, Eboshida A.

Department of Environmental Medicine, Kochi University School of Medicine, Kochi,
Nankoku, Japan. hiro-n@po.incl.ne.jp

Whole genome scan analyses have revealed that the chromosomal region 3p21.3,
which contains a gene cluster of the CC chemokine receptor, is possibly critical 
for the pathogenesis of allergic inflammation. Japanese cedar pollinosis is
mediated by a type I allergy and induces seasonal rhinitis and conjunctivitis in 
humans as the most common form of hay fever in spring in Japan, although the
candidate genes for cedar pollinosis remain to be elucidated. We sequenced CCR1, 
CCR2, CCR3, CCR5, and CCXCR1 using the PCR restriction fragment length
polymorphism method in subjects with cedar pollinosis and controls. We found 8
polymorphisms of A111G, Arg127Cys and Arg252Gln in CCXCR1, T885C in CCR1,
Val64Ile and T780C in CCR2, T51C in CCR3 and Arg223Gln in CCR5. The transmission 
disequilibrium test using 60 children with pollinosis and their parents and an
association study using unrelated adult subjects (151 patients and 157 controls) 
showed a significant association of 64Ile in CCR2 and 51C in CCR3 with cedar
pollinosis. The frequency of haplotype 64Ile/780C/51C in pollinosis was
significantly higher than in controls. Our results suggest that CCR2 and CCR3
genes are candidate genes for Japanese cedar pollinosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17135764 [PubMed - indexed for MEDLINE]

436: Pediatr Pulmonol. 2007 Jan;42(1):60-5.

Changing trends in sex specific prevalence rates for childhood asthma, eczema,
and hay fever.

Osman M, Tagiyeva N, Wassall HJ, Ninan TK, Devenny AM, McNeill G, Helms PJ,
Russell G.

Department of Child Health, University of Aberdeen, Aberdeen, Scotland, UK.

Numerous surveys of school-aged children have shown increasing asthma prevalence 
with a less publicized but noticeable change in the male to female ratio. We
sought to confirm this change in the sex ratio in four questionnaire-based
surveys and investigate possible explanations. Identical questionnaire surveys
were performed in 1989 (n=3,390), 1994 (n=4,047), 1999 (n=3,540) and 2004
(n=1,920) in school-children aged 9-11 years. Over these 15 years the male to
female ratio (M:F) significantly narrowed for wheeze (1.34 to 0.98:1 P < 0.0002),
for asthma (1.74 to 1.02:1 P < 0.0001), for eczema (1.42:1 to 0.81:1 P < 0.0001) 
and for hay fever (1.46 to 0.93:1 P < 0.0001). The diagnosis of asthma in
children with wheeze was more commonly made in boys in 1989 relative risk RR 1.32
(1.12, 1.56), even in those with accompanying eczema and/or hay fever RR 1.20
(0.99, 1.45). By 2004 this sex bias in diagnosis was no longer present, RR 1.01
(0.91, 1.12) for wheeze and 1.02 (0.85, 1.21) for those with wheeze and eczema
and/or hay fever. From 1989 to 2004 no significant difference in sex distribution
changes between older and younger children occurred, making secular trends in the
onset of puberty in females an unlikely contributory factor. The disappearance of
the bias to diagnose asthma in symptomatic males but not in females may be partly
responsible for the narrowing of the sex ratio, but other factors such as those
enhancing the expression of asthma and atopy in females may also be implicated.
(c) 2006 Wiley-Liss, Inc.

PMID: 17133524 [PubMed - indexed for MEDLINE]

437: Curr Opin Pulm Med. 2007 Jan;13(1):13-8.

The connection between allergic rhinitis and bronchial asthma.

Corren J.

Allergy Research Foundation, Los Angeles, California 90025, USA. jcorren@ucla.ed

PURPOSE OF REVIEW: The relationship between allergic rhinitis and asthma has
intrigued practicing physicians since the turn of the century. Investigations
during the past two decades have led to an increased understanding of this
relationship. RECENT FINDINGS: A growing body of evidence clearly demonstrates
that patients with allergic rhinitis, in the absence of asthma, have distinct
abnormalities of lower airway function, including alterations in physiology,
histology and biochemistry. In addition, epidemiologic surveys have consistently 
shown allergic rhinitis as an independent risk factor for developing asthma, and 
that preexisting abnormalities in lung function may predispose to lower airway
disease development. Clinical trials show that specific allergen immunotherapy
for children and adults with seasonal allergic rhinitis reduces the risk of
developing asthma. In patients with established asthma and concomitant allergic
rhinitis, several medications have significant effects upon the upper and lower
airways, including intranasal corticosteroids, oral antihistamines, and
leukotriene receptor antagonists. SUMMARY: Our understanding of the natural
history of allergic rhinitis could lead to improvements in early intervention,
potentially preventing the progression of allergic rhinitis to asthma. Aggressive
treatment of rhinitis in patients with concomitant asthma may enhance asthma
outcomes and quality of life for all patients with these chronic diseases.

Publication Types: 
    Review

PMID: 17133119 [PubMed - indexed for MEDLINE]

438: Int J Tuberc Lung Dis. 2006 Nov;10(11):1268-72.

Findings on the atopic triad from a Danish twin registry.

Thomsen SF, Ulrik CS, Kyvik KO, Skadhauge LR, Steffensen I, Backer V.

Department of Respiratory Medicine, Bispebjerg Hospital, Copenhagen, Denmark.
sft@city.dk

OBJECTIVE: To estimate to what extent the same genetic and environmental risk
factors influence asthma, hay fever and eczema. DESIGN: From the nationwide
Danish Twin Registry, twin cohorts born between 1953 and 1982 were contacted for 
a questionnaire survey, and a total of 29 183 twin individuals (86%) responded.
Subjects were classified as cases when responding affirmatively to three
questions about the lifetime occurrence of asthma, hay fever and eczema. Variance
components twin analysis was conducted using maximum likelihood methods. RESULTS:
The phenotypic (within-subject) correlations in liability between the different
diseases were 0.57 (95% CI 0.54-0.59) for asthma and hay fever, 0.40 (95% CI
0.36-0.42) for asthma and eczema, and 0.33 (95% CI 0.29-0.36) for hay fever and
eczema. Decomposition of these correlations into their genetic and environmental 
contributions showed that shared genes explained between 70% and 85% of the
correlation between the different diseases. The remaining parts were explained by
environmental factors shared between the diseases. CONCLUSION: To a large extent,
atopic diseases share a common genetic background, although disease-specific
genes also play a considerable role. These results can prove informative when
counselling families with atopy, and may furthermore be used to guide the search 
for pleiotropic genes of importance for these diseases.

Publication Types: 
    Twin Study

PMID: 17131787 [PubMed - indexed for MEDLINE]

439: Allergol Int. 2006 Dec;55(4):379-86.

Omalizumab is effective and safe in the treatment of Japanese cedar
pollen-induced seasonal allergic rhinitis.

Okubo K, Ogino S, Nagakura T, Ishikawa T.

The Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.
ent-kimi@nms.ac.jp

BACKGROUND: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollen is 
a substantial problem in Japan. Omalizumab, a novel humanized monoclonal
anti-immunoglobulin E (IgE) antibody, has already been proven to reduce symptoms 
associated with SAR. We investigated the safety and efficacy of omalizumab in the
treatment of patients with Japanese cedar pollen-induced SAR compared to placebo.
METHODS: A randomized, placebo-controlled, double-blind study was conducted in
100 Japanese patients with a history of moderate-to-severe SAR induced by
Japanese cedar pollens. Omalizumab (150, 225, 300, or 375mg) or placebo was
administered subcutaneously every 2 or 4 weeks based on serum total IgE and body 
weight at baseline. The primary efficacy variable was the mean of daily nasal
symptom medication scores (sum of the daily nasal symptom severity score and
daily nasal rescue medication score) during the treatment period. Secondary
efficacy variables included the daily ocular symptom medication score and related
variables. RESULTS: Primary and all secondary efficacy variable scores were
significantly lower in the omalizumab group than in the placebo group (P < .01). 
Serum free IgE levels markedly decreased in the omalizumab group and were
associated with clinical efficacy. The overall incidence of injection site
reactions was higher in the omalizumab group than in the placebo group; however, 
the adverse reaction profile was similar between the two groups when excluding
injection site reactions. No anti-omalizumab antibodies were detected.
CONCLUSIONS: Omalizumab was effective and safe in the treatment of SAR induced by
Japanese cedar pollen.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 17130680 [PubMed - indexed for MEDLINE]

440: Int Arch Allergy Immunol. 2007;142(3):239-46. Epub 2006 Nov 15.

Safety and efficacy of Juniperus ashei sublingual-swallow ultra-rush pollen
immunotherapy in cypress rhinoconjunctivitis. A double-blind, placebo-controlled 
study.

Vervloet D, Birnbaum J, Laurent P, Hugues B, Fardeau MF, Massabie-Bouchat YP,
Aferiat-Derome A, André C.

UPRES EA 3287, Service de Pneumologie, Hôpital Sainte-Marguerite, Marseille,
France.

BACKGROUND: The safety and efficacy of high-dose sublingual-swallow immunotherapy
(SLIT) has been established in pollen rhinoconjunctivitis. This treatment has now
been evaluated using an ultra-rush incremental dose regimen with a Juniperus
ashei allergen extract in patients allergic to Cupressus sempervirens and
Cupressus arizonica. METHODS: Patients received either placebo or SLIT.
Evaluation of safety was based on the frequency of adverse events during the
incremental dose period (half a day) and during maintenance therapy (4 months).
Evaluation of efficacy was based on symptom and medication scores at the pollen
peak. RESULTS: Seventy of the 76 patients included completed the study. There
were no drop-outs during the rush procedure. One patient in the active group
dropped out during the maintenance therapy due to adverse events: gastric pain
and vomiting. There was also 1 drop-out in the placebo group due to pregnancy.
Adverse events were infrequent, local and mild. Symptom scores for rhinitis and
conjunctivitis were not statistically different between groups, but there was a
marked and significant (p < 0.03) decrease of the medication score (about 50%)
and nasal steroid consumption (about 75%) in the active treatment group. An
increase from baseline of serum IgE and IgG4 J. ashei-specific antibodies was
only observed in actively treated patients (p < 0.04 and p < 0.01, respectively).
CONCLUSIONS: The tolerability and safety of high-dose ultra-rush SLIT were
comparable to those reported in previous SLIT studies. SLIT with J. ashei
extract, due to its high Jun a 1 content, significantly reduced nasal steroid
consumption in patients allergic to European cypress.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17114889 [PubMed - indexed for MEDLINE]

441: Expert Opin Investig Drugs. 2006 Dec;15(12):1615-25.

Novel therapeutic interventions for allergic rhinitis.

Passalacqua G, Ciprandi G.

University of Genoa, Padiglione Maragliano, Allergy and Respiratory Diseases,
Department of Internal Medicine, Largo Rossana Benzi 10, Genoa, Italy.
passalacqua@unige.it

Allergic rhinitis is a high-prevalence disease, affecting 10 - 20% of the general
population. Allergic rhinitis is sustained by an IgE-mediated reaction and by a
complex inflammatory network of cells, mediators and cytokines that becomes
chronic when exposure to allergen persists. A T(H)2-biased immune response is the
background of the allergic inflammation. The current therapeutic strategy is
mainly based on drugs (antihistamines, nasal corticosteroids, cromones and
decongestants) and allergen immunotherapy. Drugs are (overall) effective in
controlling symptoms but do not modify the immune background that leads to
allergic inflammation and safety concerns may be present, especially for
prolonged treatments. Immunotherapy can modify the allergic response but there is
still room for improvement. Nowadays, several approaches are under investigation 
to optimise the management of allergic rhinitis. On one hand, new drugs and
antimediators are being developed. On the other hand, attempts are being made to 
selectively block relevant signal pathways of allergic reaction. Finally, one of 
the major goals is to modify the T(H)2-biased immune response by improving the
characteristics and modes of action of allergen immunotherapy.

Publication Types: 
    Review

PMID: 17107285 [PubMed - indexed for MEDLINE]

442: Int J Pediatr Otorhinolaryngol. 2007 Feb;71(2):205-9. Epub 2006 Nov 9.

Nasal carriage of Staphylococcus aureus in children with allergic rhinitis and
the effect of intranasal fluticasone propionate treatment on carriage status.

Baysoy G, Arslan S, Karabay O, Uyan AP.

Abant Izzet Baysal University Medical School, Department of Pediatrics and
Infectious Diseases, 14280 Bolu, Turkey. baysoy_g@ibu.edu.tr

OBJECTIVE: The aim of this study is to determine the rate of nasal carriage of
Staphylococcus aureus (NCSA) in children with allergic rhinitis (AR) and to
determine the effect of intranasal fluticasone propionate spray on the NCSA.
PATIENTS AND METHODS: Nasal swabs were taken from the children admitted to
general pediatrics and pediatric pulmonology clinics. Patients were divided into 
two groups according to the presence or absence of AR. Diagnosis of AR was based 
on the patient's symptoms. Nasal swabs were taken from AR patients before and
after the treatment with intranasal fluticasone propionate, and from the control 
group at the beginning and after 2 months. RESULTS: Whole NCSA rate was 17.9%; it
was 21.4% for AR patients and 15.9% for control group, respectively (p>0.05).
Treatment with intranasal fluticasone propionate spray did not influence NCSA in 
AR patients. CONCLUSION: It seemed that NCSA was not increased in children with
AR and treatment with intranasal fluticasone propionate spray did not change NCSA
in AR patients. It is obvious that better understanding of the factors affecting 
the acquisition and loss of NCSA might increase our knowledge about the
relationship between NCSA, allergic airway diseases and their treatments.

PMID: 17097153 [PubMed - indexed for MEDLINE]

443: Curr Opin Allergy Clin Immunol. 2006 Dec;6(6):455-60.

Peptide immunotherapy for allergic diseases using a rice-based edible vaccine.

Hiroi T, Takaiwa F.

Department of Allergy and Immunology, Tokyo Metropolitan Institute of Medical
Science, Tokyo, Japan.

PURPOSE OF REVIEW: Plant pollens are the most common cause of seasonal allergic
disease. The number of patients undergoing treatment for allergies to the pollen 
of Japanese cedar (major antigens: Cry j 1 and Cry j 2) has increased steadily
each year. Integration of an effective, safe and inexpensive clinical program
would be greatly improved by addressing deficiencies in systemically delivered
immunotherapy. RECENT FINDINGS: We have demonstrated that feeding mice transgenic
rice seeds accumulating the T-cell epitope peptides of Cry j 1 and Cry j 2 before
systemic challenge with total protein of cedar pollen inhibits the development of
allergen-specific IgE, IgG and CD4 T-cell proliferative responses. The levels of 
allergen-specific CD4 T-cell-derived allergy-associated T-helper 2 cytokine of
IL-4, IL-5, and IL-13 and histamine release in serum were also significantly
decreased. Moreover, clinical symptoms were inhibited in an experimental
sneezing-mouse model. SUMMARY: Plant-based edible vaccine has been shown to be
effective for treatment of Japanese cedar pollinosis. When rice seeds containing 
T-cell epitopes derived from cedar pollen allergens were orally administered to
mice, immune tolerance leading to reduction of allergen-specific IgE, T-cell
proliferative reaction and histamine could be induced, resulting in suppression
of allergic-specific symptoms such as sneezing.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17088651 [PubMed - indexed for MEDLINE]

444: J Allergy Clin Immunol. 2006 Nov;118(5):1142-8. Epub 2006 Sep 25.

Efficacy and safety of ciclesonide nasal spray for the treatment of seasonal
allergic rhinitis.

Ratner PH, Wingertzahn MA, van Bavel JH, Hampel F, Darken PF, Shah T.

Sylvana Research, Department of Pediatrics, University of Texas Health Science
Center, San Antonio, TX 78229, USA. phratner@swbell.net <phratner@swbell.net>

BACKGROUND: Allergic rhinitis (AR), an inflammatory disease of the nasal mucosa, 
affects approximately 25% of adults and 40% of children in the United States.
Ciclesonide nasal spray is a corticosteroid being developed as a hypotonic
formulation for AR. OBJECTIVE: We sought to evaluate the efficacy, safety, and
tolerability of ciclesonide nasal spray in adult and adolescent patients with
seasonal AR (SAR). METHODS: In this double-blind study patients (age, >or=12
years) were randomized to receive 200 microg of intranasal ciclesonide (n = 164) 
or placebo (n = 163) once daily for 28 days. The primary measure was morning and 
evening patient-assessed reflective total nasal symptom score (TNSS).
Additionally, instantaneous TNSSs, physician-assessed overall nasal signs and
symptoms severity, and the results of the Rhinoconjunctivitis Quality of Life
Questionnaire were evaluated. Adverse events were monitored throughout the study.
RESULTS: Ciclesonide significantly improved average morning and evening
reflective and instantaneous TNSSs compared with placebo over days 1 to 14 (P <
.001). Improvements were also noted over days 1 to 28 (P < .001) and over days 15
to 28 (P = .011). Ciclesonide was well tolerated. CONCLUSION: Intranasal
ciclesonide was superior to placebo in relieving nasal symptoms in adult and
adolescent patients with SAR. These results confirm the dose range-finding study 
in patients with SAR and support the efficacy of ciclesonide in AR. CLINICAL
IMPLICATIONS: In a clinical setting ciclesonide was shown to be safe and
effective in the treatment of SAR in adolescent and adult patients.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17088141 [PubMed - indexed for MEDLINE]

445: J Allergy Clin Immunol. 2006 Nov;118(5):1126-32. Epub 2006 Aug 28.

The role of allergic rhinitis in nasal responses to sudden temperature changes.

Graudenz GS, Landgraf RG, Jancar S, Tribess A, Fonseca SG, Faé KC, Kalil J.

Division of Immunology and Clinical Allergy, Internal Medicine Department,
Polytechnical Institute, State University of São Paulo, Brazil. gustavog@usp.br
<gustavog@usp.br>

BACKGROUND: Air conditioning-induced rhinitis in allergic individuals is a common
epidemiologic finding, but its physiopathology is still controversial. The aim of
this study was to describe and compare the effects of experimental air
conditioning temperature changes on the nasal mucosa of individuals with
persistent allergic rhinitis compared with a control group. METHODS: A
case-control challenge study was performed in a laboratory of thermal comfort
with experimental twin challenge chambers set at a 12 degrees C difference in
temperature. A group of 32 patients with persistent allergic rhinitis and a group
of 16 control subjects were exposed for 30 minutes, 3 times alternately in each
chamber. Nasal symptom scores were recorded and nasal samples collected before,
immediately after, and 24 and 48 hours after the challenge. RESULTS: The rhinitis
group showed a higher symptom score, epithelial shedding, percentage of
eosinophils, total inflammatory cells, leukotriene C(4), eosinophil cationic
protein, albumin, and tryptase levels compared with controls. There was also a
significant increase in symptom score, total cells recovered, percentage of
eosinophils, epithelial shedding, albumin, myeloperoxidase, and soluble
intercellular adhesion molecule 1 in both groups compared with baseline levels.
CONCLUSION: Sudden temperature changes led to a more pronounced inflammatory
nasal response in the rhinitis group with the recruitment and activation of
eosinophils. CLINICAL IMPLICATIONS: Persistent allergic rhinitis is a risk factor
for developing sudden temperature change-related rhinitis even in the absence of 
allergen exposure.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17088139 [PubMed - indexed for MEDLINE]

446: J Allergy Clin Immunol. 2006 Nov;118(5):1110-6. Epub 2006 Aug 7.

IL-13 is essential to the late-phase response in allergic rhinitis.

Miyahara S, Miyahara N, Matsubara S, Takeda K, Koya T, Gelfand EW.

Division of Cell Biology, Department of Pediatrics, National Jewish Medical and
Research Center, Denver, CO 80206, USA.

BACKGROUND: The pathophysiology of the early- and late-phase nasal response to
allergen challenge is not completely defined. Recent technical advances enable
direct monitoring of these responses in mice. OBJECTIVE: IL-13 is detected in the
nasal membranes of both human beings and mice with allergic rhinitis, but its
role in disease pathogenesis is unclear. We measured early and late nasal
allergic responses after treatment with soluble IL-13Ralpha2-IgG fusion protein
(sIL-13Ralpha2-Fc), and in IL-13-deficient mice (IL-13(-/-)). METHODS: IL-13(-/-)
mice (BALB/c background) and wild-type mice were sensitized to ovalbumin by
intraperitoneal injection and then challenged intranasally with ovalbumin without
sedation. The sIL-13Ralpha2-Fc or control human IgG was administered by
intraperitoneal (i.p.) injection 24 hours and 1 hour before each ovalbumin
challenge. Early nasal responses after the 4th ovalbumin challenge and late nasal
responses 24 hours after the 6th ovalbumin challenge were assessed. RESULTS:
Sensitized/challenged wild-type mice treated with sIL-13Ralpha2-Fc or IL-13(-/-) 
mice demonstrated significantly reduced late nasal responses in face of
persistent nasal tissue eosinophilia; the early nasal response was little
affected by targeting IL-13. Goblet cell hyperplasia was not detected in nasal
membranes. CONCLUSION: The data indicate that IL-13 is a major contributor to the
development of a late nasal response with little influence on the early response,
and without affecting nasal eosinophilic inflammation. Inhibition of IL-13 may
have an important therapeutic application in preventing the persistent nasal
blockage in allergic rhinitis. CLINICAL IMPLICATIONS: Current therapies for
allergic rhinitis may not take into account the important differences in the
pathophysiology of the early and late responses and the important role of IL-13
in sustaining chronic nasal congestion and obstruction.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17088137 [PubMed - indexed for MEDLINE]

447: J Allergy Clin Immunol. 2006 Nov;118(5):1105-9. Epub 2006 Jun 27.

Comment in:
    J Allergy Clin Immunol. 2007 Jun;119(6):1557-8; author reply 1558-9.

The lower airway pathology of rhinitis.

Ciprandi G, Cirillo I.

Azienda Ospedaliera Universitaria San Martino, Genoa, Italy. gio.cip@libero.it
<gio.cip@libero.it>

There is a close link between allergic rhinitis (AR) and lower airways disorders,
and this concept has been clarified and confirmed in several studies. AR
constitutes a main risk factor for new-onset asthma. Furthermore, numerous
epidemiologic surveys indicate that AR is very frequently associated with asthma.
Bronchial hyperreactivity, a component of asthma, has often been reported to be
present in patients with AR. Bronchial hyperreactivity in AR might represent a
prognostic factor for further progress to asthma. In this regard forced
expiratory flow at 25% and 75% of pulmonary volume has been proposed as an early 
marker of bronchial involvement in patients with AR who perceive only nasal
symptoms. A close structural and functional relationship between the upper and
lower airways has been recently demonstrated. Finally, adequate treatment of AR
might positively affect the course of asthma. Taking these facts into
consideration, a new diagnostic approach should be considered in managing
patients with AR: a possible bronchial involvement must be sought in each
patient.

Publication Types: 
    Review

PMID: 17088136 [PubMed - indexed for MEDLINE]

448: J Allergy Clin Immunol. 2006 Nov;118(5):985-98. Epub 2006 Sep 18.

Pharmacologic rationale for treating allergic and nonallergic rhinitis.

Greiner AN, Meltzer EO.

Allergy and Asthma Medical Group and Research Center and the University of
California San Diego School of Medicine, San Diego, CA 92123, USA.
greineran@yahoo.com <greineran@yahoo.com>

Allergic rhinitis (AR) and perennial nonallergic rhinitis (PNAR) represent
conditions affecting millions of individuals across the world. Although the
diagnosis of AR might be presumptively based on the types of symptoms and the
history of allergen triggers, confirmation requires documentation of specific IgE
reactivity. In contrast, PNAR is a condition with similar symptomatology but in
which the patient has no identifiable specific allergic sensitivities. This
review presents the diverse options of currently available pharmacologic agents
for the treatment of AR and PNAR, including intranasal corticosteroids,
H1-antihistamines, decongestants, cromolyn sodium, antileukotrienes,
anticholinergics, capsaicin, anti-IgE, and intranasal saline. Furthermore,
appropriate stepped-up, stepped-down pharmacotherapeutic algorithms are described
for the various forms of rhinitis.

Publication Types: 
    Comparative Study
    Review

PMID: 17088121 [PubMed - indexed for MEDLINE]

449: Clin Exp Allergy. 2006 Nov;36(11):1425-35.

Probiotics in the treatment of Japanese cedar pollinosis: a double-blind
placebo-controlled trial.

Xiao JZ, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N, Miyaji K,
Iwatsuki K, Togashi H, Enomoto K, Enomoto T.

Food Research and Development Laboratory, Morinaga Milk Industry Co Ltd, Zama,
Japan. j_xiao@morinagamilk.co.jp

BACKGROUND: Probiotic bacteria may be effective in the treatment of allergic
inflammation and food allergy, but efficacy and underlying mechanisms remain
unclear. OBJECTIVE: The present study investigated the effects of probiotic
strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis
(JCPsis). METHODS: In a randomized, double-blind, placebo-controlled trial, 44
JCPsis subjects received BB536 or placebo for 13 weeks during the pollen season. 
Subjective symptoms and self-care measures were recorded daily and blood samples 
were taken before and during intervention to measure blood levels of parameters
related to JCPsis. RESULTS: BB536 intake was associated with a significant
reduction in number of subjects prematurely terminated due to severe symptoms and
pollinosis medication (P=0.0057 vs. placebo group). Comparison of subjective
symptom scores indicated significant decreases in rhinorrhea, nasal blockage and 
composite scores in the BB536 group compared with the placebo group. Comparison
of medical scores showed marked improvements in all symptoms on BB536 intake. A
T-helper type 2 (Th2)-skewed immune response occurring along with pollen
dispersion was observed. BB536 significantly suppressed increases in plasma
thymus- and activation-regulated chemokine and tended to suppress elevations of
Japanese cedar pollen (JCP)-specific IgE. CONCLUSION: These results suggest the
efficacy of BB536 in relieving JCPsis symptoms, probably through the modulation
of Th2-skewed immune response.

Publication Types: 
    Randomized Controlled Trial

PMID: 17083353 [PubMed - indexed for MEDLINE]

450: Proteomics. 2006 Dec;6(23):6317-25.

Proteome analysis of maize pollen for allergy-relevant components.

Petersen A, Dresselhaus T, Grobe K, Becker WM.

Molecular and Clinical Allergology, Research Center Borstel, Borstel, Germany.
apetersen@fz-borstel.de

Over the last few decades, the cultivation of maize (Zea mays) has strongly
increased in Central Europe. We therefore decided to study the allergen
composition and the allergenic potency of its pollen in comparison with pollen
from timothy grass (Phleum pratense), a typical representative of the native
grasses. We found that 65% of the sera reactive to timothy pollen also bound to
maize pollen proteins. By using 2-DE immunoblotting, followed by incubation with 
mAbs directed against known allergens or protein sequencing, those IgE-reactive
components were further classified. Although novel, maize-specific pollen
allergens could not be found, the presence of crossreacting allergens belonging
to groups 1 and 13 (Zea m 1 and 13), both having high IgE prevalence, as well as 
the presence of the less important group 3 and 12 allergens was found. The
structural variability of Zea m 1 and Zea m 13 was determined by sequencing
clones isolated from a maize pollen cDNA library. This revealed sequence
identities of 72 and 70%, respectively, to the corresponding Phl p 1 and Phl p 13
allergens of timothy grass pollen. IgE-crossreactivity was further studied using 
immunoblot inhibition tests. Here, timothy pollen extract completely blocked IgE 
binding to maize, whereas maize pollen extract blocked IgE reactivity to only
some timothy pollen allergens.

PMID: 17080481 [PubMed - indexed for MEDLINE]

451: Allergol Int. 2006 Sep;55(3):261-9.

Inhibition of the antigen provoked nasal reaction by second-generation
antihistamines in patients with Japanese cedar pollinosis.

Okubo K, Gotoh M.

Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.
ent-kimi@nms.ac.jp

BACKGROUND: Epinastine hydrochloride and fexofenadine hydrochloride, the
second-generation antihistamines, are largely used in the indication of allergic 
rhinitis in Japan. The purpose of this study was to compare the protective
efficacy of epinastine hydrochloride or fexofenadine hydrochloride using a nasal 
provocation test with Japanese cedar pollen allergen. METHODS: A single-dose,
placebo-controlled, single-blind crossover clinical study was conducted in
patients with Japanese cedar pollinosis. The pollen exposure was done by the
antigen provocation by disc method and involved repeated provocation five times
per day. RESULTS: Among the active agents studied-epinastine hydrochloride and
fexofenadine hydrochloride-epinastine hydrochloride significantly decreased the
number of sneezing attacks and the quantity of nasal discharge for 3 hours after 
drug administration compared with placebo, a finding supported by the quantity of
nasal discharge in the nasal findings. In this study, fexofenadine hydrochloride 
showed no significant difference compared with placebo. CONCLUSIONS: This study
demonstrates better protection with epinastine hydrochloride than with
fexofenadine hydrochloride or placebo in a nasal provocation test with Japanese
cedar pollen allergen.

PMID: 17075266 [PubMed - indexed for MEDLINE]

452: Allergy. 2006 Dec;61(12):1454-8.

Comment in:
    Allergy. 2007 Jun;62(6):708.

Turkish physicians' perception of allergic rhinitis and its impact on asthma.

Civelek E, Soyer OU, Gemicioglu B, Sekerel BE.

Hacettepe University Faculty of Medicine, Pediatric Allergy and Asthma Unit,
Ankara, Turkey.

BACKGROUND: The clinical association of rhinitis and asthma has been recognized
for centuries, leading to a current definition of 'one airway, one disease'.
Current findings indicate that the optimal treatment of rhinitis might improve
coexisting asthma. OBJECTIVES: To evaluate perception of the asthma-rhinitis
association and to determine their capability in managing rhinitis. METHODS:
Participants of three national asthma meetings, in 2004, were asked to complete a
questionnaire which, aside from demographic queries, elicited responses in order 
to reflect agreement or not with the given statements. RESULTS: Of the 354
attendees, 220 (62%) responded to the questionnaire. Although over 80% reported
good perception of the asthma-rhinitis association, only one-third were examining
nasal mucosa of asthmatics, and over 70% believed sinus X-ray, blood eosinophil
count, and determination of total serum IgE were required to diagnose allergic
rhinitis. Between 20% and 40% of the physicians reported misuse of medications
for rhinitis. CONCLUSIONS: This survey documented that the asthma-rhinitis
association is generally recognized by physicians treating asthma in Turkey.
However, there are certain training needs in terms of attitude towards
examinations and appropriate use of laboratories and medications for rhinitis.
Improved understanding/management of rhinitis may contribute to asthma care as
well as patient satisfaction and adherence to treatment.

PMID: 17073877 [PubMed - indexed for MEDLINE]

453: J Physiol Pharmacol. 2006 Sep;57 Suppl 4:289-96.

Testing of cough reflex sensitivity in children suffering from allergic rhinitis 
and common cold.

Plevkova J, Varechova S, Brozmanova M, Tatar M.

Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius
University, Martin, Slovakia. plevkova@jfmed.uniba.sk

Cough associated with upper respiratory tract disorders is a common and
troublesome problem in children and little is known about the etiology of this
type of cough. This study examined the capsaicin cough sensitivity (CS) in
children suffering from allergic rhinitis (AR) and upper respiratory tract
infection (URI), comparing it with that in healthy children taken as controls
(C). CS to capsaicin, spirometry, skin prick tests, and nose-throat examination
were performed in 61 children grouped by the diagnosis of AR, URI, and C. The
results, in order of C vs. AR vs. URI, expressed as a geometric mean (+/-95% CI) 
log(10) muM of capsaicin for C2 (the lowest concentration of capsaicin in mumol/l
required to induce >or=2 coughs) were: 1.8 (1.6-1.9) vs. 1.0 (0.8-1.2) vs. 0.48
(0.2-0.8), P<0.001 and for C5 (the lowest concentration of capsaicin in mumol/l
required to induce >or=5 coughs) 2.9 (2.8-2.9) vs. 2.6 (2.5-2.6) vs. 2.1
(2.0-2.3), P<0.05. We found that CS in children with AR, even when tested out of 
pollen season, was significantly heightened compared with controls. CS in
children with URI was extremely high compared with both C and AR groups. We
conclude that pathological processes in the nose of any etiology could cause a
sensitization of the cough reflex with decreased cough threshold during
asymptomatic period of AR. Cough also is enhanced by acute inflammation in the
upper airways in nonatopic children.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17072057 [PubMed - indexed for MEDLINE]

454: Ann Allergy Asthma Immunol. 2006 Oct;97(4):454-6.

Safety of the intranasal toll-like receptor 4 agonist CRX-675 in allergic
rhinitis.

Casale TB, Kessler J, Romero FA.

Division of Allergy and Immunology, Department of Internal Medicine, Creighton
University, Omaha, Nebraska 68131, USA. tbcasale@creighton.edu

BACKGROUND: CRX-675 is an aqueous formulation of a toll-like receptor 4 agonist
and an inducer of TH1 responses. Studies in allergic dogs showed that
pretreatment with CRX-675 reduced nasal congestion induced by allergen challenge.
OBJECTIVE: To study the safety of intranasal CRX-675 treatment in patients with
seasonal allergic rhinitis. METHODS: We conducted a single-center, randomized,
double-blind, placebo-controlled, dose-escalating safety trial of single doses of
CRX-675 given intranasally before intranasal ragweed challenges. Patients with
ragweed-induced seasonal allergic rhinitis received increasing concentrations of 
ragweed to determine the dose that would result in a 30% reduction in nasal
volume (PD30) during screening. Two weeks later, each patient was rechallenged
with their assigned PD30 ragweed dose. Fourteen days later, patients were treated
with either placebo (n = 16) or CRX-675 (2, 20, 100, or 200 microg intranasally, 
n = 12 per arm) 24 hours before a subsequent PD30 ragweed challenge. Patients
were rechallenged with ragweed 14 days thereafter. RESULTS: No serious or severe 
adverse events were reported. Most adverse events were mild (grade 1) and either 
were considered unrelated to CRX-675 or resolved without intervention. The
adverse event profile of CRX-675-treated patients was similar to that of
placebo-treated patients, and no dose-related toxic effects were observed. There 
was no clear trend in the ability of CRX-675 to inhibit nasal allergen challenge 
responses, but improvement in nasal symptom scores was observed at 100 microg.
CONCLUSIONS: This preliminary trial suggests that intranasally applied CRX-675 is
safe at the doses tested. Appropriate dosing and timing will ultimately define
its potential therapeutic role for allergies.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17069098 [PubMed - indexed for MEDLINE]

455: Eur Ann Allergy Clin Immunol. 2005 Oct;37(8):303-8.

Cost effectiveness of sublingual immunotherapy in children with allergic rhinitis
and asthma.

Berto P, Bassi M, Incorvaia C, Frati F, Puccinelli P, Giaquinto C, Cantarutti L, 
Ortolani C.

Pbe consulting, Verona, Italy. patrizia.berto@pbe.it

BACKGROUND: Economic evaluations are increasingly relevant in order to provide
support for decision makers when judging about alternative ways to allocate
public funds. Aim of this study was to evaluate the economic effect of treatment 
with high dose sublingual immunotherapy (SLIT) in children. METHODS: The study
involved one allergy center, located in the north of Milan, Italy. From the
existing records of patients seen for allergic disease, we extracted all children
and adolescents with allergic disease, who had 1-year data prior to receiving
SLIT and 3-year data on SLIT. Outcome measures (number of exacerbations, visits, 
absence from nursery or school), direct costs (euros spent on drugs, specialist
visits, SLIT) and indirect costs (costs resulting from children school and
parental work loss) were analysed. A second analysis compared a sub-group of
allergic asthmatic children with a control group for costs, based on records of
patients not SLIT-treated, extracted from a network-database of paediatricians.
RESULTS: 135 patients were extracted, of which 46 had perennial, and 89 had
seasonal allergy with comparable gender and age distribution. A substantial
reduction was found in all outcome measures during SLIT compared with the before 
period. The average annual cost/patient was 2672 before SLIT initiation and
_629/year during SLIT. Similar results were found for allergen subgroups. The
asthma sub-analysis involved 41 children with SLIT and 35 controls. Again, SLIT
patients showed a substantial reduction in outcome measures; the direct
cost/patient over the whole follow-up (4 years) was _1182 for SLIT patients and
_1100 for controls. CONCLUSION: High dose SLIT may be effective in reducing the
cost of allergic rhinitis and asthma and comparably expensive to conventional
treatment in children with allergic asthma over a 4 years follow-up.

PMID: 17066648 [PubMed - indexed for MEDLINE]

456: Allergol Immunopathol (Madr). 2006 Sep-Oct;34(5):194-8.

Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass
pollen carbamylated allergoid in rhinitic patients. A double-blind,
placebo-controlled study.

Palma-Carlos AG, Santos AS, Branco-Ferreira M, Pregal AL, Palma-Carlos ML, Bruno 
ME, Falagiani P, Riva G.

Clinical Allergy Immunology Center, CAIC, Lisbon, Portugal.

BACKGROUND: The aim of this study was to confirm the clinical efficacy and safety
of a preseasonal sublingual immunotherapy (SLIT) in a group of allergic patients 
with seasonal rhinoconjunctivitis with or without mild intermittent or mild
persistent asthma. The immunotherapy was administered through the oral mucosa
with a monomeric carbamylated allergoid (allergoid SLIT) for grass pollens. A
secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal
reactivity. METHODS AND RESULTS: A single-center, randomized, double-blind,
placebo-controlled study was performed. Patients were selected and randomly
allocated to two groups: one group received active treatment (allergoid SLIT) for
2 years and the other received placebo. Both groups received the necessary drug
treatment throughout the trial. Thirty-three outpatients (20 men and 13 women,
mean age: 30 years; range: 19-43) attending our center were enrolled in the
study. Symptoms and medications were scored on diary cards during the pollen
season. An allergen nasal challenge was performed at baseline and after 2 years
of SLIT to evaluate nasal reactivity. Because the clinical scores were
non-normally distributed, the Mann-Whitney and the Chi-square tests for
intergroup comparisons and the Wilcoxon test for intragroup comparisons were
used. The results were evaluated after 1 and 2 years of treatment. Between the
first and second years of treatment, no changes in the scores for the placebo
group were found, while for the active vaccine group significant decreases were
found in rhinorrhea (p < 0.03), sneezing (p < 0.03), and conjunctivitis (p <
0.02). Symptom scores after nasal challenge decreased (p < 0.03) after 2 years'
treatment. Nasal steroid use significantly decreased in the active treatment
group during May and June in both the years of treatment (p < 0.02). Only two
mild local adverse events were reported in the active group and none was reported
in the placebo group. CONCLUSIONS: The results of this study show that the
allergoid SLIT is safe and effective in decreasing symptom scores and drug use in
rhinitic patients allergic to grass pollen.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17064648 [PubMed - indexed for MEDLINE]

457: Am J Rhinol. 2006 Sep-Oct;20(5):425-9.

Nasal levels of nitric oxide as an outcome variable in allergic upper respiratory
tract disease: Influence of atopy and hayfever on nNO.

Moody A, Fergusson W, Wells A, Bartley J, Kolbe J.

Green Lane Respiratory Services, Auckland City Hospital, Auckland, New Zealand.

BACKGROUND: The role of nasal levels of nitric oxide (nNO) as noninvasive marker 
of inflammation and as an outcome variable in allergic upper respiratory tract
disease has not been defined. Our aim is to determine in patients with perennial 
allergic rhinitis (i) whether nNO is elevated, (ii) whether increased nNO is
correlated with upper respiratory tract symptoms (discrimination), and (iii)
whether changes in symptom scores are associated with changes in nNO levels
(responsiveness). METHODS: Subjects (n = 38) with perennial rhinitis were studied
weekly for 3 weeks. At each visit they completed a validated symptom
questionnaire and had expired NO and nNO measured. RESULTS: Nasal NO levels were 
higher in those allergic to house-dust mite and cat. Nasal NO levels in subjects 
with perennial rhinitis were not elevated compared with non-atopic asymptomatic
subjects. The intra-week reproducibility of nNO measurements was poor. There was 
no relationship between the symptom scores and nasal NO levels (discrimination). 
When analysis was confined to nasal symptoms, a weak but negative correlation was
identified. Changes in symptom scores from week to week were not correlated with 
changes in nNO levels (responsiveness). CONCLUSIONS: Nasal NO levels were not
elevated in subjects with perennial rhinitis, and nNO levels were neither
discriminatory nor responsive. The measurement of nNO therefore appears not to be
a useful marker of disease activity in subjects with allergic rhinitis.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17063731 [PubMed - indexed for MEDLINE]

458: Allergy Asthma Proc. 2006 Sep-Oct;27(5):378-82.

Cross-reactivity between Parietaria species using the major rParj1 and rParj2
allergens.

Bonura A, Artale A, Marino M, Amoroso S, Marcucci F, Geraci D, Colombo P.

Istituto di Biomedicina e di Immunologia Molecolare Alberto Monroy del Consiglio 
Nazionale delle Ricerche, Palermo, Italy.

Parietaria pollen is one of the most important outdoor allergenic sources in all 
the Mediterranean countries, with a large number of subjects showing a positive
skin prick test to both P. judaica and P. officinalis pollen extracts. A
cross-reactivity between the two species has been already reported although few
data are known at the molecular level. Twenty-five consecutive patients with
Parietaria pollen allergy were selected on the basis of their clinical history.
Skin prick test to P. judaica and officinalis extracts was performed. In vitro
IgE measurement to both allergenic sources was performed by using a quantitative 
assay. ELISA inhibition experiments were made by using the rParj1 and rParj2
allergens. All the patients showed a positive skin prick test to both Parietaria 
species. Quantitative IgE measurement showed similar antibody concentration for
P. judaica and P. officinalis extracts. ELISA inhibition experiments demonstrated
that the cross-reactivity between the two species was due to the presence of the 
Parj1 and Parj2 allergens in the extracts with a high conserved IgE epitopes
content. We conclude that P. judaica and P. officinalis pollens contain highly
cross-reactive species-specific major allergens useful for the diagnosis and
therapy of both allergenic sources.

PMID: 17063667 [PubMed - indexed for MEDLINE]

459: Allergy Asthma Proc. 2006 Sep-Oct;27(5):371-7.

A 10-year aerobiological study (1994-2003) in the Mediterranean island of Crete, 
Greece: trees, aerobiologic data, and botanical and clinical correlations.

Gonianakis MI, Baritaki MA, Neonakis IK, Gonianakis IM, Kypriotakis Z,
Darivianaki E, Bouros D, Kontou-Filli K.

The Heraklion Aerobiology Group, Heraklion, Greece. gonianos@forthnet.her.gr

Pollen grains from the plant cover of a given area participate largely in the
composition of aeroflora (pollen and molds) of this area. Association of allergic
respiratory disorders with concentration of allergenic particles in the
atmosphere is well documented, and aerobiologic studies are of great relevance. A
10-year volumetric aerobiologic study was conducted in the city of Heraklion,
located in the center of the north-shore of the island of Crete, Greece. Main
allergenic families and genera encountered were, in descending order of frequency
Oleaceae, Quercus, Platanaceae, Cupressaceae, Pinaceae, Populus, Moraceae, and
Corylaceae. Concentrations noted for most of these aeroallergens were much lower 
than those reported from other European regions. In parallel, an atopic
population of 576 individuals, exhibiting allergic symptoms mainly of the
respiratory tract were subjected to a battery of skin-prick tests. A fair degree 
of agreement between total pollen counts and positive skin-prick test frequencies
for the families of Oleaceae, Platanaceae, and Cupressaceae was noted. On the
contrary a poor degree of concordance was noted for the rest of the families and 
genera.

PMID: 17063666 [PubMed - indexed for MEDLINE]

460: Allergy Asthma Proc. 2006 Sep-Oct;27(5):363-70.

A 10-year aerobiological study (1994-2003) in the Mediterranean island of Crete, 
Greece: grasses and other weeds, aerobiological data, and botanical and clinical 
correlations.

Gonianakis M, Neonakis I, Gonianakis I, Baritaki M, Kypriotakis Z, Potamias G,
Bouros D, Kontou-Fili K.

The Heraklion Aerobiology Group, Heraklion, Greece. gonianos@forthnet.her.gr

Grasses and weeds contain species that produce abundant pollen grains and have
been implicated as causative agents in both asthma and allergic rhinitis. In this
study, we present the pollen counts of allergenic grasses and weeds on the island
of Crete and show their impact on allergic individuals. Heraklion is located at
the center of the north shore of Crete and has been monitored with a Burkard
7-day volumetric spore trap since 1994, to determine the identity, concentration,
and seasonal variation of airborne pollen grains. Data from 10 consecutive years 
were recorded, analyzed, and correlated to the growth of respective plants on
this island. The island's vegetation and blossoming periods have been
investigated by conducting field trips. In parallel, an atopic population of 576 
individuals with a convincing history of allergic respiratory disease-rhinitis
and/or asthma-was subjected to skin-prick tests with 50 common allergens.
Quantitatively, there was a fair agreement between total pollen counts and
positive skin-prick test frequencies for Parietaria (Urticaceae family). For the 
majority of the grass and weed genera, strongly positive skin test responses were
observed frequently, despite rather low pollen counts.

PMID: 17063665 [PubMed - indexed for MEDLINE]

461: Int Arch Allergy Immunol. 2007;142(2):151-7. Epub 2006 Oct 20.

Airborne pollen concentrations and the incidence of allergic asthma and
rhinoconjunctivitis in northern Italy from 1992 to 2003.

Ridolo E, Albertini R, Giordano D, Soliani L, Usberti I, Dall'Aglio PP.

Department of Clinical Sciences, University of Parma, Parma, Italy.

BACKGROUND: Aeroallergens and the environment play an important role in the
pathogenesis of respiratory allergies. In a 12-year study carried out in Northern
Italy (geographic area of Parma), the effects of airborne pollen and
meteorological conditions on the incidence of allergic asthma and
rhinoconjunctivitis were evaluated. PATIENTS AND METHODS: Among 9,060 subjects
examined for respiratory pathologies at our Allergy Unit, Parma Hospital, Italy, 
from 1992 to 2003, only 1,054 positive to only one type of inhalant allergen in
the skin prick test were studied, to avoid bias of cross-reactivity. Allergy and 
clinical aspects were compared with the duration of the pollination period, and
peaks and total concentrations of airborne pollen. RESULTS: Our data showed a
significantly growing trend of allergy to mites, pets and birch pollen and a
significant increase in asthma, and a significantly decreasing trend of positive 
reactions to grasses and a decrease in rhinoconjunctivitis. At the same time,
there was a significant decrease in total pollen counts, concentration peaks and 
pollination period of grasses. A significant increase was only observed in
ragweed and ash-olive total and peak pollen concentrations. CONCLUSIONS:
Significant correlations between the increasing incidence in asthma and allergy
to mites, pets and birch pollen are shown. The decrease in the total pollen count
and concentration peaks of grass pollen was correlated to the decreasing trend of
rhinoconjunctivitis. The trend of increasing concentrations of ash-olive and
ragweed pollen was not accompanied by an increase in the related allergy.
Copyright 2007 S. Karger AG, Basel.

PMID: 17057413 [PubMed - indexed for MEDLINE]

462: Ann Allergy Asthma Immunol. 2006 Sep;97(3):389-96.

Comparison of cetirizine-pseudoephedrine and placebo in patients with seasonal
allergic rhinitis and concomitant mild-to-moderate asthma: randomized,
double-blind study.

Nathan RA, Finn AF Jr, LaForce C, Ratner P, Chapman D, de Guia EC, Hewlett D,
Kramer B.

Asthma and Allergy Associates, Colorado Springs 80907, USA. DrRNathan@aol.com

BACKGROUND: Allergic rhinitis (AR) and asthma are common concurrent conditions.
OBJECTIVES: To evaluate the effects of cetirizine hydrochloride (5
mg)-pseudoephedrine hydrochloride (120 mg) (cetirizine-D) twice daily on AR and
asthma symptoms, pulmonary function, and asthma-related quality of life in 274
patients with confirmed seasonal AR and concomitant mild-to-moderate asthma.
METHODS: In this multicenter, randomized, double-blind, placebo-controlled study,
after a 1-week screening period, patients took cetirizine-D or placebo for 4
weeks. The primary efficacy variable, AR total symptom severity complex score,
was derived from patient daily diary ratings of sneezing, runny nose, itchy nose,
postnasal drip, and nasal congestion. Asthma symptom severity total scores were
derived from twice-daily diary ratings of wheezing, coughing, shortness of
breath, and chest tightness. Pulmonary function was tested at clinic visits and
by patients each morning and evening. Patients completed the Asthma Quality of
Life Questionnaire at each visit. All tests were 2-sided, with statistical
significance at the .05 level. RESULTS: Cetirizine-D reduced total symptom
severity complex scores by 42.3% overall vs 23.6% with placebo (P < .001). Asthma
symptom severity total scores were significantly improved with cetirizine-D at
most times vs placebo. Cetirizine-D treatment was also associated with
significantly improved Asthma Quality of Life Questionnaire overall scores.
Pulmonary function test results were neutral. Cetirizine-D was well tolerated,
with discontinuation and adverse event rates similar to placebo. Somnolence
occurred in 8 patients (5.8%) taking cetirizine-D and in 1 (0.7%) taking placebo.
CONCLUSIONS: Treatment with cetirizine-D twice daily significantly reduced
rhinitis and asthma symptoms and improved overall asthma quality of life in
patients with seasonal AR and concomitant mild-to-moderate asthma.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17042147 [PubMed - indexed for MEDLINE]

463: Ann Allergy Asthma Immunol. 2006 Sep;97(3):375-81.

Impact of azelastine nasal spray on symptoms and quality of life compared with
cetirizine oral tablets in patients with seasonal allergic rhinitis.

Berger W, Hampel F Jr, Bernstein J, Shah S, Sacks H, Meltzer EO.

Southern California Research, Mission Viejo 92691, USA. weberger@uci.edu

BACKGROUND: In fall 2004, the first Azelastine Cetirizine Trial demonstrated
statistically significant improvements in the total nasal symptom score (TNSS)
and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores with the use 
of azelastine nasal spray vs oral cetirizine in patients with seasonal allergic
rhinitis (SAR). OBJECTIVE: To compare the effects of azelastine nasal spray vs
cetirizine on the TNSS and RQLQ scores in patients with SAR. METHODS: This
2-week, double-blind, multicenter trial randomized 360 patients with
moderate-to-severe SAR to azelastine, 2 sprays per nostril twice daily, or
cetirizine, 10-mg tablets once daily. The primary efficacy variable was the
12-hour reflective TNSS (rhinorrhea, sneezing, itchy nose, and nasal congestion).
Secondary efficacy variables were individual symptom scores and the RQLQ score.
RESULTS: Azelastine nasal spray and cetirizine significantly improved the TNSS
and individual symptoms compared with baseline (P < .001). The TNSS improved by a
mean of 4.6 (23.9%) with azelastine nasal spray compared with 3.9 (19.6%) with
cetirizine. Significant differences favoring azelastine nasal spray were seen for
the individual symptoms of sneezing and nasal congestion. Improvements in the
RQLQ overall (P = .002) and individual domain (P < or = .02) scores were greater 
with azelastine nasal spray. Both treatments were well tolerated. CONCLUSIONS:
Azelastine nasal spray and cetirizine effectively treated nasal symptoms in
patients with SAR. Improvements in the TNSS and individual symptoms favored
azelastine over cetirizine, with significant differences for nasal congestion and
sneezing. Azelastine nasal spray significantly improved the RQLQ overall and
domain scores compared with cetirizine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17042145 [PubMed - indexed for MEDLINE]

464: Ann Allergy Asthma Immunol. 2006 Sep;97(3):336-42.

Identification of italian cypress (Cupressus sempervirens) pollen allergen Cup s 
3 using homology and cross-reactivity.

Togawa A, Panzani RC, Garza MA, Kishikawa R, Goldblum RM, Midoro-Horiuti T.

Department of Pediatrics, Child Health Research Center, University of Texas
Medical Branch, Galveston 77555-0366, USA.

BACKGROUND: The prevalence of seasonal allergic diseases of the upper airways is 
increasing in industrialized countries. The Cupressaceae are important causes of 
pollinosis, particularly in Europe. OBJECTIVE: To determine whether the pollen
from Cupressus sempervirens (Italian cypress) contains a pathogenesis-related
group 5 (PR-5) protein, similar to that found in other allergenic Cupressaceae
pollens. METHODS: Messenger RNA was purified from Italian cypress pollen, and
complementary DNA (cDNA) was synthesized. cDNAs for PR-5 proteins were amplified 
by polymerase chain reaction and extended by rapid amplification of cDNA ends
methods. Recombinant Cup s 3 was expressed in Escherichia coli as a fusion
protein. Inhibition enzyme-linked immunosorbent assays were used to test the
allergenicity of Cup s 3. RESULTS: Three cDNAs were cloned. These clones had
approximately 95% identity to Jun a 3 and Cup a 3. Recombinant Cup s 3.0102
maltose-binding protein inhibited the IgE from most patients from binding to an
extract of Italian cypress. The extent of inhibition suggested that antibodies to
Cup s 3 were a prominent component of the IgE response to Italian cypress pollen.
CONCLUSION: Cup s 3, an allergen of Italian cypress pollen, was identified based 
on cross-reactivity and homology with other pollen PR-5 proteins, despite an
apparently low level of protein expression. Variations in the content of Cup s 3 
in the pollen from different regions or trees should be considered in the choice 
of extracts for diagnosis and specific immunotherapy for Italian cypress pollen
hypersensitivity.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17042139 [PubMed - indexed for MEDLINE]

465: Qual Life Res. 2007 Mar;16(2):191-201. Epub 2006 Oct 11.

Once-daily sublingual allergen-specific immunotherapy improves quality of life in
patients with grass pollen-induced allergic rhinoconjunctivitis: a double-blind, 
randomised study.

Rak S, Yang WH, Pedersen MR, Durham SR.

Section of Allergy, Sahlgrenska University Hospital, Göteborg, Sweden.
sabina.rak@medfak.gu.se

The effect of sublingual immunotherapy on quality of life (QoL) was examined in
patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were
randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T
Phleum pratense extract; GRAZAX or placebo. Treatment was initiated 8 weeks
before the start of the grass pollen season and continued throughout. If symptoms
were present, patients received loratadine or placebo rescue medication. There
were three major findings: in patients using loratadine, grass allergen tablets
provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life
Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with
75,000 SQ-T tablet than with placebo at first and second seasonal visit,
respectively; in patients not using loratadine, grass allergen tablets improved
QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ-T
tablet at second seasonal visit; grass tablets (without loratadine) had a greater
effect on QoL than loratadine alone. RQLQ score was 26% (p = 0.014) greater with 
75,000 SQ-T tablets than loratadine at second seasonal visit. These data show
that sublingual immunotherapy with grass allergen tablets improves QOL in
allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater
than rescue antihistamine alone.

Publication Types: 
    Randomized Controlled Trial

PMID: 17033900 [PubMed - indexed for MEDLINE]

466: Int J Immunopathol Pharmacol. 2006 Jul-Sep;19(3):629-38.

Relationship between specific serum IgE to Ascaris lumbricoides and onset of
respiratory symptoms in Bangladesh immigrants.

Di Lorenzo G, Pacor ML, Mansueto P, Esposito-Pellitteri M, Scichilone N, Ditta V,
Lo Bianco C, Leto-Barone MS, Di Fede G, Corrocher R, Mansueto S, Rini GB.

Dipartimento di Medicina Clinica e delle Patologie Emergenti, Università degli
Studi di Palermo, Italy. dilo601@unipa.it

The role of helminths in asthma and/or rhinitis and in allergic sensitization is 
still unclear. We assessed the relationship between Ascaris-specific IgE,
respiratory symptoms and allergic sensitization in Bangladesh immigrants. 246
individuals were examined from 1996 to 2001. Serum total IgE, Ascaris IgE,
specific IgE to inhalant allergens, skin prick tests (SPT) and parasitological
evaluation of the stool were performed. Total serum IgE were significantly higher
in Ascaris-IgE positive (> 0.35 kU/L) individuals (806.5 [409.0-1436.0] kU/L vs. 
207.0 [127.0-332.5] kU/L; P < 0.0001) and in subjects with respiratory symptoms
(413.0 [239.0-1096.0] kU/L vs. 259.5 [147.0-387.0] kU/L), (P < 0.0001), but not
in SPT positive subjects (413.0 [179.0-894.0] kU/L vs. 404.6 [305.0-1201.0] kU/L 
(P = 0.5). Ascaris-specific IgE were detected in 48 subjects with respiratory
symptoms (40.0%) and in 46 subjects without respiratory symptoms (36.5%) (P =
0.5). The SPT positivity was similar between Ascaris-IgE seropositive (38.2%) and
Ascaris-IgE seronegative (38.1%) subjects (P = 0.9). Total IgE and length of stay
in Italy correlated with SPT positivity (OR 5.6 [CI 95% 1.5-19.8], P = 0.007, and
OR 1.5 [CI 95% 1.3-1.7], P< 0.0001), and with respiratory symptoms (OR 13.7 [CI
95% 3.0-62.4];, P = 0.0007, and OR 2.4 [CI 95% 1.9-3.0], P < 0.0001). Ascaris-IgE
were negatively associated with SPT positivity (OR 0.3 [CI 95% 0.1-0.8], P =
0.02) and with respiratory symptoms (OR 0.1 [CI 95% 0.04-0.7], P = 0.01). Our
findings favour the role of environmental factors in the development of
respiratory symptoms in immigrants, irrespective of Ascaris-IgE.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17026848 [PubMed - indexed for MEDLINE]

467: N Engl J Med. 2006 Oct 5;355(14):1445-55.

Comment in:
    N Engl J Med. 2007 Jan 4;356(1):86-7; author reply 87.    N Engl J Med. 2007 Jan 4;356(1):86; author reply 87.

Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic
rhinitis.

Creticos PS, Schroeder JT, Hamilton RG, Balcer-Whaley SL, Khattignavong AP,
Lindblad R, Li H, Coffman R, Seyfert V, Eiden JJ, Broide D; Immune Tolerance
Network Group.

Department of Medicine, Division of Allergy and Clinical Immunology, Johns
Hopkins University School of Medicine, Baltimore, USA. pcretic@jhmi.edu

BACKGROUND: Conjugating immunostimulatory sequences of DNA to specific allergens 
offers a new approach to allergen immunotherapy that reduces acute allergic
responses. METHODS: We conducted a randomized, double-blind, placebo-controlled
phase 2 trial of a vaccine consisting of Amb a 1, a ragweed-pollen antigen,
conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory
sequence of DNA (AIC) in 25 adults who were allergic to ragweed. Patients
received six weekly injections of the AIC or placebo vaccine before the first
ragweed season and were monitored during the next two ragweed seasons. RESULTS:
There was no pattern of vaccine-associated systemic reactions or clinically
significant laboratory abnormalities. AIC did not alter the primary end point,
the vascular permeability response (measured by the albumin level in nasal-lavage
fluid) to nasal provocation. During the first ragweed season, the AIC group had
better peak-season rhinitis scores on the visual-analogue scale (P=0.006),
peak-season daily nasal symptom diary scores (P=0.02), and midseason overall
quality-of-life scores (P=0.05) than the placebo group. AIC induced a transient
increase in Amb a 1-specific IgG antibody but suppressed the seasonal increase in
Amb a 1-specific IgE antibody. A reduction in the number of
interleukin-4-positive basophils in AIC-treated patients correlated with lower
rhinitis visual-analogue scores (r=0.49, P=0.03). Clinical benefits of AIC were
again observed in the subsequent ragweed season, with improvements over placebo
in peak-season rhinitis visual-analogue scores (P=0.02) and peak-season daily
nasal symptom diary scores (P=0.02). The seasonal specific IgE antibody response 
was again suppressed, with no significant change in IgE antibody titer during the
ragweed season (P=0.19). CONCLUSIONS: In this pilot study, a 6-week regimen of
the AIC vaccine appeared to offer long-term clinical efficacy in the treatment of
ragweed allergic rhinitis. (ClinicalTrials.gov number, NCT00346086
[ClinicalTrials.gov] .). Copyright 2006 Massachusetts Medical Society.

Publication Types: 
    Clinical Trial, Phase II
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17021320 [PubMed - indexed for MEDLINE]

468: Expert Opin Pharmacother. 2006 Oct;7(14):1989-2001.

Rupatadine: pharmacological profile and its use in the treatment of allergic
disorders.

Picado C.

University of Barcelona, Servei de Pneumologia i Allèrgia Respiratoria, Hospital 
Clínic, c/Villarroel 170, 08036 Barcelona, Spain. cpicado@ub.edu

Rupatadine is a once-daily, non-sedating, selective and long-acting new drug with
a strong antagonist activity towards both histamine H(1) receptors and
platelet-activating factor receptors. The use of rupatadine is indicated in adult
and adolescent patients (> 12 years of age) suffering from intermittent and
persistent allergic rhinitis and chronic idiopathic urticaria. In the treatment
of these diseases, rupatadine is at least as effective as ebastine, cetirizine,
loratadine and desloratadine. A very good safety profile of rupatadine has been
evidenced in various studies, including a long-term (1-year) safety study.
Rupatadine does not present drug-drug interactions with azithromycin, fluoxetine 
and lorazepam, but should not be administered concomitantly with known CYP3A4
inhibitors.

Publication Types: 
    Review

PMID: 17020424 [PubMed - indexed for MEDLINE]

469: Occup Environ Med. 2007 Feb;64(2):101-7. Epub 2006 Oct 3.

Hay fever and asthma symptoms in conventional and organic farmers in The
Netherlands.

Smit LA, Zuurbier M, Doekes G, Wouters IM, Heederik D, Douwes J.

Institute for Risk Assessment Sciences, Division of Environmental Epidemiology,
Utrecht University, Utrecht, The Netherlands. l.smit@iras.uu.nl

BACKGROUND: Farming has been associated with respiratory symptoms and with
protection against atopy. To date, effects of organic farming on respiratory
health have not been studied. AIMS: To (1) compare hay fever and asthma-like
symptoms in organic and conventional farmers and (2) assess associations between 
current and childhood farm exposures and respiratory health effects by conducting
a survey. METHODS: Questionnaire data from 1205 conventional and 593 organic
farmers were evaluated. Associations between health effects and farm exposures
were assessed by logistic regression analyses. RESULTS: Organic farmers reported 
less wheezing with shortness of breath and slightly more hay fever than
conventional farmers. However, organic farming was not an independent determinant
of hay fever when adjusted for farming practices and potential confounders.
Livestock farmers who grew up on a farm had a threefold lower prevalence of hay
fever than crop farmers without a farm childhood (odds ratio (OR) 0.3, 95%
confidence interval (CI) 0.1 to 0.5). Both crop farmers who grew up on a farm and
livestock farmers who did not grow up on a farm had a reduced prevalence,
although less pronounced and not statistically significant. Use of disinfectants 
containing quaternary ammonium compounds was positively related to hay fever (OR 
2.1, 95% CI 1 to 4.4). No effects of farming practices were found for asthma.
CONCLUSIONS: Our study adds to the evidence that a farm childhood in combination 
with current livestock farming protects against allergic disorders. This effect
was found for both organic and conventional farmers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17018582 [PubMed - indexed for MEDLINE]

470: Clin J Sport Med. 2006 Sep;16(5):401-5.

Patterns of allergic reactivity and disease in Olympic athletes.

Katelaris CH, Carrozzi FM, Burke TV, Byth K.

Department of Clinical Immunology and Allergy, Westmead Hospital, Sydney,
Australia. chk@allergyimmunol.com.au

OBJECTIVE: Because the Sydney Olympic Games were being held in the spring, we
wished to examine the prevalence of allergic disorders in the Australian Olympic 
and Paralympic athletes and to examine patterns of allergic reactivity and
medication use for the treatment of allergic symptoms. DESIGN: A survey case
series of Australian Olympic and Paralympic athletes. SETTING: Screening was
conducted on team processing days. PARTICIPANTS: Prospective members of the
Australian Olympic and Paralympic teams. INTERVENTION: A questionnaire seeking
information on the presence of allergic disorders, symptoms, family history, and 
medication use was administered. Skin-prick tests (SPT) for sensitivity to common
aeroallergens was performed. OUTCOME MEASURES: Athletes were classified as atopic
or non-atopic, and patterns of reactivity were examined according to sporting
category. RESULTS: Of the athletes, 56% had a positive SPT to at least 1
allergen, with 34% reacting to at least 1 seasonal allergen. There was no
significant association between skin test reactivity and sporting category. Of
the athletes, 37% had allergic rhinoconjunctivitis (AR/C), whereas 24% had
seasonal allergic rhinoconjunctivitis (SAR/C). Approximately one-third of all
those with AR/C had a history of asthma, whereas approximately one-fifth had a
history of atopic dermatitis. Swimmers were most likely to have asthma, AR/C, and
positive skin tests to any allergen. Very few athletes with self-reported AR/C
took any medication to relieve their symptoms. CONCLUSIONS: Allergic disorders
are common among athletes from all sports. The known impact of AR/C on quality of
life necessitates that it be screened for and managed appropriately.

PMID: 17016116 [PubMed - indexed for MEDLINE]

471: Pediatr Allergy Immunol. 2006 Nov;17(7):524-6.

Erratum in:
    Pediatr Allergy Immunol. 2007 Feb;18(1):90.

Allergic conjunctivitis in children with asthma, rhinitis and eczema in a
secondary outpatient clinic.

Gradman J, Wolthers OD.

Children's Clinic Randers, Randers, Denmark. j.gradman@dadlnet.dk

Little evidence is available on the prevalence of allergic conjunctivitis in
pediatric populations. The objective of this study was to assess the cumulative
prevalence of allergic conjunctivitis in children with rhinitis, asthma and
eczema in a secondary pediatric outpatient clinic. Children aged 5-15 yr referred
during the period of 2002-2004 in whom allergic conjunctivitis, asthma, allergic 
rhinitis or eczema was diagnosed were included in a retrospective survey. At
referral patient characteristics, history, symptoms, signs and results of type 1 
allergy tests were entered into an electronic form. Four hundred and fifty-eight 
children with a mean age of 9.4 yr were studied. Of 316, 324 and 149 children
with rhinitis, asthma or eczema, respectively, 133 (42%), 78 (24%) and 45 (30%)
had concomitant allergic conjunctivitis. One hundred and thirty-seven (30%) had
allergic conjunctivitis, of whom 133 (97%) also had allergic rhinitis, 77 (56%)
asthma and 45 (33%) eczema. One hundred and twenty-five (91%) of the children
with allergic conjunctivitis had positive allergy tests to one or more allergens,
sensitization to house dust mites being more frequent in chronic allergic
conjunctivitis than in acute allergic conjunctivitis (95% vs. 53%; p < 0.01).
Sensitization to grass was more frequent in children with acute allergic
conjunctivitis (78% vs. 57%; p = 0.03). In a secondary pediatric outpatient
clinic allergic conjunctivitis is a frequent co-morbidity to allergic rhinitis
and to asthma and eczema. Allergic conjunctivitis need to be included as an
important co-morbidity in future guidelines on asthma, rhinitis and eczema
management.

PMID: 17014628 [PubMed - indexed for MEDLINE]

472: Pediatr Allergy Immunol. 2006 Nov;17(7):519-23.

Prevalence of allergic rhinitis and nasal smear eosinophilia in 11- to 15 yr-old 
children in Shiraz.

Miri S, Farid R, Akbari H, Amin R.

Immunology, Asthma and Allergy Research Institute, Tehran University of Medical
Sciences, Tehran, Iran. md_saramiri@yahoo.com

Allergic rhinitis (AR) is a common condition among schoolchildren. The prevalence
rate of AR differs among countries and even among regions within the same
country. The objective of this study was to determine the prevalence of nasal
symptoms and signs of AR and nasal smear eosinophilia in 11- to 15-yr-old
children in Shiraz. A total of 4584 children aged 11-15 yr of both sexes were
surveyed from May 1995 to April 1996, and nasal symptoms and signs of AR
(sneezing, rhinorrhea, nasal blockage, itching, color change, mucosal swelling,
nasal wetness, and nasal crease), based on questionnaire and ear, nose and throat
(ENT) examination were recorded. In addition, smears were taken from nasal
secretions and stained. The results compared with nasal smears related to 340
healthy children. 1008 (22%) schoolchildren had nasal symptoms of AR (based on
the questionnaire), 445 (9.7%) were identified as having nasal symptoms and signs
of AR (based on the questionnaire and ENT specialist examination), and 226 (5.8%)
had nasal symptoms and signs of AR associated with nasal eosinophilia (based on
the questionnaire, ENT specialist examination and positive nasal smear for
eosinophilia). Nasal eosinophilia was present in 274 (62%) children with nasal
symptoms and signs of AR. This survey showed that prevalence of nasal symptoms
and signs of AR was high in schoolchildren in Shiraz. Nasal smear eosinophilia
had a diagnostic specificity of 96% and sensitivity of 62% and seems to be a
potentially valuable test for AR.

PMID: 17014627 [PubMed - indexed for MEDLINE]

473: Allergy. 2006 Nov;61(11):1310-5.

Influence of physical inactivity on the prevalence of hay fever.

Kohlhammer Y, Zutavern A, Rzehak P, Woelke G, Heinrich J.

GSF - National Research Center for Environment and Health, Institute of
Epidemiology, Neuherberg, Germany.

BACKGROUND: Atopic diseases constitute a major public health problem, increasing 
constantly in frequency and severity. While treatments are improving, the main
cause for an increasing trend of hay fever and its definite triggers remain
unclear. The aim of our study was to assess whether physical inactivity could be 
a risk factor for hay fever. METHODS: We analysed data of a cohort of children
aged 5-14 years at baseline (1992-1993) who were followed up until 2003-2005.
Parental-reported information on physical activity (being active, doing sports)
was obtained for 2429 children participating at the baseline survey (active: n = 
1923; semi-active: n = 364; inactive: n = 142). A total of 1703 children (70.1%) 
were reapproached at least once during follow-up. Logistic regression models were
applied to study associations between hay fever, allergic sensitization and
physical activity, adjusted for potentially relevant confounders such as age,
gender, study site, parental education, breastfeeding, crowding, daycare,
dampness or visible moulds, contact to cats, current or prior environmental
tobacco smoke exposure and parental atopy. RESULTS: Significantly higher rates of
hay fever were seen for inactive children [aOR 2.39 (95% CI 1.31-4.36) for
baseline survey 1992-1993 and aOR 1.76 (95% CI 1.14-2.71) for the
follow-up-period until 2005]. In addition, the relative risk of incident cases of
hay fever increased depending on inactivity [aRR 1.50 (95% CI 1.05-2.13)]. No
association was found between physical inactivity and allergic sensitization
assessed by radioallergosorbent test determinations. CONCLUSIONS: Although the
underlying biological mechanisms could not be clarified, increasing physical
activity in childhood is suggested to prevent hay fever.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17002707 [PubMed - indexed for MEDLINE]

474: Allergy. 2006 Nov;61(11):1305-9.

Swimming pool attendance and hay fever rates later in life.

Kohlhammer Y, Döring A, Schäfer T, Wichmann HE, Heinrich J; KORA Study Group.

GSF, National Research Center for Environment and Health, Institute of
Epidemiology, Neuherberg, Germany.

BACKGROUND: Exposure to chlorination by-products through swimming pool attendance
showed adverse health effects on children. The aim of our study was to assess
whether pool attendance in childhood would be related to higher rates of allergic
diseases in adulthood, with special regard to hay fever. METHODS: 2606 adults
aged 35-74 years provided retrospectively collected information on swimming pool 
attendance and medical history, including data on atopic diseases. Information
was assessed by a combination of a personal interview and a self-administered
questionnaire. Logistic regression models were applied to study associations
between hay fever and swimming pool attendance, adjusted for potentially relevant
confounders, such as age, gender, region, education and smoking. RESULTS: Higher 
rates of hay fever could be seen when frequently exposed at school age (aOR:
1.74, 95% CI: 1.09-2.77), frequently exposed during the past 12 months (aOR:
1.32, 95% CI: 0.92-1.89) and ever exposed (aOR: 1.65, 95% CI: 0.98-2.78).
Strongest associations were found for the youngest subjects and were dose-related
to the extent of current and school-age pool attendance. CONCLUSIONS: Impaired
integrity of the lung epithelial by exposure to chlorination by-products might
facilitate a closer contact to allergens and therefore could result in higher
rates of hay fever.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17002706 [PubMed - indexed for MEDLINE]

475: J Pharmacol Toxicol Methods. 2007 May-Jun;55(3):297-302. Epub 2006 Aug 16.

Biological assay using T cell response for Cry-consensus peptide designed for the
peptide-based immunotherapy of Japanese cedar pollinosis.

Kozutsumi D, Tsunematsu M, Yamaji T, Kino K.

Research and Development Section I, Pharmaceuticals Development Department, Meiji
Dairies Corporation, 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
daisuke_kozutsumi@meiji-milk.com

INTRODUCTION: Cry-consensus peptide is a linearly linked peptide of T-cell
epitopes for the management of Japanese cedar (JC) pollinosis and is expected to 
become a new drug for immunotherapy. However, the mechanism of T-cell epitopes in
allergic diseases is not well understood, and thus, a simple in vitro procedure
for evaluation of its biological activity is desired. METHODS: Peripheral blood
mononuclear cells (PBMC) were isolated from 27 JC pollinosis patients and 10
healthy subjects, and cultured in vitro for 4 days in the presence of
Cry-consensus peptide and (3)H-thymidine. The relationship between growth
stimulation (stimulation index; SI) and antigen-specific IgE levels in serum was 
also investigated in JC pollinosis patients. Moreover, to confirm the importance 
of the primary sequence in Cry-consensus peptide, heat-treated Cry-consensus
peptide and a mixture of the amino acids of which Cry-consensus peptide is
composed, and their (3)H-thymidine uptake was compared with Cry-consensus
peptide. Finally, whether Cry-consensus peptide stimulates PBMCs from healthy
subjects was investigated. RESULTS: The mean SI of JC patients showed a good
correlation with Cry-consensus peptide concentration in the culture medium;
however, the SI was independent of the anti-Cry j 1 IgE level. Heat-denatured
Cry-consensus peptide retained a PBMC proliferation stimulatory effect comparable
to the original Cry-consensus peptide, while the mixture of amino acids
constituting Cry-consensus peptide did not stimulate PBMC proliferation. PBMCs
from healthy subjects did not respond to Cry-consensus peptide at all.
DISCUSSION: These data indicate that the PBMC response of patients suffering from
JC pollinosis to Cry-consensus peptide is specific for the sequence of T cell
epitopes thereof and may be useful for the evaluation of the efficacy of
Cry-consensus peptide in vivo.

PMID: 16996752 [PubMed - indexed for MEDLINE]

476: Arch Otolaryngol Head Neck Surg. 2006 Sep;132(9):1001-7.

Differential expression of surfactant protein A in the nasal mucosa of patients
with allergy symptoms.

Wootten CT, Labadie RF, Chen A, Lane KF.

Department of Otolaryngology, Division of Pulmonary and Critical Care Medicine,
Vanderbilt University, Nashville, Tenn, USA. christopher.t.wooten@vanderbilt.edu

OBJECTIVE: To characterize surfactant protein A (SP-A) expression in human nasal 
tissue and correlate differential expression of SP-A with symptoms suggestive of 
allergic rhinitis. DESIGN: Allergic rhinitis symptom data were prospectively
collected in the form of the Rhinitis Symptom Utility Index, the
Rhinoconjunctivitis Quality of Life Questionnaire, and a Visual Analog Scale.
Immunohistochemical staining for SP-A was performed on resected nasal tissue.
Quantitative polymerase chain reaction amplification of the SP-A gene referenced 
to beta-actin was performed on complementary DNA samples synthesized from total
RNA isolates. SETTING: Academic tertiary referral center, department of
otolaryngology laboratories. PATIENTS: Twenty-five consecutive patients
undergoing nasal surgery. MAIN OUTCOME MEASURES: Immunohistochemical staining of 
SP-A in human nasal mucosa and submucosa, polymerase chain reaction amplification
of SP-A messenger RNA, and rhinitis symptom scores. RESULTS: Immunostaining
localized SP-A to the mucosa and submucosal glands in specimens. Quantitative
polymerase chain reaction demonstrated correlation between SP-A messenger RNA
concentration and the total Rhinitis Symptom Utility Index score (0.51, P = .009)
as well as "sneezing over the previous week" (0.40, P = .049), "runny nose over
the previous week" (0.55, P = .005), and "sneezing today" (0.47, P = .02).
CONCLUSIONS: To our knowledge, this is the first report of SP-A expression in
human nasal tissue. Furthermore, the degree of expression correlated with
severity of disease as measured by the Rhinitis Symptom Utility Index in patients
with allergic rhinitis symptoms.

PMID: 16982978 [PubMed - indexed for MEDLINE]

477: Clin Pediatr (Phila). 2006 Oct;45(8):697-704.

The role of intranasal corticosteroids in the management of pediatric allergic
rhinitis.

Kaari J.

Department of Pediatrics, School of Osteopathic Medicine, University of Medicine 
and Dentistry of New Jersey, Turnersville, NJ 08012, USA.

Allergic rhinitis (AR) is currently the most common chronic disease in children
in the United States, affecting as many as 40% of the children in the population.
AR can substantially decrease a child's quality of life and can contribute to
school absenteeism. Intranasal corticosteroids (INS) are thought to be the most
effective treatment choice for controlling the symptoms of AR. However, parent
and physician concerns over INS safety in children have often led to INS being
used as a second-line treatment option. More recently, safety studies have shown 
that the newer INS agents have improved safety profiles compared with older INS
agents. The newer INS drugs have been found to have minimal adverse effects on
growth and hypothalamic-pituitary-adrenal-axis function in children, which is a
concern when prescribing corticosteroids. This review will discuss the
pathophysiology, diagnosis, and classification of AR. The mechanism of action,
efficacy, and safety of INS will also be discussed by focusing on clinical
evidence. Furthermore, other considerations, such as parent or caregiver
education and patient compliance, will be reviewed.

Publication Types: 
    Review

PMID: 16968954 [PubMed - indexed for MEDLINE]

478: J Asthma. 2006 Aug;43(6):421-6.

Sensitization to Alternaria and Cladosporium in patients with respiratory allergy
and outdoor counts of mold spores in Ankara atmosphere, Turkey.

Bavbek S, Erkekol FO, Ceter T, Mungan D, Ozer F, Pinar M, Misirligil Z.

Department of Allergic Diseases, Faculty of Medicine, Ankara University, Ankara, 
Turkey. bavbek@medicine.nakara.edu.tr

Sensitization to Alternaria and Cladosporium has been reported to be 3% to 30% in
European countries. However, in Turkey, there is limited data about the
prevalence of sensitization to these molds and the intensity of the two mold
spores in Ankara atmosphere. This study was designed to evaluate the
sensitization to Alternaria and Cladosporium in patients with respiratory allergy
in Ankara and also the concentration of the two molds in Ankara
atmosphere.Allergic rhinitis and asthma patients living in Ankara were included
in the study. Demographic and diagnostic data of the patients were recorded. A
skin prick test with extracts supplied by three different laboratories was used
to evaluate the sensitization to Alternaria and Cladosporium. Mold spores were
measured using a Burkard 7-day recording volumetric spore trap in Ankara
atmosphere during a year.Overall sensitization to the two molds was found to be
14.8%, and isolated Alternaria or Cladosporiumsensitization was 3%. Considering
the positive reaction to at least one of the three suppliers, the sensitization
rate was 11.9% and 8.1% for Alternaria and Cladosporium, respectively. Cochran's 
Q homogenization test demonstrated that the positive and negative reaction were
not homogeneous among three laboratories. The total number of mold spores in
Ankara atmosphere was 429,264 spores/m3 of which 75.5% and 6% were constituted by
Cladosporium and Alternaria, respectively.The prevalence of Cladosporium and
Alternaria sensitization in respiratory allergy patients is quite similar to
European countries; however, our data indicate that commercial mold extracts
should be standardized to establish the real sensitization rates. Additionally,
considering the great numbers of these mold spores in Ankara atmosphere,
long-term follow-up studies are needed to evaluate the relationship between the
mold load and sensitization patterns.

PMID: 16952858 [PubMed - indexed for MEDLINE]

479: Allergy Asthma Proc. 2006 Jul-Aug;27(4):319-24.

The determination of asthma, rhinitis, eczema, and atopy prevalence in 9- to
11-year-old children in the city of Izmir.

Karaman O, Turgut CS, Uzuner N, Olmez D, Babayigit A, Kose S, Tezcan D.

Dokuz EylüI University Faculty of Medicine, Division of Pediatric Allergy,
Inciralti, Izmir 35340, Turkey.

The International Study of Asthma and Allergies in Childhood (ISAAC) phase II was
designed to allow comparisons between populations in different countries and to
investigate possible etiologic factors. This study was conducted to better
delineate the prevalence and etiologic factors of asthma, rhinitis, and eczema in
Izmir (Turkey) and to be included in the international comparisons by using a
standard methodology of ISAAC phase II. The questionnaire was distributed to 2112
students in the 3rd, 4th, and 5th grades of 12 selected primary schools in urban 
and rural boroughs of Izmir. One thousand two hundred seventeen of these
questionnaires were evaluated and physical examinations and skin-prick tests were
performed on 1098 of these children. The prevalence values were 15.9% for recent 
wheezing and 4.8% for physician-diagnosed asthma. The prevalence of sneezing or
runny or blocked nose in the past 12 months when the child did not have a cold or
flu was 30%. The prevalence of physician-diagnosed allergic rhinitis was 17%. The
prevalence of an itchy rash that was coming and going for at least 6 months was
7.2% and the prevalence of physician-diagnosed eczema was 4.9%. Atopic
sensitization prevalence in the population was 8.8% with house-dust mite
sensitization being the most frequent one. Secretion rales and sibilant wheezing 
rhoncus were detected in 2.7% of children by chest auscultation. In 1.1% of
children flexural dermatitis was detected. Objective tests are necessary for
epidemiologic studies of the aforementioned diseases.

PMID: 16948344 [PubMed - indexed for MEDLINE]

480: Int Arch Allergy Immunol. 2006;141(4):384-9. Epub 2006 Aug 30.

Nasal resistance and allergic inflammation depend on allergen type.

Gelardi M, Maselli Del Giudice A, Candreva T, Fiorella ML, Allen M, Klersy C,
Marseglia GL, Ciprandi G.

Dipartimento di Oculistica e Otorinolaringoiatria, Università di Bari, Bari,
Italy.

BACKGROUND: Allergic rhinitis is characterized by inflammatory cell infiltrate
and increased nasal airflow resistance. OBJECTIVE: The aim of this study was to
evaluate the relationship between sensitization type, inflammatory cell pattern, 
and nasal airflow resistance in a group of rhinitics with monosensitization.
METHODS: Seventy-seven subjects (40 males and 37 females, with a mean age of 33
+/- 4.4 years) suffering from allergic rhinitis were studied. Skin prick test,
nasal cytology and electronic rhinomanometry were assessed in all subjects.
RESULTS: The number of subjects monosensitized to house dust mites was 23, to
grasses 20, to cypress 17, to Parietaria 11, and to olive tree 6. Significant
differences were observed between each type of allergen sensitization concerning 
both the nasal airflow resistance (p = 0.002) and the nasal cytology pattern:
eosinophils (p = 0.004), degranulated eosinophils (p = 0.002), mast cells (p =
0.006) and degranulated mast cells (p = 0.008). Furthermore, goblet cells were
higher in house dust mite-sensitized subjects compared with the pollen-sensitized
group (p = 0.018), in which a prevalence of eosinophils, degranulated
eosinophils, mast cells and degranulated mast cells was observed (p = 0.049, p < 
0.001, p = 0.022 and p = 0.007, respectively). Nasal resistances were higher in
the pollen group (p = 0.001). CONCLUSIONS: This study provides evidence that
inflammatory cell pattern and nasal resistance depend on the type of allergen
sensitization.

PMID: 16943677 [PubMed - indexed for MEDLINE]

481: Allergy. 2006 Oct;61(10):1209-15.

The type of sensitizing allergen can affect the evolution of respiratory allergy.

Marogna M, Massolo A, Berra D, Zanon P, Chiodini E, Canonica GW, Passalacqua G.

Pneumology Unit, Cuasso al Monte, Macchi Hospital Foundation, Varese, Italy.

BACKGROUND: Numerous factors affect the evolution of respiratory allergy, in
children, but little is known in adults. We assessed in a prospective study the
influence of the type of allergen on the progression of disease. METHODS:
Outpatients, with respiratory allergy underwent skin tests and pulmonary
function/methacholine challenge at baseline and after 3 years. Patients were
subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In
polysensitized subjects a single relevant allergen (mites, grasses, birch,
Parietaria) was identified based on symptom distribution and when needed on nasal
challenge. RESULTS: 6750 patients (age range 12-46) were studied. Of them, 17.8% 
were monosensitized but this percentage decreased to 10.4% after 3 years (P <
0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. 
After 3 years, the patients with bronchial responsiveness increased from 18% to
58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for
Parietaria, with a significant difference among allergens (P < 0.05). Almost the 
same was seen in monosensitized subjects, being mites most likely to cause a
worsening. All patients with BHR at baseline received immunotherapy. In these
patients the onset of new sensitizations was significantly lower than in the
group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared
more frequently. CONCLUSION: The different type of allergen influences the course
of the disease, as well as the use of immunotherapy.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16942571 [PubMed - indexed for MEDLINE]

482: Allergy. 2006 Oct;61(10):1184-90.

Sublingual immunotherapy in children modulates allergen-induced in vitro
expression of cytokine mRNA in PBMC.

Savolainen J, Jacobsen L, Valovirta E.

Department of Pulmonary Diseases and Clinical Allergology, University of Turku,
Turku, Finland.

BACKGROUND: During subcutaneous immunotherapy (SCIT), there is a local mucosal
shift from Th2 to Th1 type cytokine predominance and downregulation of
interleukin (IL)-5 and eosinophilia. According to recent studies IL-10- and
transforming growth factor (TGF)-beta-induced tolerance is another key phenomenon
in SCIT. Few data to date is available on mechanisms and roles of these cytokines
in sublingual immunotherapy (SLIT). SCOPE: This study was undertaken to analyse
the allergen-induced in vitro mRNA expression of IL-4, IL-5, IL-10, TGF-beta and 
interferon (IFN)-gamma during SLIT in peripheral blood mononuclear cells (PBMC)
of children with allergic rhinitis (AR). METHODS: Ten patients with AR undergoing
pollen SLIT with a weekly dose of 200,000 SQ-U, 10 with a weekly dose of 24,000
SQ-U of glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus
glutinosa and 10 with placebo were included in the study. Peripheral blood
mononuclear cell samples were collected and stimulated with pollen allergen
extract prior to the treatment, after 1 and 2 years of the treatment. The
cytokine mRNA expression was assessed using kinetic real time reverse
transcription polymerase chain reaction (RT-PCR; TaqMan). RESULTS: The in vitro
allergen-induced mRNA expression of IL-5 by PBMC in the placebo group at 1 (P =
0.0065) and 2 (P = 0.013) years of therapy were increased in comparison with the 
highest dose. The expression of IL-10 mRNA was increased in the highest dose
group (P = 0.0016) and the lower dose group (P = 0.034) at 2 years of therapy
when compared with placebo. The change in the expression of allergen-induced
TGF-beta had an inversed correlation with the change of IL-5 (r = -0.38, P =
0.036) and positive correlation with the change of IL-10 (r = 0.58, P = 0.0019). 
CONCLUSIONS: Sublingual immunotherapy induced a dose-dependent systemic
allergen-specific immunological response in children with AR. During high-dose
SLIT, there was activation of regulatory cytokine IL-10 and an inhibitory effect 
on IL-5 expression increase that was associated with TGF-beta.

Publication Types: 
    Comparative Study
    In Vitro
    Randomized Controlled Trial

PMID: 16942566 [PubMed - indexed for MEDLINE]

483: Allergy. 2006 Oct;61(10):1177-83.

Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract
in children.

Valovirta E, Jacobsen L, Ljørring C, Koivikko A, Savolainen J.

Turku Allergy Centre, Turku, Finland.

BACKGROUND: Subcutaneous immunotherapy has been the principal approach of
immunotherapy in the treatment of allergic diseases. Several clinical studies
with birch, alder or hazel pollen extract conducted as subcutaneous immunotherapy
have been published suggesting a well-tolerated and clinically effective
treatment. Only a few clinical studies of sublingual immunotherapy (SLIT) with
these allergens have been published. This study investigated the clinical
efficacy, safety and dose-response relationship of SLIT in children suffering
from rhinoconjunctivitis with/without asthma. METHODS: Eighty-eight children
(5-15 years) with a history of tree pollen-induced allergic rhinoconjunctivitis
with/without seasonal asthma for >or=2 years were included. Allergy to tree
pollen was confirmed by positive skin-prick test, positive specific IgE and
positive conjunctival provocation test. The extract used was a glycerinated
mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa 100,000
SQ-U/ml. Children were randomized into three groups receiving SLIT 5 days a week 
for up to 18 months; dose group 1: accumulated weekly dose of 24,000 SQ-U; dose
group 2: accumulated weekly dose of 200,000 SQ-U; and placebo. RESULTS: In the
birch pollen season, dose group 2 showed a significant reduction of symptom (P = 
0.01) and medication scores (P = 0.04) compared with placebo. Dose group 1 showed
a significant reduction of symptom scores (P = 0.03). There were no statistical
differences between dose groups 1 and 2. All children tolerated the treatment
well. CONCLUSION: SLIT with tree pollen extract provided dose-dependent benefits 
in tree pollen-allergic children in terms of significantly reduced symptoms and
medication use. The treatment was well tolerated.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16942565 [PubMed - indexed for MEDLINE]

484: Allergy. 2006 Oct;61(10):1173-6.

Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a
phase-1 study.

Larsen TH, Poulsen LK, Melac M, Combebias A, Andre C, Malling HJ.

Allergy Clinic, National University Hospital, Copenhagen, Denmark.

BACKGROUND: A single-centre, randomized, double-blind, placebo-controlled study. 
Aims: To compare the safety and tolerability of four different sublingual
immunotherapy (SLIT) regimes in grass pollen allergic rhinitis. METHODS: Thirty
subjects sensitized to grass pollen were enrolled and allocated to four groups.
Sublingual immunotherapy was administered in tablets daily for 10 days. Groups 1 
and 2 received incremental sublingual doses of 100, 200, 300, 400 and 500 IR,
Group 1 daily and Group 2 increments every second day. Repeated constant dose
regimens of 300 IR and 500 IR were administered in Groups 3 and 4 respectively.
Safety assessments included adverse events (AE), vital signs, electrocardiogram
(ECG) and clinical laboratory tests. RESULTS: Sublingual immunotherapy 300 IR
(Group 3) administered in a constant dose and incremental doses up to 500 IR
(Groups 1 and 2) were generally well tolerated. The majority of AEs were mild to 
moderate, the most common being oral pruritus, throat irritation and swollen
tongue. Severe local AEs (swelling of throat) were observed only for Group 4. No 
serious systemic AEs were reported. There were no relevant changes in clinical
laboratory, vital signs and ECG data. CONCLUSION: Adverse events were mostly
local (sublingual), were not severe and resolved rapidly. Using a 5-day induction
regimen high-dose treatment up to 500 IR could be administered without important 
side-effects, in contrast to initiating with a constant dose of 500 IR. The data 
indicate that a short dose increase phase may reduce the incidence of AEs when
high-dose SLIT is administered.

Publication Types: 
    Clinical Trial, Phase I
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16942564 [PubMed - indexed for MEDLINE]

485: Med Sci Monit. 2006 Sep;12(9):CR372-7.

Seasonal asymptomatic lower airway hyperresponsiveness in patients with allergic 
rhinitis.

Modrzyński M, Zawisza E.

The Regional Allergology Outpatient Euromedica, Grudziadz, Poland.
euromedica@lekarz.net

BACKGROUND: Allergic rhinitis is considered a risk factor for bronchial asthma.
It therefore seems essential to identify patients threatened with this disease in
whom no disturbing bronchial symptoms have occurred. The study's aim was to
evaluate the incidence of nonspecific bronchial hyperactivity based on exercise
results in pollinosis patients. MATERIAL/ METHODS: The study group comprised 27
patients with seasonal allergic rhinitis allergic to tree pollens but without
asthma symrptom. Exercise provocation tests were performed before, during, and
after completion of the pollination period. During the pollination period,
specific IgE (sIgE) and nasal eosinophilia were also determined. Twelve patients 
allergic to Artemisia pollen made up the control group. The results were also
evaluated in relation to desensitization therapy. RESULTS: In the study group a
pathological result of the provocation test was obtained in 1 patient (3.7%)
before the pollination period, in 7 patients (25.9%) during, and in 4 patients
(11.8%) after its completion. The subjects with a positive test result had higher
levels of nasal eosinophilia, while there was no relation between the result and 
sIgE levels. Only one case of positive exercise challenge was identified among
the desensitized patients. CONCLUSIONS: During the pollination period,
nonspecific bronchial hyperreactivity develops in some patients with seasonal
allergic rhinitis; it can be sustained for some time after the disappearance of
pollens from the atmosphere and can he identified using an exercise challenge.
Incidence of bronchial hyperreactivity in desensitized patients was lower than in
those subjected to symptomatic treatment.

PMID: 16940930 [PubMed - indexed for MEDLINE]

486: Prostaglandins Other Lipid Mediat. 2006 Sep;80(3-4):144-54. Epub 2006 Jul
25.

Different mechanisms between thromboxane A2- and leukotriene D4-induced nasal
blockage in guinea pigs.

Tanaka Y, Mizutani N, Fujii M, Nabe T, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi,
Misasagi, Yamashina, Kyoto, Japan.

Although thromboxane (TX)A2 is involved in allergic rhinitis, the mechanisms
inducing nasal blockage have not been elucidated. We evaluated the roles of nasal
mucosal vascular changes following intranasal instillation of the TXA2 analog
U-46619 or leukotriene (LT)D4 to induce nasal blockage in a guinea pig model of
allergic rhinitis. Both U-46619- and LTD4-induced nasal blockages in sensitized
animals were swiftly and completely suppressed by a vasoconstrictor, naphazoline.
The nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester
relieved LTD4-induced nasal blockage, but not U-46619-induced nasal blockage.
Although both agonists produced vasodilatation of nasal mucosa in vivo, LTD4
caused vasodilatation while U-46619 caused vasoconstriction in vitro. Both LTD4- 
and U-46619-induced nasal blockages in vivo should depend on vasodilatation of
nasal mucosa. LTD4-induced nasal blockage is induced by direct vasodilatation via
nitric oxide. In contrast, U-46619-induced nasal blockage may be associated with 
contraction of a certain vein that should exist at the exit of capacitance
vessels, leading to congestion of the nasal mucosa.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16939879 [PubMed - indexed for MEDLINE]

487: Ann Allergy Asthma Immunol. 2006 Aug;97(2):158-63.

Comment in:
    Ann Allergy Asthma Immunol. 2006 Aug;97(2):125.

Multiple daily administrations of low-dose sublingual immunotherapy in allergic
rhinoconjunctivitis.

Bordignon V, Burastero SE.

Bassano del Grappa (VI), Italy.

BACKGROUND: Sublingual immunotherapy (SLIT) is an efficacious treatment for
allergic rhinoconjunctivitis. OBJECTIVE: To investigate whether the number of
daily administrations of SLIT can affect its efficacy. METHODS: In an open study,
64 patients with allergic seasonal rhinoconjunctivitis to grass or birch pollens 
were assigned to the following 2-year daily treatment schedules: "3-3" group, 1
drop 3 times daily for 2 years; "2-3" group, 1 drop twice daily in year 1 and 1
drop 3 times daily in year 2; "1-3" group, 1 drop once daily in year 1 and 1 drop
3 times daily in year 2; and control group, no treatment. One fifth of the
allergen concentration recommended by the manufacturer as maintenance treatment
was used throughout the study. Patients were monitored for skin reactivity to the
allergen used for SLIT using an end point dilution technique and for drug use.
RESULTS: No treatment-related adverse effects were observed. Skin reactivity to
allergen decreased compared with controls in the first treatment year only in the
"3-3" group and in all treated patients in year 2. Drug use decreased in the
first treatment year in the "3-3" and "2-3" groups vs controls. This outcome
extended to "1-3" patients in treatment year 2. Antihistamine use decreased
significantly compared with baseline in year 1 in "3-3" and "2-3" patients and in
all treated patients in year 2. No changes were observed in controls. CONCLUSION:
The number of daily administrations seems to correlate with the efficacy of SLIT.

Publication Types: 
    Randomized Controlled Trial

PMID: 16937744 [PubMed - indexed for MEDLINE]

488: Ann Allergy Asthma Immunol. 2006 Aug;97(2):141-8.

Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in
pediatric patients 3 to 18 years of age: a meta-analysis of randomized,
placebo-controlled, double-blind trials.

Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G,
Canonica GW.

Allergy & Respiratory Diseases, Department of Internal Medicine, University of
Genoa, Italy.

OBJECTIVE: To evaluate the efficacy of sublingual immunotherapy (SLIT) in the
treatment of allergic rhinitis in children. DATA SOURCES: A comprehensive search 
of the EMBASE, MEDLINE, LILACS, and CINAHL databases from January 1966 to
February 10, 2006, was performed. STUDY SELECTION: Randomized, double-blind,
placebo-controlled trials of SLIT in the treatment of allergic rhinitis in
patients 18 years or younger were selected. Outcomes measured were symptom scores
and rescue medication use. Analysis was performed with standardized mean
differences (SMDs) and a random-effects model. RESULTS: Seventy articles were
identified and reviewed. Ten studies, published between 1990 and 2004, fulfilled 
the selection criteria. Five hundred seventy-seven patients were initially
included in the studies. Of these patients, 484 (245 SLIT and 239 placebo) had a 
final clinical evaluation and could be evaluated. A relevant heterogeneity due to
widely differing scoring systems was found. Overall, there was a significant
reduction in both symptoms (SMD, 0.56, 95% confidence interval, 1.01-0.10; P =
.02) and medication use (SMD, 0.76; 95% confidence interval, 1.46-0.06; P = .03) 
after immunotherapy. The subanalyses performed for treatment duration and type of
allergen showed that SLIT for more than 18 months and with pollen extracts was
effective compared with SLIT courses shorter than 18 months and with mites.
CONCLUSION: The results of this meta-analysis showed that,compared with placebo, 
SLIT with standardized extracts is effective in pediatric patients with allergic 
rhinitis.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 16937742 [PubMed - indexed for MEDLINE]

489: Eur Ann Allergy Clin Immunol. 2006 Jun;38(6):186-94.

Iberian study of aeroallergens sensitisation in allergic rhinitis.

Pereira C, Valero A, Loureiro C, Dávila I, Martinez-Cócera C, Murio C, Rico P,
Palomino R.

Iberian Chapter, SLAAI.

BACKGROUND: Allergic rhinitis (AR) is a prevalent allergic disease in Iberian
countries, but there are no recent epidemiological studies that characterize this
pathology according to clinical classification and aeroallergens sensitisation.
This is a clinical study, representative of each country METHODS: Descriptive,
observational cross-sectional, population-based study carried-out in Portugal and
Spain. 3397 consecutive patients (5 regions in Spain and 3 regions in Portugal)
were selected for clinical observation and skin prick tests were carried out
using the same panel of standardized aeroallergens. RESULTS: 3225 patients (aged 
10-50 years old) completed the study (IC 95%, SE 15). Intermittent rhinitis makes
up 36% of the entire sample. Of them, intermittent AR mild forms represented 82% 
in Spain and 92% in Portugal that is, 87% for Iberian countries. Persistent types
of rhinitis showed exactly the same rate of severity in Portugal and Spain, 44%
mild and 56% moderate/severe. Seasonal forms represent 37% while 63% were
perennial. BA was present in 49% of AR patients. There were significant
differences between aeroallergens according to the different regions considered. 
Mites and grass pollens are the most relevant aeroallergens in Spanish and
Portuguese AR patients, while Alternaria showed higher positive rates among 10-20
year old patients. CONCLUSIONS: This study characterizes the AR patients in
Iberian countries according to the ARIA classification. No correlation was
observed between this classification and the conventional (seasonal/perennial).
Our results also characterize the allergic cutaneous pattern of aeroallergen
sensitisation using the same panel of standardized allergens and show differences
between the different regions analysed.

PMID: 16929745 [PubMed - indexed for MEDLINE]

490: Pediatr Allergy Immunol. 2006 Sep;17(6):444-9.

Seasonal changes of proapoptotic soluble Fas ligand level in allergic rhinitis
combined with asthma.

Mezei G, Lévay M, Sepler Z, Héninger E, Kozma GT, Cserháti E.

1st Department of Pediatrics, Faculty of Medicine, Semmelweis University,
Budapest, Hungary. mezei@gyer1.sote.hu

The function of apoptosis is to eliminate unnecessary or dangerous cells. The
balance between production and death is important in the control of cell numbers 
within physiological ranges. Cells involved in allergic reactions may have
altered apoptosis. The aim of this study was to examine the seasonal changes of
programmed cell death in children with pollen allergy. We measured serum levels
of soluble Fas (sFas) and soluble Fas ligand (sFasL), and examined whether there 
was any correlation between soluble apoptosis markers and development of asthma
and or rhinitis in children with pollen allergy. We examined two groups of
patients with ragweed pollen allergy. The first group consisted of 17 children
with 'rhinitis only'. The second group consisted of 16 children with 'asthma +
rhinitis'. For seasonal analysis we pooled the two groups and termed this the
'ragweed sensitive' group (n = 33, 5-18 yr, 25 boys, eight girls). Measurements
(sFas and sFasL) were taken during the ragweed pollen allergy season, while
control measurements were performed during the symptom-free period. There was no 
difference in sFas levels measured during and after [1941 +/- 68, 1963 +/- 83
pg/ml (mean+/-s.e.m, respectively)] the pollen season in the 'ragweed sensitive' 
group. The sFasL level showed seasonal change, which was significantly higher (p 
= 0.0086) in the symptomatic period compared to the symptom-free state (99 +/- 13
and 53 +/- 16 pg/ml, respectively). There was a difference between the 'rhinitis 
only' and the 'asthma + rhinitis' groups in the measured parameters of apoptosis.
Children having allergic rhinitis combined with asthma had a significantly (p =
0.03) higher sFas level in the symptom-free state than the 'rhinitis only' group 
did (2115 +/- 156 and 1820 +/- 52 pg/ml, respectively). During the allergic
symptom state the sFasL level of the 'asthma + rhinitis' group was significantly 
higher (p = 0.025) than that of the 'rhinitis only' group (125 +/- 20 and 75 +/- 
14 pg/ml, respectively). In conclusion, the increased level of sFasL during the
pollen season may signal its role in the pathogenesis of allergic airway
diseases. There was no seasonal change in sFas levels in the examined ragweed
allergic group, however in the symptomatic period we observed a diminished level 
of antiapoptotic factor (sFas) and an elevated level of proapoptotic factor
(sFasL) if there was a combined disease with pollen allergic asthma. We suggest
that there is a deviation in the apoptotic reaction in children that may increase
the seasonal allergic inflammation.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16925690 [PubMed - indexed for MEDLINE]

491: Pediatr Allergy Immunol. 2006 Sep;17(6):396-407.

The effects of grass pollen allergoid immunotherapy on clinical and immunological
parameters in children with allergic rhinitis.

Keskin O, Tuncer A, Adalioglu G, Sekerel BE, Saçkesen C, Kalayci O.

Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine,
Hacettepe, Ankara, Turkey.

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe
administration of high allergen doses. There is limited information on the
effects of allergoid immunotherapy in children with allergic rhinitis. To
investigate the immunological and clinical effects of allergoid immunotherapy in 
children with allergic rhinitis due to grass pollen allergy. Children with
allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n
= 26, no immunotherapy) groups. Children in the immunotherapy group received
seven injections of grass pollen allergoid immunotherapy before grass pollen
season and continued to receive maintenance immunotherapy for 27 months. All
patients were offered a pharmacotherapy regimen to be used on demand during the
pollen seasons. Clinical and laboratory parameters were compared between the
immunotherapy and control groups. The rhinoconjunctivitis symptom-medication
score and asthma symptom score were lower in the immunotherapy group after 1 yr
of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal 
reactivity as determined by nasal provocation testing for grass pollen were
significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The
seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic
protein levels were prevented after the first year of immunotherapy (p < 0.05 for
both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and
grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end 
of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 
levels in the culture supernatants showed a steady decline from baseline at first
and second year of immunotherapy (p < 0.001) but remained unchanged in the
control group. Allergoid immunotherapy is an effective method in the treatment of
grass pollen-induced allergic rhinitis in children and prevents the seasonal
increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels
and decreased IL-4 production in peripheral blood mononuclear cell culture
supernatants may account for the observed clinical effects.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16925684 [PubMed - indexed for MEDLINE]

492: Allergy. 2006 Sep;61(9):1138-40.

High incidence of sensitization to ornamental plants in allergic rhinitis.

Mahillon V, Saussez S, Michel O.

Clinic of ENT, Saint-Pierre University Hospital, Free University of Brussels,
Brussels, Belgium.

BACKGROUND: A few indoor plants have been described as potential allergens, in
single case reports of allergic rhinitis. There is no data evaluating the
prevalence of allergic sensitization to these plants. AIM: The relationship
between owning indoor ornamental plants with the risk to be sensitized has been
evaluated in atopic rhinitis. METHODS: A group of 59 patients with allergic
rhinitis were submitted to skin prick tests (SPT) using both the leafs of their
own plant and commercial extracts of the most frequent airborne allergens. A
control group of 15 healthy subjects was tested with the same allergens. RESULTS:
While no subject from the control group developed a significant SPT to any of the
tested plants, 78% of allergic rhinitis had positive SPT to at least one plant,
the most frequent sensitization being Ficus benjamina, yucca, ivy and palm tree. 
CONCLUSION: In allergic rhinitis, indoor plants should be considered as potential
allergens.

PMID: 16918519 [PubMed - indexed for MEDLINE]

493: Allergy. 2006 Sep;61(9):1117-24.

Association between exposure to farming, allergies and genetic variation in
CARD4/NOD1.

Eder W, Klimecki W, Yu L, von Mutius E, Riedler J, Braun-Fahrländer C, Nowak D,
Holst O, Martinez FD; the ALEX-Team.

Arizona Respiratory Center, University of Arizona, Tucson, AZ 85724, USA, and Dr 
von Hauner Children's Hospital, University of Munich, Germany.

BACKGROUND: Caspase recruitment domain protein (CARD) 4 has been recently
identified as an intracellular pattern recognition receptor that interacts with
muropeptides found in common Gram-negative bacteria. We therefore aimed to
explore whether the previously observed inverse association between exposure to
microbial products and asthma and allergies in childhood is modified by genetic
variation in CARD4. METHODS: We genotyped 668 children [mean age 9.3 (SD 1.5)
years] enrolled in the cross-sectional ALEX study for seven haplotype tagging
single nucleotide polymorphisms in CARD4. We studied the association of asthma,
hay fever and allergen-specific serum immunoglobulin E with exposure to a farming
environment and with levels of endotoxin and muramic acid measured in house dust 
samples. We tested whether these associations differed between the genotypes of
the polymorphisms under study. RESULTS: A strong protective effect of a farming
environment on allergies was only found in children homozygous for the T allele
in CARD4/-21596, but not in children carrying the minor allele (C). Among the
former, farmers' children had a significantly lower frequency of sensitization
against pollen (5.8%), hay fever (1.7%) and atopic asthma symptoms (1.7%)
compared with children not living on a farm (19.4%, 13.0% and 7.6%, P<0.01, <0.01
and <0.05, respectively). Conversely, no significant difference in prevalence of 
these phenotypes by farming status was found among children with a C allele in
CARD4/-21596 (14.3%, 7.1% and 8.0%vs 16.5%, 9.0% and 5.7%, respectively).
CONCLUSION: Polymorphisms in CARD4 significantly modify the protective effect of 
exposure to a farming environment.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16918516 [PubMed - indexed for MEDLINE]

494: Allergy. 2006 Sep;61(9):1086-96.

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in
collaboration with GA2LEN).

Bousquet J, van Cauwenberge P, Aït Khaled N, Bachert C, Baena-Cagnani CE,
Bouchard J, Bunnag C, Canonica GW, Carlsen KH, Chen YZ, Cruz AA, Custovic A,
Demoly P, Dubakiene R, Durham S, Fokkens W, Howarth P, Kemp J, Kowalski ML,
Kvedariene V, Lipworth B, Lockey R, Lund V, Mavale-Manuel S, Meltzer EO, Mullol
J, Naclerio R, Nekam K, Ohta K, Papadopoulos N, Passalacqua G, Pawankar R, Popov 
T, Potter P, Price D, Scadding G, Simons FE, Spicak V, Valovirta E, Wang DY, Yawn
B, Yusuf O; GA2LEN.

University Hospital and INSERM U454, Montpellier, France.

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an
evidence-based and step-wise approach based on the classification of the
symptoms. The ARIA workshop, held in December 1999, published a report in 2001
and new information has subsequently been published. The initial ARIA document
lacked some important information on several issues. This document updates the
ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. 
Literature published between January 2000 and December 2004 has been included.
Only a few studies assessing nasal and non-nasal symptoms are presented as these 
will be discussed in a separate document.

Publication Types: 
    Review

PMID: 16918512 [PubMed - indexed for MEDLINE]

495: Allergy Asthma Proc. 2006 May-Jun;27(3):254-64.

Expanding choices in intranasal steroid therapy: summary of a roundtable meeting.

Blaiss MS, Benninger MS, Fromer L, Gross G, Mabry R, Mahr T, Marple B, Stoloff S.

Department of Pediatrics and Medicine, University of Tennessee Health Science
Center, Memphis, Tennessee, USA. mblaiss@allergymemphis.com

Intranasal steroids (INSs) are recommended as first-line treatment for allergic
rhinitis (AR) and a wealth of data exist supporting them as safe and effective.
Our goal was to develop a consensus to help physicians choose between INSs by
focusing on clinical profiles and patient preferences and providing expert advice
on choosing the appropriate INS for each patient. Experts from specialties that
manage patients with AR attended a roundtable meeting to discuss INS therapy.
Besides comparisons with other pharmacologic agents, they examined the effects of
INS on nasal anatomy, patient preferences for INS, and benefits of product
selection based on patient profile. The literature on INSs in AR was reviewed,
examining properties of the various drugs, delivery devices, formulations, and
patient preference data. Nasal anatomy and physiology must be considered to
optimize INS deposition in the nose. Teaching patients proper technique for using
INS devices is important to prevent nasal injury and may help concentrate drug
effect on affected tissues. INS therapies differ somewhat in biological
properties and specific formulation; however, all are considered safe and
effective treatment for AR. Patients exhibit different clinical profiles, which
play a role in INS selection. Patients can clearly identify sensory
characteristics of INS and therefore establish product preference. Patient
preference also can guide physicians in choosing the appropriate agent for each
patient. Control of AR requires a systematic approach to treatment selection and 
follow-up. Treatment selection should be matched with clinical profile and
patient preferences.

Publication Types: 
    Consensus Development Conference
    Research Support, Non-U.S. Gov't

PMID: 16913270 [PubMed - indexed for MEDLINE]

496: Allergy Asthma Proc. 2006 May-Jun;27(3):248-53.

Is the usage of intranasal glucocorticosteroids alone in allergic rhinitis
sufficient?

Can D, Tanaç R, Demir E, Gülen F, Veral A.

Division of Pediatric Allergy and Pulmonology, Behcet Uz Children Hospital,
Izmir, Turkey. ddcan15@hotmail.com

Recently, it is claimed that the usage of the intranasal glucocorticosteroids
alone, instead of H1-antihistamines + intranasal glucocorticosteroids, reduces
the complaints in moderate-to-severe seasonal allergic rhinitis (SAR). This study
aims to evaluate the efficacy of the intranasal glucocorticosteroids alone during
the pollen season by using objective and subjective parameters. Twenty-four
patients (mean age, 12.17 +/- 2.26 years) with SAR sensitive to pollen are
included in this study. The patients were divided into two groups randomly.
Twelve patients in group I were given H1-antihistamine (loratadine) + intranasal 
glucocorticosteroid (mometasone furoate), and 12 patients in group II were given 
only intranasal glucocorticosteroid (mometasone furoate) for 12 weeks. To
evaluate the results, subjective parameters (daytime nasal symptoms score,
daytime eye symptoms score, and nighttime symptoms score) and objective
parameters (nasal smear, nasal peak inspiratory flow [NPIF], and nasal biopsy)
are used. With regard to the baseline data, it was observed that both groups had 
a significant decrease in total symptom score (p < 0.01), a significant increase 
in NPIF values (p < 0.01), and a significant decrease in the number of
eosinophils in both nasal smear and biopsy (p < 0.01) after treatment. Comparing 
groups I and II in terms of treatment success, the improvement in daytime nasal
symptoms score (p < 0.01 versus p < 0.01), daytime eye symptoms score (p < 0.01
versus p < 0.01), and total symptom score (p < 0.versus p < 0.01) was not
different. However, there was a significant improvement in nighttime symptoms
score between groups I and II (p < 0.01 versus p > 0.05). Furthermore, NPIF and
nasal biopsy findings did not differ between groups (p > 0.05). The usage of
H1-antihistamine + intranasal glucocorticosteroid has no superiority over the
administration of intranasal glucocorticosteroid alone for treatment of SAR in
pollen season. However, this finding needs to be confirmed in larger series
studies.

Publication Types: 
    Randomized Controlled Trial

PMID: 16913269 [PubMed - indexed for MEDLINE]

497: Allergy Asthma Proc. 2006 May-Jun;27(3):240-2.

A review of the roles of allergic rhinitis in childhood obstructive sleep apnea
syndrome.

Ng DK, Chan CH, Hwang GY, Chow PY, Kwok KL.

Department of Paediatrics, Kwong Wah Hospital, Hong Kong, SAR, China.
dkkng@ha.org.hk

The aim of this study was to review the literature to evaluate the association
between allergic rhinitis (AR) and obstructive sleep apnea syndrome (OSAS) in
childhood. A PubMed literature search (January 1970 to February 2005) was
conducted using the following key words: obstructive sleep apnea, allergic
rhinitis, and mouth breathing. The retrieved articles were reviewed and the
levels of evidence were assessed. AR affected approximately 40% of children and
OSAS occurred in 2% of children. AR is a risk factor for OSAS because AR is
associated with nasal obstruction, enlargement of tonsils and adenoids, and an
elongated face, which, taken together, constitute a smaller upper airway size.
Adequate treatment of AR is helpful to decrease the severity of OSAS and prevent 
emergence of an elongated face, which predispose for OSAS. There is convincing
evidence that AR increases the risk of OSAS in children. Appropriate treatment of
AR regularly could prevent the occurrence of OSAS and reduce the severity of
existing OSAS.

Publication Types: 
    Review

PMID: 16913267 [PubMed - indexed for MEDLINE]

498: Allergy Asthma Proc. 2006 May-Jun;27(3):231-9.

Validation of the nighttime symptoms score as a clinically relevant measure of
allergic rhinitis.

Santanello NC, DeMuro-Mercon C, Shah SR, Schenkel EJ, Ratner PH, Dass SB,
Norquist JM, Philip G.

Merck Research Laboratories, Rahway, New Jersey, USA. nancy_santanello@merck.com

The aim of this study was to validate the nighttime symptoms score (NSS), which
incorporates individual scores for difficulty going to sleep and nighttime
awakening caused by nasal symptoms and nasal congestion on awakening, as a
clinically relevant measure of allergic rhinitis (AR). Fifty-five general season 
AR (SAR) symptom items were generated by interviews with 14 patients with
symptomatic SAR without concomitant asthma for use in an Importance Rating
Questionnaire (IRQ). A second group of patients (n = 83) with symptomatic AR
without asthma rated the importance of each item on the IRQ. Correlation
coefficients were calculated to examine the relationships between the six sleep
quality questions on the IRQ and the other AR symptoms and between the symptom
questions of the NSS, the Daytime Nasal Symptoms Score (DNSS), and the individual
domains of the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). The
majority (94%) of patients with active AR reported some degree of symptoms
relating to sleep quality. The six sleep quality items on the IRQ were selected
by 71-84% of patients. The sleep quality items were more highly correlated with
each other (r = 0.48-0.85) than with the four items of the DNSS (r = 0.01-0.42). 
There was a moderate-to-strong correlation of the RQLQ sleep domain with the two 
sleep questions of the NSS (r = 0.44-0.57). The individual symptom questions of
the NSS and the DNSS were only moderately correlated with each other. Sleep
quality questions measure aspects of SAR that are not captured by daytime SAR
symptoms. The results show that the NSS is a valid and relevant clinical measure 
of the impact of nighttime sleep disturbance on AR patients.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 16913266 [PubMed - indexed for MEDLINE]

499: Allergy Asthma Proc. 2006 May-Jun;27(3):224-30.

A practical approach to allergic rhinitis and sleep disturbance management.

Davies MJ, Fisher LH, Chegini S, Craig TJ.

Department of Medicine, Division of Pulmonary, Allergy, and Critical Care,
Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.

Sleep quality can be significantly impacted by nasal congestion, a common symptom
related to allergic rhinitis (AR). This may lead to decreased learning ability,
productivity at work or school, and a reduced quality of life. A number of
inflammatory cells and the release of inflammatory mediators lead to increased
nasal congestion, causing disrupted sleep and subsequent daytime somnolence.
Therefore, it is important to treat AR with medications that improve congestive
symptoms without worsening sedation. Second-generation antihistamines and
anticholinergic drugs are well tolerated but have little effect on congestion and
therefore are limited in their ability to reduce AR-associated daytime
somnolence. However, intranasal corticosteroids reduce congestion, improve sleep 
and sleep problems, and reduce daytime sleepiness, fatigue, and inflammation.
Montelukast, a leukotriene receptor antagonist, has joined the approved therapies
for AR. Montelukast significantly improves both daytime and nighttime symptoms.
AR treatment should endeavor to improve daytime and nighttime symptoms, sleep,
and productivity thereby improving quality of life.

Publication Types: 
    Review

PMID: 16913265 [PubMed - indexed for MEDLINE]

500: Allergy Asthma Proc. 2006 May-Jun;27(3):214-23.

Efficacy of desloratadine, 5 mg, compared with fexofenadine, 180 mg, in patients 
with symptomatic seasonal allergic rhinitis.

Berger WE, Lumry WR, Meltzer EO, Pearlman DS.

Allergy and Asthma Associates of Southern California, Mission Viejo, California
92691, USA. WEBerger@uci.edu

This is the first U.S.-based study to compare efficacy and safety of
desloratadine with fexofenadine in subjects with symptomatic seasonal allergic
rhinitis (SAR). In this double-blind study, subjects were randomized to
desloratadine, 5 mg (n = 290),fexofenadine, 180 mg (n = 288), or placebo (n =
144) once daily for 15 days. Primary end point was mean change from baseline to
study end in morning instantaneous total symptom score (AM NOW TSS) excluding
congestion. Secondary measures included change from baseline in the
morning/evening reflective TSS (AM/PM PRIOR TSS) excluding congestion, AM NOW
individual symptom score (AM NOW ISS) including congestion, and the AM/PM PRIOR
ISS including congestion. Subjects self-evaluated their symptoms on a five-point 
scale. Mean AM NOW TSSs were significantly reduced from baseline at day 15 with
desloratadine (p = 0.006) and fexofenadine (p = 0.024) versus placebo.
Desloratadine and fexofenadine were not statistically different (p = 0.491); the 
upper limit of the 95% CI for desloratadine to fexofenadine (0.259) was within
the prespecified noninferiority margin of 0.7 U. Decrease in mean AM/PM PRIOR TSS
excluding congestion was comparable between desloratadine and fexofenadine (p =
0.405; CI = 0.221) but was significantly greater with both active treatments
versus placebo (desloratadine, p < 0.001;fexofenadine, p = 0.003). Desloratadine 
and fexofenadine provided greater reduction in the AM NOW ISS and AM/PM PRIOR ISS
(both including congestion) versus placebo; reductions were comparable between
active treatments. All treatments were well tolerated. Desloratadine, 5 mg, and
fexofenadine, 180 mg, provide comparable efficacy and tolerability in the
treatment of SAR. Both treatments are significantly more effective than placebo.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16913264 [PubMed - indexed for MEDLINE]

501: Allergy Asthma Proc. 2006 May-Jun;27(3):208-13.

Mast cell inhibitor R112 is well tolerated and affects prostaglandin D2 but not
other mediators, symptoms, or nasal volumes in a nasal challenge model of
allergic rhinitis.

Guyer BJ, Shimamoto SR, Bradhurst AL, Grossbard EB, Dreskin SC, Nelson HS.

Department of Medicine, National Jewish Medical and Research Center, Denver,
Colorado, USA. guyerb@parknicollet.com

Understanding of the role played by mast cells in allergic rhinitis (AR) has led 
to the development of novel therapies. The aim of this study was to determine the
safety and tolerability of R112, an inhibitor of the tyrosine kinase Syk, in an
allergen challenge model of AR. We also examined the effects of R112 on symptoms,
mediator release, and nasal airway volumes. This double-blinded, randomized,
placebo-controlled, crossover trial enrolled 20 out-of-season volunteers with AR.
One intranasal dose of R112 or vehicle was administered and followed by an
allergen challenge. In addition to safety monitoring, symptoms; changes in
histamine, tryptase, and prostaglandin D2 (PGD2) content of nasal secretions; and
acoustic rhinometry were determined over a 15-minute period. R112 was well
tolerated. Adverse events were similar between treatments. Five minutes after
allergen instillation, PGD2 was decreased when subjects received R112 compared
with vehicle (93.4 +/- 23.0 pg/mL versus 171.6 +/- 23.0 pg/mL; p = 0.03), and
this correlated with rhinorrhea (p = 0.05). However, at 10 minutes, changes in
PGD2, tryptase, and histamine were not significant (46.8 +/- 9.2 pg/mL versus
68.6 +/- 9.2 pg/mL, p = 0.1; 9.5 +/- 2.7 ng/mL versus 16.6 +/- 2.9 ng/mL, p =
0.09; and 1.5 +/- 1.6 ng/mL versus 3.5 +/- 1.6 ng/mL, p = 0.4). No differences
were found in symptoms or in acoustic rhinometry between treatment groups.
Single-dose R112 appears safe and significantly reduces PGD2 but not histamine or
tryptase release in response to allergen challenge in subjects with AR.

Publication Types: 
    Clinical Trial, Phase I
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16913263 [PubMed - indexed for MEDLINE]

502: Allergy Asthma Proc. 2006 May-Jun;27(3):202-7.

Improved quality of life among seasonal allergic rhinitis patients treated with
olopatadine HCl nasal spray 0.4% and olopatadine HCl nasal spray 0.6% compared
with vehicle placebo.

Hampel FC Jr, Ratner PH, Amar NJ, van Bavel JH, Mohar D, Fairchild CJ, Wall GM,
Brubaker MJ, Drake M, Crenshaw KM.

Central Texas Health Research, New Braunfels and San Antonio, Texas, 78130, USA. 
fchampel@aol.com

Seasonal allergic rhinitis (SAR) exerts a significant adverse impact on
health-related quality of life (QoL) and productivity of those who suffer from
it. Unfortunately, some therapies for SAR also have a negative impact. Therefore,
it is important to scrutinize the influence of new SAR therapies on patients' QoL
and ability to function. The purpose of this study was to evaluate the effect of 
a new nasal antihistamine, olopatadine, on QoL in SAR patients. In a multicenter,
randomized, double-blind SAR study comparing olopatadine 0.6 and 0.4% to placebo 
nasal spray, patients completed the Rhinoconjunctivitis Quality of Life
Questionnaire (RQLQ) at baseline and after 2 weeks of treatment. The RQLQ is a
validated questionnaire that addresses overall QoL and 7 domains of impairment
associated with rhinoconjunctivitis (activities, sleep, non--nose/eye allergy
symptoms, practical problems, nasal symptoms, eye symptoms, and emotional
impairment). The overall RQLQ mean changes from baseline with olopatadine 0.6%
(-1.1 +/- 1.4) and 0.4% (-1.1 +/- 1.3) nasal sprays were superior (p < 0.05) to
placebo (-0.8 +/- 1.2). Olopatadine spray 0.6% was superior to placebo in six of 
the seven RQLQ domains and olopatadine 0.4% was superior to placebo in five RQLQ 
domains (p < 0.05). The correlation between the olopatadine 0.6% mean total
symptom scores and mean RQLQ score was r = 0.66 (p < 0.0001), indicating that the
enhancement in QoL derived from olopatadine therapy was significantly associated 
with symptom reduction. Olopatadine nasal spray is an effective antiallergy
medication that significantly improves the QoL of patients suffering from SAR.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16913262 [PubMed - indexed for MEDLINE]

503: Allergy Asthma Proc. 2006 May-Jun;27(3):197-201.

Effect of tetanus immunization on t-helper cytokine production in adults with and
without allergic rhinitis.

Gentile D, Trecki J, Patel A, Fausnight T, Angelini B, Skoner D.

Dept. of Pediatrics, Allegheny Singer Research Institute, Allegheny General
Hospital, Pittsburgh, Pennsylvania 15212, USA. Dgentile@wpahs.org

Epidemiological evidence links T-helper type 2 (Th2) cytokine responses to the
pathogenesis of atopy/asthma. It is hypothesized that certain immunizations may
induce/amplify Th2 cytokine responses. The objective of this study was to
determine whether Th cytokine responses to immunization with tetanus toxoid
differ in adults with and without allergic rhinitis (AR). Thirty subjects were
enrolled (15 AR and 15 non-AR subjects as confirmed by history and allergy skin
testing). Blood was collected before (day 0) and on days 3, 7, 14, and 28 after
immunization with tetanus toxoid. Peripheral blood mononuclear cells (PMNCs) were
purified and cultured with either PHA or tetanus toxoid for 2 or 6 days,
respectively. Supernatants were harvested and assayed for IFN-gamma and IL-13
levels (pg/mL) by EIA. Results were normalized by log transformation and analyzed
by stepwise regression. Baseline (day 0) cytokine values were similar in both
groups. PHA and tetanus-induced IFN-gamma were increased (p < 0.05) in non-AR
(3.2 +/- 0.3 and 1.4 +/- 0.3 on day 7, and 3.5 +/- 0.2 and 1.9 +/- 0.2 on day 14,
respectively) compared with AR subjects (2.3 +/- 0.3 and 0.9 +/- 0.3 on day 7,
and 2.7 +/- 0.3 and 1.2 +/- 0.3 on day 14, respectively). PHA-induced, but not
tetanus-induced, IL-13 production was increased (p < 0.05) in non-AR compared
with AR subjects on day 7 (p < 0.05). PHA-induced IL-13 production was 3.1 +/-
0.2 in non-AR and 2.6 +/- 0.3 in AR subjects on day 7. These results indicate
differential Th cytokine responses in AR and non-AR subjects after immunization
with tetanus toxoid. Future studies are warranted and may result in the
identification of potential prevention/treatment strategies for atopy/asthma.

Publication Types: 
    Controlled Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16913261 [PubMed - indexed for MEDLINE]

504: Clin Exp Allergy. 2006 Aug;36(8):1039-48.

Gene and protein expression of protease-activated receptor 2 in structural and
inflammatory cells in the nasal mucosa in seasonal allergic rhinitis.

Dinh QT, Cryer A, Trevisani M, Dinh S, Wu S, Cifuentes LB, Feleszko WK, Williams 
A, Geppetti P, Fan Chung K, Heppt W, Klapp BF, Fischer A.

Department of Internal Medicine, Charité-Universitätsmedizin Berlin, Berlin,
Germany. q-thai.dinh@charite.de

BACKGROUND: Protease-activated receptor 2 (PAR 2) has been shown to be
responsible for trypsin and mast cell tryptase-induced airway inflammation. Here,
the present study aimed to explore the expression of PAR 2 in the nasal mucosa of
seasonal allergic rhinitis (SAR). METHODS: Study subjects were recruited for the 
study by medical history, physical examination and laboratory screening tests.
Using immunohistochemistry, laser-assisted cell picking and subsequently
real-time PCR, nasal mucosa biopsies of SAR patients were investigated for PAR 2 
gene and protein expression in complex tissues of the nasal mucosa. RESULTS: Gene
and protein expression of PAR 2 was firstly detected in nasal mucosa of SAR
patients. The relative gene expression level of PAR 2 was significantly increased
in complex tissues of the nasal mucosa of SAR (6.21+/-4.02 vs. controls:
1.38+/-0.86, P=0.004). Moreover, PAR 2 mRNA expression in epithelial cells (SAR: 
4.78+/-4.64 vs. controls: 0.84+/-0.61, P=0.003) but not in mucus (SAR:
1.51+/-1.15 vs. controls: 1.35+/-1.02, P=0.78) and endothelial cells (SAR:
1.20+/-0.57 vs. controls: 1.73+/-1.30, P=0.5) was found to be significantly
changed in the nasal mucosa in SAR. Using double immunohistochemistry the present
study demonstrated that the total numbers of mast cells (P=0.0003) and
eosinophils (P=0.03) and the numbers of eosinophils expressing PAR 2 (P=0.006)
were significantly elevated in the nasal mucosa of SAR compared with the
controls. CONCLUSION: The abundant presence and distribution of gene and protein 
expression of PAR 2 in different cell types in the nasal mucosa under normal
situation, the increased expression of PAR 2 in epithelial cells and the
increased number of eosinophils with PAR 2 suggest that PAR 2 may contribute to
the pathogenesis of allergic diseases such as SAR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16911360 [PubMed - indexed for MEDLINE]

505: B-ENT. 2006;2(2):55-62.

Levocetirizine as treatment for symptoms of seasonal allergic rhinitis.

Jorissen M, Bertrand B, Stiels B, Vandenbulcke K.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital
Leuven, Belgium.

OBJECTIVES: The aim of this study was to assess the effectiveness and safety of
levocetirizine in the treatment of the symptoms of seasonal allergic rhinitis
(SAR) in patients consulting their primary care doctor. METHODS: Open-label
uncontrolled and non-randomised multi-centre study including patients presenting 
symptoms of SAR and treated with levocetirizine tablets, 5 mg OD, for 4 weeks.
Inclusion criteria: patients with nasal symptoms who were not on treatment or not
responsive to treatment, or affected by excessive adverse events due to the
antihistamines used previously. There were two visits (initial and after four
weeks). Primary end point: efficacy as measured by T4SS (combined score of
sneezing, rhinorrhoea, nasal and ocular pruritus, ranging from 0 to 12 recorded
by the patient); change in Clinical Global Impression (CGI-c) as rated by the
general practitioner, subjective satisfaction with and preference for
levocetirizine. Secondary end points: treatment-related adverse events. RESULTS: 
1290 patients were evaluated. Before the start of the study, 61.2% did not use
any medication, 36.4% took anti-histamines which were not effective, and 27.0% of
those previously treated patients experienced excessive adverse events.
Statistically significant decreases (p < 0.01) compared to baseline were observed
for each individual symptom of the itemised T4SS as well as for the global T4SS. 
The CGI-c improved in 91.1% of the patients who had received treatment previously
and 96.8% of those who had not. Of the patients who had received treatment
previously, 91.7% (p < 0.01) were satisfied with the study treatment and 84.5% of
these patients reported they would prefer levocetirizine in future. All adverse
events (somnolence, fatigue, headache, dry mouth) decreased by comparison with
previous treatments after levocetirizine was used. CONCLUSION: Levocetirizine
showed an improvement in symptom control for SAR and was preferred by patients
compared to the antihistamines they had taken previously. Levocetirizine was well
tolerated.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 16910288 [PubMed - indexed for MEDLINE]

506: Chest. 2006 Aug;130(2):429-35.

Allergic rhinitis and sinusitis in asthma: differential effects on symptoms and
pulmonary function.

Dixon AE, Kaminsky DA, Holbrook JT, Wise RA, Shade DM, Irvin CG.

Pulmonary and Critical Care Medicine, University of Vermont, Burlington, 05401,
USA. anne.dixon@vtmednet.org

BACKGROUND: Allergic rhinitis and sinusitis are frequently associated with
asthma. The purpose of this study was to determine the impact of self-reported
allergic rhinitis and sinusitis on lower airway disease in a large cohort of
participants with well-characterized asthma. METHODS: A cohort study of
participants in two trials of the American Lung Association-Asthma Clinical
Research Centers: 2,031 asthmatics in the Safety of Inactivated Influenza Vaccine
in Asthma in Adults and Children (SIIVA) trial and 488 asthmatics in the
Effectiveness of Low Dose Theophylline as Add-on Treatment in Asthma (LODO)
trial. At baseline, participants reported the presence of allergic rhinitis and
sinusitis, and then lung function and asthma control were measured. During the
trials, participants were monitored for asthma exacerbations. RESULTS: More than 
70% of participants reported either allergic rhinitis or sinusitis. Sinusitis was
more common in female patients (odds ratio, 1.46 [SIIVA]), those with
gastroesophageal reflux disease (odds ratio, 2.21 [SIIVA]), and those of white
race (odds ratio, 1.53 [SIIVA]). Similar associations were seen for allergic
rhinitis. LODO participants with allergic rhinitis and sinusitis had increased
asthma symptoms and a trend toward more sleep disturbance. Participants with
allergic rhinitis had higher baseline lung function than those without allergic
rhinitis measured by peak flow (91.2% vs 95.8% in the SIIVA trial). Participants 
with sinusitis had similar lung function to those without sinusitis. Participants
with and without allergic rhinitis had similar exacerbation rates. In the LODO
trial only, participants with sinusitis had increased asthma exacerbations (5.68 
per patient per year vs 3.72 per patient per year). CONCLUSION: Allergic rhinitis
and sinusitis are associated with more severe asthmatic symptoms and, in patients
with poorly controlled asthma, more exacerbations but are not associated with low
lung function.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 16899841 [PubMed - indexed for MEDLINE]

507: Sci Total Environ. 2006 Oct 15;370(1):39-50. Epub 2006 Aug 8.

Relationship between climate, pollen concentrations of Ambrosia and medical
consultations for allergic rhinitis in Montreal, 1994-2002.

Breton MC, Garneau M, Fortier I, Guay F, Louis J.

Institut des Sciences de l'Environnement, Université du Québec à Montréal,
Montreal, Canada.

The aim of this study is to evaluate the influence of meteorological factors on
Ambrosia pollen concentrations and its impact on medical consultations for
allergic rhinitis of residents from various socio-economic levels in Montréal
(Québec, Canada) between 1994 and 2002. The study was conducted to recognize the 
sensitivity of pollen productivity to daily climate variability in order to
estimate the consequences on human health vulnerability in the context of global 
climate change. Information related to medical consultations for allergic
rhinitis due to pollen comes from the Quebec Health Insurance Board (Régie de
l'assurance-maladie du Québec). Ambrosia pollen concentration was measured by the
Aerobiology Research Laboratories (Nepean, Ontario). Daily temperature (maximum, 
minimum, and mean) and precipitation data were obtained from the Meteorological
Service of Canada. Socio-economic data come from the 1996 and 2001 census data of
Statistics Canada. Between 1994 and 2002, during the Ambrosia pollen season, 7667
consultations for allergic rhinitis due to pollen were recorded. We found a
significant association between the number of medical consultations and pollen
levels. Significant associations were detected for over-consultation the day of
exposure, 1, 2, 3 and 5 days after exposure to high levels of pollen. The
consultation rate is higher from low-income residents (3.10 consultations per
10,000 inhabitants) than for high-income (1.65 consultations per 10,000
inhabitants). Considering the demonstrated impact of pollen levels on health, it 
has become critical to ensure adequate monitoring of Ambrosia and its
meteorological sensivity in the context of the anticipated climate change and its
potential consequences on human health.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16899280 [PubMed - indexed for MEDLINE]

508: Curr Allergy Asthma Rep. 2006 Sep;6(5):420-6.

Pollen immunotherapy: selection,prevention, and future directions.

McEldowney SJ, Bush RK.

William S. Middleton VA Hospital,2500 Overlook Terrace, Madison, WI 53705, USA.

Pollens are an important cause of allergic rhinitis and asthma. Pollen
immunotherapy is effective and potentially curative. It has been shown to prevent
new sensitizations, to prevent the development of asthma in children, and to
induce long-term benefit. Standardization of allergen extracts is necessary to
improve immunotherapy safety and efficacy. Knowledge of the local plant taxonomy 
and allergen cross-reactivity is important in selecting clinically relevant
vaccines. In general, allergenic cross-reactivities correspond to taxonomic
relations. Tree and weed species demonstrate variable degrees of
cross-reactivity. Most grasses have extensive allergenic cross-reactivity.
Mechanism of action continues to be an area of investigation, including the
induction of immunoglobulin G blocking antibodies. Sublingual immunotherapy,
concurrent anti-immunoglobulin E use, hypoallergic peptides, and DNA vaccines are
other promising technologies.

Publication Types: 
    Review

PMID: 16899205 [PubMed - indexed for MEDLINE]

509: Ann Allergy Asthma Immunol. 2006 Jul;97(1):61-5.

Allergenic contribution of the IgE-reactive domains of the 1,3-beta-glucanase Ole
e 9: diagnostic value in olive pollen allergy.

Palomares O, Villalba M, Quiralte J, Rodríguez R.

Departamento de Bioquímica y Biología Molecular, Facultad de Química, Universidad
Complutense de Madrid, Madrid, Spain.

BACKGROUND: Designing of methods for an accurate diagnosis is a main goal of
allergy research. Olive pollen allergy is currently diagnosed using commercially 
available pollen extracts that do not allow identification of the molecules that 
elicit the disease. OBJECTIVE: To analyze the suitability of using the N- and
C-terminal domains (NtD and CtD, respectively) of the 1,3-beta-glucanase Ole e 9,
a major allergen from olive pollen, for in vitro diagnosis. METHODS: Serum
samples from 55 olive-allergic patients were assayed using enzyme-linked
immunosorbent assay to study hypersensitive patients with IgE reactivity to Ole e
9. The specific IgEs to NtD and CtD, obtained by recombinant technology, were
determined by means of immunoblotting, enzyme-linked immunosorbent assay, and
inhibition assays. RESULTS: Thirty-one of 33 serum samples from Ole e 9-allergic 
patients were IgE reactive to recombinant NtD (rNtD) (n = 26 [79%]), recombinant 
CtD (rCtD) (n = 22 [67%]), or both (n = 17 [52%]). Nine patients (27%) were
exclusively reactive to rNtD and 5 (15%) to rCtD. Inhibition assays of IgE
binding to Ole e 9 with a mixture of both domains abolished 90% of the binding,
whereas 44% and 45% were abolished when rNtD and rCtD were used, respectively.
CONCLUSIONS: Because sensitization to NtD or CtD of Ole e 9 could be correlated
to vegetable food-latex-pollen cross-reactivity processes or to the exacerbation 
and persistence of asthma, respectively, these molecules could be used in vitro
as markers of disease to classify patients and to design a patient-tailored
immunotherapy approach.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16892783 [PubMed - indexed for MEDLINE]

510: J Allergy Clin Immunol. 2006 Aug;118(2):434-40.

Efficacy and safety of sublingual immunotherapy with grass allergen tablets for
seasonal allergic rhinoconjunctivitis.

Dahl R, Kapp A, Colombo G, de Monchy JG, Rak S, Emminger W, Rivas MF, Ribel M,
Durham SR.

Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Denmark.

BACKGROUND: Allergen immunotherapy (desensitization) by injection is effective
for seasonal allergic rhinitis and has been shown to induce long-term disease
remission. The sublingual route also has potential, although definitive evidence 
from large randomized controlled trials has been lacking. OBJECTIVE: The aim was 
to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX,
ALK-Abelló, Hørsholm, Denmark) compared with placebo in patients with seasonal
rhinoconjunctivitis. METHODS: A longitudinal, double-blind, placebo-controlled,
parallel-group study that included 51 centers from 8 countries. Subjects were
randomized (1:1) to receive a grass allergen tablet or placebo once daily. A
total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis 
for at least 2 years and confirmation of IgE sensitivity (positive skin prick
test and serum-specific IgE) were included in the study. Subjects commenced
treatment at least 16 weeks before the grass pollen season, and treatment was
continued throughout the entire season. RESULTS: The primary efficacy analysis
showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a 
reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared
with placebo. Side effects mainly comprised mild itching and swelling in the
mouth that was in general well tolerated and led to treatment withdrawal in less 
than 4% of participants. There were no serious local side effects and no severe
systemic adverse events. CONCLUSION: Sublingual immunotherapy with grass allergen
tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was
well tolerated with minor local side effects. CLINICAL IMPLICATIONS: The grass
allergen tablet represents a safe alternative to injection immunotherapy suitable
for home use.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16890769 [PubMed - indexed for MEDLINE]

511: J Investig Allergol Clin Immunol. 2006;16(4):271-3.

Simultaneous allergy to vine pollen and grape.

Mur P, Feo Brito F, Bartolomé B, Galindo PA, Gómez E, Borja J, Alonso A.

Allergy Unit, Hospital Santa Barbara, Puertollano, Ciudad Real, Spain.
pilarmurgimeno@saludalia.com

We report the case of an 18-year-old female student suffering from seasonal
rhinoconjunctivitis with sensitization to pollens from vine and also from grass, 
olive, and Chenopodiaceae plants who had recently developed episodes of itching, 
maculopapular rash, and facial angioedema after eating grapes. Testing revealed
positive reactions to vine pollen and grapes, and specific IgE were found for
both allergens. Immunoblotting and inhibition assays revealed cross-reactivity
between the allergenic structures of vine pollen and grape fruit and also among
botanically unrelated pollens.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16889288 [PubMed - indexed for MEDLINE]

512: J Investig Allergol Clin Immunol. 2006;16(4):253-7.

Pollen specific immunotherapy is not a risk factor for de novo sensitization to
cross-reacting allergens in monosensitized subjects.

Asero R.

Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, MI, Italy.
r.asero@libero.it

BACKGROUND: Some studies have suggested that specific immunotherapy (SIT) may
cause de novo sensitization to allergenic proteins to which patients were not
previously allergic. This event might theoretically involve cross-reacting pollen
allergens, such as profilin or polcalcins, posing a risk of SIT-induced
polysensitization to pollens in patients who were originally monosensitized.
OBJECTIVES: The aim of this study was to assess whether injection SIT with
commercial pollen extract represents a risk factor for the de novo development of
sensitization to different pollens in monosensitized patients. METHODS: The study
involved 142 subjects diagnosed as being monosensitized to a single pollen: 64
patients who were administered a 3-year course of injection SIT and 78 controls. 
Subjects underwent control skin prick tests (SPT) with a series of 8 seasonal
airborne allergens at least 3 years after the first visit. Patients with 5 or
more new sensitivities on SPT were considered to be de novo polysensitized.
RESULTS: At the end of the 3-year follow-up period, the proportion of
polysensitized subjects was identical in previously monosensitized patients who
underwent SIT and control individuals (11% and 10%, respectively). Individuals
who were polysensitized were significantly younger than those who were not (mean 
age +/- SD, 21.6 +/- 11.0 years vs. 31.6 +/- 15.6 years; P < .05). Conclusion:
SIT does not represent a risk factor for progression towards multiple pollen
sensitization in monosensitized pollen-allergic patients.

PMID: 16889283 [PubMed - indexed for MEDLINE]

513: Int J Urol. 2006 Jul;13(7):1028-30.

Asthenospermia in hay fever patients improved by stopping treatment with
histamine H1 receptor antagonists.

Hayashi T, Yoshida S, Ohno R, Ishii N, Terao T, Yamada T.

Department of Urology, Saitama Medical Center, Saitama Medical School, Kawagoe,
Japan. hayashi@saitama-med.ac.jp

We report two cases of asthenospermia, which appeared to be associated with
exposure to histamine H1 receptor antagonists. A 44-year-old man and a
35-year-old man had continued the treatment with fexofenadine hydrochloride and
cetirizine hydrochloride, respectively, under the diagnosis of hay fever. They
and their wives had been examined as infertile couples. Infertility evaluations
revealed no problems with their wives; the patients, however, were found to have 
a low sperm motility (<10%). On suspicion of adverse effects of the histamine H1 
receptor antagonists, they stopped treatment with these drugs, which resulted in 
a complete reversal of spermatic dysfunction. Current information identifies the 
potential fertility hazards of histamine H1 receptor antagonists.

Publication Types: 
    Case Reports

PMID: 16882083 [PubMed - indexed for MEDLINE]

514: Int Arch Allergy Immunol. 2006;141(2):110-8. Epub 2006 Jul 21.

The major allergen of olive pollen Ole e 1 is a diagnostic marker for
sensitization to Oleaceae.

Palomares O, Swoboda I, Villalba M, Balic N, Spitzauer S, Rodríguez R, Valenta R.

Departamento de Bioquímica y Biología Molecular, Facultad de Química, Universidad
Complutense de Madrid, Madrid, Spain.

BACKGROUND: Trees of the family Oleaceae are important allergen sources, with a
strongly varying geographic distribution. For example, olive pollen is an
important allergen source in Mediterranean countries, whereas ash pollen
dominates in Northern and Central Europe and North America. The aim of this study
was to compare the profiles of olive and ash pollen allergens and to study the
degree of cross-reactivity using populations of allergic patients selectively
exposed to olive or ash pollen. METHODS: Olive and ash pollen extracts were
analyzed by IgE immunoblotting using sera from Spanish patients highly exposed to
olive pollen and Austrian patients without olive but ash pollen exposure. IgE
cross-reactivity was studied by qualitative immunoblot inhibition assays and
semiquantitative ELISA inhibitions using olive, ash, birch, mugwort, timothy
grass pollen extracts and the major olive pollen allergen, Ole e 1. RESULTS:
Spanish and Austrian patients exhibited an almost identical IgE-binding profile
to olive and ash pollen allergens, with major reactivity directed against Ole e
1, and its homologous ash counterpart, Fra e 1. IgE inhibition experiments
demonstrated extensive cross-reactivity between olive and ash pollen allergens.
However, whereas cross-reactions between profilins and calcium-binding allergens 
also occurred between unrelated plant species, cross-reactivity to Ole e 1 was
confined to plants belonging to the Oleaceae. CONCLUSIONS: Ole e 1 is a marker
allergen for the diagnosis of olive and ash pollen allergy. Copyright (c) 2006 S.
Karger AG, Basel.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16864978 [PubMed - indexed for MEDLINE]

515: Ann Agric Environ Med. 2006;13(1):25-32.

Prediction of airborne Alnus pollen concentration by using ARIMA models.

Rodríguez-Rajo FJ, Valencia-Barrera RM, Vega-Maray AM, Suárez FJ,
Fernández-González D, Jato V.

Department of Plant Biology and Soil Sciences, Sciences Faculty of Ourense,
University of Vigo, Ourense, 32004, Spain. javirajo@uvigo.es

To take preventative measures to protect allergic people from the severity of the
pollen season, one of aerobiology's objectives is to develop statistical models
enabling the short- and long-term prediction of atmospheric pollen
concentrations. During recent years some attempts have been made to apply Time
Series analysis, frequently used in biomedical studies and atmospheric
contamination to pollen series. The aim of this study is to understand the
behaviour of atmospheric alder pollen concentrations in northwest Spain in order 
to develop predictive models of pollen concentrations by using Time Series
analysis. The prediction line proposed for Oviedo and Ponferrada are similar
(Arima 2,0,1) while in Vigo a more accurate model founded by Arima (3,0,1) and in
Leon (1,0,1) was used. The results suggest that Ponferrada and Oviedo are the
cities in northwest Spain where Alnus pollen allergic individuals should to take 
preventive measures to protect themselves from the severity of the pollen season.
Alnus pollen values higher than 30 grains/m3, a quantity considered sufficient to
trigger severe allergy symptoms of other trees of the Betulaceae family, could be
reached during 25 days in some years. The predicted lines conformed with the
observed values overall in the case of Leon and Ponferrada. Time Series
regression models are especially suitable in allergology for evaluating
short-term effects of time-varying pollen appearance in the atmosphere.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16841868 [PubMed - indexed for MEDLINE]

516: J Pharmacol Toxicol Methods. 2007 Mar-Apr;55(2):127-34. Epub 2006 May 24.

A comprehensive model of allergic rhinitis in guinea pigs.

Al Suleimani M, Ying D, Walker MJ.

Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine,
University of British Columbia, Vancouver, BC, Canada V6T 1Z3.

INTRODUCTION: The economic and social impact of allergic rhinitis is substantial.
The effectiveness of currently available medications is limited and therefore
investigations for more effective drugs is essential. This study was intended to 
establish a model of allergic rhinitis in guinea pigs that can be utilized for
further investigation of new drugs. METHODS: Male Dunkin Hartley guinea pigs were
sensitized intranasally to, and challenged with, ovalbumin. Sneezing (SN) and
nose rubbing (NR) response to allergen challenge were observed on day 21
post-initiation of sensitization in conscious guinea pigs. Nasal blockade (NB),
leukocyte infiltration, and lung inflation pressure (LIP) were assessed in the
same guinea pigs 23-28 days post-initiation of sensitization. A ventilator/flow
method was used to measure NB and LIP. Leukocyte infiltration into nasal lavage
fluid 60 min after challenge in the same animals was recorded as total and
differential cell counts. RESULTS: Sensitized guinea pigs produced acute allergic
responses after allergen challenge. This was characterized by increases in SN,
NR, NB, and eosinophil infiltration. In addition, intranasal allergen challenge
did not change lung inflation pressure. DISCUSSION: Allergen-induced rhinitis in 
guinea pigs resembles that in humans. The model reported in this study can be
used to reflect the effectiveness of drugs currently used to treat allergic
rhinitis and to investigate new potential drugs for the treatment of allergic
rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16829141 [PubMed - indexed for MEDLINE]

517: Immunology. 2006 Jul;118(3):392-401.

PS80 interferes with the antiallergic effect of Cry-consensus peptide, a novel
recombinant peptide for immunotherapy of Japanese cedar pollinosis, at very low
concentration through modulation of Th1/Th2 balance.

Kozutsumi D, Tsunematsu M, Yamaji T, Murakami R, Yokoyama M, Kino K.

Research and Development Section, Pharmaceuticals Development Department, Meiji
Dairies Corporation, Kanagawa, Japan.

Polysorbate 80 (PS80 or Tween-80) is often used as an additive to promote the
rapid solubilization of pharmaceuticals in aqueous solutions. We investigated
whether coinjection of a minimal amount of PS80 had a modulatory effect on the
immunotherapeutic effects of Cry (Cryptomeria)-consensus peptide, a novel peptide
developed for the therapeutic management of Japanese cedar pollinosis, using a
Cry j 1-sensitized mouse model with experimental allergic rhinitis. Subcutaneous 
challenge with Cry-consensus peptide plus 50 microg/ml of PS80 did not affect the
antigen-specific proliferation of splenocytes, but decreased the potency of
Cry-consensus peptide to inhibit antigen-specific interleukin (IL)-5 production
by the cells significantly in comparison with challenge with Cry-consensus
peptide alone. However, there was no significant difference between the effect of
Cry-consensus peptide administration on interferon (IFN)-gamma production in the 
presence and absence of PS80, indicating that PS80 interfered with the T helper 1
(Th1)-dominant T helper balance induced by Cry-consensus peptide challenge.
Moreover, the increase in the level of antigen-specific immunoglobulin G2a
(IgG2a) induced by Cry-consensus peptide challenge was inhibited slightly but
unambiguously by PS80 coinjection. These in vitro experiments indicated that PS80
induces Th2-type differentiation of T helper cells through preferential
inhibition of IFN-gamma expression relative to IL-5 expression in splenocytes in 
a concentration-dependent manner. In naïve mice, sensitization by Cry-consensus
peptide with PS80 induced antigen-specific IL-5 production more potently than
sensitization by Cry-consensus peptide alone, and when PS80 was added to bone
marrow-derived dendritic cells, the endocytosis of fluorescence-labelled
Cry-consensus peptide was dramatically inhibited in a concentration-dependent
manner. Therefore, we conclude that PS80 has an immunomodulatory effect on the
antigen-specific response resulting in a shift towards Th2 predominance with
respect to the antigen recognition stage. Taken together, our findings suggest
that PS80 might decrease the efficacy of Cry-consensus peptide through modulation
of the efficiency of antigen endocytosis and/or of the direction of successive T 
helper cell differentiation.

PMID: 16827900 [PubMed - indexed for MEDLINE]

518: Genes Immun. 2006 Sep;7(6):514-21. Epub 2006 Jul 6.

A network-based analysis of allergen-challenged CD4+ T cells from patients with
allergic rhinitis.

Benson M, Carlsson L, Guillot G, Jernås M, Langston MA, Rudemo M, Andersson B.

Department of Pediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden.
mikael.benson@vgregion.se

We performed a network-based analysis of DNA microarray data from
allergen-challenged CD4(+) T cells from patients with seasonal allergic rhinitis.
Differentially expressed genes were organized into a functionally annotated
network using the Ingenuity Knowledge Database, which is based on manual review
of more than 200,000 publications. The main function of this network is the
regulation of lymphocyte apoptosis, a role associated with several genes of the
tuber necrosis factor superfamily. The expression of TNFRSF4, one of the genes in
this family, was found to be 48 times higher in allergen-challenged cells than in
diluent-challenged cells. TNFRSF4 is known to inhibit apoptosis and to enhance
Th2 proliferation. Examination of a different material of allergen-stimulated
peripheral blood mononuclear cells showed a higher number of interleukin-4(+)
type 2 CD4(+) T (Th2) cells in patients than in controls (P<0.01), as well as a
higher number of non-apoptotic Th2 cells in patients (P<0.01). The number of Th2 
cells expressing TNFRSF4, TNFSF7 and TNFRSF1B was also significantly higher in
patients. Treatment with anti-TNFSF4 resulted in a significantly decreased number
of Th2 cells (P<0.05). A logical inference from all this is that the
proliferation of allergen-challenged Th2 cells is associated with a decreased
apoptosis of Th2 cells and an increase in TNFRSF4 signalling.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16826235 [PubMed - indexed for MEDLINE]

519: Exp Mol Med. 2006 Jun 30;38(3):302-9.

Analysis of the variations in IL-28RA gene and their association with allergic
rhinitis.

Chae SC, Park YR, Li CS, Lee JH, Yang YS, Zhang Q, Kim KS, Chung HT.

Genome Research Center for Immune Disorders, Wonkwang University School of
Medicine, Iksan, Chonbuk 570-749, Korea.

IL-28RA is one of the important candidate genes for complex trait of genetic
diseases, but there is no published information of the genetic variation in this 
gene. We scanned the seven exons and their boundary introns sequence of IL-28RA
including the promoter regions to analyze genetic variation sites, and identified
eighteen single nucleotide polymorphisms (SNPs) and two variation sites. We chose
seven SNPs (g.-1193 A>C, g.-30 C>T, g.17654 C>T, g.27798 A>G, g.31265 C>T,
g.31911 C>T and g.32349 G>A) of them for large sample size genotyping, and
assessed the association of genotype and allele frequencies of these SNPs between
allergic rhinitis patients and non-allergic rhinitis controls. We also compared
the genotype frequencies between Korean controls and Han Chinese control or
Korean Chinese control. We investigated the frequencies of haplotype constructed 
by these SNPs between allergic rhinitis patients and non-allergic rhinitis
controls. Our results suggested that the g.32349 G>A polymorphism of IL-28RA
might be associated with susceptibility to allergic rhinitis (P=0.032), but seems
to have no relationship with serum total IgE levels. The haplotype frequencies by
these SNPs also show significant association between controls and allergic
rhinitis patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16819289 [PubMed - indexed for MEDLINE]

520: J Allergy Clin Immunol. 2006 Jul;118(1):220-5. Epub 2006 May 11.

A network-based analysis of the late-phase reaction of the skin.

Benson M, Langston MA, Adner M, Andersson B, Torinssson-Naluai A, Cardell LO.

Department of Pediatrics, Queen Silvia Children's Hospital, SE-41685 Gothenburg, 
Sweden. mikael.benson@vgregion.se

BACKGROUND: The late-phase reaction (LPR) of the skin is an in vivo model of
allergic inflammation. OBJECTIVE: We sought to identify disease-associated
pathways in the LPR using a network-based analysis. METHODS: The LPR was examined
by means of DNA microarray analysis of skin biopsy specimens from 10 patients
with allergic rhinitis and 10 healthy control subjects. The results were further 
analyzed in 2 different materials consisting of nasal fluids and
allergen-challenged CD4(+) T cells from patients with allergic rhinitis. RESULTS:
The DNA microarray analysis revealed several genes of known relevance to allergy.
The eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes
Charcot-Leyden crystal protein differed most in expression. A network-based
analysis showed upregulation of IL-4- and CCL4-dependent pathways and
downregulation of a TGF-beta-induced pathway. CCL4 is expressed by CD4(+) T cells
and chemotactic for eosinophils. We hypothesized that allergen induces release of
CCL4 from T(H)2 cells and that this contributes to influx of eosinophils. Further
analysis showed increase of CCL4 protein in nasal fluids from allergic patients
during the season. Allergen challenge of PBMCs resulted in proliferation of T(H)2
cells and increased production of CCL4 in CD4(+) T cells from allergic patients. 
An analysis of the DNA microarray data revealed a significant correlation between
CCL4 and the eosinophil marker CLC. CONCLUSION: A network-based analysis of the
LPR showed increased activity of IL-4- and CCL4- dependent pathways and
downregulation of the TGF-beta-induced pathway. Allergen-induced release of CCL4 
from T(H)2 cells might contribute to influx of eosinophils during the LPR.
CLINICAL IMPLICATIONS: Involvement of multiple interacting pathways indicates
that it might be difficult to identify one single mediator as a biomarker or drug
target in allergic inflammation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16815159 [PubMed - indexed for MEDLINE]

521: J Allergy Clin Immunol. 2006 Jul;118(1):143-51. Epub 2006 May 19.

Neonatal exposure with LPS and/or allergen prevents experimental allergic airways
disease: development of tolerance using environmental antigens.

Wang Y, McCusker C.

Meakins-Christie Laboratories, 3626 St Urbain, Montreal, Quebec H2X 2P2, Canada.

BACKGROUND: Studies show that children in rural environments develop less asthma 
and allergic rhinitis than their urban counterparts. This may be a result, in
part, of neonatal exposure to environmental antigens such as LPS and/or early
exposure to allergens. OBJECTIVE: This study examined the effects of neonatal
allergen and/or LPS exposure on subsequent immune responses to allergen. METHODS:
Newborn mice were exposed to LPS and/or ovalbumin. At age 6 weeks, these animals 
were sensitized and challenged with ovalbumin, and airway inflammation,
hyperresponsiveness, and cytokine expression were assessed. RESULTS: Animals
exposed to LPS in the neonatal period developed T cells expressing CD25 and IL-10
on sensitization and challenge. They demonstrated abrogation of airway
hyperresponsiveness and significant decreases in IL-13 from bronchoalveolar
lavage fluid and in specific IgE. IL-4-expressing spleen cells were also
significantly decreased. Mice exposed in the neonatal period to ovalbumin
demonstrated airway hyporesponsiveness after subsequent ovalbumin sensitization
and challenge and did not produce specific IgE. In contrast, these animals showed
increases in IFN-gamma. Animals exposed to both LPS and ovalbumin developed a
response characterized by IL-10 and IFN-gamma-expressing T cells. CONCLUSION:
This suggests that mucosal antigen exposure in the neonatal period results in
inhibition of allergic responses to environmental allergens. Early LPS exposure
directs mucosal responses toward tolerance, whereas ovalbumin exposure follows
the T(H)1-type response on subsequent sensitization. CLINICAL IMPLICATIONS: This 
study suggests that prevention of airways allergy may be best achieved by
appropriate exposure of the airway mucosa early in life to environmental
antigens.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16815150 [PubMed - indexed for MEDLINE]

522: Ear Nose Throat J. 2005 Jul;84(7):426-30.

Comparison of intranasal hypertonic dead sea saline spray and intranasal aqueous 
triamcinolone spray in seasonal allergic rhinitis.

Cordray S, Harjo JB, Miner L.

Academic Programs at Southern Nazarene University, Tulsa, Okla, USA.
scordray@cfaith.com

Intranasal corticosteroids are well known to be efficacious in the treatment of
allergic rhinitis. Nasal irrigation with saline, including hypertonic saline, has
long been recommended for the treatment of sinonasal disease, and it has been
shown to have a positive effect on the physiology of the nasal mucosa. Until now,
no study of the clinical efficacy of intranasal hypertonic Dead Sea saline as a
monotherapy for seasonal allergic rhinitis has been reported. We conducted a
prospective, randomized, single-blind, placebo-controlled comparison of
intranasal hypertonic Dead Sea saline spray and intranasal aqueous triamcinolone 
spray in 15 patients with seasonal allergic rhinitis. Results were based on a
7-day regimen. Based on Rhinoconjunctivitis Quality of Life Questionnaire scores,
clinically and statistically significant (p < 0.0001) improvements were seen in
both active-treatment groups; as expected, the corticosteroid spray was the more 
effective of the two treatments. No significant improvement occurred in the
control group. Our preliminary results not only confirm the efficacy of
intranasal corticosteroid therapy in moderate-to-severe allergic rhinitis, they
also suggest that the Dead Sea saline solution can be an effective alternative in
mild-to-moderate allergic rhinitis, particularly with respect to nasal and eye
symptoms. The hypertonicity of the Dead Sea solution may have a positive effect
on the physiology of the nasal mucosa by improving mucociliary clearance. In
addition, the dominant cation in the Dead Sea solution--magnesium--probably
exerts anti-inflammatory effects on the nasal mucosa and on the systemic immune
response.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16813032 [PubMed - indexed for MEDLINE]

523: Allergol Immunopathol (Madr). 2006 Mar-Apr;34(2):82-3.

Randomized open comparison of the safety of SLIT in a no-updosing and traditional
updosing schedule in patients with Parietaria allergy.

Guerra L, Compalati E, Rogkakou A, Pecora S, Passalacqua G, Canonica GW.

Allergy and Respiratory Diseases, Department of Internal Medicine, University of 
Genoa, Genoa, Italy.

BACKGROUND: Due to optimal safety of sublingual immunotherapy (SLIT), it was
suggested that a slow up-dosing phase maybe not necessary, and therefore the
treatment will be more patient-friendly, avoiding dosing mistakes. PATIENTS:
Twenty adult patients suffering allergic rhinitis due to Parietaria, were
enrolled. Half of them received the traditional schedule and the other half
immediately started with 200 STU. RESULTS: No difference was observed between the
traditional up-dosing treatment schedule and no-up-dosing treatment schedule in
terms of side effects, even mild local side effects, even mild local side effects
was greater with traditional regimen.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16808019 [PubMed - indexed for MEDLINE]

524: Chin Med J (Engl). 2006 Jun 20;119(12):991-7.

Intranasal application of Epstein-Barr virus/lipoplex to abrogate eosinophillia
in murine model of allergic rhinitis.

Han DM, Zhou B, Wang T, Wang XD, Fan EZ.

Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Tongren
Hospital, Capital University of Medical Sciences, Beijing 100730, China.

BACKGROUND: Currently anti-inflammatory therapy with steroids for allergic
rhinitis need long-term repeated administration, although it is effective. Gene
therapy is being suggested to substitute it. The aim of this study was to
investigate nonviral vector mediated exogenous gene expression in COS-7 cells in 
vitro and the effect of intranasal mouse interleukin (mIL)-12 transgene
expression on allergen induced eosinophil infiltration of nasal mucosa in a
murine model of allergic rhinitis. METHODS: In vitro COS-7 cells were infected
with Epstein-Barr virus (EBV)/lipoplex. The expression of IL-12 p70 in cell
culture supernatant was examined by enzyme-linked immunosorbent assay (ELISA). In
mice with ovalbumin (OVA) induced allergic rhinitis, EBV/lipoplex was
administered by nasal drops before OVA challenge once a day from day 1 to day 10.
The expression of IL-12 mRNA and protein, the change of eosinophil count in nasal
mucosa and serum total IgE were measured 24 hours after the last challenge.
RESULTS: EBV/lipoplex could effectively transfect COS-7 cells. The expression of 
IL-12 p70 in cell culture supernatant was significantly more than in blank
control. IL-12 via EBV plasmid vector transduction could be overexpressed in
vivo. In pGEG.mIL-12 treated models, the nasal mucosa revealed a high level of
widespread mIL-12 transduction by immunohistochemistry and in situ hybridization.
Histological evaluation revealed marked suppression of eosinophil infiltration in
nasal mucosa. The eosinophil count in allergic rhinitis group [(26.5 +/-
9.8)/high-power field (HPF)] was significantly increased over control group
[(0.40 +/- 0.52)/HPF] (F = 56.94, P < 0.01), while the count in IL-12 gene
therapy group [(4.60 +/- 2.63)/HPF] was significantly less than that of allergic 
group (F = 56.9, P < 0.01). Serum total IgE between in gene therapy mice [(88.83 
+/- 6.71) ng/ml] and allergic rhinitis mice [(103.1 +/- 5.7) ng/ml] showed a
significant difference (F = 1216, P < 0.05). CONCLUSIONS: Nonviral EBV plasmid
vector, pGEG.mIL-12 was able to overexpress exogenous gene both in vitro and in
murine nasal mucosa in vivo. IL-12 overexpression via EBV/lipoplex could stem
allergen induced eosinophil infiltration in nasal mucosa in murine models of
allergic rhinitis, which may suggest a new cytokine immunogenetic therapy for
allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16805982 [PubMed - indexed for MEDLINE]

525: Ann Allergy Asthma Immunol. 2006 Jun;96(6):851-7.

Comparison of fluticasone propionate aqueous nasal spray and oral montelukast for
the treatment of seasonal allergic rhinitis symptoms.

Martin BG, Andrews CP, van Bavel JH, Hampel FC, Klein KC, Prillaman BA, Faris MA,
Philpot EE.

Southwest Allergy and Asthma Research, San Antonio, Texas 78229, USA.
swallergy@sbcglobal.net

BACKGROUND: Few studies have directly compared the efficacy of intranasal
corticosteroids with that of leukotriene receptor antagonists for the treatment
of daytime and nighttime symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE:
To compare fluticasone propionate aqueous nasal spray, 200 microg daily, with
oral montelukast, 10 mg daily, for the relief of SAR symptoms. METHODS: Patients 
with SAR 15 years or older were randomized to receive either fluticasone
propionate (n = 367) or montelukast (n = 369) in this double-blind, double-dummy,
parallel-group study. The primary efficacy measure was the mean change from
baseline in daytime total nasal symptom scores (TNSSs) (the sum of 4 daytime
individual nasal symptom scores [INSSs] assessing nasal congestion, itching,
rhinorrhea, and sneezing), averaged across weeks 1 and 2. Secondary efficacy
measures included the 4 daytime INSSs, nighttime TNSSs (the sum of 3 nighttime
INSSs assessing congestion on awakening, difficulty going to sleep, and nighttime
awakenings), and the 3 nighttime INSSs averaged across weeks 1 and 2. RESULTS:
Mean changes from baseline in daytime TNSSs (P < .001), all daytime INSSs (P <
.001), nighttime TNSSs (P < .001), and all nighttime INSSs (P < or = .02) showed 
significant differences favoring fluticasone propionate over montelukast across 2
weeks of treatment. CONCLUSION: Compared with montelukast, fluticasone propionate
provided significantly greater improvement in daytime and nighttime SAR symptoms.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16802774 [PubMed - indexed for MEDLINE]

526: Ann Allergy Asthma Immunol. 2006 Jun;96(6):779-86.

The role of antileukotriene therapy in seasonal allergic rhinitis: a systematic
review of randomized trials.

Rodrigo GJ, Yañez A.

Departamento de Emergencia, Hospital Central de las Fuerzas Armadas, and Clinica 
Respirar, Benito Nardone, Montevideo, Uruguay. gurodrig@adinet.com.uy

OBJECTIVE: To evaluate the effect of oral leukotriene receptor antagonists as
monotherapy or combined with other drugs in the treatment of seasonal allergic
rhinitis. DATA SOURCES: The MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing 
and Allied Health), and Cochrane databases; review articles; and references of
included trials. STUDY SELECTION: Published (1966-2005) randomized controlled
trials with nasal and eye symptoms and quality-of-life scores as primary
outcomes. RESULTS: Seventeen studies including 6,231 adults with seasonal
allergic rhinitis were selected. Oral leukotriene antagonists significantly
reduced daytime nasal symptoms (standardized mean difference [SMD], -0.24; 95%
confidence interval [CI], -0.33 to -0.16), nighttime nasal symptoms (SMD, -0.23; 
95% CI, -0.30 to -0.16), and eye symptoms and significantly improved quality of
life compared with placebo. There were no significant differences between oral
leukotriene antagonists and oral histamine H1 antagonists on nasal and eye
symptoms and quality-of-life overall score. We also found that leukotriene
receptor antagonists were inferior to intranasal corticosteroids for decreasing
daytime (SMD, 0.41; 95% CI, 0.27 to 0.56) and nighttime nasal symptoms. The
combination of leukotriene receptor antagonists plus histamine H1 antagonists
produced greater relief of eye symptoms compared with histamine H1 antagonists
alone. Finally, intranasal corticosteroids significantly reduced nasal congestion
compared with leukotriene receptor antagonists plus histamine H1 antagonists.
CONCLUSIONS: Leukotriene receptor antagonists were better than placebo,
equivalent to oral histamine H1 antagonists, and inferior to intranasal
corticosteroids for treating seasonal allergic rhinitis. Alternatively,
leukotriene receptor antagonists plus histamine H1 antagonists were more
effective than histamine H1 antagonists alone but inferior to intranasal
corticosteroids.

Publication Types: 
    Comparative Study
    Review

PMID: 16802764 [PubMed - indexed for MEDLINE]

527: South Med J. 2006 Jun;99(6):593-9.

Efficacy and central nervous system impairment of newer-generation prescription
antihistamines in seasonal allergic rhinitis.

Spangler DL, Brunton S.

Atlanta Allergy and Asthma Clinic, 1965 N. Park Place, N.W., Atlanta, GA 30339,
USA. akspangler@mindspring.com

Allergic rhinitis is a highly prevalent disorder and oral antihistamines are
often used to manage patient symptoms. Older-generation antihistamines, such as
diphenhydramine and chlorpheniramine, are effective at relieving the symptoms of 
seasonal allergic rhinitis (SAR); however, they are associated with adverse
events, including sedation and impairment, at, or above, the recommended dose.
Newer-generation antihistamines, such as desloratadine, cetirizine and
fexofenadine, were developed to minimize adverse events. In this article, studies
examining newer-generation antihistamines in adults and children were reviewed.
The clinical evidence confirms that desloratadine, cetirizine and fexofenadine
are effective at managing the symptoms of SAR in adults and children; however,
cetirizine is more likely to cause sedation. Physician intervention is paramount 
to SAR symptom management. It is essential that appropriate treatment relieves
SAR symptoms with absent or minimal adverse events. This is particularly
important for those patients involved in skilled and cognitive activities or
safety-critical jobs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16800414 [PubMed - indexed for MEDLINE]

528: Allergy. 2006;61 Suppl 81:29-31.

Future developments in sublingual immunotherapy.

Didier A.

Service de Pneumologie et d'Allergologie, Hôpital Larrey, Toulouse, France.

The increasing prevalence of allergic rhinitis and its progression to asthma has 
severe implications for patients and health care systems in many countries. An
ideal therapy is one that is effective not only against symptoms but also towards
the natural progression of the allergic disease. Immunotherapy is recognized to
achieve both these aims. Administration of allergens by the sublingual route, a
modality with a very low rate of systemic reactions, is widely considered a
treatment of choice. However, if it is to be universally accepted, more
developments are required. Although, it is effective against grass and other
seasonal pollens, further controlled trials are needed to confirm its efficacy
against perennial allergens. Additional studies, particularly in paediatric
populations, are needed to confirm its long-term effects on disease progression. 
New vaccine developments, which take into account the increasing understanding of
the underlying immune mechanisms and that exploit molecular engineering
techniques will create allergens that are effective, stable, risk free and easy
to administer.

Publication Types: 
    Review

PMID: 16792604 [PubMed - indexed for MEDLINE]

529: Allergy. 2006;61 Suppl 81:20-3.

Sublingual immunotherapy in the treatment of adult allergic rhinitis patients.

Canonica GW, Passalacqua G.

Allergy & Respiratory Diseases, DIMI, University of Genoa, Padiglione Maragliano,
Genoa, Italy.

Sublingual immunotherapy (SLIT) was accepted for clinical use by the medical
community only 15 years after the first controlled trial published. The
acceptance of SLIT has been driven by the evidence base of a large number of
clinical trials confirming the efficacy and a recent meta-analysis study.
Although SLIT is self-managed by the patient, this does not generate problems
with compliance. The safety profile, assessed in clinical trials and
postmarketing surveillance studies, is satisfactory with no reports of systemic
adverse reactions. New data are available on the persisting, long-lasting effect 
of SLIT and on the association with the prevention of asthma in paediatric
patients. However, there is only indirect evidence for such persistence and
duration of effect in adult patients. Key priorities for further investigation
are the mechanisms of action, the efficacy in asthma, the cost/effectiveness and 
the identification of those patients who will achieve the maximum benefit with
SLIT.

Publication Types: 
    Review

PMID: 16792602 [PubMed - indexed for MEDLINE]

530: Allergy. 2006 Jul;61(7):855-9.

Five-year follow-up on the PAT study: specific immunotherapy and long-term
prevention of asthma in children.

Niggemann B, Jacobsen L, Dreborg S, Ferdousi HA, Halken S, Høst A, Koivikko A,
Koller D, Norberg LA, Urbanek R, Valovirta E, Wahn U, Möller C; PAT Investigator 
Group.

Department of Pediatric Pneumology and Immunology, Charité, Berlin, Germany.

BACKGROUND: A 3-year course of specific immunotherapy (SIT) in children with hay 
fever to grass and/or birch pollen significantly reduced the risk of developing
asthma. To investigate the long-term preventive effect, we performed a follow
up--2 years after termination of immunotherapy. METHODS: A total of 183 children,
aged 6-14 years with grass and/or birch pollen allergy could be investigated 2
years after discontinuation of SIT or no treatment. Conjunctival provocation
tests (CPTs) and methacholine bronchial provocation tests were carried out during
the season and winter after 5 years. The development of asthma was assessed by
clinical evaluation. RESULTS: The significant improvement in hay fever and CPT
results observed after 3 years of SIT persisted at the 5-year follow-up. No
difference in bronchial responsiveness to methacholine was found after 5 years
because of spontaneous improvement during the follow-up period in the control
patients. The immunotherapy-treated children had significantly less asthma after 
5 years as evaluated by clinical symptoms [odds ratio 2.68 (1.3-5.7)] in favor of
SIT for prevention of development of asthma and significantly less patients
reported an increase in asthma scores (P < 0.01). CONCLUSION: Immunotherapy for 3
years with standardized allergen extracts of grass and/or birch shows long-term
clinical effect and preventive effect on development of asthma in children with
seasonal rhinoconjunctivitis.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 16792584 [PubMed - indexed for MEDLINE]

531: J Investig Allergol Clin Immunol. 2006;16(3):162-8.

Safety and immunological changes during sublingual immunotherapy with
standardized quality grass allergen tablets.

Malling HJ, Lund L, Ipsen H, Poulsen L.

Allergy Clinic, National University Hospital, Copenhagen, Denmark.
hans.joergen.malling@rh.hosp.dk

Immunotherapy is the only treatment for allergy that has the potential to alter
the natural course of the disease. Sublingual immunotherapy for grass
pollen-induced rhinoconjunctivitis has been developed to make immunotherapy
available to a broader group of allergic patients. Here, a safe dose range and
the safety during daily sublingual administration were investigated for a new
tablet-based sublingual immunotherapy for grass pollen allergy. Simultaneously,
immunological changes were monitored. A randomized, double-blind,
placebo-controlled phase I trial was undertaken, with stepwise dose-escalation
during the dose-finding period, and afterwards with daily dosing 8 weeks prior to
and 15 weeks during the grass pollen season (2500, 25000, or 75000 standardized
quality tablet [SQ-T] units, or placebo). Fifty-two participants with grass
pollen-induced rhinoconjunctivitis and a positive skin prick test and specific
IgE to Phleum pratense entered the trial. During the daily-dose treatment
periods, 67% of the participants reported adverse events. The most frequent were 
itching in the mouth, eyes, or throat, and rhinitis, and most were mild and
resolved within 1 day. Two participants withdrew due to adverse events (sting and
blisters in the mouth and itching in the mouth). Time- and dose-dependent
increases of P pratense-specific IgG, IgA, IgE, and IgE-competing components were
found in serum during the first 8 weeks of daily dosing, indicating that the
treatment had a significant allergen-specific effect on the immune system. In
conclusion, the grass allergen tablet, administered in a dose of 75000 SQ-T once 
daily, was well tolerated and displayed systemic immunogenicity.

Publication Types: 
    Clinical Trial, Phase I
    Randomized Controlled Trial

PMID: 16784009 [PubMed - indexed for MEDLINE]

532: Clin Exp Allergy. 2006 Jun;36(6):742-7.

The effect of allergic rhinitis on adenosine concentration in exhaled breath
condensate.

Vass G, Huszár E, Augusztinovicz M, Baktai G, Barát E, Herjavecz I, Horváth I.

Department of Pathophysiology, National Korányi Institute for Pulmonology,
Budapest, Hungary.

BACKGROUND: Patients with allergic rhinitis (AR) frequently develop asthma. This 
initiating inflammation in the lower airways may result in increased levels of
inflammatory mediators such as adenosine in the exhaled breath. OBJECTIVE: We
compared adenosine levels in exhaled breath condensate (EBC) and both exhaled and
nasal nitric oxide (NO) levels of AR patients and healthy control subjects. We
also tested whether inhalation through inflamed nasal cavity during EBC sampling 
influences adenosine concentrations in exhaled air. METHODS: Exhaled and nasal NO
levels were measured and EBC samples (at oral inhalation) were collected from 27 
patients and 15 healthy controls. EBC collection was repeated after 15 min with
subjects inhaling through their nose. Adenosine was measured by HPLC and NO was
determined by chemiluminescence. RESULTS: The concentration of EBC adenosine was 
higher in patients with AR than in healthy controls (12.4+/-1.3 nM vs. 6.5+/-0.7 
nM, P=0.0019) and this was accompanied by an increase in the concentration of
exhaled NO (10.2+/-1.3 ppb vs. 5.3+/-0.5 ppb; P=0.0099, respectively). No
difference in nasal NO was detected. EBC adenosine concentration showed a
significant positive correlation with the level of exhaled NO. In contrast to
healthy control subjects, patients with rhinitis had higher levels of exhaled
adenosine when inhaling via the nose instead of the mouth (17.7+/-2.8 nM,
P=0.007). CONCLUSION: When compared with healthy subjects, patients with AR
exhibit an increased concentration of exhaled adenosine and a related increase in
exhaled NO concentration. EBC adenosine is further increased when rhinitis
patients inhale through their nose than via their mouth. Our data suggest that
non-asthmatic patients with rhinitis may have subclinical inflammation in their
lower airways.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16776675 [PubMed - indexed for MEDLINE]

533: Pediatr Allergy Immunol. 2006 Jun;17(4):259-68.

Do the leukotriene receptor antagonists work in children with grass
pollen-induced allergic rhinitis?

Keskin O, Alyamac E, Tuncer A, Dogan C, Adalioglu G, Sekerel BE.

Hacettepe University Faculty of Medicine, Pediatric Allergy and Asthma Unit,
Hacettepe, Ankara, Turkey.

Although cysteinyl-leukotriene receptor antagonists were recently approved for
use in allergic rhinitis (AR), there has been no study to date investigating
their application in children. The aim was to evaluate whether montelukast
provides any benefit in nasal allergen challenge-induced symptoms in children,
and whether it could improve the control provided by an antihistamine during
pollen season. Two randomized studies, one a double-blind, placebo-controlled,
nasal allergen challenge study and one an open-label, cross-over, parallel-group 
clinical study, were performed in 18 (11.7+/-0.7 years) and 32 children
(10.5+/-0.5 years), respectively, with grass pollen allergy. In the first study, 
the effect of a single dose of montelukast and its combination with loratadine
were compared with placebo on nasal responses induced by allergen challenge. In
the second study, the additive effect of montelukast to loratadine was tested in 
an open-label cross-over clinical study. In the challenge study, early-phase and 
late-phase nasal reactions peaked at 15 min and 4 h after the challenge
respectively. During the early phase, combination improved total nasal symptoms
(p=0.004) during the first hour and sneezing (p=0.012) at 15 min compared with
placebo group. During the late phase, montelukast (p=0.017) and combination
(p=0.011) caused less nasal obstruction at 4 h and combination caused less
sneezing at 6 h (p=0.015). In the clinical trial, montelukast provided protection
on seasonal increase in pulmonary symptoms [0 (0, 14) vs. 6.5 (0, 27.7); p=0.016]
and on the decrease in FEF25-75 [-0.09 (-0.34, 0.17) vs. -0.28 (-0.66, 0.02);
p=0.002]. However, there was no improvement in nasal symptoms and flows. Although
we showed protection against nasal challenge-induced congestion with montelukast,
we were not able to show the same in the clinical study possibly because of low
pollen counts and mildness of the symptoms of the patients with AR. However,
montelukast provided better control of pulmonary symptoms and protection from
seasonal decrease in lung function, indicating its potential therapeutic benefit 
in children with AR.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 16771779 [PubMed - indexed for MEDLINE]

534: J Ethnopharmacol. 2006 Oct 11;107(3):424-30. Epub 2006 Apr 18.

Effects of cryptoporus polysaccharide on rat allergic rhinitis associated with
inhibiting eotaxin mRNA expression.

Xie QM, Deng JF, Deng YM, Shao CS, Zhang H, Ke CK.

Medical School of Zhejiang University, Hnagzhou 310031, China. xieqm@zju.edu.cn

Aqueous extract from the fruiting body of Cryptoporus volvatus has been reported 
to present anti-tumor, anti-allergy, anti-inflammation and immunomodulatory
activities. However, the effect mechanisms of anti-allergy and anti-inflammation 
are poorly understood. The aim of study is to evaluate whether Cryptoporus
polysaccharides (CP) extracted from fruiting body of Cryptoporus volvatus
decrease the development of nasal symptoms, airway hyperresponsiveness (AHR) to
methacholine (MCh) and the infiltration of eosinophils in nasal mucosa in rat
model of allergic rhinitis, and investigate a possible action mechanism of CP by 
detecting the expression of eotaxin mRNA in nasal mucosa and lung tissues. Rats
were immunized with ovalbumin and consecutive topical antigen instillation was
performed. Repeated intranasal ovalbumin challenge caused rhinitis symptom, AHR
to MCh, eosinophil infiltration and histological alterations into the nasal
mucosa and increase of eotaxin mRNA expression in nasal mucosa and lung tissue
were examined. Pretreatment with CP 3, 9 and 27 mg kg(-1) (ig) decreased the
numbers of sneezing 27.4%, 38.4% and 44.3% and nasal rubbing 27.5%, 34.9% and
47.7% comparison with model group, respectively. CP caused a dose-related
inhibition of MCh-induced AHR. CP 27 mg kg(-1) decreased the expression of
eotaxin mRNA in the nasal mucosa by 35%. These results suggest CP can relieve the
symptom, eosinophil infiltration and injury of tissue in nasal mucosa and lung
tissue and AHR of allergic rhinitis in rats. Its action mechanism may be
associated with the decrease of eotaxin mRNA expression.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16765544 [PubMed - indexed for MEDLINE]

535: Int Arch Allergy Immunol. 2006;140(4):327-33. Epub 2006 Jun 2.

Eosinophilic inflammation, remodeling of lower airway, bronchial responsiveness
and cough reflex sensitivity in non-asthmatic subjects with nasal allergy.

Hara J, Fujimura M, Myou S, Furusho S, Abo M, Oribe Y, Ohkura N, Herai Y, Sone T,
Waseda Y, Yasui M, Kasahara K.

Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University
Graduate School of Medicine, Kanazawa City, Ishikawa, Japan.
hara@med3.m.kanazawa-u.ac.jp

BACKGROUND: It has been reported that nasal allergy influences the lower airway
inflammation and functions. We elucidated whether nasal allergy would contribute 
to lower airway inflammation and functions. METHODS: 266 subjects aged 21-39
years were interviewed with special emphasis on history of asthma and nasal
allergies (perennial allergic rhinitis (PAR) and seasonal allergic rhinitis
(Japanese cedar pollinosis; PO)). Symptomatic subject was defined when nasal
symptoms were present during a 3-week study period. Pulmonary function,
provocative concentration of methacholine causing a 20% fall in forced expiratory
volume in 1 s (PC20), capsaicin cough threshold defined as capsaicin
concentration eliciting 5 or more coughs (C5) and eosinophil percentage in
hypertonic saline-induced sputum were measured. RESULTS: Based on the interview, 
232 subjects without asthma were divided into symptomatic (n = 25) and
asymptomatic (n = 22) PAR, PO on-season (n = 15) and off-season (n = 36), and
non-nasal allergy subjects (control) (n = 134). Sputum eosinophils were
significantly greater in symptomatic PAR than another four groups (p < 0.01).
FEV1/FVC ratio was significantly lower in PAR than control (p < 0.05). Maximum
mean expiratory flow was lower in PAR than control (asymptomatic: p < 0.05,
symptomatic: p = 0.06). C5 was not different among groups. PAR tended to have a
lower PC20 compared to control (symptomatic: p = 0.078; asymptomatic: p = 0.086).
CONCLUSIONS: These results suggest that eosinophilic inflammation occurred in
symptomatic period of PAR may contribute to development of lower airway
remodeling and bronchial hyperresponsiveness. Reversely, PO may not be associated
with lower airway eosinophilic inflammation or abnormal bronchial functions.
Nasal allergy dose not influence the cough reflex sensitivity. Copyright 2006 S. 
Karger AG, Basel.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16757921 [PubMed - indexed for MEDLINE]

536: Eur Ann Allergy Clin Immunol. 2006 Mar;38(3):90-3.

Occupational respiratory allergy to cyclamen pollen: a case report.

Ariano R, Mistrello G, Panzani RC.

U.O.C. Medicina Interna, Ambulatorio di Allergologia ed Immunologia Clinica,
A.S.L no 1, Imperiese, Italy.

A case of cyclamen (Cyclamen persicum) pollen allergy is described on a flower
cultivator. The diagnosis was assessed by skin test, methacoline test, nasal
provocation test and RAST. SDS-PAGE and immunoblotting have shown an intense
response against a 18 kDa component and a weaker one at 100 Kda. A RAST
inhibition against Cupressus sempervirens and Acacia floribundia showed no
identity with cyclamen. This case confirm the cyclamen allergenity, in
professional exposure. The nasal challenge prove to be very useful to confirm
allergic sensitizations an we emphasize the necessity of preventive measures of
protection for those florists who cultivate cyclamen plants.

Publication Types: 
    Case Reports

PMID: 16752694 [PubMed - indexed for MEDLINE]

537: Eur Ann Allergy Clin Immunol. 2006 Mar;38(3):87-9.

Monoid sublingual immunotherapy.

Palma-Carlos AG, Santos AS, Branco-Ferreira M, Pregal AL, Palma-Carlos ML.

Clinical Allergy Immunology Center, CAIC, Lisbon, Portugal.

Sublingual monoid immunotherapy with monomeric allergoids has been largely used
in Europe in the last few years. An open trial of allergoid in tablets has been
done in rhinitic patients allergic to house dust mites, grass pollens and
Parietaria with clear improvement in clinics and drug consumption scores. In a
second phase a double blind placebo controlled trial of grass pollens allergoids 
have been done in hay fever patients with significant decrease on the scores of
rhinorrea, sneezing and conjunctivitis nasal steroid consumption and clinical
score after serial nasal challenges. Monomeric allergoids are an efficace and
safe immunotherapy in allergic rhinitis.

Publication Types: 
    Meta-Analysis

PMID: 16752693 [PubMed - indexed for MEDLINE]

538: Adv Ther. 2006 Mar-Apr;23(2):373-84.

Efficacy and safety of butterbur herbal extract Ze 339 in seasonal allergic
rhinitis: postmarketing surveillance study.

Käufeler R, Polasek W, Brattström A, Koetter U.

Max Zeller Sohne AG, Romanshorn, Switzerland.

The efficacy and safety of the butterbur leaf extract Ze 339 (carbon dioxide
extract from the leaves of Petasites hybridus L., 8 mg petasines per tablet) were
tested in patients with seasonal allergic rhinitis. In an open postmarketing
surveillance study, 580 patients were treated with an average of 2 tablets of Ze 
339 daily for 2 weeks. Symptoms of rhinorrhea, sneezing, nasal congestion, itchy 
eyes and nose, red eyes, and skin irritation were evaluated on a visual analogue 
scale. Symptoms of seasonal allergic rhinitis improved in 90% of patients.
Differences observed before and after therapy were significant and clinically
relevant for all symptoms. Improvement reported by the end of the study was found
to be inversely related to symptom severity as described at baseline. Efficacy,
tolerability, and improvement in quality of life were positively rated by 80%,
92%, and 80% of patients, respectively. A total of 44% of patients were given an 
antiallergic comedication. This combination did not result in a better effect
than was attained with Ze 339 monotherapy. Adverse events occurred at a rate of
3.8%, and gastrointestinal complaints were predominantly nonspecific. Results of 
this postmarketing surveillance trial are consistent with observations documented
in previous randomized, double-blind, prospective, controlled trials of the same 
extract that were conducted according to Good Clinical Practice (GCP). Butterbur 
leaf special extract Ze 339 was confirmed by 3 GCP trials and 2 postmarketing
surveillance trials to be safe and efficacious in the treatment of patients with 
seasonal allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16751170 [PubMed - indexed for MEDLINE]

539: Drugs. 2006;66(7):931-8.

Comment in:
    Drugs. 2006;66(7):939-40.

Ultra-short-course seasonal allergy vaccine (Pollinex Quattro).

McCormack PL, Wagstaff AJ.

Adis International Limited, 51 Centorian Drive, Mairangi Bay, Auckland 1311, New 
Zealand. demail@adis.co.nz

This novel ultra-short-course seasonal allergy vaccine, containing
glutaraldehyde-modified allergens and the adjuvants 3-deacylated monophosphoryl
lipid A (MPL) and L-tyrosine, requires a preseasonal course of only four
injections to be effective in the treatment of seasonal allergic rhinitis. In
patients with seasonal allergic rhinitis and/or allergic asthma, a four-injection
vaccination course with either the grass pollen or tree pollen allergy vaccine
significantly reduced skin prick sensitivity reactions, significantly elevated
allergen-specific IgG levels and significantly reduced the seasonally induced
boost of IgE. Preseasonal vaccination of adult patients with either grass pollen 
or tree pollen allergy vaccine significantly reduced the median combined
symptom/medication score compared with placebo. Similarly, preseasonal
vaccination of children and adolescents with allergies to grass pollen or tree
pollen significantly reduced the global symptom and medication use scores
compared with the previous pollen season. Postmarketing surveillance indicated
that after a course of vaccination, 82% of patients experienced reduced symptoms 
and 62% reduced their rescue medication use compared with the previous season.
The allergy vaccine was generally well tolerated. Local reactions, mainly
injection-site redness and swelling, were more common than systemic reactions.
There were no serious adverse events.

PMID: 16740007 [PubMed - indexed for MEDLINE]

540: Eur Respir J. 2006 Oct;28(4):756-62. Epub 2006 May 31.

Erratum in:
    Eur Respir J. 2006 Dec;28(6):1292.

Prevalence and socioeconomic associations of asthma and allergic rhinitis in
northern [corrected] Africa.

Georgy V, Fahim HI, El-Gaafary M, Walters S.

Dept of Public Health and Epidemiology, Public Health Building, University of
Birmingham, Birmingham, B15 2TT, UK.

The aims of the current study were to ascertain the prevalence of asthma and
allergic rhinoconjunctivitis symptoms in Cairo, Egypt (northern Africa), and to
elucidate the socioeconomic factors associated with symptom prevalence and
severity. A translated and adapted version of the International Study of Asthma
and Allergies in Childhood (ISAAC) questionnaire was distributed to a sample of
2,645 11-15-yr-olds in state and fee-paying schools in Cairo. The overall
prevalences of wheeze ever, wheeze during the last year and physician-diagnosed
asthma were 26.5% (697 out of 2,631), 14.7% (379 out of 2,570) and 9.4% (246 out 
of 2,609), respectively. The prevalence of rhinoconjunctivitis was 15.3% (399 out
of 2,616). Asthma symptoms were independently associated with attendance at a
state school, parental asthma, age, history of rhinitis and owning a pet cat.
Rhinoconjunctivitis was independently associated with attendance at a state
school, father's education, parental history of asthma, asthma symptoms and
owning a pet cat. In spite of a higher prevalence of severe asthma symptoms in
state schools prevalence of physician diagnosis of asthma was the same in both
school types, suggesting inequalities in access to healthcare. In conclusion, the
prevalence of physician-diagnosed asthma in Cairo was 9.4%, while the prevalence 
of rhinoconjunctivitis was 15.3%. There is a higher prevalence and increased
severity of asthma symptoms in children of lower socioeconomic groups, as defined
by state school attendance in Cairo.

PMID: 16737986 [PubMed - indexed for MEDLINE]

541: Otolaryngol Head Neck Surg. 2006 Jun;134(6):997-1000.

Leukotriene C4 synthase A-444C gene polymorphism in patients with allergic
rhinitis.

Eskandari HG, Unal M, Oztürk OG, Vayisoğlu Y, Muşlu N.

Department of Biochemistry, Mersin University School of Medicine, Mersin, Turkey.
geskandari@hotmail.com

OBJECTIVE: To determine the frequency of leukotriene C4 synthase A-444C
polymorphism in allergic rhinitis patients. STUDY DESIGN AND SETTING: A
prospective, randomized, case-controlled study. Blood samples were obtained from 
85 patients with allergic rhinitis and 95 healthy individuals. After the
extraction of DNA from the blood samples, the leukotriene C4 synthase A-444C
polymorphism was studied by a real-time polymerase chain reaction method.
RESULTS: The AC and CC genotype frequencies were statistically higher in the
study group (P = 0.048 and P = 0.037, respectively). In addition, the AC
polymorphism carried an increased risk of developing allergic rhinitis (odds
ratio = 2.18, 95% confidence interval, 1.173-4.053, P = 0.014). CONCLUSION: The C
allele of the leukotriene C4 synthase gene increases the risk of developing
allergic rhinitis. SIGNIFICANCE: The leukotriene C4 synthase A-444C gene
polymorphism is important in susceptibility to allergic rhinitis and this is the 
first study of this gene polymorphism in allergic rhinitis. EBM RATING: B-3b.

PMID: 16730545 [PubMed - indexed for MEDLINE]

542: Ann Allergy Asthma Immunol. 2006 May;96(5):713-8.

Skin test reactivity and Der p-induced interleukin 10 production in patients with
asthma or rhinitis infected with Ascaris.

Ponte EV, Lima F, Araújo MI, Oliveira RR, Cardoso LS, Cruz AA.

Respiratory Disease Center, University Hospital Professor Edgard Santos,
Salvador, Brazil. evponte@yahoo.com.br

BACKGROUND: Helminth infections have been associated with reduced reactivity to
aeroallergens, which could be related to interleukin 10 (IL-10) production, as
reported in schistosomiasis. OBJECTIVE: To compare skin responses to
aeroallergens with Der p specific IL-10 production in patients with asthma or
rhinitis according to Ascaris infection status. METHODS: Cross-sectional study of
113 patients with asthma or rhinitis from a region endemic for geohelminths.
Stool examinations and skin prick tests to aeroallergens were performed in all
the patients. Der p specific IL-10 production was measured in the supernatant of 
peripheral blood mononuclear cell (PBMC) cultures of a subsample of 53 patients. 
RESULTS: Forty-seven patients had Ascaris in their stool samples. Skin test
results were positive in 77% of Ascaris-infected patients and in 71% of
uninfected individuals. Median levels of Der p specific IL- 10 in PBMC cultures
of infected and uninfected patients were similar (7.8 and 8.4 pg/mL,
respectively). The lack of association remained when parasite load was taken into
account and when patients with evidence of previous infection were removed from
the uninfected group. CONCLUSIONS: In patients with asthma or rhinitis living in 
an urban area endemic for geohelminths, we found no association between Ascaris
infection and skin reactivity to aeroallergens. Furthermore, there was no
difference in Der p specific IL-10 production by PBMCs. These negative findings
indicate that different from what is observed in Schistosoma infection, Ascaris
lumbricoides infection in individuals living in an urban area does not induce
strong regulatory responses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16729785 [PubMed - indexed for MEDLINE]

543: Ann Allergy Asthma Immunol. 2006 May;96(5):673-8.

Comment in:
    Ann Allergy Asthma Immunol. 2006 May;96(5):638-9.

Efficacy and safety of mometasone furoate vs nedocromil sodium as prophylactic
treatment for moderate/severe seasonal allergic rhinitis.

Pitsios C, Papadopoulos D, Kompoti E, Manoussakis E, Garris V, Petalas K, Tassios
I, Baibas N, Kontou-Fili K, Saxoni-Papageorgiou P, Papadopoulos NG.

Department of Allergology and Clinical Immunology, Laikon General Hospital,
Athens, Greece.

BACKGROUND: The preventive use of medications has been proposed to be effective
in the treatment of seasonal rhinitis. OBJECTIVE: To evaluate the efficacy and
safety of mometasone furoate and nedocromil sodium nasal sprays as prophylactic
treatment for moderate to severe seasonal allergic rhinitis (SAR). PATIENTS:
Sixty-one patients were recruited from 3 referral allergy centers. Inclusion
criteria were history of SAR for 2 years or longer, sensitization to relevant
local pollen (grasses, Parietaria, and olive), and age older than 12 years.
METHODS: An open-label, randomized, parallel-group, "real-life" study design was 
used. Patients received mometasone furoate nasal spray once daily or nedocromil
sodium nasal spray 3 times daily starting 2 to 4 weeks before the pollen season
and continuing for up to 4 months. Instructions regarding the use of additional
medications were given. Diary cards recording symptoms, use of medication, and
adverse events were kept by the patients. RESULTS: All 61 patients completed the 
study. The prophylactic use of mometasone furoate vs nedocromil sodium led to
significantly more days without symptoms (75.1% vs 54.5%; P < .001). The
mometasone furoate group also had lower nasal symptom scores (mean, 1.4 vs 2.9;
median, 0 vs 2; P < .001) and was more satisfied (93.1% vs 43.5%; P < .001). No
serious adverse event was recorded, and there was no difference between the
treatments in any adverse event. CONCLUSIONS: Prophylactic administration of
mometasone furoate before the pollen season is safe and may lead to improved
control of SAR compared with the use of nedocromil sodium.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16729779 [PubMed - indexed for MEDLINE]

544: Curr Opin Otolaryngol Head Neck Surg. 2006 Jun;14(3):197-201.

Sublingual immunotherapy for allergic rhinitis: an update.

Burastero SE.

San Raffaele Scientific Institute, Milan, Italy. s.burastero@hsr.it

PURPOSE OF REVIEW: The inter-relationship between allergy and nasal diseases has 
long been known. Failure to address when allergy is a contributing factor
diminishes the possibility of a successful surgical intervention. Sublingual
immunotherapy is recommended by the World Health Organization to treat allergic
rhinitis and is widely used in Europe. Many clinical trials and rigorous
meta-analysis support its efficacy. The criteria, however, for the integration of
this treatment (with the surgical management of those allergic patients who
suffer chronic nasal obstruction, severe drug-resistant hypertrophy and increase 
in glandular structures of the inferior turbinates) are not fully established. We
review here the most recent literature on the efficacy and safety of sublingual
immunotherapy. The purpose is to stimulate the use of complementary approaches by
ear, nose and throat doctors and allergologists, and to improve the management of
patients with persistent allergic rhinitis. RECENT FINDINGS: In addition to the
results of clinical trials, postmarketing surveillance has confirmed the high
safety profile of sublingual immunotherapy in adults and children, its positive
impact on the quality of life, and the reduction of the personal and social cost 
of allergy. Sublingual immunotherapy can prevent new allergic sensitizations and 
maintain its beneficial effect for years after its discontinuation. SUMMARY:
Sublingual immunotherapy is a highly efficacious and well tolerated form of
immunotherapy for allergic rhinitis, and it is capable of interfering with
disease progression. Sublingual immunotherapy should be integrated with surgical 
intervention to achieve optimal outcomes in allergic subjects with chronic nasal 
obstruction.

PMID: 16728900 [PubMed - indexed for MEDLINE]

545: Allergy Asthma Proc. 2006 Mar-Apr;27(2):159-63.

Pharmacoeconomics of allergen immunotherapy compared with symptomatic drug
treatment in patients with allergic rhinitis and asthma.

Ariano R, Berto P, Tracci D, Incorvaia C, Frati F.

Allergy and Clinical Immunology Unit, General Hospital, Bordighera, Italy.

Only a few studies analyzed the pharmacoeconomics of allergen immunotherapy
compared with drug treatment in subjects with allergic rhinitis and asthma. This 
study was aimed at evaluating whether allergen immunotherapy has an economic
advantage on standard antiallergic drugs in patients with pollen-induced rhinitis
and asthma. Thirty patients with rhinitis and asthma caused by Parietaria pollen 
were included in the study, 20 (11 men and 9 women; mean age, 35.45 +/- 10.45
years) were treated with subcutaneous immunotherapy by a Parietaria judaica
extract (Alustal, Stallergénes, Antony, France) by a conventional build-up
schedule in 12 weeks and a maintenance treatment every 4 weeks for 3 years, and
10 (6 men and 4 women; mean age, 31.90 +/- 10.97 years) were treated with
antiallergic drugs. Each patient was evaluated before starting the treatment and 
annually for 6 years in the pollen period of Parietaria by means of nose, eyes,
and lung symptom scores, along with drug consumption registered in diary cards.
In other specifically designated cards general practitioner's or specialist's
visits, the number of desensitizing injections and the number of boxes of
antiallergic drugs were registered. A significant difference in favor of
immunotherapy plus drug treatment versus drug treatment alone was observed,
reaching a cost reduction of approximately 15% the second year and 48% the third 
year, with a highly statistical significance that was maintained up to the sixth 
year, i.e., 3 years after stopping immunotherapy, when an 80% reduction was
found. The net saving for each patient at the final evaluation corresponded to
euros 623 (dollars 830)/year. These findings confirm some previous observations
in studies from Germany and the United States that subcutaneous immunotherapy has
significant economic advantages over antiallergic drug treatment in the long
term.

Publication Types: 
    Comparative Study

PMID: 16724637 [PubMed - indexed for MEDLINE]

546: Allergy Asthma Proc. 2006 Mar-Apr;27(2):145-7.

Serum-soluble Fas antigen level in patients with allergic rhinitis: its relation 
to specific immunotherapy.

Kinikli G, Ateş A, Turgay M, Aydoğan N, Tokgöz G.

Department of Clinical Immunology and Rheumatology, Ankara University Medical
School, Turkey.

There have been conflicting reports on the relationship between Fas/Fas
ligand-mediated apoptosis and allergic response. Specific immunotherapy (SIT) is 
widely used for treatment of allergic diseases. It has long been apparent that
SIT results in a reduction in antigen-specific lymphoproliferation, but it is
unclear by what mechanism T-cell responses are inhibited by SIT in vivo. In this 
study, we examined serum-soluble Fas (sFas) levels in patients with allergic
rhinitis and healthy subjects. We also examined the effect of SIT on sFas level. 
Seventy-two patients with allergic rhinitis and 20 healthy subjects were included
in this study. Twenty-eight patients were newly diagnosed and 44 patients were
treated with SIT for a 5-year or 7-year duration. Serum sFas levels were measured
by a sandwich enzyme-linked immunoassay. Mean serum sFas level was 7931 +/- 2861 
pg/mL in newly diagnosed patients with allergic rhinitis during the pollen
season, 8426 +/- 2846 pg/mL in patients with allergic rhinitis treated by SIT for
a 5-year duration, 8490 +/- 2256 pg/mL in patients with allergic rhinitis treated
by SIT for a 7-year duration, and 7493 +/- 3450 pg/mL in healthy subjects. Serum 
sFas level was not found to be significantly different among the study groups (p 
> 0.05). These findings suggest that there is no relation between sFas level and 
the etiopathogenesis of allergic inflammation in patients with allergic rhinitis 
and mechanism of action of SIT.

PMID: 16724634 [PubMed - indexed for MEDLINE]

547: Respir Res. 2006 May 23;7:81.

Pre-natal and post-natal exposure to respiratory infection and atopic diseases
development: a historical cohort study.

Zutavern A, von Klot S, Gehring U, Krauss-Etschmann S, Heinrich J.

GSF- Institut für Epidemiologie, Neuherberg, Germany. anne.zutavern@gsf.de

BACKGROUND: According to the hygiene hypothesis, infections in early life protect
from allergic diseases. However, in earlier studies surrogate measures of
infection rather than clinical infections were associated with decreased
frequencies of atopic diseases. Exposure to infection indicating sub-clinical
infection rather than clinical infection might protect from atopic diseases.
OBJECTIVE: to investigate whether exposure to acute respiratory infections within
pregnancy and the first year of life is associated with atopic conditions at age 
5-14 years and to explore when within pregnancy and the first year of life this
exposure is most likely to be protective. METHODS: Historical cohort study:
Population level data on acute respiratory infections from the routine reporting 
system of the former German Democratic Republic were linked with individual data 
from consecutive surveys on atopic diseases in the same region (n = 4672).
Statistical analyses included multivariate logistic regression analysis and
polynomial distributed lag models. RESULTS: High exposure to acute respiratory
infection between pregnancy and age one year was associated with overall reduced 
odds of asthma, eczema, hay fever, atopic sensitization and total IgE. Exposure
in the first 9 months of life showed the most pronounced effect. Adjusted odds
ratio's for asthma, hay fever, inhalant sensitization and total IgE were
statistical significantly reduced up to around half. CONCLUSION: Exposure to
respiratory infection (most likely indicating sub-clinical infection) within
pregnancy and the first year of life may be protective in atopic diseases
development. The post-natal period thereby seems to be particularly important.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16719901 [PubMed - indexed for MEDLINE]

548: Drug Metab Pharmacokinet. 2006 Apr;21(2):133-9.

Population pharmacokinetics of pranlukast hydrate dry syrup in children with
allergic rhinitis and bronchial asthma.

Nakade S, Ueda S, Ohno T, Nakayama K, Miyata Y, Yukawa E, Higuchi S.

Pharmacokinetic Research Institute, Ono Pharmaceutical Co., Ltd., Wadai Tsukuba, 
Ibaraki, Japan. s.nakade@ono.co.jp

This study aimed to assess the steady-state pharmacokinetics of pranlukast, a
leukotriene receptor antagonist, in children with allergic rhinitis and bronchial
asthma, and to clarify factors affecting apparent clearance (CL/F). A total of
192 plasma samples were obtained from 98 children (rhinitis 64, asthma 13,
complications 21), aged 3-14 years in 2 clinical trials. Plasma concentration of 
pranlukast was determined by liquid chromatography connected with a tandem mass
spectrometer and analyzed by a population approach using NONMEM program. The
plasma concentration-time course of pranlukast was described by using a
one-compartment model with the first-order absorption and lag time. The
robustness of the population pharmacokinetic model was evaluated by using 200
bootstrap samples. The results of population pharmacokinetic analysis showed that
only age was a factor affecting the CL/F per body weight, with CL/F decreasing
with increasing age. No significant variation was seen in the CL/F between
rhinitis and asthma. The interindividual variability in the CL/F and the residual
variability were 19.7% and 48.4%, respectively. All the parameters fell within
10% of the bootstrapped mean. In conclusion, the results show that age is the
most influential factor for explaining interindividual variability in CL/F, and
the difference in diseases does not affect CL/F.

PMID: 16702733 [PubMed - indexed for MEDLINE]

549: Arch Otolaryngol Head Neck Surg. 2006 May;132(5):547-9.

The use of a screening questionnaire to determine the incidence of allergic
rhinitis in singers with dysphonia.

Hamdan AL, Sibai A, Youssef M, Deeb R, Zaitoun F.

Department of Otolaryngology-Head and Neck Surgery, American University of Beirut
Medical Center, Beirut, Lebanon. alhamdan@svclb.com

OBJECTIVES: To report the incidence of allergic rhinitis in singers with
nonspecific laryngeal examination findings and to correlate the incidence of
allergic rhinitis with their vocal symptoms when present. DESIGN: A retrospective
review of all the medical records of singers with nonspecific laryngeal findings 
who presented to a specialty voice center for either vocal training or therapy
between June 2002 and September 2005. SETTING: Specialty voice center.
PARTICIPANTS: Forty-five singers with nonspecific laryngeal findings who
presented to a specialty voice center for either vocal training or therapy. MAIN 
OUTCOME MEASURES: A standardized validated questionnaire for evaluation of
allergic rhinitis was filled out by all the subjects. A score above 0 was
considered positive. RESULTS: The total prevalence of allergic rhinitis was 87%
(39 of 45 subjects). The singers with vocal symptoms were approximately 15% more 
likely to have allergic rhinitis than those with no vocal symptoms (92% vs 84%). 
Singers with more than 2 vocal symptoms had a 25% higher likelihood of having
allergic rhinitis. CONCLUSIONS: The incidence of allergic rhinitis in singers is 
extremely high. Hidden respiratory allergies may affect the professional voice.
Proper awareness and a multidisciplinary approach are indispensable for proper
diagnosis and treatment.

PMID: 16702573 [PubMed - indexed for MEDLINE]

550: Prim Care Respir J. 2006 Feb;15(1):58-70. Epub 2005 Dec 27.

Comment in:
    Prim Care Respir J. 2006 Feb;15(1):10-2.

International Primary Care Respiratory Group (IPCRG) Guidelines: management of
allergic rhinitis.

Price D, Bond C, Bouchard J, Costa R, Keenan J, Levy ML, Orru M, Ryan D, Walker
S, Watson M.

Department of General Practice, University of Aberdeen, Foresterhill Health
Centre, Westburn Road, Aberdeen, AB25 2AY, UK. David@respiratoryresearch.org

The association between the upper and lower airways has been recognised for
almost 2000 years. Epidemiological data suggest that most asthma patients also
suffer from allergic rhinitis, and that both diseases share similar trigger
factors and pathophysiology. This IPCRG Guideline on the management of rhinitis
in primary care is fully consistent with the ARIA guidelines. It highlights the
treatment goals and the classification of the condition according to symptom
frequency (intermittent or persistent) and severity (mild or moderate-severe). It
covers the need for allergen avoidance, pharmacologic therapy including
immunotherapy, alternative therapies, management of ocular symptoms, the
management of co-existing allergic rhinitis and asthma, and the need for
follow-up and ongoing care for patients with rhinitis.

Publication Types: 
    Practice Guideline
    Research Support, Non-U.S. Gov't

PMID: 16701759 [PubMed - indexed for MEDLINE]

551: Monaldi Arch Chest Dis. 2006 Mar;65(1):44-6.

Practice parameters for sublingual immunotherapy.

Ortolani C, Agostinis F, Amoroso S, Ariano R, Barbato A, Bassi M, Cadario G,
Campi P, Cardinale F, Ciprandi G, D'Anneo R, Di Gioacchino M, Di Rienzo V,
Fiocchi A, Galimberti M, Galli E, Giovannini M, Incorvaia C, La Grutta S,
Lombardi C, Marcucci F, Marseglia G, Minelli M, Musarra A, Nettis E, Novembre E, 
Pajno G, Patriarca G, Pezzuto F, Piras P, Pucci S, Romano A, Romano C, Quercia O,
Scala G, Schiavino D, Senna G, Sforza G, Tosca M, Tripodi S, Frati F.

Casa di Cura Ambrosiana, Cesano Boscone, Milan, Italy.

The efficacy and safety of sublingual immunotherapy (SLIT) are currently
supported by clinical trials, meta-analysis and post-marketing surveys. Practice 
parameters for clinical use of SLIT are proposed here by a panel of Italian
specialists, with reference to evidence based criteria. Indications to SLIT
include allergic rhinoconjunctivitis, asthma, and isolated conjunctivitis
(strength of recommendation: grade A). As to severity of the disease, SLIT is
indicated in moderate/severe intermittent rhinitis, persistent rhinitis and mild 
to moderate asthma (grade D). SLIT may be safely prescribed also in children aged
three to five years (grade B), and its use in subjects aged more than 60 years is
not prevented when the indications and contraindication are ascertained (grade
D). The choice of the allergen to be employed for SLIT should be made in
accordance with the combination of clinical history and results of skin prick
tests (grade D). Polysensitisation, i.e. the occurrence of multiple positive
response does not exclude SLIT, which may be done with the clinically most
important allergens (grade D). As to practical administration, co-seasonal, pre
co-seasonal, and continuous schedules are available, being the latter recommended
for perennial allergens or for pollens with particularly prolonged pollination,
such as Parietaria (grade D). For pollens with relatively short pollination, such
as grasses and trees (cypress, birch, alder, hazelnut, olive) the pre co-seasonal
and perennial schedules are preferred (grade C). The build-up phases suggested by
manufacturers can be safely used (grade A), but they can be modified according to
the patient's tolerance (grade C). A duration of SLIT of 3-5 years is recommended
to ensure a long-lasting clinical effect after the treatment has been terminated 
(grade C).

Publication Types: 
    Comparative Study
    Review

PMID: 16700194 [PubMed - indexed for MEDLINE]

552: J Investig Allergol Clin Immunol. 2006;16(2):86-93.

Erratum in:
    J Investig Allergol Clin Immunol. 2006;16(4):273.

Effect of probiotic Bifidobacterium longum BB536 [corrected] in relieving
clinical symptoms and modulating plasma cytokine levels of Japanese cedar
pollinosis during the pollen season. A randomized double-blind,
placebo-controlled trial.

Xiao JZ, Kondo S, Yanagisawa N, Takahashi N, Odamaki T, Iwabuchi N, Iwatsuki K,
Kokubo S, Togashi H, Enomoto K, Enomoto T.

Food Research and Development Laboratory, Morinaga Milk Industry Co., Ltd., Zama,
Japan. j_xiao@morinagamilk.co.jp

Probiotic microorganisms have been shown to be effective in the treatment of
allergic inflammation and food allergy, but their efficacy remains controversial.
This study tested the effect of a yogurt supplemented with a probiotic strain
Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis
(JCPsis). Forty subjects with a clinical history of JCPsis were given yoghurt
either containing BB536 (BB536 yoghurt) or without BB536 (placebo yoghurt) at 2 X
100 g per day for 14 weeks, in a randomized, double-blind, placebo-controlled
trial. Subjective symptoms and self-care measures were recorded daily and blood
samples were taken before and during the intervention (at weeks 4, 9, and 14) to 
measure the blood parameter levels related to JCPsis. Yoghurt supplemented with
BB536 significantly alleviated eye symptoms compared with placebo yoghurt (odds
ratio 0.31; 95% confidence interval 0.10-0.97; p = 0.044). Although no
statistically significant differences were detected, nasal symptoms such as
itching, rhinorrhea, and blockage, as well as throat symptoms tended to be
relieved with the BB536 yoghurt. BB536 tended to suppress the decreasing blood
levels of interferon-gamma (IFN-y) and the increasing blood eosinophil rates; a
significantly higher IFN-gamma level was observed for the difference from
baseline at week 4. A decreased trend in the difference from baseline levels of
JCP-specific IgE levels was also observed at week 4 in the BB536 group compared
with the placebo group. In conclusion, these results suggest that intake of
BB536-supplemented yoghurt may relieve JCPsis symptoms, probably through a
modulating effect on Th balance.

Publication Types: 
    Randomized Controlled Trial

PMID: 16689181 [PubMed - indexed for MEDLINE]

553: Am J Rhinol. 2006 Mar-Apr;20(2):224-6.

Decongestion test in patients with allergic rhinitis: functional evaluation of
nasal airflow.

Ciprandi G, Cirillo I, Vizzaccaro A, Pallestrini E, Tosca MA.

Ospedale San Martino, Genoa, Italy. gio.cip@libero.it

BACKGROUND: Rhinomanometry measures nasal airflow that is frequently impaired in 
allergic rhinitis. Decongestion tests consist of spraying an intranasal
vasoconstrictor drug to evaluate the reversibility of nasal airflow limitation.
The aim of this study was to evaluate the decongestion test in patients with
seasonal allergic rhinitis (SAR) caused by pollen sensitization, perennial
allergic rhinitis (PAR) caused by sensitization to perennial allergens only, or
mixed allergic rhinitis (MAR) caused by sensitization to both allergens. METHODS:
One hundred twenty-three subjects (112 men and 11 women, mean age, 22.9 +/- 5.7
years) were studied; 40 subjects had PAR, 43 subjects had MAR, and 40 subjects
had SAR. Total symptom score (including: nasal itching, sneezing, rhinorrhea, and
nasal obstruction) was assessed. Rhinomanometry and decongestion tests were
performed in all subjects. RESULTS: Nasal symptom severity was superimposable in 
the three groups (p was not significant). After decongestion tests, an increase
of nasal airflow and a decrease of nasal resistance was shown in PAR (p < 0.01), 
MAR (p < 0.001), and SAR subjects (p < 0.001). The intergroup analysis showed
that SAR patients had less reversibility than PAR (p < 0.01). CONCLUSION: This
study provides the first evidence of the different response to decongestion
tests, taking into consideration the causal allergens.

PMID: 16686394 [PubMed - indexed for MEDLINE]

554: Ann Allergy Asthma Immunol. 2006 Apr;96(4):606-14.

Comment in:
    Ann Allergy Asthma Immunol. 2006 Jul;97(1):121-2.

Efficacy of diphenhydramine vs desloratadine and placebo in patients with
moderate-to-severe seasonal allergic rhinitis.

Raphael GD, Angello JT, Wu MM, Druce HM.

Pfizer Consumer Healthcare, Morris Plains, New Jersey 07950, USA.

BACKGROUND: Previous studies have shown that diphenhydramine and desloratadine
effectively relieve symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE: To
compare the relative efficacy of 50 mg of diphenhydramine hydrochloride, 5 mg of 
desloratadine, and placebo in relieving symptoms in patients with
moderate-to-severe SAR. METHODS: In this 1-week, multicenter, parallel-group,
randomized, double-blind, double-dummy, placebo-controlled study, 610 patients
with moderate-to-severe SAR received 50 mg of diphenhydramine hydrochloride 3
times daily, 5 mg of desloratadine once daily, or placebo. Daily 24-hour
reflective total nasal symptom scores (TNSSs) (primary end point), total symptom 
scores, and individual symptom scores were evaluated. A global evaluation of
response to treatment was conducted at 2 posttreatment visits. RESULTS: The mean 
reduction from baseline in 24-hour reflective TNSSs relative to the placebo
response was 77.6% for the diphenhydramine group (P < .001) and 21.0% for the
desloratadine group (P = .12). A TNSS between-treatment difference of -1.81
(46.7%; P < .001) was observed when comparing diphenhydramine with desloratadine.
A similar between-treatment difference was observed for the 24-hour reflective
total symptom score comparing diphenhydramine to desloratadine (-3.35; 45.5%; P <
.001). Diphenhydramine provided clinically and statistically significant
reductions vs placebo and desloratadine in all individual symptoms, including
nasal congestion. Desloratadine had a tendency toward improvement compared with
placebo for most individual symptom scores. However, a statistically significant 
result was reached only for sneezing (-0.27; 33.9%; P = .04). CONCLUSIONS:
Diphenhydramine, 50 mg, given for 1 week provided statistically significant and
clinically superior improvements in symptoms compared with 5 mg of desloratadine 
in patients with moderate-to-severe SAR. Somnolence occurred more frequently with
diphenhydramine (22.1%) compared with desloratadine (4.5%) and placebo (3.4%).

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16680933 [PubMed - indexed for MEDLINE]

555: Ann Allergy Asthma Immunol. 2006 Apr;96(4):600-5.

Effect of pretreatment with fexofenadine on the safety of immunotherapy in
patients with allergic rhinitis.

Ohashi Y, Nakai Y, Murata K.

Ishikiriseiki Hospital, Osaka, Japan. ohsymcr@circus.ocn.ne.jp

BACKGROUND: Allergen-specific immunotherapy, although not a cure, remains the
only treatment available that can alter the natural course of an allergic
disease. However, the risk of allergen specific immunotherapy-related systemic
reactions (SRs), reported to occur in approximately 1% to 14% of patients and
which can range from mild to fatal in seriousness, represents a barrier to
implementing this unique and effective treatment option. OBJECTIVE: To explore
the possibility that pretreatment with the H1-antihistamine fexofenadine could
prevent the occurrence of severe SRs induced by immunotherapy in Japanese
patients with allergic rhinitis. METHODS: In this open-label, multicenter study, 
134 patients receiving immunotherapy for allergic rhinitis were randomized 1:1 to
a group receiving pretreatment with fexofenadine hydrochloride (60 mg) 2 hours
before immunization injection (n = 67) or to a control group receiving no
pretreatment (n = 67). Patients were further grouped into those who received
cedar pollen immunotherapy and those who received dust mite immunotherapy.
RESULTS: Pretreatment with fexofenadine 2 hours before immunotherapy
significantly reduced the occurrence of severe SRs (P = .03), significantly
increased the proportion of patients receiving cedar pollen immunotherapy who
achieved the target maintenance dose (TMD) (P = .03), and significantly reduced
the length of time to attain the TMD (P = .047 and P = .003 for patients
receiving cedar pollen and dust mite immunotherapy, respectively). CONCLUSIONS:
This study suggests a novel role for fexofenadine in enhancing the safety of
immunotherapy and increasing the proportion of patients achieving the TMD.

Publication Types: 
    Randomized Controlled Trial

PMID: 16680932 [PubMed - indexed for MEDLINE]

556: Ann Allergy Asthma Immunol. 2006 Apr;96(4):586-92.

Hypersensitivity to black locust (Robinia pseudoacacia) pollen: "allergy
mirages".

Compés E, Hernández E, Quirce S, Palomares O, Rodríguez R, Cuesta J, Sastre J,
Villalba M.

Fundación Jiménez Díaz, Allergy Department, Universidad Autónoma de Madrid,
Spain.

BACKGROUND: The allergenicity of the ornamental tree Robinia pseudoacacia, or
black locust, is unknown. OBJECTIVE: To evaluate the prevalence of sensitization 
to R. pseudoacacia pollen, its possible allergenic cross-reactivity with other
common pollens, and the potential implication of pollen panallergens (profilin,
polcalcin, and 1,3-beta-glucanase) as a cause of sensitization to R. pseudoacacia
pollen. METHODS: Skin prick testing with R. pseudoacacia pollen was performed in 
149 patients with pollinosis. Nasal challenge with R. pseudoacacia pollen was
performed in 10 patients. The prevalence of sensitization to the recombinant
forms of profilin (rChe a 2), polcalcin (rChe a 3), and the N-terminal of the
1,3-beta-glucanase (rNtD of Ole e 9) was investigated. Immunoblotting,
enzyme-linked immunosorbent assay, and competitive inhibition assays were
performed with R. pseudoacacia pollen and recombinant pollen allergens. RESULTS: 
Sixty-four patients (43%) had positive skin prick test reactions to R.
pseudoacacia pollen. Nasal challenge results were positive in 5 sensitized
patients and negative in 4 controls and 1 sensitized patient. The allergenic
profile of R. pseudoacacia pollen comprises at least the panallergen profilin, a 
calcium-binding protein, and a 1,3-beta-glucanase. The prevalence of
sensitization to rChe a 2, rChe a 3, and rNtD of Ole e 9 was 60%, 33%, and 87%,
respectively, among patients sensitized to R. pseudoacacia pollen. Binding of IgE
to R. pseudoacacia extract was completely inhibited by Robinia, Chenopodium,
Olea, Cupressus, and Lolium extracts. CONCLUSIONS: The high prevalence of R.
pseudoacacia pollen sensitization in patients with pollinosis is likely to be due
to cross-sensitization to panallergens (profilin, polcalcin, and
1,3-beta-glucanase) from other common pollens. This phenomenon may lead to a
diagnosis of "allergy mirages."

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16680930 [PubMed - indexed for MEDLINE]

557: Allergy. 2006 Jun;61(6):750-8.

Is outdoor air pollution associated with physician visits for allergic rhinitis
among the elderly in Toronto, Canada?

Villeneuve PJ, Doiron MS, Stieb D, Dales R, Burnett RT, Dugandzic R.

Air Health Effects Division, Environmental Contaminants Bureau, Health Canada,
Ottawa, Ontario, Canada.

BACKGROUND: While a number of studies suggest that air pollution is associated
with allergic rhinitis in children, findings among adults have been equivocal.
The aim of this study was to examine the relationship between outdoor air
pollution and physician visits for allergic rhinitis among individuals>or=65
years of age in Toronto, Canada. METHODS: Physician visits were identified by
using data from the Ontario provincial health insurance plan that is made
available to all residents. Our analyses are based on 52,691 physician visits for
allergic rhinitis among individuals>or=65 years of age in the Toronto
metropolitan area between 1995 and 2000. Generalized linear models were used to
regress daily counts of physician visits against daily measures of gaseous and
particulate components of air pollution after controlling for seasonality,
potential confounders (temperature, relative humidity, aeroallergens),
overdispersion and serial correlation. RESULTS: A large number of comparisons
were undertaken, with most showing no statistically significant associations
between daily levels of air pollution and the number of physician visits for
rhinitis. In contrast, an interquartile increase in the 10-day average of ragweed
particles increased the mean number of daily rhinitis consultations by 6.4% (95% 
CI=0.7-12.4%). CONCLUSIONS: Our findings suggest that outdoor air pollution is a 
poor predictor of physician visits for allergic rhinitis among the elderly.

PMID: 16677246 [PubMed - indexed for MEDLINE]

558: Allergy. 2006 Jun;61(6):737-42.

Erratum in:
    Allergy. 2006 Sep;61(9):1153.

Effect of montelukast on lung function in asthma patients with allergic rhinitis:
analysis from the COMPACT trial.

Price DB, Swern A, Tozzi CA, Philip G, Polos P.

Department of General Practice and Primary Care, University of Aberdeen,
Foresterhill Health Centre, Aberdeen UK.

BACKGROUND: The Clinical Outcomes with Montelukast as a Partner Agent to
Corticosteroid Therapy (COMPACT) trial demonstrated that montelukast added to
budesonide (MNT + BD) was as efficacious as double the dose of budesonide (dBD)
in improving morning peak expiratory flow (AM PEF) in adult asthmatics. Recent
studies have demonstrated that montelukast is also effective in treating daytime 
and nighttime allergic rhinitis (AR) symptoms in asthmatic patients. This
analysis was designed to examine whether asthmatic patients with comorbid AR
respond differently than patients without comorbid AR in terms of asthma control 
(lung function). METHODS: There were 216 asthmatic patients in the MNT+BD group
and 184 patients in the dBD group with AR. Treatment differences in the change
from baseline in AM PEF were compared. Least square (LS) mean and 95% confidence 
interval (CI) were derived from an anova model adjusting for baseline and study
site. RESULTS: There was a 9.2% increase in AM PEF from baseline in the MNT+BD
group compared with a 6% increase in the dBD group. The LS mean difference
[(MNT+BD)-dBD] was 14.2 l/min (P=0.028). Other secondary endpoints were similar
between groups. CONCLUSION: In the subgroup of asthmatic patients with AR, a
combined treatment approach that included montelukast and budesonide provided
significantly greater efficacy in reducing airflow obstruction compared with
doubling the dose of budesonide. These results support recommendations by the
Allergic Rhinitis and its Impact on Asthma initiative that suggest a unified
approach aimed at treating the airway inflammation common to both diseases is
beneficial for the large proportion of asthmatics who also suffer from AR.

PMID: 16677244 [PubMed - indexed for MEDLINE]

559: Allergy. 2006 Jun;61(6):731-6.

Comment in:
    Allergy. 2006 Jun;61(6):653-5.

Effects of intranasal fluticasone and salmeterol on allergen-induced nasal
responses.

Parameswaran K, Fanat A, O'Byrne PM.

Firestone Institute for Respiratory Health, St Joseph's Healthcare, and
Department of Medicine, McMaster University, Hamilton, Canada.

BACKGROUND: Combination of inhaled steroid and long-acting beta-agonists has
synergistic effects in asthma. OBJECTIVE: To investigate whether nasal
corticosteroid and long-acting beta-agonists have synergistic effects on
allergen-induced nasal responses. METHODS: The effects of intranasal treatment
with fluticasone p-MDI (50 microg bid), salmeterol p-MDI (25 microg bid), their
combination, and placebo, on nasal symptoms, eosinophil differential cell count
and albumin in nasal lavage fluid (measures of inflammation and leakage
respectively) and nasal electrical potential difference (measure of epithelial
integrity) were studied in 11 atopic subjects with rhinitis, in a randomized,
partially-blinded, 4-period, cross-over study. The measurements were made at
baseline, at the end of 1 week of treatment, and immediately after a nasal
allergen provocation. RESULTS: Allergen-induced sneeze, postnasal drip and nasal 
obstruction were significantly reduced by fluticasone, but not by salmeterol.
Eosinophil count in postallergen nasal lavage fluid was significantly less after 
fluticasone (median 1.9%, IQR 4.6) and salmeterol treatment (median 2.5%, IQR
8.5) compared with placebo (median 12.5%, IQR 27.9). Compared with placebo, both 
fluticasone and salmeterol attenuated allergen-induced change in nasal potential 
(mean change from baseline -18.5, +0.4 and -7.2% respectively) and the increase
in nasal albumin (median 154, 119 and 130 ng/ml respectively). Combination
treatment did not have any additional benefits over the individual therapies.
CONCLUSIONS: Although salmeterol has anti-inflammatory properties, intranasal
salmeterol or its combination with fluticasone do not offer any added benefit
over intranasal fluticasone alone for allergen-induced nasal responses.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16677243 [PubMed - indexed for MEDLINE]

560: Allergy. 2006 Jun;61(6):725-30.

Increased expression of lipoxygenase enzymes during pollen season in nasal
biopsies of pollen-allergic patients.

Plewako H, Holmberg K, Oancea I, Rak S.

Asthma and Allergy Research Group, Department of Respiratory Medicine and
Allergology, The Sahlgrenska University Hospital, Göteborg, Sweden.

BACKGROUND: Exposure of patients sensitized to pollen triggers development of
seasonal allergic rhinitis symptoms (SAR). Eicosanoids are a group of arachidonic
acid metabolites contributing to the symptoms of SAR. The aim of this study was
to investigate seasonal changes in the expression of enzymes of the eicosanoid
pathway in the nasal mucosa of patients with SAR. METHODS: Twenty SAR patients
allergic to birch or grass and eight healthy subjects were included in the study.
Patients registered rhinoconjunctivitis symptoms and use of rescue medication
before and during the pollen season. Nasal biopsies were obtained before and
around the peak of the season, sectioned and stained using markers for
eosinophils, mast cells, T cells and neutrophils. Antibodies against the
following enzymes were also used: cyclo-oxygenase (COX-1, COX-2), 5-lipoxygenase 
(5-LO), 5-lipoxygenase-activating factor (FLAP), LTA4 hydrolase (LTA4h) and LTC4 
synthase (LTC4s). RESULTS: During the pollen season symptoms of
rhinoconjunctivitis and medication score increased significantly (P=0.001;
P=0.001 respectively). During the pollen season numbers of eosinophils (P=0.02)
and cell positive 5-LO (P=0.02), LTC4s (P=0.04) and LTA4h (P=0.02) increased
significantly. During season number of mast cells and cells expressing 5-LO and
LTA4h were higher in SAR than in healthy controls group (P=0.02; P=0.01; P=0.03
respectively). CONCLUSION: In sensitized patients exposure to pollen allergen
results in increased expression of enzymes of the eicosanoid pathway.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16677242 [PubMed - indexed for MEDLINE]

561: Allergy. 2006 Jun;61(6):712-6.

Rhinitis symptoms and IgE sensitization as risk factors for development of later 
allergic rhinitis in adults.

Bodtger U, Poulsen LK, Linneberg A.

Allergy Clinic 7551, Copenhagen University Hospital, Copenhagen, Denmark.

BACKGROUND: Rhinitis symptoms and IgE-sensitization often mismatch. Asymptomatic 
sensitization is an established risk factor for later rhinitis, whereas it is not
clear whether rhinitis is a risk factor for later development of
IgE-sensitization. OBJECTIVE: To investigate whether nonallergic rhinitis is a
risk factor for later development of IgE-sensitization in adults during an 8-year
follow-up period, and whether asymptomatic sensitization is a risk factor for
later development of rhinitis. METHODS: In a population-based study of 15-69
years olds in 1990, 734 subjects were re-examined in 1998. On both occasions
questionnaires on rhinitis symptoms were completed and serum IgE (against birch, 
grass, mugwort, cat, dog, and Dermatophagoides pteronyssinus) were determined
(positive if >or=0.35 kUA/l). Asymptomatic sensitization: positive IgE levels
without any rhinitis symptoms. Nonallergic rhinitis: rhinitis symptoms and no
sensitization. RESULTS: Asymptomatic sensitization to pollens, pets, or house
dust mite was significantly associated with onset of rhinitis symptoms, also when
changing baseline cut-off for sensitization to >or=0.1 or >or=0.7 kUA/l. The
8-year incidence of pollen-related rhinitis was 15.1% and 2.6% in subjects
sensitized and nonsensitized to pollens, respectively (odds ratio 6.1, 95% CI
2.3-16.0). Persistent or intermittent nonallergic rhinitis was not significantly 
associated with later sensitization, yet a positive trend for development was
observed in nonallergic pollen-related rhinitis. CONCLUSION: Asymptomatic
sensitization but not nonallergic rhinitis was a significant risk factor for
later development of allergic rhinitis.

PMID: 16677240 [PubMed - indexed for MEDLINE]

562: Allergy. 2006 Jun;61(6):705-11.

Classification and management of allergic rhinitis patients in general practice
during pollen season.

Van Hoecke H, Vastesaeger N, Dewulf L, Sys L, van Cauwenberge P.

Department of Otorhinolaryngology, Ghent University, Ghent, Belgium.

BACKGROUND: Allergic rhinitis (AR) represents a major challenge in primary care. 
The Allergic Rhinitis and its Impact on Asthma (ARIA) group proposed a new
classification for AR and developed evidence-based guidelines for the management 
of this disease. We conducted this study to further characterize the classes of
AR described by ARIA, and to evaluate whether the management of AR in general
practice is in accordance with the ARIA guidelines. METHODS: During the pollen
season of 2003, 95 Belgian general practitioners (GPs) enrolled 804 patients who 
presented with symptoms of AR. For each patient, a questionnaire comprising the
clinical presentation and management was completed. RESULTS: In 64% of the
patients, AR was classified as intermittent and in 36% as persistent. Persistent 
rhinitis caused more discomfort than intermittent rhinitis. Only 50% of the
patients had ever undergone allergy testing. Among them, 51% were allergic to
both seasonal and perennial allergens. Eighty-two per cent of the persistent
rhinitics were allergic to at least one seasonal allergen and 72% of the
intermittent rhinitics to at least one perennial allergen. When compared strictly
with the ARIA recommendations, 49% of the patients with mild and/or intermittent 
AR were overtreated, whereas about 30% of those with moderate/severe persistent
rhinitis were undertreated. CONCLUSION: This study confirms that the previous
classification of AR into 'seasonal' and 'perennial' is not satisfactory and that
intermittent and persistent AR are not equivalent to seasonal and perennial AR
respectively. Furthermore, persistent rhinitis has been shown to be a distinct
disease entity. Further efforts are required to disseminate and implement
evidence-based diagnostic and treatment guidelines for AR in primary care
practice.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16677239 [PubMed - indexed for MEDLINE]

563: Allergy. 2006 Jun;61(6):699-704.

Comment in:
    Allergy. 2006 Jun;61(6):653-5.

The diagnosis of asthma using a self-questionnaire in those suffering from
allergic rhinitis: a pharmaco-epidemiological survey in everyday practice in
France.

Demoly P, Bozonnat MC, Dacosta P, Daures JP.

Exploration des Allergies - Maladies Respiratoires and INSERM U454 - IFR3,
Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier
Cedex, France.

BACKGROUND: All recent guidelines recommend a search for asthma utilizing both
specific interrogation and pulmonary function tests in patients suffering from
allergic rhinitis. Although the mandatory place of spirometry has not been
confirmed, a self-questionnaire containing nine specific questions on asthma
symptoms in different daily life situations was found to be capable of
discriminating asthmatics from nonasthmatics in a rhinitic population. OBJECTIVE:
We addressed the questions of prevalence of asthma using a validated
self-questionnaire and what might be the risk factors of being asthmatic
according to that specific self-questionnaire. METHODS: Between April 2003 and
September 2004, nearly 12,000 rhinitis patients were enrolled by more than 2300
physicians (78% general practitioners, 22% ear nose and throat specialists).
Patients were consulting for an exacerbation of chronic rhinitis and did not have
a previous diagnosis of asthma. Both doctors and patients filled out a specific
questionnaire on rhinitis and asthma. RESULTS: Almost 30% of the patients had at 
least three positive answers to the self-questionnaire and could possibly be
considered as asthmatics. We found five independent clinical risk factors for
having >or=3 positive answers to the self-questionnaire. Severity of rhinitis
(moderate-severe vs mild, OR=1.84; 95% CI=1.68-2.00), diagnosis of allergy (yes
vs no) (OR=1.86; 95% CI=1.68-2.00), body mass index (<or=18.5 vs >30) (OR=0.51;
95% CI=0.39-0.66), type of rhinitis (persistent vs intermittent) (OR=1.25; 95%
CI=1.15-1.37), and patient age (<or=25 vs >47) (OR=0.73; 95% CI=0.65-0.80).
CONCLUSION: Asthma symptoms are frequent in rhinitics without a prior history of 
asthma. Several variables were shown to be predictive of asthma in these
patients.

PMID: 16677238 [PubMed - indexed for MEDLINE]

564: Allergy. 2006 Jun;61(6):693-8.

Prevalence, classification and perception of allergic and nonallergic rhinitis in
Belgium.

Bachert C, van Cauwenberge P, Olbrecht J, van Schoor J.

Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.

BACKGROUND: Allergic rhinitis (AR) and noninfectious, nonallergic rhinitis (NINA)
are common disorders, which may prompt patients to seek medical help. METHODS: We
performed a survey in a representative sample of the Belgian population (n=4959) 
with an overall prevalence of self-declared recent rhinitis symptoms of 39.3%.
Detailed information on patients having experienced nasal symptoms over the past 
year was then obtained from a random sample of respondents (n=743). RESULTS: The 
adjusted prevalence was 29.8% for AR and 9.6% for NINA, respectively. According
to the ARIA classification, there was significantly more 'persistent'
symptomatology in the AR group (40.8%) than in NINA (23.5%) (P<0.001), and more
'moderate/severe' symptom intensity in AR (75.4%) than in NINA (53.1%) (P<0.001).
Allergic rhinitis patients suffered from a greater number of symptoms than NINA
patients (P<0.001). Asthma, skin and food allergy as co-morbidities were all
found to be significantly more prevalent in the AR vs the NINA group (P<0.05 for 
all). The percentage of consulting patients (total: 66.8%), who subjectively
perceived their rhinitis as moderate/severe, was 94.0%, whereas 75.6% of these
patients were classified accordingly based on ARIA criteria. CONCLUSIONS: We
found a high prevalence of self-declared rhinitis symptoms in the Belgian
population, AR being about three times more prevalent than NINA. In addition, AR 
patients suffered from a greater number of symptoms and displayed a more
'persistent' and 'moderate-severe' ARIA profile than NINA. About 75% of patients 
seeking medical help suffer from 'moderate to severe' forms of rhinitis.

PMID: 16677237 [PubMed - indexed for MEDLINE]

565: Allergy. 2006 Jun;61(6):671-80.

Comment in:
    Allergy. 2006 Jun;61(6):653-5.    Allergy. 2006 Oct;61(10):1234.

Factors responsible for differences between asymptomatic subjects and patients
presenting an IgE sensitization to allergens. A GA2LEN project.

Bousquet J, Anto JM, Bachert C, Bousquet PJ, Colombo P, Crameri R, Daëron M,
Fokkens W, Leynaert B, Lahoz C, Maurer M, Passalacqua G, Valenta R, van Hage M,
Van Ree R.

Service des Maladies Respiratoires, University Hospital, Montpellier, France.

The synthesis of allergen-specific IgE is required for the development of
allergic diseases including allergic rhinitis and allergic asthma (patients), but
many individuals with allergen-specific IgE do not develop symptoms (asymptomatic
subjects). Differences may exist between asymptomatic subjects and patients.
Whether the presence of allergen-specific IgE translates into clinical allergy
most likely depends on a complex interplay of multiple factors. These include a
family history of atopy, the levels of total serum IgE and, allergen-specific IgE
or IgG, epitope-specificity of IgE and their degree of polyclonality (mono- vs
polysensitized), as yet unidentified serum factors, the balance of T regulatory
cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor
for IgE (FcepsilonRI) and other factors regulating the activation of
FcepsilonRI-bearing cells. Asymptomatic subjects may be more often monosensitized
than patients who may be more often polysensitized. There are many unanswered
important questions that need to be addressed in order to better understand how
IgE sensitization translates into clinical allergy. The assessment of differences
between the asymptomatic and symptomatic groups of subjects represent one of the 
scientific programs of Global Allergy and Asthma European Network funded by the
European Union and the hypotheses underlying these differences are presented in
this paper.

PMID: 16677235 [PubMed - indexed for MEDLINE]

566: Allergy. 2006 Jun;61(6):665-70.

Nasal nitric oxide and nasal allergy.

Struben VM, Wieringa MH, Feenstra L, de Jongste JC.

Department of Otorhinolaryngology, Erasmus Medical Centre, Rotterdam, the
Netherlands.

Measurements of nasal nitric oxide (nNO) are attractive because they are
completely noninvasive and can easily be performed. The measurements may be
useful in the early diagnosis of patients with chronic airway disorders such as
Kartager's syndrome and cystic fibrosis. The possible use of nNO measurements in 
the diagnosis and treatment of allergic rhinitis still needs to be further
evaluated because of the variable and also contradicting findings of nNO
concentrations in this disease. In this review we will discuss the origin,
production and measurement of nNO as well as the effect of allergic rhinitis,
nasal allergen challenge and medication on nNO. Subsequently, we examine
published data on allergic rhinitis and nNO, and summarize the effect of
treatment of rhinitis on nNO. Finally, we discuss the potential future role for
nNO in the diagnosis and management of allergic rhinitis.

Publication Types: 
    Review

PMID: 16677234 [PubMed - indexed for MEDLINE]

567: Curr Opin Allergy Clin Immunol. 2006 Jun;6(3):175-9.

Does acupuncture or Chinese herbal medicine have a role in the treatment of
allergic rhinitis?

Xue CC, Li CG, Hügel HM, Story DF.

The RMIT Chinese Medicine Research Group, School of Health Sciences, RMIT
University, Bundoora, Victoria, Australia. charlie.xue@rmit.edu.au

PURPOSE OF REVIEW: Complementary medicines, including acupuncture and Chinese
herbal medicine, are being used increasingly for the management of allergies such
as allergic rhinitis. Until relatively recently, however, evidence for the
efficacy and safety of these therapies in allergic conditions has been lacking.
RECENT FINDINGS: A limited number of well conducted studies, all with small
sample sizes, have demonstrated the promising therapeutic potential of
acupuncture and Chinese herbal medicine for allergic rhinitis. The possible
additional benefit of combining the two therapies, however, is yet to be
confirmed. There are concerns about the appropriateness of the sham/placebo
controls that have been used in acupuncture studies and also about the safety
evaluation of individual herbs and herbal formulations. In addition to well
established symptom scores and specific quality of life questionnaires, the
concurrent use of conventional anti-allergy medications has been utilized as an
outcome measure in a number of trials that have evaluated the effectiveness of
acupuncture and Chinese herbal medicine for allergic rhinitis. SUMMARY:
Tentatively, it appears that acupuncture and Chinese herbal medicine can be
effective treatments for allergic rhinitis. Confirmatory evidence, however, is
needed from large and, ideally, multi-centre trials.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16670510 [PubMed - indexed for MEDLINE]

568: Respir Med. 2006 Dec;100(12):2177-82. Epub 2006 May 2.

Genetic and environmental contributions to hay fever among young adult twins.

Thomsen SF, Ulrik CS, Kyvik KO, von Bornemann Hjelmborg J, Skadhauge LR,
Steffensen I, Backer V.

Department of Respiratory Medicine, Bispebjerg Hospital, DK-2400 Copenhagen NV,
and The Danish Twin Registry, University of Southern Denmark, Odense, Denmark.
sft@city.dk

BACKGROUND: The susceptibility to develop hay fever is putatively the result both
of genetic and environmental causes. We estimated the significance and magnitude 
of genetic and environmental contributions to hay fever among young adult twins. 
METHODS: From the birth cohorts 1953-82 of The Danish Twin Registry 11,750 twin
pairs were identified through a nationwide questionnaire survey. Subjects were
regarded hay fever cases when responding affirmatively to the question 'Do you
have, or have you ever had hay fever?' Latent factor models of genetic and
environmental effects were fitted to the observed data using maximum likelihood
methods. RESULTS: The overall cumulative prevalence of hay fever was 12.6%.
Identical twins were significantly more likely to be concordant for hay fever
than were fraternal twins (P<0.001). Additive genetic effects accounted for 71%
and non-shared environmental effects accounted for 29% of the individual
susceptibility to hay fever. The same genes contributed to the susceptibility to 
hay fever both in males and in females. In families with asthma, the
susceptibility to develop hay fever was, in addition to genes, to a great extent 
ascribable to family environment, whereas the aetiology of 'sporadic' hay fever
was mainly genetic. CONCLUSIONS: The susceptibility to develop hay fever is
attributable to major genetic influences. However, effects of family environment 
and upbringing are also of importance in families where asthma is present. These 
results indicate that different sub-forms of hay fever may have different
aetiologies.

Publication Types: 
    Twin Study

PMID: 16650971 [PubMed - indexed for MEDLINE]

569: J Pharmacol Toxicol Methods. 2007 Jan-Feb;55(1):65-70. Epub 2006 Mar 18.

Enzyme-linked immunosorbent assay of a linear, recombinant peptide designed for
immunotherapy of Japanese cedar pollinosis.

Kozutsumi D, Shimizu K, Morikubo K, Ohshiba Y, Yamaji T, Kino K.

Research and Development Section, Pharmaceuticals Development Department, Meiji
Dairies Corporation, 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
daisuke_kozutsumi@meiji-milk.com

INTRODUCTION: Cry-consensus peptide, a recombinant T-cell epitope peptide for
immunotherapy of Japanese cedar pollinosis, is a linear peptide that does not
have disulfide bonds because no cysteine residue exists in the molecule. We
examined whether a sandwich enzyme-linked immunosorbent assay (ELISA) could be
performed for linear peptides such as Cry-consensus peptide. METHODS: The
3-dimensional conformation of Cry-consensus peptide was examined by (1)H NMR
analysis. Nineteen monoclonal antibodies (mAbs) that recognized various domains
of Cry-consensus peptide were established to use in a sandwich ELISA. The
relationship between the recognition sites of mAbs and the sensitivity of the
ELISA was investigated to optimize the selection of the combination of the
capture and the detection antibodies. ELISA inhibitors in serum and plasma were
also studied to improve the stability and the sensitivity of determination.
RESULTS: (1)H NMR analysis of Cry-consensus peptide suggested that Cry-consensus 
peptide molecule had no portions with rigid conformation. The sensitivity of the 
ELISA showed a good correlation with the distance between the respective binding 
sites of the capture and the detection antibodies. Human serum albumin and
alpha1-acid glycoprotein strongly inhibited the binding of the capture mAb to
Cry-consensus peptide in a dose-dependent manner, and heparin also inhibited the 
binding in the concentration at which it is used as anticoagulant. Taken
together, the findings indicated that an optimized method showed good linearity
and minimal variation from 0 to 1000 ng/ml of Cry-consensus peptide. DISCUSSION: 
These data indicate that this method is useful for monitoring Cry-consensus
peptide concentrations in plasma or serum.

Publication Types: 
    Validation Studies

PMID: 16650781 [PubMed - indexed for MEDLINE]

570: Clin Exp Allergy. 2006 May;36(5):676-84.

Effects of levocetirizine as add-on therapy to fluticasone in seasonal allergic
rhinitis.

Barnes ML, Ward JH, Fardon TC, Lipworth BJ.

Asthma & Allergy Research Group, Department of Medicine and Therapeutics,
Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, UK.

BACKGROUND: Addition of H(1) antagonists to intranasal corticosteroid treatment
of allergic rhinitis (AR) is common in clinical practice and recommended by
guidelines, despite some evidence that the additive benefits are negligible.
OBJECTIVE: To assess additional benefits of 5 mg levocetirizine dihydrochloride
in seasonal AR patients using 200 mcg fluticasone propionate nasal spray once
daily. METHODS: In a double-blind placebo-controlled crossover study of 27
patients, following 2 weeks without treatment, subjects used fluticasone with
levocetirizine or identical placebo for 2 weeks each. Assessments were the
Juniper mini Rhinoconjunctivitis Quality-of-Life Questionnaire (mini-RQLQ),
domiciliary peak nasal inspiratory flow (PNIF), total nasal symptoms (TNS) scores
and nasal nitric oxide concentrations. Effects were interpreted and tested
against minimal clinically important differences. RESULTS: Add-on effects for
levocetirizine vs. placebo excluded any clinically significant benefits: mean
effects (one sided 95% confidence intervals) were mini-RQLQ -0.11 (-0.34), PNIF
+0.57 (+5.23), and TNS -0.11 (-0.60). Numbers needed to treat (95% confidence
intervals) by outcome were mini-RQLQ 14 (5 to 49), PNIF 4 (3-7), and TNS 3 (2-6).
No significant within or between treatment effects were seen for nasal nitric
oxide. CONCLUSION: Contrary to current practice, the present results demonstrate 
that for the majority of patients, antihistamine add-on to effective nasal
steroid treatment is inappropriate. Further work is required to confirm that this
is also true in the most severe cases, and the available evidence needs to be put
into guidelines and implemented.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16650054 [PubMed - indexed for MEDLINE]

571: Clin Exp Allergy. 2006 May;36(5):658-65.

Artemisia and Ambrosia hypersensitivity: co-sensitization or co-recognition?

Asero R, Wopfner N, Gruber P, Gadermaier G, Ferreira F.

Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano (MI), Italy.
r.asero@libero.it

BACKGROUND: Ragweed and mugwort have nearly identical flowering periods. Clinical
and serological studies showed that ragweed and mugwort sensitization are often
associated and this poses relevant clinical problems in patients for whom
specific immunotherapy is warranted. OBJECTIVE: To establish whether the
concurrent ragweed and mugwort pollen hypersensitivity is the result of
co-sensitization or of co-recognition by using purified recombinant allergens.
METHODS: Sensitization to ragweed and mugwort pollen was assessed by skin prick
test (SPT) in all patients reporting allergic symptoms in August and September.
IgE reactivity of sera from 42 patients (26 Amb+/Art+, 14 Amb+/Art-, and two
Amb-/Art+) to ragweed and mugwort pollen extract as well as to several
recombinant ragweed (rAmb a 1, rAmb a 5, rAmb a 6, rAmb a 8, rAmb a 9, and Amb a 
10) and mugwort (rArt v 1, rArt v 4, rArt v 5, rArt v 6, and three EF-hand
calcium-binding protein) allergens was detected by dot-blot and ELISA analyses.
RESULTS: IgE reactivity of 372 weed pollen-allergic patients was studied. Mugwort
reactivity was strongly associated with ragweed hypersensitivity: only 10/147
(7%) mugwort-hypersensitive patients were not sensitized to ragweed, whereas
225/362 (62%) ragweed-hypersensitive patients were not sensitized to mugwort. In 
vitro, 90% of ragweed-allergic patients reacted with rAmb a 1. Reactivity to
other ragweed allergens ranged between 20% and 35%. Forty-six percent of the
mugwort-sensitized patients recognized rArt v 1%, 25% reacted to Art v 4, Art v
5, and Art v 6, and 7% recognized the three-EF hand calcium-binding protein.
Immunoblot inhibition experiments showed that pre-incubation with ragweed pollen 
extract only weakly decreased IgE reactivity to mugwort allergens. CONCLUSION:
Patients showing both ragweed- and mugwort-positive SPT and/or RAST are
co-sensitized. Future studies will establish whether IgE reactivity translates
into clinical symptoms and, hence, if co-sensitized patients should undergo
specific immunotherapy with extracts of both mugwort and ragweed pollen.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16650052 [PubMed - indexed for MEDLINE]

572: Am J Otolaryngol. 2006 May-Jun;27(3):190-9.

Factors contributing to nasal allergic late phase eosinophilia.

Kramer MF, Jordan TR, Klemens C, Hilgert E, Hempel JM, Pfrogner E, Rasp G.

Department of Oto-Rhino-Laryngology, Klinikum Grosshadern,
Ludwig-Maximilians-University Munich, Munich, Germany.
mathias.kramer@med.uni-muenchen.de

OBJECTIVE: This study focused on factors contributing to eosinophilia after
intranasal allergen challenge. METHODS: Nasal secretions of 13 allergic
individuals were gained over a period of 8 hours after nasal allergen challenge. 
Early and late phase reactions were determined by acoustic rhinometry and changes
of volume and total protein in nasal secretions. Eosinophilia was demonstrated by
nasal eosinophilic cationic protein. Interleukin (IL)-5; the chemokines IL-8,
monocyte chemotactic protein (MCP)-1 and MCP-3, and eotaxin; soluble vascular
cell adhesion molecule 1 (sVCAM-1); and the leukotriene C4 (LTC4) were analyzed
by enzyme-linked immunosorbent assay for their suggested impacts on tissue
eosinophilia. RESULTS: By means of rhinometry, we observed in 69% an alternating 
type of late phase response, followed by a bilateral (15%) or unilateral (8%)
type. A biphasic kinetic could be demonstrated by changes in nasal volume and
total protein of nasal secretions, reflecting the early and late phase responses.
A typical late phase kinetic was observed for IL-5, MCP-1, eotaxin, sVCAM-1, and 
LTC4. Interleukin 8 was characteristic for early phase reaction but increased in 
late phase as well. We could not detect any MCP-3 in our samples. CONCLUSIONS:
Our data point to a relevant role of the T(H)2 cytokine IL-5; of the chemokines
IL-8, MCP-1, and eotaxin; of the adhesion molecule sVCAM-1; and of the
leukotriene LTC4 for the allergic late phase eosinophilia.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16647984 [PubMed - indexed for MEDLINE]

573: Expert Opin Pharmacother. 2006 May;7(7):941-51.

Once-daily immediate-release fexofenadine and sustained-release pseudoephedrine
combination: a new treatment option for allergic rhinitis.

Mansfield LE.

Texas Tech Regional Health Science Center, El Paso, TX 79902, USA.
immunman@pol.net

Allergic rhinitis symptoms, in particular nasal congestion, can have a
significant impact on patient quality of life, resulting in reduced productivity 
and daytime sleepiness. Newer-generation antihistamines are commonly used to
treat allergic rhinitis; however, in patients with severe congestion, a
combination of a newer-generation antihistamine and a decongestant is
particularly beneficial. A new once-daily fexofenadine/pseudoephedrine
combination has been developed and recently approved in the US. The combination
provides an effective, well-tolerated antihistamine and a reliable,
sustained-release pseudoephedrine system. In addition, small tablet size and
once-daily dosing may provide patients with increased convenience and improve
adherence. In summary, the combination of immediate-release
fexofenadine/sustained-release pseudoephedrine offers an important additional
option for the treatment of allergic rhinitis.

Publication Types: 
    Review

PMID: 16634716 [PubMed - indexed for MEDLINE]

574: J Allergy Clin Immunol. 2006 Apr;117(4):810-6. Epub 2006 Feb 8.

Double-blind, placebo-controlled study with a modified therapeutic vaccine of
Salsola kali (Russian thistle) administered through use of a cluster schedule.

Colás C, Monzón S, Venturini M, Lezaun A.

Servicio de Alergia, Hospital Clínico Lozano Blesa, Zaragoza, Spain.
algc-colas@hcu-lblesa.es

BACKGROUND: The inhalation of Salsola kali pollen is a common cause of
respiratory diseases in Europe and North America. OBJECTIVE: To evaluate the
efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic
vaccine of S kali. METHODS: The trial was randomized, double-blind, and
placebo-controlled using a rush protocol in the build-up phase. Sixty patients
with rhinoconjunctivitis (19 also had mild asthma) were randomly allocated to
receive either active treatment (polymerized extract) or placebo. The final
distribution was 41 patients in the active and 19 in the placebo group. Side
effects were registered. Symptom and medication scores and the number of days
free of symptoms during the pollen season were assessed to evaluate the clinical 
efficacy. A Rhinoconjunctivitis Quality of Life Questionnaire was completed in
the previous pollen season (before treatment) and during the pollen season 1 year
later (in the trial). Dose-response skin tests were performed at baseline and at 
the end of the trial. RESULTS: There was a significant difference (P < .05) in
symptom and medication scores between both groups during the pollen season, with 
the active group the one that had fewer symptoms and lower intake of medication. 
The number of days without symptoms was higher in the active group (P < .05).
This group also had a significant improvement in the Rhinoconjunctivitis Quality 
of Life Questionnaire and a reduction in skin sensitivity. No moderate or severe 
systemic reactions were registered. CONCLUSION: Immunotherapy with this modified 
vaccine of S kali pollen is safe and efficacious to treat patients clinically
sensitive to this pollen. CLINICAL IMPLICATIONS: Patients allergic to S kali
(Russian thistle) can be successfully treated with immunotherapy to improve
symptoms of allergic rhinitis and asthma, reduce medication use, and improve
quality of life parameters.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16630938 [PubMed - indexed for MEDLINE]

575: J Allergy Clin Immunol. 2006 Apr;117(4):802-9.

Comment in:
    Evid Based Med. 2006 Dec;11(6):173.    J Allergy Clin Immunol. 2007 Feb;119(2):515; author reply 515-7.

Sublingual immunotherapy with once-daily grass allergen tablets: a randomized
controlled trial in seasonal allergic rhinoconjunctivitis.

Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S.

Royal Brompton and Harefield Hospitals National Health Service Trust and Imperial
College, National Heart and Lung Institute, London, United Kingdom.
s.durham@imperial.ac.uk

BACKGROUND: Specific immunotherapy is the only treatment modality that has the
potential to alter the natural course of allergic diseases. Sublingual
immunotherapy has been developed to facilitate access to this form of treatment
and to minimize serious adverse events. OBJECTIVE: To investigate the efficacy
and safety of sublingual grass allergen tablets in seasonal allergic
rhinoconjunctivitis. METHODS: A multinational, multicenter, randomized,
placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 
countries included 855 participants age 18 to 65 years who gave a history of
grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick
test and elevated serum allergen-specific IgE to Phleum pratense. Participants
were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX;
ALK-Abelló, Hørsholm, Denmark) or placebo for sublingual administration once
daily. Mean duration of treatment was 18 weeks. RESULTS: Average
rhinoconjunctivitis scores during the season showed moderate reductions of
symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T
(P = .0710; P = .0470) compared with placebo. Significantly better
rhinoconjunctivitis quality of life scores (P = .006) and an increased number of 
well days (P = .041) were also observed. Efficacy was increased in the subgroup
of patients who completed the recommended preseasonal treatment of at least 8
weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication
use, 29%, P = .0120). No safety concerns were observed. CONCLUSION: This study
confirms dose-dependent efficacy of the grass allergen tablet. Although further
studies are required, the greater tolerability of the tablet may permit
immunotherapy to be available to a much broader group of patients with impaired
quality of life caused by grass pollen allergy. CLINICAL IMPLICATIONS: For
patients with grass pollen allergy, sublingual immunotherapy is well tolerated
and can reduce symptoms and improve quality of life.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16630937 [PubMed - indexed for MEDLINE]

576: Clin Exp Allergy. 2006 Apr;36(4):458-64.

Effects of a reversible beta-tryptase and trypsin inhibitor (RWJ-58643) on nasal 
allergic responses.

Erin EM, Leaker BR, Zacharasiewicz A, Higgins LA, Nicholson GC, Boyce MJ, de Boer
P, Jones RC, Durham SR, Barnes PJ, Hansel TT.

Clinical Studies Unit, National Heart and Lung Institute (NHLI), Imperial
College, London, UK.

BACKGROUND: beta-Tryptase is a multifunctional mast cell serine protease released
during mast cell degranulation and tryptase/trypsin inhibitors are a novel
potential therapeutic approach for allergic inflammatory diseases. OBJECTIVES:
This study was performed to assess the effects of RWJ-58643 on nasal symptoms,
eosinophil influx, and cytokine and chemokine release following nasal allergen
challenge (NAC). METHODS: Male patients with grass pollen allergic rhinitis
(n=16) out of season received single doses of RWJ-58643 (100, 300, 600 microg) or
matched placebo given 30 min before NAC in a double-blind, randomized crossover
design. A single dose of 200 microg budesonide was studied in an open-label
extension phase. NAC was performed with Timothy grass pollen (ALK) via a nasal
device, and nasal lavage was performed at times 0 (pre-drug, pre-allergen), 0.5
(30 min post-drug, pre-NAC) 1.5, 2.5, 4.5, 6.5, 8.5, and 24 h after drug
administration. Nasal lavage mediators were analysed using a sensitive
multiplexed bead immunoassay system. RESULTS: Low-dose RWJ-58643 (100 microg) and
budesonide (200 microg) significantly reduced symptoms, eosinophils and levels of
IL-5 following NAC. However, higher doses of RWJ-58643 (300 and 600 microg)
caused a late eosinophilia and preceding increases in IL-5 compared with placebo.
CONCLUSIONS: This study suggests that combined beta-tryptase and trypsin
inhibition has therapeutic potential in allergic inflammation, however, this
property is dose responsive and higher doses are ineffective and may cause
eosinophilia.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16630150 [PubMed - indexed for MEDLINE]

577: Allergy. 2006 May;61(5):556-62.

Trends in prevalence of asthma, allergic rhinitis and atopic dermatitis in
5-7-year old Swiss children from 1992 to 2001.

Grize L, Gassner M, Wüthrich B, Bringolf-Isler B, Takken-Sahli K, Sennhauser FH, 
Stricker T, Eigenmann PA, Braun-Fahrländer C; Swiss Surveillance Programme on
Childhood Allergy and Respiratory symptoms with respect to Air Pollution
(SCARPOL) team.

Institute of Social and Preventive Medicine, University of Basel, Basel,
Switzerland.

BACKGROUND: Changing occurrence rates of asthma, allergic rhinitis and atopic
dermatitis are of public health concern and require surveillance. Changes in
prevalence rates of these atopic diseases were monitored during 10 years and
their trend with time was determined taking into account the influence of
personal and environmental risk factors. METHODS: Four cross-sectional surveys in
5-7-year old children were performed in seven different communities in
Switzerland between 1992 and 2001. Prevalence of respiratory and allergic
symptoms and of affecting risk factors including parental environmental concern
were assessed using a standardized parental questionnaire. RESULTS: A total of
988 (74.1%), 1778 (79.0%), 1406 (82.6%) and 1274 (78.9%) children participated,
respectively, in the 1992, 1995, 1998 and 2001 surveys. Prevalence rates of
asthma and hay fever symptoms remained quite stable over time (wheeze/past year: 
8.8%, 7.8%, 6.4% and 7.4%, sneezing attack during pollen season: 5.0%, 5.6%, 5.4%
and 4.6%). Rates of reported atopic dermatitis symptoms (specific skin rash/past 
year: 4.6%, 6.5%,7.4% and 7.6%) showed an increase over time, but those of
diagnosis of eczema did not show a clear pattern (18.4%, 15.7%, 14.0% and 15.2%).
Stratified analysis by parental environmental concern and by parental atopy
showed similar trends. Rates of atopic dermatitis symptoms showed significant
increase in girls but stayed stable in boys. CONCLUSION: Results of these four
consecutive surveys suggest that the increase in prevalence of asthma and hay
fever in 5-7-year old children living in Switzerland may have ceased. However,
symptoms of atopic dermatitis may still be on the rise, especially among girls.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16629784 [PubMed - indexed for MEDLINE]

578: Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004460.

Capsaicin for allergic rhinitis in adults.

Cheng J, Yang XN, Liu X, Zhang SP.

Guangdong College of Pharmacy, Clinical Department, Guangzhou, China, 510224.
chengjing1137@126.com

BACKGROUND: Allergic rhinitis represents a global health problem. Non-specific
nasal hyperresponsiveness is an important feature of allergic and non-allergic
rhinitis. This phenomenon is believed to result from the effect of allergic
inflammation on the sensory nerves that supply the upper airway mucosa. A
pharmacologic agent that has proved useful in the investigation of effects of
neuronal stimulation is capsaicin, the pungent component of hot pepper.
Intranasal capsaicin specifically stimulates afferent nerves consisting mostly of
unmyelinated C fibers and some myelinated A-delta fibers. As a result it can
trigger central and axonal reflexes, the latter being putatively mediated by the 
release of neuropeptides. Capsaicin as a blocking agent of neuropeptides, blocks 
the axon reflex and may exert a curative effect on allergic rhinitis. OBJECTIVES:
To assess the effectiveness of capsaicin for allergic rhinitis in adults. SEARCH 
STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group
Specialised Register, the Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to 2006) and EMBASE
(1974 to 2006). We assessed bibliographies from included studies, and contacted
authors of known studies for additional information about published and
unpublished trials. The date of the most recent search was January 2006.
SELECTION CRITERIA: Randomised controlled trials of capsaicin for allergic
rhinitis in adults were included. DATA COLLECTION AND ANALYSIS: Three reviewers
read each paper, blind to its identity. Decisions concerning inclusion were made 
by simple majority. We all performed quality assessment independently. MAIN
RESULTS: One small trial did not find evidence that intranasal capsaicin had a
therapeutic effect in allergic rhinitis. A small pharmacological effect on
clinical histamine dose response was found. After treatment, leukotriene levels
in nasal lavage did not increase in the capsaicin group. AUTHORS' CONCLUSIONS:
There is insufficient evidence to assess the use of capsaicin in clinical
practice.

Publication Types: 
    Review

PMID: 16625604 [PubMed - indexed for MEDLINE]

579: J Med Assoc Thai. 2005 Sep;88 Suppl 4:S348-51.

Montelukast in general pediatric practices.

Ngamphaiboon J.

Department of Pediatrics, Allergy and Immunology Unit, Faculty of Medicine,
Chulalongkorn University, Bangkok, Thailand. ngamphaiboon_j@yahoo.com

Allergic diseases, e.g., allergic rhinitis, atopic dermatitis and asthma, are
common problems in children. Researches on the pathogenesis of allergic diseases 
have led to the development of new specific antiinflammatory medications,
including Montelukast, which blocks the interaction of cysteinyl leukotrienes to 
their receptors and resulting downstream events. Several studies have
demonstrated the effect of regular Montelukast therapy on asthma, allergic
rhinitis, viral-induced wheezing in bronchiolitis and chronic rhinitis symptoms. 
Evidence base medicine now shows that Montelukast can be used as a monotherapy in
mild persistent asthma and can be an add-on drug to inhaled corticosteroid (ICS) 
in moderate to severe persistent asthma. Even in allergic rhinitis, Montelukast
has a role in controlling rhinitis symptoms. Montelukast demonstrated a safety
profile similar to placebo and more safety than ICS. Moreover Montelukast can
improve quality of life in patients with asthma and comorbid allergic rhinitis.

PMID: 16623053 [PubMed - indexed for MEDLINE]

580: J Pediatr (Rio J). 2006 Mar-Apr;82(2):137-43.

Prevalence of allergic rhinitis among adolescents from Distrito Federal, Brazil: 
comparison between ISAAC phases I and III.

Borges WG, Burns DA, Felizola ML, Oliveira BA, Hamu CS, Freitas VC.

Hospital de Base do Distrito Federal, DF, Brazil. wellingtonborges@terra.com.br

OBJECTIVE: To determine the prevalence of allergic rhinitis in a random group of 
schoolchildren aged 13 to 14 years in Brasilia, Brazil, to evaluate tendencies
over 6 years and to compare prevalence rates among different socioeconomic
groups. METHODS: Two cross-sectional studies were undertaken 6 years apart, using
the ISAAC (phases I and III) written questionnaire. Thirty-nine schools were
chosen at random from eight administrative regions in Brasilia, and were
classified into three groups according to the socioeconomic conditions of the
population. RESULTS: A total of 3,009 questionnaires were collected. Of these
53.5% related to female children and 80% to students from public schools.
Prevalence rates for diagnosed rhinitis, recent rhinitis and allergic rhinitis
were 20, 29.3 and 12.2%, respectively. Rhinitis was more prevalent in private
schools than in public ones (17.8 versus 14.1%) and sufferers were predominantly 
female. Prevalence rates were also higher among populations with higher
socioeconomic status (23.5 versus 12.2%). Comparison with the 1996 data revealed 
significant increases in the prevalence of diagnosed rhinitis (12.7 versus 20%, p
= 0.001). These increases were observed at all socioeconomic levels. CONCLUSIONS:
A large number of 13 and 14-year-old children resident in the Distrito Federal
exhibit symptoms indicative of rhinitis and the majority of them have allergic
rhinitis. Over a six-year period the prevalence of allergic rhinitis increased
significantly, predominantly affecting females and with greater prevalence among 
students at private school and from families with higher socioeconomic status.

Publication Types: 
    Comparative Study

PMID: 16614769 [PubMed - indexed for MEDLINE]

581: J Agric Food Chem. 2006 Apr 19;54(8):2915-20.

Anti type I allergic property of Japanese butterbur extract and its mast cell
degranulation inhibitory ingredients.

Shimoda H, Tanaka J, Yamada E, Morikawa T, Kasajima N, Yoshikawa M.

Research and Development Division, Oryza Oil & Fat Chemical Company, Ltd.,
Ichinomiya, Aichi 493-8001, Japan. kaihatsu@mri.biglobe.ne.jp

Pollenosis is a disease that affects 1 in 10 of the Japanese population. During
the season of cedar pollen dispersal, many patients suffer from symptoms such as 
sniffling, sternutation, and itching of the eyes. Japanese butterbur is a popular
vegetable and is one of the few domestic vegetables in Japan. The anti type I
allergic effects of an aqueous ethanol extract from aerial parts of Japanese
butterbur (JBE) were evaluated in rats and RBL-2H3 mast cells. In the passive
cutaneous anaphylaxis reaction in rats, a single oral treatment of JBE (1000
mg/kg) was found to suppress the reaction. In IgE-sensitized RBL-2H3 cells, JBE
(10-100 microg/mL) inhibited beta-hexosaminidase release, leukotriene
C(4)/D(4)/E(4) synthesis, and TNF-alpha production. Moreover, a high
concentration of JBE (1000 microg/mL) suppressed smooth muscle constriction
induced by histamine (10 microM) and leukotriene D(4) (10 nM) in a guinea pig
trachea strip. The search for components in JBE with an inhibitory activity on
mast cell degranulation was guided by inhibition of beta-hexsosaminidase release.
Two eremophilane-type sesquiterpenes, six polyphenolic compounds, and two
triterpene glycosides were isolated. Of these compounds, fukinolic acid, a
principal polyphenol constituent, showed potent inhibitory activity (IC(50) value
= 2.1 microg/mL). Consequently, On the basis of its inhibition of mast cell
activation and direct smooth muscle reaction induced by released mediators, JBE
was found to suppress the type I allergic reaction.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16608208 [PubMed - indexed for MEDLINE]

582: Int J Tuberc Lung Dis. 2006 Apr;10(4):371-7.

Prevalence and trend of self-reported asthma and other allergic disease symptoms 
in Morocco: ISAAC phase I and III.

Bouayad Z, Aichane A, Afif A, Benouhoud N, Trombati N, Chan-Yeung M, Aït-Khaled
N.

Service des Maladies Respiratoires, Hôpital 20 Août, Centre Hospitalier
Universitaire (CHU) Ibn Rochd, Casablanca, Morocco.

BACKGROUND: The prevalence of asthma and other allergic diseases is increasing in
many parts of the world. OBJECTIVE: To determine the prevalence of asthma,
rhinoconjunctivitis and skin allergy symptoms in Morocco as part of the
International Study of Asthma and Allergic Diseases in Children (ISAAC). METHODS:
The survey was conducted using the standardised method of ISAAC Phase III in four
centres in Morocco-Casablanca, Marrakech, Ben Slimane and Boulmane-with
respectively 1777, 1689, 1008 and 1254 13-14-year-old schoolchildren
participating. A comparison of the results with ISAAC Phase I was carried out in 
two centres. RESULTS: The prevalence of self-reported symptoms of wheeze in the
last 12 months (6.4-16.2%), nasal symptoms (27.9-52.8%), rhinoconjonctivitis
(8.8-28%) and eczema (13.3-20.2%) varied between centres, and were highest in
Casablanca, the largest city in Morocco. Significant increases in almost all
symptoms were found in the two centres of Casablanca and Marrakech between ISAAC 
Phase I and Phase III. CONCLUSION: Morocco could be classified as a country with 
an intermediate burden of asthma (between 10% and 15%) and other allergic
disorders. The prevalence of these symptoms has increased in the past 5 years.

Publication Types: 
    Multicenter Study

PMID: 16602399 [PubMed - indexed for MEDLINE]

583: Int Arch Allergy Immunol. 2006;140(2):121-30. Epub 2006 Apr 3.

Sensitization to Lolium multiflorum grass pollen in pollinosis patients:
evaluation of allergenic fractions recognized by specific IgE antibodies.

Sopelete MC, Moreira PF, Silva DA, Cunha-Júnior JP, Vieira FA, Sung SS, Taketomi 
EA.

Laboratory of Allergy and Clinical Immunology, Biomedical Science Institute,
Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil.

BACKGROUND: Lolium multiflorum (Lm) pollen allergens are the major causative
agents for rhinoconjunctivitis in Southern Brazil. There have been no studies
about the sensitization and allergenic cross-reactivity between Lm and other
grass pollens. We evaluated the sensitization of Brazilian pollinosis patients to
Lm pollen allergens through skin prick test (SPT) and immunoassays (ELISA and
immunoblot). METHODS: Serum samples from 60 patients with pollinosis and positive
SPT to grass pollen extracts (Lm+ group), 30 patients with negative SPT to grass 
pollen, but positive SPT to mite extracts (Lm- group), and 30 nonatopic subjects 
(NA group) were tested by SPT, ELISA, and immunoblot using Lm extract. Inhibition
immunoassays with Lolium perenne (Lp), mixed grass (Gmix) and Lm extracts were
also performed. RESULTS: A high concordance was found between the Gmix and Lm
extracts in SPT. Positivity rates in SPT were also highly concordant with
IgE-ELISA results. The assay was able to detect Lm-specific IgE in >95% of Lm+
patients. A significant self- and cross-inhibition was observed in IgE-ELISA,
reflecting a high cross-reactivity between the grass pollen allergens. Immunoblot
revealed 13 IgE-binding Lm fractions, from which the bands 28-30 kDa and 31-34
kDa were recognized by >90% of Lm+ patients. CONCLUSION: Lm-specific IgE
antibodies are highly cross-reactive with pollen proteins from other grass
species. The results indicate that Lm extracts could be used in both SPT and
ELISA for a more specific evaluation of IgE responses to Lm grass pollen in
Brazilian pollinosis patients.

PMID: 16601349 [PubMed - indexed for MEDLINE]

584: J Investig Allergol Clin Immunol. 2006;16(1):24-33.

Aerobiological and allergenic analysis of cupressaceae pollen in Granada
(Southern Spain).

Diaz de la Guardia C, Alba F, de Linares C, Nieto-Lugilde D, López Caballero J.

Departamento de Botánica, Facultad de Ciencias, Universidad de Granada, Granada, 
Spain. cdiaz@ugr.es

Cupressaceae pollen has been cited in recent years as one of the major airborne
allergens of the Mediterranean region, prompting us to conduct an exhaustive
analysis on the aerobiological behaviour of this pollen in the Iberian Peninsula 
and the repercussion that it has had on the atopic population. The aerobiological
study, performed from 1996 to 2003 in the city of Granada (S. Spain), used a
volumetric Hirst collector. The results indicate that this pollen is present in
the air most of the year, registering a high incidence during the winter months. 
This type of pollen behaved irregularly in the air, fluctuating yearly,
seasonally, and within the same day. Temperature and humidity were the parameters
that most directly influence the variability of this allergen, while rainfall
prior to flowering increased pollen production. The predictive models used
estimated a high percentage of the levels reached over the short term by this
pollen in the atmosphere of Granada. The clinical study performed with atopic
patients showed that some 30% of the population with pollinosis are sensitive to 
Cupressaceae pollen, affecting people of both genders equally. On the other hand,
the most sensitive age group was 21-40 years of age, while children and the
elderly registered almost negligible values. Most of the sensitive subjects
resided within the city or in the metropolitan area, where environmental
pollution reached high levels, while the pathology was found to be less frequent 
in rural zones. The most frequent symptoms were upper-respiratory ailments and an
asthmatic profile.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16599245 [PubMed - indexed for MEDLINE]

585: Allergy Asthma Proc. 2006 Jan-Feb;27(1):63-7.

A novel air filtration delivery system improves seasonal allergic rhinitis.

Morris RJ, Helm TJ, Schmid W, Hacker D.

Allergy and Asthma Care, P.A., Minneapolis, Minnesota 55369, USA.
rmorris@allergy-care.net

Twenty percent of the United States population has respiratory allergies. The
preferable treatment for allergies is avoidance. Bedrooms offer the best
opportunity for allergen avoidance. Most previous studies of air filtration only 
measured the effect on allergen particle counts, but few have addressed the
clinical efficacy. This study measured the effects of a novel laminar flow air
filtration device (PureNight) on seasonal ragweed allergies. Seventy-seven
percent of the subjects improved significantly on symptom scores, an average of
26% improvement in the morning and 24% in the evening. Daytime sleepiness and
quality of life scores also improved significantly in all subjects. Tolerability 
was excellent. The PureNight device provided significant clinical improvement of 
allergic symptoms during ragweed hay fever season.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16598995 [PubMed - indexed for MEDLINE]

586: Allergy Asthma Proc. 2006 Jan-Feb;27(1):59-62.

Allergic rhinitis in Korean immigrants to the United States.

Kim AS, Majmudar SP, Yu BH.

Rush University Medical Center, Chicago, Illinois 60612, USA.

The prevalence of allergic rhinitis among Korean immigrants to the United States 
is unknown. However, after arrival in the United States, many develop allergic
rhinitis for the first time. This study is undertaken to investigate and
establish some contributing environmental factors and the time until onset of
allergic rhinitis in Korean immigrants to the United States living in Chicago.
Information regarding 246 patients of Korean origin who presented to a Chicago
allergy/immunology clinic from 1993 to 1998 were analyzed by retrospective chart 
review. The diagnosis of allergic rhinitis was established by history, physical
examination, and skin testing for immediate hypersensitivity to airborne
allergens. The mean residential time in the United States of our patients was
13.5 years (range, 2-38 years). The mean interval from arrival in the United
States to onset of symptoms was 8 years (range, 0-24 years) The most commonly
identified allergens were ragweed pollen (59%), cat pelt (44%), cocklebur pollen 
(41%), house-dust mite (35%), and Penicillium (29%). We conclude that the
spectrum of responsible allergens in Korean immigrants closely resembles that
seen in native citizens of the United States and that environmental factors play 
an important role in the pathogenesis of allergic rhinitis in this population.

PMID: 16598994 [PubMed - indexed for MEDLINE]

587: Allergy Asthma Proc. 2006 Jan-Feb;27(1):12-6.

Managing impairment in patients with allergic rhinitis.

Stokes J, Fenstad E, Casale TB.

Division of Allergy/Immunology, Department of Medicine, Creighton University,
Omaha, Nebraska 68131, USA.

Allergic rhinitis is a common medical problem in both the adult and the pediatric
population. A main complication of this disease is a reduction in the patient's
quality of life. Individuals with either seasonal or perennial allergic rhinitis 
often are impaired, adversely affecting work and/or school performance. This
impairment can result from the disease itself and the treatment thereof. Oral
antihistamines are the mainstay of treatment for allergic disease.
First-generation antihistamines are considered sedating and frequently are
impairing even when sedation is absent. Second-generation antihistamines show
some class variability regarding impairment but as a group are clearly less
impairing than their first-generation predecessors. Second-generation
antihistamines are the preferred medication when antihistamines are necessary.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16598987 [PubMed - indexed for MEDLINE]

588: Allergy Asthma Proc. 2006 Jan-Feb;27(1):9-11.

Allergic rhinitis: managing the adult spectrum.

Slavin RG.

Division of Allergy and Immunology, St. Louis University School of Medicine, St. 
Louis, Missouri 63104, USA. slavinrg@slu.edu

With the general population increasing in age, clinicians will be seeing more
elderly patients. Many present with bothersome rhinitis. A number of
physiological and anatomic changes associated with age predispose the elderly
population to develop rhinitis. A number of categories of rhinitis occur in
elderly people and it is important to make the correct diagnosis. Appropriate
therapy is available but the clinician must be wary of side effects, particularly
to antihistamines and decongestants that may be more severe in elderly patients.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16598986 [PubMed - indexed for MEDLINE]

589: Allergy Asthma Proc. 2006 Jan-Feb;27(1):2-8.

Allergic rhinitis: managing the pediatric spectrum.

Meltzer EO.

Allergy and Asthma Medical Group and Research Center, San Diego, California
92123, USA. EOMELTZER@aol.com

Allergic rhinitis (AR) is the most common chronic disease in the pediatric
population and its prevalence is increasing. AR can significantly impact a
child's health. It causes uncomfortable symptoms, impairs quality of life, and
can predispose to the development of comorbidities such as asthma. Although
allergen avoidance is the first step in AR management, it often is impractical.
Fortunately, there are a number of pharmacologic agents available for the
treatment of AR. When choosing a medication, attention should be paid to the
substance's risk/benefit ratio. First-line therapy consists of second-generation 
antihistamines, which lack many of the unwanted side effects caused by
first-generation compounds, and intranasal corticosteroids, which are the
preferred agents for children with persistent symptoms. Other pharmacologic
options include decongestants, leukotriene-receptor antagonists, and intranasal
cromolyn sodium. Allergen immunotherapy can be a valuable adjunctive modality.
Issues of compliance and convenience also are important considerations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16598985 [PubMed - indexed for MEDLINE]

590: Ann Allergy Asthma Immunol. 2006 Mar;96(3):466-71.

The role of major olive pollen allergens Ole e 1, Ole e 9, and Ole e 10 on mice
sensitization.

Barral P, Villalba M, Rodriguez R, Batanero E.

Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas,
Universidad Complutense, Madrid, Spain.

BACKGROUND: Olive pollen is an important cause of allergy in Mediterranean
countries. To date, 10 allergens (Ole e 1 to Ole e 10) have been isolated and
characterized. Animal models of olive pollen allergy are suitable tools for
testing the efficacy and safety of new forms of immunotherapy. OBJECTIVES: To
characterize the immune response in mice sensitized with olive pollen extract and
to compare it with that of allergic patients. METHODS: BALB/c mice were
sensitized by 4 intraperitoneal injections of olive pollen extract in aluminum
hydroxide. The allergic state was proved by measuring serum specific IgG1 and
total IgE antibody levels. The IgG1 responses to olive pollen allergens were
assayed by immunoblotting and enzyme-linked immunosorbent assay. Competition
experiments between human IgE and mouse IgG1 binding to olive pollen allergens
were performed. RESULTS: Sensitization with olive pollen extract induced high
levels of specific IgG1 and total IgE in all tested animals. Immunoblotting
experiments showed that the mouse IgG1 binding pattern to pollen extract was
complex and heterogeneous, as occurs with human IgE. High IgG1 antibody levels to
the major olive pollen allergens described for humans were detected in serum
samples from sensitized mice, whereas minor olive pollen allergens induced no
significant IgG1 response. Coincubation of mouse serum samples with a cocktail of
Ole e 1, Ole e 9, and Ole e 10 resulted in a significant decrease (60%) in IgG1
binding to olive pollen extract. Specific mouse IgG1 strongly inhibited human IgE
binding to olive pollen allergens. CONCLUSIONS: This mouse model of olive pollen 
sensitization mimics immunologic features of human pollinosis and could be a
useful tool for designing novel forms of immunotherapy for olive pollen allergy
based on allergen cocktails.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16597082 [PubMed - indexed for MEDLINE]

591: Ann Allergy Asthma Immunol. 2006 Mar;96(3):431-6.

Association between response to decongestion testing and sensitizations and
allergic inflammation.

Ciprandi G, Cirillo I, Klersy C, Vizzaccaro A, Tosca MA, Marseglia GL.

Dipartimento Patologie Testa-Collo, Padiglione Specialità (piano terzo), Azienda 
Ospedale-Università San Martino, Genoa, Italy. gio.cip@libero.it

BACKGROUND: Rhinomanometry is used to measure nasal airflow, which is frequently 
impaired in allergic rhinitis (AR). Decongestion testing consists of spraying an 
intranasal vasoconstrictor drug to evaluate recovery of nasal airflow. OBJECTIVE:
To evaluate the relationships among type and number of sensitizations, nasal
airflow recovery after topical vasoconstrictor drug use, and allergic
inflammation. METHODS: A total of 123 patients (112 men and 11 women; mean +/- SD
age, 22.9 +/- 5.7 years) were studied: 40 with perennial AR (PAR), 43 with mixed 
AR (MAR), and 40 with seasonal AR (SAR). Patients with anatomic nasal defects
were excluded. Total symptom scores (including nasal itching, sneezing,
rhinorrhea, and nasal obstruction), sensitizations, nasal eosinophils, and
cytokines (including interleukin 4 [IL-4], IL-5, and interferon-gamma) were
evaluated. Electronic rhinomanometry and decongestion testing were performed in
all the patients. RESULTS: After administration of a topical nasal
vasoconstrictor agent, mean nasal airflow significantly increased from 471 to 580
mL/s (P < .001). In 12 patients (3 with PAR, 3 with MAR, and 6 with SAR), no
increase was shown. Changes from baseline were different in the PAR, MAR, and SAR
populations (PAR vs MAR, P < .001; PAR vs SAR, P < .001; and MAR vs SAR, P =
.25). Type of sensitization (MAR, PAR, or SAR), concentration of eosinophils, and
levels of IL-4, IL-5, and interferon-gamma were associated with nasal airflow
recovery of at least 120 mL/s. CONCLUSIONS: This study provides the first
evidence of a different response to decongestion testing taking into
consideration the type of AR.

PMID: 16597077 [PubMed - indexed for MEDLINE]

592: Biol Pharm Bull. 2006 Apr;29(4):689-92.

Effects of hop extracts on nasal rubbing and sneezing in BALB/c mice.

Takubo M, Inoue T, Jiang S, Tsumuro T, Ueda Y, Yatsuzuka R, Segawa S, Watari J,
Kamei C.

Department of Medicinal Pharmacology, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences, Japan.

The effects of hop extracts (Humulus lupulus L.) on histamine release from rat
peritoneal mast cells and human basophilic KU812 cells were studied. Hop water
extract (HWE) and XAD-4 50% methanol fraction of HWE (MFH) inhibited histamine
release from rat mast cells induced by compound 48/80 at concentrations of 100
and 10 mug/ml, respectively. Almost the same findings were observed with
A23187-induced histamine release from KU812 cells. Next, we studied the effects
of hop extracts on antigen-induced nasal rubbing and sneezing in sensitized
BALB/c mice. HWE caused a significant inhibition of nasal rubbing and sneezing at
a dose of 500 mg/kg. MFH also inhibited nasal rubbing and sneezing
dose-dependently. A significant difference was observed from 100 mg/kg in nasal
rubbing and 200 mg/kg in sneezing. The effects of both extracts became clear
after repeated administration. HWE and MFH significantly inhibited both nasal
rubbing and sneezing, respectively, after consecutive treatment for 15 d at
smaller doses compared with single administration. This finding indicates that
the active component of hop is included in MFH, which was absorbed to Amberlite
XAD-4 and eluted with 50% methanol. These results clearly demonstrated that hop
extracts may be effective in the relief of symptoms of allergic rhinitis.

PMID: 16595900 [PubMed - indexed for MEDLINE]

593: Curr Allergy Asthma Rep. 2006 May;6(3):232-8.

Treating allergic rhinitis in pregnancy.

Piette V, Daures JP, Demoly P.

Numerous pregnant women suffer from allergic rhinitis, and particular attention
is required when prescribing drugs to these patients. In addition, physiologic
changes associated with pregnancy could affect the upper airways. Evidence-based 
guidelines on the management of allergic rhinitis have been published. Medication
can be prescribed during pregnancy when the apparent benefit of the drug is
greater than the apparent risk. Usually, there is at least one "safe" drug from
each major class used to control symptoms. All glucocorticosteroids are
teratogenic in animals but, when the indication is clear (for diseases possibly
associated, such as severe asthma exacerbation), the benefit of the drug is far
greater than the risk. Inhaled glucocorticosteroids (eg, beclomethasone or
budesonide) have not been incriminated as teratogens in humans and are used by
pregnant women who have asthma. A few H1-antihistamines can safely be used as
well. Most oral decongestants (except pseudoephedrine) are teratogenic in
animals. There are no such data available for intranasal decongestants. Finally, 
pregnancy is not considered to be a contraindication for the continuation of
immunotherapy.

Publication Types: 
    Review

PMID: 16579874 [PubMed - indexed for MEDLINE]

594: Asian Pac J Allergy Immunol. 2005 Dec;23(4):213-9.

Detection of amino acids in human nasal mucosa using microdialysis technique:
increased glutamate in allergic rhinitis.

Lee HS, Goh EK, Wang SG, Chon KM, Kim HK, Roh HJ.

Department of Otorhinolaryngology, College of Medicine, Pusan National
University, Busan, Korea.

Amino acids, the smaller basic biochemical units of neuropeptides, have not been 
evaluated in the nasal cavity. The purpose of this study was to measure the
concentration of neurotransmitting amino acids of the central nervous system,
glutamate, aspartate, serine, taurine (2-aminoethane sulfonic acid; a
conditionally essential amino acids), and GABA (gamma-amino-butyric acid; an
amino acid produced in the brain), in nasal mucosa of allergic rhinitis patients 
and normal controls using a microdialysis technique. A microdialysis probe
appropriate for use on human nasal mucosa was developed using Cuprophan hollow
fiber. Glutamate concentration in allergy group was significantly higher (p =
0.004) than in control group, while the concentrations of the other four amino
acids showed no significant difference between the two groups. Our findings and
review of the literature suggest that glutamate is one of the most potent
neurotransmitters associated with the parasympathetic nerve in the nasal cavity, 
and that the microdialysis technique is useful in studying the pharmacokinetics
in situ and local organ chemistry of the nasal cavity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16572741 [PubMed - indexed for MEDLINE]

595: Asian Pac J Allergy Immunol. 2005 Dec;23(4):169-74.

The efficacy and safety of 30 mg fexofenadine HCl bid in pediatric patients with 
allergic rhinitis.

Ngamphaiboon J, Direkwattanachai C, Visitsunthorn N, Vangveeravong M, Tiensuwan
M.

Department of Pediatric, Faculty of Medicine, Chulalongkorn University, Bangkok, 
Thailand. ngamphaiboon_j@yahoo.com

Allergic rhinitis is one of the most common chronic disorders in children. It is 
also one of the most common causes of absence from school. This study reports on 
the efficacy and safety of a twice-daily oral dose of fexofenadine HCl 30 mg in
Asian children aged 6-11 years diagnosed with seasonal or perennial allergic
rhinitis. A total of 100 children with a history of allergic rhinitis for more
than one year and a positive prick skin test response to at least one of the
common aeroallergens in Thailand were enrolled in this multi-center, open-label, 
non comparative study. The severity of individual symptoms such as sneezing,
rhinitis, etc. and adverse events were recorded in diary cards by the patients in
form of scores as well as by the investigator at each visit. The total symptom
score (TSS) with or without blocked nose at baseline, week 1 and week 2 was
recorded. The TSS was defined as the sum of the individual symptom scores except 
for the nasal blockage score, as nasal blockage was not expected to respond to
antihistamine treatment. Only patients with a total symptom score > or = 6 were
included in the study. There was a statistically significant improvement at p <
0.01 for the TSS with or without blocked nose and for each symptom score such as 
blocked nose, sneezing, rhinorrhea, itchy nose/palate and/or throat, and
itchy/watery/red eyes from baseline to week 1 and week 2. Additionally, there was
a statistically significant improvement between week 1 and week 2 for itchy
nose/palate and/or throat and itchy/watery/red eyes (p < 0.05). The Kappa measure
of agreement was statistically significant at p < 0.001 between investigator's
and patient's/parent's assessment, indicating the same degree of satisfaction
with the overall effectiveness of the treatment. Fexofenadine 30 mg bid is
effective in reducing the total symptom score of allergic rhinitis including
blocked nose and is generally well tolerated. It is not cardiotoxic and is safe
for pediatric patients as young as 6 years of age.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16572735 [PubMed - indexed for MEDLINE]

596: J Clin Pharmacol. 2006 Apr;46(4):461-7.

Safety, tolerability, and exposure of ciclesonide nasal spray in healthy and
asymptomatic subjects with seasonal allergic rhinitis.

Nave R, Wingertzahn MA, Brookman S, Kaida S, Matsunaga T.

ALTANA Pharma AG, Byk-Gulden-Str. 2, 78467 Konstanz, Germany.

Ciclesonide is an intranasal corticosteroid in development for the treatment of
allergic rhinitis. To assess the safety, tolerability, and pharmacokinetics of
ciclesonide, adult healthy volunteers and asymptomatic subjects with seasonal
allergic rhinitis were randomized to receive intranasal ciclesonide or placebo
for 14 days. Serum concentrations of ciclesonide and its active metabolite,
desisobutyryl-ciclesonide, were measured using high-performance liquid
chromatography assay with tandem mass spectrometric detection, with lower limits 
of quantification of 25 and 10 pg/mL, respectively. Adrenal function was
monitored by diurnal serum free and 24-hour urine cortisol concentrations.
Despite the use of a sensitive assay and a high ciclesonide dose (800 microg/d), 
serum levels of ciclesonide and desisobutyryl-ciclesonide were below the lower
limits of quantification for the majority of samples assayed. Ciclesonide was
well tolerated and did not appear to affect serum or urine free cortisol levels. 
The low systemic exposure and favorable safety profile support the continued
clinical development of ciclesonide nasal spray.

Publication Types: 
    Clinical Trial, Phase I
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16554455 [PubMed - indexed for MEDLINE]

597: Rhinology. 2006 Mar;44(1):68-73.

Hyperresponsiveness of congestive nasal reflexes in allergic rhinitis.

Sheahan P, Walsh RM, Walsh MA, Costello RW.

Department of Otorhinolaryngology, Royal College of Surgeons in Ireland, Dublin, 
Ireland.

BACKGROUND: Nasal secretory hyperresponsiveness is well documented in allergic
rhinitis, and is mediated in part by neural mechanisms. In contrast,
reflex-mediated congestion is poorly documented in both normal and allergic
subjects. OBJECTIVE: To characterize congestive responses to unilateral nasal
bradykinin challenge in normal and allergic subjects, and to investigate whether 
congestive hyperresponsiveness is present in allergic rhinitis. METHODS: Normal
subjects (n = 13), and subjects with out-of-season seasonal allergic rhinitis
(SAR) (n = 16) underwent a unilateral nasal challenge protocol using filter paper
disks, using Hartman's solution and bradykinin as challenge substances.
Congestive responses were measured using acoustic rhinometry. RESULTS: Normal
subjects demonstrated a transient ipsilateral congestive response, and a
circumscribed contralateral congestive response away from the major flow limiting
section. Subjects with SAR demonstrated a more persistent ipsilateral congestive 
response, and a more pronounced, generalized contralateral congestive response
affecting all areas of the contralateral nasal cavity. Significant differences
were present between normal and SAR subjects. CONCLUSION: Congestive reflexes are
present in normal and allergic subjects. Congestive hyperresponsiveness is
present in allergic rhinitis.

PMID: 16550954 [PubMed - indexed for MEDLINE]

598: Pulm Pharmacol Ther. 2007;20(3):244-9. Epub 2006 Mar 10.

The effect of 4 weeks treatment with desloratadine (5mg daily) on levels of
interleukin (IL)-4, IL-10, IL-18 and TGF beta in patients suffering from seasonal
allergic rhinitis.

Tworek D, Bocheńska-Marciniak M, Kupczyk M, Górski P, Kuna P.

Division of Pneumonology and Allergy, Medical University of Lodz, 22 Kopcińskiego
Str., 90-153 Lodz, Poland.

Anti-inflammatory effect of desloratadine (DL), including, but not limited to
depression of production of IL-4, IL-6 and IL-8, has been shown in several in
vitro experiments but only a few in vivo studies refer to this findings. The
purpose of our study was to evaluate the influence of DL on levels of IL-4,
IL-10, IL-18 and TGF-beta in sera of patients with seasonal allergic rhinitis
(SAR). Sixty-nine subjects suffering from SAR with hypersensitivity to grass
pollen were included into the evaluation of clinical efficacy of DL (5mg once
daily). None of them was taking any H(1) receptor antagonist during the pollen
season before inclusion into the study. Samples of peripheral blood were taken
before and after 4 weeks of treatment. Levels of cytokines were determined using 
the ELISA method. The mean level of IL-4 was 0.212+/-0.07pg/ml before and
0.221+/-0.1pg/ml after the treatment (p=0.52); IL-10 5.13+/-3.14 and 4.71+/-0.88 
(p=0.69); IL-18 54.45+/-26.09 and 44.80+/-22.42 (p=0.48); TGF beta 949.17+/-401.5
and 955.7+/-391.2 (p=0.97)pg/ml before and after the treatment, respectively.
Unless in vitro DL demonstrates not only anti-allergic but also anti-inflammatory
activities data from this in vivo study in a group of patients suffering from SAR
do not support previous pre-clinical findings.

Publication Types: 
    Clinical Trial

PMID: 16530440 [PubMed - indexed for MEDLINE]

599: J Med Genet. 2006 Mar;43(3):e10.

Highly significant linkage to chromosome 3q13.31 for rhinitis and related
allergic diseases.

Brasch-Andersen C, Haagerup A, Børglum AD, Vestbo J, Kruse TA.

BACKGROUND: Allergic diseases such as asthma and rhinitis have closely related
phenotypes and often occur with atopy. They show strong familial and
intra-individual clustering, suggesting overlapping disease aetiology. Various
loci and candidate genes have been suggested to underlie allergy. Many or all are
still inconclusive. Following genome-wide scans on multiple phenotypes, we
previously suggested that chromosome 3q13.12-q21.2 harbours an allergy locus.
OBJECTIVE: To identify candidate loci in the Danish population, two additional
independent sets of sib-pair families were fine-scale mapped in candidate regions
showing maximum likelihood scores (MLS) > or =1.5 in the genome-wide scans.
RESULTS: Twenty eight microsatellite markers in a denser map on chromosome 3q
were analysed in 236 allergy sib-pair families including 125 sib pairs with
rhinitis. We report significant evidence for linkage to chromosome 3q13.31 for
rhinitis (MLS 5.55, identity by descent (IBD) 63.9%) and atopy (increased
specific immunoglobulin E) (MLS 3.71, IBD 61.7%). We obtained an MLS of 5.1 (IBD 
67.3%) at 3q13.31 when sib pairs with both rhinitis and atopy were analysed.
CONCLUSION: This study reports the first statistically significant evidence for a
genetic susceptibility locus for rhinitis and to our knowledge shows the most
significant evidence to date of linkage for any allergy phenotype.

Publication Types: 
    Letter
    Research Support, Non-U.S. Gov't

PMID: 16525028 [PubMed - indexed for MEDLINE]

600: J Hum Genet. 2006;51(4):292-7. Epub 2006 Mar 4.

Identification of single nucleotide polymorphisms in FOXJ1 and their association 
with allergic rhinitis.

Li CS, Chae SC, Lee JH, Zhang Q, Chung HT.

Department of Microbiology and Immunology, School of Medicine, Wonkwang
University, Iksan, 570-749, Chonbuk, South Korea.

Forkhead-box J1 (FOXJ1) is a presumed transcription factor that can suppress T
cell activity, at least partially, through the repression of NFkappaB activity.
Thus, dysregulation of FOXJ1 is thought to be associated with autoimmune diseases
and/or other inflammatory diseases. To investigate the association between single
nucleotide polymorphisms (SNPs) of human FOXJ1 and allergic rhinitis, we scanned 
the whole human FOXJ1 gene, including the promoter region, by direct sequencing
of DNA from 32 individuals. We identified seven SNPs, three of which (g.-460C>T, 
g.1805G>T, and g.3375G>C) were chosen for large sample size genotyping (n=713),
and to assess the genotype frequencies of these SNPs between controls and
allergic rhinitis patients. We also investigated the relationships of each
genotype with serum total IgE levels in allergic rhinitis patients, and compared 
the frequencies of haplotypes constructed by these SNPs between the two groups.
Our results suggest that the SNPs g.-460C>T, g.1805G>T and g.3375G>C in the human
FOXJ1 gene might be associated with susceptibility to allergic rhinitis
(P=0.0184, 0.0076, and 0.0143, respectively). The main haplotype, CGG, also
revealed a significant association with allergic rhinitis (P=0.000018). However, 
no significant association was found between serum total IgE levels and the
genotypes of these polymorphisms.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16518568 [PubMed - indexed for MEDLINE]

601: J Asthma. 2006 Mar;43(2):165-7.

Links between bronchial asthma and allergic rhinitis in the Oita Prefecture,
Japan.

Matsuno O, Miyazaki E, Takenaka R, Ando M, Ito T, Sawabe T, Shigenaga T, Ito K,
Sugisaki K, Kumamoto T.

Division of Pulmonary Medicine, Department of Brain and Nerve, Oita University
Faculty of Medicine, Oita, Japan. matsuno@med.oita-u.ac.jp

Recent studies have strengthened the concept that bronchial asthma and allergic
rhinitis are manifestations of an inflammatory process within a continuous
airway. This study was performed to compare clinical findings in asthma with or
without rhinitis in Japan. Nasal symptoms were present in 99.6% of asthma
patients. The prevalence of allergic rhinitis in patients with asthma was 52.4%. 
Bronchial asthma attacks in one third of patients with rhinitis were coincident
with worsening of nasal symptoms. In adults (> 16 years of age), rhinitis
frequently preceded asthma, whereas asthma preceded rhinitis in children (< 16
years of age). The frequency of rhinitis in asthma decreases with increasing age.
This study demonstrated a clear link between upper and lower airway disorders in 
Japan.

Publication Types: 
    Comparative Study

PMID: 16517435 [PubMed - indexed for MEDLINE]

602: J Biotechnol. 2006 Jul 25;124(3):602-14. Epub 2006 Mar 3.

Protective efficiency of dendrosomes as novel nano-sized adjuvants for DNA
vaccination against birch pollen allergy.

Balenga NA, Zahedifard F, Weiss R, Sarbolouki MN, Thalhamer J, Rafati S.

Department of Biotechnology, Faculty of Science, University of Tehran, Tehran,
Iran.

We evaluated the use of a novel gene porter (Den123--a nontoxic self-assembled
dendritic spheroidal nanoparticle made of biodegradable monomers), aiming to
enhance and improve the desired immune response in protection from allergy.
Footpad DNA immunization in Balb/c mice was done three times using the Bet v 1a
gene with or without Den123 with 2-week intervals followed by sensitization with 
rBetv1 (5 microg) in alum twice in a weekly interval. Different doses of
pCMV-Betv1 were used (10 microg and 100 microg). The protective role of different
formulations was evaluated by measuring the IgG1, IgG2a and IgE antibody
production, cytokine release of isolated splenocytes and beta-hexosaminidase
release from the RBL cells. Higher and increasing ratios of IgG2a/IgG1 were seen 
in mice which received plasmids in combination with Den123. Den123 and DNA
vaccine synergistically enhanced the Interferon gamma released from splenocytes. 
In the presence of Den123, IgE inhibition was independent of the dose and type of
the injected DNA. All DNA-pre-immunized mice demonstrated low basophil
degranulation. It is therefore concluded that administration of the DNA entrapped
in Den123 nanoparticles results in sustained release of plasmids, Th1/Th2
balanced immune response with promising IgE inhibition. Also higher amounts of
DNA contributed to stronger Th1 response.

PMID: 16515817 [PubMed - indexed for MEDLINE]

603: Med J Malaysia. 2005 Dec;60(5):672-6; quiz 677.

Recent trends in the diagnosis and management of allergic rhinitis.

Elango S.

Department of Otolaryngology, International Medical University, Jalan Rasah,
70300, Seremban, Negeri Sembilan.

Allergic rhinitis is a global health issue and its prevalence is increasing.
Allergic rhinitis and asthma coexist in many patients. Allergic rhinitis is an Ig
E mediated reaction. Prostaglandins and Leukotriens do not play a significant
role in the pathogenesis of allergic rhinitis. Skin prick test and Enzyme linked 
immunosorbent assays (ELISA) are useful as diagnostic tests. The three major
modalities of treatment for allergic rhinitis are allergen avoidance,
pharmacotherapy and immunotherapy.

Publication Types: 
    Review

PMID: 16515128 [PubMed - indexed for MEDLINE]

604: Allergy. 2006 Apr;61(4):498-502.

Brassica oleracea pollen, a new source of occupational allergens.

Hermanides HK, Laheÿ-de Boer AM, Zuidmeer L, Guikers C, van Ree R, Knulst AC.

Department of Dermatology/Allergology, University Medical Center Utrecht,
Utrecht, The Netherlands.

BACKGROUND: Vegetable pollen is a rare source of occupational allergens.
Occupational allergy has only been described in the case of paprika pollen and
tomato pollen. We describe a new source of occupational pollen allergy. AIM: To
study the incidence and the impact of broccoli and cauliflower pollen allergy in 
employees involved in classical plant breeding. METHODS: Fifty-four employees of 
five companies working with cauliflower (Brassica oleracea botrytis) and broccoli
(B. oleracea italica/cymosa) pollen were eligible for complete evaluation.
Allergy to cauliflower and broccoli pollen was evaluated by questionnaire and
determination of sensitization by radioallergosorbent test (RAST) and skin-prick 
tests (SPT). SPT and RAST were performed with a panel of commercial and homemade 
extracts from cauliflower and broccoli pollen. RESULTS: Work-related symptoms
such as rhinitis, conjunctivitis, asthma and urticaria caused by B. oleracea
pollen were reported by 44% of the participants (24/54), of whom all but one had 
positive SPT for cauliflower- and/or broccoli-pollen/flower extracts and 58%
(14/24) had positive RAST results. Symptoms had developed within the first 2
years in 33% of the patients. Six patients had to stop or change work.
CONCLUSIONS: Brassica oleracea pollen is a new source of occupational allergen
with strong allergenic potential leading to symptoms in almost half of the
exposed employees.

PMID: 16512813 [PubMed - indexed for MEDLINE]

605: Allergy. 2006 Apr;61(4):461-76.

Pollen-food syndromes associated with weed pollinosis: an update from the
molecular point of view.

Egger M, Mutschlechner S, Wopfner N, Gadermaier G, Briza P, Ferreira F.

Department of Molecular Biology, Division of Allergy and Immunology, University
of Salzburg, Salzburg, Austria.

Pollinosis patients often display adverse reactions upon the ingestion of
plant-derived foods as a result of immunoglobulin E (IgE) cross-reactive
structures shared by pollen and food allergen sources. The symptoms of such
pollen-food syndromes (PFS) or class 2 food allergies range from local oral
allergy syndrome to severe systemic anaphylaxis. Two clinical syndromes, the
celery-mugwort-spice syndrome and the mugwort-mustard-allergy syndrome have been 
described in association with weed pollinosis. However, other associations
between weed pollinosis and hypersensitivity to certain kinds of food have also
been observed, like the mugwort-peach, the ragweed-melon-banana, the
plantain-melon, the pellitory-pistachio, the goosefoot-fruit, the Russian
thistle-saffron, and the hop-celery association. The number of allergen sources
involved, the allergens, and influencing factors including geography, diet, and
food preparation contribute to the high clinical complexity of PFS. So far, known
causative cross-reactive allergens include profilins, lipid transfer proteins,
and high-molecular weight allergens and/or glycoallergens. The current usage of
nonstandardized allergen extracts poses additional problems for both diagnosis
and therapy of PFS patients. Further identification and characterization of
involved allergens is inescapable for better understanding of PFS and vaccine
development. Panels of recombinant allergens and/or hypo-allergens are promising 
tools to improve both PFS diagnostics and therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16512809 [PubMed - indexed for MEDLINE]

606: Clin Exp Allergy. 2006 Mar;36(3):325-30.

Intranasal steroid reduces exhaled bronchial cysteinyl leukotrienes in allergic
patients.

Failla M, Biondi G, Provvidenza Pistorio M, Gili E, Mastruzzo C, Vancheri C,
Crimi N.

Department of Internal and Specialistic Medicine, Section of Respiratory
Medicine, University of Catania, Catania, Italy.

BACKGROUND: Allergic rhinitis (AR) precedes and is often associated with
bronchial asthma. Indeed, local and systemic inflammations in both conditions are
very similar. Cysteinyl-leukotrienes (cys-LTs) are generated during early- and
late-phase allergic reactions and induce smooth-muscle contraction, microvascular
leakage, and mucous hypersecretion. Cys-LTs are detected in exhaled breath
condensate (EBC) of asthmatics and regardless of bronchial symptoms, they are
also found in EBC of rhinitic patients. OBJECTIVE: To evaluate cys-LTs in EBC of 
allergic patients and to assess the activity of nasal fluticasone propionate (FP)
on EBC cys-LTs levels. METHODS: Cys-LTs coefficient of variation (CV) was
evaluated from different EBC in 5 healthy volunteers. Cys-LTs levels from EBCs in
13 healthy controls and 56 allergic rhinitic (n=31) and rhinitic/asthmatic (n=25)
patients were also evaluated at baseline. Subsequently patients were randomized
to receive either FP 100 microg/day per nostril or placebo for 2 weeks and then
re-evaluated for EBC cys-LTs. RESULTS: The CV was 14.12%. EBC cys-LTs in allergic
patients were significantly higher than in healthy subjects (70.9 vs. 20.6 pg/mL 
(median), P<0.05), while it did not differ between asthmatic/rhinitic and purely 
rhinitic patients. Treatment significantly reduced cys-LTs (from 93.6 to 19.9
pg/mL, P<0.001). This effect was evident both in asthmatic/rhinitic and in
rhinitic patients. CONCLUSION: Treatment of AR with FP significantly reduces the 
levels of cys-LTs, major noninvasive markers of lower airway inflammation,
suggesting that upper and lower airway inflammation is present and should be thus
treated as a whole in subjects with AR with and without asthma.

Publication Types: 
    Randomized Controlled Trial

PMID: 16499643 [PubMed - indexed for MEDLINE]

607: Clin Exp Allergy. 2006 Mar;36(3):283-92.

Immunological characteristics of subjects with asymptomatic skin sensitization to
birch and grass pollen.

Assing K, Nielsen CH, Poulsen LK.

Allergy Clinic, Department 7551, National University Hospital, Copenhagen,
Denmark. K.ASSING@RH.DK

BACKGROUND: Asymptomatic skin sensitization (AS) has been shown to be a risk
factor for respiratory allergic disease. OBJECTIVE: We investigated allergen and 
recall antigen-driven T cell proliferation, cytokine production and T cell
expression of the chemokine receptor CCR4, in cultures derived from symptomatic
atopics (SA), subjects with AS and healthy controls (HC). Numbers of
allergen-specific precursor T cells in all three groups were also estimated.
METHODS: Peripheral blood mononuclear cells from the three groups were isolated
and stimulated with allergen and tetanus toxoid. Proliferation, cytokine
production and CCR4 expression were measured by flow cytometry. RESULTS: A
significantly increased proportion of CD4(+) memory T cells proliferated in
response to allergen in SA as compared with subjects with AS (P<0.001) and HC
(P<0.001). Only in SA was expansion of CD4(+)CCR4(+) T cells, after allergen
stimulation observed. SA had higher frequencies of allergen-specific T cells than
subjects with AS and HC (P=0.02, for both). With regard to allergen-induced
production of T-helper type 1 (Th1) and Th2 cytokines, subjects with AS and HC
resembled each other, while differing significantly from SA. CONCLUSION: We
conclude, that subjects with AS, although clearly IgE sensitized, have
significant diminished numbers of allergen-specific T cells as well as decreased 
allergen-induced CD4(+) memory T cell proliferation as compared with SA. To a
large extent, our findings are capable of explaining the immunological
characteristics associated with AS. Our findings may serve as better prognostic
markers for subsequent allergic progression, than previously described clinical
and paraclinical characteristics.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16499638 [PubMed - indexed for MEDLINE]

608: Ann Allergy Asthma Immunol. 2006 Feb;96(2):363-8.

Effect of desloratadine therapy on symptom scores and measures of nasal patency
in seasonal allergic rhinitis: results of a single-center, placebo-controlled
trial.

Meltzer EO, Jalowayski AA, Vogt K, Iezzoni D, Harris AG.

Allergy and Asthma Medical Group and Research Center, San Diego, California
92123, USA. eomeltzer@aol.com

BACKGROUND: Desloratadine reduces symptoms and maintains nasal airflow in
patients with seasonal allergic rhinitis (SAR) during experimental allergen
exposure. OBJECTIVE: To compare the effects of desloratadine and placebo on
symptom scores, quality of life (QOL), and nasal airway patency in patients with 
SAR during the allergy season. METHODS: Adults with symptomatic SAR were
randomized in a double-blind manner to receive desloratadine, 5 mg, or placebo
for 14 days. Patient-rated SAR symptoms were recorded twice daily (morning and
evening). On days 1 and 15, SAR symptoms were scored jointly (investigator and
patient), nasal airflow was measured using 4-phase rhinomanometry, and QOL and
the overall condition of SAR were rated. Overall treatment response was scored on
day 15. Adverse events were recorded. RESULTS: At day 15, total symptom (P = .03)
and total nasal symptom (P = .02) scores and patient morning-rated individual
nasal symptom scores (except nasal stuffiness) (P < or = .04) decreased
significantly from baseline with desloratadine vs placebo. Flow in the descending
expiratory nasal airflow phase was significantly greater (P = .046) and the
percentage increase in total inspiratory nasal airway resistance was less (P =
.03) in the desloratadine group vs the placebo group. The overall condition of
SAR was less severe (P = .045), the therapeutic response was greater (P = .004), 
and the nasal symptom domain of the QOL score was significantly better (P = .03) 
in the desloratadine group. Adverse event rates were similar in both groups.
CONCLUSION: Desloratadine treatment for 14 days improved nasal airflow and
resistance as well as symptom and QOL scores in patients with symptomatic SAR
during the allergy season.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16498861 [PubMed - indexed for MEDLINE]

609: Ann Allergy Asthma Immunol. 2006 Feb;96(2):263-77; quiz 277-8, 315.

Comment in:
    Ann Allergy Asthma Immunol. 2006 Feb;96(2):255.

Experimental models for the evaluation of treatment of allergic rhinitis.

Day JH, Ellis AK, Rafeiro E, Ratz JD, Briscoe MP.

Division of Allergy and Immunology, Kingston General Hospital, Kingston, Ontario,
Canada. dayj@kgh.kari.net

OBJECTIVE: To review the experimental models used for the clinical evaluation of 
treatments for allergic rhinitis. DATA SOURCES: Peer-reviewed clinical studies
and review articles were selected from the PubMed database using the following
relevant keywords: allergic rhinitis in combination with efficacy, wheal and
flare, nasal challenge, park, cat room, or exposure unit. Regulatory guidance
documents on allergic rhinitis were also included. STUDY SELECTION: The authors' 
knowledge of the field was used to limit references with emphasis on recent
randomized and controlled studies. References of historical significance were
also included. RESULTS: Traditional outpatient studies are universally accepted
in the evaluation of treatment for allergic rhinitis. Experimental models provide
ancillary information on efficacy at different stages of treatment development.
Skin histamine and allergen challenge, as well as direct nasal challenge with
histamine and allergen, are often used as early steps in assessing drug efficacy.
Exposure units, park settings, and cat rooms better approximate real life by
drawing on the natural mode of allergen exposure and delivering the sensitizing
allergen to allergic individuals in the ambient air. Park studies make use of
allergens in the outdoors, whereas cat rooms and exposure units present the
sensitizing allergens indoors, with the latter providing consistent predetermined
allergen levels. Exposure unit and park studies are acknowledged for the
determination of onset of action and are also suited to the measurement of
duration of effect and other measures of efficacy. Onset and duration of effect
are 2 important pharmacodynamic properties of antihistamines and nasal
corticosteroids as determined by the Allergic Rhinitis and Its Impact on Asthma
and the European Academy of Allergology and Clinical Immunology workshop group.
CONCLUSIONS: All challenge models serve as important instruments in the
evaluation of antiallergic medications and provide additional information to
complement traditional studies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16498847 [PubMed - indexed for MEDLINE]

610: Mil Med. 2005 Dec;170(12):1026-8.

Allergic rhinitis in the Middle East.

Waibel KH.

Allergy and Immunology Service, Department of Medicine, Dwight D. Eisenhower Army
Medical Center, Fort Gordon, GA 30905-5650, USA.

BACKGROUND: Current military operations in the Middle East involve active duty,
National Guard, and reserve troops from all services. Despite common
misconceptions, the desert environment in this region has significant
aeroallergen seasons that may exacerbate allergic rhinitis. OBJECTIVE: To review 
perennial and seasonal aeroallergen trends in the Middle East. RESULTS: Most
countries have significant grass and weed pollen seasons during April to May and 
September to October, respectively. Indigenous trees such as date palm, acacia,
and mesquite have specific pollen seasons from March to May. Mold allergens are
perennial with seasonal peaks, whereas house dust mite is common in humid coastal
regions. CONCLUSIONS: Seasonal and perennial allergens observed in the United
States are also found in the Middle East. Furthermore, the prevalence of allergic
rhinitis in these countries suggests that local aeroallergens exacerbate
symptoms. Health care providers should counsel deploying soldiers with allergic
rhinitis regarding relevant allergen trends, ensuring that these individuals have
appropriate medications.

PMID: 16491940 [PubMed - indexed for MEDLINE]

611: Arch Otolaryngol Head Neck Surg. 2006 Feb;132(2):164-72.

Comparison of montelukast and pseudoephedrine in the treatment of allergic
rhinitis.

Mucha SM, deTineo M, Naclerio RM, Baroody FM.

Section of Otolaryngology-Head and Neck Surgery, The Pritzker School of Medicine,
The University of Chicago, Chicago, IL 60637, USA.

OBJECTIVE: To compare montelukast sodium and pseudoephedrine hydrochloride in the
treatment of seasonal allergic rhinitis. DESIGN: A 2-week, parallel, randomized, 
double-blind study with rolling enrollment. SETTING: Tertiary care medical
center. PATIENTS: A total of 58 adult subjects with ragweed allergic rhinitis as 
documented by positive findings on a skin test to ragweed and history of symptoms
during previous seasons. INTERVENTIONS: After recording their own baseline nasal 
symptoms, nasal peak inspiratory flow (NPIF), and diurnal and nocturnal
rhinoconjunctivitis quality of life (QOL) scores, subjects were randomized to
receive daily morning oral doses of either pseudoephedrine hydrochloride (240 mg)
or montelukast sodium (10 mg) for 2 weeks. They recorded their nasal symptoms and
NPIF twice daily during this time, and at the end of the study, they completed
another QOL questionnaire and 2 tolerability profiles. MAIN OUTCOME MEASURES:
Nasal symptoms, NPIF, QOL scores, and tolerability profiles. RESULTS: Both active
treatments resulted in significant improvements from baseline in all symptoms of 
allergic rhinitis as well as in all the domains of the QOL questionnaires. When
changes from baseline were compared between treatments, there were no significant
differences except in the symptom of nasal congestion, for which pseudoephedrine 
was more effective than montelukast. Both treatments resulted in a significant
increase in NPIF over baseline with no significant difference between treatments.
Both drugs were well tolerated with no differences in the tolerability profiles
between treatments. CONCLUSIONS: Pseudoephedrine and montelukast are equivalent
in improving symptoms and QOL and increasing nasal airflow in patients with
seasonal allergic rhinitis. The lack of the usual adverse effects in the
pseudoephedrine group is ascribed to morning dosing.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16490874 [PubMed - indexed for MEDLINE]

612: Respir Res. 2006 Feb 9;7:23.

Relation between air pollution and allergic rhinitis in Taiwanese schoolchildren.

Hwang BF, Jaakkola JJ, Lee YL, Lin YC, Guo YL.

School and Graduate Institute of Occupational Safety and Health, College of
Public Health, China Medical University, 91, Hsueh-Shih Road, Taichung, 40402,
Taiwan. bhwang@dwu.edu.tw

BACKGROUND: Recent findings suggest that exposure to outdoor air pollutants may
increase the risk of allergic rhinitis. The results of these studies are
inconsistent, but warrant further attention. The objective of the study was to
assess the effect of relation between exposure to urban air pollution and the
prevalence allergic rhinitis among school children. METHODS: We conducted a
nationwide cross-sectional study of 32,143 Taiwanese school children. We obtained
routine air-pollution monitoring data for sulphur dioxide (SO2), nitrogen oxides 
(NOx), ozone (O3), carbon monoxide (CO), and particles with an aerodynamic
diameter of 10 microm or less (PM10). A parent-administered questionnaire
provided information on individual characteristics and indoor environments
(response rate 92%). Municipal-level exposure was calculated using the mean of
the 2000 monthly averages. The effect estimates were presented as odds ratios
(ORs) per 10 ppb change for SO2, NOx, and O3, 100 ppb change for CO, and 10
microg/m3 change for PM10. RESULTS: In two-stage hierarchical model adjusting for
confounding, the prevalence of allergic rhinitis was significantly associated
with SO2 (adjusted odds ratio (OR) = 1.43, 95% confidence interval (CI): 1.25,
1.64), CO (aOR = 1.05, 95% CI: 1.04, 1.07), and NOx (aOR = 1.11, 95% CI: 1.08,
1.15). Contrary to our hypothesis, the prevalence of allergic rhinitis was weakly
or not related to O3 (aOR = 1.05, 95% CI: 0.98, 1.12) and PM10 (aOR = 1.00, 95%
CI: 0.99, 1.02). CONCLUSION: Persistent exposure to NOx, CO, and SO2 may increase
the prevalence of allergic rhinitis in children.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16469096 [PubMed - indexed for MEDLINE]

613: Curr Med Res Opin. 2006 Feb;22(2):275-85.

A double blind, placebo controlled trial of inert cellulose powder for the relief
of symptoms of hay fever in adults.

Emberlin JC, Lewis RA.

National Pollen and Aerobiology Research Unit, Institute of Health, University of
Worcester, Worcester, WR2 6AJ, UK. j.emberlin@worc.ac.uk

OBJECTIVE: An inert cellulose powder has been on sale in the UK since 1994 as a
remedy for hay fever but no scientific trials have been conducted previously. It 
is applied to the inside of the nose where it forms a gelatinous coating. The
principal aim was to determine if there is a significant difference in the amount
and type of rescue medication required for adult hay fever sufferers to control
their symptoms while using either the inert cellulose powder or a placebo. The
second objective was to see whether the cellulose powder resulted in an
improvement in symptom control. RESEARCH DESIGN: A double blind, placebo
controlled study was conducted of 97 adult hay fever sufferers, over the grass
pollen season of 2004. Participants (selectively recruited to be living within
the catchment area of a 50-km radius from Worcester, UK) were assigned randomly
to two groups (A, Active and B, Placebo) matched by age by decades and gender. Of
those completing the trial, group A had 19 males and 28 females and group B had
21 males and 29 females. There were no significant differences between the groups
in age distributions, severity of symptoms over the last 2 years or in medication
taken. They completed daily symptom diary score cards and were allowed to take
any medications they wished in addition to the inert cellulose powder or placebo 
because medication use was taken as an outcome measure. Results were analysed in 
relation to pollen counts. RESULTS: Significant differences were found in the
amounts of rescue medication taken by the active and placebo groups (p < 0.05).
More people in the placebo group took rescue treatments than those in the active 
group.No significant differences were found (p < 0.01) between the active and
placebo groups in Likert scores for any of the rhinitis nasal symptoms or in the 
total Likert symptom daily scores. No adverse events were reported during the
study. CONCLUSIONS: The amount of rescue medication taken by the placebo group
was significantly more than that taken by the active group both overall,
considering all types of medication, and also in the individual cases of
antihistamines, nasal sprays and eye drops. These results provide evidence that
the inert cellulose powder reduces the need to take rescue medication for the
symptoms of hay fever.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16466599 [PubMed - indexed for MEDLINE]

614: Int J Mol Med. 2006 Mar;17(3):511-5.

Evaluation of the anti-allergic activity of Citrus unshiu using rat basophilic
leukemia RBL-2H3 cells as well as basophils of patients with seasonal allergic
rhinitis to pollen.

Kobayashi S, Tanabe S.

Department of Food and Life-Science, Takasaki University of Health and Welfare,
Japan.

The anti-allergic activity of the 50% methanol extract of Citrus unshiu powder
(MEC) was examined. Fifty percent methanol extract of MEC powder showed potent
inhibitory activity against histamine release from basophils of patients
suffering from seasonal allergic rhinitis to ceder pollen. To examine this
anti-allergic mechanism in detail, we next used rat basophlilic leukemia RBL-2H3 
cells. MEC significantly inhibited IgE-induced histamine and beta-hexosaminidase 
release from RBL-2H3 cells. Since MEC contains a variety of flavonoids, we
selected nobiletin, hesperetin, and hesperidin (hesperetin glycoside) as
representative compounds, and further evaluated these inhibitory activities.
Among the flavonoids tested, hesperetin was the most potent, while hesperidin had
far less, if any, inhibitory activity. The mechanism by which flavonoids
inhibited the degranulation process was then examined. As a result, hesperetin
and nobiletin suppressed the phosphorylation of Akt-1, direct downstream effector
of phosphatidylinositol 3-kinase (PI3-K). Thus, it was assumed that these
flavonoids suppressed IgE-mediated stimulation of basophils through PI3-K pathway
and that proper intake of Citrus unshiu would be favorable for managing seasonal 
allergic rhinitis to ceder pollen.

PMID: 16465400 [PubMed - indexed for MEDLINE]

615: Respiration. 2007;74(2):184-91. Epub 2006 Feb 1.

Chlorine in breath condensate--a measure of airway affection in pollinosis?

Davidsson A, Soderstrom M, Sjosward KN, Schmekel B.

Faculty of Health Sciences, Department of Medicine and Care, Section of Clinical 
Physiology, University Hospital, Linkoping, Sweden. anette.davidsson@lio.se

BACKGROUND: Infiltration of inflammatory cells in bronchial mucosa and glandular 
hypersecretion are hallmarks of asthma. It has been postulated that exhaled
breath condensate (EBC) mirrors events in epithelial lining fluid of airways,
such as presence of local inflammation as well as glandular hypersecretion. It is
also well known that eosinophil cationic protein (ECP) and cysteinyl-leukotrienes
(cys-LT) are released by circulating inflammatory cells when triggered by antigen
stimulation in asthma patients. OBJECTIVES: The aim of this study was to evaluate
whether chlorine and/or cys-LT in EBC would reflect changes of exposure of
airborne pollen in patients with asthma. Methods: EBC and serum were collected
from 23 patients with allergic asthma during a pollen season and repeated 5
months later during a period with no aeroallergens. Chlorine was measured by
means of a sensitive coulometric technique and cys-LT by an EIA technique. Serum 
ECP was measured and lung function tests were performed and symptoms noted during
both occasions. RESULTS: Significantly higher concentrations of chlorine in EBC
(p = 0.007) and ECP in serum (p = 0.003) were found during the pollen season
compared to post-season. Chlorine levels tended to be higher in patients who
reported of chest symptoms compared to those who denied symptoms during the
pollen season (p = 0.06). Areas under the receiver-operated characteristic curves
(AUC(ROC)) were compared and similar discriminative power to identify
exacerbations of asthma was recorded by chlorine in EBC (range 0.67-0.78) and ECP
in serum (range 0.64-0.78). CONCLUSION: It is concluded that chlorine in EBC and 
ECP in serum decreased significantly post-season, and this is suggested to mirror
the decrement in airborne antigen. It is furthermore proposed that chlorine in
EBC and ECP in serum tend to have a similar capacity to identify seasonal
variations in airborne pollen in patients with asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16462136 [PubMed - indexed for MEDLINE]

616: J Allergy Clin Immunol. 2006 Feb;117(2):319-25.

Efficacy and safety of specific immunotherapy with SQ allergen extract in
treatment-resistant seasonal allergic rhinoconjunctivitis.

Frew AJ, Powell RJ, Corrigan CJ, Durham SR; UK Immunotherapy Study Group.

Allergy & Inflammation Research Subdivision, School of Medicine, University of
Southampton, UK. ajf@eaaci.org

BACKGROUND: Specific immunotherapy is widely used to treat allergic rhinitis, but
few large-scale clinical trials have been performed. OBJECTIVE: We sought to
assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard 
grass pollen in patients with moderately severe seasonal allergic rhinitis
inadequately controlled with standard drug therapy. METHODS: We performed a
double-blind, randomized, placebo-controlled study of 410 subjects (203
randomized to 100,000 standardized quality units [SQ-U] maintenance, 104 to
10,000 SQ-U, and 103 to placebo). Three hundred forty-seven (85%) completed
treatment. Groups were well matched for demographics and symptoms. RESULTS:
Across the whole pollen season, mean symptom and medication scores were 29% and
32% lower, respectively, in the 100,000-SQ-U group compared with those in the
placebo group (both P < .001). Over the peak pollen season, mean symptom and
medication scores were 32% and 41% lower, respectively, than those in the placebo
group. The 10,000-SQ-U group had 22% less symptoms than the placebo group over
the whole season (P < .01), but medication scores reduced by only 16% (P = .16). 
Quality-of-life measures confirmed the superiority of both doses to placebo.
Local and delayed side effects were common but generally mild. Clinically
significant early and delayed systemic side effects were confined to the
100,000-SQ-U group, but no life-threatening reactions occurred. CONCLUSIONS: One 
season of immunotherapy with Alutard grass pollen reduced symptoms and medication
use and improved the quality of life of subjects with moderately severe hay
fever. The 100,000-SQ-U regimen was more effective, but the 10,000-SQ-U regimen
caused fewer side effects.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16461133 [PubMed - indexed for MEDLINE]

617: J Allergy Clin Immunol. 2006 Feb;117(2):263-8.

Grass pollen immunotherapy as an effective therapy for childhood seasonal
allergic asthma.

Roberts G, Hurley C, Turcanu V, Lack G.

University Child Health, University of Southampton, Hants, UK.
g.c.roberts@soton.ac.uk

BACKGROUND: Few studies have investigated the use of specific immunotherapy (SIT)
for childhood seasonal allergic asthma. OBJECTIVE: We sought to examine the
efficacy and safety of SIT with Alutard SQ grass pollen (Phleum pratense Alutard 
SQ; ALK-Abelló, Hørsholm, Denmark) in children with seasonal allergic asthma.
METHODS: A randomized, double-blind, placebo-controlled study assessing the
efficacy of grass pollen SIT over 2 pollen seasons was performed. Children (3-16 
years) with a history of seasonal allergic asthma sensitized to grass pollen (P
pratense) and requiring at least 200 microg of inhaled beclomethasone equivalent 
per day were enrolled. Subjects with symptomatic asthma or rhinoconjunctivitis
outside the grass pollen season were excluded. The primary outcome measure was a 
combined asthma symptom-medication score during the second pollen season.
Secondary outcome measures included end-point titration skin prick testing and
conjunctival and bronchial provocation testing to allergen, sputum eosinophilia, 
exhaled nitric oxide, and adverse events. RESULTS: Thirty-nine subjects were
enrolled. Thirty-five subjects provided data for analysis. The use of SIT was
associated with a substantial reduction in asthma symptom-medication score
compared with that after placebo (P = .04). There were also significant
reductions in cutaneous (P = .002), conjunctival (P = .02), and bronchial (P =
.01) reactivity to allergen after SIT compared with that after placebo. The 2
groups had similar levels of airway inflammation, despite a trend toward less
inhaled steroid use in the active group. No serious adverse events were reported,
and no subjects withdrew because of adverse events. CONCLUSION: The study has
shown that SIT is effective and well tolerated in children with seasonal allergic
asthma to grass pollen.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16461125 [PubMed - indexed for MEDLINE]

618: J Proteome Res. 2006 Feb;5(2):330-8.

Comparative proteomics of nasal fluid in seasonal allergic rhinitis.

Ghafouri B, Irander K, Lindbom J, Tagesson C, Lindahl M.

Division of Occupational and Environmental Medicine, Department of Molecular and 
Clinical Medicine, Linköping University, Sweden.

A comparative proteomic approach was applied to examine nasal lavage fluid (NLF) 
from patients with seasonal allergic rhinitis (SAR, n = 6) and healthy subjects
(controls, n = 5). NLF samples were taken both before allergy (pollen) season and
during season, and proteins were analyzed by two-dimensional gel electrophoresis 
(2-DE) and matrix assisted laser desorption/ionization time-of-flight mass
spectrometry (MALDI-TOF MS) after tryptic cleavage. Twenty proteins were selected
and quantified. During allergy season, the levels of six sialylated isoforms of
PLUNC (palate lung nasal epithelial clone) were lower in SAR patients than
controls, as were the levels of six isoforms of von Ebner's gland protein (VEGP),
including a previously undescribed form with N-linked glycosylation, and of
cystatin S. PLUNC is a new innate immunity protein and VEGP and cystatin S are
two endogenous proteinase inhibitors. By contrast, the levels of an acidic form
of alpha-1-antitrypsin were higher in SAR patients than controls. One previously 
unidentified NLF protein was found in all samples from the SAR patients during
allergy season but not in any sample before allergy season: this protein was
identified as eosinophil lysophospholipase (Charcot-Leyden crystal
protein/galactin 10). MS/MS analysis of the N-terminus of the protein showed
removal of Met and acetylation of Ser. Altogether, these findings illustrate the 
potential use of proteomics for identifying protein changes associated with
allergic rhinitis and for revealing post-translational modifications of such new 
potential markers of allergic inflammation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16457599 [PubMed - indexed for MEDLINE]

619: Ann Agric Environ Med. 2005;12(2):173-6.

Nasal provocative test in patients allergic to pollen.

Wojdas A, Rapiejko P, Zielnik-Jurkiewicz B, Kantor I.

Department of Otolaryngology, Military Medical Institute, Warsaw, Poland.
awojdas@lekarz.net

Nasal provocative test (NPT) can be defined as a method for recreating upper
respiratory tract response to natural allergens or irritants. It can be used in
solving nasal patophisiology problems: establishing whether and how the patient's
nose is sensitive to antigens or irritants; quantitative evaluation of
sensitivity; establishing factors influencing sensitivity. This method is
employed to confirm clinical diagnosis in cases where difficulties arise in
interpretation of diagnostic tests. The study based on nasal provocative tests
establish an allergy to pollen in cases of pollinosis, and select appropriate
components for the desensitising vaccine. Sample group included 53 patients, 29
were females and 24 were males, aged 15-42 years, selected from 1,021 patients
diagnosed between 1999-2002 in the Allergology Department of the ENT Department
of the MMI. The sample patients were diagnosed based on additional tests with
allergic inflammation of the nasal mucosa caused by allergy to pollen of such
plants as birch, grass, rye, mugwort and plantain. Research methods included:
subjective physical examination, prick tests, total and specific IgE levels in
serum, nasal provocative tests and rhinomanometric examination. Allergen solution
was administered onto the mucosa with a calibrated atomiser. NPT solutions
containing pollen of birch, grass, rye, mugwort and plantain were used.
Provocative test was considered positive if, following allergen provocation,
rhinomanometric examination revealed an increase in respiratory resistance by at 
least 40 % in comparison with the control test. On the basis of the study, 2
conclusions were drawn: 1) Nasal provocative test is an essential element in
diagnostics of allergic nasal obstruction. 2) Rhinomanometry, as an objective
method of examining nasal patency, is crucial for evaluating the nasal
provocative test.

Publication Types: 
    Clinical Trial

PMID: 16457469 [PubMed - indexed for MEDLINE]

620: Otolaryngol Head Neck Surg. 2006 Feb;134(2):255-9.

Nasal airflow recovery after decongestion test is associated with bronchial
hyperreactivity in patients with allergic rhinitis.

Ciprandi G, Cirillo I, Klersy C, Vizzaccaro A, Tosca MA, Marseglia GL.

Azienda Ospedaliera Universitaria San Martino, Genoa, Italy. gio.cip@libero.it

BACKGROUND: The decongestion test involves spraying an intranasal vasoconstrictor
drug to evaluate the recovery of nasal airflow. OBJECTIVE: The aim of this study 
was to assess the relationship between pulmonary function (assessed by spirometry
and methacholine challenge) and nasal airflow recovery after a topical
vasoconstrictor had been administered in patients with allergic rhinitis
(perennial, seasonal, or mixed allergic rhinitis). METHODS: A total of 150
subjects were studied. The total symptom score, sensitization, and pulmonary
function were all assessed. All subjects underwent rhinomanometry and the
decongestion test. RESULTS: Univariate analysis revealed that nasal symptoms and 
spirometric parameters (except FEF(25-75) in subjects with seasonal allergic
rhinitis) were not. Only bronchial hyperreactivity, assessed by methacholine
challenge, proved to be significantly (and independently) associated with outcome
(OR 1.45, P = 0.025). CONCLUSIONS: This study provides the first evidence of an
association between a positive response to the decongestion test and bronchial
hyperreactivity, assessed by methacholine challenge, in patients with allergic
rhinitis.

PMID: 16455374 [PubMed - indexed for MEDLINE]

621: Eur Ann Allergy Clin Immunol. 2005 Nov;37(9):345-9.

Analysis of the positivity rate in IgE positive patients to food allergens in
Verona Hospital laboratory during 2003.

Caruso B, Senna GE, Rizzotti P.

Laboratory of Clinical Chemistry, Ospedale Civile Maggiore Borgo Trento, Verona.

BACKGROUND: It has been known for some time now that reactions to allergens, not 
only those inhaled but also those in food, varies with age in atopical patients. 
OBJECTIVE: To evaluate the specific IgE positivity percentage in order to improve
laboratory diagnosis in subjects with suspected food allergy. METHODS: The
positivity percentages of specific IgE were analysed (UniCAP100-Pharmacia) taking
into consideration the two age brackets of below and above 12 years. The below 12
years age bracket was then further divided into pre-school age (3-5 years) and
school age (6-12 years). RESULTS: By measuring the simple positivity percentage
for specific IgE to food allergens, there is a clear decrease as the child
matures in reactions to milk and eggs and an increase towards food IgEs that
cross-react with grass and tree pollens or other inhaled allergens like moulds
and mites. CONCLUSION: It will be necessary in the future to have the diagnostic 
means to identify this cross-reaction problem by using recombinant allergens that
can demonstrate the combined reaction between inhaled and food allergens.

Publication Types: 
    Comparative Study

PMID: 16453967 [PubMed - indexed for MEDLINE]

622: Allergy Asthma Proc. 2005 Sep-Oct;26(5):391-6.

Efficacy and safety of desloratadine/pseudoephedrine tablet, 2.5/120 mg two times
a day, versus individual components in the treatment of patients with seasonal
allergic rhinitis.

Chervinsky P, Nayak A, Rooklin A, Danzig M.

Northeast Medical Research Associates, 49 State Road, Suite 203, North Dartmouth,
MA 02747, USA.

Although antihistamines are highly effective in alleviating many symptoms
associated with seasonal allergic rhinitis (SAR), relief from nasal congestion is
variable. The efficacy of desloratadine, an effective antihistamine, in
combination with pseudoephedrine, a potent nasal decongestant, was evaluated to
determine whether combination therapy was more effective than individual
component therapy in reducing nasal congestion, as well as other SAR symptoms.
This multicenter, randomized, double-blind, three-arm study included 650 patients
with SAR. For 2 weeks, patients were administered a combination tablet of
desloratadine plus pseudoephedrine (desloratadine/pseudoephedrine, 2.5/120 mg)
twice per day (b.i.d.), desloratadine (5 mg) once per day, or pseudoephedrine
(120 mg) b.i.d. Patients assessed the severity of their SAR symptoms twice daily 
on symptom diary cards. The primary variable-change from baseline in the
reflective A.M./P.M. total symptom score, excluding nasal congestion-was
significantly superior (-6.7) compared with desloratadine (-5.4) or
pseudoephedrine (-5.3) alone (p < or = 0.001 versus either group). Secondary
efficacy variables including total symptom scores (plus congestion), total nasal 
symptom scores, and total nonnasal symptom scores were significantly reduced
after desloratadine/pseudoephedrine therapy compared with the individual
components. The most frequently reported adverse events were insomnia, headache, 
and dry mouth. Desloratadine/pseudoephedrine, 2.5/120 mg b.i.d., therapy was more
effective in reducing total symptom scores of SAR, including nasal congestion,
than were the individual components. These results support the use of this
combination therapy over desloratadine or pseudoephedrine alone.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial

PMID: 16450574 [PubMed - indexed for MEDLINE]

623: Allergy Asthma Proc. 2005 Sep-Oct;26(5):382-90.

An approach of immunoneurological aspects in nasal allergic late phase.

Jordan TR, Rasp G, Pfrogner E, Kramer MF.

Department of Otorhinolaryngology-Head and Neck Surgery,
Ludwig-Maximilians-University, Munich, Germany.

This examination is an approach of the allergic early phase reaction (EPR) and
late-phase reaction (LPR) via quality of life (QoL), acoustic rhinometry, and
eosinophilic cationic protein (ECP), interleukin (IL)-5, and leukotriene C4
(LTC4). Results are discussed under consideration of a possible neurological
participation in the occurrence and persistence of the allergic inflammatory
process. Thirteen patients suffering from seasonal allergic rhinitis were
challenged intranasally by their specific allergen. In a time window of 8 hours
after provocation, patients completed QoL questionnaires, and underwent acoustic 
rhinometry. Nasal secretions were analyzed for total protein, ECP, IL-5, and LTC4
The need to sneeze and a runny nose were the strongest symptoms during the EPR
and LPR. Restriction of overall QoL persisted much longer than any other symptom.
Evaluation of acoustic rhinometry revealed an EPR in 100% and a LPR in 92%. The
EPR was marked by increases in volume of nasal secretions, total protein, and
elevations in LTC4. Allergic LPR was marked by increases in nasal secretions,
total protein, ECP, IL-5, and LTC4. Both the need to sneeze as strongest and
announcing symptom of the allergic LPR and the persisting restriction in overall 
QoL seem to propose a possible neurological participation in the development of
the allergic late-phase inflammation and consequent hyperresponsiveness of the
nasal mucosa. In addition, the persistence and enhancement of the nasal cycle
during the allergic LPR can be interpreted in favor of a hypothetical activation 
of the autonomous nervous system. LTC4 enters this discussion as a promising link
at the immunoneurological interface.

PMID: 16450573 [PubMed - indexed for MEDLINE]

624: Allergy Asthma Proc. 2005 Sep-Oct;26(5):352-5.

Conifer pollen sensitivity in western New York: cedar pollens.

Deane PM.

University of Rochester, Rochester, New York, USA.

Cedar pollens might be significant allergens in areas where they have not been so
considered but are prevalent. Eastern red cedar (Juniperus virginiana) and white 
cedar (Thuja occidentalis, American arbor vitae) are common plants in western New
York. We analyzed skin test results from 158 patients with asthma, rhinitis, or
both; 102 had positive skin tests to at least one pollen. Among those, 52
patients (51%) had positive skin tests to at least one of the cedar pollens.
Patients sensitive on skin testing to cedar pollen were strongly likely (p <
0.0001) to be sensitive to deciduous tree, grass, or ragweed pollen. Sensitivity 
on skin testing to indigenous cedar pollens is common in our area of western New 
York and therefore could be clinically significant.

PMID: 16450568 [PubMed - indexed for MEDLINE]

625: Allergy Asthma Proc. 2005 Sep-Oct;26(5):336-40.

The relationships of rhinitis and asthma.

Meltzer EO.

Allergy and Asthma Medical Group and Research Center, 9610 Granite Ridge Drive,
Suite B, San Diego, CA 92123, USA.

Rhinitis and asthma are common airway conditions; however, recent data suggest
that they both can be clinical manifestations of a systemic inflammatory process 
within the respiratory tract. The link between these two airway disorders has
been called the "integrated airway hypothesis." Several epidemiological studies
have established an association between rhinitis and asthma, and approximately
19-38% of patients with allergic rhinitis have coexistent asthma. Additionally,
an understanding of the biology of the two airway disorders suggests that
systemic inflammation after local allergen challenge links the upper and lower
airways. More recently, data from clinical studies in patients with rhinitis and 
coexistent asthma have highlighted that an improved control of nasal symptoms
frequently results in improved asthma symptom scores. To clarify the
relationships between upper and lower airway disorders and to establish the
potential benefits of an integrated airways management approach, additional
studies are warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16450565 [PubMed - indexed for MEDLINE]

626: Eur J Obstet Gynecol Reprod Biol. 2007 Mar;131(1):21-7. Epub 2006 Jan 25.

Population-based case-control study of allergic rhinitis during pregnancy for
birth outcomes.

Somoskövi A, Bártfai Z, Tamási L, Kocsis J, Puhó E, Czeizel AE.

Department of Respiratory Medicine, School of Medicine, Semmelweis University,
Budapest, Hungary. akos@pulm.sote.hu <akos@pulm.sote.hu>

OBJECTIVE: Allergic rhinitis is frequent in women of childbearing age including
pregnancy. The present study aimed to estimate the effect of maternal allergic
rhinitis on birth outcomes, in particular congenital abnormalities, preterm birth
and low birthweight newborns. STUDY DESIGN: Analysis of the population-based data
of the Hungarian Case-Control Surveillance of Congenital Abnormalities between
1980 and 1996. RESULTS: The evaluation of data did not reveal any teratogenic
potential of allergic rhinitis and indeed a lower prevalence of total congenital 
abnormalities was found. In addition, a protective effect could be observed for
preterm birth due to longer gestational age (adjusted t=2.97, p=0.003).
CONCLUSION: Allergic rhinitis is not risk factor for pregnant women.

PMID: 16442692 [PubMed - indexed for MEDLINE]

627: Ann Allergy Asthma Immunol. 2006 Jan;96(1):92-7.

Impact of occupational and inhalant allergy on rhinitis-specific quality of life 
in employees of bell pepper greenhouses in the Netherlands.

Groenewoud GC, de Groot H, van Wijk RG.

Department of Allergology, Erasmus Medical Center, Rotterdam, the Netherlands.
g.groenewoud@erasmusmc.nl

BACKGROUND: Rhinitis symptoms among bell pepper greenhouse employees can be
caused by an allergy to occupational allergens, such as bell pepper pollen and
predatory mites, and common inhalant allergens. OBJECTIVES: To estimate the
effect of sensitization to these allergens on rhinitis-specific quality of life
(QoL) during and outside the flowering period and to evaluate whether the QoL of 
sensitized employees is comparable with that of chrysanthemum greenhouse
employees with rhinitis and an average population sample with perennial rhinitis.
METHODS: We invited 233 employees with rhinitis symptoms to complete 2 rhinitis
QoL questionnaires and to undergo skin prick testing with common inhalant
allergens and occupational allergen extracts. Multiple regression analysis was
used to estimate the impact of sensitization to the various allergens on QoL.
RESULTS: Sensitization to bell pepper pollen had a significant negative effect on
all the domain and mean QoL scores. The other allergens had no effect on QoL. A
significant decrease in all the rhinitis scores was found outside the flowering
period. There were no relevant differences in the mean scores of the different
domains for both occupational groups. Greenhouse employees scored higher on
limitations in activities and much lower on emotional, sleeping, and practical
problems compared with individuals with perennial rhinitis. CONCLUSIONS: Bell
pepper greenhouse employees are impaired in QoL because of their sensitization to
bell pepper pollen, suggesting that bell pepper pollen is the most important
occupational allergen in greenhouse workers with allergic symptoms. A common
allergy does not have more impact on a person's day-to-day life than an
occupational allergy; however, there is a clear difference in the way in which an
occupational group is hampered compared with a nonoccupational group.

Publication Types: 
    Comparative Study

PMID: 16440539 [PubMed - indexed for MEDLINE]

628: Ann Allergy Asthma Immunol. 2006 Jan;96(1):69-75.

Physician-diagnosed asthma and allergic rhinitis in Manitoba: 1985-1998.

Dik N, Anthonisen NR, Manfreda J, Roos LL.

Department of Community Health Sciences, Faculty of Medicine, University of
Manitoba, Winnipeg, Manitoba. natdik@cpe.umanitoba.ca

BACKGROUND: A worldwide increase has been noted in the prevalence of asthma, but 
the data for other allergic disorders are less consistent. OBJECTIVE: To study
14-year trends in utilization of physician resources for asthma and compare them 
to trends for allergic rhinitis. METHODS: We studied visits to physicians by
Manitoba residents for asthma (International Classification of Diseases, Ninth
Revision, Clinical Modification [ICD-9-CM] code 493) and allergic rhinitis (ICD-9
code 477) between 1985 and 1998. Prevalence and incidence of physician resources 
utilization were calculated annually for the total population and by age groups. 
Aggregate statistics and frequency of physician resources utilization were also
analyzed. RESULTS: The prevalence and incidence of physician resources
utilization for asthma increased more than for allergic rhinitis; differences
were most striking in the youngest age groups. In adults, the differences were
smaller and changed little with time. Most of the increase in asthma care
occurred in children and in people without allergic rhinitis. Overall, 17% of
Manitobans were diagnosed as having asthma, and the average asthmatic patient
made 6 visits. Approximately 14% had an allergic rhinitis diagnosis, each person 
being seen twice on average. Coexistence of asthma and allergic rhinitis led to
increased physician resources utilization for each of the conditions.
CONCLUSIONS: Trends in utilization of physician resources for allergic rhinitis
differed strikingly from trends for asthma, particularly in the youngest age
group. Asthma and allergic rhinitis affected comparable proportions of the
population, but a diagnosis of asthma resulted in much higher utilization of
physician resources. The relationship of physician-diagnosed asthma and atopy, as
indicated by the diagnosis of allergic rhinitis, appears to have weakened with
time in children but not in adults.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16440535 [PubMed - indexed for MEDLINE]

629: Ann Allergy Asthma Immunol. 2006 Jan;96(1):60-8.

Efficacy of montelukast during the allergy season in patients with chronic asthma
and seasonal aeroallergen sensitivity.

Busse WW, Casale TB, Dykewicz MS, Meltzer EO, Bird SR, Hustad CM, Grant E, Zeldin
RK, Edelman JM.

Department of Medicine, University of Wisconsin Medical School, Madison,
Wisconsin 53792, USA. wwb@medicine.wisc.edu

BACKGROUND: Montelukast has proven efficacy in the treatment of chronic asthma
and seasonal allergic rhinitis, but it has not been evaluated in the
subpopulation of asthmatic patients with seasonal asthma symptoms. OBJECTIVE: To 
determine the effectiveness of montelukast treatment in improving the control of 
asthma symptoms during the allergy season in patients with active asthma and
seasonal aeroallergen sensitivity. METHODS: Adults with a history of chronic
asthma who are also symptomatic during the allergy season and with skin test
sensitivity to seasonal aeroallergens were enrolled in a randomized,
parallel-group, multicenter study with a 1-week, single-blind, placebo run-in
period followed by 3 weeks of double-blind treatment during the spring of 2004.
After the run-in period, eligible patients were randomly assigned to receive
either oral montelukast (10 mg) or placebo. Daytime and nighttime asthma symptom 
scores, beta-agonist use, and morning and evening peak expiratory flow rates were
recorded daily using an electronic diary. The primary end point was mean change
from baseline to week 3 in the daytime asthma symptom score. RESULTS: Of 455
randomized patients, 433 completed the study. Compared with placebo, treatment
with montelukast resulted in a significant improvement from baseline in the
daytime asthma symptom score (-0.54 vs -0.34; P = .002) and in beta-agonist use, 
nighttime symptoms, and peak expiratory flow rates. Few patients in the
montelukast and placebo groups discontinued study participation because of asthma
(1.3% and 3.0%, respectively). CONCLUSION: In patients with chronic asthma and
seasonal aeroallergen sensitivity, montelukast treatment provided significant
asthma control during the allergy season compared with placebo.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16440534 [PubMed - indexed for MEDLINE]

630: Ann Allergy Asthma Immunol. 2006 Jan;96(1):37-44.

Effects of rupatadine vs placebo on allergen-induced symptoms in patients exposed
to aeroallergens in the Vienna Challenge Chamber.

Stuebner P, Horak F, Zieglmayer R, Arnáiz E, Leuratti C, Pérez I, Izquierdo I.

Allergy Centre Vienna West, Vienna, Austria.

BACKGROUND: Rupatadine is a novel compound with potent dual antihistamine and
platelet-activating factor antagonist activities and no sedative effects.
OBJECTIVE: To evaluate the efficacy of rupatadine, 10 mg once daily, and placebo 
on allergen-induced symptoms (including nasal congestion), nasal airflow, nasal
secretion, and subjective tolerability in response to grass pollen in a
controlled allergen-exposure chamber. METHODS: In a randomized, double-blind,
placebo-controlled, crossover trial, 45 patients with a history of seasonal
allergic rhinitis received rupatadine or placebo every morning for 8 days in 2
different periods separated by a 14-day washout interval. On day 8 of each
crossover period, patients underwent a 6-hour allergen exposure in the Vienna
Challenge Chamber, where a constant and homogeneous concentration of
aeroallergens was maintained. Subjective and objective assessments were performed
online during the exposure. RESULTS: Subjective single and composite nasal and
nonnasal symptoms were consistently less severe with rupatadine use than with
placebo use starting from the first evaluation at 15 minutes to the end of the
6-hour Vienna Challenge Chamber challenge, with the most significant effects seen
for nasal rhinorrhea, nasal itching, sneezing attacks, and total nasal symptoms
(P < .001 for all). All the other symptoms (including nasal congestion, P < or = 
.005) were also significantly reduced with active treatment compared with placebo
use. Mean secretion weights and overall feeling of complaint were significantly
lower with rupatadine therapy than with placebo use (P < or = .001). Overall,
rupatadine treatment was well tolerated. CONCLUSION: Rupatadine treatment is
effective and well tolerated in patients with allergen-induced symptoms exposed
to aeroallergens in a controlled exposure chamber.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16440531 [PubMed - indexed for MEDLINE]

631: Int Arch Allergy Immunol. 2006;139(3):175-80. Epub 2006 Jan 26.

Prophylactic intranasal treatment with fragments of 1,3-beta-glucanase olive
pollen allergen prevents airway inflammation in a murine model of type I allergy.

Palomares O, Batanero E, Cañamero M, Villalba M, Rodríguez R.

Departamento de Bioquímica y Biología Molecular, Facultad de Química, Universidad
Complutense de Madrid, and Departamento de Anatomía Patológica, Hospital Ruber
Internacional, Spain.

BACKGROUND:Olive pollen is an important cause of allergy in Mediterranean
countries. More than 50% of olive-pollen-allergic patients are sensitized against
the 1,3-beta-glucanase Ole e 9. To date, prophylactic and therapeutic treatments 
using purified recombinant allergens have not been studied in animal models of
olive pollen allergy. METHODS: BALB/c mice were immunized against Ole e 9
combining intraperitoneal injections of the allergen in Al(OH)3 with airway
allergen challenges. A prophylactic treatment was performed by intranasal
administration of a mixture of the recombinant fragments of the allergen prior to
Ole e 9 sensitization. Serum levels of specific IgE, IgG1, IgG2a and IgG2b were
measured by ELISA, and total IgE levels by sandwich ELISA. Bronchoalveolar lavage
and lungs from mice were collected to study airway inflammation by light
microscopy. RESULTS: BALB/c mice immunized against Ole e 9 developed a
predominantly Th2-like immune response with allergen-specific immunoglobulin
induction and airway inflammation accompanied by the infiltration of eosinophils,
lymphocytes, and neutrophils in the lung. Prophylactic treatment by intranasal
application of the recombinant fragments of Ole e 9 avoids airway inflammation
induced by sensitization with this allergen although the levels of Ole e
9-specific antibodies remain unchanged. CONCLUSIONS: Prophylactic intranasal
treatment with recombinant fragments of Ole e 9 prevents airway inflammation
triggered by immunization to this allergen in a murine model of type I allergy.
Copyright (c) 2006 S. Karger AG, Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16439855 [PubMed - indexed for MEDLINE]

632: J Investig Allergol Clin Immunol. 2005;15(4):277-82.

Influence of age and gender on serum eotaxin concentration in healthy and
allergic people.

Targowski T, Jahnz-Rózyk K, Plusa T, Glodzinska-Wyszogrodzka E.

Department of Internal Medicine, Pneumonology and Allergology, Military Institute
of Medicine, Warsaw, Poland. tomasz.targowski@xl.wp.pl

BACKGROUND: Eotaxin is one of the important chemokines that modulate allergic
inflammation. In many studies a correlation between an elevated serum
concentration of eotaxin, allergen exposure and allergic symptoms has been
confirmed. Influence of other factors on eotaxin concentration is feebly
recognized. We made an attempt to assess the influence of age and gender on the
serum eotaxin level in healthy people and in patients with intermittent
IgE-mediated rhinoconjunctivitis (AR). METHODS: The serum eotaxin level was
measured in 245 healthy people and 241 patients with AR before the pollen season 
with the ELISA technique (KITS, R&D USA, pg/ml). The parametric tests and linear 
regression analysis were used in statistical calculations. RESULTS: There were no
differences between the allergic group and the healthy one in the mean age
(accordingly: 31.3 +/- 11.6 yrs. vs. 31.6 +/- 12.5 yrs.; p=0.1) and the mean
serum eotaxin content (118.1 +/- 44.9 pg/ml vs. 116.3 +/- 34.8 pg/ml; p=0.3). A
significant relationship between the serum eotaxin level, gender and age was
revealed in both groups and regression models were derived. A linear correlation 
between age (semi-partial correlation beta = 0.47, p = 0.0000001) and gender
(semi-partial correlation beta = 0.3, p = 0.0000001), on the one side, and the
serum eotaxin level, on the other, was found for the allergic people. In the
control group a similar relationship between the serum eotaxin level and age
(semi-partial correlation coefficient beta = 0.63, p = 0.0000001) and gender
(semi-partial correlation factor beta = 0.23, p = 0.000006) was observed.
CONCLUSIONS: Age and sex significantly influence the serum eotaxin content in
healthy people and patients with IgE-mediated rhinoconjunctivitis.

PMID: 16433209 [PubMed - indexed for MEDLINE]

633: Mol Immunol. 2006 May;43(12):1927-32. Epub 2006 Jan 23.

Recombinant glutathione-S-transferase a major allergen from Alternaria alternata 
for clinical use in allergy patients.

Shankar J, Singh BP, Gaur SN, Arora N.

Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.

Recombinant proteins are used for vaccines, therapy and diagnosis of many
diseases. Biological activity of these may differ from native counterpart and
needs investigation. The present study aimed to compare recombinant (r) and
native (n) glutathione-S-transferase (GST) from Alternaria alternata.
Glutathione-S-transferase sequence showed an ORF of 696bp encoding 26-kDa protein
with N-terminus conserved domain. Secondary structure of both forms was
comparable with melting temperature of 57 and 59 degrees C, respectively. rGST
and nGST showed similar enzymatic activity, allergenicity and potency by ELISA
inhibition. Histamine release was comparable in 14/17 patients for both the GSTs.
rGST and nGST induced proliferation in PBMC at different concentration. Cell
supernatant revealed higher IL-4 and IL-5 levels with low levels of IFN-gamma. In
summary, recombinant and native GST demonstrated similar physio-chemical,
biological and immunological properties and induced comparable cell mediated and 
humoral response to be used for diagnosis and specific immunotherapy for the
fungal allergy cases.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16430961 [PubMed - indexed for MEDLINE]

634: Pediatr Allergy Immunol. 2006 Feb;17(1):11-6.

Association between neopterin in cord blood, urinary neopterin in early childhood
and the development of atopic dermatitis, asthma and hay fever.

Horak E, Murr C, Streif W, Schroecksnadel K, Schennach H, Fuchs D.

Division of Biological Chemistry Biocentre, University Hospital for Children and 
Adolescents, Anichstrasse 35, A-6020 Innsbruck, Austria.
elisabeth.horak@uklibk.ac.at

It is generally accepted that the increased prevalence of atopic disease is due
to a disturbed balance of T-helper (Th)1/Th2-type immunity. Upon stimulation by
the Th1-type cytokine interferon (IFN)-gamma, human monocytes/macrophages release
large amounts of neopterin. Thus, the determination of neopterin concentrations
is an indirect measure of the levels of IFN-gamma and allows us to monitor
Th1-type immune response. We evaluated whether neopterin concentrations in the
neonatal cord blood could be a valuable marker predicting atopic disease in early
childhood and whether there is a difference in actually determined urinary
neopterin concentrations in children with and without atopic disease. Five
hundred and five children born during 1997-1999 were enrolled, with cord blood
neopterin data available at birth. The International study of asthma and
allergies in childhood (ISAAC) questionnaire was used to assess the prevalence of
wheezy bronchitis (asthma), atopic dermatitis and allergic rhinitis. Morning
urinary samples were collected and urinary neopterin concentration was measured
by high-pressure liquid chromatography. By the average age of 6 yr, the
prevalence of atopic disease in the last 12 months was 31%. There was no
significant correlation between cord blood and urinary neopterin concentrations
at age 6 yr, and between cord blood neopterin and later atopic disease. Urinary
neopterin concentrations were significant lower in children with a family history
of atopic disease (p = 0.02). In this study, cord blood neopterin concentration
was not a predictor for atopic disease in early childhood. Family history of
atopic disease was associated with lower urinary neopterin levels at age 6 yr,
which might mirror a Th1/Th2 imbalance.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16426249 [PubMed - indexed for MEDLINE]

635: Coll Antropol. 2005 Dec;29(2):671-6.

Poaceae pollen concentrations in the atmosphere of three inland Croatian sites
(2003-2004).

Peternel R, Hrga I, Hercog P, Culig J.

Zagreb Public Health Institute, Zagreb, Croatia.
renata.peternel@publichealth-zagreb.hr

The aim of the study was to determine the length of Poaceae pollen season,
intradiurnal, daily and monthly pollen variation, and the effect of some
meteorological parameters on atmospheric pollen concentration, at three
monitoring sites in inland Croatia during the 2003-2004 period. Seven-day Hirst
volumetric pollen and spore traps were used for pollen sampling. At all three
monitoring sites considerably higher precipitation and lower average temperature 
in 2004 led to a marked decrease in the grass pollen concentration in the air at 
all three monitoring sites. The highest grass pollen concentrations were recorded
in Ivanić Grad (typical rural area), considerably lower in Samobor (effect of
forest vegetation), and lowest in Zagreb (urban area). The highest atmospheric
Poaceae pollen concentrations in inland Croatia were generally recorded in May
and June. The highest intradiurnal concentrations were recorded between 8.00 and 
12.00 a.m. Results of this aeropalynologic study are expected to help in
preventing the symptoms of allergic reaction in individuals with Poaceae pollen
hypersensitivity.

Publication Types: 
    Multicenter Study

PMID: 16417180 [PubMed - indexed for MEDLINE]

636: Allergy. 2006 Feb;61(2):198-201.

Twelve-year follow-up after discontinuation of preseasonal grass pollen
immunotherapy in childhood.

Eng PA, Borer-Reinhold M, Heijnen IA, Gnehm HP.

Department of Pediatrics, Kantonsspital Aarau, Aarau, Switzerland.

BACKGROUND: In a previous controlled study, we demonstrated that preseasonal
grass pollen immunotherapy for 3 years was effective in children. Moreover, a
significant clinical benefit could still be observed 6 years after
discontinuation of specific immunotherapy (SIT). In the current study, we
examined the same group of patients again to investigate whether there is a
prolonged benefit 12 years after SIT is stopped. METHODS: Twenty-two patients
with previous SIT (from 1989 through 1991) or standardized seasonal
pharmacotherapy only were prospectively followed during the grass pollen season
of 2003. Primary end points were symptom score, medication use, and combined
symptom and medication score. In addition, skin prick test reactivity,
development of new sensitizations, and prevalence of seasonal asthma were
evaluated. RESULTS: Total hay fever symptom score (P < 0.03), use of medication
(P < 0.05), and combined symptom and medication score (P < 0.03) remained lower
in patients with previous SIT when compared with the control group. Decreased
immediate skin response to grass pollen returned 12 years after cessation of SIT.
The percentage of new sensitization, however, continued to be significantly
smaller in patients with previous SIT (58%) compared with the controls (100%, P <
0.05). There was a tendency for lower prevalence of seasonal asthma in the
post-SIT group (P = 0.08). CONCLUSION: This prospective controlled prolonged
follow-up study demonstrates the ongoing clinical benefit 12 years after
discontinuation of SIT. Furthermore, the reduction in onset of new sensitization,
which was found 6 years after discontinuation of SIT, is sustained 6 years later.

PMID: 16409196 [PubMed - indexed for MEDLINE]

637: Allergy. 2006 Feb;61(2):185-90.

Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics 
with rhinoconjunctivitis.

Dahl R, Stender A, Rak S.

Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Denmark.

BACKGROUND: The best way to prevent allergy symptoms is to treat the allergic
condition. Specific immunotherapy with grass allergen tablets 75,000 SQ-T
(Grazax, Phleum pratense, ALK-Abelló) is safe and efficacious in
rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma,
we aimed to confirm safety and efficacy in grass allergic subjects with asthma
and rhinoconjunctivitis. METHODS: A randomized, double-blind, placebo-controlled,
multicentre trial was performed 10-14 weeks prior to and during the grass pollen 
season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets
or placebo. The primary end points were average asthma medication and symptom
scores during the grass pollen season, and secondary variables were average
rhinoconjunctivitis symptom and medication scores during the grass pollen season.
Additionally, number of well days was defined post hoc. RESULTS: Differences in
asthma medication and symptom scores between the treatment groups were
negligible. The mean difference in asthma medication score was below 0.1 and 0.3 
for asthma symptom score [a single inhalation of salbutamol (200 microg) was
scored 2]. No serious adverse events were reported. A reduction in
rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036)
reduction in medication score was found in the grass pollen season for subjects
treated with the grass allergen tablet compared with placebo. Well days increased
by 54% (P = 0.002). CONCLUSIONS: Self-administration of the grass allergen tablet
was safe. The treatment did not impair asthma control and confirmed considerable 
symptom prevention and reduced medication use. It addresses the allergic
condition and represents a baseline treatment for grass pollen allergy.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 16409194 [PubMed - indexed for MEDLINE]

638: Allergy. 2006 Feb;61(2):181-4.

Safety of a SQ-standardised grass allergen tablet for sublingual immunotherapy: a
randomized, placebo-controlled trial.

Kleine-Tebbe J, Ribel M, Herold DA.

Allergy and Asthma Center Westend, Berlin, Germany.

BACKGROUND: Sublingual treatment of grass pollen induced rhinoconjunctivitis
might provide easier access to specific immunotherapy (SIT) and minimize the risk
of serious adverse events (AEs) compared to subcutaneous SIT. AIM OF THE STUDY:
To identify a safe dose range for once-daily administration of a grass allergen
tablet in participants with grass pollen induced seasonal rhinoconjunctivitis.
METHODS: A randomized, double blind, placebo-controlled Phase I trial was
conducted outside the grass pollen season. Seven dosage groups [25,000, 75,000,
150,000, 300,000, 500,000, 750,000, or 1,000,000 standardized quality tablet
(SQ-T)], consisting of 12 participants randomized either to active treatment or
placebo (3 : 1) daily for 28 days, commenced treatment in a staggered manner at
intervals of approximately 1 week to allow for intermittent safety reviews.
RESULTS: The grass allergen tablet did not cause any serious, systemic or
significant (leading to withdrawal) AEs. The overall incidence of AEs was 74%
(1,013 events); all of mild or moderate intensity and most considered
treatment-related. The most frequently reported treatment-related AEs, including 
irritation of the throat, and itching sensations in the mouth and ears, increased
with dose. These were primarily mild in intensity, started shortly after
medication intake and lasted for minutes to a few hours maximum. Objective oral
findings were also dose-dependent. No clinically significant observations were
found in safety laboratory, vital signs and 12-lead ECG. CONCLUSIONS: A
sublingual grass allergen tablet in doses up to 1,000,000 SQ-T daily caused no
serious or systemic AEs displaying a safety profile that allows further
investigation as once-daily self-medication.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16409193 [PubMed - indexed for MEDLINE]

639: Allergy. 2006 Feb;61(2):173-80.

The role of Foxp3+ T cells in long-term efficacy of prophylactic and therapeutic 
mucosal tolerance induction in mice.

Winkler B, Hufnagl K, Spittler A, Ploder M, Kállay E, Vrtala S, Valenta R, Kundi 
M, Renz H, Wiedermann U.

Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology
and Pathophysiology, Medical University of Vienna, Vienna, Austria.

BACKGROUND: Mucosal tolerance induction is suggested as treatment strategy for
allergic diseases. Using a murine model of birch pollen (BP) allergy we
investigated the long-term efficacy and the underlying mechanisms of mucosal
tolerance induction with two structurally different molecules in a prophylactic
and in a therapeutic set-up. METHODS: The three-dimensional major BP allergen Bet
v 1 or a nonconformational hypoallergenic fragment thereof was intranasally
applied before (prophylaxis) or after sensitization (therapy). RESULTS: In the
prophylactic application both the Bet v 1 allergen and the fragment prevented
allergic sensitization, and this effect lasted for 1 year. In the therapeutic
approach established allergic immune responses were also suppressed after
treatment with either of the molecules. However, a long-lasting curative effect
(6 months) was only achieved with the Bet v 1 allergen but not with the Bet v 1
fragment. Real-time reverse transcriptase polymerase chain reaction (RT-PCR)
analysis of splenocytes revealed that tolerance induction with the Bet v 1
allergen was associated with enhanced expression of transforming growth factor
(TGF)-beta, interleukin (IL)-10, and Foxp3 mRNA in CD4+ T cells, whereas
treatment with the fragment led to the induction of either Foxp3 (prophylaxis) or
IL-10 (therapy) alone. CONCLUSION: From these data we concluded (i) that the
mechanisms underlying peripheral tolerance are linked to the conformation of the 
antigen, (ii) that mucosal tolerance is mediated by separate regulatory cell
subsets, and (iii) that the long-term efficacy of immunosuppression is associated
with the presence of Foxp3+ T cells.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16409192 [PubMed - indexed for MEDLINE]

640: J Photochem Photobiol B. 2006 Apr 3;83(1):21-6. Epub 2006 Jan 10.

PUVA treatment of the nasal cavity improves the clinical symptoms of allergic
rhinitis and inhibits the immediate-type hypersensitivity reaction in the skin.

Csoma Z, Koreck A, Ignacz F, Bor Z, Szabo G, Bodai L, Dobozy A, Kemeny L.

Department of Dermatology and Allergology, University of Szeged, P.O. Box 427,
H-6701 Szeged, Hungary.

We earlier reported that intranasal irradiation with the 308 nm xenon chloride
(XeCl) ultraviolet-B laser and irradiation with a combination of ultraviolet-B
(UVB), ultraviolet-A (UVA) and visible light (VIS) is highly effective in the
treatment of allergic rhinitis and inhibit the immediate-type hypersensitivity
reaction in the skin. Since photochemotherapy with 8-methoxypsoralen (8-MOP) plus
UVA light (PUVA) is widely used in the treatment of different inflammatory skin
disorders due to its immunosuppressive effect, in the present study we
investigated the efficacy of intranasal PUVA treatment in allergic rhinitis and
the effect of PUVA treatment on the skin prick test (SPT) reaction. An open study
was performed in 17 patients with hay fever. Intranasal PUVA therapy was given
four times weekly for 3 weeks. The treatment was started with a fluence of 0.5x
of the individual minimal phototoxic dose (MPD) and the dosages were gradually
increased. Evaluation was based on the symptom scores. The effect of PUVA
treatment on the allergen-induced wheal formation was also studied in the SPT.
PUVA treatment of the nasal cavity significantly decreased the nasal symptoms of 
the patients with allergic rhinitis. Treatment of the skin with PUVA also
significantly suppressed the allergen-induced wheal formation in the SPT
reaction. These data suggest that intranasal PUVA phototherapy is also an
effective modality in the treatment of allergic rhinitis.

Publication Types: 
    Clinical Trial

PMID: 16406552 [PubMed - indexed for MEDLINE]

641: Ann Epidemiol. 2006 Aug;16(8):614-21. Epub 2006 Jan 10.

Dietary intake of seaweed and minerals and prevalence of allergic rhinitis in
Japanese pregnant females: baseline data from the Osaka Maternal and Child Health
Study.

Miyake Y, Sasaki S, Ohya Y, Miyamoto S, Matsunaga I, Yoshida T, Hirota Y, Oda H; 
The Osaka Maternal And Child Health Study Group.

Department of Public Health, Fukuoka University School of Medicine, Japan.
miyake-y@cis.fukuoka-u.ac.jp

PURPOSE: It may be worthwhile to assess the possible protective effect of the
traditional Japanese diet on allergic disorders. This cross-sectional study
investigated the relationship between dietary intake of seaweed, vegetables,
fruit, antioxidants, fiber, and minerals and the prevalence of allergic rhinitis.
METHODS: Study subjects were 1002 Japanese pregnant women. Allergic rhinitis
(including cedar pollinosis) was defined as present if subjects had received drug
treatment at some point during the previous 12 months. Information on dietary
factors was collected by using a self-administered diet history questionnaire.
RESULTS: Seaweed intake was associated independently with a decreased prevalence 
of allergic rhinitis. Significant inverse dose-response relationships were found 
between calcium and phosphorus intake and allergic rhinitis prevalence. There
also was a tendency for an inverse association between magnesium consumption and 
allergic rhinitis. Additional adjustment for calcium or magnesium intake
apparently did not influence the inverse association with seaweed consumption.
Consumption of vegetables, fruit, vitamins C and E, fiber, and zinc showed no
association with allergic rhinitis, whereas a significant positive relationship
was observed between beta-carotene intake and allergic rhinitis. CONCLUSIONS:
High dietary intake of seaweed, calcium, magnesium, and phosphorus may be
associated with a decreased prevalence of allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16406247 [PubMed - indexed for MEDLINE]

642: Rhinology. 2005 Dec;43(4):266-70.

Inhibitory effects of facemasks and eyeglasses on invasion of pollen particles in
the nose and eye: a clinical study.

Gotoh M, Okubo K, Okuda M.

Department of Otorhinolaryngology, Nippon Medical School Chiba Hokusoh Hospital, 
Chiba, Japan. m.gotoh@nms.ac.jp

The incidence of Japanese cedar pollinosis is estimated to be about 13% of the
Japanese population. In Japan it is generic to wear a facemask and eyeglasses to 
prevent pollen inhalation. We examined the usefulness of a facemask and
eyeglasses in cooperation with volunteers. The number of pollen particles in the 
nasal cavity and on the conjunctiva was unchanged by wearing a facemask and
eyeglasses. However, the pollen invasion rate was lower in subjects with a
facemask and eyeglasses than in subjects without a facemask and eyeglasses. The
decrease in pollen invasion rate in the nasal cavity due to wearing a facemask
was statistically significant. This suggested that wearing a facemask has a
protective effect on pollen invasion to the nose. The pollen invasion rate in the
nasal cavity and on the conjunctiva was increased with increases in the wind
speed. It may be difficult to avoid pollen even when wearing a facemask and
eyeglasses when the wind speed is high. Further study is required to clarify the 
relationship between the amount of allergens and clinical symptoms.

PMID: 16405270 [PubMed - indexed for MEDLINE]

643: Am J Rhinol. 2005 Nov-Dec;19(6):591-8.

Montelukast effectively treats the nighttime impact of seasonal allergic
rhinitis.

Meltzer EO, Philip G, Weinstein SF, LaForce CF, Malice MP, Dass SB, Santanello
NC, Reiss TF.

Allergy and Asthma Medical Group and Research Center, San Diego, CA 92109, USA.

BACKGROUND: Nighttime problems constitute a significant burden on the quality of 
life of patients with seasonal allergic rhinitis (SAR). The aim of this study was
to evaluate the effectiveness of montelukast on nighttime AR symptoms. METHODS:
In seven multicenter, double-blind, parallel-group trials, nighttime problems
were assessed as the nighttime symptoms score (NSS), an average of three
individual symptom scores: difficulty going to sleep, nighttime awakening, and
nasal congestion on awakening (each rated 0 = none to 3 = severe). Patients (aged
15-82 years) were randomized to receive montelukast, 10 mg (n = 1751), placebo (n
= 1557), or the positive control loratadine, 10 mg (n = 1616). RESULTS: In a
combined analysis, changes from baseline (mean +/- SE) in NSS were -0.28 +/-
0.01, -0.16 +/- 0.01, and -0.24 +/- 0.01 for the montelukast, placebo, and
loratadine groups, respectively. Difference versus placebo in least-squares mean 
change from baseline were -0.11 (95% confidence interval, -0.14, -0.08; p < or = 
0.001) for montelukast and -0.09 (-0.12, -0.06; p < or = 0.001) for loratadine.
Strong baseline correlations (R > 0.70; p < 0.001) of NSS and two of its
individual symptoms with the sleep domain of the validated Rhinoconjunctivitis
Quality of Life Questionnaire support the validity and importance of measuring
nighttime morbidity in SAR. Furthermore, a clinically important benefit of
montelukast on the nighttime impact of SAR was shown using an analysis anchored
on the Patient's Global Evaluation. CONCLUSION: These data underscore the
importance of nighttime problems in patients with SAR and the need to treat
nighttime symptoms. In these studies, montelukast significantly improved the NSS,
a clinically relevant and valid measure in patients with SAR.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16402647 [PubMed - indexed for MEDLINE]

644: Am J Rhinol. 2005 Nov-Dec;19(6):560-6.

Does nitrogen dioxide affect inflammatory markers after nasal allergen challenge?

Barck C, Lundahl J, Holmström M, Bylin G.

Division of Respiratory Medicine and Allergology, Karolinska Institutet,
Department of Medicine, Karolinska University Hospital Huddinge, Stockholm,
Sweden.

BACKGROUND: Exposure to high ambient levels of nitrogen dioxide (NO2) enhances
the bronchial inflammatory reaction to allergen in humans. We tested whether this
NO2 effect occurs also in the upper airways. METHODS: Sixteen allergic subjects
with rhinitis and mild asthma were exposed at rest to either purified air or 500 
microg/m3 NO2 for 30 minutes, followed 4 hours later by a nasal allergen
challenge. Nasal lavage was performed before air/NO2 exposure, before allergen
challenge, and 1, 4 and 18 hours after allergen challenge. Symptoms were
recorded. RESULTS: The percentage of eosinophils and neutrophils, eosinophil
cationic protein, and myeloperoxidase were similar after exposure to air +
allergen and to NO2 + allergen. We noticed a tendency to increased sneezing the
day after exposure to NO2 + allergen. CONCLUSION: The priming effect of an
ambient brief NO2 exposure on subsequent allergic response was not noticeable in 
activation of inflammatory cells and mediators in the upper airways.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16402641 [PubMed - indexed for MEDLINE]

645: Ann Allergy Asthma Immunol. 2005 Dec;95(6):579-85.

Prevalence and severity of symptoms of asthma, rhinitis, and eczema in 13- to
14-year-old children in Taipei, Taiwan.

Yan DC, Ou LS, Tsai TL, Wu WF, Huang JL.

Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang
Gung Children's Hospital and Chang Gung University, Taoyuan, Taiwan.

BACKGROUND: The prevalence of asthma and allergic diseases in children has
increased worldwide. OBJECTIVE: To perform the phase 3 survey of the
International Study of Asthma and Allergies in Children (ISAAC) to report the
time trend of the prevalence and severity of asthma and allergic diseases in
children in Taipei. METHODS: Two junior high schools in each of the 12 school
districts in Taipei were randomly chosen to enter the study. All students aged 13
to 14 years in the chosen schools were invited to participate in written and
video questionnaires in Chinese (identical to those of the ISAAC phase 1 survey).
The study was performed between December 1, 2001, and January 31, 2002. All data 
analysis followed the protocol of the ISAAC and then was submitted to the ISAAC
International Data Center. RESULTS: Of 6653 eligible children from 23 high
schools (1 school refused participation), 6381 (95.9%) participated. The
prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in the
past 12 months in 13- to 14-year-old children increased by 37%, 51%, and 193%,
respectively, on written questionnaires during a 7-year period. The severity of
asthma symptoms, including more than 4 wheezing attacks in the past 12 months,
wheezing that disturbs sleep more than once per week, and wheezing that limited
speech in the past 12 months, did not show any significant changes on written
questionnaires during the 7 years. CONCLUSION: The increasing prevalence of
symptoms of asthma, allergic rhinitis, and atopic eczema in 13- to 14-year-old
children in Taipei in a 7-year period is a significant burden on public health
systems in Taiwan.

PMID: 16400899 [PubMed - indexed for MEDLINE]

646: Ann Allergy Asthma Immunol. 2005 Dec;95(6):525-9.

Comment in:
    Ann Allergy Asthma Immunol. 2005 Dec;95(6):498.

Sexual dysfunction in patients with allergic rhinoconjunctivitis.

Kirmaz C, Aydemir O, Bayrak P, Yuksel H, Ozenturk O, Degirmenci S.

Division of Allergy and Immunology, Department of Internal Medicine, Celal Bayar 
University, Manisa, Turkey. ckirmaz@yahoo.com

BACKGROUND: Sexual dysfunction in chronic diseases has recently attracted
attention owing to its impact on quality of life (QoL). Allergic
rhinoconjunctivitis (ARC) affects QoL, causing limitations in many areas.
However, there has not been research on changes in sexual function in patients
with ARC. OBJECTIVE: To report the effect of ARC and its treatment on sexual
function in men and women. METHODS: Forty-three sexually active patients with
seasonal ARC aged 22 to 49 years were included in the study. The control group
was composed of 40 healthy individuals aged 22 to 46 years. Conjunctival symptom 
scores (CSSs) and nasal symptom scores (NSSs) of patients with symptomatic ARC
were determined, as were sexual function scores (SFSs) using the Female Sexual
Function Index and the International Index of Erectile Function during allergen
exposure in the pollination period and after treatment with oral desloratadine, 5
mg/d, for 30 days. The SFSs were evaluated in the control group. RESULTS: The
CSSs and NSSs significantly improved in treated ARC (P < .001). In women, Female 
Sexual Function Index results in symptomatic ARC were significantly lower than in
treated ARC and controls (P = .003). In men, International Index of Erectile
Function results in treated ARC (P = .001) and controls (P < .001) were
significantly higher than in symptomatic ARC. Furthermore, correlation between
improvement in CSSs and NSSs and that of SFSs was determined (P = .007 for women;
P = .001 for men). CONCLUSION: Improvement in sexual function as a variable of
QoL may accompany the treatment of symptoms in patients with ARC.

PMID: 16400890 [PubMed - indexed for MEDLINE]

647: Pediatrics. 2006 Jan;117(1):34-42.

Changes in prevalence of asthma and allergies among children and adolescents in
Italy: 1994-2002.

Galassi C, De Sario M, Biggeri A, Bisanti L, Chellini E, Ciccone G, Petronio MG, 
Piffer S, Sestini P, Rusconi F, Viegi G, Forastiere F.

Regional Health Agency, Emilia-Romagna, Bologna, Italy. claudia.galassi@cpo.it

BACKGROUND: Several studies conducted during the 1990s indicated an increase in
the prevalence of symptoms of asthma; more recent investigations suggest that the
trend is stabilizing or may even be reversing. OBJECTIVE: We compared 2
cross-sectional surveys conducted in 1994 and 2002 in 8 areas in northern and
central Italy, to evaluate prevalence changes for asthma, allergic rhinitis, and 
eczema. METHODS: The International Study of Asthma and Allergies in Childhood
methods and questionnaires were used to investigate 6- to 7-year-old children
(16,115 and 11,287 questionnaires completed by parents in 1994-1995 and 2002,
respectively) and 13- to 14-year-old adolescents (19,723 and 10,267
questionnaires completed by adolescents in 1994-1995 and 2002, respectively). In 
each phase, the overall response rate was >90%. Prevalence changes were
calculated as the absolute difference between the prevalence recorded on the 2
occasions. RESULTS: The prevalence of wheeze (past 12 months) increased slightly 
among children (change: 0.8%; 95% confidence interval [CI]: 0.0% to 1.6%) and was
rather stable among adolescents. Symptoms of allergic rhinitis (children: change:
5.2%; 95% CI: 4.0% to 6.4%; adolescents: change: 4.1%; 95% CI: 1.9% to 6.3%) and 
symptoms of atopic eczema (children: change: 4.4%; 95% CI: 3.6% to 5.2%;
adolescents: change: 2.1%; 95% CI: 1.2% to 3.0%) increased clearly in both age
groups. There was some heterogeneity across the centers among adolescents,
especially for allergic rhinitis, with larger increases seen in the 3
metropolitan areas. The changes observed paralleled profound family changes, ie, 
better parental education, higher rates of maternal employment, and lower rates
of exposure to parental smoke. These factors, however, do not explain all of the 
observed changes in prevalence. CONCLUSIONS: The results indicate that the
epidemiologic features of asthma and allergies in Italy are changing rapidly,
although the causes are still uncertain.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16396858 [PubMed - indexed for MEDLINE]

648: Curr Med Res Opin. 2006 Jan;22(1):151-7.

Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal
allergic rhinitis: a pharmacodynamic study of onset of action and efficacy.

Horak F, Zieglmayer UP, Zieglmayer R, Kavina A, Marschall K, Munzel U, Petzold U.

Ear, Nose and Throat, University Clinic Vienna, Vienna, Austria.
friedrich.horak@vienna.at

OBJECTIVE: To assess the efficacy and onset of action of azelastine nasal spray
and desloratadine tablets in patients with allergen-induced seasonal allergic
rhinitis (SAR). RESEARCH DESIGN AND METHODS: 46 adult patients with a history of 
SAR were exposed to a controlled grass pollen concentration for 6 h in the Vienna
Challenge Chamber (VCC) in each treatment period according to a randomised,
double-blind (double-dummy), three-period, three-sequence crossover design
(wash-out period of 12 days). Single doses of study medication (one puff nasal
spray into each nostril of azelastine, 0.2 mg, or placebo before swallowing one
encapsulated tablet of desloratadine, 5 mg) were administered 2 h after the start
of the allergen challenge. Results of subjective and objective assessments were
recorded throughout the challenge. RESULTS: Efficacy of azelastine nasal spray
was significantly superior compared to desloratadine tablets (p = 0.005) and
placebo (p < 0.001). Desloratadine was significantly better than placebo (p <
0.001). Decrease both in Major Nasal Symptom Score (MNSS) and in Total Nasal
Symptom Score (TNSS) was fastest after azelastine treatment. Improvement of nasal
symptom severity was most pronounced after azelastine treatment for all nasal
symptoms including nasal congestion. Onset of action was 15 min for azelastine
compared to 150 min for desloratadine. Both active preparations were safe and
well tolerated. CONCLUSIONS: This study confirms the usefulness of azelastine
nasal spray for the symptomatic treatment of seasonal allergic rhinitis.
Concerning onset of action in particular, the results favour the topical
treatment over systemic therapy.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16393441 [PubMed - indexed for MEDLINE]

649: Clin Exp Allergy. 2005 Dec;35(12):1608-14.

Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions
following allergen challenge.

Erin EM, Zacharasiewicz AS, Nicholson GC, Tan AJ, Higgins LA, Williams TJ,
Murdoch RD, Durham SR, Barnes PJ, Hansel TT.

National Heart and Lung Institute (NHLI) Clinical Studies Unit, Imperial College,
London, UK.

BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 
2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders.
OBJECTIVE: This study was performed to assess the effect of 7 days of topical
corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils,
cytokines and chemokines obtained by nasal lavage and filter paper methods.
METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of
season received nasal challenge following matched placebo (twice daily into each 
nostril for 7 days) and fluticasone propionate (100 microg twice daily into each 
nostril for 7 days). Chemokine and cytokine levels were analysed using a
sensitive automated bead immunoassay system at intervals up to 8 h after NAC.
RESULTS: Levels of cytokines and chemokines from filter paper were generally
higher than from nasal lavage. Fluticasone propionate caused a reduction in
symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5,
IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05
for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin,
RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P
< 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15,
TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone
propionate has selective inhibitory effects on Th2 cytokine synthesis following
nasal challenge, while also decreasing release of chemokines, but not affecting
levels of Th1 cytokines.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16393327 [PubMed - indexed for MEDLINE]

650: Clin Exp Allergy. 2006 Jan;36(1):32-9.

Absence of systemic immunologic changes during dose build-up phase and early
maintenance period in effective specific sublingual immunotherapy in children.

Dehlink E, Eiwegger T, Gerstmayr M, Kampl E, Bohle B, Chen KW, Vrtala S, Urbanek 
R, Szépfalusi Z.

Department of Pediatrics and Juvenile Medicine and Department of Pathophysiology,
Centre for Physiology and Pathophysiology, Medical University of Vienna, Vienna, 
Austria.

BACKGROUND: Sublingual immunotherapy (SLIT) has been reported to be a safe
treatment for inhalant allergies in children. Yet the immunologic mechanisms
resulting in clinical improvement are poorly understood. OBJECTIVE: To identify
early systemic immunologic changes during the first 8 weeks of clinically
effective SLIT to grass pollen, tree pollen or house dust mite in paediatric
patients with allergic rhinoconjunctivitis and/or asthma. METHODS: Peripheral
blood mononuclear cells and plasma samples of 13 children with reduced symptoms
after 1 year of SLIT were obtained before therapy and at 2 and 8 weeks after the 
initiation of SLIT. Allergen-specific lymphocyte proliferation assays were
performed, and allergen-induced cytokine production (IL-2, IL-4, IL-10,
IFN-gamma, and TGF-beta(1)) was measured by ELISA and flow cytometry.
Allergen-specific IgE, IgG1, IgG4, and IgA levels in plasma samples were
determined in ELISA. RESULTS: During the first 8 weeks of successful SLIT,
allergen-specific lymphoproliferation (n=13) as well as levels of
allergen-specific intracellular (n=8) and secreted cytokines (n=9) did not change
significantly. In addition, no alterations in levels of allergen-specific Igs
(n=7) were observed. CONCLUSION: We could not find any early systemic immunologic
changes during the first 8 weeks of clinically effective SLIT to inhalant
allergens in paediatric patients with allergic rhinoconjunctivitis and/or asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16393263 [PubMed - indexed for MEDLINE]

651: Int J Immunopathol Pharmacol. 2005 Oct-Dec;18(4):715-22.

Determinants of bronchial hyperresponsiveness in subjects with rhinitis.

Di Lorenzo G, Pacor ML, Mansueto P, Esposito Pellitteri M, Lo Bianco C, Ditta V, 
Leto-Barone MS, Napoli N, Di Fede G, Rini GB.

Dipartimento di Medicina Clinica e delle Patologie Emergenti, Universitá degli
Studi di Palermo, Italy. dilo601@unipa.it

Subjects with rhinitis but without asthma may have coexisting bronchial
hyperresponsiveness, although the reasons for this are uncertain. To evaluate the
factors that determine BHR in rhinitis we examined 410 patients with symptomatic 
rhinitis with forced expiratory volume in 1 second (FEV1) and forced vital
capacity (FVC)>or=80% of the predicted value. In all subjects a skin prick test
(SPT) was performed, a determination of total serum IgE and an eosinophils count 
in the blood. Of the 410 subjects we found that 161 (39.3%) exhibited a
methacholine PD20 of 800 mg or less (Group A), whereas 249 (60.7%) had a
methacholine PD20 more of 800 mg (Group B). Despite the matched mean values for
FEV1 and FVC, compared with Group B, Group A had a lower predicted forced
expiratory flow between 25% and 75%(FEF25%-75%) (86.7 +/- 12.0 vs. 93.7 +/- 7.3, 
P < 0.0001). A great portion of the subjects of the Group Ain respect to subjects
of the Group B were exposed to passive smoke (37.8% vs. 22.0%, P = 0.0008),
reported having mothers with asthma (34.1% vs. 6.0%, P < 0.0001), presented a
positive skin prick test (93.7% vs. 67.0%, P < 0.0001), had higher levels of
total serum IgE (geometric mean of Log10 2.46 +/- 0.27 kU/L vs. 2.06 +/- 0.38
kU/L, P < 0.0001) and higher blood eosinophil counts (geometric mean of Log10
2.67 +/- 0.07 x 10(-3) mL vs. 2.57 +/- 0.09 x 10(-3) mL, P < 0.0001), and
reported increased nasal obstruction (2.0 (95% CI 1.8 to 2.2) vs. 0.6 (95% CI 0.5
to 0.7), P < 0.0001). Logistic regression demonstrates that nasal obstruction (OR
2.19, 95% CI 1.72 to 2.80) and the presence of positive SPT (OR 6.15, 95% CI 2.42
to 15.61) were the most available predictors to discriminate between subjects
with BHR and subjects without BHR. In addition, BHR was positively related to
blood eosinophil counts (OR= 2.80, 95% CI 1.54 to 5.07), FEF25%-75% values (OR=
2.72, 95% CI 1.23 to 5.99) and familiarity (mother) for asthma (OR = 2.45, 95% CI
1.10 to 5.46). Whereas passive smoke and total serum IgE were not positively
related to BHR. Increased nasal obstruction and the presence of positive SPT were
the most available predictors to discriminate between subjects with and without
BHR. Finally, BHR was positively related to blood eosinophil counts, FEF25%-75%
values and to familiarity (mother) for asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16388720 [PubMed - indexed for MEDLINE]

652: J Allergy Clin Immunol. 2006 Jan;117(1):158-62. Epub 2005 Dec 2.

Severity and impairment of allergic rhinitis in patients consulting in primary
care.

Bousquet J, Neukirch F, Bousquet PJ, Gehano P, Klossek JM, Le Gal M, Allaf B.

University Hospital and Institut National de la Santé et de la Recherche Médicale
U454, Montpellier, France. jean.bousquet@wanadoo.fr

BACKGROUND: Allergic rhinitis is a disease impairing quality of life, sleep, and 
work. A new classification for allergic rhinitis, Allergic Rhinitis and its
Impact on Asthma (ARIA), has recently been proposed. OBJECTIVE: To study the
effect of allergic rhinitis using ARIA definitions to determine severity and
duration. METHODS: A total of 3052 patients consulting general practitioners for 
allergic rhinitis were studied. Patients were classified according to the 4
classes of ARIA. In all patients, quality of life (Rhinoconjunctivitis
Quality-of-Life Questionnaire), sleep (Jenkins questionnaire), and work
performance (Allergy-Specific Work Productivity and Activity Impairment
questionnaire) were assessed. RESULTS: Mild intermittent rhinitis was diagnosed
in 11% of the patients, mild persistent rhinitis in 8%, moderate/severe
intermittent rhinitis in 35%, and moderate/severe persistent rhinitis in 46%. The
severity of rhinitis has more of an effect on quality of life, sleep, daily
activities, and work performance than the duration of rhinitis. In
moderate/severe rhinitis, more than 80% of patients report impaired activities,
as opposed to only 40% with mild rhinitis. CONCLUSION: It seems that the term
moderate/severe should be replaced by severe. A study in the general population
is necessary, however, to assess the prevalence of the 4 ARIA classes of allergic
rhinitis, especially in patients who are not consulting physicians for their
symptoms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16387600 [PubMed - indexed for MEDLINE]

653: J Allergy Clin Immunol. 2006 Jan;117(1):134-40. Epub 2005 Dec 2.

Comment in:
    J Allergy Clin Immunol. 2007 Dec;120(6):1471-2; author reply 1472-3.

Omalizumab pretreatment decreases acute reactions after rush immunotherapy for
ragweed-induced seasonal allergic rhinitis.

Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG, Mokhtarani M,
Seyfert-Margolis V, Asare A, Bateman K, Deniz Y; Immune Tolerance Network Group.

Creighton University School of Medicine, Omaha, NE 68131, USA.
tbcasale@creighton.edu

BACKGROUND: Rush immunotherapy (RIT) presents an attractive alternative to
standard immunotherapy. However, RIT carries a much greater risk of acute
allergic reactions, including anaphylaxis. OBJECTIVES: We hypothesized that
omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in
enhancing both safety and efficacy of RIT. METHODS: Adult patients with ragweed
allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind,
parallel-group, placebo-controlled trial. Patients received either 9 weeks of
omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush
(maximal dose 1.2-4.0 mug Amb a 1) or placebo immunotherapy, then 12 weeks of
omalizumab or placebo plus immunotherapy. RESULTS: Of the 159 patients enrolled, 
123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in
immunotherapy patients, and free IgE levels declined >10-fold in omalizumab
patients. Patients receiving omalizumab plus immunotherapy had fewer adverse
events than those receiving immunotherapy alone. Post hoc analysis of groups
receiving immunotherapy demonstrated that addition of omalizumab resulted in a
5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P =
.026). On an intent-to-treat basis, patients receiving both omalizumab and
immunotherapy showed a significant improvement in severity scores during the
ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P
= .044). CONCLUSION: Omalizumab pretreatment enhances the safety of RIT for
ragweed allergic rhinitis. Furthermore, combined therapy with omalizumab and
allergen immunotherapy may be an effective strategy to permit more rapid and
higher doses of allergen immunotherapy to be given more safely and with greater
efficacy to patients with allergic diseases.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16387596 [PubMed - indexed for MEDLINE]

654: Respir Res. 2005 Dec 28;6:153.

Greater risk of incident asthma cases in adults with allergic rhinitis and effect
of allergen immunotherapy: a retrospective cohort study.

Polosa R, Al-Delaimy WK, Russo C, Piccillo G, Sarvà M.

Dipartimento di Medicina Interna e Specialistica, University of Catania, Catania,
Italy. rp5@soton.ac.uk

Asthma and rhinitis are often co-morbid conditions. As rhinitis often precedes
asthma it is possible that effective treatment of allergic rhinitis may reduce
asthma progression. The aim of our study is to investigate history of allergic
rhinitis as a risk factor for asthma and the potential effect of allergen
immunotherapy in attenuating the incidence of asthma. Hospital-referred
non-asthmatic adults, aged 18-40 years between 1990 and 1991, were
retrospectively followed up until January and April 2000. At the end of follow
up, available subjects were clinically examined for asthma diagnosis and history 
of allergen specific immunotherapy, second-hand smoking and the presence of pets 
in the household. A total of 436 non-asthmatic adults (332 subjects with allergic
rhinitis and 104 with no allergic rhinitis nor history of atopy) were available
for final analyses. The highest OR (odds ratio) associated with a diagnosis of
asthma at the end of follow-up was for the diagnosis of allergic rhinitis at
baseline (OR, 7.8; 95%CI, 3.1-20.0 in the model containing the covariates of
rhinitis diagnosis, sex, second-hand smoke exposure, presence of pets at home,
family history of allergic disorders, sensitization to Parietaria judaica; grass 
pollen; house dust mites; Olea europea: orchard; perennial rye; and cat
allergens). Female sex, sensitization to Parietaria judaica and the presence of
pets in the home were also significantly predictive of new onset asthma in the
same model. Treatment with allergen immunotherapy was significantly and inversely
related to the development of new onset asthma (OR, 0.53; 95%CI, 0.32-0.86). In
the present study we found that allergic rhinitis is an important independent
risk factor for asthma. Moreover, treatment with allergen immunotherapy lowers
the risk of the development of new asthma cases in adults with allergic rhinitis.

PMID: 16381607 [PubMed - indexed for MEDLINE]

655: Allergol Immunopathol (Madr). 2005 Nov-Dec;33(6):303-6.

Total serum IgE: adult reference values in Valencia (1981-2004). Usefulness in
the diagnosis of allergic asthma and rhinitis.

Campos A, Reyes J, Blanquer A, Liñares T, Torres M.

Service of Allergic Diseases, La Fe University Hospital, Valencia, Spain.
campos_ang@gva.es

BACKGROUND: The reference values for total serum IgE are accepted to vary
according to the geographical area involved. In 1981 we published the reference
values for a donor population in the city of Valencia (Spain) and its
metropolitan area. Since then, we have noted an increase in the prevalence of
asthma and rhinitis in countries with a Western lifestyle, including Spain. AIM: 
To update the adult reference values for total serum IgE in the city of Valencia 
and its metropolitan area, and to determine their diagnostic usefulness in asthma
and allergic rhinitis. MATERIAL AND METHODS: We studied two groups of 69 and 100 
individuals each. One group comprised apparently healthy blood donors, as
assessed by a routine blood bank study protocol and the application of a
questionnaire to exclude perceived allergic or parasitic diseases, while the
other group consisted of individuals with atopic respiratory disease (bronchial
asthma and allergic rhinitis) studied in our service in the same time period
(spring 2004). Total serum IgE was determined by the UniCAP method developed by
Pharmacia. RESULTS: The geometric mean of total serum IgE among blood donors was 
46.65 kU/l (95% CI: 15.5-77.8) versus 204.29 kU/l (95% CI: 93.3-515) among
allergic subjects. The difference between the two groups was statistically
significant. No significant difference was found between our donor sample in 1981
and the sample in the present study. Establishing an arbitrary cut-off point of
1.65 standard deviations (SD)(equivalent to 95 % of the donor population), we
obtained a figure of > 183 kU/l whereby 44% of all allergic individuals presented
a value below this cut-off point. To practical effects, these allergic patients
behaved as low responders (LRs) in relation to total IgE, whereas the remaining
individuals were high responders (HRs) in relation to total IgE. CONCLUSIONS: Our
data confirm the current validity of the reference values obtained in 1981, which
continue to be significantly different from those of the UniCAP method for
Swedish donors. The population of allergic subjects can be divided into two
subgroups: subjects with total IgE levels similar to those of the donors, which
we refer to as LRs, and which represent 44% of all allergic subjects, and a
second subgroup with total IgE values above those of the donors (HRs), who would 
therefore be the only subjects that would be identified by individual serum IgE
study.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 16371216 [PubMed - indexed for MEDLINE]

656: Allergol Immunopathol (Madr). 2005 Nov-Dec;33(6):296-302.

Health-economic analyses of subcutaneous specific immunotherapy for grass pollen 
and mite allergy.

Petersen KD, Gyrd-Hansen D, Dahl R.

Health Economics, Institute of Public Health, University of Southern
Denmark-Odense University, Denmark. kdpetersen@health.sdu.dk

OBJECTIVE: To investigate the health and monetary consequences of treating
allergy with specific immunotherapy (SIT) compared with symptomatic
treatment/standard care among patients with grass pollen or mite allergy.
METHODS: We performed an economic analysis based on 253 grass- and/or mite
allergic patients who started SIT from 1.1.1996 to 1.1.2002 at the Allergy Unit, 
Aarhus University Hospital and at a specialist practice in Aarhus. Relevant data 
were collected before, during and after SIT treatment from the national health
service based on each patient's personal identification number and medical
records and from a specifically designed questionnaire. A cost-benefit analysis
including direct and indirect costs before, during and after SIT was performed.
In addition direct costs were related to the clinical effect (improvement in
well-being) in the form of a cost-effectiveness analysis. RESULTS: The direct
cost per patient/year before SIT (equivalent to standard care) was DKK 2,580. The
investment in SIT was DKK 27,545 (in present values) per patient over a 4-year
period. After SIT the cost was reduced to DKK 1,072 per patient/year. In the long
term, prospective introduction of SIT incurred additional present-value direct
costs of DKK 13,676 per patient treated and DKK 2,784 per patient/year of
improved well-being. However, when indirect costs were included in the economic
evaluation SIT was shown to be net beneficial. CONCLUSION: This study reveals
that SIT is associated with initial resource investments and subsequent resource 
savings in the long term compared with standard care. When all consequences are
measured in monetary terms, and assuming that sick days are associated with a
loss of productivity, this analysis suggests that SIT increases societal welfare.
This conclusion also holds if there is no loss of productivity.

Publication Types: 
    Multicenter Study

PMID: 16371215 [PubMed - indexed for MEDLINE]

657: MedGenMed. 2005 Jan 27;7(1):27.

Omalizumab: a monoclonal anti-IgE antibody.

Belliveau PP.

Department of Pharmacy Practice, Massachusetts College of Pharmacy-Worcester,
Worcester, Massachusetts, USA.

OBJECTIVES: To describe allergic asthma and allergic rhinitis pathophysiology and
review the pharmacologic, pharmacokinetic, pharmacodynamic, efficacy, and safety 
data for omalizumab. METHODS: MEDLINE, In-Process & Other Non-Indexed Citations, 
and EMBASE Drugs & Pharmacology were searched using olizumab, omalizumab, E25,
rhuMAb-E25, and anti-IgE. Combinations of rhinitis, asthma, and IgE captured
information on disease pathophysiology. RESULTS: Omalizumab is a monoclonal
antibody targeting the high-affinity receptor binding site on human
immunoglobulin (Ig)E. Bound IgE is not available for basophil binding,
degranulation is attenuated, and allergic symptoms are reduced. In asthma trials,
omalizumab reduced inhaled corticosteroid and rescue medication requirements and 
improved asthma control and asthma quality of life in moderate to severe allergic
asthmatics with disease poorly controlled by inhaled corticosteroids. In trials
of patients with poorly controlled moderate to severe seasonal allergic rhinitis 
(SAR), omalizumab reduced the severity of exacerbations and rescue medication
use, and improved rhinitis-related quality of life. Benefits were also observed
in trials utilizing combinations of immunotherapy and omalizumab for SAR and in
trials of perennial allergic rhinitis (PAR). Omalizumab has been well tolerated. 
Although malignant neoplasms have been observed in treated patients, they were
likely not related to omalizumab therapy. CONCLUSIONS: Omalizumab has
demonstrated efficacy in children, adults, and adolescents with uncontrolled
moderate to severe allergic asthma and allergic rhinitis. Long-term safety beyond
52 weeks needs continued evaluation.

Publication Types: 
    Review

PMID: 16369332 [PubMed - indexed for MEDLINE]

658: Allergy. 2006 Jan;61(1):111-8.

Changes in airway inflammation following nasal allergic challenge in patients
with seasonal rhinitis.

Bonay M, Neukirch C, Grandsaigne M, Leçon-Malas V, Ravaud P, Dehoux M, Aubier M.

Unité 700 INSERM, Faculté Xavier Bichat, Paris Cedex, France.

BACKGROUND: Seasonal allergic rhinitis could predispose to the development of
chronic bronchial inflammation as observed in asthma. However, direct links
between nasal inflammation, bronchial inflammation and airway responsiveness in
patients with seasonal allergic rhinitis and without asthma are not fully
understood. The aim of this study was to analyse the changes induced by allergic 
nasal challenge outside the pollen season in airway responsiveness and bronchial 
inflammation of patients with seasonal allergic rhinitis. METHODS: Nine patients 
were evaluated after either grass pollens or placebo nasal challenge in a
randomized cross-over double-blinded trial. Nasal parameters were recorded hourly
and airway responsiveness was assessed by methacholine challenge. Cytological
examinations and cytokine measurements were performed in nasal lavage and induced
sputum. Eosinophil activation was investigated by eosinophil-cationic protein
expression and secretion. RESULTS: Airway responsiveness was increased after
allergic nasal challenge. Total eosinophils and eosinophils expressing
eosinophil-cationic protein were increased in induced sputum after allergic nasal
challenge. Both eosinophil number and eosinophil-cationic protein concentration
in induced sputum were correlated to methacholine responsiveness. CONCLUSIONS:
These results suggest that eosinophils participate to the bronchial inflammation 
in patients with seasonal allergic rhinitis following allergic nasal challenge
outside the pollen season and might explain changes in airway responsiveness.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16364165 [PubMed - indexed for MEDLINE]

659: Allergy. 2006 Jan;61(1):104-10.

Sensitization to blackgram in patients with bronchial asthma and rhinitis:
clinical evaluation and characterization of allergens.

Kumari D, Kumar R, Sridhara S, Arora N, Gaur SN, Singh BP.

Allergy and Immunology Section, Institute of Genomics and Integrative Biology,
Delhi, India.

BACKGROUND: Legumes are important causative agents of type I hypersensitivity in 
south Asia and Europe but such studies are lacking in Indian population. The
present study investigates blackgram sensitization in asthma and rhinitis
patients and identifies immunoglobulin E (IgE)-binding proteins. METHODS:
Respiratory allergy patients were evaluated using standard questionnaire and skin
prick tests (SPT) with common foods and aeroallergens. Blackgram-specific IgE
level was estimated by enzyme-linked immunosorbent assay (ELISA) and
sensitization was established by a double-blind, placebo-controlled food
challenge (DBPCFC). The cross-reactivity of blackgram with other legumes was
studied by immunobiochemical methods. RESULT: Of 816 patients, 35 gave history of
blackgram hypersensitivity. From these, 16 patients were SPT positive and 14
showed elevated specific IgE (three times of negative control) to blackgram.
DBPCFC established blackgram sensitivity in four of 14 patients. Immunoblotting
with individual patient's sera recognized eight most prevalent allergens of 78,
56, 47, 43, 40, 30, 28 and 16 kDa. Roasted blackgram showed six major allergens
whereas 47, 43 and 28 kDa proteins retained IgE reactivity upon boiling.
Blackgram extract required 14 ng of self protein for 50% ELISA inhibition whereas
roasted and boiled blackgram required 16 and 120 ng protein. ELISA and immunoblot
inhibition show partial inhibition to blackgram proteins by lentil, limabean and 
pea. CONCLUSION: Blackgram induces IgE-mediated reactions in 1.7% of asthma and
rhinitis patients and contains eight major IgE-binding components, of which six
retained IgE reactivity after roasting. Blackgram shares allergenicity with
lentil and limabean.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16364164 [PubMed - indexed for MEDLINE]

660: Allergy. 2006 Jan;61(1):35-42.

Variation of T-cell activation in allergic subjects during natural pollen
exposure.

Koscher V, Milhe F, El Biaze M, Vervloet D, Magnan A.

Faculté de Médecine de Marseille, Université de la Méditerranée, Assistance
Publique Hôpitaux de Marseille, Service de Pneumo-Allergologie, INSERM,
Marseilles, France.

BACKGROUND: Allergic inflammation is characterized by a Th2 activation. However, 
little is known about dynamics of T-cell cytokine production during natural
allergen exposure. The aim of this study was to assess the Th1/Th2 balance in
cypress allergic patients compared with controls, and variations of this balance 
over the pollen season. METHODS: Twenty cypress allergic patients and 10 controls
were studied, distributed during two consecutive pollen seasons. Cytokine
production was assessed by flow cytometry and ELISA. The variation of cytokine
production during the pollen season was analyzed among patients in four
occasions, and the preseason values were compared with controls. IL-13 and
IFN-gamma-containing T cells were assessed among whole blood cells and PBMC. In
addition the effect of specific stimulation by Juniperus ashei pollen extract was
studied. RESULTS: Compared with controls, IL-13-producing T cells were increased 
in allergics in any case. By contrast, compared with controls, allergic
IFN-gamma-producing T cells were decreased in whole blood, but not in PBMC, and
were increased after specific stimulation. During the season, an increase in
IFN-gamma- and a decrease in IL-13-producing T cells occurred in patients,
whatever the culture conditions. CONCLUSION: These results show that the allergic
T-cell activation is not limited to a Th2 profile: allergen-stimulated T cells
are able to produce IFN-gamma at baseline, and the Th1/Th2 ratio increases during
the pollen season.

Publication Types: 
    Comparative Study

PMID: 16364154 [PubMed - indexed for MEDLINE]

661: B-ENT. 2005;Suppl 1:45-62; quiz 63-4.

Management of allergic rhinitis.

Van Cauwenberge P, Van Hoecke H.

Dept of Otorhinolaryngology, Ghent University Hospital, Ghent.

Due to its high and increasing prevalence, its impact on quality of life, the
association with multiple comorbidities and the considerable socio-economic
burden, allergic rhinitis is a major respiratory disorder and represents a global
health concern. The ARIA working group has proposed a new classification for
allergic rhinitis into intermittent or persistent, based on the duration of
symptoms. The severity of allergic rhinitis is graded according to the impact of 
the disease on the quality of life. The diagnosis of allergic rhinitis involves a
thorough history and clinical examination. In patients suspected of having
persistent AR a complete and systematic nasal examination is an absolute
requirement. Anterior rhinoscopy provides limited information. Nasal endoscopy is
more useful, not to confirm AR but in particular to exclude other conditions,
such as polyps, foreign bodies, tumours and septal deformations. To confirm the
allergic origin of rhinitis symptoms, allergy tests must be performed. The first 
choice test is the skin prick test. Patients with allergic rhinitis should be
evaluated for asthma and patients with asthma should be evaluated for rhinitis. A
stepwise therapeutic approach is recommended based on the duration and severity
of disease. The treatment of allergic rhinitis consists of allergen avoidance,
pharmacotherapy and immunotherapy.

Publication Types: 
    Review

PMID: 16363267 [PubMed - indexed for MEDLINE]

662: Psychiatr Serv. 2005 Dec;56(12):1593-9.

A comparison of service use and costs among adults with ADHD and adults with
other chronic diseases.

Hinnenthal JA, Perwien AR, Sterling KL.

Department of Health Economic and Outcomes Research, Ingenix in Eden Prairie,
Minnesota, USA.

OBJECTIVE: This study compared health service use and costs among adults with
attention-deficit hyperactivity disorder (ADHD) and adults with depression,
diabetes, or seasonal allergic rhinitis (seasonal allergy). METHODS: Pharmacy and
medical claims data from January 1, 1999, to December 31, 2001, were obtained
from a large U.S. managed care plan. Patients were divided into one of four
mutually exclusive cohorts (ADHD, depression, diabetes, or seasonal allergy) on
the basis of their diagnosis or prescriptions. Age, gender, comorbid conditions, 
and type of dominant provider were compared for the four groups. Thereafter,
general linear models with post-hoc multiple comparison tests were used to
compare health service use and costs by site of service. RESULTS: The study
population included 143,561 patients. The four mutually exclusive groups included
58,017 with depression, 45,479 with diabetes, 33,272 with a seasonal allergy, and
6,793 had ADHD. Comorbid mental health conditions occurred with significantly
greater frequency among patients with ADHD and among those with depression than
among patients in the other groups. Patients with ADHD and those with depression 
received care from a mental health provider significantly more often than those
with diabetes or a seasonal allergy. Patients with ADHD had fewer average
outpatient, inpatient, and emergency department visits than patients with
depression or diabetes, and office visit frequency for patients with ADHD was
significantly different from that of patients with a seasonal allergy. Annual
total costs were lowest among patients with a seasonal allergy ($2,743), which
were not significantly different than the costs for patients with ADHD ($3,020). 
CONCLUSIONS: Adult ADHD poses an economic burden that is less than that of
depression or diabetes but greater than that of a seasonal allergy.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16339625 [PubMed - indexed for MEDLINE]

663: J Allergy Clin Immunol. 2005 Dec;116(6):1264-6.

How do topical nasal corticosteroids improve sleep and daytime somnolence in
allergic rhinitis?

Craig TJ, Hanks CD, Fisher LH.

Allergy, Asthma and Immunology Section, Penn State University, Hershey Medical
Center, Hershey, PA 17033, USA.

Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness.
This improvement with therapy may be secondary to anti-inflammatory effects,
leading to a reduction of inflammatory mediators, or to a mechanical reduction of
congestion directly leading to improvement in sleep disturbance. We combined our 
data from 3 placebo-controlled studies of intranasal corticosteroids in patients 
with perennial rhinitis to determine whether a correlation between the reduction 
of congestion and improved sleep and daytime somnolence existed. The pooled data 
of budesonide, flunisolide, and fluticasone demonstrated significantly decreased 
nasal congestion, sleep problems, and sleepiness in treated patients. The data
demonstrated a correlation between a reduction in nasal congestion and an
improvement of sleep (P < .01) and daytime somnolence (P = .01). Thus, topical
intranasal corticosteroids should be used to decrease nasal congestion and to
improve sleep and daytime somnolence in patients manifesting these symptoms.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16337455 [PubMed - indexed for MEDLINE]

664: Treat Respir Med. 2005;4(6):439-46.

Impact of nasal congestion on quality of life and work productivity in allergic
rhinitis: findings from a large online survey.

Shedden A.

Schering-Plough Corporation, Kenilworth, New Jersey 07033, USA.

BACKGROUND: Allergic rhinitis is the most common allergic disease in the US. The 
predominant symptom of this condition is nasal congestion, which has a
significant impact on quality of life and work productivity. This large survey
was conducted to determine the impact of nasal congestion on the above parameters
in individuals with allergic rhinitis, and treatment patterns for this symptom.
METHODS: Participants were recruited voluntarily via telephone surveys and
internet advertisements. Respondents with nasal congestion as a symptom of their 
allergic rhinitis (or who were primary caregivers to a child with nasal
congestion associated with allergic rhinitis) were eligible for participation and
completed a 52-question internet survey. Data were normalized to the US adult
population using a weighting algorithm. RESULTS: Of the 2355 individuals with
allergic rhinitis screened for participation in the survey, 2002 (85%) had nasal 
congestion. This was considered severe by 40% of respondents, compared with fewer
than 30% who considered any other individual allergy symptom to be severe. Nasal 
congestion was the symptom that most adults and children wished to prevent, and
it affected most respondents at work or school, had a notable emotional impact,
and interfered with their ability to perform daily activities. Only 13% of
participants receiving allergic rhinitis medication of any type, including
over-the-counter medications, claimed to be very satisfied with treatment, and
only 20% adhered completely to prescribing instructions. Although intranasal
corticosteroids are recommended as first-line therapy for nasal congestion, only 
30% of respondents with severe nasal congestion received treatment with
intranasal corticosteroids. CONCLUSIONS: Nasal congestion affects most
individuals with allergic rhinitis, and has a notable impact on quality of life, 
emotional function, productivity, and the ability to perform daily activities.
Patients need to be better educated on the appropriate use of medications,
particularly intranasal corticosteroids, to manage their nasal congestion.

PMID: 16336028 [PubMed - indexed for MEDLINE]

665: Swiss Med Wkly. 2005 Sep 17;135(37-38):538-48.

Ragweed (Ambrosia) progression and its health risks: will Switzerland resist this
invasion?

Taramarcaz P, Lambelet B, Clot B, Keimer C, Hauser C.

Service of Allergology and Immunology, University Hospital of Geneva and Medical 
School, Switzerland.

The purpose of this article is to alert physicians for the environmental and
health threats of Ambrosia artemisiifolia (common ragweed) in Switzerland.
Switzerland borders several heavily ragweed colonised areas. Up to 12% of the
population suffers from allergies (hay fever, asthma) to ragweed pollen in these 
areas. Switzerland is beginning to be invaded by this plant. Currently, the
ragweed pollen counts are still low but can reach local peaks that induce
symptoms in allergic individuals. Ragweed allergy, however, is still rare in
Switzerland. Because the amount of ragweed pollen was increasing in the last few 
years, identification and surveillance of ragweed plant foci was started.
Colonisation is currently systematically monitored in Geneva and southern Tessin.
Major accumulation of ragweed foci have been detected in the canton of Geneva,
the western shore of the lake of Geneva belonging to the canton of Vaud, and in
the southern part of the canton of Tessin, aside from minor foci registered all
over Switzerland. The routes of ragweed invasion are presented and discussed.
Current measures of ragweed containment and needs for the future are presented.
The urge for these measures at an early stage of ragweed spread is underlined by 
the impracticability of eradication in highly colonised areas. The costs of
preventing ragweed spread in Switzerland are likely to be several magnitudes
lower than the treatment of a significant percentage of the Swiss population for 
ragweed pollen allergy. Because areas can change from low to heavy ragweed
colonisation within a few years, the current window of opportunity to prevent
further colonisation by ragweed should not be missed.

Publication Types: 
    Review

PMID: 16333764 [PubMed - indexed for MEDLINE]

666: Drug Saf. 2005;28(12):1101-18.

The safety and efficacy of desloratadine for the management of allergic disease.

Berger WE.

Department of Pediatrics, Division of Allergy and Immunology, University of
California, Irvine, California, USA. weberger@uci.edu

Allergic disease is an increasing problem worldwide. Allergic rhinitis, an
inflammatory response to an allergen, affects an estimated 20-40 million people
in the US, while chronic idiopathic urticaria is a dermatoallergic condition that
affects 0.1-3% of people in the US and Europe. The primary goals of treatment for
allergic rhinitis are to reduce symptoms, which include sneezing, rhinorrhoea and
nasal congestion, improve quality of life and prevent the sequelae associated
with this disease, while the goal for chronic idiopathic urticaria is the rapid
and prolonged control of symptoms. Quantitatively, histamine is the most abundant
mediator present during an allergic episode - thus, antihistamines (historically 
called histamine H(1) receptor antagonists, now called H(1) receptor inverse
agonists) are a first-line defense against allergic rhinitis and chronic
idiopathic urticaria. Although first-generation antihistamines can cause sedation
and cognitive impairment, second-generation antihistamines are relatively
non-sedating and free of such adverse events owing to their comparative inability
to penetrate the blood-brain barrier. Desloratadine is one such second-generation
antihistamine and is indicated for the treatment of allergic diseases, including 
allergic rhinitis and chronic idiopathic urticaria. It has proven efficacy
against the symptoms associated with seasonal and perennial allergic rhinitis,
including nasal congestion, and chronic idiopathic urticaria. As a result, it has
been shown to improve patients' quality of life. The safety and efficacy profiles
of desloratadine are well established, and published postmarketing analyses have 
assessed >54 000 patients. Although earlier second-generation antihistamines have
been associated with cardiovascular adverse effects, desloratadine has been shown
to be safe and well tolerated at nine times the recommended dose. In addition, it
has been shown to not interact with concomitantly administered drugs and food.
Overall, current data indicate that desloratadine is a safe and effective
treatment for allergic diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16329713 [PubMed - indexed for MEDLINE]

667: J Asthma. 2005 Nov;42(9):765-8.

Does specific immunotherapy injection cause an increase in bronchial reactivity?

Keskin O, Tuncer A, Yildirim S, Bursali B, Adalioglu G, Sekerel BE.

Pediatric Allergy and Asthma Unit, Ihsan Dogramaci Children's Hospital, Hacettepe
University School of Medicine, Ankara, Turkey.

BACKGROUND: Several well-controlled studies have proven the clinical benefit of
specific immunotherapy (SIT) for seasonal allergic rhinitis (AR). However,
whether subcutaneous SIT injection could cause a transient increase in bronchial 
reactivity (BR) remains unknown. OBJECTIVE: To investigate whether subcutaneous
SIT injection, either during or outside the pollen season, could cause an
increase in BR in children with pollen allergy. METHODS: Twenty-two children
(mean age 13.6 +/- 0.7 years) with AR who were receiving maintenance SIT for 15
months were included in the study. Pre-injection BR of the patients was evaluated
with methacholine provocation test immediately before maintenance dose of SIT
during the peak pollen season and outside the season. The post-injection test was
administered 24 hours after SIT injection. RESULTS: There was no difference in
FEV1 measures recorded during [98(93-109)%] and outside [102(96-111)%] the pollen
season. There was no significant difference between pre- [64(7-64) mg/mL] and
post-allergen injection [32(7.5-64) mg/mL] BR outside the pollen season (p =
0.9). A trend towards improvement following allergen injection [64(5.4-64)] as
compared to pre-allergen injection [14.6(3.5-64)] was shown during the pollen
season (p = 0.053). Although PC20 measures in the pollen season were lower than
outside the season, the difference was not significant. The percentage of the
patients with bronchial hyperreactivity was 62% during and 43% outside the
season. CONCLUSION: SIT injections both during and outside the pollen season
cause no increase in BR in children with AR. This calls into question the
necessity of empirical dose reduction during the pollen season.

PMID: 16316871 [PubMed - indexed for MEDLINE]

668: Ann Allergy Asthma Immunol. 2005 Nov;95(5):474-9.

Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of
seasonal allergic rhinitis to mountain cedar.

Ratner PH, Hampel FC, Amar NJ, van Bavel JH, Mohar D, Marple BF, Roland PS, Wall 
GM, Brubaker MJ, Drake M, Turner D, Silver LH.

Sylvana Research, San Antonio, Texas 78229, USA. phratner@swbell.net

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine
hydrochloride is being developed for the treatment of seasonal allergic rhinitis 
(SAR) to mountain cedar. OBJECTIVE: To evaluate the safety and efficacy of 2
concentrations of olopatadine nasal spray vs placebo nasal spray in patients with
SAR to mountain cedar. METHODS: This was a multicenter, randomized, double-blind,
placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 
12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 
sprays per nostril twice daily for 2 weeks. Patients evaluated morning and
evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny
nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and
ocular symptoms. RESULTS: Olopatadine spray (0.4% and 0.6%) was statistically
significantly superior to placebo for percentage change from baseline in overall 
reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically
significantly superior to placebo for reducing the reflective and instantaneous
assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and
watery eyes. Olopatadine spray exhibited a safety profile comparable with that of
placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided
statistically significant improvements in allergic rhinitis symptoms compared
with placebo regarding TNSSs and individual symptoms, including congestion, itchy
and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to
mountain cedar. Olopatadine nasal spray administered twice daily was safe and
well tolerated in adolescents and adults.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16312171 [PubMed - indexed for MEDLINE]

669: Med Clin North Am. 2006 Jan;90(1):17-38.

Allergic rhinitis: impact of the disease and considerations for management.

Greiner AN.

Allergy and Asthma Medical Group and Research Center, and University of
California at San Diego, San Diego, CA 92123, USA. greineran@yahoo.com

AR is a common condition affecting individuals of all ages. Those afflicted with 
AR often suffer from associated inflammatory conditions of the mucosa,such as AC,
rhinosinusitis, asthma, otitis media with effusion, and other atopic conditions, 
such as eczema and food allergies. Lack of treatment or treatment with suboptimal
therapy may result in reduced quality of life and compromise productivity at work
or school. Although environmental controls may prove difficult to implement, and 
not all controls appear adequately to mitigate symptoms of AR, they continue to
represent a foundation for treatment.Many different classes of medications are
now available, and they have been shown to be effective and safe in a large
number of well-designed, double-blind, placebo-controlled clinical trials. Some
of the over-the-counter medi-cations have been associated with increased
sedation, potentially leading to accidents and fatalities at work or while
operating complex machinery, such as automobiles. Only immunotherapy with
increasing doses of individually targeted allergens results in sustained changes 
in the immune system.Although anti-IgE is probably only the first successful
immunomodulator commercially available to treat AR, monoclonal antibodies will
remain too costly, at least in the near future, to find their way into routine AR
treatment.

Publication Types: 
    Review

PMID: 16310522 [PubMed - indexed for MEDLINE]

670: Clin Exp Allergy. 2005 Nov;35(11):1457-61.

Allergic rhinitis with or without concomitant asthma: difference in perception of
dyspnoea and levels of fractional exhaled nitric oxide.

Aronsson D, Tufvesson E, Bjermer L.

Institution of Clinical Medicine and Science, Department of Respiratory Medicine 
and Allergology, Lund, Sweden.

BACKGROUND/AIM: Allergic rhinitis (AR) is a risk factor for developing clinical
asthma. Moreover, AR is often associated with bronchial hyper-responsiveness
(BHR). The aim of the present study was to investigate whether patients with AR
and asthma differed from AR with or without BHR in degree of perception of
dyspnoea and airway inflammation, measured as fractionated exhaled nitric oxide
(NO). MATERIALS: Twenty-nine patients with seasonal AR (timothy) were
investigated with metacholine challenge test. Fourteen healthy non-reactive
subjects served as controls. METHODS: (1) Metacholine challenge test, cut-off
value forced expiratory volume in 1 s (FEV(1)) PD20 2,000 microg. Slope value for
metacholine was calculated as %fall in FEV(1)/mol metacholine. Dyspnoea during
challenge was measured with a 10-graded modified Borg score. (2) Measurement of
fractional-exhaled nitric oxide (FENO) at flow rate 50 mL/s. RESULTS: Eighteen
patients reported AR only, without asthma symptoms, and 12 (67%) were BHR. Eleven
subjects had both rhinitis and asthma symptoms. Patients with rhinitis and asthma
reported significantly more dyspnoea per percent fall in FEV(1) compared with
those with rhinitis and BHR. Moreover, those with rhinitis and asthma had
significantly higher NO values compared with those with rhinitis and BHR.
CONCLUSION: The difference between rhinitis patients with or without asthma
symptoms seems to be mainly a question of perception of dyspnoea. However, FENO
measurement indicates that dyspnoea may also be associated with increased
inflammatory activity in the peripheral airways.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16297142 [PubMed - indexed for MEDLINE]

671: Clin Exp Allergy. 2005 Nov;35(11):1423-31.

Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy
during the season.

Onbasi K, Sin AZ, Doganavsargil B, Onder GF, Bor S, Sebik F.

Department of Internal Medicine, Division of Immunology and Allergy, Ege
University School of Medicine, Izmir, Turkey.

BACKGROUND:The oesophagus is normally devoid of eosinophils. There are some
disorders accompanying with eosinophil infiltration. Food allergy has been
reported as a common reason, especially in children but some other studies have
also indicated that aeroallergens might have a role in oesophageal eosinophil
accumulation. OBJECTIVE:In this study we investigated whether there is any
eosinophil recruitment in the oesophagus of pollen-allergic patients who had
respiratory symptoms during the season. METHODS:Thirty-eight symptomatic patients
(allergic rhinitis (AR) with or without asthma) who had sensitization to grass
pollen were included in the study during the pollen season. Controls were
composed of 25 healthy non-atopics and 24 patients diagnosed as having
gastro-oesophageal reflux disease. Reflux was excluded in allergic and non-atopic
groups, whereas the presence of allergy was eliminated in control groups.
Gastrointestinal endoscopy was performed in all participants, and biopsy
specimens were taken from both the proximal and the distal oesophagus to evaluate
eosinophil accumulation. At the same time, blood eosinophil numbers were counted.
Results Oesophageal eosinophil accumulation was found in 10 allergic patients
(26%) and in five patients (21%) with gastro-oesophageal reflux disease but none 
of the healthy controls had eosinophils (0%) (P<0.05). Blood eosinophils were
higher in these 10 patients than the rest of the 28 patients without
infiltration. In this group, blood eosinophils were also correlated with the
number of accumulated eosinophils in the oesophagus (P<0.001). There was more
intense eosinophil infiltration at the distal part of the oesophagus in the
reflux group when compared with the allergic group (mean 7.6+/-5.6 vs.
3.2+/-3.7). Nevertheless, eosinophils were found to be concentrated (mean
5.5+/-7.3) in the proximal oesophagus of allergic patients, although it was
1.7+/-1.5 in reflux patients (P>0.05). Conclusion Our results showed that
eosinophil infiltration might be observed in oesophageal tissue of patients with 
respiratory tract allergy during the symptomatic period. This finding may
possibly reflect the systemic and common mucosal aspects of allergic
inflammation.

PMID: 16297137 [PubMed - indexed for MEDLINE]

672: J Altern Complement Med. 2005 Oct;11(5):863-9.

The effect of Gencydo injections on hayfever symptoms: a therapeutic causality
report.

Baars EW, De Bruin A.

Louis Bolk Instituut, Driebergen, The Netherlands. e.baars@louisbolk.nl

OBJECTIVES: The aim of this study was to study the effect of Gencydo (Weleda AG, 
Arlesheim, Switzerland) injections on hayfever symptoms. DESIGN: This is a
therapeutic causality report based on the practices of 13 Dutch general
practitioners. SUBJECTS: Thirteen (13) patients with a mean history of hayfever
with grass pollen allergy of 9 years duration, who in previous years used
conventional hayfever medication because of the severity of symptoms during the
pollen season. INTERVENTIONS: Gencydo injections were given in 12 patients before
the onset of and during the grass pollen season, and in one patient during the
grass pollen season only. OUTCOME MEASURES: Nasal and non-nasal hayfever symptom 
severity, use of rescue medication (antihistamines or corticosteroids), and
subjective experiences of patients were used as outcome measures. RESULTS: Nine
(9) of 13 patients showed no increase of symptom severity during the so-called
pollen season. Both the mean maximal total nasal symptom score per patient and
the mean total nasal symptom score for the entire study group during the days
with a grass pollen count >100 were mild. Percentages of individual "strong" or
"severe" nasal symptom scores were low. There was no statistically significant
difference in mean total nasal symptom score between the period when the pollen
count was <100 and the period when it was >100. Conventional rescue medication
for hayfever was used only eight times, all by one person. Nine (9) patients
(69%) reported an improvement of symptoms (eight patients cited strong
improvement and one patient noted slight improvement). CONCLUSIONS: There are
clear indications that Gencydo treatment was effective in a large subgroup of the
research population.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16296919 [PubMed - indexed for MEDLINE]

673: Endocr J. 2005 Oct;52(5):617-21.

Familial occurrence of silent thyroiditis.

Nakamura S, Isaji M, Ishimori M.

Department of Internal Medicine, Gifu Red Cross Hospital, Japan.

Two brothers and their mother, who had allergic rhinitis caused by Japanese cedar
pollen, developed silent thyroiditis in spring. In addition, these three patients
had the same HLA haplotype. Another brother, the father, and the paternal
grandmother, who did not have allergic rhinitis caused by Japanese cedar pollen, 
did not show symptoms of silent thyroiditis. The present study indicates that
genetic and/or environmental factors are important in the development of this
familial type of silent thyroiditis.

Publication Types: 
    Case Reports

PMID: 16284442 [PubMed - indexed for MEDLINE]

674: Ann Allergy Asthma Immunol. 2005 Oct;95(4):361-71.

Effects of adjuvant therapy with 0.1% olopatadine hydrochloride ophthalmic
solution on quality of life in patients with allergic rhinitis using systemic or 
nasal therapy.

Berger W, Abelson MB, Gomes PJ, Beck M, Kimura S, Westbrook T, Storms W, Galant
S.

Southern California Research, Mission Viejo, California, USA. weberger@uci.edu

BACKGROUND: Allergic rhinoconjunctivitis patients are often treated with nasal or
systemic allergy therapy, forgoing therapy for ocular symptoms. This treatment
regimen leaves important aspects of the allergic reaction untreated and affects
quality of life (QoL). The Rhinoconjunctivitis Quality of Life Questionnaire and 
the Allergic Conjunctivitis Quality of Life Questionnaire quantify separate
aspects of QoL. OBJECTIVE: To determine the benefit gained in QoL, measured by
these questionnaires, when antiallergy eyedrops (olopatadine) were added to
patients' preexisting regimens of nasal or systemic allergic rhinitis treatment. 
METHODS: This was a 4-week prospective, multicenter, open-label, crossover,
environmental QoL study. Visit 1 randomized patients to treatment group A or B
and included baseline examinations and questionnaires. Group A instilled
olopatadine twice daily and concomitantly with previously prescribed nasal or
systemic antiallergy medication for 2 weeks. Group B received no ocular therapy
and used only previously prescribed antiallergy medication for 2 weeks. Treatment
group crossover occurred at visit 2. Patients again completed the questionnaires 
at visits 2 and 3. RESULTS: Two hundred patients completed the study, 97 in group
A and 103 in group B. Groups A and B experienced ocular allergic symptoms for
3.88 and 3.96 days, respectively, during the week before baseline. At visits 2
and 3, questionnaire scores were significantly improved for each group when
olopatadine was added compared with the nontreatment periods. By visit 2,
olopatadine improved QoL by 49% compared with 5% in the nontreated group (P <
.001). CONCLUSIONS: In this study, 90.5% of patients with allergic rhinitis
treated nasally or systemically also had ocular allergic symptoms. Adding
olopatadine to these patients' medication regimens significantly improved ocular 
allergic symptoms and overall QoL.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 16279567 [PubMed - indexed for MEDLINE]

675: Ann Allergy Asthma Immunol. 2005 Oct;95(4):350-3.

Comment in:
    Ann Allergy Asthma Immunol. 2005 Oct;95(4):314.

Allergic rhinitis and ear pain in flight.

Ohrui N, Takeuchi A, Tong A, Iwata M, Nakamura A, Ohashi K.

Aeromedical Laboratory, Japan Air Self-Defense Force, Tachikawa, Tokyo 190-8585, 
Japan. aml025@asdf.mail.jda.go.jp

BACKGROUND: Ear pain is the most common physiologic incident in hypobaric chamber
training in the Japan Air Self-Defense Force, and the incidence of ear pain has
been gradually increasing. There has been a concomitant increase in the incidence
of allergic rhinitis in Japan. We hypothesized that the increased incidence of
ear pain may be due to the increased incidence of eustachian tube dysfunction
associated with allergic rhinitis. OBJECTIVE: To explore whether there is an
association between allergic rhinitis and ear pain experienced in hypobaric
chamber training. METHODS: We examined 9 years of training records and noted
whether there was a seasonal influence on the occurrence of ear pain in 7047
trainees. In addition, we studied the prevalence of allergic rhinitis among
trainees during a representative training year using a questionnaire method,
noting association between allergic rhinitis and the occurrence of ear pain.
RESULTS: Comprehensive review of training records showed 429 (6.1%) of 7047
trainees complained of ear pain. Ear pain occurred more often in spring than the 
other 3 seasons. The questionnaire data showed 202 (23.0%) of 878 trainees had
allergic rhinitis. Trainees with allergic rhinitis complained of ear pain more
often in the spring than trainees without allergic rhinitis. CONCLUSIONS: Active 
allergic rhinitis is closely associated with the occurrence of ear pain in
hypobaric chamber training. A similar phenomenon might occur in an actual flight.
Special attention should be paid to not only common cold but also allergic
rhinitis in both hypobaric chamber training and actual flights.

Publication Types: 
    Comparative Study

PMID: 16279565 [PubMed - indexed for MEDLINE]

676: Ann Pharmacother. 2005 Dec;39(12):2056-64. Epub 2005 Nov 8.

Treatment for allergic rhinitis and chronic idiopathic urticaria: focus on oral
antihistamines.

Morgan MM, Khan DA, Nathan RA.

Asthma and Immunology of North Texas, McKinnney, USA.

OBJECTIVE: To review the efficacy and safety of first- and newer-generation
antihistamines for the management of allergic rhinitis and chronic idiopathic
urticaria (CIU), with a focus on management in the pharmacy. DATA SOURCES: A
literature review was performed using MEDLINE (1966-October 2005), with no time
or language restrictions. Key words or phrases used were histamine,
antihistamine(s), first- and second-generation, allergic rhinitis, chronic
idiopathic urticaria, quality of life, impairment, sedation, cost-effectiveness, 
astemizole, cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine,
hydroxyzine, ketotifen, and mizolastine. Additional references were found in the 
bibliographies of the articles cited. STUDY SELECTION AND DATA EXTRACTION:
Clinical trials and other experimental studies of the use of antihistamines for
the management of allergic rhinitis and CIU were selected. Review papers and
guidelines were also included. DATA SYNTHESIS: First-generation antihistamines
are effective at ameliorating the symptoms of allergic rhinitis and CIU; however,
they are associated with adverse effects due to a lack of selectivity for the
histamine H(1)-receptor and an ability to bind to cerebral H(1)-receptors.
Newer-generation agents, in general, possess high H(1)-receptor selectivity and a
low tendency to cross the blood-brain barrier, while maintaining efficacy. In
general, safety at elevated doses has been demonstrated for the newer
antihistamines, although higher rates of sedation and impairment have been
reported with increasing doses for some agents. CONCLUSIONS: Pharmacists can play
an important role in the management of allergic rhinitis and CIU by considering
the relative advantages of newer-generation agents when reviewing treatment
options.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16278258 [PubMed - indexed for MEDLINE]

677: Ann Pharmacother. 2005 Dec;39(12):1984-9. Epub 2005 Nov 8.

Mometasone furoate improves congestion in patients with moderate-to-severe
seasonal allergic rhinitis.

Berger WE, Nayak AS, Staudinger HW.

Department of Pediatrics, Division of Allergy and Immunology, University of
California, Irvine, 92691, USA. werber@uci.edu

BACKGROUND: A recent survey estimated that 85% of patients with allergic rhinitis
experience nasal congestion. This symptom considerably impacts quality of life.
OBJECTIVE: To evaluate the effectiveness of mometasone furoate nasal spray (MFNS)
in subjects with seasonal allergic rhinitis (SAR) experiencing moderate-to-severe
nasal congestion. METHODS: Data were obtained from 4 randomized, double-blind,
placebo-controlled studies of MFNS 200 microg once daily in patients with SAR.
Subject-evaluated nasal congestion score data (score range 0-3) from subjects
receiving MFNS or placebo were analyzed as a pool and grouped according to
baseline score (all pts. with scores >2.5, >2.75, or 3.0). The 2-week average
change in score from baseline was analyzed. RESULTS: Significant improvements in 
mean nasal congestion score were seen with MFNS (n = 490) versus placebo (n =
492; p < 0.001). Overall, there was a 27% improvement in this score in patients
receiving MFNS versus 13% with placebo. MFNS produced significant reductions in
the nasal congestion score compared with placebo, even in patients with the most 
severe baseline congestion (0.98 vs 0.52; p < 0.001). Improvements in scores from
baseline of 32%, 33%, and 34% were seen with MFNS versus 22%, 21%, and 18% with
placebo (for baseline scores of >2.5, >2.75, or 3.0, respectively), confirming
the effectiveness of MFNS regardless of congestion severity. This represents an
improvement approximating a decrease from severe to moderate congestion or from
moderate-to-severe to mild-to-moderate congestion. MFNS was well tolerated.
CONCLUSIONS: MFNS 200 microg once daily produces statistically significant
improvements in nasal congestion score compared with placebo, alleviating severe 
congestion in patients with moderate-to-severe SAR.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16278257 [PubMed - indexed for MEDLINE]

678: Int Arch Allergy Immunol. 2006;139(1):25-30. Epub 2005 Nov 3.

Lack of association between the IL13 variant Arg110Gln and susceptibility to
cedar pollinosis in a Japanese population.

Cheng L, Hirota T, Enomoto T, Tamari M, Akahoshi M, Matsuda A, Shimizu M,
Takahashi N, Enomoto K, Yamasaki A, Mao XQ, Hopkin JM, Shirakawa T.

Department of Otorhinolaryngology, The First Affiliated Hospital of Nanjing
Medical University, Nanjing, China. teirai@hotmail.com

BACKGROUND: Interleukin (IL)-13 has come to be appreciated as a molecule
critically involved in allergic inflammatory responses. Recent studies revealed
that a common variant in the coding region of the IL13 gene, Arg110Gln, has been 
implicated in the development of asthma and atopy. METHODS: To assess whether the
IL13 variant Arg110Gln is associated with cedar pollinosis, one of the most
common atopic diseases in the Japanese population, we examined the Arg110Gln
variant using PCR-RFLP to compare the genotype and allele frequencies between 95 
patients with cedar pollinosis and 95 healthy control subjects. Relationships
between the Arg110Gln variant and the pollinosis-related traits, e.g. rhinitis
severity, eosinophil counts in nasal secretion and serum total and
allergen-specific IgE levels, were also investigated. RESULTS: The frequencies of
the minor allele Gln110 were 25.8% in patients with cedar pollinosis and 30.9% in
healthy control subjects (p > 0.05). There was also no significant difference in 
the genotype frequencies between cases and controls (p > 0.05). In addition, we
found no significant association of the Arg110Gln variant with any of the
pollinosis-related phenotypes (p > 0.05). CONCLUSIONS: Our data suggest lack of
evidence for identifying the variant Arg110Glnat the IL13 locus as a genetic risk
factor involved in the development of Japanese cedar pollinosis. (c) 2006 S.
Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16272823 [PubMed - indexed for MEDLINE]

679: Respir Res. 2005 Nov 7;6:132.

Downregulation of peroxisome proliferator-activated receptors (PPARs) in nasal
polyposis.

Cardell LO, Hägge M, Uddman R, Adner M.

Department of Otorhinolaryngology, Lund University, Malmö University Hospital,
Malmö, Sweden. Lars-Olaf.Cardell@med.lu.se

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR) alpha, betadelta
and gamma are nuclear receptors activated by fatty acid metabolites. An
anti-inflammatory role for these receptors in airway inflammation has been
suggested. METHODS: Nasal biopsies were obtained from 10 healthy volunteers and
10 patients with symptomatic allergic rhinitis. Nasal polyps were obtained from
22 patients, before and after 4 weeks of local steroid treatment (fluticasone).
Real-time RT-PCR was used for mRNA quantification and immunohistochemistry for
protein localization and quantification. RESULTS: mRNA expression of PPARalpha,
PPARbetadelta, PPARgamma was found in all specimens. No differences in the
expression of PPARs were obtained in nasal biopsies from patients with allergic
rhinitis and healthy volunteers. Nasal polyps exhibited lower levels of PPARalpha
and PPARgamma than normal nasal mucosa and these levels were, for PPARgamma,
further reduced following steroid treatment. PPARgamma immunoreactivity was
detected in the epithelium, but also found in smooth muscle of blood vessels,
glandular acini and inflammatory cells. Quantitative evaluation of the epithelial
immunostaining revealed no differences between nasal biopsies from patients with 
allergic rhinitis and healthy volunteers. In polyps, the PPARgamma
immunoreactivity was lower than in nasal mucosa and further decreased after
steroid treatment. CONCLUSION: The down-regulation of PPARgamma, in nasal
polyposis but not in turbinates during symptomatic seasonal rhinitis, suggests
that PPARgamma might be of importance in long standing inflammations.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16271155 [PubMed - indexed for MEDLINE]

680: Allergy Asthma Proc. 2005 Jul-Aug;26(4):275-82.

Comparative efficacy of cetirizine and fexofenadine for seasonal allergic
rhinitis, 5-12 hours postdose, in the environmental exposure unit.

Day JH, Briscoe MP, Rafeiro E, Ratz JD, Ellis AK, Frankish CW, Chapman D, deGuia 
EC, Kramer B, Warner C.

Department of Medicine, Queen's University, Kingston, Ontario, Canada.

In a previous study, cetirizine and fexofenadine similarly relieved seasonal
allergic rhinitis symptoms in the first 5 hours, but cetirizine was more
effective at 21-24 hours postdose. This randomized, double-blind,
placebo-controlled study compared the response to treatment between 5 and 12
hours. Eligible ragweed allergic subjects were exposed to pollen in the
Environmental Exposure Unit and randomized (n = 599) to a single dose of
cetirizine, 10 mg; fexofenadine, 180 mg; or placebo (2.5:2.5:1). The primary
efficacy end point was the change from baseline in total symptom severity complex
(TSSC) score at 12 hours postdose. TSSC score was the sum of self-rated scores (0
= absent to 3 = severe) for runny nose, sneezing, itchy nose/palate/throat, and
itchy/watery eyes, recorded half-hourly. Mean baseline TSSC scores were similar: 
9.2, cetirizine and fexofenadine; 8.9, placebo. Reductions in TSSC scores from
baseline were 4.3 at 12 hours and 5.0 overall (i.e., average over 5-12 hours
postdose) for cetirizine and 3.4 and 4.4, respectively, for fexofenadine.
Cetirizine produced a 26% greater reduction in TSSC at 12 hours (p = 0.001) and
14% greater reduction in TSSC overall (p = 0.006) compared with fexofenadine.
Cetirizine and fexofenadine reduced TSSC scores (p < 0.001) and individual
symptoms (p < 0.05) more than placebo. However, cetirizine was more effective
than fexofenadine (p < 0.05) for runny nose and sneezing (12 hours and overall), 
itchy/watery eyes (12 hours), and itchy nose/throat/palate (overall). Incidence
of treatment-emergent adverse events and somnolence were similar among groups:
cetirizine, 25.3 and 0.8%, respectively; fexofenadine, 29.6 and 0%, respectively;
placebo, 35.0 and 0%, respectively. In conclusion, cetirizine produced greater
relief of seasonal allergic rhinitis symptoms than fexofenadine at 12 hours
postdose and over the 5- to 12-hour postdose period.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16270720 [PubMed - indexed for MEDLINE]

681: Allergy. 2005 Dec;60(12):1524-9.

Single dose topical corticosteroid inhibits IL-5 and IL-13 in nasal lavage
following grass pollen challenge.

Erin EM, Leaker BR, Zacharasiewicz AS, Higgins LA, Williams TJ, Boyce MJ, de Boer
P, Durham SR, Barnes PJ, Hansel TT.

National Heart and Lung Institute (NHLI) Clinical Studies Unit, Imperial College,
London, UK.

BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory
exudates following nasal allergen challenge (NAC), and permits cells and released
mediators to be evaluated. Objective: To determine the effects of a single dose
of topical steroid on eosinophils and levels of chemokines and cytokines in nasal
lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients 
with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season
received either nasal budesonide (100 microg per nostril) or matched placebo
before allergen challenge in a double blind two-way crossover design. A
semi-automated mixed bead array system was employed to measure multiple
chemokines and cytokines in small volumes (50 microl) of nasal lavage
supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms
together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages
between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also
detected following allergen challenge. A single dose of nasal budesonide caused a
decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective
abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels
of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single
dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13
responses following NAC. This model should be convenient for testing novel
anti-inflammatory and immunoregulatory agents intended for the treatment of
allergic rhinitis.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16266385 [PubMed - indexed for MEDLINE]

682: J Toxicol Environ Health A. 2006 Feb;69(3-4):229-35.

Correlation of Asian dust storm events with daily clinic visits for allergic
rhinitis in Taipei, Taiwan.

Chang CC, Lee IM, Tsai SS, Yang CY.

Institute of Public Health, Kaohsiung Medical University, Kaohsiung.

In spring, windblown dust storms originating in the deserts of Mongolia and China
head toward Taipei city. These occurrences are known as Asian dust storm (ADS)
events. The objective of this study was to assess the possible associations of
ADS on the daily clinical visits for allergic rhinitis of residents in Taipei,
Taiwan, during the period 1997-2001. Forty-nine dust storms were identified and
classified as index days. Daily clinical visits for allergic rhinitis on the
index days were compared with clinical visits on the comparison (non-ADS) days.
Two non-ADS days for each index day, 7 d before the index day and 7 d after the
index day, were selected. The effects of dust storms on clinic visits for
allergic rhinitis were prominent 2 d after the event (19%). However, the
association was not statistically significant. There may not have been enough
power to detect associations resulting from the inadequate sample size of
allergic rhinitis visits on ADS days. Further study is needed to clarify this
association.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16263693 [PubMed - indexed for MEDLINE]

683: Expert Opin Emerg Drugs. 2005 Nov;10(4):689-705.

Emerging anti-inflammatory agents for allergic rhinitis.

Ciprandi G, Passalacqua G.

Dipartimento Patologie Testa-Collo, Azienda Ospedaliera Universitaria San
Martino, Allergologia-U.O. ORL, Largo R. Benzi 10, 16132 Genoa, Italy.
gio.cip@libero.it

Allergic rhinitis (AR) is a high-prevalence disease, affecting 10-15% of the
general population. AR is sustained by an IgE-mediated reaction, and by a complex
inflammatory network of cells, mediators and cytokines that becomes chronic when 
exposure to allergen persists. A T helper 2 (TH2)-biased immune response is the
basis for the allergic inflammation. The current therapeutic strategy is mainly
based on drugs (antihistamines, nasal corticosteroids, cromones, decongestants)
and allergen immunotherapy. Drugs are overall effective in controlling symptoms, 
but do not modify the immune background that leads to allergic inflammation, and 
safety concerns may be present especially for prolonged treatments. Immunotherapy
can modify the allergic response, but there is still space for improvement.
Nowadays, several approaches are under investigation to optimise the management
of AR. On one hand, new drugs and antimediators are being developed; on the other
hand, attempts are made to selectively block relevant signal pathways of allergic
reaction. Finally, one of the major goals is to modify the TH2-biased immune
response by improving the characteristics and modes of action of allergen
immunotherapy.

Publication Types: 
    Review

PMID: 16262558 [PubMed - indexed for MEDLINE]

684: J Laryngol Otol. 2005 Oct;119(10):799-805.

Immunotherapy for allergic rhinitis--a United Kingdom survey and short review.

Dhanasekar G, Izzat AB, D'Souza AR.

City Hospital, Birmingham, UK.

Allergic rhinitis (AR) is a common condition which is treated using different
modalities, including immunotherapy. The aim of this study was to survey the
current management strategies among ENT consultants in the UK in treating AR, and
their views on immunotherapy. The study design was a postal questionnaire survey 
and the setting a university teaching hospital. Participants were consultant
members of the British Association of Otolaryngologists - Head and Neck Surgeons 
(BAO-HNS). The main outcome measures were common treatment modalities adopted by 
the survey group to treat AR, and the number of consultants practising
immunotherapy. The majority (81.1 per cent) of the consultants surveyed practise 
medical therapy with or without surgery. Immunotherapy is advised by 26 per cent 
of ENT consultants, but only 6.6 per cent currently administer immunotherapy.

Publication Types: 
    Multicenter Study
    Review

PMID: 16259657 [PubMed - indexed for MEDLINE]

685: Expert Opin Pharmacother. 2005 Nov;6(14):2511-23.

Review of desloratadine for the treatment of allergic rhinitis, chronic
idiopathic urticaria and allergic inflammatory disorders.

DuBuske LM.

Immunology Research Institute of New England, Gardner, MA 01440, USA.
ldubuske@aol.com

Desloratadine is a once-daily, non-sedating, non-impairing, selective histamine
H1-receptor antagonist. It relieves the symptoms of seasonal allergic rhinitis
(including nasal obstruction and congestion, and morning symptoms), perennial
allergic rhinitis and chronic idiopathic urticaria by blocking multiple critical 
steps in the systemic allergic cascade and downregulating key allergy-induced
inflammatory mediators. It also relieves asthma symptoms and decreases rescue
medication use in patients with seasonal allergic rhinitis and comorbid asthma.
Numerous clinical studies have demonstrated that desloratadine is safe, well
tolerated and free of serious cardiac effects. Pharmacokinetic studies have
demonstrated a low propensity for drug-drug or drug-food interactions. This
review outlines the mechanism of action, efficacy and safety of desloratadine for
the treatment of allergic inflammatory disorders.

Publication Types: 
    Review

PMID: 16259582 [PubMed - indexed for MEDLINE]

686: Vascul Pharmacol. 2005 Oct;43(4):267-76. Epub 2005 Oct 27.

Evaluation of nasal barrier dysfunction at acute- and late-phase reactions in a
guinea pig model of allergic rhinitis.

Elovsson S, Smailagic A, Erjefalt I, Zackrisson C, Eriksson C, Wang X.

Department of Clinical Study Management, AstraZeneca R&D Lund, Sweden.

Allergic rhinitis is a common disease characterized by the symptoms of pruritus, 
sneezing, hypersecretion and nasal blockage. Increased mucosal barrier
permeability has been suggested to be an indicator for the severity of allergic
rhinitis. This study investigates the passage of radiolabelled albumin from the
nasal mucosal circulation into the lumen in guinea pigs intraperitoneally
sensitized and intranasally challenged with antigen. In order to characterize the
allergic rhinitis model, we evaluated a number of potential influencing factors
in nasal plasma exudation, including antigen doses, volumes of antigen solution
used, and animal position during the nasal lavage, and the conditions of nasal
lavage. The number of eosinophils and levels of histamine and leukotriene B4 in
the nasal lavage and eosinophils in the nasal mucosa were determined at the early
and late phases after antigen challenge. We also compared the effects of topical 
nasal treatments for allergic rhinitis on nasal inflammatory responses. Our
results demonstrate that, in the guinea pig nasal mucosa, topical challenge with 
antigens induces plasma exudation and histamine release at the acute-phase
reaction, and plasma exudation and eosinophil infiltration at the late-phase
reaction. These changes are similar to those reported in human allergic rhinitis.
Alterations of nasal plasma exudation, histamine release and eosinophil influx
were dependent upon the concentrations and volumes of antigens. An antihistamine 
inhibited the acute-phase reaction partially, whereas budesonide inhibited
effects at the late-phase reaction. We suggest that this model of guinea pig
allergic rhinitis with the early and late responses may be useful for
high-throughout screening of new drugs.

PMID: 16257271 [PubMed - indexed for MEDLINE]

687: Eur J Pharmacol. 2005 Nov 7;524(1-3):155-8. Epub 2005 Oct 26.

Effects of mometasone furoate on a rat allergic rhinitis model.

Tsumuro T, Ogawa M, Minami K, Takubo M, Rahman A, Fujii Y, Kamei C.

Department of Medicinal Pharmacology, Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences, Japan.

The present study was undertaken to clarify the effects of mometasone on nasal
symptoms induced by repeated intranasal application of antigen in sensitized rats
in comparison with that of chlorpheniramine. Rats received mometasone
intranasally or chlorpheniramine orally 1 h before a topical antigen challenge
for 7 days. Mometasone caused a decrease in the instances of nasal rubbing and an
inhibition of this response was observed during the treatment period. Almost
identical findings were observed with chlorpheniramine. This response was
inhibited, even after the interruption of mometasone treatment, while such an
effect was not observed with chlorpheniramine. On day 36, the changes in
sensitivity to histamine were investigated. Unlike chlorpheniramine,
hypersensitivity to histamine was significantly reduced in the mometasone-treated
group. The passive cutaneous anaphylaxis titers were elevated and reached a
maximum 8 days after the start of the topical antigen challenge. The passive
cutaneous anaphylaxis titer in the mometasone-treated group was significantly
lower than that in the control group. The results indicated that mometasone is
effective in allergic rhinitis, not only during the period of application, but
also after the interruption of application.

Publication Types: 
    Comparative Study

PMID: 16256103 [PubMed - indexed for MEDLINE]

688: Asian Pac J Allergy Immunol. 2005 Jun-Sep;23(2-3):69-78.

Clinico-immunologic evaluation of allergy to Himalayan tree pollen in atopic
subjects in India--a new record.

Bist A, Kumar L, Roy I, Ravindran P, Gaurs SN, Singh AB.

Institute of Genomics and Integrative Biology, Delhi University Campus, Delhi,
India.

Exposure to local pollen allergens has a direct bearing on the prevalence of
allergic symptoms among the inhabiting atopic population. The populations in the 
Himalayas and around it are exposed to a variety of pollen grains from trees
growing in the region, but the pollen-population interaction has not been
clinically investigated. Himalayan tree pollen from five different taxa, i.e.
Alnus nitida (AN), Betula utilis (BU), Cedrus deodara (CD), Mallotus phillipensis
(MP) and Quercus incana (QI) were evaluated for their allergenicity in the Indian
population by in vivo (skin prick test) and in vitro (ELISA)
clinico-immunological methods. The presence of specific IgE against these tree
pollen in the sera of skin test positive patients was taken as evidence for
sensitization to these pollen. The average skin positivity in atopic populations 
recorded at different allergy centers in India varied from 2.2% against AN, to
4.7% against MP pollen. Significantly raised specific IgE against these pollen
were observed in the sera of hypersensitive patients. The sensitization pattern
to Himalayan tree pollen in these atopic populations varied. It was concluded
that skin prick test positivity and raised IgE antibodies specific to AN, BU, CD,
MP and QI established Himalayan tree pollen as important sensitizers in the
atopic populations of India. A high incidence of skin sensitivity was observed to
pollen antigens of Cedrus deodara, Mallotus phillipensis and Quercus incana in
patients of Chandigarh residing in the hills and foothills of the Himalayas while
Alnus nitida, Betula utilis and Cedrus deodara were important sensitizers in
Delhi patients. The skin sensitization pattern against these pollen was in
accordance with the level of exposure to these pollen of the subjects residing in
that part of the country.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16252835 [PubMed - indexed for MEDLINE]

689: Respir Res. 2005 Oct 19;6:118.

Psoriasin, one of several new proteins identified in nasal lavage fluid from
allergic and non-allergic individuals using 2-dimensional gel electrophoresis and
mass spectrometry.

Bryborn M, Adner M, Cardell LO.

Department of Otorhinolaryngology, Malmo University Hospital, Lund University,
Malmo, Sweden. malin.bryborn@med.lu.se

BACKGROUND: Extravasation and luminal entry of plasma occurs continuously in the 
nose. This process is markedly facilitated in patients with symptomatic allergic 
rhinitis, resulting in an increased secretion of proteins. Identification of
these proteins is an important step in the understanding of the pathological
mechanisms in allergic diseases. DNA microarrays have recently made it possible
to compare mRNA profiles of lavage fluids from healthy and diseased patients,
whereas information on the protein level is still lacking. METHODS: Nasal lavage 
fluid was collected from 11 patients with symptomatic allergic rhinitis and 11
healthy volunteers. 2-dimensional gel electrophoresis was used to separate
proteins in the lavage fluids. Protein spots were picked from the gels and
identified using mass spectrometry and database search. Selected proteins were
confirmed with western blot. RESULTS: 61 spots were identified, of which 21 were 
separate proteins. 6 of these proteins (psoriasin, galectin-3, alpha enolase,
intersectin-2, Wnt-2B and hypothetical protein MGC33648) had not previously been 
described in nasal lavage fluids. The levels of psoriasin were markedly
down-regulated in allergic individuals. Prolactin-inducible protein was also
found to be down-regulated, whereas different fragments of albumin together with 
Ig gamma 2 chain c region, transthyretin and splice isoform 1 of Wnt-2B were
up-regulated among the allergic patients. CONCLUSION: The identification of
proteins in nasal lavage fluid with 2-dimensional gelelectrophoresis in
combination with mass spectrometry is a novel tool to profile protein expression 
in allergic rhinitis and it might prove useful in the hunt for new therapeutic
targets or diagnostic markers for allergic diseases. Psoriasin is a potent
chemotactic factor and its down-regulation during inflammation might be of
importance for the outcome of the disease.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16236163 [PubMed - indexed for MEDLINE]

690: Chin Med J (Engl). 2005 Oct 5;118(19):1595-603.

Efficacy of intramuscular BCG polysaccharide nucleotide on mild to moderate
bronchial asthma accompanied with allergic rhinitis: a randomized, double blind, 
placebo-controlled study.

Li J, Luo DF, Li SY, Sun BQ, Zhong NS.

Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of
Guangzhou Medical College, Guangzhou 510120, China. jingli1016@vip.163.com

BACKGROUND: Atopy is a state of allergy to common antigens and is founded on an
immune disturbance of exuberant Th2 activity and IgE production. There is also
epidemiological and experimental evidence that exposure to mycobacteria has the
potential to suppress the development of asthma or atopy. Since Th1 and Th2
immune mechanisms are significantly antagonistic, it is hypothesized that
mycobacterial exposure may moderate atopic disease by modification of immune
responses. METHODS: One hundred and twenty mild to moderate persistent asthmatics
accompanied with allergic rhinitis were randomly divided into four groups with
one injection every other day for 18 times for group A with 1 ml of normal
saline, B with 0.5 mg of Bacillus Calmette-Guérin polysaccharide nucleotide
(BCG-PSN) and C with 1 mg of BCG-PSN, 36 times for group D with 0.5 mg of
BCG-PSN. Markers for the severity of asthma and rhinitis including the amount of 
inhaled corticosteriod, bronchodilator and oral H1 blocker-loratidine being used 
to obtain optimal symptomatic control, symptom scores of asthma and allergic
rhinitis, peak expiratory flow (PEF), histamine provocative dose that produces at
least a 20% change in forced expiratory volume with in 1 second (PD20-FEV1),
blood IgE levels as well as dermatophagoides pteronysinus (DP) and
dermatophagoides farinae (DF) skin prick test were measured every visit for 6
months. RESULTS: There were no differences for symptom scores of asthma, daily
use of bronchodilator, PEF, PD20-FEV1, blood IgE as well as DF and DP skin prick 
test among the four groups. Score for allergic rhinitis decreased significantly
in groups B, C and D on day 36 and 72 as compared with group A (P < 0.05). Score 
for allergic rhinitis increased after day 72 in group B and C while it was
significantly lower in group D (P < 0.05). The patients in group D used less
amount of inhaled beclomethosone than other groups (P < 0.05) from day 72 after
the treatment to day 180. Oral loratadine consumption in groups B, C and D was
significantly less on day 36 and 72 as compared with their baseline and group A
after the treatment (P < 0.05). Group D maintained significantly lower dosage of 
oral loratadine until day 150 comparing with its baseline and group A.
CONCLUSIONS: BCG-PSN has a symptomatic effect on allergic rhinitis. BCG-PSN may
reduce the dosage of non-sedative H1 blocker loratadine as well as the dosage of 
inhaled beclomethosone in the treatment of mild to moderate asthma and allergic
rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 16232343 [PubMed - indexed for MEDLINE]

691: Int Arch Allergy Immunol. 2005 Dec;138(4):312-8. Epub 2005 Oct 11.

Meta-analysis of the efficacy of ebastine 20 mg compared to loratadine 10 mg and 
placebo in the symptomatic treatment of seasonal allergic rhinitis.

Ratner P, Falqués M, Chuecos F, Esbrí R, Gispert J, Peris F, Luria X, Rosales MJ.

Sylvana Research Associates, San Antonio, Texas, USA.

BACKGROUND: Few randomized studies have compared the efficacy of ebastine and
loratadine in the symptomatic treatment of seasonal allergic rhinitis (SAR).
METHODS: A meta-analysis was performed on data from four randomized,
double-blind, placebo-controlled, parallel-group clinical trials comparing the
efficacy of ebastine 20 mg once daily versus loratadine 10 mg once daily in the
symptomatic treatment of SAR symptoms. Primary efficacy variable was the mean
change in the overall mean daily reflective total symptom score (TSS), i.e. the
sum of five rhinitis symptom scores: nasal discharge, nasal congestion, nasal
itching, sneezing and total eye symptoms (itchy/watery eyes) over the first 2
weeks of treatment compared to baseline. RESULTS: There were 2,089 patients in
the population analyzed: 749, 739 and 601 patients in the ebastine 20 mg,
loratadine 10 mg and placebo groups, respectively. Compared to baseline, overall 
mean daily reflective TSS over the first 2 weeks of treatment was -3.61 (35.4%
reduction from baseline) in the ebastine group, -3.05 (29.0% reduction) in the
loratadine group and -2.30 (22.7% reduction) in the placebo group. Statistically 
significant differences in the mean change from baseline were found when
comparing ebastine and loratadine (p<0.001), ebastine and placebo (p<0.0001), and
loratadine and placebo (p<0.0001). The global effect (i.e. the difference in
overall mean daily reflective TSS over the first 2 weeks of treatment) of
ebastine compared with loratadine over the first 2 weeks of treatment was -0.56
(95% confidence interval, CI, -0.86 to -0.26), and it was sustained during the
whole (4-week) period studied. The global effects of ebastine and loratadine
compared with placebo were -1.30 (95% CI, -1.61 to -0.99) and -0.74 (95% CI,
-1.05 to -0.43), respectively. Secondary variables (reflective and snapshot
individual symptom scores) showed the same trend. Conclusions: This meta-analysis
confirms that ebastine 20 mg has a good efficacy profile, inducing a greater
decrease from baseline in mean rhinitis symptom scores than loratadine 10 mg or
placebo. Copyright (c) 2005 S. Karger AG, Basel.

Publication Types: 
    Comparative Study
    Meta-Analysis

PMID: 16224195 [PubMed - indexed for MEDLINE]

692: Rhinology. 2005 Sep;43(3):215-20.

Nasal cytologies--impact of sampling method, repeated sampling and interobserver 
variability.

Deutschle T, Friemel E, Starnecker K, Riechelmann H.

Department of Otorhinolaryngology, University of Ulm, Medical School, Ulm,
Germany. tom.deutschle@medizin.uni-ulm.de

The influence of sampling technique, repeated sampling and the interobserver
variability on quantitative analysis of nasal cytologies were explored. Nasal
cytologies from 12 healthy and 4 allergic volunteers were repeatedly collected
with a total of three different sampling techniques. Cells were demonstrated by
May-Grünwald-Giemsa staining and by immunostaining for CD45 and eosinophil
peroxidase (EPO). To determine the interobserver variability specimens were
evaluated by three observers with various levels of nasal cytology experience.
When adjusted for the variability due to sampling method and repeated sampling,
the staining index for CD45+ cells was 53.4 +/- 11% (interindividual coefficient 
of variation: 0.21) with an average intraindividual coefficient of variation of
0.14. For CD45, staining indices differed significantly between the washing
techniques and the nasal swabs (p<0.01). Repeated sampling did significantly
influence the staining indices of specimens collected with nasal swabs (p<0.05). 
Subjects with nasal allergy had less CD45+ cells in their nasal cytologies than
the non-allergic subjects (p=0.02). A high level of compliance for the
quantitative analysis of nasal cytologies between three observers was found
(kappa(w) range 0.95-0.98). For studies that require repeated sampling, the
lavage will be recommended as best suitable to obtain nasal cytologies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16218516 [PubMed - indexed for MEDLINE]

693: Otolaryngol Head Neck Surg. 2005 Oct;133(4):538-43.

The effects of short-term immunotherapy using molecular standardized grass and
rye allergens compared with symptomatic drug treatment on rhinoconjunctivitis
symptoms, skin sensitivity, and specific nasal reactivity.

Klimek L, Mewes T, Wolf H, Hansen I, Schnitker J, Mann WJ.

Department of Otorhinolaryngology, Mainz University Hospital, Bielefeld, Germany.

BACKGROUND: The efficacy and safety of short-term immunotherapy with molecular
standardized allergens (STI) has been demonstrated by double-blind
placebo-controlled clinical trials. The aim of this study was to compare STI with
symptomatic drug treatment. METHODS: Forty-eight patients with
rhinoconjunctivitis to grass and/or rye pollen were treated either with STI
(ALK(7), n = 24) plus anti-allergic drugs or anti-allergic drugs, alone (n = 24) 
in a prospective, randomized study. Symptoms and use of drugs were reported in
patient diaries and titrated nasal provocation and skin prick tests were
performed at baseline, before, and after season. RESULTS: Median overall symptom 
(P = 0.022, U test) and medication scores (P = 0.003) were significantly lower in
the STI group, as was the result for a simultaneous analysis of conjunctival,
nasal, and bronchial symptom scores and medication (P = 0.005). Sensitivity in
the nasal provocation test decreased in the STI group but not in the drug-treated
group. These differences became significant directly after STI (P = 0.027) as
well as after the grass pollen season (P < 0.001). Skin sensitivity did not
change in the STI group but increased in the drug-treated group after season,
with a significant difference between the two groups for the erythema (P <
0.001). CONCLUSIONS: STI reduces grass pollen-induced rhinoconjunctivitis
symptoms and drug use, and specific nasal reactivity and skin sensitivity, more
efficiently than a standard symptomatic treatment.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16213926 [PubMed - indexed for MEDLINE]

694: Otolaryngol Head Neck Surg. 2005 Oct;133(4):467-87; discussion 488.

Erratum in:
    Otolaryngol Head Neck Surg. 2005 Dec;133(6):999.

Optimal duration of allergic rhinitis clinical trials.

Krouse JH, Roland PS, Marple BF, Wall GM, Hannley M, Golla S, Hunsaker D.

Department of Otolaryngology-Head and Neck Surgery, Wayne State University,
Detroit, MI 48201, USA. jkrouse@med.wayne.edu

OBJECTIVE: Guidelines have been published by the Food and Drug Administration
(FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) for
the conduct of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis
(PAR) studies. These guidelines have differences regarding the duration of such
trials: the FDA suggests 2 weeks for SAR and 4 weeks for PAR but the EMEA
suggests 2 to 4 weeks for SAR and 6 to 12 weeks for PAR trials. In the interest
of global harmonization, it would be desirable to have a uniform duration of such
trials so that investigators, internationally, would be able to readily compare
results for various types of treatments based on a single standard. Therefore, we
performed an evidence-based review to answer the clinical question, What is the
optimal duration for SAR and PAR clinical trials? METHODS: We performed a MEDLINE
search of the published literature from 1995 to the present. We used appropriate 
search terms, such as allergic rhinitis, seasonal allergic rhinitis, perennial
allergic rhinitis, SAR, and PAR, to identify pertinent articles. These articles
were reviewed and graded according to the evidence quality. RESULTS: After an
initial screening of more than 300 articles, 138 articles were analyzed
thoroughly. No study specifically addressed the question of the optimal duration 
of SAR or PAR clinical trials. CONCLUSIONS: We conclude that the current FDA
(draft) guidelines calling for a study length of 2 weeks for the assessment of
drug efficacy for SAR and 4 weeks for the study of drug efficacy in PAR are
appropriate and that longer study periods are not likely to add meaningfully to
the assessment of drug efficacy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16213915 [PubMed - indexed for MEDLINE]

695: Int Arch Allergy Immunol. 2005 Nov;138(3):209-16. Epub 2005 Oct 4.

The effect of desloratadine on eosinophil/basophil progenitors and other
inflammatory markers in seasonal allergic rhinitis: a placebo-controlled
randomized study.

Cyr MM, Hayes LM, Crawford L, Baatjes AJ, Keith PK, Denburg JA.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

BACKGROUND: Eosinophil/basophil (Eo/B) progenitors fluctuate in the peripheral
circulation during seasonal allergen exposure in atopic subjects. Several drugs
have been shown to modulate Eo/B progenitor levels in the peripheral blood but,
to date, the possible effect of antihistamines on Eo/B progenitors has not been
explored. Our objective was to evaluate whether the antihistamine desloratadine
(DL) can modulate peripheral blood Eo/B progenitors or other markers of allergic 
inflammation. METHODS: We performed a randomized double-blind placebo-controlled 
study on the effects of DL on peripheral blood Eo/B progenitors in subjects with 
symptomatic, seasonal allergic rhinitis during a ragweed pollen season.
Forty-five subjects were randomized to treatment for 4 weeks with DL 20 mg daily 
or placebo. RESULTS: The expected fall in the number of Eo/B progenitors from
baseline to 2 weeks of treatment was seen in the placebo group [median drop of
1.0 colony-forming unit (CFU)/10(6) cells], and was greater than in the DL group 
(median drop of 0.0 CFU/10(6) cells) (p = 0.013). The change in histamine
concentration per colony from baseline to 2 weeks of treatment was lower in the
DL group (median decrease of 6.1 pg/colony) compared to placebo (median increase 
of 1.8 pg/colony) (p = 0.01). An increase in the nasal lavage eotaxin
concentration from baseline to 4 weeks of treatment was statistically significant
in the placebo group but not in the DL group. Eo/B CFU were not affected by
varying in vitro concentrations of DL. Conclusion: These results suggest that DL 
can modulate aspects of allergic inflammation in vivo through mechanisms other
than simple blockade of H1 histamine receptors.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16210859 [PubMed - indexed for MEDLINE]

696: J Physiol Pharmacol. 2005 Sep;56 Suppl 4:227-36.

Induced sputum eosinophils, bronchial reactivity, and cough sensitivity in
subjects with allergic rhinitis.

Tatar M, Petriskova J, Zucha J, Pecova R, Hutka Z, Raffajova J, Brozmanova M.

Department of Pathophysiology, Jessenius School of Medicine, Comenius University,
Martin, Slovakia. tatar@jfmed.uniba.sk

Some patients with allergic rhinitis and no clinical evidence of asthma exhibit
bronchial hyperresponsiveness. In the present study, induced sputum and
acetylcholine and capsaicin challenges were assessed in four groups of adult
subjects: allergic rhinitis (AR), allergic rhinitis with lower airway symptoms
(ARLA), mild stable asthma (BA), and healthy volunteers (C) to correlate lower
airway inflammatory markers with bronchial and cough reactivity. Patients with AR
(n = 13) and ARLA (n = 11) did not take any anti-inflammatory drugs. Those with
BA (n = 9) used inhaled corticosteroids and C (n = 10) were respiratory symptoms 
free. The patients underwent capsaicin cough challenge and sputum induction with 
hypertonic saline during the first visit, and acetylcholine bronchial challenge
on a separate day. We found that the percentage of eosinophils in induced sputum 
was significantly higher in patients with AR, ARLA, and BA than in C 14.5
+/-1.8(SE) vs. 13.5 +/-2.9 vs. 13.9 +/-4.0 vs. 3.6 +/-0.8 %, respectively
(P=0.012). In contrast, acetylcholine PD(20) in patients with AR, ARLA, and BA
was significantly lower than in C 5.6 +/-0.9 vs. 4.1 +/-0.4 vs. 2.8 +/-0.4 vs.
12.9 +/-2.7 mg, respectively (P=0.0001). Neither the eosinophil percentage nor
PD20, nor cough sensitivity appreciably differed across the patients groups.
Sputum eosinophils correlated significantly with the acetylcholine PD(20)
(r=0.37, P=0.016). We conclude that eosinophilic inflammation of lower airways
and increased bronchial reactivity were present in adult patients with allergic
rhinitis.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16204798 [PubMed - indexed for MEDLINE]

697: J Physiol Pharmacol. 2005 Sep;56 Suppl 4:185-95.

Effects of intranasal histamine on the cough reflex in subjects with allergic
rhinitis.

Plevkova J, Brozmanova M, Pecova R, Tatar M.

Department of Pathophysiology, Jessenius Medical School, Comenius University,
Martin, Slovakia. plevkova@jfmed.uniba.sk

In the present study we investigated the effects of nasal histamine on the
intensity of coughing and the effects of intensified nasal breathing following
nasal histamine on cough sensitivity (CS) in 14 subjects with seasonal allergic
rhinitis. The study consisted of two parts performed one week apart. First,
baseline CS to capsaicin was determined, followed by intranasal histamine
challenge (4 mg/ml, 0.1 ml) and the count of the number of coughs to inhaled
capsaicin on the background of most intensive nasal symptoms (sneezing, itching, 
rhinorrhea, and nasal blockage) evoked by histamine. In the second part, CS was
determined after intranasal histamine followed by 10 min of intensified nasal
breathing through the nose or mouth in a randomized order at 2-day intervals. The
number of coughs induced after intranasal histamine was significantly higher,
compared with intranasal saline, [9 (7-12) vs. 4.5 (4-6), P<0.001]. CS also was
significantly increased after nasal histamine, but nasal intensified breathing
failed to cause any changes in CS. We conclude that stimulation of nasal mucosa
with histamine enhanced the cough response in subjects with allergic rhinitis.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16204792 [PubMed - indexed for MEDLINE]

698: J Physiol Pharmacol. 2005 Sep;56 Suppl 4:171-8.

Cough sensitivity in allergic rhinitis.

Pecova R, Vrlik M, Tatar M.

Department of Pathophysiology, Jessenius Medical School, Comenius University,
Martin, Slovakia. pecova@jfmed.uniba.sk

The objective of this study was to evaluate capsaicin cough sensitivity in pollen
sensitive patients with allergic rhinitis at the time of grass pollen season and 
out of it. Cough reflex sensitivity was defined as the lowest capsaicin
concentration that evoked 2 or more coughs (C2). Capsaicin aerosol in doubled
concentrations (from 0.02 to 200 micromol) was inhaled by a single breath. Two
groups of pollen sensitive rhinitis subjects and a group of healthy controls were
studied. The C2 for the 23 pollen sensitive patients of the first group, studied 
out of pollen season (January-February), was 0.22 micromol/l (0.06-0.76)
(geometric mean + 95% CI), which was substantially lower than the 4.29 micromol/l
(2.54-7.26) in 24 healthy volunteers (P=0.0001). In another group of 15 pollen
sensitive patients, C2 was 0.84 micromol/l (0.14-5.20) out of pollen season and
0.11 micromol/l (0.03-0.33) during the pollen season (May-June) (P=0.04). We
conclude that pollen-sensitive subjects who suffer of seasonal allergic rhinitis 
have significantly greater capsaicin cough sensitivity, regardless of them being 
in or out of pollen season. Subclinical inflammatory changes in the lower airways
are probably responsible for this effect.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16204790 [PubMed - indexed for MEDLINE]

699: Ann Allergy Asthma Immunol. 2005 Sep;95(3):272-82.

Efficacy, cost-effectiveness, and tolerability of mometasone furoate,
levocabastine, and disodium cromoglycate nasal sprays in the treatment of
seasonal allergic rhinitis.

Lange B, Lukat KF, Rettig K, Holtappels G, Bachert C.

Institut für Atemwegsforschung GmbH, Düsseldorf, Germany. dnreblange@aol.com

BACKGROUND: Current guidelines recommend intranasal glucocorticosteroids as
first-line therapy for seasonal allergic rhinitis. OBJECTIVE: To compare the
efficacy, cost-effectiveness, and tolerability of the topical glucocorticosteroid
mometasone furoate, the topical antihistamine levocabastine hydrochloride, and
the cromone disodium cromoglycate in seasonal allergic rhinitis. METHODS: This
study was performed during the 2003 grass pollen season as an open, randomized,
parallel-group, single-center study of 123 patients assigned to receive
mometasone furoate (200 microg once daily), levocabastine hydrochloride (200
microg twice daily), or disodium cromoglycate (5.6 mg 4 times daily). Symptom
scores and nasal inspiratory peak flow measurements were recorded in a patient
diary. The global efficacy of the study medication was evaluated by patients
after treatment. Eosinophil cationic protein concentrations were measured in
nasal secretions before and after treatment. Cost-effectiveness was evaluated as 
medication cost per treatment success. RESULTS: Mometasone furoate therapy was
significantly superior to the use of levocabastine or disodium cromoglycate with 
respect to all nasal symptoms, the global evaluation of efficacy, and eosinophil 
cationic protein concentration. Furthermore, mometasone furoate therapy was
significantly superior to disodium cromoglycate therapy with respect to nasal
inspiratory peak flow. Medication cost per treatment success was lowest with
mometasone furoate use and highest with levocabastine use. CONCLUSION: This is
the first study to compare mometasone furoate nasal spray with nonsteroidal
topical treatments for seasonal allergic rhinitis. Mometasone furoate nasal spray
was confirmed as a first-choice topical treatment option for seasonal allergic
rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16200819 [PubMed - indexed for MEDLINE]

700: Biosci Biotechnol Biochem. 2005 Sep;69(9):1652-60.

Effect of milk fermented with Lactobacillus acidophilus strain L-92 on symptoms
of Japanese cedar pollen allergy: a randomized placebo-controlled trial.

Ishida Y, Nakamura F, Kanzato H, Sawada D, Yamamoto N, Kagata H, Oh-Ida M,
Takeuchi H, Fujiwara S.

R&D Center, Calpis Co., Ltd., Fuchinobe, Kanagawa 229-0006, Japan.

A placebo-controlled, single-blind study was conducted to evaluate the effects of
Lactobacillus acidophilus strain L-92 (L-92) on the symptoms of Japanese
cedar-pollen allergy. This study was carried out during the 2002 and 2003 seasons
of Japanese cedar pollination. Twenty-three in-house volunteers were asked to
drink 100 ml of heat-treated milk fermented with L-92 containing 5 x 10(10) of
the bacteria, twice a day, for 6 consecutive weeks. A similar study was carried
out during the 2003 season for 10 weeks, but the daily dose of bacteria was 2 x
10(10). A significant improvement of the ocular symptom-medication score (SMS)
was observed in 2002 and of the score of distress of life in 2003. These data
show that a daily oral intake of not less than 2 x 10(10) heat-treated L-92 cells
improved the symptoms of Japanese cedar pollinosis, thereby contributing to
reduce the dose of concomitant medications. However, no blood parameter was
significantly affected in these trials.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 16195581 [PubMed - indexed for MEDLINE]

701: Acta Pharm. 2005 Jun;55(2):123-38.

Anti-IgE therapy with omalizumab in asthma and allergic rhinitis.

Dodig S, Richter D, Cepelak I, Benko B.

Special Hospital for Respiratory Diseases in Children and Adolescents, Reference 
Center for Clinical Pediatric Allergology of the Croatian Ministry of Health
Zagreb, Croatia. slavica.dodig@zg.t-com.hr

The pharmacology, efficacy, dosage, adverse effects, and economics of anti IgE
(omalizumab) are discussed. Omalizumab is the generic name for the human/murine
chimeric (recombinant humanized) monoclonal IgG antibody. Anti-IgE prevents IgE
from attaching to effector cells, and thereby blunts IgE-mediated inflammatory
responses. After subcutaneous administration its absorption is slow, reaching
peak concentration in serum after an average of 7-8 days. At recommended doses,
serum free IgE levels decrease within 1 hour following the first dose and are
maintained between doses. Dose and dosing frequency are adjusted according to
body mass and serum total IgE concentration before the start of treatment.
Omalizumab administered subcutaneously is an effective treatment for add-on
therapy in patients with poorly controlled, moderate-to-severe allergic asthma
and allergic rhinitis (adults and adolescents > 12 years). It reduces the
requirement for inhaled corticosteroids while protecting against disease
exacerbation. Omalizumab is well tolerated, but the safety profile requires
long-term assessment in adults as well as in children.

Publication Types: 
    Review

PMID: 16179127 [PubMed - indexed for MEDLINE]

702: Mayo Clin Proc. 2005 Sep;80(9):1170-6.

Evaluation of the optimal oral antihistamine for patients with allergic rhinitis.

Meltzer EO.

Allergy and Asthma Medical Group and Research Center, 9610 Granite Ridge Dr,
Suite B, San Diego, CA 92123, USA. eomeltzer@aol.com

Because of its bothersome symptoms, allergic rhinitis (AR) is 1 of the top 10
reasons for patient visits to primary care physicians. This highly prevalent
disease also results in loss of productivity, both at work and in school. Oral
antihistamines are one of the most frequently prescribed medications for the
management of AR and, with several agents available, it is important to discern
the specific benefits and detriments of each. To assess the differences in
efficacy and safety factors among antihistamines, the Individual therapeutic
window of each agent can be used as a comparative reference tool because it
defines the dose range over which an antihistamine is efficacious and free of
adverse effects. As such, the therapeutic window includes both undesired effects,
such as sedation, and desired properties, such as rapid onset of action, long
duration of efficacy, broad age range of applicability, and potential to Improve 
quality of life. Therefore, agents with broad therapeutic windows, based on both 
efficacy and safety, are expected to be more favorable; this therapeutic window
should be understood by the primary care physician when prescribing a medication.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16178497 [PubMed - indexed for MEDLINE]

703: Pediatr Allergy Immunol. 2005 Sep;16(6):501-6.

The prevalence of peanut sensitization and the association to pollen
sensitization in a cohort of unselected adolescents--The Odense Adolescence
Cohort Study on Atopic Diseases and Dermatitis (TOACS).

Mortz CG, Andersen KE, Bindslev-Jensen C.

Department of Dermatology, Odense University Hospital, Odense C, Denmark.
mortz@allergi.sdu.dk

In the last decade an increased occurrence of peanut hypersensitivity and severe 
anaphylactic reactions to peanut have been reported. However, few prevalence
studies have been performed in unselected populations. This study evaluated the
point prevalence of peanut hypersensitivity in Danish adolescents. The point
prevalence of peanut allergy confirmed by oral challenge was estimated to 0.5%.
The number of adolescents sensitized to peanut by specific immunoglobulin E (IgE)
(CAP FEIA) and skin prick test (SPT) were higher (5.8% resp. 3.4%). In
adolescents without clinically relevant peanut sensitization most cases were
sensitized to grass pollen and the IgE class for grass was higher than for
peanut. A correlation between peanut and pollen (grass) sensitization is
therefore plausible. Before a positive SPT or specific IgE measurement to peanut 
is considered clinically relevant in a patient, the case history should be
evaluated together with examination for pollen sensitization.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16176397 [PubMed - indexed for MEDLINE]

704: Pediatr Allergy Immunol. 2005 Sep;16(6):478-86.

Bronchial hyper-responsiveness predicts the development of mild clinical asthma
within 2 yr in school children with hay-fever.

Ferdousi HA, Zetterström O, Dreborg S.

Department of Paediatrics, University Hospital of Linköping, Linköping, Sweden.

In children with mild asthma, symptoms are not always apparent. Therefore,
results of tests play an important role for the diagnosis. First, to investigate 
whether children with bronchial hyper-responsiveness (BHR) but no symptoms of
asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim
was to find out the diagnostic properties of tests for asthma/allergic
inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms 
of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to 
diagnose asthma in a group of children with hay fever. Twenty-eight children with
pollinosis, 12 of them with a history of asthma for the first time during the
season 1992, were studied during the birch pollen season and in the autumn of
1994. During both periods, the bronchial hyper-reactivity was estimated by
methacholine bronchial provocation tests (MBPT), bronchial variability by peak
expiratory flow rate variability, subjective symptoms of asthma by visual
analogue scale (VAS) and bronchial inflammation by serum and urine levels of
inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16
children with BHR but without clinical asthma in 1992 had developed asthma in
1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992
had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in
1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained
their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28
hay-fever children had a positive IHCA tests and 24 had positive MBPT. In
relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was
high, but the specificity low, whereas the specificity of most other tests was
high, but based on few individuals. In relation to DDA both the IHCA test
(65-80%) and the MBPT test (79-85%) had a high sensitivity and it was three to
six times more likely to find a positive test among asthmatics than in
non-asthmatics. Children with hay fever without clinical asthma have a high risk 
of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and 
the MBPT showed a high sensitivity.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16176394 [PubMed - indexed for MEDLINE]

705: Int Arch Allergy Immunol. 2005 Oct;138(2):105-10. Epub 2005 Sep 19.

Possible relationship between systemic side effects and sensitization to rPar j 2
in allergic patients submitted to an ultra-rush (20 min) sublingual immunotherapy
and selected by component resolved diagnosis.

Rossi RE, Monasterolo G, Coco G, Operti D.

Allergy Unit National Health Service, Regione Piemonte, Cuneo, Italy.
immunoway@libero.it

BACKGROUND: The pollen of Parietaria spp., a weed of the Urticaceae family, is a 
major cause of respiratory allergy in the Mediterranean area, where the most
common species are Parietaria judaica and Parietaria officinalis. In this study, 
we evaluated the specific serum IgE-binding profiles to individual P. judaica
pollen recombinant major allergen, and Phleum pratense cytoskeletal profilin and 
a 2-EF-hand calcium-binding allergen homologous to cross-reactive Parietaria
pollen allergens, in patients allergic to pollen with positive skin test towards 
Parietaria spp. extract. METHODS: The present observation included 220 patients
from the province of Cuneo, north-west Italy, all suffering from
rhino-conjunctivitis and/or asthma selected on the basis of skin test positive to
P. judaica extract. The sera were evaluated for specific IgE reactivity to P.
judaica pollen major recombinant(r) allergen Par j 2, Phleum pratense pollen
allergens rPhl p 7 (2-EF-hand calcium binding protein) and rPhl p 12 (profilin), 
both identified as cross-reactive Parietaria spp. allergens, using Pharmacia CAP 
System. Out of 220 patients, 37 patients with IgE reactivity to rPar j 2 and 105 
patients sensitized to at least one timothy pollen major allergen (i. e. rPhl p
1, rPhl p 2, natural Phl p 4 and rPhl p 6) were submitted to an ultra-rush
protocol of sublingual immunotherapy (SLIT). The occurrence of adverse reactions 
were evaluated in both groups. RESULTS: All 220 patients with pollinosis and
positive in vivo skin prick tests had in vitro positive CAP results to P. judaica
natural extract. On the contrary, in these patients the prevalence of Par j
2-specific IgE was only 33.2% (73/220). In fact, 116/220 (52.7%) patients with
serum specific IgE to crude Parietaria pollen extract had specific IgE to Phl p
12, 18/220 (8.1%) subjects with specific IgE to rPhl p 12 also exhibited specific
IgE to Phl p 7 and 26/220 (11.8%) subjects had specific IgE against rPhl p 7.
Particularly, geometric mean (25th-75th percentile) of specific IgE to rPar j 2
were as follows: 2.87 kUA/l (1.005-7.465). Out of 73 patients with specific IgE
to rPar j 2, 7 subjects (9.6%) had also specific IgE to rPhl p 7, 12 (16.4%) had 
specific IgE to rPhl p 12 and 4 (4.1%) patients had specific IgE to both
recombinant allergens. Of 37 patients under an ultra-rush protocol of SLIT, 3
subjects (8.1%) experienced generalized urticaria, and 1 of them also had
diarrhea 3 h after the last dose of Parietaria judaica extract oral-vaccine
administration. On the contrary, no systemic reactions were observed in 105
patients after Phleum pratense extract oral intake after a similar ultra-rush
SLIT protocol (p = 0.0046). CONCLUSIONS: In the light of present findings,
allergen extract-based diagnosis, in vivo and in vitro, cannot discriminate
allergic patients that are genuinely sensitized to Parietaria spp. major
allergens or to other major allergens to which current immunotherapeutic allergy 
extracts are standardized. Therefore, in vitro component resolved diagnosis is
the unique tool to define the disease eliciting molecule(s). Finally, during
sublingual immunotherapy, not only the dose of allergen, but also the biochemical
characteristic of the major allergen administered may be an important factor in
determining possible systemic reactions. (c) 2005 S. Karger AG, Basel

PMID: 16174987 [PubMed - indexed for MEDLINE]

706: Clin Exp Allergy. 2005 Sep;35(9):1192-6.

Effect of salbutamol on nasal symptoms and mast cell degranulation induced by
adenosine 5' monophosphate nasal challenge.

Russo C, Zeng D, Prosperini G, Spicuzza L, Guarino F, Polosa R.

Dipartimento di Medicina Interna e Specialistica, University of Catania, Via
Passo Gravina 187, 95125 Catania, Italy.

BACKGROUND: In addition to its well-known functional agonism at the level of
beta(2) adrenergic receptors on airways smooth muscle cells, salbutamol appears
to have additional protective effects, possibly through an inhibition of mast
cell activation. OBJECTIVE: The aim of this study is to provide the first
evidence in vivo of inhibition of human mast cell activation by salbutamol.
METHODS: Nine atopic subjects received placebo and salbutamol (5 mg/mL) 15 min
before an adenosine 5' monophosphate (AMP) nasal provocation in a double-blind
crossover study design. The nasal lavage was collected from these subjects prior 
to or 3, 5, 15 or 30 min after the AMP nasal challenge, and concentrations of
histamine and tryptase in the nasal lavage were measured. RESULTS: AMP nasal
provocation produced considerable sneezing and induced a transient increase in
histamine and tryptase release with peak values achieved at 3 min after the
challenge in all the subjects studied. Compared with placebo, salbutamol
significantly attenuated the release of histamine and tryptase induced by AMP
challenge (P=0.048 and 0.020, respectively). Moreover, the AMP-induced sneezing
was also inhibited by pre-treatment with salbutamol (P=0.004). CONCLUSIONS:
Intranasal salbutamol attenuates nasal symptoms and inhibits histamine and
tryptase release caused by AMP nasal provocation thus supporting the hypothesis
that salbutamol may play an additional protective role in the airways by
inhibiting mast cell activation.

Publication Types: 
    Randomized Controlled Trial

PMID: 16164447 [PubMed - indexed for MEDLINE]

707: J Allergy Clin Immunol. 2005 Sep;116(3):608-13.

Allergen-specific immunotherapy with recombinant grass pollen allergens.

Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O.

Department of Internal Medicine and Allergology, Wroclaw Medical University,
Wroclaw, Poland. mjutel@ak.am.wroc.pl

BACKGROUND: Allergen-specific immunotherapy uses aqueous extracts of natural
source materials as a basis for preparations to down regulate the allergic
response. Recombinant DNA technology has enabled the cloning of many allergens,
thus facilitating investigations aimed at improving efficacy and safety of
immunotherapy. OBJECTIVE: To determine the effectiveness of a mixture of 5
recombinant grass pollen allergens in reducing symptoms and need for symptomatic 
medication in patients allergic to grass pollen. METHODS: A randomized,
double-blind, placebo-controlled study of subcutaneous injection immunotherapy
was performed in subjects with allergic rhinoconjunctivitis, with or without
asthma. Primary endpoint was a symptom medication score compiled from separate
symptom and medication scores. Secondary endpoints included a rhinitis quality of
life questionnaire, conjunctival provocation, and specific antibody responses.
RESULTS: The symptom medication score showed significant improvements in subjects
receiving recombinant allergens as opposed to placebo, with reductions in both
symptoms and medication usage. The rhinitis quality of life questionnaire
revealed clinically relevant significant improvements in overall assessment and
in 5 of 7 separate domains, and conjunctival provocation showed a clear trend in 
favor of active treatment. All treated subjects developed strong
allergen-specific IgG(1) and IgG(4) antibody responses. Some patients were not
sensitized to Ph l p 5 but nevertheless developed strong IgG antibody responses
to that allergen. CONCLUSION: A recombinant allergen vaccine can be a effective
and safe treatment to ameliorate symptoms of allergic rhinitis. The clinical
benefit is associated with modification of the specific immune response with
promotion of IgG(4) and reduction of IgE antibodies consistent with the induction
of IL-10-producing regulatory T cells.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 16159631 [PubMed - indexed for MEDLINE]

708: Clin Ther. 2005 Jul;27(7):979-92.

Erratum in:
    Clin Ther. 2005 Oct;27(10):1669.

Comment in:
    Clin Ther. 2006 Jan;28(1):146-7; author reply 147-9.

A review of the evidence from comparative studies of levocetirizine and
desloratadine for the symptoms of allergic rhinitis.

Passalacqua G, Canonica GW.

Allergy and Respiratory Diseases, Department of Internal Medicine, University of 
Genoa, Italy. passalacqua@unige.it

BACKGROUND: Levocetirizine and desloratadine are newer antihistamines indicated
for the treatment of allergic rhinitis and chronic idiopathic urticaria.
OBJECTIVE: This article discusses the pharmacokinetics and pharmacodynamics of
levocetirizine and desloratadine and reviews studies that have directly compared 
the effects of these 2 drugs in allergic rhinitis and urticaria. METHODS:
Relevant articles were identified through a search of MEDLINE from 1999 through
2004 using the main search terms levocetirizine and desloratadine. RESULTS:
Levocetirizine is absorbed rapidly and reaches a steady-state plasma
concentration more quickly than does desloratadine. It is also metabolized to a
lesser extent than desloratadine, has a lower V(d), and has higher specificity
for histamine(1) receptors. Eight well-controlled trials were identified that
directly compared the effects of levocetirizine and desloratadine in the skin and
nose of healthy individuals and patients with allergic rhinitis. Drug activity
was measured in terms of wheal, flare, and itch reactions; nasal symptoms or
symptom scores; increases in concentrations of inflammatory markers; or facial
thermography. In most of these trials, levocetirizine had a faster onset and
greater consistency of effect than desloratadine. The differences in the
pharmacokinetic and pharmacodynamic profiles of the 2 drugs may partially explain
these clinical findings. CONCLUSIONS: Levocetirizine may be preferred to
desloratadine as a treatment option for allergic rhinitis because of its faster
onset of action and greater consistency of effect. Although comparative studies
in chronic idiopathic urticaria are not available, data from histamine-induced
wheal and flare studies in healthy volunteers suggest that levocetirizine may be 
more effective in preventing itching than desloratadine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Review

PMID: 16154477 [PubMed - indexed for MEDLINE]

709: Respir Res. 2005 Sep 7;6:100.

Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis.

Fransson M, Adner M, Erjefält J, Jansson L, Uddman R, Cardell LO.

Department of Oto-Rhino-Laryngology, Malmö University Hospital, Lund University, 
Malmö, Sweden. Mattias.Fransson@med.lu.se

BACKGROUND: Toll-like receptors enable the host to recognize a large number of
pathogen-associated molecular patterns such as bacterial lipopolysaccharide,
viral RNA, CpG-containing DNA and flagellin. Toll-like receptors have also been
shown to play a pivotal role in both innate and adaptive immune responses. The
role of Toll-like receptors as a primary part of our microbe defense system has
been shown in several studies, but their possible function as mediators in
allergy and asthma remains to be established. The present study was designed to
examine the expression of Toll-like receptors 2, 3 and 4 in the nasal mucosa of
patients with intermittent allergic rhinitis, focusing on changes induced by
exposure to pollen. METHODS: 27 healthy controls and 42 patients with seasonal
allergic rhinitis volunteered for the study. Nasal biopsies were obtained before 
and during pollen season as well as before and after allergen challenge. The
seasonal material was used for mRNA quantification of Toll-like receptors 2, 3
and 4 with real-time polymerase chain reaction, whereas specimens achieved in
conjunction with allergen challenge were used for immunohistochemical
localization and quantification of corresponding proteins. RESULTS: mRNA and
protein representing Toll-like receptors 2, 3 and 4 could be demonstrated in all 
specimens. An increase in protein expression for all three receptors could be
seen following allergen challenge, whereas a significant increase of mRNA only
could be obtained for Toll-like receptor 3 during pollen season. CONCLUSION: The 
up-regulation of Toll-like receptors 2, 3 and 4 in the nasal mucosa of patients
with symptomatic allergic rhinitis supports the idea of a role for Toll-like
receptors in allergic airway inflammation.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16146574 [PubMed - indexed for MEDLINE]

710: Otolaryngol Head Neck Surg. 2005 Sep;133(3):429-35.

Nasal obstruction is the key symptom in hay fever patients.

Ciprandi G, Cirillo I, Klersy C, Marseglia GL, Caimmi D, Vizzaccaro A.

Cirillo and Vizzaccaro Ospedale Marina Militare, Genoa, Italy. gio.cip@libero.it

BACKGROUND: Allergic rhinitis is characterized by a Th2-dependent inflammation.
Nasal obstruction largely depends on allergic inflammation. OBJECTIVE: The aim of
this study was to evaluate the possible role of the symptom nasal obstruction in 
assessing patients with hay fever. METHODS: Fifty patients (mean age, 23.7 +/-
4.9 years) with hay fever were evaluated both during and outside pollen season.
All of them had moderate-severe grade of nasal obstruction. Total symptom score
(TSS), rhinomanometry, nasal lavage, nasal scraping, spirometry, and methacholine
bronchial challenge were performed in all subjects. RESULTS: During the pollen
season, patients with severe nasal obstruction showed significantly higher values
of TSS, IL-4, IL-5, IL-8, nasal eosinophils and neutrophils, and significantly
lower values of nasal airflow, IFNgamma, FEV1, FVC, and FEF 25-75 in comparison
with patients with moderate nasal obstruction. Twenty (83%) patients with severe 
nasal obstruction showed bronchial hyperreactivity (BHR), whereas only 6 (25%)
patients with moderate nasal obstruction had BHR. Outside the pollen season
overlapping results were observed. CONCLUSIONS: This study provides evidence
about the key role played by nasal obstruction in assessing patients with
allergic rhinitis.

PMID: 16143195 [PubMed - indexed for MEDLINE]

711: Ann Allergy Asthma Immunol. 2005 Aug;95(2):197-203.

Effect of histamine and adenosine 5'-monophosphate provocation on sputum
neutrophils and related mediators in atopic patients.

Pohl D, Beier J, Buhl R, Beeh KM.

Pulmonary Department, Internal Medicine, University Hospital, Mainz, Germany.

BACKGROUND: Airway hyperresponsiveness and inflammation can be noninvasively
studied by bronchial provocation using direct (histamine) or indirect (adenosine 
5'-monophosphate [AMP]) stimuli and induced sputum. OBJECTIVE: To report on the
immediate effects of histamine and AMP challenge on induced sputum neutrophil
counts and related mediator levels. METHODS: We performed a single-masked,
randomized, placebo-controlled, 3-way, crossover, methodological study in 14
atopic patients (median age, 25 years; 8 males; mean +/- SD forced expiratory
volume in 1 second, 99% +/- 5%) without anti-inflammatory medication use. At
baseline, sputum induction was performed. Bronchial challenges with AMP,
histamine, or placebo were performed 48 hours later. Thirty minutes after
challenge, sputum induction was performed again. Challenge periods in each
patient were separated by more than 2 weeks. Sputum cells and the mediators
leukotriene B4, interleukin 8, myeloperoxidase, and albumin were quantified.
RESULTS: Comparing median challenge-induced relative changes in cells and
mediators, neither histamine nor AMP challenge altered the induced sputum
neutrophil counts (histamine, 2.7%; AMP, 2.95%; placebo, -2%; P > .07 for all),
interleukin 8 levels (histamine, 2.4 ng/mL; AMP, -3.8 ng/mL; placebo, -0.2 ng/mL;
P > .06), leukotriene B4 levels (histamine, -4.8 pg/mL; AMP, 3 pg/mL; placebo, 6 
pg/mL; P > .08), or myeloperoxidase levels (histamine, 0.16 microg/mL; AMP, 0
microg/mL; placebo, -0.03 microg/mL; P > .07). Sputum albumin levels were
increased after histamine challenge compared with AMP and placebo challenge (P < 
.01 for both). CONCLUSIONS: Histamine and AMP provocation have no major effects
on induced neutrophil counts and related mediator levels in atopic patients,
whereas histamine challenge induces plasma leakage. Potential interactions of
noninvasive methods to evaluate airway reactivity and inflammation should be
carefully considered.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 16136771 [PubMed - indexed for MEDLINE]

712: Ann Allergy Asthma Immunol. 2005 Aug;95(2):167-74.

Influence of patient care provider on patient health outcomes in allergic
rhinitis.

Szeinbach SL, Williams PB, Kucukarslan S, Elhefni H.

College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Szeinbach.1@osu.edu

BACKGROUND: Diagnosing and managing the symptoms of allergic rhinitis are largely
the responsibility of family physicians and allergists, but some patients choose 
self-management. However, few data are available to determine how the choice of
care relates to measures of patient outcomes, such as the ability to perform
activities, quality of life, and productivity. OBJECTIVE: To examine and compare 
patients' ability to perform activities, quality of life, productivity, and
symptoms according to care provider: family physician, allergist, or
self-management. METHODS: A questionnaire was developed and mailed to 2,065
patients enrolled in a 500,000-member managed care organization. Patients were
identified by diagnostic codes for allergic rhinitis as determined from a
retrospective examination of medical and prescription claims records between
January 1, 2000, and December 31, 2000. RESULTS: Chi-squared Tests revealed
statistically significant differences for symptoms, family history, testing,
immunotherapy, and test value among patient care providers. Multivariate analysis
of variance revealed statistically significant differences for activities,
symptoms, and quality of life among patient care providers. Findings support the 
use of diagnostic testing to improve patient outcomes. Symptoms were
statistically significantly associated with measures of productivity.
CONCLUSIONS: Patient outcomes vary with respect to patient care group. It is
imperative that patients suspected of having allergic rhinitis undergo
appropriate evaluation and testing. Outcomes can be optimized if allergists and
family physicians have access to appropriate diagnostic tools, such as skin
testing and serologic tests for specific IgE antibodies.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16136767 [PubMed - indexed for MEDLINE]

713: Allergy. 2005 Oct;60(10):1301-7.

Desloratadine reduces systemic allergic inflammation following nasal provocation 
in allergic rhinitis and asthma patients.

Reinartz SM, Overbeek SE, Kleinjan A, van Drunen CM, Braunstahl GJ, Hoogsteden
HC, Fokkens WJ.

Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The
Netherlands.

BACKGROUND: Preclinical studies have demonstrated that some second-generation
antihistamines have anti-inflammatory effects. It is not known whether these
effects are also demonstrable in vivo. In this study we investigated the effect
of treatment with desloratadine (DL) on systemic inflammation and on nasal and
bronchial mucosal inflammation after nasal allergen provocation (NP) in subjects 
with grass-pollen-allergic rhinitis and asthma. METHODS: Twenty-six subjects with
grass-pollen-allergic rhinitis and asthma were randomly allocated to 8 days of
treatment with DL (n = 13) or placebo (n = 13) outside the grass pollen season.
On day 7 they underwent nasal provocation with grass pollen allergen. Nasal and
bronchial biopsies were taken for immunohistochemical evaluation, and blood
samples were analysed. Rhinitis and asthma symptoms, peak nasal inspiratory flow 
and peak expiratory flow, were also measured at specified times. RESULTS: The
number of circulating eosinophils decreased during DL treatment, and there was a 
reduced increase in circulating eosinophils after NP in these subjects. There was
also a significant reduction in early bronchial clinical response. There was no
significant lessening in the severity of the nasal symptoms. Nasal and bronchial 
mucosal inflammation parameters did not alter under DL treatment. CONCLUSION:
These data suggest that treatment with DL reduces systemic eosinophilia and
prevents the increase in circulating eosinophils after NP. DL also significantly 
reduces the early bronchial clinical response to NP. However, airway mucosal
inflammation is not altered by 1 week of treatment.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16134997 [PubMed - indexed for MEDLINE]

714: Monaldi Arch Chest Dis. 2005 Jun;63(2):79-83.

Comment in:
    Monaldi Arch Chest Dis. 2005 Jun;63(2):72-3.

Bronchial hyperreactivity and spirometric impairment in patients with allergic
rhinitis.

Cirillo I, Vizzaccaro A, Tosca MA, Negrini S, Negrini AC, Marseglia G, Ciprandi
G.

Ospedale Principale della Marina Militare, Reparto di Medicina, Allergologia e
Fisiopatologia Respiratoria, La Spezia, Italy.

BACKGROUND: The Link between allergic rhinitis and asthma is well known.
Bronchial hyperreactivity (BHR) may be present in rhinitics. The present study is
aimed at evaluating a large group of subjects suffering from allergic rhinitis
alone to investigate the presence of spirometric impairment and BHR both during
and outside the pollen season. METHODS: 360 rhinitics (subdivided in 3 groups:
seasonal, SAR, perennial, PAR, and polysensitized, PolysR) were investigated by
spirometry and methacholine challenge. RESULTS: There was a significant seasonal 
difference concerning the number of rhinitics with impaired FEV1 (p<0.01 for SAR,
p<0.02 for PAR, and p<0.03 for PolysR) and FEF25-75 (p<0.05 for SAR, p<0.03 for
PAR, and p<0.05 for PolysR) as well as with BHR (p<0.05 for SAR and p<0.03 for
PAR). CONCLUSIONS: This study evidences that an impairment of spirometric
parameters and BHR may be observed in patients with allergic rhinitis alone.
Thus, careful evaluation of lower airways should be performed in patients with
allergic rhinitis alone.

PMID: 16128221 [PubMed - indexed for MEDLINE]

715: Phytother Res. 2005 Jun;19(6):530-7.

Treating intermittent allergic rhinitis: a prospective, randomized, placebo and
antihistamine-controlled study of Butterbur extract Ze 339.

Schapowal A; Study Group.

Allergy Clinic, Landquart, Switzerland. andreas@schapowal.ch

BACKGROUND: Intermittent allergic rhinitis (IAR) causes patients distress and
impairs their work performance and quality of life. A variety of medicines are
used by sufferers whose anguish frequently leads to trying new treatments,
increasingly from herbal sources. METHODS: Prospective, randomized, double-blind,
parallel group comparison study of Butterbur extract (Ze 339; 8 mg total
petasine; one tablet thrice-daily), fexofenadine (Telfast 180, one tablet
once-daily) and placebo in 330 patients. Protocol and analysis were according to 
the latest guidelines on new treatments for allergic rhinitis. The primary
efficacy variable was a change in symptoms from baseline to endpoint during
daytime. The secondary efficacy variables were: (a) as per primary variable
(evening/night); (b) Physician's global assessment; (c) Responder rates. Safety
was closely monitored. FINDINGS: Both active treatments were individually
significantly superior to placebo (p<0.001) in improving symptoms of IAR, while
there were no differences between the two active treatments (p=0.37). Superiority
to placebo was similarly shown during the evening/night (p<0.001), by physicians'
own assessment and by responder rates. Both treatments were well tolerated.
INTERPRETATION: Butterbur Ze 339 and Fexofenadine are comparably efficacious
relative to placebo. Despite being a herbal drug, Butterbur Ze 339 has now been
subject to a series of well controlled trials and should be considered as an
alternative treatment for IAR. Copyright (c) 2005 John Wiley & Sons, Ltd.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16114089 [PubMed - indexed for MEDLINE]

716: Int Arch Allergy Immunol. 2005 Sep;138(1):73-9. Epub 2005 Aug 11.

Seasonal rhinitis, clinical characteristics and risk factors for asthma.

Bozkurt B, Karakaya G, Kalyoncu AF.

Department of Chest Diseases, Adult Allergy Unit, Hacettepe University School of 
Medicine, TR-06100 Sihhiye, Ankara, Turkey. bulent_bozkurt7@hotmail.com

BACKGROUND: The aim was to determine the clinical characteristics of patients
with seasonal rhinitis (SR) and to disclose differences in the treatment of SR
between an adult allergy clinic and other clinics over time. METHODS: A
retrospective study was conducted based on clinical records of 774 out of 955
patients diagnosed with SR in an adult allergy clinic between 1 January 1991 and 
31 December 2003. RESULTS: The mean age of the patients was 29.1 +/- 9.29 years
and 62.7% were female. The most common major complaints of the patients were
nasal symptoms in 82.3%. The mean duration of the disease was 6.76 +/- 6.8 years.
The patients were symptomatic with a mean of 3.5 +/- 1.7 months a year, mostly
during the period between April and July. Skin prick tests were positive in 685
patients (90.3%), where the most common sensitivity was against timothy grass
(85.1%). The most common accompanying allergic diseases were food
hypersensitivity in 14%, bronchial asthma in 13.4%, and drug allergy and/or
intolerance in 9.6%. Although the use of specific immunotherapy and short-acting 
sedative antihistamines decreased over time, the use of nasal steroids and
long-acting nonsedative antihistamines tended to increase before admission to our
clinic. Older age (OR: 1.77, 95% CI: 1.06-2.94), presence of familial atopy (OR: 
1.72, 95% CI: 1.04-2.85), respiratory symptoms (OR: 2.10, 95% CI: 1.75-2.50),
ocular symptoms (OR: 0.77, 95% CI: 0.61-0.98) and metal allergy (OR: 0.25, 95%
CI: 0.07-0.89) were associated with the development of asthma in patients with
SR. CONCLUSION: SR lasts approximately 3.5 months and the main cause in Ankara,
Turkey is grass pollen sensitivity. Patients with any other allergic conditions
make up 39.8% of the patients. SR patients are referred to allergy clinics quite 
late, which might be due to SR not being considered as a serious disease.
Copyright (c) 2005 S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 16103690 [PubMed - indexed for MEDLINE]

717: Pediatr Allergy Immunol. 2005 Aug;16(5):408-15.

The prevalence, severity and seasonal variations of asthma, rhinitis and eczema
in Taiwanese schoolchildren.

Kao CC, Huang JL, Ou LS, See LC.

Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang
Gung Children's Hospital and Chang Gung University, 259 Wen-Hwa First Road,
Kweishan, Taoyuan, Taiwan.

The prevalence of asthma is increasing in Taiwan but data remain limited. The aim
of this study was to determine the prevalence, severity, demographic and seasonal
variations of asthma, rhinitis, and eczema in Taiwan. Using a one-stage
stratified cluster random sampling, first grade (aged 6-8) and eighth grade (aged
13-15) students from Taoyuan, northern Taiwan, were invited to participate in
this survey. The results showed a total of 6190 students, 3079 aged 6-8 and 3111 
aged 13-15, completed this survey. In general, children aged 6-8 had
significantly higher prevalence rates of diagnosed asthma, rhinitis, and eczema
than children aged 13-15 (12.2%, 29.8%, and 10.2% vs. 9.6%, 18.3%, and 4.7%,
respectively). Similarly, children aged 6-8 had significantly higher proportions 
of allergic symptoms, except for exercise-induced wheezing (5.8% vs. 17.8%, p <
0.0001). Among those with allergic disorders, children aged 6-8 presented a
greater severity of wheezing attacks in the last 12 months. As regards gender,
boys aged 6-8 had a significantly higher proportion of asthma or rhinitis
symptoms than girls aged 6-8 but not in children aged 13-15. In children aged
6-8, asthma and rhinitis peaked in winter, especially in December. However,
children aged 13-15 had two peaks (winter and summer) for asthma or rhinitis.

PMID: 16101933 [PubMed - indexed for MEDLINE]

718: Vet Immunol Immunopathol. 2005 Oct 18;108(1-2):185-7.

DNA vaccination against Japanese cedar pollinosis in dogs suppresses type I
hypersensitivity by controlling lesional mast cells.

Masuda K.

Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama,
Kanagawa 230-0045, Japan. kmasuda@rcai.riken.jp

Sensitization to allergens of Japanese cedar pollen is known to cause canine
atopic dermatitis as approximately 10% of atopic dogs in Japan were positive to
the pollen allergen. Among the two major allergens of Japanese cedar pollen,
since Cry j 1 is more important than Cry j 2 as an antigen to increase IgE in
atopic dogs sensitized to Japanese cedar pollen, Cry j 1 can be a target for
immunotherapy. In our study, efficacy of DNA vaccination with a plasmid
containing the gene of a major allergen of Japanese cedar (Cryptomeria japnonica,
CJ) pollen, Cry j 1, was examined using a dog model experimentally sensitized to 
CJ pollen allergen. Cry j 1 DNA plasmid and a vector plasmid (pCAGGS) were
injected into six dogs and three dogs, respectively, five times with an interval 
of 1.5 month. After the treatment with Cry j 1 DNA plasmid, production of IgE
against Cry j 1 decreased in four of the six dogs in the treatment group, whereas
it increased in the three dogs of the control group. The reactivity to the pollen
allergen in intradermal testing and provocation testing were obviously reduced in
the treatment group, but not in the control group. The number of mast cells in
alveolar area of the lung in the treatment group was smaller than that in the
control group. Cry j 1 DNA plasmid was also injected into three atopic dogs
sensitive to Cry j 1, resulting in improvement of clinical signs in the
pollination season. These findings indicated that Cry j 1 DNA plasmid could
regulate mast cell-mediated reaction against Cry j 1, which could be an
alternative and effective treatment for CJ pollinosis.

PMID: 16098609 [PubMed - indexed for MEDLINE]

719: Ann Allergy Asthma Immunol. 2005 Jul;95(1):72-8.

The effect of natural pollen exposure on eosinophil apoptosis and its
relationship to bronchial hyperresponsiveness in patients with seasonal allergic 
rhinitis.

Kurt E, Bavbek S, Aksu O, Erekul S, Misirligil Z.

Department of Allergic Diseases, Ankara University, Medical Faculty, Ankara,
Turkey. emelharm@yahoo.com

BACKGROUND: Limited data suggest that there is increased eosinophilic
inflammation in the airways of patients with seasonal allergic rhinitis (SAR)
during pollen season even if they do not have asthma. OBJECTIVE: To investigate
the effect of natural pollen exposure on inflammatory cells and apoptosis of
eosinophils and its association with bronchial hyperresponsiveness (BHR) during
and out of pollen season in SAR patients sensitized to only grass pollens.
METHODS: Forty SAR patients and 10 patients with nonallergic rhinitis (NAR) from 
Ankara, Turkey, were recruited to participate in the study. Two induced sputum
samples were taken from SAR patients during pollen season (May-June) and out of
pollen season (November-January), but only 1 induced sputum sample was taken from
NAR patients. Slides of induced sputum were evaluated by 2 cytologists with the
use of light microscopy after cytocentrifuged and dyed with May-Grünwald-Giemsa
stain. Induced sputum samples were sufficient for differential cell counts in 14 
SAR and 7 NAR patients. RESULTS: Eosinophil counts in SAR patients were
statistically higher in pollen season (19.4% +/- 16.2%) compared with out of
season (4.6% +/- 6.9%, P = .003) and with NAR patients (4.7% +/- 9.5%, P = .01). 
The apoptotic eosinophil counts in SAR patients were statistically higher out of 
pollen season (3.0% +/- 4.5%) than in pollen season (0.38% +/- 0.80%, P = .02)
and higher than those of NAR patients (0.14% +/- 0.26%, P = .005). The apoptotic 
ratio was statistically higher after pollen season compared with pollen season
(0.720% +/- 0.394% vs 0.044% +/- 0.116%, P = .002). Blood eosinophil counts of
SAR patients were increased during the pollen season (364 +/- 187/mm3) compared
with out of season (278 +/- 219/mm3, P = .04) and with NAR patients (85 +/-
54/mm3, P = .001). The number of SAR patients who had BHR during the pollen
season (7/14) was higher than the number who had BHR out of season (2/14, chi2 = 
4.2, P = .04). CONCLUSION: Our data indicate that changes in eosinophil counts
and eosinophil apoptosis may be related to the changes of natural pollen exposure
and seasonal changes of BHR in SAR patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16095145 [PubMed - indexed for MEDLINE]

720: Ann Allergy Asthma Immunol. 2005 Jul;95(1):26-32.

Influence of sociodemographic factors on quality of life during pollen season in 
seasonal allergic rhinitis patients.

Laforest L, Bousquet J, Neukirch F, Aubier M, Pietri G, Devouassoux G, Pacheco Y,
Van Ganse E.

Pharmacoepidemiology Unit, EA 3091, University Hospital, Lyon, France.

BACKGROUND: Quality of life (QOL) is an important outcome in asthma and seasonal 
allergic rhinitis (SAR), and its determinants are imperfectly understood. More
specifically, the influence of sociodemographic factors on QOL in patients with
SAR has been so far little investigated. OBJECTIVE: To examine the changes of QOL
during the pollen season in patients with isolated SAR or SAR associated with
asthma. METHODS: A prospective cohort study was conducted in southern France.
Outpatients aged 18 to 60 years and regularly treated by respiratory physicians
for SAR (with or without associated asthma) were identified. Patients were
recruited before the grass or ragweed pollination period. At peak pollination,
patients completed the French versions of the Mini Rhino-conjunctivitis Quality
of Life Questionnaire (mini-RQLQ) and the 12-item Short-Form Health Survey
(SF-12) physical component summary (PCS) and mental component summary (MCS).
RESULTS: A total of 135 patients was included, 83 with isolated SAR and 52 with
associated asthma (mean age, 35.4 years; SD, 10.6 years; 56% female). At pollen
peak, QOL scores were lower in women for all instruments, with significant
effects on SF-12 MCS and PCS scores in multivariate analyses. Likewise, a
university-level education was an independent predictor of higher SF-12 PCS and
MCS scores. Patients who lived in rural areas had significantly poorer QOL at
pollen peak, as measured by the mini-RQLQ (P = .002) and SF-12 PCS (P = .008). No
influence of age, presence of an animal at home, or smoking status could be
identified on any QOL scores. CONCLUSIONS: Being a woman, living in the
countryside, and having a lower education level were all independent predictors
of poorer QOL of SAR patients. These factors must be taken into account when
interpreting QOL of patients with SAR. Further studies are needed to confirm
these results.

PMID: 16095138 [PubMed - indexed for MEDLINE]

721: Value Health. 2005 Jul-Aug;8(4):506-16.

Cost and utilization impacts of oral antihistamines in the California Medi-Cal
program.

Hay JW, Leahy M.

Department of Pharmaceutical Economics and Policy, University of Southern
California, Los Angeles, CA 90089, USA. jhay@usc.edu

OBJECTIVES: Newer oral allergic rhinitis (AR) medications, the second-generation 
antihistamines (SGAs) have gained widespread acceptance because of their efficacy
and reduced side effects relative to first-generation antihistamines (FGAs).
There are no empirical studies comparing the costs of treatment of SGAs relative 
to FGAs. METHODS: We analyzed data from a 20% beneficiary sample (approximately
120,000 continuously enrolled beneficiaries per year) for the Medi-Cal
Fee-for-Service program during 1999 to 2000. AR medications available under
Medi-Cal included three SGA medications (loratadine, fexofenadine, and
cetirizine) and over 200 FGA products containing either diphenhydramine or
chlorpheniramine or both. Because multiple medications were evaluated, a sample
selection model was estimated using a two-stage multinomial logistic--variance
components regression framework. RESULTS: SGA medications have significantly
lower total direct health-care treatment costs per patient than FGA medications
with costs ranging from US 347 dollars to US 448 dollars less (P < 0.001),
despite higher AR medication costs. Total drug expenditures were also not
significantly different for patients using SGA or FGA medications despite SGA
prescriptions averaging US 47 dollars higher than FGAs. Emergency department
visits, inpatient admissions and physician office visits were also significantly 
lower for patients using SGA medications. CONCLUSIONS: Significant cost and
utilization reductions were associated with all of the SGA medications relative
to FGA drugs, despite their higher acquisition costs. If facing higher copayments
for prescription AR drugs, many patients, particularly lower income patients, may
choose cheaper over-the-counter (OTC) FGAs rather than SGAs. Our analysis finds
this might lead to increased overall health-care treatment costs, unless Medicaid
and health insurance plans subsidize OTC AR medications.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16091028 [PubMed - indexed for MEDLINE]

722: Treat Respir Med. 2005;4(4):289-96.

A preference evaluation study comparing the sensory attributes of mometasone
furoate and fluticasone propionate nasal sprays by patients with allergic
rhinitis.

Meltzer EO, Bardelas J, Goldsobel A, Kaiser H.

Allergy and Asthma Medical Group & Research Center, San Diego, CA 92123, USA.

OBJECTIVE: Data on intranasal corticosteroids suggest that individual product
attributes may influence patient preference for therapy in allergic rhinitis. The
study objective was to compare product sensory attributes and their impact upon
patient preference for scent-free mometasone furoate nasal spray (MFNS) versus
fluticasone propionate nasal spray (FPNS) in patients with symptomatic allergic
rhinitis. METHODS: In a double-blind, crossover study, 100 patients were
randomized to MFNS microg followed by FPNS 200 microg, or vice versa. Patients
rated the study drugs by completing an individual product sensory attributes
questionnaire at the end of each period of drug administration. An overall
sensory preference questionnaire was completed following crossover. RESULTS: A
significantly greater number of patients preferred MFNS to FPNS (p < 0.05). MFNS 
was superior for a number of individual sensory attributes based on mean patient 
ratings: significantly fewer patients perceived scent/odor (immediately and 2
minutes after drug administration; p < 0.001), taste (immediately after drug
administration; p = 0.002), and after-taste (2 minutes after drug administration;
p = 0.007) with MFNS compared with FPNS. Similarly, product sensory attribute
preference data demonstrated that twice the number of patients preferred MFNS to 
FPNS for scent/odor (p = 0.0005), immediate taste (p = 0.005), and after-taste (p
= 0.005). Fifty-four percent of patients said they would choose a prescription
for MFNS compared with 33% for FPNS (p = 0.03). In addition, 47% of patients
would be more likely to comply (use daily as directed) with MFNS compared with
25% with FPNS (p = 0.03). CONCLUSION: Several individual sensory attributes of
MFNS were rated significantly superior to FPNS. Overall, based on the tested
sensory attributes, patients preferred MFNS to FPNS therapy for the treatment of 
allergic rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16086602 [PubMed - indexed for MEDLINE]

723: J Allergy Clin Immunol. 2005 Aug;116(2):445-52.

Biased use of VH5 IgE-positive B cells in the nasal mucosa in allergic rhinitis.

Coker HA, Harries HE, Banfield GK, Carr VA, Durham SR, Chevretton E, Hobby P,
Sutton BJ, Gould HJ.

The Randall Division of Cell and Molecular Biophysics, King's College London,
London.

BACKGROUND: IgE antibody-producing B cells are enriched in the nasal mucosa in
patients with allergic rhinitis because of local class switching to IgE. The
expressed IgE VH genes also undergo somatic hypermutation in situ to generate
clonal families. The antigenic driving force behind these events is unknown.
OBJECTIVE: To examine the possible involvement of a superantigen in allergic
rhinitis, we compared the variable (VH) gene use and patterns of somatic mutation
in the expressed IgE heavy-chain genes in nasal biopsy specimens and blood from
allergic patients and the IgA VH use in the same biopsy specimens and also those 
from nonallergic controls. METHODS: We extracted mRNA from the nasal biopsy
specimens of 13 patients and 4 nonallergic control subjects and PBMCs from 7
allergic patients. IgE and IgA VH regions were RT-PCR amplified, and the DNA
sequences were compared with those of control subjects. We constructed a
molecular model of VH5 to locate amino acids of interest. RESULTS: We observed a 
significantly increased frequency of IgE and IgA VH5 transcripts in the nasal
mucosa of the allergic patients compared with the normal PBMC repertoire. Within 
IgE and IgA VH5 sequences in the nasal mucosa, the distribution of replacement
amino acids was skewed toward the immunoglobulin framework regions. Three of 4
nonintrinsic hotspots of mutation identified in the VH5 sequences were in
framework region 1. The hotspots and a conserved VH5-specific framework residue
form a tight cluster on the surface of VH5. CONCLUSION: Our results provide
evidence for the activity of a superantigen in the nasal mucosa in patients with 
allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16083804 [PubMed - indexed for MEDLINE]

724: Allergy. 2005 Sep;60(9):1132-8.

The time course of the bilateral release of cytokines and mediators after
unilateral nasal allergen challenge.

Wagenmann M, Schumacher L, Bachert C.

ENT Department, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.

BACKGROUND: Late phase reactions after allergen challenge can be understood as a 
correlate of the inflammatory reaction in allergic rhinitis. METHODS: To
investigate which cytokines are involved in it and to dissect direct and indirect
effects of nasal allergen challenge, we performed unilateral nasal allergen
provocation with the disc method in 12 seasonal allergic volunteers. Symptom
scores, nasal secretions and nasal airflow were quantified. In the secretions
that were collected in the early phase and for 8 h after provocation, we measured
histamine, and the cytokines interleukin (IL)-1beta, IL-8, IL-4, and the natural 
antagonist of IL-1beta, IL-1 receptor type 1 (IL-1Ra) using enzyme-linked
immunosorbent (ELISA)-assays. Control challenges with diluent instead of allergen
were performed in all subjects. RESULTS: We demonstrated a bilateral increase in 
nasal secretion weights in the early and late phase. Histamine was significantly 
increased in the early and late phase in nasal secretions from both nostrils.
IL-1beta increased in the late phase only, where it was also found on the
unchallenged, contralateral side. Its antagonist IL-1Ra was found in very high
quantities (1000-fold higher than IL-1beta) but demonstrated only marginal
changes after provocation. IL-8 was increased in both nostrils early and late
after challenge, whereas IL-4 was significantly elevated in the late phase.
CONCLUSIONS: We described the time course of mediator and cytokine release into
nasal secretions after allergen challenge. We hypothesize that the observed
indirect effects on the unchallenged, contralateral side can be at least
partially attributed to neuronal reflexes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16076297 [PubMed - indexed for MEDLINE]

725: J Clin Invest. 2005 Aug;115(8):2067-9.

Comment on:
    J Clin Invest. 2005 Aug;115(8):2169-79.

Spring brings breezes, wheezes, and pollen oxidases.

Ritsick DR, Lambeth JD.

Department of Pathology and Laboratory Medicine, Emory University School of
Medicine, Atlanta, Georgia 30322, USA.

While the release of pollen into the air is essential for the reproduction of
plants, the accidental yet inevitable uptake of pollen into human airways can
cause symptoms of seasonal allergies and asthma. The symptomatic response to
pollen is caused by granulocytes that produce inflammation, which is due in part 
to oxidative stress through the action of NADPH oxidases. The recruitment of
these inflammatory granulocytes was previously thought to depend entirely on the 
activation of an adaptive immune response. In this issue of the JCI, Boldogh et
al. demonstrate that pollens contain endogenous NADPH oxidase activity, which
functions to generate local "danger signals" in nearby airway epithelium. These
signals in turn trigger the early recruitment of granulocytes, even in the
absence of the adaptive immune response. These findings suggest that inhibition
of the pollen oxidase may provide a way to antagonize allergic inflammation at a 
very early step.

Publication Types: 
    Comment

PMID: 16075049 [PubMed - indexed for MEDLINE]

726: Pediatrics. 2005 Aug;116(2):e255-62.

Early respiratory infections, asthma, and allergy: 10-year follow-up of the Oslo 
Birth Cohort.

Nafstad P, Brunekreef B, Skrondal A, Nystad W.

Department of General Practice and Community Medicine, Medical Faculty,
University of Oslo, Pb 1130 Blindern, 0316 Oslo, Norway. per.nafstad@fhi.uio.no

OBJECTIVE: It has been hypothesized that early infections protect against the
development of atopic disease, but there have been few long-term follow-up
studies. We estimated the associations between early respiratory infections and
doctor-diagnosed asthma, allergic rhinitis, and skin-prick sensitization in
children at 10 years of age in the Oslo Birth Cohort, established in 1992-1993.
We also considered birth order and attendance at a child care center as proxy
measures of increased exposure to infections early in life. METHODS: A total of
2540 children were followed from birth to the age of 10 years. Experiences of
respiratory infections were recorded in follow-up surveys at 6 and 12 months. At 
age 10, questions were asked about current symptoms of asthma and allergic
rhinitis and about having ever received a doctor diagnosis for these diseases. A 
subsample (n = 1740) of the cohort was tested for skin-prick test reactivity.
RESULTS: Current asthma was related to lower respiratory tract infection
(adjusted odds ratio [OR]: 2.1; 95% confidence interval: 1.3-3.0) and croup
(adjusted OR: 2.3; 95% confidence interval: 1.3-4.2) in the first year. ORs for
allergic rhinitis and skin-prick sensitization were smaller but mainly positive. 
Birth order and child care attendance at age 1 year were not significantly
associated with any of the studied outcomes. CONCLUSIONS: Early respiratory
infections did not protect against the development of asthma, allergic rhinitis, 
or sensitization to common allergens during the first 10 years of life but
increased the risk for asthma symptoms at age 10 in this population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16061578 [PubMed - indexed for MEDLINE]

727: Immunol Allergy Clin North Am. 2005 Aug;25(3):597-612, vii-viii.

Positioning of glucocorticosteroids in asthma and allergic rhinitis guidelines
(versus other therapies).

Joos GF, Brusselle GG, Van Hoecke H, Van Cauwenberge P, Bousquet J, Pauwels RA.

Department of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, 
B-9000 Ghent, Belgium. guy.joos@ugent.be

Asthma and allergic rhinitis are both characterized by airway inflammation, and
glucocorticosteroids form the cornerstone of their pharmacologic treatment. All
patients with asthma should be prescribed rapid-acting inhaled beta2-agonists as 
needed to use as rescue therapy in case of symptoms. As soon as patients
experience symptoms at least once a week, controller medications should be
started on a daily basis to achieve and maintain control of their asthma.
Intranasal corticosteroids are given as first-line therapy for moderate to severe
persistent rhinitis. Depending on the dominant symptom, H1-antihistamines,
decongestants, or ipratropium can be added after re-evaluation.

Publication Types: 
    Comparative Study
    Review

PMID: 16054545 [PubMed - indexed for MEDLINE]

728: Drug Saf. 2005;28(8):707-19.

Fetal safety of drugs used in the treatment of allergic rhinitis: a critical
review.

Gilbert C, Mazzotta P, Loebstein R, Koren G.

Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital
for Sick Children, The University of Toronto, 555 University Avenue, Toronto M5G 
1X8, Ontario, Canada.

Allergic rhinitis is the most common allergic disease. Pharmacological
interventions are often not used in pregnancy because of alarming information in 
drug labels and patient information, even when evidence for safety
exists.Low-risk therapies could include immunotherapy, intranasal sodium
cromoglycate (cromolyn sodium), beclometasone, budesonide and first-generation
antihistamines. In a meta-analysis examining the safety of first-generation
antihistamines in pregnancy, 200 000 first trimester exposures failed to show
increased teratogenic risk. Loratadine is the most studied second-generation
antihistamine (with a total patient cohort of 2147 women who were exposed) and
does not appear to increase the risk of major congenital malformations; however, 
it has not been as well studied as the earlier antihistamines. Since
desloratadine is the principal metabolite of loratadine, it can be assumed that a
similar safety profile would fit for desloratadine as was described for
loratadine although no direct human studies have been done. Decongestants have
not been conclusively proven to affect the fetal outcome and may be used for
short-term relief when no other safer alternatives are available.Intranasal
corticosteroids have not been associated with an increase in congenital
malformations in humans. Based on efficacy and the fact that there would be
little systemic absorption, they can be considered a first-line treatment over
oral antihistamines, decongestants and mast cell stabilisers; however, the number
of controlled trials in pregnancy is limited. Intranasal corticosteroids are
associated with minimal systemic effects in adults and are the most effective
therapy for allergic rhinitis. Benefit-risk considerations must, therefore, be
done but favour their first-line use during pregnancy.Because fetal safety is
paramount, recommendations should be based both on the safety of the drugs during
pregnancy and the comparative efficacy of the agent in the treatment of the
underlying condition. This review exemplifies the fact that there are many safe
treatment options for the clinician when dealing with allergic rhinitis during
pregnancy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16048356 [PubMed - indexed for MEDLINE]

729: Allergol Immunopathol (Madr). 2005 Jul-Aug;33(4):221-3.

Safety and tolerability of ultra-rush (20 minutes) sublingual immunotherapy in
patients with allergic rhinitis and/or asthma.

Gammeri E, Arena A, D'Anneo R, La Grutta S.

Respiratory Center Disease-USL 5, Messina, Italy.

BACKGROUND: The safety and good tolerability of sublingual immunotherapy (SLIT)
has already been proved in allergic patients, but only one study has investigated
the occurrence of immediate adverse reactions in allergic patients after a 2-hour
ultra-rush regimen of SLIT performed with a chemically modified extract
(sublingual monomeric allergoid, Lais, Lofarma S.p.A., Milan). The objective of
the present study was to evaluate the occurrence of immediate adverse reactions
in allergic patients after a very fast (20 minutes) ultra-rush regimen of
sublingual allergoid SLIT. METHODS AND RESULTS: We studied 105 patients: 28
children (20 male, mean age 13.3 +/- 2.1 yr) and 77 adults (29 male, mean age
34.7 +/- 9.9 years) with a history of intermittent/persistent rhinitis or
intermittent/mild persistent asthma due to House Dust Mite (n = 56), Parietaria
(n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the
administration, every five minutes, of increasing doses of the sublingual
allergoid SLIT. All patients tolerated the treatment very well. Only one patient 
out of 105 (0.9%) had a mild local symptoms (gastric pirosis) that occurred 30
minutes after the last initial dose and spontaneously disappeared as the
treatment was continued. CONCLUSIONS: These data show the excellent safety and
tolerability profile of an ultra-rush SLIT regimen performed with a chemically
modified extract, even when high doses were administered through an extremely
short induction phase (20 minutes), thus confirming the previously reported
results.

Publication Types: 
    Clinical Trial

PMID: 16045861 [PubMed - indexed for MEDLINE]

730: J Am Acad Nurse Pract. 2005 Aug;17(8):295-301.

Management of seasonal allergic rhinitis: comparative efficacy of the
newer-generation prescription antihistamines.

Conboy-Ellis K.

University of Tampa, Tampa, FL 33606, USA. eellis4729@aol.com

PURPOSE: To discuss the efficacy and safety of second-generation prescription
antihistamines, cetirizine, desloratadine, and fexofenadine, and to inform nurse 
practitioners (NP) who are in a position to optimally manage patients presenting 
with seasonal allergic rhinitis (SAR). DATA SOURCES: Selected published clinical 
trials. CONCLUSIONS: NP, who are ideally placed to successfully manage the
majority of patients with SAR, should be fully aware of the treatment options
available. Although first-generation over-the-counter antihistamines are
convenient to use and are readily accessible, patients run the risk of
experiencing adverse effects, such as sedation. For this reason,
second-generation antihistamines should be considered a better alternative;
however, they need to be evaluated individually on the basis of their proven
efficacy and safety. Both cetirizine and fexofenadine are equally effective at
relieving the symptoms of SAR; however, cetirizine has been shown to be more
likely to cause sedation and impairment. IMPLICATIONS FOR PRACTICE: If left
untreated, SAR can have a substantial effect on patients' quality of life,
resulting in fatigue, irritability, sleep disorders, and cognitive impairment.

Publication Types: 
    Review

PMID: 16045589 [PubMed - indexed for MEDLINE]

731: Ann Agric Environ Med. 2005;12(1):17-20.

Correlation between conjunctival provocation test results and conjunctival
symptoms in pollinosis - preliminary report.

Lipiec A, Rapiejko P, Samoliński B, Krzych E.

Department of the Prevention of Environmental Hazards, Medical University of
Warsaw, Poland. alipiec@al.pl

The aim of the study was to investigate the correlation between the level of
reactivity in conjunctival provocation test and conjunctival symptoms that
develop during the pollination season in grass allergic patients. Conjunctival
provocation test with grass pollen allergens was performed in 22 patients
suffering from pollinosis. During grass pollination season all patients monitored
their symptoms with Symptoms Score Cards. A parallel measurement of the level of 
grass pollen count was carried out on a daily basis by volumetric method. The
mean grass pollen count which triggered the reaction in individual patients
depended on the results of conjunctival provocation test. The lowest pollen count
level was observed in cases of patients with positive conjunctival provocation
test at low allergen extract concentration of 160 and 500 BU/ml, whereas the
highest count in cases of 1,600 BU/ml. The difference between the results was
found to be statistically significant. A threshold grass pollen concentration for
conjunctival symptoms was established at the level of 22 grains/m (3). We
conclude that the patients with pollinosis and high reactivity in conjunctival
provocation test develop conjunctival symptoms earlier during grass pollination
season than the patients who are characterised by lower reactivity during
conjunctival provocation test.

PMID: 16028860 [PubMed - indexed for MEDLINE]

732: Acta Otolaryngol. 2005 Jul;125(7):736-44.

Comparative study of two Japanese rhinoconjunctivitis quality-of-life
questionnaires.

Okuda M, Ohkubo K, Goto M, Okamoto H, Konno A, Baba K, Ogino S, Enomoto M, Imai
T, So N, Ishikawa Y, Takenaka Y, Manndai T, Crawford B.

Nippon Medical School, Tokyo, Japan. mok655nms.ac.jp@nifty.com

CONCLUSION: Two questionnaires were used to assess quality of life (QOL) in
allergic rhinitis: the Japanese translation of the Rhino-conjunctivitis Quality
of Life Questionnaire (RQLQJ) and an original Japanese QOL questionnaire (JRQLQ).
Either questionnaire may be used to assess QOL depending on differences in target
domains. OBJECTIVES: Although pollinosis is a common disease which has a major
impact on patient QOL, no internationally standardized questionnaire has been
available in Japan until now. The aim of this study was to compare two currently 
available QOL questionnaires for allergic rhinitis in Japan-the RQLQJ and
JRQLQ-in terms of their appropriateness for clinical use and their psychometric
properties. MATERIAL AND METHODS: A multicenter, inter-group, cross-sectional
study was conducted in 187 adult symptomatic patients with Japanese cedar
pollinosis in 2003. Patient scores on the two questionnaires were compared in
terms of both overall and comparable domains. We also examined the acceptability,
construct and reliability of both questionnaires. RESULTS: The questionnaires
were highly correlated in terms of both overall and comparable domain scores. In 
addition, both questionnaires had equal and satisfactory psychometric validity,
demonstrating that they are both useful tools for assessing QOL in rhinitis.
However, when compared with each other, the JRQLQ focuses mainly on activities of
daily life and is simpler, while the RQLQJ focuses mainly on rhinitis-related
health and is more responsive.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16012036 [PubMed - indexed for MEDLINE]

733: Rhinology. 2005 Jun;43(2):99-103.

Quality of life assessment in Thai patients with allergic rhinoconjunctivitis
using the SF-36 questionnaire (Thai version).

Bunnag C, Leurmarnkul W, Jareoncharsri P, Tunsuriyawong P, Assanasen P, Pawankar 
R.

Rhinology and Allergy Division, Department of Otorhinolaryngology, Faculty of
Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
sicbg@mahidol.ac.th

The health related quality of life (QOL) of patients with allergic rhinitis
and/or conjunctivitis (ARc) as measured by the SF-36 questionnaire, has been
shown to be impaired in a similar way to that of asthmatic patients in France and
several other countries. We used the SF-36 questionnaire (Thai version) to
evaluate the QOL of Thai ARc patients compared to healthy subjects. The SF-36
questionnaire (Thai version) consists of 36 items covering 8 dimensions and one
health transition report question. Higher scores indicated better QOL. The
internal consistency reliability of the questionnaire was analysed using
Cronbach's alpha-coefficient. A total of 705 healthy persons and 900 ARc patients
were included in this study. The mean difference of the scores between healthy
and ARc groups in each dimension showed higher scores in the healthy group. This 
difference was statistically significant (p < 0.05 and p < 0.001) for all
dimensions, except for the Social Functioning dimension. The internal reliability
of the SF-36 questionnaire was confirmed by Cronbach's alpha-coefficient which
was above 0.7 for seven of the dimensions; the exception was the Social
Functioning dimension. Men were shown to have higher scores than women in several
dimensions. In conclusion, this study has confirmed that the SF-36 questionnaire 
is sensitive enough to discriminate ARc patients from healthy persons with high
reliability. QOL of ARc patients was significantly more impaired than healthy
persons and hypertensive patients in several dimensions. These findings were
similar to reports from other countries using the same instruments. Therefore the
SF-36 questionnaire (Thai version) can be a useful tool in evaluating the impact 
of ARc on a patient's QOL and the improvement in QOL after therapeutic
intervention in Thai patients.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16008063 [PubMed - indexed for MEDLINE]

734: Rhinology. 2005 Jun;43(2):86-92.

Seasonal non-allergic rhinitis (SNAR)--a new disease entity? A clinical and
immunological comparison between SNAR, seasonal allergic rhinitis and persistent 
non-allergic rhinitis.

Wedbäck A, Enbom H, Eriksson NE, Movérare R, Malcus I.

Lung and Allergy Clinic, County Hospital, Halmstad, Sweden.

We have earlier described a group of patients suffering from rhino-conjunctivitis
during the early pollen season, but with negative allergological investigation.
The present study aimed to evaluate this syndrome called Seasonal Non-Allergic
Rhinitis (SNAR). Seventeen patients with SNAR were compared with 20 patients with
seasonal allergic rhinitis (SAR) and 13 patients with persistent non-allergic
rhinitis (PNAR). They were analyzed with skin prick tests (SPT) and nasal
provocation tests (NPT) with pollen extracts, and for IgE antibodies in serum and
inflammation mediators in nasal lavage. Daily symptoms and medicine consumption
were recorded. Late reactions after SPT occurred in two SNAR, eight SAR and two
PNAR patients. Weak immediate and late reactions after NPT were induced in 3/15
and 7/15 SNAR patients, respectively, and in 1/13 and 5/13 PNAR patients. All SAR
patients had immediate and 9/18 had late reactions. The total IgE levels were
lower in SNAR compared to SAR. In the SNAR group 1/15 was positive in Phadiatop. 
Increased tryptase levels after NPT were only observed in SAR. The SNAR patients 
had high daily symptom scores already before birch pollen season. Sneezing was
more common in SNAR and SAR than in PNAR; eye-symptoms more prominent in SAR than
in SNAR or PNAR. SNAR seems to be different from SAR and PNAR regarding
immunological mechanism and symptom period. We conclude that the cause of SNAR is
unknown.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16008061 [PubMed - indexed for MEDLINE]

735: Int J Pediatr Otorhinolaryngol. 2005 Aug;69(8):1065-9. Epub 2005 Apr 26.

Acoustic estimation of voice when incorrect resonance function of the nose takes 
place.

Niedzielska G.

Department of Paediatric Otolaryngology, Phoniatry and Audiology, Medical
University, Chodzki 2, Lublin 20-093, Poland. ped-orl@dsk.lublin.pl

Phonation is a sensitive indicator of palatopharyngeal obstruction and its
physiological force. The aim of the study was to evaluate the influence of
nasality on the voice quality. The study was carried out on 125 patients divided 
into three subgroups. The first was created of the patients treated due to
allergic rhinitis, the second was composed of patients with adenoids, the third
one consisted of patients with cleft palate. The following acoustic parameters
were assessed: Fo, Jitter, Shimmer, Fo-tremor, NNE, HNR, SNR. The results of the 
experimental and control groups were analysed statistically with Student's
t-test. The performed acoustic tests of voice confirmed statistically significant
elevation of Fo, HNR and SNR frequency in the studied group as compared with the 
control group.

PMID: 16005348 [PubMed - indexed for MEDLINE]

736: J Allergy Clin Immunol. 2005 Jul;116(1):73-9.

IL-9 and c-Kit+ mast cells in allergic rhinitis during seasonal allergen
exposure: effect of immunotherapy.

Nouri-Aria KT, Pilette C, Jacobson MR, Watanabe H, Durham SR.

Upper Respiratory Medicine, Imperial College London at the National Heart and
Lung Institute, London, United Kingdom.

Background IL-9 is an important stimulus for tissue infiltration by mast cells, a
feature requiring concomitant activation of c-Kit. Objectives We assessed IL-9
expression and c-Kit + mast cells in the nasal mucosa of patients with allergic
rhinitis during seasonal pollen exposure and observed the effects of allergen
immunotherapy. Methods We studied 44 patients with seasonal rhinitis and asthma
before and 2 years after a double-blind trial of grass pollen immunotherapy.
Nasal mucosal IL-9 + cells and c-Kit + mast cells were assessed by means of
immunochemistry. Cell types expressing IL-9 protein were determined by means of
dual immunofluorescence. IL-9 mRNA-positive cells were assessed by means of in
situ hybridization, and their phenotype was determined by using sequential
immunohistochemistry and in situ hybridization. Results Nasal mucosal c-Kit +
mast cells were increased during the pollen season ( P = .0001). IL-9
mRNA-positive cells also tended to increase ( P = .1) and correlated with nasal
EG2 + eosinophils ( r = 0.47, P = .05) and IL-5 mRNA-positive cells ( r = 0.54, P
= .02). The cell sources of IL-9 included T cells, eosinophils, neutrophils, and 
mast cells. When compared with placebo, successful pollen immunotherapy markedly 
inhibited seasonal increases in nasal mucosal c-Kit + mast cells ( P = .001) and 
the seasonal expression of IL-9 mRNA-positive cells ( P = .06). Immunotherapy
also inhibited IL-9 protein expression from nonendothelial cell sources ( P =
.0007). Conclusion IL-9 is upregulated in the nasal mucosa during the pollen
season and correlates with tissue infiltration by eosinophils. Successful pollen 
immunotherapy is associated with inhibition of seasonal increases in both nasal
c-Kit + mast cells and eosinophils. This effect might be explained, at least in
part, by the reduced local expression of IL-9.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15990777 [PubMed - indexed for MEDLINE]

737: Am J Epidemiol. 2005 Aug 1;162(3):212-21. Epub 2005 Jun 29.

Comment in:
    Am J Epidemiol. 2006 Feb 15;163(4):394-5; author reply 395-6.

Cancer mortality among US men and women with asthma and hay fever.

Turner MC, Chen Y, Krewski D, Ghadirian P, Thun MJ, Calle EE.

R. Samuel McLaughlin Centre for Population Health Risk Assessment, Institute of
Population Health, University of Ottawa, Ottawa, Ontario, Canada.
mturner@uottawa.ca

The relation between self-reported physician-diagnosed asthma and/or hay fever
and cancer mortality was explored in a prospective cohort study of 1,102,247 US
men and women who were cancer-free at baseline. During 18 years of follow-up,
from 1982 to 2000, there were 81,114 cancer deaths. Cox proportional hazards
models were used to obtain adjusted relative risks for all cancer mortality and
for cancer mortality at 12 sites associated with allergy indicators. There were
significant inverse associations between a history of both asthma and hay fever
and overall cancer mortality (relative risk (RR) = 0.88, 95% confidence interval 
(CI): 0.83, 0.93) and colorectal cancer mortality (RR = 0.76, 95% CI: 0.64, 0.91)
in comparison with persons with neither of these allergic conditions. A history
of hay fever only was associated with a significantly lowered risk of pancreatic 
cancer mortality, and a history of asthma only was associated with a
significantly lowered risk of leukemia mortality. In never smokers, these
associations persisted but were no longer significant. Results for mortality from
cancer at other sites were less consistent. Collectively, these results suggest
an inverse association between a history of allergy and cancer mortality;
however, the strength of evidence for this association is limited.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15987724 [PubMed - indexed for MEDLINE]

738: Eur Ann Allergy Clin Immunol. 2005 May;37(5):187-93.

Urban versus rural environment--any differences in aeroallergens sensitization in
an allergic population of Cova da Beira, Portugal?

Loureiro G, Rabaça MA, Blanco B, Andrade S, Chieira C, Pereira C.

Immunoallergology Department, Coimbra University Hospital, Portugal.

Cova da Beira is an interior central region of Portugal, with a population of
93000 inhabitants divided in urban and rural living areas. The aim of this study 
was to access the prevalence of aeroallergens sensitisation in an allergic
population, according to the urban and the rural environmental exposure and
according to age. 1096 patients observed for suspected allergic symptoms, for a
five-year period (1995-2000) were submitted to skin prick tests and were included
in this study. They were divided in two environmental exposure groups (A: urban; 
B: rural) and in to four age subgroups (subgroup I: < or = 10yr; subgroup II:
11-20yr; subgroup III: 21-40yr; subgroup IV: >40yr). The total population
included 444 male (40.5%) and 652 female (59.4%) with an average age of 26.5 +/- 
17.2 yr. 83% of the 1096 performed SPT were positive. The frequency of
aeroallergens sensitisation, comparing the urban versus the rural environment,
was respectively: D. pteronyssinus 32% and 34.7%, D. farinae 28.5% and 30.7%,
moulds mixture 15.3% and 12%, cat dander 17.1% and 15.2%, dog dander 11% and 10%,
grasses mixture 51.3% and 36.4%, Parietaria judaica 29.4% and 14%, Olea europea
30.2% and 23.3%. The sensitisation to indoor aeroallergens, was similar in all
the age subgroups and it was lower than that to pollens. There were important
differences concerning the pollen sensitisation, when comparing the urban and the
rural environmental exposure. We admit that pollution could enhance the
sensitisation to pollens in the urban environment.

Publication Types: 
    Comparative Study

PMID: 15984318 [PubMed - indexed for MEDLINE]

739: Clin Ther. 2005 May;27(5):543-53.

Effectiveness of azelastine nasal spray compared with oral cetirizine in patients
with seasonal allergic rhinitis.

Corren J, Storms W, Bernstein J, Berger W, Nayak A, Sacks H; Azelastine
Cetirizine Trial No. 1 (ACT 1) Study Group.

Allergy Research Foundation, Inc., Los Angeles, California 90025, USA.
joncorren@hotmail.com

BACKGROUND: Azelastine nasal spray and oral cetirizine are selective histamine
H(1)-receptor antagonists that are approved in the United States for the
treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: The objective of the
present study was to compare the efficacy and tolerability of azelastine nasal
spray administered at the recommended dosage of 2 sprays per nostril twice daily 
with those of cetirizine in the treatment of moderate to severe SAR. METHODS:
This multicenter, randomized, double-blind, parallel-group, 2-week comparative
study was conducted during the 2004 fall allergy season in patients with moderate
to severe SAR. After a 1-week placebo lead-in period, patients were randomized to
receive azelastine nasal spray 2 sprays per nostril twice daily plus placebo
tablets or cetirizine 10-mg tablets once daily plus a placebo saline nasal spray 
for the 2-week double-blind treatment period. The primary efficacy variables were
(1) change from baseline to day 14 in the 12-hour reflective total nasal symptom 
score (TNSS), which combines scores for rhinorrhea, sneezing, itchy nose, and
nasal congestion, and (2) onset of action, based on the instantaneous TNSS over 4
hours after the first dose of study drug. During the double-blind treatment
period, patients recorded their symptom scores on diary cards twice daily
(morning and evening). Patients aged > or =18 years also completed the
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and on day
14. RESULTS: Three hundred seven patients were randomized to treatment, and 299
completed 2 weeks of study treatment. The age of the population ranged from 12 to
74 years (mean, 35 years), 62.9% were female, and 69.6% were white. Over 2 weeks 
of treatment, both groups had significant improvements in the TNSS compared with 
baseline (P < 0.001). The overall change in TNSS was significantly greater with
azelastine nasal spray compared with cetirizine (29.3% vs 23.0% improvement,
respectively; P = 0.015). In terms of onset of action, azelastine nasal spray
significantly improved the instantaneous TNSS compared with cetirizine at 60 and 
240 minutes after the initial dose (both, P = 0.040). Scores on each domain of
the RQLQ were significantly improved in both groups compared with baseline (P <
0.001); the overall RQLQ score was significantly improved with azelastine nasal
spray compared with cetirizine (P = 0.049). Both treatments were well tolerated. 
CONCLUSION: In this 2-week study in patients with moderate to severe SAR,
azelastine nasal spray was well tolerated and produced significantly greater
improvements in TNSS and total RQLQ score compared with cetirizine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 15978303 [PubMed - indexed for MEDLINE]

740: Eur Arch Otorhinolaryngol. 2006 Jan;263(1):86-90. Epub 2005 Jun 23.

Intranasal trigeminal sensitivity in subjects with allergic rhinitis.

Doerfler H, Hummel T, Klimek L, Kobal G.

Department of Gastroenterology, University of Erlangen-Nürnberg Medical School,
Krankenhausstrasse 12, 91054 Erlangen, Germany.

Trigeminal nerve endings of the human nasal mucosa are activated by chemical,
physical or thermal stimuli. Activation of these A(delta) and C fibers can be
quantified through the recording of chemo-somatosensory event-related potentials 
(ERP). The aim of this study was to investigate whether allergy-related
activation of trigeminal nerve endings leads to changes in their responsiveness
to intranasal trigeminal stimulation. Gaseous carbon dioxide (CO(2)) stimuli were
applied in three sessions (baseline, after NaCl solution and after allergen
application) to the nasal mucosa of 13 subjects with allergic rhinitis.
Chemo-somatosensory ERP were recorded, and subjects rated the intensity of
rhinitis symptoms. Administration of allergen produced a significant shortening
of chemo-somatosensory ERP peak latencies P1 and N1. Observed changes of
latencies were in line with rhinitis symptoms subjects indicated during the
session. In addition, there was a negative relation between the general symptom
score and ERP peak latencies, obtained both at baseline and after allergen
exposure. In conclusion, it is hypothesized that in patients suffering from
allergic rhinitis, nasal itching and sneezing after allergen exposure are, at
least in part, clinical correlates of the activation of trigeminal nerve endings 
due to local inflammatory mechanisms. The correlations between ERP latencies and 
the patients' symptoms indicate that ERP latencies may possess a predictive value
of the subjects' responsiveness to allergens.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15976993 [PubMed - indexed for MEDLINE]

741: Am J Epidemiol. 2005 Jul 15;162(2):125-32. Epub 2005 Jun 22.

Comment in:
    Am J Epidemiol. 2005 Jul 15;162(2):133-8; discussion 139.    Am J Epidemiol. 2006 Jan 1;163(1):99-100; author reply 100.

Sibship characteristics and risk of allergic rhinitis and asthma.

Westergaard T, Rostgaard K, Wohlfahrt J, Andersen PK, Aaby P, Melbye M.

Division of Epidemiology Research, Danish Epidemiology Science Centre, Statens
Serum Institut, Copenhagen, Denmark. twe@ssi.dk

Studying associations between sibship characteristics and allergic diseases in
detail may contribute clues to their etiology. The authors studied associations
between sibship characteristics and risk of self-reported allergic rhinitis and
asthma among 31,145 pregnant women participating in a nationwide study in Denmark
during 1997-2000. Increasing sibship size was associated with a decreased risk of
allergic rhinitis and asthma with allergic rhinitis but not with asthma without
allergic rhinitis. The protective effect of having older siblings was stronger
than the protective effect of having younger siblings for both allergic rhinitis 
and asthma with allergic rhinitis. There was no association between interval to
closest older or younger sibling and risk of allergic rhinitis or asthma with
allergic rhinitis, while the risk of asthma without allergic rhinitis increased
with intervals of 2 or more years compared with less than 2 years to the nearest 
older sibling. The protective effect of having siblings on the risk of asthma
with allergic rhinitis could be explained by a protective effect of siblings on
the risk of allergic rhinitis alone. In conclusion, our findings suggest that
different etiologic mechanisms are involved for allergic rhinitis and asthma with
respect to the effect of sibship characteristics. Furthermore, the findings that 
allergic rhinitis was associated with the number of younger siblings but not with
the age interval to younger siblings support the hypothesis of an influence of
postnatal mechanisms and suggest that these mechanisms may not necessarily be
operating only in early life.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15972945 [PubMed - indexed for MEDLINE]

742: Allergy Asthma Proc. 2005 Mar-Apr;26(2):109-12.

Aeroallergen hypersensitivity: comparing patients with nasal polyps to those with
allergic rhinitis.

Van Lancker JA, Yarnold PA, Ditto AM, Tripathi A, Conley DB, Kern RC, Harris KE, 
Grammer LC.

Division of Allergy-Immunology, Northwestern University Feinberg School of
Medicine, 676 North St. Clair, Chicago, IL 60611, USA.

Immunoglobulin E-mediated allergy generally has not been considered to be
important in the pathogenesis of nasal polyps, despite elevated immunoglobulin E 
in polyp exudates, tissue eosinophilia, and degranulated mast cells. In previous 
reports, patients with nasal polyps were more likely to have positive skin tests 
to perennial than to seasonal allergens. It is postulated that nasal polyps
result from the constant nature of perennial allergen exposure. The objective of 
this report is to compare the prevalence of sensitization to six aeroallergens in
a group of nasal polyp (NP) patients, a group of allergic rhinitis (AR) patients,
and those subjects with positive skin tests in the National Health and Nutrition 
Examination Survey (NHANES) II. Twenty-five consecutive NP patients evaluated
over a 3-month period of time at Northwestern Allergy and Immunology Outpatient
Center, in addition to 50 of the allergic rhinitis patients evaluated over the
same time, were chosen randomly. All were skin tested with the following
antigens: dog, cat, dust mite, grass, tree, and ragweed. Published skin test data
from the NHANES II study of 14,367 individuals was obtained also. The percent of 
NP patients, AR patients, and NHANES II subjects with sensitization to perennial 
allergens was 72, 96, and 7.6%, respectively. The difference between the AR and
NP patients was statistically significant (p = 0.006). The percent of NP, AR, and
NHANES II subjects sensitized to seasonal allergens was 84, 86, and 17.7%,
respectively. No statistical significance existed between the AR and NP patients,
regarding seasonal allergens. Although the AR and NP had similar levels of
reactivity to perennial and seasonal allergens, the NHANES II group was more than
twice as likely to be sensitized to a seasonal allergen. The NP and AR groups
were similar in prevalence of reactivity to seasonal allergens, but the NP
patients in our population actually were less likely to be sensitized to
perennial allergens than individuals with AR.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15971468 [PubMed - indexed for MEDLINE]

743: Allergy Asthma Proc. 2005 Mar-Apr;26(2):103-7.

Ragweed skin test responsiveness correlates with specific immunoglobulin E
levels.

Stokes J, Kessler R, Philip G, Casale TB.

Division of Allergy/lmmunology, Department of Medicine, Creighton University, 601
North 30th Street, Omaha, Nebraska 68131, USA.

Evaluation for allergic rhinitis requires an objective measure of atopy. Serum
eosinophils, total and specific immunoglobulin E (IgE), and skin testing have
been used as this measure. The objective of our study was to examine the
relationship between in vitro allergy tests and in vivo responsiveness. We
compared eosinophil counts, total IgE, and the specific IgE radioallergosorbent
test (RAST) measurements to end point skin test titrations with ragweed. Forty
subjects > or = 18 years of age with at least a 2-year history of moderate to
severe ragweed-allergic rhinitis and a positive skin-prick test to ragweed
participated in this study with 33 subjects having data for all measurements. End
point skin tests were performed by intradermal injection of 0.03 mL of threefold 
dilutions of standardized short ragweed extract into the forearm.
Ragweed-specific IgE was significantly correlated to end point wheal and erythema
concentrations. The results were similar whether the endpoint wheal (r = -0.714; 
p < 0.001) or erythema (r = 0.862; p < 0.001) concentration was used, and the
correlation between these two values was significant (r = 0.97; p < 0.001).
However, 8 of 33 subjects had a negative specific IgE RAST value for ragweed.
There was a significant relationship between ragweed-specific IgE and total IgE
(r = 0.72; p < 0.01). No significant correlations were found between blood
eosinophils and either total IgE, ragweed-specific IgE, and end point wheal or
erythema concentrations. Skin test responsiveness to ragweed correlated with in
vitro ragweed-specific IgE levels, but these tests are not equivalent indicators 
of the degree of IgE-mediated sensitivity.

Publication Types: 
    Comparative Study

PMID: 15971467 [PubMed - indexed for MEDLINE]

744: Allergy Asthma Proc. 2005 Mar-Apr;26(2):95-102.

Antihistamines: treatment selection criteria for pediatric seasonal allergic
rhinitis.

Blaiss MS.

Allergy and Asthma Care, Wolf River Boulevard, Suite 200, Germantown, TN 38138,
USA.

Given the absolute numbers of children suffering from seasonal allergic rhinitis 
(SAR) and the fact that this number is rising, there is an unquestionable need
for safe and effective treatments for the disease. The limited seriousness of the
symptoms of SAR belies their true impact: the disease can have a profound effect 
on children's quality of life and impair learning performance. Furthermore, SAR
has been linked to a number of comorbid conditions and forms part of the
"allergic march" to more serious diseases such as asthma. Antihistamines are
administered to relieve the symptoms of SAR, but they do not represent a
homogeneous group. For example, older-generation antihistamines are associated
with side effects such as impaired psychomotor performance. Newer-generation
antihistamines must be evaluated individually based on their proven efficacy and 
safety so as to tailor treatment to each child's needs. Effective and safe
treatment of SAR, with an antihistamine that does not cause sedation, should
improve children's quality of life and could prevent the development of more
serious conditions, thus reducing morbidity and possible future health care
expenditure.

Publication Types: 
    Review

PMID: 15971466 [PubMed - indexed for MEDLINE]

745: Int Arch Allergy Immunol. 2005 Aug;137(4):310-4. Epub 2005 Jun 20.

Nasal rinsing with hypertonic solution: an adjunctive treatment for pediatric
seasonal allergic rhinoconjunctivitis.

Garavello W, Di Berardino F, Romagnoli M, Sambataro G, Gaini RM.

Department of Otorhinolaryngology, University Milano-Bicocca, Monza, Italy.
werner.garavello@unimib.it

BACKGROUND: Recent but limited evidence suggests that nasal lavage with
hypertonic saline may be useful as an adjunctive treatment modality in the
management of pediatric allergic rhinitis. The aim of this study was to clarify
whether nasal irrigation with hypertonic solution should be routinely recommended
to children with seasonal grass pollen rhinoconjunctivitis. METHODS: Fourty-four 
children with seasonal grass pollen rhinoconjunctivitis were recruited.
Twenty-two patients were randomized to receive three-times daily nasal rinsing
with hypertonic saline during the pollen season, which lasted 7 weeks. Twenty-two
patients were allocated to receive no nasal irrigation and were used as controls.
Twenty patients per group completed the study. A mean daily rhinoconjunctivitis
score based on the presence of nasal discharge and obstruction as well as ocular 
symptoms as reddening and itching were calculated for each week of the pollen
season. Patients were allowed to use oral antihistamines when required and the
mean number of drugs taken per week was also calculated. RESULTS: The mean weekly
rhinoconjunctivitis score in the active group was reduced during the whole pollen
period. This difference was statistically significant in week 6 and 7 of therapy.
A markedly reduced intake of oral antihistamines was also observed in patients
allocated to nasal rinsing, being statistically significant in 5 of the 7 weeks. 
No adverse effect was reported in the active group. CONCLUSIONS: This study
supports the use of nasal rinsing with hypertonic saline in the pediatric patient
with seasonal allergic rhinoconjunctivitis. This treatment proved to be
tolerable, inexpensive and effective.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15970639 [PubMed - indexed for MEDLINE]

746: Int Arch Allergy Immunol. 2005 Aug;137(4):303-9. Epub 2005 Jun 20.

BCG immunization at birth and atopic diseases in a homogeneous population of
Spanish schoolchildren.

García-Marcos L, Suárez-Varela MM, Canflanca IM, Garrido JB, Quirós AB,
López-Silvarrey Varela A, Hernández GG, Guillén-Grima F, Díaz CG, González IH,
Pena AA, Monge RB.

Cartagena Clinical and Research Unit and Department of Pediatrics, University of 
Murcia, Spain.

BACKGROUND: The role of immunization with bacillus Calmette-Guérin (BCG) in the
prevalence of asthma, hay fever and atopic dermatitis is not definitely
established and seems to be influenced by ethnic background. The aim of this
study was to analyze the relationship between this immunization and the
prevalence of those diseases in a homogeneous population of Spanish
schoolchildren. METHODS: The International Study of Asthma and Allergies in
Childhood (ISAAC) core and environmental questionnaires were used in four
different centers of the Spanish North Atlantic coast. Bilbao, San Sebastián and 
Asturias have a universal BCG immunization policy during the first days of life, 
whereas La Coruña discontinued this practice in 1989. Except for this center,
immunization coverage was above 90%. A random sample of schools of Asturias or
all schools in the city district (rest of centers) with children 6 and 7 years
old was surveyed. RESULTS: The participation rate was above 70%. After excluding 
those children born outside Spain, the numbers were 6,762 immunized and 2,828
nonimmunized. After adjusting for gender, age, smoking habits of the father and
mother, truck traffic near the household, older and younger siblings and having a
cat or a dog during the first year of the child's life, the adjusted ORs of the
BCG-immunized children suffering from asthma, hay fever and atopic dermatitis
were respectively 0.87 (95% CI 0.76-1.00), 0.87 (0.75-1.01) and 0.89 (0.76-1.05).
CONCLUSIONS: BCG immunization offers a weak but significant protection against
asthma and hay fever in Spanish schoolchildren. Copyright 2005 S. Karger AG,
Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15970638 [PubMed - indexed for MEDLINE]

747: Auris Nasus Larynx. 2005 Sep;32(3):231-6.

A study of the effectiveness of chemosurgery with trichloroacetic acid for
Japanese cedar pollenosis in terms of the chemical mediator levels in the nasal
discharge and results of nasal provocation testing.

Yao K, Sato K, Usui D, Kurihara R, Iguchi Y, Nishiyama K, Tianyi L, Kamijo T,
Masaki T, Okamoto M.

Department of Otorhinolaryngology, Kanagawa Dental College at Yokohama, 3-31-6,
Tsuruya-chou, Kanagawa-ku, Yokohama-shi, Kanagawa-ken 221-0835, Japan.
yaokazuo@med.kitasato-u.ac.jp

OBJECTIVE: The purpose of the present study was to investigate the effectiveness 
of chemosurgery with 80w/v% trichloroacetic acid (TCA) for the treatment of
Japanese cedar pollenosis. The effectiveness of this treatment was evaluated in
terms of the levels in the nasal washings of the chemical mediators histamine and
eosinophil cationic protein, and the reactivity in the nasal provocation test.
METHODS: Patients of cedar pollenosis were divided into two groups, the
TCA-treated group (n=90) and the group that was not treated with TCA
(nonTCA-treated group) (n=79), according to whether or not they received TCA
treatment. In both the groups, the levels of the two aforementioned mediators in 
the nasal washings were measured during the pollen dispersal season. In addition,
allergen provocation tests were performed using the disk method in volunteers
from both the groups during the non-pollen dispersal season. The results of the
above two determinations were compared statistically between the two groups.
RESULTS: The results revealed significantly lower levels of the two mediators in 
the TCA-treated group than in the nonTCA-treated group (p<0.01). There was also a
greater tendency for the subjects in the TCA-treated group as compared to those
in the nonTCA-treated group to show negative reactivity in the allergen
provocation test (p<0.01). CONCLUSION: Regional suppression of the allergic
reaction to Japanese cedar pollen appears to occur as a result of chemosurgery
with TCA performed as a day surgery.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15955653 [PubMed - indexed for MEDLINE]

748: Allergy. 2005;60 Suppl 80:5-19.

Erratum in:
    Allergy. 2005 Oct;60(10):1335.

Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and 
safety of mometasone furoate.

van Drunen C, Meltzer EO, Bachert C, Bousquet J, Fokkens WJ.

Department of Otorhinolaryngology, Academic Medical Center, University of
Amsterdam, The Netherlands.

Mometasone furoate nasal spray (MFNS; Nasonex, Schering-Plough Corporation,
Kenilworth, NJ, USA) is an effective and well-tolerated intranasal corticosteroid
approved for the prophylactic treatment of seasonal allergic rhinitis, and the
treatment of perennial allergic rhinitis. MFNS is a potent molecule with a rapid 
onset of action and excellent safety and efficacy profiles. Having recently
received approval for the treatment of nasal polyposis, data indicate that MFNS
may also be effective in rhinosinusitis.

Publication Types: 
    Review

PMID: 15948774 [PubMed - indexed for MEDLINE]

749: Allergol Immunopathol (Madr). 2005 May-Jun;33(3):151-6.

The prevalence of allergic rhinitis in urban and rural areas of Eskişehir-Turkey.

Cingi C, Cakli H, Us T, Akgün Y, Kezban M, Ozudogru E, Cingi E, Ozdamar K.

ENT Department, Osmangazi University, Medical Faculty, Turkey. CCINGI@OGU.EDU.TR

Allergic rhinitis is the most common allergic disease in our country. The
epidemiology of allergic rhinitis varies according to the geographic regions of
the country. The aim of this study was to find out if it also differs in urban
and rural areas of the same region. The study groups were randomly selected in
order to sample high school students living in small towns or villages in rural
areas and in the city center. Initially the screening questionnaires about
allergic rhinitis were responded by the students at school. Then the
questionnaires were evaluated. Seven hundred eighty-three students who had a
positive questionnaire outcome were underwent an ENT examination. Then skin tests
and blood analysis were performed to two hundred forty-six students who were
diagnosed as allergic rhinitis clinically. Prick test results was found to be
positive 61.8% in urban areas and 46.7% in rural areas. The comparison of the
ratios of urban and rural areas was significant. Similar results were obtained in
serum specific Ig E analysis. The correlation of specific Ig E levels and skin
prick test results was significant in all allergens. Allergic rhinitis is a
medical and economic problem all over the world and further epidemiologic
investigations should be performed.

Publication Types: 
    Comparative Study

PMID: 15946628 [PubMed - indexed for MEDLINE]

750: Allergol Immunopathol (Madr). 2005 May-Jun;33(3):142-4.

Safety and tolerability of ultra-Rush (20 minutes) sublingual immunotherapy in
patients with allergic rhinitis and/or asthma.

Gammeri E, Arena A, D'Anneo R, La Grutta S.

Respiratory Center Disease-USL 5, Messina, Italy.

BACKGROUND: The safety and good tolerability of sublingual immunotherapy (SLIT)
has already been proved in allergic patients, but only one study has investigated
the occurrence of immediate adverse reactions in allergic patients after a 2-hour
ultra-rush regimen of SLIT performed with a chemically modified extract
(sublingual monomeric allergoid, Lais, Lofarma S.p.A., Milan). The objective of
the present study was to evaluate the occurrence of immediate adverse reactions
in allergic patients after a very fast (20 minutes) ultra-rush regimen of
sublingual allergoid SLIT. METHODS AND RESULTS: We studied 105 patients: 28
children (20 male, mean age 13.3 +/- 2.1 yr) and 77 adults (29 male, mean age
34.7 +/- 9.9 years) with a history of intermittent/persistent rhinitis or
intermittent/mild persistent asthma due to House Dust Mite (n = 56), Parietaria
(n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the
administration, every five minutes, of increasing doses of the sublingual
allergoid SLIT. All patients tolerated the treatment very well. Only one patient 
out of 105 (0.9%) had a mild local symptom (gastric pirosis) that occurred 30
minutes after the last initial dose and spontaneously disappeared as the
treatment was continued. CONCLUSIONS: These data show the excellent safety and
tolerability profile of an ultra-rush SLIT regimen performed with a chemically
modified extract, even when high doses were administered through an extremely
short induction phase (20 minutes), thus confirming the previously reported
results.

Publication Types: 
    Clinical Trial

PMID: 15946626 [PubMed - indexed for MEDLINE]

751: Br J Nutr. 2005 Apr;93(4):529-35.

Association of fatty acids in serum phospholipids with hay fever, specific and
total immunoglobulin E.

Kompauer I, Demmelmair H, Koletzko B, Bolte G, Linseisen J, Heinrich J.

GSF-National Research Center for Environment and Health, Institute of
Epidemiology, Neuherberg, Germany.

The dietary intake of certain fatty acids might contribute to the development of 
allergic diseases such as hay fever and asthma. We investigated the association
between the concentrations of fifteen fatty acids in serum phospholipids, as a
marker of dietary intake and metabolism, and hay fever, allergic sensitisation
and total IgE in adults. Data from a population-based cross-sectional study on
respiratory health, including the measurement of fatty acids in the serum
phospholipids of 740 adults between 20 and 64 years of age, were analysed.
Positive associations were found between hay fever and arachidonic acid, and
allergic sensitisation and oleic acid. No other fatty acids showed any
association with hay fever or allergic sensitisation. Elevated levels of total
IgE were not related to fatty acids. Concentrations of long-chain n-3 fatty
acids, trans fatty acids or saturated fatty acids in serum phospholipids were not
associated with allergic diseases in adults in this study. The present result on 
the association between hay fever and arachidonic acid is consistent with current
hypotheses but warrants further research.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15946416 [PubMed - indexed for MEDLINE]

752: Pediatr Allergy Immunol. 2005 Jun;16(4):315-20.

Modest increase in seasonal allergic rhinitis and eczema over 8 years among
Estonian schoolchildren.

Annus T, Riikjärv MA, Rahu K, Björkstén B.

Tartu University Children's Hospital, Tartu, Estonia. triine.annus@mail.de

We studied time trends in the prevalence of asthma and allergic diseases in
Estonian children born before and after the collapse of the Soviet Union, as this
event markedly altered the lifestyle in Estonia. Two identical cross-sectional
studies were performed as part of phase I and phase III of the International
Study of Asthma and Allergies in Childhood (ISAAC). Children, aged 6-7 yr (n =
3070 in 1993-94 and 2383 in 2001-02) and 13-14 yr (n = 3476 and 3576,
respectively), completed ISAAC core-written questionnaires, and 13-14-yr olds (n 
= 3427 and 3259, respectively) also video questionnaires. The prevalence of
respiratory symptoms was mostly similar in the two studies. Despite this, the
prevalence of diagnosed asthma increased. This was probably due to modified
diagnostic criteria and increased awareness. Furthermore, the prevalence of
rhinitis during the pollen season increased, e.g., rhinitis in May from 1.7% to
3.5%; sex-adjusted prevalence odds ratio (POR) 2.09 (95% confidence interval
1.47-2.96) in 6-7-yr olds, and from 2.6% to 5.5%; POR 2.22 (1.72-2.87) in
13-14-yr olds. The prevalence of flexural dermatitis also increased from 12.0% to
13.5%; POR 1.20 (1.02-1.41) in 6-7-yr olds, and from 7.7% to 9.4%; POR 1.26
(1.07-1.50) in 13-14-yr olds. The increase was similar in children born before
and after the regaining of Estonian independence, indicating that the influence
of factors related to a Western lifestyle and affecting the prevalence of
allergic symptoms is not restricted to infancy, but may be operative throughout
childhood.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15943595 [PubMed - indexed for MEDLINE]

753: Allergy. 2005 Jul;60(7):882-7.

Seasonal and perennial allergic rhinitis: is this classification adherent to real
life?

Ciprandi G, Cirillo I, Vizzaccaro A, Tosca M, Passalacqua G, Pallestrini E,
Canonica GW.

Head-Neck Department, S. Martino Hospital, Genoa, Italy.

BACKGROUND: Allergic rhinitis is traditionally subdivided into seasonal (SAR) and
perennial (PAR), although the new definitions of persistent and intermittent were
recently proposed. We assessed the validity of the traditional classification in 
a large group of subjects suffering from allergic rhinitis alone. METHODS: Young 
males referred to a Navy Military Hospital for routine fitness visit, and
reporting symptoms of rhinitis alone were selected. According to the
sensitization they were subdivided into (i) sensitized to pollens only (seasonal,
SAR), (ii) to perennial allergens only (perennial, PAR) and (iii) to both (mixed,
MAR). Spirometry, methacholine challenge, severity and characteristics of
symptoms were assessed in all participants. RESULTS: Of 19 325 subjects, 2347 had
allergic rhinitis. Seventy-two percent of the subjects had MAR, 17% SAR and 11%
PAR. Ocular involvement and irritative symptoms were more frequent in SAR (P <
0.03), whereas obstruction was predominant in PAR (P < 0.01). Nasal symptoms
varied according to the period of the year in SAR (P < 0.01) and PAR (P < 0.03). 
An overt bronchial obstruction was detected in 12% of PAR patients, in 7.8% of
MAR, and in 4.2% of SAR. forced expiratory volume/1 s was significantly lower
during season in SAR patients only (P < 0.05). The FEF25-75 was impaired in 22.5%
MAR patients, 21% PAR, and 14% SAR, with a seasonal change in SAR (P < 0.05) and 
PAR (P < 0.001). Bronchial hyperreactivity was present in 82.2% of PAR, 73.6% of 
MAR, and 53.5% of SAR, with a seasonal change in SAR (P < 0.001) and MAR (P <
0.05). CONCLUSIONS: This study provides evidence that up to 80% of allergic
rhinitics have a mixed form, and SAR and PAR definitions are poorly adherent to
real life. Lung involvement is frequent in patients reporting nose symptoms
alone.

Publication Types: 
    Validation Studies

PMID: 15932377 [PubMed - indexed for MEDLINE]

754: Allergy. 2005 Jul;60(7):875-81.

Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and
asthma.

Dahl R, Nielsen LP, Kips J, Foresi A, Cauwenberge P, Tudoric N, Howarth P,
Richards DH, Williams M, Pauwels R; SPIRA Study Group.

Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Denmark.

BACKGROUND: Studies suggest that nasal treatment might influence lower airway
symptoms and function in patients with comorbid rhinitis and asthma. We
investigated the effect of intranasal, inhaled corticosteroid or the combination 
of both in patients with both pollen-induced rhinitis and asthma. METHODS: A
total of 262 patients were randomized to 6 weeks' treatment with intranasal
fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate
(IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in
a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks 
prior to the pollen season and patients recorded their nasal and bronchial
symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients
were assessed for lung function, methacholine responsiveness, and induced sputum 
cell counts. RESULTS: Intranasal fluticasone propionate significantly increased
the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea
during the pollen season, compared with IHFP or intranasal or inhaled placebo. In
contrast, only IHFP significantly improved morning peak-flow, forced expiratory
volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the
sputum eosinophils and methacholine responsiveness. CONCLUSIONS: In patients with
pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is
needed to control the seasonal increase in nasal and asthmatic symptoms.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15932376 [PubMed - indexed for MEDLINE]

755: Clin Med Res. 2004 Feb;2(1):5-12.

Asthma and atopy in rural children: is farming protective?

Naleway AL.

Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon 97227, 
USA. allison.naleway@kpchr.org

The prevalence of asthma and other atopic diseases has recently increased,
especially in urban and modernized regions of the world. The majority of
published prevalence surveys report that asthma and atopy are less common among
children living in rural areas. While many exposures differ in rural and urban
areas of the world, several recent studies have suggested that agricultural
exposures in early childhood may decrease the risk of developing atopic disease. 
Livestock exposure, in particular, seems to be important, but additional research
is needed to pinpoint the underlying mechanisms behind this apparent protective
effect of rural and farm living. Additionally, prospective studies are needed to 
more closely examine the timing of farm exposures in relation to the onset of
asthma and atopy, and to determine if the apparent protective effects of farming 
persist into adulthood.

Publication Types: 
    Review

PMID: 15931330 [PubMed - indexed for MEDLINE]

756: Thorax. 2005 Jun;60(6):445-50.

Comment in:
    Thorax. 2005 Oct;60(10):793-4.

Association of asthma and hay fever with irregular menstruation.

Svanes C, Real FG, Gislason T, Jansson C, Jögi R, Norrman E, Nyström L, Torén K, 
Omenaas E.

Institute of Medicine, University of Bergen, Norway. cecilie.svanes@med.uib.no

BACKGROUND: There is some evidence that asthmatic women are more likely to have
abnormal sex hormone levels. A study was undertaken to determine whether asthma
and allergy were associated with irregular menstruation in a general population, 
and the potential role of asthma medication for this association. METHODS: A
total of 8588 women (response rate 77%) participated in an 8 year follow up
postal questionnaire study of participants of the ECRHS stage I in Denmark,
Estonia, Iceland, Norway, and Sweden. Only non-pregnant women not taking
exogenous sex hormones were included in the analyses (n = 6137). RESULTS:
Irregular menstruation was associated with asthma (OR 1.54 (95% CI 1.11 to
2.13)), asthma symptoms (OR 1.47 (95% CI 1.16 to 1.86)), hay fever (OR 1.29 (95% 
CI 1.05 to 1.57)), and asthma preceded by hay fever (OR 1.95 (95% CI 1.30 to
2.96)) among women aged 26-42 years. This was also observed in women not taking
asthma medication (asthma symptoms: OR 1.44 (95% CI 1.09 to 1.91); hay fever: OR 
1.27 (95% CI 1.03 to 1.58); wheeze preceded by hay fever: OR 1.76 (95% CI 1.18 to
2.64)). Irregular menstruation was associated with new onset asthma in younger
women (OR 1.58 (95% CI 1.03 to 2.42)) but not in women aged 42-54 years (OR 0.62 
(95% CI 0.32 to 1.18)). The results were consistent across centres. CONCLUSIONS: 
Younger women with asthma and allergy were more likely to have irregular
menstruation. This could not be attributed to current use of asthma medication.
The association could possibly be explained by common underlying metabolic or
developmental factors. The authors hypothesise that insulin resistance may play a
role in asthma and allergy.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15923242 [PubMed - indexed for MEDLINE]

757: Eur Ann Allergy Clin Immunol. 2005 Mar;37(3):103-8.

Efficacy of sublingual coseasonal immunotherapy with a monomeric allergoid in
Cupressaceae pollen allergy--preliminary data.

Ariano R, Panzani RC, Mistrello G.

U.O. Medicina Generale, Ospedale di Bordighera, A.S.L n 1, Imperiese.

BACKGROUND: Respiratory allergy to conifers pollens is a growing phenomenon all
over the world (Mediterranean area, USA, Japan). In France and Italy Cupressus
sempervirens is the commonest offender. OBJECTIVE: To check the efficacy of
specific immunotherapy by the sublingual route using a monomeric allergoid of
Cupressus Arizonica pollen. MATERIAL AND METHODS: 20 patients and 10 controls
were randomly selected. The diagnosis was assessed on a clinical hivernal
symptomatology of allergic rhinitis, and/or asthma, positive skin test and RAST, 
and nasal provocation test to Cupressus arizonica. The extract was a monomeric
allergoid titrated in allergenic units (AU). The treatment was coseasonal from
the beginning of december to the end of march. It was not conducted double blind.
RESULTS: The evaluation of the allergenic potency of native and modified
Cupressus arizonica extracts have shown that the modified extract has a decreased
skin test IgE binding capacity. According to symptom, drug consumption scores and
nasal provocation test, there was a statistical improvement in the active group
(compared to the control group) without any side effect. DISCUSSION: The use of a
modified Cupressus arizonica extract, which is easier to prepare than Cupressus
sempervirens and which is a monomeric allergoid, has shown that by the sublingual
route, this therapeutic approach is safe and that the first results were
satisfactory without any side effect. This good tolerance was anticipated by the 
fact that, checked on 16 volunteers by skin test, the allergoid gave a less
important local reaction on skin testing than the native extract. CONCLUSION:
This study has shown that: The KCNO modified Cupressus arizonica extract has a
reduced IgE binding capacity; This monomeric allergoid is safe and effective
administrated by the oromucosal route in clinical respiratory allergy to
Cupressaceae and devoid of any side effect.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15918297 [PubMed - indexed for MEDLINE]

758: Arch Dis Child. 2005 Jun;90(6):567-73.

Comment in:
    Arch Dis Child. 2005 Jun;90(6):553-5.

Timing of routine immunisations and subsequent hay fever risk.

Bremner SA, Carey IM, DeWilde S, Richards N, Maier WC, Hilton SR, Strachan DP,
Cook DG.

Department of Community Health Sciences, St George's Hospital Medical School,
Cranmer Terrace, London SW17 0RE, UK.

BACKGROUND: Suggestions that immunisation influences allergic disease risk,
either positively (pertussis) or negatively (BCG) are of concern for vaccination 
policy. AIMS: To determine whether DTP, MMR, and BCG vaccination in infancy
influenced hay fever risk. METHODS: Case-control study of 7098 hay fever cases
and controls, within two primary care databases. One control per case was matched
for practice, age, and sex. Odds ratios (OR) were derived using conditional
logistic regression. RESULTS: Compared to those completing in month 5 (base
group) (39.3%), DTP unvaccinated children (4.3%) had a similar risk of hay fever 
(OR = 0.94, 95% CI 0.73 to 1.23). However, those completing after 12 months
(4.2%) had a reduced risk (OR = 0.60, 95% CI 0.45 to 0.76) compared to the base
group. Compared to those vaccinated in month 14 (base group) (29.5%), MMR
unvaccinated children (2.3%) had an OR of 0.79 (95% CI 0.58 to 1.08). Completion 
of MMR after two years was associated with reduced hay fever risk (OR = 0.62, 95%
CI 0.48 to 0.80) compared to the base group. The effects of late immunisation
with DTP and MMR were independent. Those vaccinated with BCG by age 2 (2.4%) had 
an odds ratio of 1.28 (95% CI 0.96 to 1.70). Adjustment for consulting behaviour,
social factors, or sibship size did not alter these associations. CONCLUSIONS:
Immunisation against DTP or MMR does not increase the risk of hay fever. The
lower confidence limit for BCG vaccination contradicts the hypothesised
protective effect. The reduced risk of hay fever among children immunised late
may be explained by a third factor causing both postponement and reduced risk
such as intercurrent febrile illnesses.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15908618 [PubMed - indexed for MEDLINE]

759: Curr Opin Pharmacol. 2005 Jun;5(3):214-20.

Histamine-mediated mechanisms in the human nasal airway.

Taylor-Clark T, Foreman J.

Department of Pharmacology, University College London, Gower Street, London WC1E 
6BT, UK.

The nasal actions of histamine were originally attributed to vascular and
neuronal H(1) receptor activation. Recent studies have identified a H(3) receptor
that contributes to histamine-induced inflammation via the inhibition of
sympathetic activity. There is also evidence that pollen-induced nasal blockage
can be treated by H(1) antagonists. However, although desloratadine might offer
relief, this is unlikely to be through inhibition of nasal H(1) receptors.
Despite evidence of an active H(2) receptor on nasal vasculature, this receptor
subtype appears to play only a minor role in nasal inflammation. The activation
of H(1) receptors cannot account for all of the acute actions of histamine in the
nasal airway.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15907905 [PubMed - indexed for MEDLINE]

760: Curr Med Res Opin. 2005 Apr;21(4):611-8.

Open-label evaluation of azelastine nasal spray in patients with seasonal
allergic rhinitis and nonallergic vasomotor rhinitis.

Lieberman P, Kaliner MA, Wheeler WJ.

Allergy and Asthma Care, Germantown, TN, USA. aac@allergymemphis.com

OBJECTIVE: The objective of the study was to evaluate the effectiveness of
azelastine (Astelin) nasal spray, a topical second-generation antihistamine, in
the treatment of symptoms of seasonal allergic rhinitis, seasonal allergic
rhinitis with nonallergic triggers (mixed rhinitis), and nonallergic vasomotor
rhinitis. RESEARCH DESIGN AND METHODS: A total of 2343 primary care physicians,
allergists, ENT specialists, and other health professionals participated in this 
2-week, open-label evaluation of azelastine nasal spray. Data were collected
through a physician questionnaire that included patient demographics, rhinitis
diagnosis, medication history, and inclusion/exclusion criteria; and two patient 
questionnaires that included symptom history, response to previous rhinitis
medications, symptom control, and level of satisfaction with azelastine nasal
spray. A completed physician questionnaire and two completed patient
questionnaires were required for each patient to be included in the analysis.
Patients who qualified for enrollment were given open-label azelastine nasal
spray and instructed to administer 2 sprays per nostril twice daily for 2 weeks. 
RESULTS: A total of 1225 health professionals enrolled 7864 patients into the
study. Completed physician and patient questionnaires were returned by 1081
health professionals and 5073 patients, 4364 of whom used azelastine nasal spray 
as their only rhinitis medication during the 2-week study period. The patients
were predominantly caucasian (82.6%) and female (61.1%), with a mean age of 50
years. The majority had a diagnosis of mixed rhinitis (51.5%), followed by
seasonal allergic rhinitis (32.3%), and nonallergic (vasomotor) rhinitis (16.2%).
After 2 weeks of treatment, the percentage of patients reporting some control or 
complete control of individual symptoms ranged from 78% for postnasal drip in
patients with nonallergic vasomotor rhinitis to 90% for sneezing in patients with
seasonal allergic rhinitis. More than 85% of patients who reported difficulty
sleeping or impairment of daytime activities due to rhinitis symptoms had
improvement in these parameters. Azelastine nasal spray was well tolerated, the
discontinuation rate due to adverse events was 2.3%. CONCLUSIONS: Azelastine
nasal spray was reported to control all rhinitis symptoms, including nasal
congestion, regardless of rhinitis diagnosis during the 2-week study period.
Patients with seasonal allergic rhinitis and patients with seasonal allergic
rhinitis plus nonallergic triggers were identified as patient types most likely
to respond to azelastine nasal spray.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15899111 [PubMed - indexed for MEDLINE]

761: Clin Exp Allergy. 2005 May;35(5):612-8.

Low socioeconomic status as a risk factor for asthma, rhinitis and sensitization 
at 4 years in a birth cohort.

Almqvist C, Pershagen G, Wickman M.

Department of Occupational and Environmental Health, Karolinska Hospital,
Stockholm, Sweden. catarina.almqvist@kbh.ki.se

BACKGROUND: The relation between socioeconomic status and allergic diseases in
childhood is controversial. Some studies have proposed childhood asthma to be
more common in families with low socioeconomic status, while sensitization to
airborne allergens seems to be more frequent in individuals with higher
socioeconomic status in childhood. OBJECTIVE: To assess the relation between
socioeconomic status and asthma, rhinitis and sensitization in an unselected
prospective birth cohort. METHODS: Four thousand and eighty-nine families with
children born 1994-1996 in predefined areas of Stockholm answered questionnaires 
on environmental factors, socioeconomic status (parental occupation), and
symptoms of allergic disease at birth, 1, 2 and 4 years of age. Blood samples
taken at 4 years from 2614 children were analysed for specific IgE to common
airborne and food allergens. Odds ratios (OR) and 95% confidence intervals (CI)
for various outcomes in relation to socioeconomic status were estimated with a
multiple logistic regression model, adjusting for potential confounders such as
heredity for allergic diseases, maternal smoking, short duration of breastfeeding
and house construction. RESULTS: There was a decreasing risk of asthma and
rhinitis with increasing socioeconomic status. The OR for asthma was 0.33 (95% CI
0.17-0.66) and for rhinitis 0.50 (0.32-0.79) comparing the highest and the lowest
socioeconomic groups, with a tendency to stronger effects in those with heredity 
for allergic disease. The risk of sensitization to food allergens also decreased 
with increasing socioeconomic status; OR 0.65 (0.41-1.02) in the highest
socioeconomic group (Ptrend=0.03), which was not clearly seen for airborne
allergens. CONCLUSION: Asthma, rhinitis and sensitization is more common in lower
than in higher socioeconomic groups after adjustment for traditional risk
factors. This may be related to additional uncontrolled differences in life style
and environmental exposures between the groups, and calls for further studies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15898983 [PubMed - indexed for MEDLINE]

762: Clin Exp Allergy. 2005 May;35(5):572-8.

Erratum in:
    Clin Exp Allergy. 2005 Nov;35(11):1504.

Immunotherapy with depigmented glutaraldehyde-polymerized extracts: changes in
quality of life.

Alvarez-Cuesta E, Aragoneses-Gilsanz E, Martín-Garcia C, Berges-Gimeno P,
Gonzalez-Mancebo E, Cuesta-Herranz J.

Servicio de Alergia. Hospital Ramón y Cajal, Madrid, Spain. jcuesta@fjd.es

BACKGROUND: Immunotherapy (IT) with modified allergens reduces allergic rhinitis 
(AR) symptoms and medications requirements. Improvement of quality of life (QOL) 
is a key point in the treatment of AR. The aim of this study was to provide
evidence of changes related to the patient's QOL (well-being) induced by a
modified (depigmented glutaraldehyde-polymerized) therapeutic vaccine and of its 
safety. MATERIAL AND METHODS: Fifty-three patients with a well-documented
clinical history of seasonal AR sensitized to Dactylis glomerata and Olea
europaea pollens were included in a randomized clinical trial. Twenty-five
patients (Group-A) received a mixture of D. glomerata and O. europaea pollen
extracts and 28 patients received placebo (group-C). Any adverse event was
recorded and graded in accordance with EAACI guidelines. RQLQ was recorded before
the treatment (pollen season 2000) and after 1 year of treatment (pollen season
2001). Dose-response skin prick test with each allergen extract was conducted at 
baseline and at the end of the study. RESULTS: Each patient received 17
injections during this period. All patients completed the trial and no systemic
adverse reactions were recorded. Symptom scores (P<0.001) and medication
requirements (P<0.001) were significantly reduced in the IT group during the
pollen season. This patient group also experienced greater and statistically
significant improvement in overall RQLQ score and in five of the seven domains,
all of them surpassing the threshold of 'minimal important difference' of 0.5
points. CONCLUSIONS: Results of this study provided evidence that IT with
depigmented, glutaraldehyde-modified allergen extracts was well-tolerated and
added beneficial effects to AR treatment in pollen allergic patients eliciting an
improvement in QOL enough to justify a change in the patient's treatment.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15898977 [PubMed - indexed for MEDLINE]

763: Clin Sports Med. 2005 Apr;24(2):e35-50, xiii.

Seasonal allergy and seasonal decrements in athletic performance.

Komarow HD, Postolache TT.

Laboratory of Allergic Disease, National Institute of Allergy and Infectious
Disease, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
komarowh@mail.nih.gov

Allergic diseases are common in all age groups and locations around the world. In
the United States, allergic diseases affect 20 to 40 million people annually,
including 10% to 30% of adults and close to 40% of children. An estimated 15
million people in the United States have been diagnosed as having asthma, with
this number on the rise. Concomitant asthma affects 67% of patients who have
allergic rhinitis. As a result of the increase in ventilation during exercise,
athletes in particular experience significant symptoms of allergy triggered by
exposure to aeroallergens. The allergic response causes nasal and conjunctival
congestion, tearing, breathing difficulties, pruritus, fatigue, and mood changes,
which affect athletic performance. Systemic symptoms of anaphylaxis from allergy,
although rare, can be life threatening. Several decades ago it was inconceivable 
that an athlete who had asthma could perform competitively, let alone win Olympic
gold medals. Today, with proper diagnosis, education, and optimal therapeutic
management, the allergic athlete can achieve great strides in all sports
endeavors. To avoid seasonal allergic flares and maximize performance, the
physician providing care for an athlete who has seasonal allergies must be aware 
of the climatic patterns of aeroallergen expression, and adjust exercise and
pharmacologic regimens accordingly. This article summarizes the effects of
allergic disease on exercise and highlights the challenges that seasonal allergy 
place on athletic performance. Doping considerations grant additional complexity 
to this issue and underscore the need for a competent, skillful, informed, and
ethical approach to treating seasonal allergy in the competitive athlete.

Publication Types: 
    Review

PMID: 15892916 [PubMed - indexed for MEDLINE]

764: Int J Immunopathol Pharmacol. 2005 Apr-Jun;18(2):277-85.

A pilot study of feasibility of ultra-rush (20-25 minutes) sublingual-swallow
immunotherapy in 679 patients (699 sessions) with allergic rhinitis and/or
asthma.

Rossi RE, Monasterolo G.

Allergy Unit, National Health Service, Regione Piemonte, Italy.
immunoway@libero.it

Few studies have evaluated the occurrence of immediate adverse reactions in
allergic patients after an ultra-rush regimen of different commercial allergen
extracts for sublingual immunotherapy (SLIT) Methods: 679 patients took part in
trials of specific ultra-rush SLIT for the treatment of IgE-mediated rhinitis
and/or IgE-mediated asthma. 14 patients received two different sublingual
allergen vaccines during two distinct SLIT sessions. On the whole, 699 SLIT
sessions were performed. The build up ultrarush phase involved the administration
every five minutes of increasing doses of either different allergen extracts. The
cumulative allergen extract solution after half an hour was several times the
dose administered at the start of subcutaneous immunotherapy (range 4.7-525
microg of major allergens). All patients tolerated the treatment very well. 122
(17.96%) had mild local symptoms (pruritus of the buccal cavity) that
spontaneously disappeared with increasing dose. Two patients allergic to
Parietaria had urticaria about three hours after the last sublingual
Parietaria-extract intake. A subject allergic to Artemisia vulgaris pollen had
urticaria and rhinitis two hours later than the last dose of vaccine. As reported
in our previous study, no immediate severe adverse reactions were observed after 
that rapidly increasing doses of allergen extract were administered in a very
short period to a large number of patients, showing the excellent safety profile 
of ultra-rush SLIT.

Publication Types: 
    Clinical Trial

PMID: 15888250 [PubMed - indexed for MEDLINE]

765: Auris Nasus Larynx. 2005 Sep;32(3):251-6.

Plantago lanceolata (English plantain) pollinosis in Japan.

Nakamaru Y, Maguchi S, Oridate N, Takagi D, Furuta Y, Fukuda S.

Department of Otolaryngology and Head and Neck Surgery, Hokkaido University
Graduate School of Medicine, West 7 North 15, Sapporo 060-8638, Japan.
nmaru@med.hokudai.ac.jp

OBJECTIVE: The objective was to ascertain the prevalence of Plantago lanceolata
(English plantain) pollinosis in Japan. METHODS: A total of 160 patients with
allergic rhinitis were examined at the Hokkaido University Hospital
Otolaryngology Clinic between January 2002 and December 2003. We investigated the
frequency of P. lanceolata antigen-specific immunoglobulin E (IgE)
antibody-positive serum using the radioallergosorbent test (RAST), the P.
lanceolata pollen counts in the Sapporo area and the clinical symptoms of
patients with allergic rhinitis caused by this pollen. RESULTS: P. lanceolata
pollen was dispersed throughout the Sapporo area from mid-May to early September,
peaking in the latter half of May. The airborne pollen count showed little
variation between years. The P. lanceolata RAST-positive rate was 12.8%, which
was close to those for ragweed and sagebrush. All subjects showed overlapping
antigen sensitization, that is, none displayed sensitization (by RAST)
exclusively to P. lanceolata. The onset of subjective symptoms peaked in June and
the symptoms worsened from April to October. CONCLUSION: P. lanceolata was
dispersed over a long period, from mid-May to early September. The P. lanceolata 
RAST-positive rate (12.8%) was similar to those for sagebrush and ragweed, which 
are dispersed during the fall. These results suggest that P. lanceolata is an
important causative agent of pollinosis in Japan.

Publication Types: 
    Case Reports

PMID: 15885951 [PubMed - indexed for MEDLINE]

766: Immunol Allergy Clin North Am. 2005 May;25(2):421-39, viii.

Immunotherapy: first do no harm.

Moss MH.

Department of Medicine, Section of Allergy, Pulmonary, and Critical Care
Medicine, University of Wisconsin Medical School, K4/934 CSC #9988, University of
Wisconsin Hospital and Clinics, 600 Highland Avenue, Madison, WI 53792, USA.
mhm@medicine.wisc.edu

Immunotherapy continues to be a treatment modality that is used most exclusively 
by allergists. The acceptance of immunotherapy for treating children with
allergic rhinitis or asthma has been limited by the lack of adequate numbers of
pediatric double-blind, placebo-controlled trials of specific allergen
immunotherapy; use of venom immunotherapy is more clearly supported by current
data. Children represent a unique group of patients where allergic disease may
not only be treated using immunotherapy resulting in reduction of symptoms,
signs, and complications of disease, but may also hold the best potential for the
evasive goal of prevention of the development of future allergic disease.

Publication Types: 
    Review

PMID: 15878464 [PubMed - indexed for MEDLINE]

767: Immunol Allergy Clin North Am. 2005 May;25(2):301-12, vi-vii.

Cognitive effects of allergic rhinitis and its treatment.

Bender BG.

Division of Pediatric Behavioral Health, National Jewish Medical and Research
Center, 1400 Jackson Street, Denver, CO 80206, USA. benderb@njc.org

Allergic rhinitis (AR) can, by itself, introduce significant sedation and
impairment of cognition and performance. AR can also impede restorative sleep,
resulting in increased fatigue and decreased daytime performance. It is not clear
whether improved alertness resulting from blocking histamine production offsets
the sedating effects of antihistamines or whether the effects of disease and
treatment combine to create even greater sedation. This article reviews and
integrates this literature, offers conclusions based on the collective evidence, 
and suggests guidelines for future research.

Publication Types: 
    Review

PMID: 15878457 [PubMed - indexed for MEDLINE]

768: Allergy. 2005 Jun;60(6):801-7.

Efficacy and safety of preseasonal-specific immunotherapy with an
aluminium-adsorbed six-grass pollen allergoid.

Corrigan CJ, Kettner J, Doemer C, Cromwell O, Narkus A; Study Group.

Guy's, King's and St Thomas's School of Medicine, London, UK.

BACKGROUND: The clinical efficacy and safety of a six-grass pollen allergoid has 
been studied. The advent of more exacting clinical guidelines and a better
appreciation of the possible mechanisms of treatment prompted this reappraisal.
METHODS: A 2-year double-blind multicentre placebo-controlled phase 3 clinical
trial was undertaken in 154 patients suffering symptoms of rhinoconjunctivitis
with or without asthma (GINA I or II). Therapy comprised two consecutive
preseasonal short-courses of subcutaneous injections using a grass pollen
allergoid adsorbed to aluminium hydroxide. RESULTS: A combined symptom and
medication score (SMS) was used as the primary end-point for clinical efficacy.
SMS from the first year showed a significant difference of 26.6% between the two 
study groups (P=0.026) and this was improved after the second year when there was
a 48.4% difference in SMS between active and placebo treatment in favour of the
allergoid (P = 0.018). Highly significant increases in grass pollen
allergen-specific IgG1 and IgG4 antibody concentrations were measured in
association with active treatment. Allergen tolerance was increased as judged by 
a conjunctival provocation test and significant improvements in quality of life
were documented using a standardized questionnaire. The allergoid was well
tolerated. CONCLUSIONS: The grass pollen allergoid was shown to be safe and
clinically efficacious in the management of hay fever with or without asthma
(GINA I or II).

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15876311 [PubMed - indexed for MEDLINE]

769: Ann Allergy Asthma Immunol. 2005 Apr;94(4):457-64.

The efficacy of short-term administration of 3 antihistamines vs placebo under
natural exposure to Japanese cedar pollen.

Hyo S, Fujieda S, Kawada R, Kitazawa S, Takenaka H.

Department of Otorhinolaryngology, Osaka Medical College, Osaka, Japan.
oto039@poh.osaka-med.ac.jp

BACKGROUND: Japanese cedar pollinosis, a common disease with morbidity of
approximately 20% in the Japanese population, is characterized by subjectively
irritating symptoms during an annual 3-month period. OBJECTIVE: To investigate
the effectiveness of cetirizine hydrochloride, loratadine, and fexofenadine
hydrochloride in reducing pollinosis symptoms induced while walking in a park
during the pollen season. METHODS: A randomized, double-masked,
placebo-controlled trial was conducted in 113 individuals with Japanese cedar
pollinosis during 2 days in March 2003 in Osaka Expo Park, Osaka, Japan.
Participants (aged 20-57 years) were divided into 4 groups according to treatment
assignment: cetirizine hydrochloride, 10 mg/d; fexofenadine hydrochloride, 120
mg/d; loratadine, 10 mg/d; and placebo (lactose), twice daily. Symptoms were
recorded hourly during the study. Furthermore, all the patients completed the
Japanese version of the Rhinoconjunctivitis Quality of Life Questionnaire before 
and after the trial. RESULTS: Self-evaluated symptom scores in all 3 active
treatment groups showed significant improvements compared with the placebo group.
Furthermore, the cetirizine group showed significant improvement in the domains
of frequency of nose blowing and nasal obstruction compared with placebo. In
addition, improvement in Japanese Rhinoconjunctivitis Quality of Life
Questionnaire scores was higher in the cetirizine group than in the loratadine
and placebo groups. CONCLUSION: Cetirizine seems to be more effective than
fexofenadine and loratadine at reducing subjective symptoms in this study
population.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15875527 [PubMed - indexed for MEDLINE]

770: J Investig Allergol Clin Immunol. 2005;15(1):22-9.

Rupatadine 10 mg and cetirizine 10 mg in seasonal allergic rhinitis: a
randomised, double-blind parallel study.

Martínez-Cócera C, De Molina M, Martí-Guadaño E, Pola J, Conde J, Borja J, Pérez 
I, Arnaiz E, Izquierdo I; Spanish Rupatadine Rhinitis Study Group.

Allergology Department, Hospital Clinico San Carlos, Madrid.

This randomised, double-blind, parallel-group, multicentre clinical trial
evaluated the efficacy and safety of rupatadine, a new antihistamine with
antiplatelet-activating factor (PAF) activity, and cetirizine in the treatment of
patients with seasonal allergic rhinitis (SAR). A total 249 patients were
randomised to receive rupatadine 10 mg once daily (127 patients) or cetirizine 10
mg (122 patients) for two weeks. The main efficacy variable was the mean total
daily symptom score (mTDSS) and was based on the daily subjective assessment of
the severity of each rhinitis symptom--nasal (runny nose, sneezing, nasal itching
and nasal obstruction) and non-nasal (conjunctival itching, tearing, and
pharyngeal itching)--recorded by patients in their diaries. The mTDSS was 0.7 for
both treatment groups (intention to treat analysis). In the investigator's global
evaluation of efficacy at the seventh day, 93.3% and 83.7% patients in the
rupatadine and cetirizine groups, respectively, showed some or great improvement 
(p = 0.022). In the per protocol analysis (n = 181), runny nose at the seventh
day of treatment was absent or mild in 81.1% of patients in the rupatadine group 
and in 68.6% of patients in the cetirizine group (p = 0.029). In any case
statistical significance was not maintained at the second week. Overall, all
treatments were well tolerated. Adverse events (AEs) were similar in both
treatment groups, i.e. headache, somnolence and fatigue/asthenia as the most
often reported. Somnolence was reported in 9.6% and 8.5% of patients treated with
rupatadine or cetirizine, respectively. The most reported AEs (67%) were mild in 
intensity. Our results suggest that rupatadine 10 mg may be a valuable and safe
alternative for the symptomatic treatment of SAR.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15864879 [PubMed - indexed for MEDLINE]

771: Eur Ann Allergy Clin Immunol. 2005 Feb;37(2):69-71.

Comparison of allergen immunotherapy and drug treatment in seasonal
rhinoconjunctivitis: a 3-years study.

Giovannini M, Braccioni F, Sella G, Contoli M, Perri G, Frati F, Incorvaia C.

Pulmonary and Allergic Diseases Department, Lugo Hospital, Ravenna, Italy.

Drug treatment and specific immunotherapy (SIT) are both effective in seasonal
rhinoconjunctivitis, but the former acts only on allergic symptoms while the
latter modifies the natural history of the disease. Only a few studies compared
the clinical efficacy of the two treatments with contrasting results. We planned 
a study to compare the efficacy of SIT (15 patients) and drug treatment (15
patients) in moderate to severe seasonal rhinoconjunctivitis caused by
sensitization to grass pollen. SIT was performed by a 5-grass extract
standardized in IR and absorbed onto calcium phosphate (Phostal, Stallergénes,
Antony, France) using the conventional build-up phase in 12 weeks and a
maintenance treatment with monthly injection for three years. Drug treatment was 
done with cetirizine as antihistamine, mometasone furoate as nasal topical
steroid, and levocabastine eyedrops. All patients registered during the pollen
season their symptoms and drug consumption. After one year 12 of 15 patients
treated with SIT had less symptoms and drug consumption in respect to baseline
compared to none in drug treated group (p = 0.021) and after three years 15 of 15
were improved in group A compared to one of 15 in group B (p = 0.008). These
findings indicate an higher efficacy of SIT in patients with seasonal rhinitis
not only in the long term but also in the first year of treatment.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15859367 [PubMed - indexed for MEDLINE]

772: Eur Ann Allergy Clin Immunol. 2005 Feb;37(2):58-9.

Physical exercise does not favour adverse reactions to allergen immunotherapy by 
the sublingual route.

Senna GE, Bonadonna P, Crivellaro MA, Incorvaia C, Sensi L, Frati F, Marcucci F.

Allergy Service, Borgo Trento Hospital, Verona, Italy.

It is generally recommended in consensus documents on allergen immunotherapy to
avoid any kind of physical exercise in the 24 hours following the administration 
of the allergen extract but such recommendation is not supported by scientific
evidence. We evaluated the risk of developing adverse reactions in a group of
patients submitted to sublingual immunotherapy by performing a controlled
exercise test. Eleven patients were included in the study, 8 treated with grass
pollen and 3 with Parietaria pollen extract by Staloral300 (Stallergénes, Antony,
France), with the build-up phase in 11 days suggested by the manufacturer and a
top dose of 300 IR. At the first maintenance dose, in all patients were measured 
heart rate, blood pressure, FEV1, and tryptase in blood. Then the maintenance
dose was assumed and the physical exercise performed by cycloergometer
maintaining a heart rate around 100 b/min and measuring again tryptase, blood
pressure and FEV1. The results showed that no patient had adverse reaction
following physical exercise, neither showed significant changes in FEV1, blood
pressure, or tryptase level, which was 5.57 +/- 4.54 mcg/l before and 5.81 +/-
4.34 mcg/l after exercise. This suggests that there is no reason to advise
against physical exercise, and particularly sporting activity, in patients
treated with sublingual immunotherapy thus avoiding to interfere with the
subject's lifestyle and consequently with his quality of life.

PMID: 15859363 [PubMed - indexed for MEDLINE]

773: Pediatr Allergy Immunol. 2005 May;16(3):209-16.

Bet v 1-specific IgA increases during the pollen season but not after a single
allergen challenge in children with birch pollen-induced intermittent allergic
rhinitis.

Keen C, Johansson S, Reinholdt J, Benson M, Wennergren G.

Department of Pediatrics, Göteborg University, Queen Silvia Children's Hospital, 
Göteborg, Sweden. christina.keen@vgregion.se

Allergen-specific immunoglobulins of the Immunoglobulin A (IgA) type have been
found in the nasal fluid of patients with allergic rhinitis. IgA may play a
protective role, but there are also data which show that allergen-specific IgA
can induce eosinophil degranulation. The aim of this study was to quantitate Bet 
v 1-specific IgA in relation to total IgA in the nasal fluid of children with
birch pollen-induced intermittent allergic rhinitis and healthy controls, after
allergen challenge and during the natural pollen season. Eosinophil cationic
protein (ECP), Bet v 1-specific IgA and total IgA were analyzed in nasal fluids
from 30 children with birch pollen-induced intermittent allergic rhinitis and 30 
healthy controls. Samples were taken before the pollen season, after challenge
with birch pollen and during the pollen season, before and after treatment with
nasal steroids. During the pollen season, but not after nasal allergen challenge,
Bet v 1-specific IgA increased in relation to total IgA in children with allergic
rhinitis. No change was found in the healthy controls. The ratio of Bet v
1-specific IgA to total IgA increased from 0.1 x 10(-3) (median) to 0.5 x 10(-3) 
in the allergic children, p < 0.001. No change was seen after treatment with
nasal steroids, although symptoms, ECP and eosinophils were reduced. In
conclusion, allergen-specific IgA in relation to total IgA increases in nasal
fluids during the pollen season in allergic children but not in healthy controls.
These findings are compatible with the hypothesis that allergen-specific IgA
plays a role in the allergic inflammation and further studies are needed to
clarify the functional role of these allergen-specific antibodies. Copyright 2005
Blackwell Munksgaard

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15853949 [PubMed - indexed for MEDLINE]

774: Rhinology. 2005 Mar;43(1):47-54.

Symptomatic and pathophysiological observations in a modified animal model of
allergic rhinitis.

Zhao Y, Woo JK, Leung PC, Chen GG, Wong YO, Liu SX, van Hasselt CA.

The Institute of Traditional Chinese Medicine, Chinese University of Hong Kong,
Shatin, N.T, Hong Kong.

There are many animal models for studying allergic rhinitis. However, they either
need a too long establishment period or fail to show significant late allergic
responses. In the model described in this paper, guinea pigs were sensitized and 
challenged intranasally with ovalbumin according to a modified protocol. As
controls, antihistamine-treatment and non-sensitized, non-treatment groups were
studied in parallel. Early and late symptoms, passive cutaneous anaphylaxis (PCA)
reaction, nitric oxide synthase (NOS) immunoreactivities, pathological changes in
nasal mucosa and nasal lavage fluid (NLF), and histamine, TXB2 and p-LTs levels
in NLF were evaluated. In contrast to the control groups, the model group
exhibited typical symptoms, including late phase nasal blockage, and increased
levels of IgG1 and IgE. Considerable eosinophil infiltration and eNOS
immunoreactivities in nasal mucosa, and increased levels of histamine, TXB2 and
p-LTs in NLF were also observed. This model was not only capable of showing
satisfactory symptomatic and pathophysiological changes in allergic rhinitis but 
also showed good responses to antihistamine treatment. The model can be
established in six weeks. For the first time, respiratory rate was employed as an
index to reflect the nasal blockage of guinea pigs and it proved to be a reliable
indicator.

PMID: 15844502 [PubMed - indexed for MEDLINE]

775: Curr Allergy Asthma Rep. 2005 May;5(3):252-8.

The role of immunoglobulin E and immune inflammation: implications in allergic
rhinitis.

Poole JA, Rosenwasser LJ.

National Jewish Medical and Research Center, University of Colorado Health
Sciences Center, Denver 80206, USA.

Immunoglobulin E (IgE) plays a critical role in the allergic inflammatory process
in diseases such as allergic rhinitis. Cross-linking IgE bound to its receptor on
cells by multivalent allergens initiates a chain of events resulting in allergic 
immune responses. Mast cells and basophils are involved in the early, immediate
response, which is marked by cellular degranulation and the release of
proinflammatory mediators, including histamine. Antigen-presenting cells are also
activated by allergen-loaded IgE, resulting in immunomodulation of T-cell
responses. The IgE molecule binds to two types of receptors, the high-affinity
(Fc epsilonRI) and low-affinity (Fc epsilonRII or CD23) receptors, that have
differing properties important in mediating allergen-induced responses. New
therapies targeting the IgE molecule reduce allergen-stimulated immune responses 
and improve the clinical symptoms in subjects with allergic rhinitis.
Understanding the role of the IgE molecule is necessary to appreciate the
development and use of novel therapies targeting its actions.

Publication Types: 
    Review

PMID: 15842964 [PubMed - indexed for MEDLINE]

776: Curr Allergy Asthma Rep. 2005 May;5(3):221-6.

Potential roles in rhinitis for protease and other enzymatic activities of
allergens.

Sehgal N, Custovic A, Woodcock A.

North West Lung Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT,
UK. nitasehgal@ukonline.co.uk

Exposure to airborne pollen, fungal allergens, and dust mite allergens is
associated with the development of allergic rhinitis. Biologic function of
allergens is considered to be a key determinant for allergenicity, and many
clinically important allergens have been shown to possess enzymatic activity. It 
is proposed that by enabling allergens to breach the integrity of the airway
epithelial barrier, proteolytic activity plays an adjuvant pro-allergic role
influencing immunogenicity. In this review, current evidence regarding enzymatic 
activity of aeroallergens is described, and the potential role of aeroallergens
in allergic rhinitis is discussed.

Publication Types: 
    Review

PMID: 15842960 [PubMed - indexed for MEDLINE]

777: Curr Allergy Asthma Rep. 2005 May;5(3):182-5.

Immunostimulatory sequences of DNA and conjugates in the treatment of allergic
rhinitis.

Broide DH.

Department of Medicine, University of California San Diego, 9500 Gilman Drive, MC
0635, La Jolla, CA 92093, USA. dbroide@ucsd.edu

Therapeutic strategies based on the use of immunostimulatory sequences of DNA
containing a CpG motif (also known as ISS DNA, or CpG DNA) are focused on
minimizing the allergenicity of immunotherapy while improving its effectiveness. 
Several ISS DNA-based methods of immunization (ISS DNA alone, ISS DNA conjugated 
to a protein allergen) have shown promise in animal models of asthma, and some of
these ISS DNA-based therapies have entered clinical trials. These ongoing
clinical trials will help to determine whether any of these ISS DNA-based
therapies are safe and effective to use in subjects with allergic rhinitis and
asthma.

Publication Types: 
    Review

PMID: 15842954 [PubMed - indexed for MEDLINE]

778: Clin Exp Allergy. 2005 Apr;35(4):473-8.

Gene profiling reveals decreased expression of uteroglobin and other
anti-inflammatory genes in nasal fluid cells from patients with intermittent
allergic rhinitis.

Benson M, Jansson L, Adner M, Luts A, Uddman R, Cardell LO.

Laboratory for Clinical and Experimental Allergy Research, Department of
Oto-Rhino-Laryngology, Malmö University Hospital, Malmö, Sweden.
mikael.benson@vgregion.se

BACKGROUND: Intermittent allergic rhinitis (IAR) results from interactions
between a large number of pro- and anti-inflammatory mediators. Little is known
about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous
analysis of the whole transcriptome in a sample. OBJECTIVE: To identify
anti-inflammatory transcripts in nasal fluid cells from patients with IAR during 
season and from healthy controls. METHODS: Nasal lavage fluids were obtained from
15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy
controls. RNA was extracted from the nasal fluid cells and pooled into one
patient- and one control pool. These were analysed with DNA microarrays
containing more than 44,927 genes and variants. RESULTS: Seventeen thousand three
hundred and fifty three genes were expressed in the controls and 17 928 in the
patients. One thousand five hundred and seventy nine of the genes had higher
expression in patients than in controls, and 1570 had lower expression in
patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory
and two were anti-inflammatory. These genes regulated key steps of inflammation, 
ranging from influx of leukocytes to immunoglobulin production. By comparison,
out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were
anti-inflammatory. The anti-inflammatory gene that decreased most in expression
in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The 
nasal fluid concentrations of uteroglobin protein were significantly lower in
patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively
(P<0.05). CONCLUSION: IAR is associated with decreased expression of uteroglobin 
and other anti-inflammatory genes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15836756 [PubMed - indexed for MEDLINE]

779: Psychother Psychosom. 2005;74(3):165-72.

Effect of self-hypnosis on hay fever symptoms - a randomised controlled
intervention study.

Langewitz W, Izakovic J, Wyler J, Schindler C, Kiss A, Bircher AJ.

Division of Psychosomatic Medicine, Department of Internal Medicine, University
Hospital Basel, Basel, Switzerland. wlangewitz@uhbs.ch

BACKGROUND: Many people suffer from hay fever symptoms. Hypnosis has proved to be
a useful adjunct in the treatment of conditions where allergic phenomena have an 
important role. METHODS: Randomised parallel group study over an observation
period of two consecutive pollen seasons. Outcome data include nasal flow under
hypnosis, pollinosis symptoms from diaries and retrospective assessments,
restrictions in well-being and use of anti-allergic medication. We investigated
79 patients with a mean age of 34 years (range 19-54 years; 41 males), with
moderate to severe allergic rhinitis to grass or birch pollen of at least 2 years
duration and mild allergic asthma. The intervention consisted of teaching
self-hypnosis during a mean of 2.4 sessions (SD 1.7; range 2-5 sessions) and
continuation of standard anti-allergic pharmacological treatment. RESULTS: Of 79 
randomised patients, 66 completed one, and 52 completed two seasons.
Retrospective VAS scores yielded significant improvements in year 1 in patients
who had learned self-hypnosis: pollinosis symptoms -29.2 (VAS score, range 0-100;
SD 25.4; p < 0.001), restriction of well-being -26.2 (VAS score, range 0-100; SD 
28.7; p < 0.001. In year 2, the control group improved significantly having
learned self-hypnosis as well: pollinosis symptoms -24.8 (SD 29.1; p < 0.001),
restriction of well-being -23.7 (SD 30.0; p < 0.001). Daily self-reports of
subjects who learnt self-hypnosis do not show a significant improvement. The
hazard ratio of reaching a critical flow of 70% in nasal provocation tests was
0.333 (95% CI 0.157-0.741) after having learnt and applied self-hypnosis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15832067 [PubMed - indexed for MEDLINE]

780: Int J Epidemiol. 2005 Dec;34(6):1302-9. Epub 2005 Apr 14.

A comparison of genetic and environmental variance structures for asthma, hay
fever and eczema with symptoms of the same diseases: a study of Norwegian twins.

Nystad W, Røysamb E, Magnus P, Tambs K, Harris JR.

Division of Epidemiology, Norwegian Institute of Public Health, Nydalen, Oslo,
Norway. wenche.nystad@fhi.no

BACKGROUND: We compared patterns of genetic and environmental influences on
variation in liability for asthma, hay fever and eczema with those for symptoms
of the same diseases, and determined how common sets of genes and environmental
factors contribute to the relationship between diseases and symptoms among
Norwegian twins. METHODS: Analyses were based on self-reported asthma, hay fever 
and eczema and symptoms of the same diseases among 3334 pairs of Norwegian twins 
aged 18-35 years. Structural equation modelling was conducted to estimate the
genetic and environmental variance structures. RESULTS: For all diseases the
concordances and the twin correlations were higher among monozygotic than among
dizygotic twins. The results of the modelling confirmed that genetic effects were
substantial for the diseases, and were more moderate for symptoms. The phenotypic
correlation between disease and symptom was 0.67 for asthma and wheeze (a/w),
0.64 for hay fever and sneeze (hf/s), and 0.54 for eczema and itch (e/i).
Decomposition of these correlations into genetic (G) and environmental (E)
pathways revealed that G = 0.48 and E = 0.19 for a/w, G = 0.40 and E = 0.24 for
hf/s, and G = 0.34 and E = 0.20 for e/i. For the diseases, the specific sources
of genetic variance accounted for more variation than the specific environmental 
variance. Variance decomposition revealed that specific sources of variance were 
primarily explained by genetic effects for diseases and by environmental
influences for symptoms. CONCLUSIONS: Genetic effects account for greater
variation in reported diseases than symptoms. Co-occurrence of diseases and
symptoms is mainly explained by genetic effects common to both phenotypes, but
non-shared environment is also important.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Twin Study

PMID: 15831566 [PubMed - indexed for MEDLINE]

781: Respirology. 2005 Mar;10(2):244-9.

Prevalence of asthma, eczema and allergic rhinitis: two surveys, 6 years apart,
in Kota Bharu, Malaysia.

Quah BS, Wan-Pauzi I, Ariffin N, Mazidah AR.

Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia,
Kelantan, Malaysia. bsquah@kb.usm.my

OBJECTIVE: This study was undertaken to determine the prevalence of asthma,
eczema, and allergic rhinitis in school children in Kota Bharu, Malaysia, and in 
so doing to determine the differences in symptom prevalence rates of asthma, and 
atopic diseases in Kota Bharu school children between 1995 and 2001. METHODOLOGY:
In two studies (1995 and 2001), year one primary school (PS) pupils (6-7 years
old) and secondary school (SS) year two pupils (13-14 years old) were randomly
selected from the district of Kota Bharu, Kelantan, Malaysia. In 1995, 3939 PS
children and 3116 SS children participated, and in 2001 3157 PS children and 3004
SS children participated. The Phase I International Study of Asthma and Allergies
in Childhood prevalence written questionnaire and video questionnaire (only shown
to SS children) were used in both studies. RESULTS: The written questionnaire
showed no significant changes in the prevalence (1995, 2001) of ever wheeze
(8.3%, 6.9%P = 0.06), current wheeze (5.4%, 4.3%P = 0.08), exercise-induced
wheeze (EIW; 3.9%, 3.7%P = 0.63), and rhinoconjunctivitis (4.6%, 5%P = 0.42)
among PS children. The prevalence of flexural itchy rash increased from 14% to
17.6% (P = 0.004) and night cough decreased from 20.4% to 17.5% (P = 0.005).
There were also no significant changes in these symptoms among SS children (1995,
2001): ever wheeze (10.7%, 12%P = 0.37), current wheeze (6.8%, 5.7%P = 0.20), EIW
(9.9%, 11.6%P = 0.28), night cough (21.6%, 24%P = 0.39), rhinoconjunctivitis
(11%, 15%P = 0.11), and flexural itchy rash (12%, 13%P = 0.11). The video
questionnaire showed no significant changes in the prevalence of symptoms in the 
previous 12 months (1995 vs 2001) for wheeze at rest (3.8%, 2.8%P = 0.12), EIW
(6.9%, 8.8%P = 0.32), waking with wheeze (1.7%, 1.7%P = 1.0), and severe wheeze
(2.1%, 3%P = 0.12). Night cough in the previous 12 months increased significantly
from 5.1% to 8.3% (P = 0.007). CONCLUSION: Although asthma and atopic disorders
are common in this country, the results revealed no major changes in the
prevalence rates of these diseases over a period of 6 years.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15823193 [PubMed - indexed for MEDLINE]

782: Prof Nurse. 2005 Apr;20(8):31-3.

Improving the management and quality of life of patients with allergic rhinitis.

Carr V.

National Heart and Lung Institute, Imperial College London.
v.carr@rbh.nthames.nhs.uk

Allergic rhinitis affects up to a fifth of the population in the West, yet there 
is little specialist care to support and manage patients, and medical and nursing
curicula fail to address the issue of allergies. This paper looks at the main
causes of allergic rhinitis and its symptoms, and describes the available
treatments to manage the conditon.

Publication Types: 
    Review

PMID: 15819315 [PubMed - indexed for MEDLINE]

783: J Immunol. 2005 Apr 15;174(8):5024-32.

Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis.

Takhar P, Smurthwaite L, Coker HA, Fear DJ, Banfield GK, Carr VA, Durham SR,
Gould HJ.

The Randall Division, King's College London, London, United Kingdom.

IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than
the peripheral blood B cell population. We have investigated the provenance of
these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted 
that expression of activation-induced cytidine deaminase and class switch
recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells
must migrate through the circulation to the nasal mucosa. Our detection of mRNA
for activation-induced cytidine, multiple germline gene transcripts, and epsilon 
circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic
control subjects, however, indicates that local CSR occurs in allergic rhinitis. 
The germline gene transcripts and epsilon circle transcripts in grass
pollen-allergic subjects are up-regulated during the season and also when
biopsies from allergic subjects are incubated with the allergen ex vivo. These
results demonstrate that allergen stimulates local CSR to IgE, revealing a
potential target for topical therapies in allergic rhinitis.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 15814733 [PubMed - indexed for MEDLINE]

784: Allergy. 2005 May;60(5):678-84.

Monophosphoryl lipid A (MPL) promotes allergen-induced immune deviation in favour
of Th1 responses.

Puggioni F, Durham SR, Francis JN.

Division of Respiratory Medicine, IRCCS Policlinic San Matteo, University of
Pavia, Pavia, Italy.

BACKGROUND: Monophosphoryl lipid A (MPL) is a nontoxic derivative of the
lipopolysaccharide (LPS) of Salmonella minnesota R595. MPL has been used as an
adjuvant in grass and tree pollen vaccines for the treatment of seasonal allergic
rhinitis. Little is known about the influence of MPL on cellular responses to
allergens in man. We therefore studied the effects of MPL in vitro on peripheral 
blood mononuclear cells (PBMC) obtained from patients with grass pollen hay
fever. METHODS: The PBMCs from 13 subjects were cultured with grass pollen Phleum
pratense extract (0, 2 and 20 microg/ml) and MPL (0 and 10 microg/ml; defined as 
an optimal concentration in preliminary studies) and after 6 days proliferative
responses were measured by thymidine incorporation and cytokine production by
enzyme-linked immunosorbent assay (ELISA). RESULTS: Proliferative responses were 
unaffected by the presence of MPL whereas MPL induced a significant increase in
allergen-induced interferon (IFN)-gamma production [allergen alone, 645 +/- 466
pg/ml (mean +/- SE) vs allergen + MPL, 3232 +/- 818 pg/ml; P < 0.001]. In
addition, there was a significant decrease in interleukin (IL)-5 production (4307
+/- 1030 pg/ml vs 2997 +/- 826 pg/ml; P < 0.01). Although MPL alone could induce 
modest increases in IL-10 production, MPL did not influence the production of
this cytokine in allergen-stimulated cultures. Addition of neutralizing antibody 
against IL-12 resulted in 95% inhibition of MPL-induced IFN-gamma production.
Depletion of monocytes from the culture system abrogated the effects of MPL on
elevated cytokine production. CONCLUSIONS: In summary, use of MPL with grass
pollen extract results in immune deviation of allergen-induced peripheral
Th2-cell responses in favour of 'protective' Th1 responses in an IL-12 and
monocyte-dependent fashion.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15813815 [PubMed - indexed for MEDLINE]

785: Allergy. 2005 May;60(5):643-9.

Comparison of nasal immunohistology in patients with seasonal rhinoconjunctivitis
treated with topical steroids or specific allergen immunotherapy.

Rak S, Heinrich C, Scheynius A.

Department of Respiratory Medicine and Allergology, Sahlgrenska University
Hospital, Göteborg, Sweden.

BACKGROUND: Specific allergen immunotherapy (SIT) and nasal steroids (NS) are
considered effective anti-inflammatory treatments for allergic rhinitis, although
their mechanism of action differs. OBJECTIVE: The aim of this study was to
examine the effect of treatment with NS and SIT on different populations of
inflammatory cells in the nasal mucosa and to compare cell numbers before and
during the birch pollen season in patients with seasonal allergic rhinitis.
METHODS: In a randomized, double-blind, double dummy comparative study, 41
patients with seasonal rhinoconjunctivitis were treated with birch SIT or NS
(budesonide 400 microg daily). Treatment with NS started before the birch pollen 
season and at the same time SIT-treated patients reached the maintenance dose.
Nasal biopsies for immunohistochemistry were obtained before the season and start
of the treatments and at the peak of the pollen season during treatment. RESULTS:
Symptoms of rhinoconjunctivitis increased significantly in both groups during the
pollen season but less in the NS-treated group and the difference between the
treatment groups was significant at the end of the season (P = 0.03).
Immunohistochemistry of nasal biopsies from NS-treated patients showed
significantly fewer CD1a+, IgE+ and Fc epsilonRI+ cells during the season
compared with preseason (P = 0.02, P = 0.001 and P = 0.0004, respectively) and
with seasonal values of the SIT-treated group (P = 0.002, P = 0.002 and P =
0.0004 respectively). CONCLUSION: Treatment with NS but not SIT decreased the
numbers of CD1a+, IgE+ and Fc epsilonRI+ cells during the birch pollen season.
Our data indicate that treatment with NS has a broader anti-inflammatory range
than SIT.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15813810 [PubMed - indexed for MEDLINE]

786: Allergy. 2005 May;60(5):638-42.

Low levels of CC16 in nasal fluid of children with birch pollen-induced rhinitis.

Johansson S, Keen C, Ståhl A, Wennergren G, Benson M.

Department of Pediatrics, Göteborg University, Queen Silvia Children's Hospital, 
Göteborg, Sweden.

BACKGROUND: Clara cell protein 16 (CC16; secretoglobin 1A1) is an
anti-inflammatory protein mainly expressed in the epithelial cells in the
airways. OBJECTIVE: To compare the levels of CC16 in nasal lavage (NAL) from
children with intermittent allergic rhinitis and healthy controls and to study
the effect of a local steroid. METHODS: Thirty schoolchildren with birch pollen
allergy and 30 healthy controls from the same schools were included in the study.
The NAL fluid was collected before the season, during the birch pollen season
and, for the patients, after 1 week of treatment with a local steroid. Symptom
scores were obtained on every occasion. CC16 and eosinophil cationic protein
(ECP) were analyzed with enzyme-linked immunosorbent assay. RESULTS: The nasal
fluid levels of CC16 were significantly lower in patients than in controls,
before and during pollen season. Before the season, the median CC16
concentrations were 9.1 (range 1.1-117) microg/l in patients and 25.7 (6.1-110.2)
microg/l in controls. During the season, the median CC16 concentrations in nasal 
fluid were 12.9 (2.3-89.7) microg/l in the allergic children and 22.0 (9.5-90.1) 
microg/l in the healthy controls (P = 0.0005). Symptom scores, nasal fluid
eosinophils and ECP were higher in patients during the season. Treatment with a
local steroid did not change the CC16 levels. CONCLUSIONS: Nasal fluid CC16
levels were lower in children with birch pollen-induced allergic rhinitis than in
healthy controls both before and during the pollen season. We speculate that
reduction in anti-inflammatory activity by CC16 may contribute to the
pathogenesis of allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15813809 [PubMed - indexed for MEDLINE]

787: Allergy Asthma Proc. 2005 Jan-Feb;26(1):41-6.

Onset of efficacy of montelukast in seasonal allergic rhinitis.

Weinstein SF, Philip G, Hampel FC Jr, Malice MP, Swern AS, Dass SB, Reiss TF.

Allergy and Asthma Specialists Medical Group and Research Center, Huntington
Beach, California 92647, USA.

Montelukast has shown efficacy for seasonal allergic rhinitis (SAR); however,
onset of action for SAR has not been presented. The aim of this study was to
determine the onset of action of montelukast, 10 mg, measured in days after
starting once-daily therapy, in spring and fall studies of SAR. Data were
analyzed from four 2-week, double-blind, placebo-controlled phase III clinical
trials. End points included the daytime nasal symptoms score, the nighttime
symptoms score, the composite symptoms score (mean of the scores for daytime
nasal symptoms and nighttime symptoms), and the daytime eye symptoms score. Using
a 0-3 scale (no symptoms to severe symptoms), daytime symptoms were rated by
patients once daily each evening; nighttime symptoms were rated once daily each
morning. Analyses of data pooled across the four evening dosing studies showed
that montelukast, compared with placebo, produced significant improvement (p < or
= 0.001) from baseline by day 2 of treatment (after 2 doses) in the daytime nasal
symptoms score, nighttime symptoms score, and composite symptoms score.
Differences between montelukast and placebo for these end points in mean change
from baseline at day 2 were -0.08 (95% CI, -0.12, -0.03), -0.08 (95% CI, -0.13,
-0.04), and -0.08 (95% CI, -0.12, -0.04), respectively. These data represented a 
mean reduction for montelukast of 11-13% in symptom scores from baseline for each
end point at day 2. When compared with the full 2-week response, these observed
differences for each end point at day 2 (after 2 doses) represented a substantial
proportion (over 70%) of the overall treatment benefits seen. Significant
improvement (p < or = 0.001) in the daytime eye symptoms score was seen by day 1 
(-0.08 [-0.12, -0.03]), after the first dose. In patients treated for SAR,
montelukast has a beneficial effect on daytime and nighttime symptoms by the 2nd 
day of daily therapy.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 15813287 [PubMed - indexed for MEDLINE]

788: Allergol Immunopathol (Madr). 2005 Mar-Apr;33(2):100-4.

Tolerance of a Salsola kali extract standardized in biological units administered
by subcutaneous route. Multicenter study.

Garde J, Ferrer A, Jover V, Pagan JA, Andreu C, Abellan A, Félix R, Milán JM,
Pajarón M, Huertas AJ, Lavín JR, de la Torre F.

Hospital General Universitario de Elche, Alicante, Spain.

BACKGROUND: Sensitivity to Salsola kali is a frequent cause of allergic
respiratory disease in various regions of Spain. However, there are very few
articles in which this allergen has been studied. METHODS AND RESULTS: In order
to evaluate the tolerance of this extract, a prospective study has been
performed. This study was observational, multi-centred and open, involving 88
patients with allergic respiratory disease due to sensitivity to Salsola, aged
between 5 and 52 years. The administration of the extract was performed
subcutaneously, through one of two treatment schedules: cluster (8 doses in 4
visits) or conventional (13 doses in 12 visits). A total of 42 adverse reactions 
were registered, in 26 patients (35 local reactions in 21 patients and 7 systemic
reactions in 6 patients). Among the 7 systemic reactions, 4 were registered with 
the cluster protocol and 2 with the conventional protocol (p = 0.329). In no
patients were serious adverse reactions registered. CONCLUSION: The subcutaneous 
administration of a Salsola extract is safe and well tolerated, both when
administered using a conventional schedule and when using a cluster schedule.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study

PMID: 15808117 [PubMed - indexed for MEDLINE]

789: Allergol Immunopathol (Madr). 2005 Mar-Apr;33(2):86-92.

Food hypersensitivity in patients with seasonal rhinitis in Ankara.

Bozkurt B, Karakaya G, Kalyoncu AF.

Department of Chest Diseases, Adult Allergy Unit, Hacettepe University School of 
Medicine, 06100 Sihhiye, Ankara, Turkey. bbozkur@hacettepe.edu.tr

BACKGROUND: Food hypersensitivity (FH) affects 1-2 % of the adult population and 
is more common in atopic individuals. The aim of this study was to determine the 
frequency of FH and risk factors for its development in patients with seasonal
rhinitis (SR) in our allergy clinic. METHODS: We performed a retrospective study 
based on the medical records of 774 patients out of 955 patients diagnosed with
SR in an adult allergy clinic between 1 January 1991 and 31 December 2003.
RESULTS: The mean age of the patients was 29.1 +/- 9.29 and 62.7 % were females. 
The most common major complaints were due to nasal symptoms in 82.3 %. The mean
duration of SR was 6.8 +/- 6.8 years. Patients were symptomatic for a mean of 3.5
+/- 1.7 months per year. Skin prick tests (SPT) with common aeroallergens were
positive in 685 patients (90.3 %), and the most common sensitivity was against
timothy (85.1 %). The most common accompanying allergic disease was FH in 14 %.
FH according to history and the results of SPT performed with food allergens were
discordant. The most common clinical manifestations of FH were oral allergy (49.1
%) and cutaneous symptoms (38.9 %). Risk factors for the development of FH in
patients with SR were dermatological symptoms, rhinitis duration > 5 years,
symptom duration > 3 months per year, SPT reactivity to Artemisia vulgaris, tree 
pollen allergens (Corylus avellena, Betula verrucosa), and bee allergy.
CONCLUSION: FH was the most common (14 %) accompanying allergic disease in
patients with SR. SPT with food allergens have limited diagnostic value for food 
allergy and/or intolerance. Risk factors for developing FH in patients with SR in
Turkey were dermatological symptoms, duration of rhinitis > 5 years, duration of 
rhinitis symptoms > 3 months per year, and SPT reactivity to Corylus avellena.

PMID: 15808115 [PubMed - indexed for MEDLINE]

790: Otolaryngol Head Neck Surg. 2005 Apr;132(4):626-9.

Eustachian tube dysfunction in allergic rhinitis.

Lazo-Sáenz JG, Galván-Aguilera AA, Martínez-Ordaz VA, Velasco-Rodríguez VM,
Nieves-Rentería A, Rincón-Castañeda C.

Otorhinolaryngology Department, Speciality Hospital No 71, Social Security
Mexican Institute, Torreón, Coahuila, México. veromart@internetual.com.mx

OBJECTIVE: To assess eustachian tube function in patients with allergic rhinitis 
and compare them with a control group. STUDY DESIGN AND SETTING: Tympanometry was
performed in 130 patients (260 ears), divided into 2 groups: 80 cases with
allergic rhinitis and 50 healthy controls. Cases underwent skin hypersensitivity 
tests. RESULTS: Cases, age 21.1 +/- 14.9; Controls, age 23.9 +/- 15.6. Most
frequent skin hypersensitivity: Dermatophagoides pt (62%), Zea Maiz (44%), and
Cockroach (37%). Tympanometry of cases showed negative values of peak
tympanometric pressure in both children and adults (P < or = 0.05). Among
children under 11 years of age, 15.5% tympanograms showed abnormal curves (13% C 
curves and 3% B curves); among the control group only normal curves were found
(type A). CONCLUSION: Allergic rhinitis patients have a higher risk of eustachian
tube dysfunction, particularly during childhood. Tympanometry is a noninvasive,
readily available procedure that may be useful in these patients to prevent
chronic middle-ear disease.

PMID: 15806058 [PubMed - indexed for MEDLINE]

791: J Allergy Clin Immunol. 2005 Apr;115(4):791-6.

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal
allergic rhinitis in a park environment.

Meltzer EO, Berkowitz RB, Grossbard EB.

Allergy and Asthma Medical Group and Research Center, 9610 Granite Ridge Drive,
Suite B, San Diego, CA 92123-2661, USA. eomeltzer@aol.com

BACKGROUND: R112 inhibits Syk kinase, a transducer of signaling through the
Fcepsilon receptor of mast cells, blocking mast cell responses to allergic
stimuli. OBJECTIVE: Examine the efficacy and safety of intranasal R112 in
volunteers with symptomatic seasonal allergic rhinitis compared with a placebo in
a park setting. METHODS: In this double-blind, placebo-controlled study of 319
volunteers with seasonal allergic rhinitis, 160 were randomized to intranasal
R112 and 159 to a vehicle control during 2 days at 2 separate locations in spring
2004. Subjects were evaluated for symptoms of allergic rhinitis (i.e., sneezes,
runny nose/sniffles, itchy nose, stuffy nose) on the basis of a possible maximum 
score of 32 for the Global Symptom Complex (GSC) scale. The primary outcome
evaluated was the difference in the reduction in GSC (area under the curve over a
period of 8 hours) from baseline between R112 and vehicle placebo. RESULTS: At
baseline, the combined GSC was approximately 18/32 and equal between treatment
groups. After 8 hours (dosing 3 mg/nostril every 4 hours x 2), R112 significantly
reduced the GSC compared with placebo (7 vs 5.4 units, respectively; P = .0005). 
Each individual symptom combined to form the GSC was also significantly improved 
in the R112 group compared with control ( P < .05). As early as 45 minutes after 
dosing, R112 showed a significant improvement in symptoms over placebo, and the
duration of action exceeded 4 hours. Adverse effects were indistinguishable
between the groups and clinically insignificant. CONCLUSION: Intranasal R112 was 
effective in this park study and is a promising new treatment for seasonal
allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15806000 [PubMed - indexed for MEDLINE]

792: J Allergy Clin Immunol. 2005 Apr;115(4):786-90.

Out-of-season recollection of drug use for seasonal IgE-mediated rhinitis: useful
but an overestimation.

Bodtger U, Malling HJ, Poulsen LK.

Allergy Clinic, National University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, 
Denmark. ub@dadlnet.dk

BACKGROUND: The history of seasonal, IgE-mediated (allergic) rhinitis is often
obtained postseasonally as a retrospective assessment. It is not known whether
recollected drug use is representative for the in-seasonal medication history.
OBJECTIVES: To investigate the agreement between in-seasonal and out-seasonal
reports on drugs and drug doses, and to investigate whether retrospective
assessment was sufficiently sensitive to detect the effect of intervention.
MATERIAL AND METHODS: Thirty-five patients allergic to birch pollen were
allocated to allergen-specific immunotherapy (SIT) or placebo in a double-blind
study. Drug use was recorded daily during the season 2000 and out-seasonally 6
months after the seasons 1999 and 2000. The mean daily drug use was transformed
into a 4-point categorical scale for simplicity and was calculated for the
out-seasonal rating and for 6 in-seasonal periods of different durations.
In-seasonal and postseasonal ratings were compared with the Cohen weighted kappa 
(kappa w). RESULTS: We observed a high level of agreement between in-seasonal and
retrospective reports of drugs used (kappa w > 0.60) and drug doses (kappa w >
0.50). The highest agreement was observed for the in-seasonal day, week, or 2
weeks with the highest drug intake. Out-seasonal ratings significantly
overestimated the daily oral and nasal antihistamine use compared with
in-seasonal periods >2 weeks. Despite being comparable pretreatment, only the SIT
group had a significant decrease in recollected total drug use during SIT.
CONCLUSION: Out-seasonal recollection of hay fever drugs represented a period of 
a maximum 14 days. It appeared sufficiently sensitive to detect the effect of
intervention.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15805999 [PubMed - indexed for MEDLINE]

793: Ann Allergy Asthma Immunol. 2005 Mar;94(3):348-54.

Efficacy and safety of an extended-release formulation of desloratadine and
pseudoephedrine vs the individual components in the treatment of seasonal
allergic rhinitis.

Pleskow W, Grubbe R, Weiss S, Lutsky B.

Radiant Research, Encinitas, California 92024, USA.
warrenpleskow@radiantresearch.com

BACKGROUND: Antihistamine-decongestant combination products generally provide
more benefit than individual components for adequately treating patients who have
seasonal allergic rhinitis (SAR) with moderate-to-severe nasal congestion.
OBJECTIVE: To compare the effectiveness and safety of a 24-hour, extended-release
formulation of desloratadine and pseudoephedrine with the individual components
in patients who have SAR with moderate-to-severe nasal congestion. METHODS:
Patients with SAR and significant nasal congestion were enrolled in a
multicenter, randomized, double-blind, double-dummy study. Patients were randomly
assigned for 2 weeks to once-daily treatment with desloratadine-pseudoephedrine, 
5/240-mg tablets; desloratadine, 5 mg; or pseudoephedrine, 240 mg. Primary
efficacy variables for the antihistamine and decongestant components of
desloratadine-pseudoephedrine were morning and evening reflective total symptom
score (TSS), excluding nasal congestion, and morning and evening reflective nasal
congestion score during the 2-week treatment period, respectively. Secondary
variables included morning instantaneous (end-of-interval) TSS (excluding
congestion), nasal congestion score, reflective morning and evening individual
symptom scores, overall condition of SAR, and therapeutic response. RESULTS: A
total of 1121 patients were enrolled in the study, and 1047 patients completed
the 2-week study. Desloratadine-pseudoephedrine was significantly more effective 
than desloratadine or pseudoephedrine monotherapy in reducing morning and evening
reflective TSS (excluding nasal congestion) during the entire treatment period.
Desloratadine-pseudoephedrine also was significantly more effective in reducing
the morning and evening reflective nasal congestion score compared with
desloratadine or pseudoephedrine monotherapy. Significant differences were seen
between the desloratadine-pseudoephedrine and monotherapy groups for changes in
morning instantaneous TSS (excluding nasal congestion) and nasal congestion
scores. No unusual or unexpected adverse events were reported. CONCLUSION:
Desloratadine-pseudoephedrine, 5/240-mg once-daily tablets, provided additional
benefit over desloratadine, 5 mg, or sustained-release pseudoephedrine, 240 mg,
monotherapy in the treatment of patients with SAR and moderate-to-severe nasal
congestion.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15801245 [PubMed - indexed for MEDLINE]

794: Ann Allergy Asthma Immunol. 2005 Mar;94(3):341-7.

Comment in:
    Ann Allergy Asthma Immunol. 2005 Mar;94(3):311-2.

Correlation between nasal symptoms and asthma severity in patients with atopic
and nonatopic asthma.

Kanani AS, Broder I, Greene JM, Tarlo SM.

Gage Occupational and Environmental Health Unit, Department of Medicine and
Public Health Sciences, University of Toronto, Ontario, Canada.

BACKGROUND: The association between allergic rhinitis and asthma has been well
recognized, and it has been postulated that rhinitis may worsen asthma.
OBJECTIVE: To investigate the severity of asthma among patients with atopic and
nonatopic asthma with and without nasal symptoms. METHODS: Atopic asthmatic
patients and nonatopic asthmatic patients were identified from the records of a
university-based asthma clinic. A comparison of demographic clinical features was
made within and between these 2 asthmatic groups, dichotomized according to the
presence or absence of rhinitis. RESULTS: A total of 178 patients were classified
as having atopic asthma and 218 as having nonatopic asthma. The atopic asthmatic 
patients with nasal symptoms compared with those without had a higher mean forced
expiratory volume in 1 second (FEV1), a higher forced vital capacity (FVC), and a
higher FEV1/FVC ratio, used fewer oral steroids, and had fewer hospitalizations. 
The nonatopic asthmatic patients with nasal symptoms compared with those without 
used more inhaled steroids (and they were also more likely to have nasal polyps
on examination). Atopic, relative to nonatopic, asthmatic patients were younger, 
had a longer duration of asthma, had a higher FEV1/FVC ratio, and took fewer oral
steroids. CONCLUSION: Contrary to current hypotheses, in this study the severity 
of asthma among atopic asthmatic patients was less in those with nasal symptoms. 
Conversely, among the nonatopic asthmatic patients, asthma was more severe among 
those with nasal symptoms than those without nasal symptoms.

PMID: 15801244 [PubMed - indexed for MEDLINE]

795: Inhal Toxicol. 2005 Mar;17(3):147-52.

Erratum in:
    Inhal Toxicol. 2005 May;17(6):315.

Seasonal allergic rhinitic and normal subjects respond differentially to nasal
provocation with acetic acid vapor.

Shusterman D, Tarun A, Murphy MA, Morris J.

Department of Medicine University of California, San Francisco, California, USA. 
dennis3@u.washington.edu

Individuals with seasonal allergic rhinitis (SAR) show a more marked nasal
obstructive response (increases in nasal airways resistance or NAR) after
provocation with chlorine gas (Cl2) than do nonrhinitic (NR) controls. We were
interested in learning whether similar differential responsiveness was apparent
after provocation with acetic acid vapor. Sixteen nonsmoking, nonasthmatic
subjects, aged 21-63 yr, equally divided by gender and nasal allergy status, were
enrolled in a single-blinded crossover study involving exposure to acetic acid
(AA) vapor (15 ppm) or air for 15 min on separate days 1 wk apart. NAR was
measured in triplicate before, immediately post-, and 15 min postexposure, was
normalized to baseline on a given exposure day, and was expressed as Net
[NAR/baseline] after acetic acid versus control (air) exposure. After log
transformation to achieve normality, the mean loge of Net [NAR/baseline] was 0.22
for SAR subjects and -0.11 for NR subjects immediately postexposure (p<.05); the 
corresponding values were 0.24 and -0.08, respectively, at 15 min postexposure
(p<.05). Inhalation of acetic acid at the (NIOSH-recommended) short-term exposure
limit of 15 ppm for 15 min produces differential nasal airflow obstruction among 
SAR versus NR subjects, with the former showing greater physiologic reactivity to
this stimulus. This differential responsiveness is consistent with our previous
findings with Cl2, indicating that there may be a generalized susceptibility
factor associated with allergic rhinitis. The response occurs with slight
subjective nasal irritation.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15788375 [PubMed - indexed for MEDLINE]

796: Clin Exp Allergy. 2005 Mar;35(3):313-8.

Bilateral nasal allergen provocation monitored with acoustic rhinometry.
Assessment of both nasal passages and the side reacting with greater congestion: 
relation to the nasal cycle.

Gotlib T, Samoliński B, Grzanka A.

Department of Otolaryngology, Medical University of Waraw, 02-097 Warsaw, Poland.
gotlib@amwaw.edu.pl

BACKGROUND: The effect of bilateral nasal provocation on nasal mucosa measured
with the use of acoustic rhinometry (AR) can be assessed for both nasal passages 
or for the side responding with greater congestion. Assessment of changes in
nasal congestion during the nasal provocation test (NPT) can be affected by the
nasal cycle (NC). The aim of this study was to find out the most accurate method 
to evaluate changes observed during bilateral nasal provocation. METHODS:
Cross-sectional areas (CSA) at the level of inferior nasal turbinate (CSA-2) were
recorded by AR in 26 volunteers with allergic rhinitis during the NC for 5-7 h
and subsequently during NPT. The risk of spontaneous total and unilateral CSA-2
decrease was established. Sensitivity of the NPT assessment for the total CSA-2
and for the side responding with greater congestion was evaluated at chosen
thresholds. These thresholds were selected in a way that the risk levels of
spontaneous decrease of unilateral and total CSA-2 were equal. RESULTS: The
assessment of the total CSA-2 was found to be more sensitive than the assessment 
of the side responding with greater congestion. The highest sensitivity and
specificity of the test was achieved by using a combination of both assessments. 
Optimum thresholds of the CSA-2 decrease for assessment at 15 min after
provocation, with this method, were 27% and 40% for the side responding with
greater congestion and for the total CSA-2, respectively. CONCLUSIONS:
Recognition of the risk of spontaneous unilateral and total CSA-2 decreases
enables introduction of combined assessment of bilateral NPT. This assessment
seems to be the most accurate method for evaluation of the test results.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 15784109 [PubMed - indexed for MEDLINE]

797: Asian Pac J Allergy Immunol. 2004 Dec;22(4):197-203.

Is the menstrual cycle affecting the skin prick test reactivity?

Kirmaz C, Yuksel H, Mete N, Bayrak P, Baytur YB.

Department of Internal Medicine, Celal Bayar University, Manisa, Turkey.

Allergen skin prick tests (SPT) are very sensitive and specific tests to detect
allergic sensitization in atopic patients. Certain factors like antihistamines,
antidepressant therapies or circadian rhythms can alter the results of SPT. In
women, the changes in endogenous hormone levels throughout the menstrual cycle
may affect the allergic responses and natural course of allergic diseases. The
aim of this study was to investigate the probable influence of the phases of the 
menstrual cycle on SPT reactivity to allergen extracts and histamine. Forty-two
female patients with seasonal allergic rhinoconjunctivitis were enrolled in the
study. Skin prick test reactivities to allergens and histamine were measured at
the beginning of the menstrual cycle (3rd or 4th day), mid-cycle (14th or 15th
day) and end-cycle (27th or 28th day) consecutively. Serum estradiol,
progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH)
levels were determined simultaneously. We observed the most significant reactions
to allergens when SPT is performed at mid-cycle. However, SPT reactivity to
histamine did not vary throughout the menstrual cycle. Serum estradiol and LH
levels showed positive correlation with SPT reactivity to allergens at mid-cycle.
Our results suggest that SPT give the best results when they are performed at
mid-cycle. Additionally, allergens seem to cause mast cell degranulation to a
greater extent in subjects in which endogenous hormones like estradiol and LH are
elevated.

PMID: 15783132 [PubMed - indexed for MEDLINE]

798: Ann Allergy Asthma Immunol. 2005 Feb;94(2):258-61.

Relationships between allergic inflammation and nasal airflow in children with
seasonal allergic rhinitis.

Ciprandi G, Tosca MA, Marseglia GL, Klersy C.

Ospedale San Martino, Genoa, Italy. gio.cip@libero.it

BACKGROUND: Allergic rhinitis is characterized by a T(H)2-dependent inflammation.
Nasal obstruction is a typical symptom of allergic rhinitis. OBJECTIVE: To
evaluate the possible relationships among nasal symptoms, allergic inflammation, 
including inflammatory cells and cytokine pattern, and nasal airflow in children 
with seasonal allergic rhinitis. METHODS: Children with seasonal allergic
rhinitis and moderate-severe nasal obstruction were evaluated during the pollen
season. Total symptom score, rhinomanometry, nasal lavage, and nasal scraping
were evaluated in all patients. Inflammatory cells were counted by conventional
staining; interleukin 5 (IL-5) and IL-8 levels were measured by immunoassay on
fluids recovered from nasal lavage. RESULTS: Twenty children (11 boys and 9
girls; mean +/- SD age, 12.9 +/- 1.7 years) participated in this study.
Eosinophil levels were significantly associated with total symptom score (r =
90.6%, P < .001), IL-5 (r = 94.9%, P < .001), and nasal flow (r = -93.6%, P <
.001). No association was elicited with IL-8 (r = 9.4%, P = .69). In a
multivariate analysis that included eosinophils, neutrophils, and IL-5,
eosinophil levels were shown to be the only independent predictor of nasal flow. 
CONCLUSIONS: This study demonstrates the close connection between T(H)2 cytokines
and eosinophil infiltration. In addition, there is clear evidence concerning the 
relationship among nasal symptoms, eosinophil infiltration, and nasal airflow.
These findings constitute evidence of the relationship between nasal airflow
impairment and eosinophilic inflammation in children with seasonal allergic
rhinitis.

PMID: 15765742 [PubMed - indexed for MEDLINE]

799: Ann Allergy Asthma Immunol. 2005 Feb;94(2):240-6.

Lack of correlation between regional pollen counts and percutaneous reactivity to
tree pollen extracts in patients with seasonal allergic rhinitis.

White JF, Levin L, Villareal M, Murphy K, Biagini R, Wellinghoff L, St Clair HG, 
Bernstein DI.

Division of Immunology-Allergy, Department of Medicine, University of Cincinnati,
Cincinnati, Ohio 45267-0563, USA.

BACKGROUND: Although seasonal patterns of tree pollination have been reported, it
is unknown if aerobiologic data correlate with patterns of in vivo sensitization.
OBJECTIVE: To evaluate the relationship between regional tree pollen exposure and
patterns of in vivo percutaneous reactivity to specific tree pollen extracts in a
local patient population with seasonal allergic rhinitis. METHODS: Patients with 
spring seasonal allergic rhinitis and percutaneous sensitivity to 1 or more
regional tree pollens were studied. Tree pollen counts were collected at the same
urban site from 1997 to 2002 and at a suburban site in 2002. Patients underwent
skin prick testing with commercial extracts of 15 indigenous tree species. Serum 
specific IgE measurements were assayed in a subset of sensitized patients.
RESULTS: Of 127 patients who reported symptoms consistent with seasonal allergic 
rhinitis during the spring pollen season, 93 qualified based on demonstration of 
at least 1 positive skin prick test result. Mean 5-year pollen counts (1997-2001)
and 2002 urban counts were highly correlated (Spearman r = 0.95, P < .001),
indicating that year-to-year pollen counts were consistent. No significant
correlation was found between mean seasonal pollen counts (urban site, 1997-2001)
and frequencies of skin prick test reactivity to specific tree pollen allergens
(Spearman r = -0.03, P = .93). No significant relationship was found between
5-year mean tree pollen counts and positive serum specific IgE tests for specific
tree pollens (Spearman r = -0.42, P = .30). Eight of 15 species elicited
percutaneous reactions in more than 50% of patients (ie, satisfying definition of
a major in vivo allergen). However, 6 of the 8 major tree allergens each
represented 5% or less of 5-year mean total tree pollen counts. CONCLUSION: No
correlation was found between overall frequencies of in vivo sensitization to
tree pollen allergens in a local population and regional pollen exposure data.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15765739 [PubMed - indexed for MEDLINE]

800: J Allergy Clin Immunol. 2005 Mar;115(3):548-54.

Association of a haplotype block spanning SDAD1 gene and CXC chemokine genes with
allergic rhinitis.

Zhang J, Noguchi E, Migita O, Yokouchi Y, Nakayama J, Shibasaki M, Arinami T.

Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, 
University of Tsukuba, Tsukuba City, Ibaraki, Japan.

BACKGROUND: Seasonal allergic rhinitis (SAR) is a common allergic disorder
characterized by episodes of sneezing, rhinorrhea, and swelling of the nasal
mucosa. Although the pathogenesis of SAR remains unclear, there does appear to be
a genetic predisposition to development of SAR. We previously identified regions 
of chromosomes 1p, 4q, and 9q linked to SAR in 48 families (188 members)
identified through children with SAR against orchard grass pollens. OBJECTIVE:
The aim of the current study was to identify susceptibility genes for SAR on 4q. 
METHODS: We screened for markers associated with SAR on 4q with 17 microsatellite
markers and then for mutations in 11 genes. We genotyped 44 single nucleotide
polymorphisms (SNPs) in 48 SAR families and performed haplotype-based haplotype
relative risk statistics implemented in the UNPHASED program. We also examined
expression of genes with human multiple tissue and immune system cDNA panels.
RESULTS: We found that 1 microsatellite marker, D4S3042, was associated with SAR 
(P = .034). The haplotype-based haplotype relative risk approach revealed that
SNPs in SDA1 domain containing 1; chemokine, CXC motif, ligand (CXCL)-9; CXCL10; 
and CXCL11 were associated with SAR (P = .001-.04). These SNPs made up a
haplotype block, and the most common haplotype of this block was transmitted
preferentially to affected offspring (P = .002). CONCLUSION: Our results suggests
that genetic variations in a haplotype block spanning the SDA1 domain containing 
1 and CXC chemokine genes on 4q21 may contribute to development of SAR in the
Japanese population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15753903 [PubMed - indexed for MEDLINE]

801: Inflamm Res. 2005 Feb;54(2):91-5.

Intracellular production of IL-2, IL-4 and IFN-gamma by peripheral blood CD3+
cells in intermittent allergic rhinitis.

Glück J, Rogala B, Mazur B.

Chair and Clinical Department of Internal Diseases, Allergology and Clinical
Immunology, Silesian University School of Medicine, ul. 3 Maja 13-15, 41-800,
Zabrze, Poland. joagluck@mp.pl

BACKGROUND: Allergic inflammation is mainly driven by type 2 T helper cells. The 
aim was to assess the changes in production of type 1 and 2 cytokines by CD3+ T
cells dependent on natural exposure to allergens in subjects with intermittent
allergic rhinitis (IAR) and in non-atopic subjects. MATERIAL: A total of 13
patients with IAR and 13 healthy non-atopics were recruited into the study. 11
patients with IAR were examined during the grass pollen season and 11 patients
outside the season, 9 of them were assessed on both occasions. METHODS: A flow
cytometric assessment of intracellular expression of IL-2, IL-4 and IFN-gamma by 
CD3+ cells was performed. For statistical analysis non-parametric tests were
used. RESULTS: A tendency to decreased production of IL-4 outside the season was 
observed (6.94% [3.42-13.33] in season vs. 2.06% [0.7-3.6] out of season). The
production of IL-4 was higher in the rhinitic group in the season than in the
control group (1.93% [1.07-4.97], p=0.0034) and production of IL-2 was higher
both in and outside the season (9.1% [3.94-15.09] and 10.0% [4.79-25.35] vs.
3.64% (2.64-5.03), p=0.037 and 0.045, respectively). IL-4/IL-2 and IL-4/IFN-gamma
ratios were higher in the IAR group in the season than outside the season.
CONCLUSION: A tendency towards a switch from a predominant type 2 response during
natural allergen exposure to its suppression outside the season was found,
together with a stable type 1 response.

PMID: 15750716 [PubMed - indexed for MEDLINE]

802: J Allergy Clin Immunol. 2005 Mar;115(3 Suppl 1):S460-82.

Clinical trial design, nasal allergen challenge models, and considerations of
relevance to pediatrics, nasal polyposis, and different classes of medication.

Akerlund A, Andersson M, Leflein J, Lildholdt T, Mygind N.

AstraZeneca, PO Box 34, S-22100 Lund, Sweden. anders.akerlund@astrazeneca.com

Clinical trials in allergic rhinitis present several specific difficulties. In
seasonal pollen-related disease, there are variations between subjects in the
extent of pollen sensitization, individual variations in exposure to pollen even 
within a set area because of lifestyle differences, and variations between
different areas in pollen counts and weather patterns. Thus, large patient
numbers are needed in multicenter trials to account for such variations when the 
standard endpoint is symptom reporting. Furthermore, a pollen season may be
relatively short (eg, lasting 6-8 weeks), and the pollen count is inconsistent
during this period. Crossover study designs are thus inappropriate, and trials
are usually conducted with a parallel-group design. This further increases the
trial sample size as it reduces statistical power. These large patient numbers
must be recruited over a very short period. Perennial house dust mite-sensitive
allergic rhinitis presents other problems. Although there is less disease
variation, it is appreciated that symptoms may be induced by nonallergic as well 
as allergic mechanisms because of the nasal hyperresponsiveness. The nonallergic 
symptoms may not be modified by treatments based on allergic disease mechanisms. 
Thus, symptom outcomes--although relevant to the patient--may not adequately
reflect the pharmacologic efficacy of the specific intervention. To control
variability and focus on allergic disease mechanisms, nasal allergen challenge
has been used in drug development. Single-dose challenges in the laboratory or in
a pollen chamber, which allow many volunteers to be studied at the same time,
have proven useful in the evaluation of drugs that afford acute symptom relief.
However, such challenges incompletely model naturally occurring disease, in which
the repeated daily exposure to allergen modifies the mucosal inflammatory cell
profile and in particular promotes the epithelial accumulation of effector cells.
This alters the response to allergen exposure. To model this, repeated low-dose
daily allergen exposure has been used to generate these mucosal changes
artificially, and early studies suggest that this may be a more valid model for
the evaluation of anti-inflammatory therapy. However, little has been published
with this model. Different disease groups are associated with their own specific 
issues in clinical trials. The pediatric population, in which allergic rhinitis
is common, has different requirements for education, quality of life evaluation, 
and adverse-event monitoring; nasal polyposis, because of the nature of the
disease, requires additional means of assessment, such as nasal endoscopy and
imaging (eg, computerized tomography scanning), as well as attention to
additional outcome measures (eg, the measurement of sense of smell). Within
clinical trial design, there are important questions to be considered in
relationship to the therapeutic intervention. Should this be given topically or
systemically? What are the appropriate timing and frequency of medication? Does
the disease itself modify the treatment efficacy, and does combination therapy
afford better clinical outcome than single-modality therapy? These issues are
discussed, and the influences of current therapies on objective outcome measures 
in allergic rhinitis are reviewed.

Publication Types: 
    Review

PMID: 15746883 [PubMed - indexed for MEDLINE]

803: J Allergy Clin Immunol. 2005 Mar;115(3 Suppl 1):S442-59.

Objective monitoring of nasal patency and nasal physiology in rhinitis.

Nathan RA, Eccles R, Howarth PH, Steinsvåg SK, Togias A.

Asthma and Allergy Associates, 2709 North Tejon, Colorado Springs, CO 80907, USA.
DrRNathan@aol.com

Nasal obstruction can be monitored objectively by measurement of nasal airflow,
as evaluated by nasal peak flow, or as airways resistance/conductance as
evaluated by rhinomanometry. Peak flow can be measured during inspiration or
expiration. Of these measurements, nasal inspiratory peak flow is the best
validated technique for home monitoring in clinical trials. The equipment is
portable, relatively inexpensive, and simple to use. One disadvantage, however,
is that nasal inspiratory peak flow is influenced by lower airway as well as
upper airway function. Rhinomanometry is a more sensitive technique that is
specific for nasal measurements. The equipment, however, requires an operator, is
more expensive, and is not portable. Thus, it is applicable only for clinic visit
measures in clinical trials. Measurements require patient cooperation and
coordination, and not all can achieve repeatable results. Thus, this objective
measure is best suited to laboratory challenge studies involving smaller numbers 
of selected volunteers. A nonphysiological measure of nasal patency is acoustic
rhinometry. This sonic echo technique measures internal nasal luminal volume and 
the minimum cross-sectional area. The derivation of these measures from the
reflected sound waves requires complex mathematical transformation and makes
several theoretical assumptions. Despite this, however, such measures correlate
well with the nasal physiological measures, and the nasal volume measures have
been shown to relate well to results obtained by imaging techniques such as
computed tomography scanning or magnetic resonance imaging. Like rhinomanometry, 
acoustic rhinometry is not suitable for home monitoring and can be applied only
to clinic visit measures or for laboratory nasal challenge monitoring. It has
advantages in being easy to use, in requiring little patient cooperation, and in 
providing repeatable results. In addition to nasal obstruction, allergic rhinitis
is recognized to be associated with impaired mucociliary clearance and altered
nasal responsiveness. Measures exist for the monitoring of these aspects of nasal
dysfunction. Although measures of mucociliary clearance are simple to perform,
they have a poor record of reproducibility. Their incorporation into clinical
trials is thus questionable, although positive outcomes from therapeutic
intervention have been reported. Measures of nasal responsiveness are at present 
largely confined to research studies investigating disease mechanisms in allergic
and nonallergic rhinitis. The techniques are insufficiently standardized to be
applied to multicenter clinical trials but could be used in limited-center
studies to gain insight into the regulatory effects of different therapeutic
modalities.

Publication Types: 
    Review

PMID: 15746882 [PubMed - indexed for MEDLINE]

804: J Allergy Clin Immunol. 2005 Mar;115(3 Suppl 1):S414-41.

Objective monitoring of nasal airway inflammation in rhinitis.

Howarth PH, Persson CG, Meltzer EO, Jacobson MR, Durham SR, Silkoff PE.

IIR Research Division, Mail Point 810, Southampton General Hospital, Tremona
Road, Southampton, Hampshire, SO16 6YD, United Kingdom. phh1@soton.ac.uk

Allergic rhinitis is an inflammatory nasal disorder in which a range of different
cells participates. A variety of approaches has been used to monitor nasal
inflammation objectively to investigate disease processes and to evaluate the
effect of therapeutic intervention. These approaches include nasal lavage, nasal 
cytology, and nasal biopsy, together with the more recently established
measurement of nasal nitric oxide (NO) concentration. Although all provide
information about nasal mucosal inflammation, the extent of information that can 
be obtained by each approach, the ease of sampling, and the complexity of sample 
handling differ. Such considerations influence the choice of approach when
measurement of nasal inflammation is to be an objective outcome parameter in a
clinical trial. In addition, the choice of approach is also determined by the
questions or hypotheses that are to be addressed. Nasal lavage is simple and
rapid to perform, is well tolerated, and provides a sample that can provide
information about luminal cell recruitment, cell activation, and plasma protein
extravasation. Nasal cytology involves sampling and recovering mucosal surface
cells. It is also easy to perform and is well tolerated in general, although some
find that the procedure causes a transient unpleasant sensation. A differential
cell count from the sample provides information about relative cell populations. 
Both nasal lavage and nasal cytology are readily applicable to clinical trials.
Nasal cytology sample handling is easier, but nasal lavage offers the advantage
of providing considerably greater information from the sample. Nasal biopsy is a 
considerably more invasive procedure and requires expertise not only in tissue
sampling but also in biopsy processing. Therefore, it is applicable only in
specialist centers. However, nasal biopsy is the only sampling technique that
directly informs about tissue cellular events, although these may be implied, in 
part from the other sampling approaches. Tissue specimens can be used to evaluate
both protein and gene expression. Measurement of nasal NO involves expensive
equipment but provides an instantaneous result, unlike the other approaches, all 
of which require sample processing and analysis. Recommendations for
standardization of measurement have been made, and measures are considered in
part to reflect allergic inflammation within the nasal mucosa. The limitations of
nasal NO are that it reflects only a certain aspect of allergic mucosal
inflammation, and that because a proportion of nasally measured NO is derived
from the sinuses under normal circumstances, nasal NO is not specific for nasal
disease. The high contribution from the sinus mucosa limits the discriminatory
ability of nasal NO to reflect nasal tissue-specific alterations. The
incorporation of measures of nasal inflammation in clinical trials has
distinguished anti-inflammatory therapy from symptomatic therapy and has the
potential to provide information about the efficacy of novel therapies for
allergic rhinitis.

Publication Types: 
    Review

PMID: 15746881 [PubMed - indexed for MEDLINE]

805: J Allergy Clin Immunol. 2005 Mar;115(3 Suppl 1):S390-413.

Clinical outcomes and adverse effect monitoring in allergic rhinitis.

Juniper EF, Ståhl E, Doty RL, Simons FE, Allen DB, Howarth PH.

Department of Clinical Epidemiology and Biostatistics, McMaster University,
Hamilton, Canada.

The subjective recording in diary cards of symptoms of itch, sneeze, nose
running, and blockage, with the use of a rating scale to indicate the level of
severity, is usual for clinical trials in allergic rhinitis. The primary outcome 
measure is usually a composite score that enables a single total symptoms score
endpoint. It is appreciated, however, that rhinitis has a greater effect on the
individual than is reflected purely by the recording of anterior nasal symptoms. 
Nasal obstruction is troublesome and may lead to sleep disturbance in addition to
impaired daytime concentration and daytime sleepiness. These impairments affect
school and work performance. Individuals with rhinitis find it socially
embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture
these and other aspects of the disease-specific health-related quality of life,
questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have
been developed and validated for clinical trial use. The adoption of
health-related quality of life questionnaires into clinical trials broadens the
information obtained regarding the effect of the therapeutic intervention and
helps focus on issues relevant to the individual patient. It must be appreciated 
that it is not only the disease that may adversely affect health-related quality 
of life; administered therapy, although intended to be beneficial, may also cause
health impairment. Adverse-event monitoring is thus essential in clinical trials.
The first-generation H 1 -histamines, because of their effect on central H 1
-receptors, are classically associated with central nervous system (CNS) effects 
such as sedation. Although this is not always perceived by the patient, it is
clearly evident with objective performance testing, and positron emission
tomography scanning has directly demonstrated the central H 1 -receptor
occupancy. The second-generation H 1 -antihistamines have reduced central H 1
-receptor occupancy and considerably reduced or absent CNS sedative effects.
Therefore, the CNS effects are entirely avoidable, and the first-generation H 1
-antihistamines should no longer be used in the management of allergic rhinitis. 
The considerably rarer but potentially very serious cardiac arrhythmogenic
effects of H 1 -antihistamines are appreciated to be molecule-specific rather
than class-specific. The in vitro screening of new compounds to eliminate the
further development of those with cardiotoxicity ideally will lead to this
adverse effect being historic. The incorporation of electrocardiogram recording
in clinical trials provides direct information relating to prolongation of QT
interval corrected for heart rate. Although administered at low doses, intranasal
steroids still have the potential for systemic absorption and adverse
consequences. However, it is appreciated that meaningful differences exist in the
bioavailability of different steroid molecules, and although a small but
statistically significant effect on growth in children has been identified with
the long-term use of intranasal beclomethasone when administered twice daily for 
1 year, this is not evident with all intranasal steroids. In addition,
twice-daily intranasal steroid administration may have more effect--from the
endocrinologic perspective--than once-daily administration in the morning, which 
coincides better with the natural diurnal variation in cortisol. Thus, once-daily
intranasal steroid administration is preferable, and when used in studies in
children, measurement of height change during the study period is an important
outcome variable together with other indices of systemic steroid bioavailability 
(eg, tests of hypothalamic-pituitary-adrenal axis function). These considerations
have even greater relevance if children are concurrently also receiving inhaled
steroids for asthma, because the total steroid load will be greater.

Publication Types: 
    Review

PMID: 15746880 [PubMed - indexed for MEDLINE]

806: Eur Rev Med Pharmacol Sci. 2004 Nov-Dec;8(6):289-94.

Epidemiology of alternaria alternata allergy: a prospective study in 6840 Italian
asthmatic children.

Cantani A, Ciaschi V.

Department of Pediatrics, Allergy and Clinical Immunology Division, University
"La Sapienza", Rome, Italy.

BACKGROUND: The prevalence of Alternaria Alternata (AA), a mold causing in
children severe asthma is scarcely known, also due to the underdiagnosis of AA
allergy, frequently due to multiple sensitizations to molds. OBJECTIVE: To
analyze this issue we prospectively studied all children attending our Division
between January 4, 1990 and December 31, 1997. METHODS: A total of 6840 children 
with asthma or allergic rhinitis were evaluated. Diagnosis was established by
family and personal history, physical examination, skin prick tests (SPTs) and
RAST (Radio Allergo-Sorbent Test) for inhalants including AA. We further
evaluated: (1) sensitization only to AA allergens without positivity for
additional inhalants; (2) prevalence of AA positivity among children with asthma 
or allergic rhinitis; (3) concordance between SPTs and RAST for allergy to molds,
(4) proportion of children treated with specific immunotherapy (SIT). RESULTS:
Among the 6840 children 213 were positive to AA (3.3%), only 89/6840 children
(1.3%) had AA monosensitization (p = 0.0001), a concordance between SPTs and RAST
was present in 21/89 (23.6%) children (p = 0.0009), and only 9 children out of 89
were SIT treated. Concerning the clinical manifestations, 83 had asthma or
allergic rhinitis, and 6 had asthma associated with atopic dermatitis. Family
history was positive in 82.9% of children. The mean onset of AA sensitivity was
at age 4 for males, and at age 5 for females. CONCLUSIONS: In childhood, AA
allergy is a genetic affection. The SPT concordance with history and clinical
examination appears to be operative. Due to life-threatening reactions in
children with AA allergy, we suggest that those with suspected inhalant allergy
be tested with AA allergens, and treated with SIT if positive.

Publication Types: 
    Comparative Study

PMID: 15745389 [PubMed - indexed for MEDLINE]

807: Eur Ann Allergy Clin Immunol. 2005 Jan;37(1):7-10.

Eosinophils, specific hyperreactivity and occurrence of late phase reaction in
allergic rhinitis.

Milanese M, Ricca V, Canonica GW, Ciprandi G.

Ospedale S.Corona, SC Pneumologia, Pietra Ligure, Italy.

BACKGROUND: Eosinophil infiltration may be considered characteristic of nasal
allergic inflammation. However, a mild inflammatory infiltrate may be present in 
asymptomatic subjects exposed to specific allergen. OBJECTIVE: We investigated
the relationship between inflammation, specific hyperreactivity and clinical late
phase reactions in allergic subjects using the ASNC model. METHODS: Sixty
allergic subjects (aged from 18 to 47 years) were enrolled among those sensitized
to pollens (n=20) and those to house dust mite with (n=20) or without (n=20)
known clinical nasal LPR. All subjects were asymptomatic. TNSS and eosinophil
number were assessed at baseline, 30 min (early phase) and 6 hours (late phase)
after ASNC. RESULTS: Eosinophil number was higher in LPR+ rhinitics than in other
groups, at baseline and during the early and late phase (p<0.001). ATD was lower 
in LPR+ rhinitics than in other groups (p<0.001). In LPR+ rhinitics, at baseline 
there was a significant correlation between eosinophils and ATD (r=0.56,
p=0.009). After allergen challenge, TNSS was significantly higher in LPR+
rhinitics than in other groups, both during early and late phase (p<0.001 for all
comparisons). CONCLUSIONS: In house dust mite sensitised subjects, LPR occurrence
after allergen challenge is associated with higher inflammation and lower ATD at 
baseline. Therefore, in house dust mite allergy minimal persistent inflammation
without symptoms can drive different clinical responses to allergen challenge.

PMID: 15745370 [PubMed - indexed for MEDLINE]

808: Ann Pharmacother. 2005 Apr;39(4):617-24. Epub 2005 Mar 1.

Comment in:
    Ann Pharmacother. 2005 Apr;39(4):736-8.

Treatment of seasonal allergic rhinitis using homeopathic preparation of common
allergens in the southwest region of the US: a randomized, controlled clinical
trial.

Kim LS, Riedlinger JE, Baldwin CM, Hilli L, Khalsa SV, Messer SA, Waters RF.

Southwest College Research Institute, Southwest College of Naturopathic Medicine 
& Health Sciences, Tempe, AZ 85282-1751, USA. l.kim@scnm.edu

BACKGROUND: Studies using homeopathy have reported beneficial effects from
treating allergy-related conditions. OBJECTIVE: To investigate the effects of a
homeopathic drug prepared from common allergens (tree, grass, weed species)
specific to the Southwest region of the US. METHODS: A 4-week, double-blind
clinical trial comparing homeopathic preparations with placebo was conducted in
the Phoenix metropolitan area during the regional allergy season from February to
May. Participants included 40 men and women, 26-63 years of age, diagnosed with
moderate to severe seasonal allergic rhinitis symptoms. Study outcomes included
allergy-specific symptoms using the rhinoconjunctivitis quality-of-life
questionnaire (RQLQ), functional quality of life using the Medical Outcomes Study
Short Form-36 (MOS SF-36), and the work productivity and activity impairment
(WPAI) questionnaire. RESULTS: Scales from the RQLQ, MOS SF-36, and WPAI
questionnaire showed significant positive changes from baseline to 4 weeks in the
homeopathic group compared with the placebo group (p < 0.05). Subjects reported
no adverse effects during the intervention period. CONCLUSIONS: These preliminary
findings indicate potential benefits of the homeopathic intervention in reducing 
symptoms and improving quality of life in patients with seasonal allergic
rhinitis in the Southwestern US.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15741420 [PubMed - indexed for MEDLINE]

809: Allergy. 2005 Apr;60(4):529-32.

The reduction of rhinitis symptoms by nasal filters during natural exposure to
ragweed and grass pollen.

O'Meara TJ, Sercombe JK, Morgan G, Reddel HK, Xuan W, Tovey ER.

Woolcock Institute of Medical Research, Royal Prince Alfred Hospital, University 
of Sydney, New South Wales, Australia.

BACKGROUND: Prototype nasal filters were developed to collect inhaled pollen.
This study evaluated the efficacy of the filters for prevention of rhinitis
symptoms during acute outdoor pollen exposure. METHODS: A randomized double-blind
design was used. Subjects (n=46) with a history of autumn exacerbation of
rhinitis and positive skin test to ragweed, Bermuda and/or Bahia grass wore
either active or placebo nasal filters for 2 h in autumn in a park containing
these species. Major and Total Symptoms scores were recorded at 0, 30, 60, 90 and
120 min. RESULTS: Subjects wearing active nasal filters had significantly reduced
scores, at all time-points compared with placebo group (all P <0.05). Of 14
individual symptoms measured, seven were significantly reduced (number of
sneezes, runny nose, itchy nose, sniffles, itchy throat; itchy eyes and watery
eyes) and another three showed a trend towards lower severity. The nasal filters 
also enabled the resolution of existing symptoms. Maximal difference in symptoms 
was seen immediately after subjects had spent 20 min sitting beside a large patch
of ragweed. CONCLUSION: This is the first clinical trial of a nasal filter. The
results suggest it has potential for enhancing rhinitis management during acute
allergen exposure.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15727589 [PubMed - indexed for MEDLINE]

810: Int Arch Allergy Immunol. 2005 Mar;136(3):281-6. Epub 2005 Feb 17.

Quality of life during pollen season in patients with seasonal allergic rhinitis 
with or without asthma.

Laforest L, Bousquet J, Pietri G, Sazonov Kocevar V, Yin D, Pacheco Y, Van Ganse 
E.

Pharmacoepidemiology Unit, EA3091 CHU Lyon-Sud, Pierre-Bénite, France.

OBJECTIVES: We studied the evolution of generic and rhinoconjunctivitis-specific 
quality of life (QOL) during pollen season in patients with isolated seasonal
allergic rhinitis (SAR) and those with asthma and concomitant SAR (AS+SAR).
Generic QOL between groups was also compared at pollen peak. METHODS: A
prospective cohort study was conducted in Southern France in 2002. Outpatients
aged 18-60, regularly visiting respiratory physicians for SAR, were recruited
before the grass (grass cohort) or ragweed pollination period (ragweed cohort).
Before the pollination period (baseline) and at peak pollination, patients
completed French versions of the Mini Rhinoconjuctivitis Quality of Life
Questionnaire (Mini-RQLQ) and physical and mental Short Form-12 (SF-12) scores
(PCS and MCS) to determine rhinoconjunctivitis and generic QOL. RESULTS: Totals
of 83 and 52 patients were included in the SAR and AS+SAR groups, respectively
(mean age=35.4; 56.4% females). Mini-RQLQ scores indicated slightly worse QOL in 
the A+SAR group at inclusion, which significantly deteriorated at the time of
pollen peak, both in the SAR (p<0.0001) and AS+SAR groups (p=0.003). In
univariate analysis, significantly higher SF-12 PCS (meaning better QOL) were
observed at pollen peak in the SAR compared with the AS+SAR group (p=0.0008),
while the difference for SF-12 MCS was more limited (p=0.05). Results were
confirmed in multivariable analyses adjusting for gender, allergy medication use 
at pollen peak, cohort of inclusion (grass/ragweed) and comorbid conditions.
CONCLUSIONS: Significant deterioration in rhinoconjunctivitis-specific QOL was
observed through the pollination period in patients with SAR and AS+SAR. At
pollen peak, AS+SAR patients experienced significantly worse physical functioning
than patients with SAR alone. Copyright (c) 2005 S. Karger AG, Basel.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15722638 [PubMed - indexed for MEDLINE]

811: Int Arch Allergy Immunol. 2005 Mar;136(3):266-72. Epub 2005 Feb 17.

Nasal eosinophils display the best correlation with symptoms, pulmonary function 
and inflammation in allergic rhinitis.

Ciprandi G, Vizzaccaro A, Cirillo I, Tosca M, Massolo A, Passalacqua G.

Head-Neck Department, S. Martino Hospital, Genoa, Italy.

BACKGROUND: The pathogenesis of allergic rhinitis and its link with asthma are
well known. Nevertheless, a complete cross-sectional evaluation of the usually
available clinical, functional and immunological parameters has never been made. 
We assessed nasal symptoms and flow, cytology, cytokines, pulmonary function and 
methacholine positivity in a large number of patients with pure pollinosis.
METHODS: Young men presenting at a military hospital for routine follow-up were
recruited for the study. They had to suffer from rhinitis alone (without asthma) 
for at least 2 years and had to have a positive skin prick test to pollens only. 
During the pollen season, they underwent symptom evaluation, measurement of nasal
flow, nasal scraping and lavage (cell count and assay for IL-4, IL-5, IL-8 and
IFNgamma), pulmonary function tests and methacholine challenge. RESULTS: Fifty
subjects (23.7+/-4.9 years old) were enrolled. All patients had high clinical
scores (9.5+/-1.6) and inflammatory cells (eosinophils: 10.5+/-4 and neutrophils 
21.3+/-6) and low nasal flow (482+/-111 ml/s). We found that the number of
eosinophils in nasal scrapings highly correlated with all the above-mentioned
parameters, including nasal flow, cytokines and spirometric values. A significant
positive correlation was found between all inflammatory cells and all cytokines. 
IL-8, IL-4 and neutrophils displayed only a partial correlation with pulmonary
parameters (FEV1, FVC and FEF25-75%), at variance wit IL-5 and eosinophils.
Methacholine test positivity significantly correlated with the number of
eosinophils in the nasal smear. CONCLUSION: Eosinophils in the nasal smear
display the best correlation with all the clinical and immunological parameters
in allergic rhinitis and also correlate well with methacholine response.
Copyright (c) 2005 S. Karger AG, Basel.

PMID: 15722636 [PubMed - indexed for MEDLINE]

812: Am J Epidemiol. 2005 Mar 1;161(5):412-22.

Opposing effects of emphysema, hay fever, and select genetic variants on lung
cancer risk.

Schabath MB, Delclos GL, Martynowicz MM, Greisinger AJ, Lu C, Wu X, Spitz MR.

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center,
Houston, TX 77030, USA.

The authors compared histories of nonmalignant respiratory diseases (asthma,
bronchitis, emphysema, hay fever, and pneumonia) in 1,553 lung cancer patients
and 1,375 healthy controls enrolled in a Texas case-control study from 1995 to
2003. They incorporated data on two biologically relevant polymorphic genes,
matrix metalloproteinase-1 and myeloperoxidase. Emphysema was associated with a
statistically significant increased lung cancer risk (odds ratio (OR) = 2.87, 95%
confidence interval (CI): 2.20, 3.76), while hay fever had a significant
protective effect (OR = 0.58, 95% CI: 0.48, 0.70). Odds ratios were consistent
after exclusion of respiratory disease diagnoses made up to 10 years before
interview. There was little association between other respiratory diseases and
lung cancer risk. Among carriers of "protective" genotypes, emphysema was
associated with a 1.7-fold increased risk (95% CI: 0.84, 3.50), as compared with 
the substantially higher risk for persons possessing one (OR = 4.98, 95% CI:
2.94, 8.44) or two (OR = 4.23, 95% CI: 1.84, 9.73) "adverse" genotypes. For hay
fever, significantly decreased risks were evident with one (OR = 0.32, 95% CI:
0.21, 0.50) or two (OR = 0.35, 95% CI: 0.19, 0.66) protective genotypes as
compared with none (OR = 0.69, 95% CI: 0.30, 1.59). The biologic role of
respiratory disease in lung cancer is unclear. Further study may yield new
insights for identification of susceptible subgroups.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15718477 [PubMed - indexed for MEDLINE]

813: Int Immunopharmacol. 2005 Apr;5(4):661-6.

The effects of allergen-specific immunotherapy on polymorphonuclear leukocyte
functions in patients with seasonal allergic rhinitis.

Soyoğul Gürer U, Büyüköztürk S, Palandüz S, Rayaman E, Colakoglu B, Cevikbaş A.

Marmara University, Faculty of Pharmacy, Department of Pharmaceutical
Microbiology, Istanbul, Turkey.

Immunotherapy plays an important role in the therapy of allergic rhinitis and
bronchial asthma. However, there is not much information about the effects of
allergen-specific immunotherapy (SIT) on the polymorphonuclear leukocyte
functions. The aim of this study was to investigate the effects of specific
immunotherapy on phagocytic and intracellular killing activities of
polymorphonuclear leukocytes (PMN) derived from patients with seasonal allergic
rhinitis. Twenty-four patients with seasonal allergic rhinitis documented to be
sensitive to grass pollen were included in this study. Patients were divided into
3 groups. Group 1 (n=7) received conventional immunotherapy whereas patients in
Group 2 (n=7) were treated with short-term immunotherapy and the third group
(n=10) were given placebo during the study process. Both phagocytic and
intracellular killing activities were significantly increased (p=0.002, p<0.0001,
respectively) by conventional immunotherapy when compared to the first
determination. In the short-term immunotherapy group, phagocytic activity was
increased very significantly (p=0.0001), whereas intracellular killing activity
was not affected (p=0.252). There were no changes in these parameters in the
placebo group. These results suggest that allergen-specific immunotherapy has an 
enhancing effect on PMNs functions in the patients with seasonal allergic
rhinitis. It should be clarified by further studies whether this enhancement
might be considered as another beneficial effect of the immunotherapy.

PMID: 15710335 [PubMed - indexed for MEDLINE]

814: Am J Rhinol. 2004 Nov-Dec;18(6):371-5.

Thresholds in nasal histamine challenge in patients with allergic rhinitis,
patients with hyperreflectory rhinopathy, and healthy volunteers.

Wuestenberg EG, Hauswald B, Huettenbrink KB.

Department for Otorhinolaryngology, University of Dresden Medical School,
Dresden, Germany.

BACKGROUND: Characteristic symptoms of hyperreflectory rhinopathy include
recurrent sneezing, nasal obstruction, and nasal secretion without an allergic
background. The diagnosis can only be made if all differential diagnoses have
been excluded. So far no clinical test has been established to reliably diagnose 
hyperreactivity of the nasal mucosa. The present study aimed to investigate
whether nasal provocation with histamine allows identification of patients with
hyperreflectory rhinopathy. MATERIALS AND METHODS: One-sided nasal challenge with
histamine was applied to 13 patients with allergic rhinitis, 13 patients with
hyperreflectory rhinitis, and 12 healthy volunteers. Histamine concentrations
used were 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 mg/mL. Test results were
quantified using a symptom score (positive at values above 3) and active anterior
rhinomanometry (positive at a reduction of airflow of 40% or more in comparison
to challenge with solvent). RESULTS: While there was a significant difference
between controls and patients with allergic rhinitis or hyperreflectory
rhinopathy, respectively, no significant difference was observed between the two 
groups of patients. Results indicated that one-sided nasal provocation with
histamine at a concentration of 1 mg/mL is sufficient to separate healthy
subjects from patients with hyperreactivity of the nasal mucosa. In terms of the 
differentiation between subjects with hyperreactivity of the nasal mucosa and
healthy controls, the sensitivity of one-sided nasal histamine provocation with 1
mg/mL was found to be 100%; its specificity was 83% if it was evaluated by
rhinomanometry and symptom score. CONCLUSION: The present results indicate that
one-sided nasal challenge with histamine at a concentration of 1 mg/mL is
sufficient to separate healthy subjects from patients with hyperreactivity of the
nasal mucosa. However, the test does not differentiate between patients with
allergic rhinitis and patients with hyperreflectory rhinitis.

PMID: 15706984 [PubMed - indexed for MEDLINE]

815: Curr Med Res Opin. 2004 Dec;20(12):1937-52.

Allergic rhinitis and impairment issues in schoolchildren: a consensus report.

Blaiss MS; Allergic Rhinitis in Schoolchildren Consensus Group.

University of Tennessee Health Science Center, Germantown, TN 38138, USA.
mblaiss@allergymemphis.com

BACKGROUND: Allergic rhinitis (AR) can have substantial negative impact on
children. Most notably, it can impede learning during the school-age years. Other
consequences include adverse behavioral and psychosocial effects, poor quality of
life, and potential impact on serious comorbidities, such as asthma. CONSENSUS
PANEL: In February 2004, in a conference sponsored by Aventis Pharmaceuticals, a 
multidisciplinary group convened to review relevant clinical data for the
purposes of developing consensus recommendations for the management of AR in
children. The consensus panel consisted of academic, school health, and medical
providers, who were identified based on previous work and publications. CONSENSUS
FINDS: The focus of discussions was to assess the degree of impact of AR in
schoolchildren and, based on this information, to determine how to improve
screening, diagnosis, prevention, and treatment, to help ensure quality of life
and maximal school performance in this population. The group considered the most 
critical factor in successful management ot be communication and collaboration
among parents, educators, and healthcare professionals. Knowledge of the common
signs and symptoms of AR in children can help to ensure early diagnosis,
appropriate intervention, and clinically favorable outcomes. Importantly, both
uncontrolled symptoms of AR, as well as adverse effects from medications, can
diminish cognitive function and learning. When choosing treatment for children
with AR, consideration must be given to the side effects of medications. All
first-generation and some second-generation antihistamines can be associated with
adverse effects on cognitive function and learning, as a result of their sedative
properties. Treatment with non-sedating second-generation antihistamine has been 
shown to improve learning potential and is an ideal choice for treatment in this 
population. CONCLUSION: Existing data indicate that further studies using
objective measures of impairment in children taking antihistamine medications
should be conducted to evaluate the impact of disease and treatment.

Publication Types: 
    Consensus Development Conference
    Research Support, Non-U.S. Gov't
    Review

PMID: 15704310 [PubMed - indexed for MEDLINE]

816: Ann Allergy Asthma Immunol. 2005 Jan;94(1):73-9.

Use of 0.06% ipratropium bromide nasal spray in children aged 2 to 5 years with
rhinorrhea due to a common cold or allergies.

Kim KT, Kerwin E, Landwehr L, Bernstein JA, Bruner D, Harris D, Drda K, Wanger J,
Wood CC; Pediatric Atrovent Nasal Spray Study Group.

West Coast Clinical Trials Inc, Long Beach, California, USA.

BACKGROUND: Rhinorrhea from common colds or allergies in children is similar to
that in adults, yet there are few data on the use of ipratropium bromide nasal
spray in children younger than 5 years. OBJECTIVE: To evaluate the safety and
efficacy of 0.06% ipratropium bromide nasal spray in 2- to 5-year-old children
with rhinorrhea from a common cold or allergies. METHODS: A total of 230 children
(43 with common colds and 187 with allergies) participated in an open-label,
multicenter study. Patients with a common cold received ipratropium bromide nasal
spray (84 microg per nostril) 3 times daily for 4 days; those with allergies
received ipratropium bromide nasal spray (42 microg per nostril) 3 times daily
for 14 days. RESULTS: In the common cold and allergy groups, 91% and 90% of the
parents, respectively, found that ipratropium bromide was either "very useful" or
"somewhat useful." Furthermore, 67% and 91% of parents in the common cold and
allergy groups, respectively, found that administration of a nasal spray was
either "extremely easy" or "very easy." Symptom scores were improved from
baseline in both groups. The nasal spray was well tolerated and was not
associated with serious or systemic anticholinergic adverse effects. Most adverse
events were infrequent and mild to moderate, and study discontinuation due to an 
adverse event occurred in less than 3% of patients. CONCLUSIONS: The 0.06%
ipratropium bromide nasal spray, 42 or 84 microg per nostril 3 times daily, is
easy to administer, safe, and effective for the control of rhinorrhea in children
aged 2 to 5 years with a common cold or allergies.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15702820 [PubMed - indexed for MEDLINE]

817: Ann Allergy Asthma Immunol. 2005 Jan;94(1):60-4.

Categorization of patients with allergic rhinitis: a comparative profile of
"sneezers and runners" and "blockers".

Khanna P, Shah A.

Department of Respiratory Medicine, Vallabhbhai Patel Chest Institute, University
of Delhi, Delhi, India.

BACKGROUND: The recent Allergic Rhinitis and Its Impact on Asthma (ARIA) workshop
report classified patients into "sneezers and runners" and "blockers" and
described a new disease severity categorization. OBJECTIVE: To sketch the profile
of these 2 groups and to evaluate the relevance of categorization. METHODS:
Patients were categorized as "sneezers and runners" (group 1) or "blockers"
(group 2). The patients responded to a questionnaire that sought information on
symptoms and associated factors. They were then categorized into seasonal
allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) groups and
"intermittent" and "persistent" disease groups and compared. RESULTS: A total of 
114 patients (72 in group 1 and 42 in group 2) participated in the study. The
significant features in group 1 were age at onset younger than 20 years (90%);
birth date between June and September (61%); family history of atopy (88%);
itching of skin (26%), eye (43%), ears (43%), and throat and palate (67%); and
aggravation with dust (93%). History of breathlessness (90%), mouth breathing
(81%), loss of smell (36%), and prior nasal surgery (31%) were significant in
group 2. Significantly more patients in group 1 had SAR (54%) and moderate-severe
intermittent disease (60%), whereas group 2 had PAR (81%) and mild persistent
(69%) disease (P = .03). Patients classified as having SAR had intermittent
disease (40, 83%) (P = .005), and those with PAR had persistent disease (51, 76%)
(P < .001). Sixteen patients (24%) classified as having PAR were in the
intermittent category, whereas 7 (17%) classified as having SAR were in the
persistent category. CONCLUSIONS: This study demonstrated that the 2 groups had
distinct clinical profiles and that it is important to categorize patients,
according to the ARIA report, into intermittent and persistent allergic rhinitis 
groups.

Publication Types: 
    Comparative Study

PMID: 15702818 [PubMed - indexed for MEDLINE]

818: Curr Med Res Opin. 2004 Dec;20(12):1959-65.

Safety of desloratadine syrup in children.

Bloom M, Staudinger H, Herron J.

Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
melvyn.bloom@spcorp.com

BACKGROUND: Allergic rhinitis (AR) and acute urticaria are common childhood
maladies. Typically, the firstline treatment options for both include
non-sedating antihistamines. First-generation antihistamines, such as
diphenhydramine and hydroxyzine, although useful, cause sedation. Desloratadine, 
an oral non-sedating antihistamine, has been shown in multiple studies to be safe
and effective in relieving the symptoms of AR and chronic idiopathic urticaria
(CIU) in adults and adolescents. OBJECTIVE AND METHODS: The current double-blind,
placebo-controlled, parallel-group, single-center studies were undertaken to
determine the safety and tolerability of desloratadine syrup in children aged 2
years-11 years with AR or CIU. Over 14 days, subjects aged 2 years-5 years were
randomly assigned to receive once a day either 1.25 mg of desloratadine syrup
(0.5 mg/mL) or matching placebo, and subjects aged 6 years-11 years were randomly
assigned to receive once a day either 2.5 mg of desloratadine syrup or matching
placebo. Safety evaluations included adverse event report collection, monitoring 
of vital signs, clinical laboratory measurements, and standard 12-lead
electrocardiogram (ECG) measurements. RESULTS: In the study involving subjects
aged 2 years-5 years (n = 111), the incidence of adverse events was 7/55 for the 
group treated with desloratadine and 6/56 for placebo. In the study involving
subjects aged 6 years-11 years (n = 120), the incidence of adverse events was
1/60 for the group treated with desloratadine and 6/60 for placebo. No severe or 
serious adverse events occurred, and no clinically relevant changes were noted in
median clinical laboratory test values or mean vital signs in either group. ECG
results from both age groups demonstrated no significant changes (p = NS) in mean
ventricular rate or PR, QRS, or QT. No subjects had a Fridericia QT(c) interval >
440 ms at day 8 or day 15. CONCLUSION: These studies demonstrate the safety of
desloratadine syrup in children aged 2 years-11 years with AR or CIU.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15701213 [PubMed - indexed for MEDLINE]

819: Int J Clin Pharmacol Res. 2004;24(2-3):79-94.

Multicenter clinical trials on a novel polyherbal formulation in allergic
rhinitis.

Saxena VS, Venkateshwarlu K, Nadig P, Barbhaiya HC, Bhatia N, Borkar DM, Gill RS,
Jain RK, Katiyar SK, Nagendra Prasad KV, Nalinesha KM, Nasiruddin K, Rishi JP,
Roy Chowdhury J, Saharia PS, Thomas B, Bagchi D.

ASA Foundation, New Delhi, India. sannidhi@del3.vsnl.net.in

Allergic rhinitis is the most frequently occurring immunological disorder. It
affects men, women and children and represents significant cost in terms of
suffering and loss of productivity. Allergy is termed as an excessive reaction to
an environmental allergen. Pollen, mold, dust, mite and animal allergens that
contact the nasal or eye lining cause sneezing, nasal congestion and itchy,
watery, swollen, red eyes. Although a broad spectrum of therapeutic options is
available, the treatment of allergic rhinitis appears to be far from
satisfactory. A novel polyherbal formulation (PF; Aller-7/NR-A2) comprising seven
medicinal herbal extracts was assessed in a multicenter clinical trial involving 
545 patients (321 males and 224 females) aged 18-59 years for 12 weeks to
evaluate its clinical efficacy in patients suffering from allergic rhinitis. A
total of 171 patients participated in double-blind, randomized,
placebo-controlled studies in three centers, while 374 patients were included in 
the open-label studies in 11 centers. The three major symptoms (sneezing,
rhinorrhea and nasal congestion) of allergic rhinitis were significantly reduced.
Significant improvement was also observed in absolute eosinophil count,
mucociliary clearance time, peak expiratory flow rate and peak nasal flow rate.
No serious adverse events that warranted cessation of treatment were observed.
Minor adverse effects were noted in both the treatment and placebo groups. Thus, 
this study demonstrates that Aller-7/NR-A2 is well tolerated and efficacious in
patients with allergic rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 15689054 [PubMed - indexed for MEDLINE]

820: Allergy. 2005 Mar;60(3):354-9.

Effect of loteprednol etabonate nasal spray suspension on seasonal allergic
rhinitis assessed by allergen challenge in an environmental exposure unit.

Krug N, Hohlfeld JM, Geldmacher H, Larbig M, Heermann R, Lavallee N, Nguyen DT,
Petzold U, Hermann R.

Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.

BACKGROUND: Loteprednol etabonate (LE) is a novel soft steroid that was designed 
to improve the benefit/risk ratio of topical corticosteroid therapy. This study
assesses the clinical efficacy and safety of three different doses of LE nasal
spray in seasonal allergic rhinitis (SAR). METHODS: In this single-center,
double-blind, placebo-controlled, parallel-group trial 165 subjects with SAR to
grass pollen received daily single doses of either 100, 200, 400 microg LE nasal 
spray, or placebo for 14 days. The patients underwent three 4-h allergen
challenges with grass pollen in an environmental exposure unit at a screening
visit (baseline) and on days 7 and 14 of treatment. Standardized nasal symptom
scores were obtained every 20 min. Nasal flow, nasal secretions, and FEV(1) were 
measured every hour during allergen challenges. RESULTS: After 14 days of
treatment, patients who received 400 microg LE had significantly lower total
nasal symptom scores compared with those receiving placebo (P = 0.007). LE400
reduced rhinorrhea, nasal congestion, nasal itching, the amount of nasal
secretions, and improved nasal flow as compared with placebo (P < 0.05). LE100
and LE200 were not significantly different from placebo. All treatments were well
tolerated. CONCLUSIONS: Loteprednol 400 microg once daily is superior to placebo 
and the only effective dose tested in improving nasal symptoms and objective
parameters in patients with SAR.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15679722 [PubMed - indexed for MEDLINE]

821: Clin Exp Allergy. 2004 Dec;34(12):1862-7.

The effect of specific immunotherapy on the expression of costimulatory molecules
in late phase reaction of the skin in allergic patients.

Plewako H, Arvidsson M, Oancea I, Hasséus B, Dahlgren U, Rak S.

Asthma and Allergy Research Group, Department of Respiratory Medicine and
Allergology, The Sahlgrenska University Hospital, 413 45 Göteborg, Sweden.

BACKGROUND: Specific immunotherapy (SIT) modulates immune responses to allergens 
resulting in improvement of allergic symptoms. However, the mechanisms behind the
clinical changes are not clear. Participation of costimulatory molecules on
antigen-presenting cells and T cells in the process of antigen recognition is
suggested to be of essential importance. The SIT effect on expression of
costimulatory molecules has not been earlier examined. METHODS: Forty-one
birch-allergic patients were treated with SIT or placebo. After 1 year of
treatment skin biopsies were obtained 24 h following allergen challenge. Sections
were stained with antibodies against: EG2 (eosinophils), CD4 (T cells), CD68
(macrophages), CD1a (Langerhans cells), CD28 (on T cells) and costimulatory
molecules (CD80, CD86). RESULTS: Following allergen challenge number of the
CD4(+) and CD68(+) cells increased significantly (P=0.002, 0.0001, respectively) 
in the placebo, but not in the SIT-treated patients. The difference between
groups was significant (P=0.003, 0.01, respectively). The numbers of EG2(+) cells
increased significantly in both groups. CD80(+) cell numbers increased in the
placebo (P=0.01) but not in the SIT group. The number of CD86(+) cells increased 
in both groups (placebo, P=0.001; SIT, P=0.01) but significantly less in the SIT 
group (P=0.05). The numbers of CD28(+) cells increased in the placebo (P=0.001)
but remained unchanged in the SIT group. The difference between the groups was
significant (P=0.05). CONCLUSION: There were lower numbers of cells expressing
costimulatory molecules in SIT-treated than in placebo-treated patients.
Decreased costimulation may lead to diminished immune response following allergen
exposure. This could be an important factor contributing to the clinical
improvement after SIT.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15663560 [PubMed - indexed for MEDLINE]

822: Med J Aust. 2005 Jan 3;182(1):28-33.

Optimising the management of allergic rhinitis: an Australian perspective.

Walls RS, Heddle RJ, Tang ML, Basger BJ, Solley GO, Yeo GT.

Department of Immunology and Allergy, Concord Hospital, NSW.
wallsr@email.cs.nsw.gov.au

Allergic rhinitis (AR) is one of the most prevalent medical conditions. It has
significant effects on quality of life and can have considerable socioeconomic
effects. The traditional classification of perennial and seasonal rhinitis does
not distinguish between provoking factors, nor does it indicate the most
appropriate treatment. A more useful classification is based on symptoms, which
may be intermittent or persistent, and vary widely in severity. The goal of
management is to achieve optimal symptom control. Therapeutic options include
allergen avoidance, pharmacotherapy and immunotherapy. Antihistamines and
intranasal corticosteroids (INCS) have become the cornerstones of therapy. A
variety of effective treatments are available for consumers to self-select,
without the advice of a doctor or pharmacist. INCS are widely recognised as the
most effective pharmacotherapy for AR, in both adults and children. The efficacy 
of various preparations is similar, but those with low systemic bioavailability
are preferred for children and for patients who are also receiving inhaled,
topical or systemic corticosteroids.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15651945 [PubMed - indexed for MEDLINE]

823: Int Arch Allergy Immunol. 2005 Feb;136(2):148-54. Epub 2005 Jan 12.

Fexofenadine improves the quality of life and work productivity in Japanese
patients with seasonal allergic rhinitis during the peak cedar pollinosis season.

Okubo K, Gotoh M, Shimada K, Ritsu M, Okuda M, Crawford B.

Nippon Medical School, Tokyo, Japan. ent-kimi@nms.ac.jp

BACKGROUND: Although currently in its infancy, quality of life (QOL) research in 
Japan is rapidly expanding and is expected to become a standard outcome measure
in clinical trials. In Japan, QOL has not previously been assessed in patients
with allergic rhinitis (AR); we report the first clinical study applying the
recently validated Japanese translations of the Rhinoconjunctivitis Quality of
Life Questionnaire (RQLQ) and Work Productivity and Activity Impairment-Allergy
Specific (WPAI-AS) Questionnaire to assess the effects of the oral antihistamine,
fexofenadine, on QOL and work productivity due to cedar pollinosis. PATIENTS AND 
METHODS: A randomized, double-blind, placebo-controlled, single-site study was
conducted during the peak cedar pollinosis season in Japan. After a 7-day run-in 
period, subjects were randomized to receive fexofenadine HCl 60 mg twice daily
(bid) or placebo for 2 weeks. RESULTS: Overall, 206 Japanese subjects with AR
were included in the intention-to- treat population (fexofenadine, n = 104, and
placebo, n = 102). Fexofenadine statistically significantly improved overall QOL 
compared with placebo (p = 0.005) and improvements were reported in the RQLQ
domains: activities (p = 0.047), practical problems (p = 0.003), nasal symptoms
(p = 0.003) and eye symptoms (p </= 0.001). Clinically significant improvements
in practical problems, eye symptoms and activity limitations, exceeding the 0.05 
level, were observed with fexofenadine. These improvements in QOL were associated
with significant symptom relief (p < 0.001 vs. placebo). Improvements in
impairment at work were also reported with fexofenadine. CONCLUSION: In Japan,
this is the first clinical study to show that fexofenadine HCl (60 mg b.i.d.)
improves overall QOL and work productivity in patients with seasonal AR using
validated Japanese instruments. Copyright (c) 2005 S. Karger AG, Basel.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15650312 [PubMed - indexed for MEDLINE]

824: Int Arch Allergy Immunol. 2005 Feb;136(2):134-41. Epub 2005 Jan 12.

Lack of detectable alterations in immune responses during sublingual
immunotherapy in children with seasonal allergic rhinoconjunctivitis to grass
pollen.

Rolinck-Werninghaus C, Kopp M, Liebke C, Lange J, Wahn U, Niggemann B.

Department of Pediatric Pneumology and Immunology, Charité, Berlin, Germany.

BACKGROUND: Recent work indicates that subcutaneous specific immunotherapy
induces specific T-cell anergy, a shift in the TH1/TH2 ratio, and antibody
production in favor of IgG4. There are few data on sublingual immunotherapy
(SLIT), especially in children. METHODS: We assessed the proliferation of
peripheral blood mononuclear cells ((3)H-thymidine incorporation) and secretion
of interleukin (IL)-4, interferon (IFN)gamma and IL-5 (ELISA) after in vitro
stimulation with allergen or phytohemagglutinin (PHA) in 29 children with
allergic rhinoconjunctivitis receiving SLIT with grass pollen before, and after 1
and 2 years of treatment in a multicenter placebo-controlled study on the
efficacy of the treatment. Further, non-specific intracellular production of
IL-4, IL-13, IFNgamma, IL-2, IL-10 and IL-5 (FACS) and serum total and specific
IgE and IgG4 (ELISA) were analyzed. RESULTS: Proliferation and IL-4 and IL-5
secretion after stimulation with allergen or PHA did not differ between the
groups. In addition, we observed no effect of SLIT on intracellular cytokine
production. IFNgamma secretion after allergen coculture was comparable between
the groups. Following PHA stimulation, IFNgamma secretion was significantly
higher in the SLIT group after 1 year, and a trend was observable already before 
and after 2 years of treatment, probably due to the inhomogeneity in the groups
despite randomization (for age and asthma). No significant changes were observed 
for sIgE/sIgG4 ratios over time either in or between the groups. CONCLUSION:
During 2 years of SLIT in children with a positive effect on rescue medication
use, we observed no significant effects on in vitro T-cell immune responses or
immunoglobulins. So far, pediatric studies demonstrating stable effects of SLIT
on such reactions are missing, probably due to limited effects of SLIT on
systemic immunologic reactions. Copyright (c) 2005 S. Karger AG, Basel.

Publication Types: 
    Clinical Trial
    In Vitro
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15650310 [PubMed - indexed for MEDLINE]

825: Clin Exp Allergy. 2005 Jan;35(1):45-51.

Induction of nasal hyper-responsiveness by allergen challenge in allergic
rhinitis: the role of afferent and efferent nerves.

Sheahan P, Walsh RM, Walsh MA, Costello RW.

Department of Otolaryngology, Royal College of Surgeons in Ireland, Dublin,
Ireland. rcostello@rcsi.ie

BACKGROUND: Hyper-responsiveness of nasal secretory function and volume changes
are features of allergic rhinitis (AR) that are mediated in part by neural
mechanisms. The finding of nasal hyper-responsiveness in subjects with AR who are
currently symptomatic, but not in those who are currently out of season and
asymptomatic, suggests that induction of neural reflexes in allergic subjects
occurs as a result of allergic inflammation. OBJECTIVES: To investigate whether
allergen exposure in subjects with asymptomatic seasonal allergic rhinitis (SAR) 
may lead to induction of neural reflexes, and to investigate the components of
the reflexes involved in this induction. METHODS: Asymptomatic subjects with
(out-of-season) SAR underwent a nasal bradykinin challenge, before and 24 h after
preceding ipsilateral (n = 11) and contralateral (n = 11) antigen challenge.
Challenges were performed and nasal secretions collected using filter paper
disks, and changes in nasal minimal cross-sectional area (A(min)) were measured
using acoustic rhinometry. RESULTS: Preceding ipsilateral antigen challenge led
to the induction of a contralateral secretory reflex (P = 0.01), which was absent
in control experiments (P = 0.34). Ipsilateral secretion weights were also
enhanced. Preceding contralateral antigen challenge also induced a contralateral 
secretory reflex (P = 0.03). Enhancement of the reduction in contralateral A(min)
was also seen (P = 0.02). Ipsilateral responses were unchanged. CONCLUSIONS:
Allergen exposure in asymptomatic allergic subjects leads to induction of neural 
reflexes, resulting in nasal hyper-responsiveness, which persists beyond the
resolution of the acute allergic response. Our data suggest that the mechanisms
of allergen-induced hyper-responsiveness involve both afferent and efferent
components.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15649265 [PubMed - indexed for MEDLINE]

826: Clin Exp Allergy. 2005 Jan;35(1):39-44.

Comment in:
    Clin Exp Allergy. 2005 Jan;35(1):1-3.

An evaluation of peripheral blood eosinophil/basophil progenitors following nasal
allergen challenge in patients with allergic rhinitis.

Wilson AM, Duong M, Crawford L, Denburg J.

Airways Research Group, Firestone Institute for Respiratory Health, St Joseph's
Healthcare, Hamilton, ON, Canada. a.m.wilson@dundee.ac.uk

OBJECTIVE: To evaluate the effect of a single nasal allergen challenge on
peripheral blood eosinophil/basophil (Eo/B) progenitor cells and induced sputum
eosinophil counts in subjects with allergic rhinitis. METHODS: Sixteen adults
entered a sequential nasal control and allergen challenge study, outside the
pollen season. Blind assessment of peripheral blood Eo/B progenitor colony
forming units (CFU), induced sputum and nasal lavage cell counts was made before 
and 24 h after both challenges. Subjects recorded their rhinitis symptoms and
nasal peak inspiratory flow, hourly at home, following both challenges. RESULTS: 
When comparing the values 24 h after the control vs. the allergen challenge,
there were no significant differences in Eo/B progenitor CFU (control (mean, SD):
3.6 (1.0)/10(6) cells; allergen: 4.4 (1.1)/10(6) cells) or sputum eosinophils
(control (median, inter-quartile range): 1.0 (0.3-1.7)%; allergen: 0.7
(0.0-1.3)%) despite a significant increase in the percentage (median
(inter-quartile range) of eosinophils in nasal lavage (control: 0.6 (0.1-0.9)%;
allergen; 1.9 (0.9-8.1)% and significant worsening of nasal peak inspiratory flow
and rhinitis symptoms. CONCLUSIONS: Despite a significant increase in nasal
symptoms and lavage eosinophil counts, a single nasal allergen challenge was not 
sufficient to elicit a measurable haemopoietic response in circulation, or an
increase in sputum eosinophil counts.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15649264 [PubMed - indexed for MEDLINE]

827: Clin Exp Allergy. 2005 Jan;35(1):34-8.

Comment in:
    Clin Exp Allergy. 2005 Jan;35(1):1-3.

Increased number of CD34+ cells in nasal mucosa of allergic rhinitis patients:
inhibition by a local corticosteroid.

Sergejeva S, Malmhäll C, Lötvall J, Pullerits T.

The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, 
Institute of Internal Medicine, Göteborg University, Gothenburg, Sweden.

BACKGROUND: Eosinophils develop from CD34+ haematopoietic progenitor cells.
Allergen exposure in susceptible individuals is known to induce a local
eosinophilic inflammation, but the effect on progenitor cells is much less
understood. OBJECTIVE: We aimed to evaluate how allergen exposure affects the
number of tissue CD34+ cells and CD34+ eosinophils in allergic rhinitis (AR)
patients and whether any such effect is influenced by local corticosteroid
treatment. Also, we evaluated changes in the number of CXC receptor 4-positive
cells (CXCR4+), since the CXCR4 ligand (stromal cell-derived factor-1 (SDF-1)) is
a potent chemoattractant for haematopoietic progenitors. METHODS: In a
double-blind, randomized study, pollen-sensitized AR patients were treated with a
nasal corticosteroid fluticasone propionate (FP, 200 microg/day) or placebo
throughout the pollen season. Nasal biopsies were taken before and during the
season. CD34 and CXCR4 were stained using immunohistochemistry. RESULTS: The
pollen season significantly increased the number of CD34+ cells, CD34+/CXCR4+
cells and CD34+ eosinophils in placebo-treated patients, but not in FP-treated
patients. The mean pollen season-induced increase in CD34+ cells, CD34+/CXCR4+
cells and CD34+ eosinophils in FP-treated patients was lower compared with
placebo-treated patients. CONCLUSION: A pollen season increases the number of
CD34+ cells in nasal tissue accompanied by an increase in the number of
CD34+/CXCR4+ haematopoietic progenitors and also the number of CD34+ eosinophils 
in subjects with AR. Treatment with a local corticosteroid provides protection
against this pollen-induced increase in tissue CD34+ cells and CD34+ eosinophils 
possibly via inhibition of allergen-induced CXCR4-mediated recruitment of CD34+
haematopoietic progenitors into airways and their further differentiation into
eosinophils within the tissue.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15649263 [PubMed - indexed for MEDLINE]

828: Allergy. 2005 Feb;60(2):251-5.

Bahia grass pollen specific IgE is common in seasonal rhinitis patients but has
limited cross-reactivity with Ryegrass.

Davies JM, Bright ML, Rolland JM, O'hehir RE.

Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, 
Melbourne Vic, Australia.

BACKGROUND: Perennial Ryegrass is a major cause of rhinitis in spring and early
summer. Bahia grass, Paspalum notatum, flowers late into summer and could account
for allergic rhinitis at this time. We determined the frequency of serum
immunoglobulin (Ig)E reactivity with Bahia grass in Ryegrass pollen allergic
patients and investigated IgE cross-reactivity between Bahia and Ryegrass.
METHODS: Serum from 33 Ryegrass pollen allergic patients and 12 nonatopic donors 
were tested for IgE reactivity with Bahia and Ryegrass pollen extracts (PE) by
enzyme-linked immunosorbent assay (ELISA), western blotting and inhibition ELISA.
Allergen-specific antibodies from a pool of sera from allergic donors were
affinity purified and tested for IgE cross-reactivity. RESULTS: Seventy-eight per
cent of the sera had IgE reactivity with Bahia grass, but more weakly than with
Ryegrass. Antibodies eluted from the major Ryegrass pollen allergens, Lol p 1 and
Lol p 5, showed IgE reactivity with allergens of Ryegrass and Canary but not
Bahia or Bermuda grasses. Timothy, Canary and Ryegrass inhibited IgE reactivity
with Ryegrass and Bahia grass, whereas Bahia, Johnson and Bermuda grass did not
inhibit IgE reactivity with Ryegrass. CONCLUSIONS: The majority of Ryegrass
allergic patients also showed serum IgE reactivity with Bahia grass PE. However, 
Bahia grass and Ryegrass had only limited IgE cross-reactivity indicating that
Bahia grass should be considered in diagnosis and treatment of patients with hay 
fever late in the grass pollen season.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15647049 [PubMed - indexed for MEDLINE]

829: Allergy. 2005 Feb;60(2):177-84.

Exposure to pets, and the association with hay fever, asthma, and atopic
sensitization in rural children.

Waser M, von Mutius E, Riedler J, Nowak D, Maisch S, Carr D, Eder W, Tebow G,
Schierl R, Schreuer M, Braun-Fahrländer C; The ALEX Study team.

Institute of Social and Preventive Medicine, University of Basel, Basel,
Switzerland.

BACKGROUND: An increasing number of studies report pet exposure to be associated 
with lower risk of asthma and allergies. This 'protective pet effect' has been
suggested to result from a modified T-helper (Th)2-cell response, or because of
increased microbial load in homes where pets are kept. We examined the
associations between pet contact and the occurrence of asthma and allergies in
children of the rural Allergy and Endotoxin (ALEX) population, taking farm animal
contact, endotoxin and cat allergen levels in mattress dust into account.
METHODS: Information about contact with pets and farm animals, asthma and allergy
were collected for 812 children by a standardized parents' questionnaire and an
interview. Mattress dust endotoxin and cat allergen levels as well as specific
IgE and IgG4 antibodies to Fel d1 were determined. RESULTS: Current contact with 
dogs was inversely associated with diagnosed hay fever (OR 0.26, 95% CI
0.11-0.57), diagnosed asthma (OR 0.29, 95% CI 0.12-0.71), sensitization to cat
allergen (OR 0.48, 95% CI 0.23-0.99) and to grass pollen (OR 0.55, 95% CI
0.33-0.94), but not with increased IgG4 levels. Early and current contact with
cats were associated with reduced risk of wheezing (OR 0.48, 95% CI 0.23-1.00,
and OR 0.49, 95% CI 0.26-0.92, respectively) and grass pollen sensitization.
Adjustment for farm animal contact but not for endotoxin and cat allergen
exposure attenuated these associations and the effect of pet was stronger among
farmers' children. CONCLUSION: Although pet exposure was very frequent in this
rural population, the inverse relation between current dog contact, asthma and
allergy was mostly explained by simultaneously occurring exposure to stable
animals or was restricted to farm children. In addition, a subtle form of pet
avoidance may contribute to the protective effect of pet.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15647038 [PubMed - indexed for MEDLINE]

830: Allergy. 2005 Feb;60(2):171-6.

Analysis of exhaled leukotrienes in nonasthmatic adult patients with seasonal
allergic rhinitis.

Cáp P, Pehal F, Chládek J, Malý M.

Department of Allergology and Clinical Immunology, Hospital Na Homolce, Institute
for Postgraduate Medical Education, Prague, Czech Republic.

BACKGROUND: Leukotrienes (LTs) are increased in exhaled breath condensate (EBC)
in patients with asthma. So far no data have been reported about LT levels in
nonasthmatic patients with seasonal allergic rhinitis (SAR). The aim of the study
was to find out whether the LT levels in EBC were increased in the nonasthmatic
adult patients with SAR both during and after the pollen season in comparison
with healthy controls and to assess the changes of the LT levels after the pollen
season. METHODS: Twenty-nine nonasthmatic adult patients with SAR underwent
measurement of exhaled LTs in the EBC during and after the pollen season.
Leukotrienes B(4), C(4), D(4) and E(4) were analysed by a specific and sensitive 
gas chromatography/mass spectrometry (GC/MS) assay and compared with 50 healthy
nonsmoking controls. Spirometry, skin prick tests and nonspecific IgE were
evaluated. RESULTS: Leukotrienes concentrations (B(4), E(4) but not D(4)) were
significantly increased in and after the pollen season in patients with SAR in
comparison with healthy controls. In most of the samples, LT C(4) was
undetectable. The values of all exhaled LTs were significantly decreased after
the pollen season compared with the seasonal baseline: LTB(4) (P = 0.023), LTD(4)
(P = 0.020), LTE(4) (P = 0.047). CONCLUSIONS: Levels of exhaled LTB(4) and LTE(4)
were higher in SAR patients than in healthy controls and decreased after the
pollen season as compared with levels in season. The SAR patients with the
highest in season LT levels had also the post-season levels elevated and this may
be an early marker of inflammatory process in the lower airways despite the
absence of clinical symptoms of asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15647037 [PubMed - indexed for MEDLINE]

831: Allergy. 2005 Feb;60(2):165-70.

Allergic rhinitis and asthma comorbidity in a survey of young adults in Italy.

Bugiani M, Carosso A, Migliore E, Piccioni P, Corsico A, Olivieri M, Ferrari M,
Pirina P, de Marco R; ISAYA (ECRHS Italy) Study Group.

Unit of Pneumology NHS-CPA-ASL 4 Turin, Italy.

BACKGROUND: Several studies have provided evidence of a strong association
between asthma and allergic or nonallergic rhinitis, leading to the hypothesis
that allergic rhinitis (AR) and asthma represent a continuum of the same disease.
AIM: The aims of our study were: (i) to measure the comorbidity of AR and asthma 
and asthma-like symptoms and (ii) to assess whether asthma, AR, and their
coexistence share a common pattern of individual risk factors. METHODS: The
subjects are participants from the Italian multicentre, cross-sectional survey on
respiratory symptoms in the young adult general population (Italian Study of
Asthma in Young Adults, ISAYA). The relationship between individual risk factors 
and asthma, AR and their coexistence, was studied by means of a multinomial
logistic regression. RESULTS: About 60% of asthmatics reported AR. On the other
hand, subjects with AR presented an eightfold risk of having asthma compared to
subjects without AR. Age was negatively associated with asthma [OR = 0.89, 95%
confidence interval (CI): 0.82-0.96], AR (OR = 0.92, 95% CI: 0.86-0.98), and
asthma associated with AR (OR = 0.83, 95% CI: 0.79-0.88). The risk of AR without 
asthma was significantly higher in the upper social classes (OR = 1.23, 95% CI:
1.08-1.39). Active current smoking exposure was positively associated with asthma
alone (OR = 1.24, 95% CI: 1.09-1.41) and negatively associated with AR with (OR =
0.69, 95% CI: 0.54-0.88) or without (OR = 0.76, 95% CI: 0.69-0.84) asthma.
CONCLUSIONS: Asthma and AR coexist in a substantial percentage of patients;
bronchial asthma and AR, when associated, seem to share the same risk factors as 
AR alone while asthma without AR seems to be a different condition, at least with
respect to some relevant risk factors.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15647036 [PubMed - indexed for MEDLINE]

832: Clin Ther. 2004 Nov;26(11):1876-89.

Current concepts and therapeutic strategies for allergic rhinitis in school-age
children.

Blaiss M.

Division of Clinical Immunology/Allergy, University of Tennessee Health Science
Center, Memphis, TN, USA. mblaiss@allergymemphis.com

BACKGROUND: Allergic rhinitis (AR) is a common debilitating disorder that can
adversely affect the quality of life and the academic performance of school-age
children. Symptoms during the day can hamper concentration and lead to learning
problems. Nocturnal symptoms can cause sleep loss and secondary daytime fatigue, 
further undermining a child's ability to function well during the school day Oral
antihistamines are the foundation of pharmacologic therapy, but there are
important differences between the agents. OBJECTIVE: The purpose of this review
is to provide an overview of the diagnostic and treatment challenges posed by AR 
in school-age children. The paper discusses and compares the available treatment 
modalities for this age group, with a focus on their beneficial and adverse
effects. METHODS: Pertinent articles were identified in the literature through a 
MEDLINE search (1990-2003). Keywords used were antihistamines cetirizine
fexofenadine loratadine desloratadine intranasal corticosteroids and CNS effects.
Results of numerous clinical trials of first-generation early second-generation
and the newer antihistamines were identified. RESULTS: This review established
that the socioeconomic costs of AR are considerable. In children aged > or =12
years, direct US expenditures (eg, physician visits, medications) in 1996
amounted to $2.3 billion. Indirect costs measured by variables such as missed
school days and poor performance also have an impact Major concerns include
underdiagnosis and inadequate treatment, increasing the risk of serious comorbid 
conditions such as asthma. Advantages and drawbacks of antihistamines show that
first-generation agents (eg, hydroxyzine) are effective and readily available
over the counter, but are associated with sedation and the potential for
suboptimal dosing. Newer agents, such as cetirizine, loratadine, desloratadine,
and fexofenadine are effective and safer than the older drugs tie, no
cardiotoxicity and less sedation). Of these, fexofenadine has been shown to be
beneficial and nonsedating, even at higher-than-recommended doses. Other
therapies reviewed include intranasal corticosteroids and leukotriene modifiers. 
CONCLUSIONS: AR has a considerable negative impact on children in terms of their 
physical, social, and psychological well-being and academic performance. An
appropriate treatment must be effective and tolerable. Of particular importance
for enhancing treatment adherence in the school-age population are pleasant taste
and ease of use of medication. A drug that has minimal or no sedative or
anticholinergic effects is optimal.

Publication Types: 
    Review

PMID: 15639699 [PubMed - indexed for MEDLINE]

833: Biofactors. 2004;21(1-4):127-31.

Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of
seasonal allergic rhinoconjunctivitis (SAR) and its mechanism.

Osakabe N, Takano H, Sanbongi C, Yasuda A, Yanagisawa R, Inoue K, Yoshikawa T.

Health & Bioscience Laboratories, Meiji Seika Kaisha Ltd., 5-3-1, Chiyoda Sakado 
350-0289, Japan. naomi_osakabe@meiji co.jp

The present study was undertaken to determine whether oral supplementation with
rosmarinic acid (RA) is an effective intervention for patients with SAR. In
addition, the anti-inflammatory mechanism of RA also estimated in the ear edema
models. CLINICAL TRIAL: Patients were treated daily with RA (200 mg or 50 mg) or 
placebo for 21 days. Patients recorded symptoms daily and profiles of
infiltrating cells and concentration of cytokines were measured in nasal lavage
fluid. Compared to placebo, supplementation with RA resulted in a significant
decrease in responder rates for each symptom. RA also significantly decreased the
numbers of neutrophils and eosinophils in nasal lavage fluid. ANIMAL STUDY:
Topical application RA showed anti-inflammatory activity 5-hours after
12-tetradecanoylphorbol 13-acetate (TPA) treatment with marked inhibition of
neutrophil infiltration. Up regulation of ICAM-1, VCAM-1 cyclooxygenase-2
(COX-2), KC and MIP-2 by TPA were markedly reduced by pre-treatment with extract 
of perilla (PE) or RA. Reactive oxygen radical production detected as
thiobarbituric acid reactive substance (TBARS), lipid peroxide (LPO) and
8-hydroxy-2'deoxyguanosine (8OH-dG), by double treatment of TPA was reduced by
pretreatment with PE or RA. RA is an effective intervention for SAR that is
mediated by inhibition of PMNL infiltration. This effect of RA is due to two
independent mechanisms: inhibition of the inflammatory response and scavenging of
ROS.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15630183 [PubMed - indexed for MEDLINE]

834: Clin Rev Allergy Immunol. 2004 Dec;27(3):181-9.

Latest developments in the management of allergic rhinitis.

Sanico AM.

Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA. amsanico@jhmi.edu

Allergic rhinitis (AR) is the most common chronic atopic disease, and it is
associated with considerable costs and comorbidities. The management of AR
includes environmental control measures, pharmacotherapy, and immunotherapy. This
article discusses several developments and findings that have recently emerged in
these three areas. The effectiveness of traditional methods of mitigating
allergen exposure, such as the use of impermeable dust mite-proof bedding covers,
has been rendered debatable. Exposure to environmental factors, such as household
pets, is known to provoke exacerbation of allergic disease but now is proposed to
have protective effects in certain settings. Changes in the choices of
pharmacotherapy continue to occur as antileukotrienes and derivatives of certain 
antihistamines are added to the armamentarium against AR. However, a critical
review of the clinical trials involving these drugs suggests that the changes are
not necessarily incremental. Innovative methods of immunomodulation are currently
being developed, with the objective of optimizing efficacy and safety.These
include alternative routes or forms of delivering immunotherapy and other novel
approaches in altering the pathobiology of AR.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15630154 [PubMed - indexed for MEDLINE]

835: Eur Cytokine Netw. 2004 Oct-Dec;15(4):317-22.

Increased expression of angiogenic markers in patients with seasonal allergic
rhinitis.

Kirmaz C, Ozbilgin K, Yuksel H, Bayrak P, Unlu H, Giray G, Kiliccioglu B.

Celal Bayar University, Medical Faculty, Department of Internal Medicine,
Division of Immunology, Manisa, Turkey. ckirmaz@mynet.com

BACKGROUND: Increased vascularity due to neo-angiogenesis is an essential part of
airway remodelling. Vascular endothelial growth factor (VEGF), CD34 and von
Willebrand's factor (FvW) are known angiogenic markers. Angiogenesis and airway
remodelling has been documented in asthma but not in allergic rhinitis.
OBJECTIVE: We aimed to investigate the presence of increased angiogenesis and its
relation to angiogenic molecules, namely VEGF, CD34 and FvW, in endothelial cells
of nasal mucosa in patients with seasonal allergic rhinitis (SAR), using three
different immunohistochemical analysis methods, namely HSCORE, microvessel
density (MVD) and vascular surface density (VSD). The findings in allergic
rhinitis were compared with the findings in nasal septal deviation (NSD), which
is not associated with increased angiogenesis. METHODS: Twenty patients with
symptomatic SAR, who were not under treatment, were enrolled in the study. Ten
patients with NSD, who needed surgical therapy, served as the control group.
Demographic characteristics did not differ between the two groups. Inferior
turbinate biopsy was obtained from SAR patients and control patients, under local
anaesthesia and during surgery respectively. All biopsies were evaluated for
angiogenesis on the basis of VEGF, CD34 and FvW by two blinded histologists using
three immunohistochemical analysis methods (HSCORE, MVD and VSD).Results. HSCORE,
estimated on the basis of each staining technique, showed statistically
significant differences among the two groups (p=0.002; p=0.045; p=0.016,
respectively). Anti-CD34 and anti-VEGF showed higher MVD values in SAR when
compared to the controls (p=0.038; p=0,009, respectively). No statistically
significant difference was found in Anti-FvW-based MVD between SAR patients and
controls (p=0.071). The measurements of VSD for FvW and VEGF from nasal biopsy
specimens displayed a statistically significant difference between the two groups
(p=0.004; p=0.0001, respectively). However, measurement of VSD for CD-34 was not 
significantly different between the groups (p=0.086). On the other hand,
morphometric data obtained by all three methods did not correlated. CONCLUSION:
There are a few studies that have investigated the essential role of angiogenesis
in the pathogenesis of allergic rhinitis. We conclude that, increased
angiogenesis may be as prominent in patients with allergic rhinitis as in
patients with non-allergic nasal pathologies and may play an important role in
the remodelling of nasal mucosa of subjects with SAR.

PMID: 15627640 [PubMed - indexed for MEDLINE]

836: Ann Agric Environ Med. 2004;11(2):205-8.

Comparison of Alnus, Corylus and Betula pollen counts in Lublin (Poland) and
Skien (Norway).

Piotrowska K.

Department of Botany, Agricultural University, Akademicka 15, 20-950 Lublin,
Poland. kpbot@agros.ar.lublin.pl

Symptoms of pollen allergy in springtime in Middle and Northern Europe are mainly
caused by pollen grains of birch, hazel and alder. The aim of the present study
was the pollen fall comparison of the mentioned taxa in Lublin (Poland) and Skien
(Norway). These sites are located approximately 1,200 km away apart by air. The
pollen monitoring was carried out by gravimetric method in 1999-2000. The start
and end of pollen seasons were defined by the 90% method. The beginning of pollen
seasons for Corylus and Betula were observed 1-3 weeks earlier in Lublin than in 
Skien, but pollen grains of Alnus appeared simultaneously in both towns. In 1999,
annual totals of Alnus, Corylus and Betula pollen grains were considerably less
numerous in Skien than in Lublin. No important differences were observed among
the pollen fall amounts of the mentioned taxa in 2000. The maximum values of
pollen grains were defined in different terms. The results of investigations
differed as regards the years compared as well as the sites.

PMID: 15627325 [PubMed - indexed for MEDLINE]

837: J Ethnopharmacol. 2005 Jan 15;96(3):445-9. Epub 2004 Nov 23.

Efficacy of Tinospora cordifolia in allergic rhinitis.

Badar VA, Thawani VR, Wakode PT, Shrivastava MP, Gharpure KJ, Hingorani LL,
Khiyani RM.

Department of Pharmacology, Indira Gandhi Medical College, Nagpur 440018, India.

The efficacy of Tinospora cordifolia (TC) extract in patients of allergic
rhinitis was assessed in a randomized double blind placebo controlled trial.
Seventy-five patients were randomly given either TC or placebo for 8 weeks. They 
were clinically examined and Hb %, TLC, DLC and nasal smear was done. At the end 
of trial baseline investigations were repeated, drug decoded and results
analyzed. With TC treatment 100% relief was reported from sneezing in 83%
patients, in 69% from nasal discharge, in 61% from nasal obstruction and in 71%
from nasal pruritus. In placebo group, there was no relief in 79% from sneezing, 
in 84.8% from nasal discharge, in 83% from nasal obstruction, and in 88% from
nasal pruritus. The difference between TC and placebo groups was highly
significant. TLC increased in 69% patients in drug treated group and in only 11% 
with placebo. After TC, eosinophil and neutrophil count decreased and goblet
cells were absent in nasal smear. After placebo, decrease in eosinophil and
neutrophil count was marginal and goblet cells were present. TC significantly
decreased all symptoms of allergic rhinitis. Nasal smear cytology and leukocyte
count correlated with clinical findings. TC was well tolerated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15619563 [PubMed - indexed for MEDLINE]

838: Arch Otolaryngol Head Neck Surg. 2004 Dec;130(12):1381-6.

Comment in:
    Arch Otolaryngol Head Neck Surg. 2005 Jun;131(6):539-40; author reply 540.

Butterbur Ze339 for the treatment of intermittent allergic rhinitis:
dose-dependent efficacy in a prospective, randomized, double-blind,
placebo-controlled study.

Schapowal A; Petasites Study Group.

Allergy Clinic, Landquart, Switzerland. andreas@schapowal.ch

OBJECTIVES: To investigate whether the efficacy and safety of Butterbur extract
Ze339 are related to dosage when administered to patients with intermittent
allergic rhinitis. DESIGN: Prospective, randomized, double-blind,
placebo-controlled, parallel-group comparison. SETTING: Multicenter, including 6 
outpatient general medicine and allergy clinics. PATIENTS: One hundred eighty-six
patients were randomized (Butterbur Ze339 high dose, 60; low dose, 65; and
placebo, 61 patients). Established diagnostic criteria for intermittent allergic 
rhinitis were confirmed by skin allergy tests in all patients. INTERVENTIONS:
High-dose group, 1 tablet 3 times daily; low-dose group, 1 tablet twice daily; or
matching placebo. All groups were treated for 2 consecutive weeks. MAIN OUTCOME
MEASURES: The main efficacy variable was change in symptoms from baseline to end 
point during the daytime. The secondary efficacy variables were Clinical Global
Impression score, change in symptoms from baseline to treatment day 7, and
responder rates. Statistical analysis was prospective, on an intention-to-treat
basis. RESULTS: Improvement in the main efficacy variable was significantly
superior in the Butterbur Ze339 groups, relative to placebo, and a significant
dose relationship was observed between the 2 Butterbur doses. The clinicians'
assessment of efficacy and the overall responder rates were significantly
superior for the active groups compared with placebo. The incidence and type of
adverse events were indistinguishable across the herbal treatment and placebo
groups. CONCLUSIONS: Butterbur Ze339 is an effective treatment for intermittent
allergic rhinitis symptoms and is well tolerated. The effects of this herbal
medicine are clear to patients and physicians in a double-blind evaluation
against placebo.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15611396 [PubMed - indexed for MEDLINE]

839: J Appl Physiol. 2005 Apr;98(4):1478-86. Epub 2004 Dec 17.

Superoxide dismutase failed to attenuate allergen-induced nasal congestion in
ragweed-sensitized dogs.

Skorohod N, Yeates DB.

Dept. of Medicine, M/C 788, Univ. of Illinois at Chicago, Chicago, IL 60612, USA.

We hypothesized that augmentation of antioxidant defenses with exogenous
superoxide dismutase (SOD), an enzyme that provides an initial defense against
oxidative injury, would attenuate allergen-induced nasal congestion in the canine
model of allergic rhinitis. Nasal congestion was evaluated by the measurements of
nasal resistance and the volume of the nasal passage. In five nonsensitized dogs,
30,000 U of SOD from bovine erythrocytes delivered by aerosol to the nasal
passages before histamine challenge reduced the histamine-induced nasal
congestion. At 30 min postchallenge, nasal resistance was 1.14 +/- 0.2
cmH2O.l(-1).min(-1) in the saline pretreatment study vs. 0.36 +/- 0.02
cmH2O.l(-1).min(-1) in the SOD pretreatment study (P < 0.05), and volume of nasal
passage was 10.9 +/- 0.5 cm3 vs. 17.4 +/- 1.3 cm3 (P < 0.05), respectively. In
five sensitized dogs, however, neither an analogous pretreatment with SOD nor
intranasal aerosolized pretreatment with 30,000 U of SOD conjugated to
polyethylene glycol attenuated ragweed-induced nasal congestion. Also, systemic
application of SOD did not attenuate responses to challenges with histamine and
ragweed in nonsensitized and sensitized dogs, respectively. The
antioxidant-induced attenuation of nasal congestion in nonsensitized dogs
confirms validity of the model and indicates the involvement of free
radical-mediated damage in the genesis of the histamine-induced congestion. In
sensitized dogs, the data do not support the hypothesis that oxidative stress is 
a clinically significant component of acute ragweed-induced nasal congestion. The
data do not support the use of SOD for acute protection against allergic
rhinitis.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 15608092 [PubMed - indexed for MEDLINE]

840: Allergy Asthma Proc. 2004 Sep-Oct;25(5):335-43.

Fexofenadine HCl 60 mg/ pseudoephedrine HCl 120 mg has a 60-minute onset of
action in the treatment of seasonal allergic rhinitis symptoms, as assessed in an
allergen exposure unit.

Berkowitz RB, McCafferty F, Lutz C, Bazelmans D, Godfrey P, Meeves S, Liao Y,
Georges G.

RxResearch, Woodstock, Georgia, USA.

Although antihistamine-decongestant combinations are frequently used for allergic
rhinitis, published data about the onset of action of these combination agents
are limited. This randomized, double-blind, placebo-controlled, parallel-group
study investigated the onset of action, efficacy, and safety of fexofenadine HCl 
60 mg/pseudoephedrine HCl 120 mg or placebo in patients with moderate-to-severe
seasonal allergic rhinitis in an allergen exposure unit. Assessments included
major symptom complex (MSC) score (sum of sneezing, itchy nose, runny nose,
watery eyes, itchy eyes, itchy ears/throat, and stuffy nose), and total symptom
complex (TSC) score (MSC symptoms plus nose blows, sniffles, postnasal drip, and 
cough). Onset of action was defined as the first time that two consecutive,
statistically significant absolute changes in MSC scores from baseline were
achieved for study drug relative to placebo. The onset of action for the
combination was 60 minutes (mean absolute MSC change from baseline: -6.9 +/- 0.3 
for the combination compared with -5.9 +/- 0.3 for placebo from a baseline of
17.0 and 16.8, respectively; p < 0.05) for the modified intention-to-treat
population (n = 486). Reductions in absolute MSC scores were significantly
greater with the combination than placebo at all subsequent time points (p <
0.01). The combination resulted in significantly greater reductions compared with
placebo for percent MSC, absolute TSC, and percent TSC scores at 60 minutes
postdose (all p < 0.05) and throughout the study (all p < 0.05). The incidence of
adverse events was 1.6 and 3.3% for the combination and placebo, respectively. In
conclusion, fexofenadine HCl 60 mg/pseudoephedrine HCl 120 mg is effective in the
treatment of patients with moderate-to-severe seasonal AR, with an onset of
action of 60 minutes and a good safety profile.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15603207 [PubMed - indexed for MEDLINE]

841: J Int Med Res. 2004 Nov-Dec;32(6):655-64.

Combination treatment using the COX-2 inhibitor meloxicam and an anti-allergic in
pollinosis.

Takechi M.

TSUCHIBASHI SHINRYOSHO (clinic), Honmachi Kochi-city, Kochi, Japan.
lunamac@ps.inforyoma.or.jp

The value of combination therapies that aim to affect both immediate and delayed 
inflammatory reactions is well known in the treatment of pollinosis. Use of a
selective cyclooxygenase-2 (COX-2) inhibitor such as meloxicam is a new approach,
however. COX-2 inhibitors target the delayed reaction, which plays a major role
in chronic nature of this allergic reaction through activation of the
arachidonate cascade and the production of prostaglandins. In this study, four
treatment regimens were compared for effectiveness in relieving the symptoms of
pollinosis: (i) an anti-allergic alone; (ii) an anti-allergic plus a conventional
non-steroidal anti-inflammatory drug; (iii) an anti-allergic plus a selective
COX-2 inhibitor; and (iv) an anti-allergic plus an oral steroid. Use of a COX-2
inhibitor plus an anti-allergic produced significantly more relief for most
symptoms. The significance of this is as yet unclear, but it is hoped that these 
results will further our understanding of chronic inflammation.

Publication Types: 
    Clinical Trial

PMID: 15587760 [PubMed - indexed for MEDLINE]

842: Immunogenetics. 2005 Jan;56(10):760-4. Epub 2004 Dec 4.

The suggestive association of eotaxin-2 and eotaxin-3 gene polymorphisms in
Korean population with allergic rhinitis.

Chae SC, Park YR, Oh GJ, Lee JH, Chung HT.

Genome Research Center for Immune Disorders, Wonkwang University School of
Medicine, Iksan, Chonbuk, 570-749, Korea.

The eotaxin gene family (eotaxin, eotaxin-2 and eotaxin-3) has been implicated in
the recruitment of eosinophils, basophiles and Th2 lymphocytes that are central
aspects of allergic diseases. To determine whether single-nucleotide
polymorphisms (SNPs) of the eotaxin-2 and eotaxin-3 genes are associated with
susceptibility to allergic rhinitis, we scanned 178 allergic rhinitis patients
and 281 controls without allergic rhinitis using the direct sequencing and
single-base extension (SBE) methods. We also calculated the haplotype frequencies
between +179T>C and +275C>T of eotaxin-2 and +2497T>G of eotaxin-3 in both
controls and allergic rhinitis patients. The haplotype frequency between controls
and allergic rhinitis patients was suggestively associated (P=0.0001). The
genotype frequencies of eotaxin-3 +2497T>G in allergic rhinitis patients were
suggestively different from those in non-allergic rhinitis controls (P=<0.0007). 
Our results strongly suggest that the SNP of eotaxin-3 might be associated with
susceptibility to allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15580493 [PubMed - indexed for MEDLINE]

843: J Allergy Clin Immunol. 2004 Dec;114(6):1384-8.

Remission of allergic rhinitis: An 8-year observational study.

Bodtger U, Linneberg A.

Allergy Clinic, Copenhagen University Hospital, Copenhagen, Denmark. ub-all@rh.dk

BACKGROUND: Allergic rhinitis (AR) and sensitization are considered chronic
conditions. However, few studies have reported remission rates in adults.
OBJECTIVE: We sought to estimate the incidence of remission of AR during an
8-year period. METHODS: Participants in a population-based study of 15- to
69-year-old patients in 1990 were invited to a follow-up in 1998. Questionnaires 
on respiratory symptoms and serum for specific IgE (s-IgE) analyses were
collected at both visits in 734 subjects (69% of those invited). Pollen AR was
defined as rhinitis symptoms on pollen exposure within the last 12 months and
s-IgE levels of class 2 or greater against pollen (birch, grass, or mugwort).
This was similar for AR to animals (cat or dog) or house dust mites (HDMs).
Remission of AR was defined as AR at baseline but no rhinitis symptoms at
follow-up and sensitization (s-IgE level class > or =2 at baseline and class <2
at follow-up). RESULTS: Remission of AR occurred in 12% (pollen AR), 19% (animal 
AR), and 38% (HDM AR; overall, 17%) and was predicted by low s-IgE levels. Age,
sex, asthma, atopic predisposition, age at AR onset, and AR duration had no
predictive value. A decrease in s-IgE level was observed in only 22% of remitting
subjects yet was seen significantly more often than in nonremitting subjects
(7.4%). Remission of sensitization occurred in 6% (HDM) to 11% (pollen-furry
animal) and was predicted on the basis of low s-IgE levels (class 2) at baseline.
CONCLUSION: Remission of AR symptoms was relatively infrequent, and remission of 
both symptoms and IgE sensitization was rare. The results underline the chronic
nature of AR in adulthood.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15577841 [PubMed - indexed for MEDLINE]

844: Allergy. 2005 Jan;60(1):4-12.

Comment in:
    Allergy. 2005 Jan;60(1):1-3.

Sublingual immunotherapy for allergic rhinitis: systematic review and
meta-analysis.

Wilson DR, Lima MT, Durham SR.

University Hospital Birmingham NHS Trust, Birmingham, UK.

Allergic rhinitis is a common condition which, at its most severe, can
significantly impair quality of life despite optimal treatment with
antihistamines and topical nasal corticosteroids. Allergen injection
immunotherapy significantly reduces symptoms and medication requirements in
allergic rhinitis but its use is limited by the possibility of severe systemic
reactions. There has therefore been considerable interest in alternative routes
for delivery of allergen immunotherapy, particularly the sublingual route. The
objective was to evaluate the efficacy of sublingual immunotherapy (SLIT),
compared with placebo, for reductions in symptoms and medication requirements.
The Cochrane Controlled Clinical Trials Register, MEDLINE (1966-2002), EMBASE
(1974-2002) and Scisearch were searched, up to September 2002, using the terms
(Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). All
studies identified by the searches were assessed by the reviewers to identify
Randomized Controlled Trials involving participants with symptoms of allergic
rhinitis and proven allergen sensitivity, treated with SLIT or corresponding
placebo. Data from identified studies was abstracted onto a standard extraction
sheet and subsequently entered into RevMan 4.1. Analysis was performed by the
method of standardized mean differences (SMD) using a random effects model.
P-values < 0.05 were considered statistically significant. Subgroup analyses were
performed according to the type of allergen administered, the age of participants
and the duration of treatment. Twenty-two trials involving 979 patients, were
included. There were six trials of SLIT for house dust mite allergy, five for
grass pollen, five for parietaria, two for olive and one each for, ragweed, cat, 
tree and cupressus. Five studies enrolled exclusively children. Seventeen studies
administered the allergen by sublingual drops subsequently swallowed, three by
drops subsequently spat out and two by sublingual tablets. Eight studies involved
treatment for less than 6 months, 10 studies for 6-12 months and four studies for
greater than 12 months. All included studies were double-blind placebo-controlled
trials of parallell group design. Concealment of treatment allocation was
considered adequate in all studies and the use of identical placebo preparations 
was almost universal. There was significant heterogeneity, most likely due to
widely differing scoring systems between studies, for most comparisons. Overall
there was a significant reduction in both symptoms (SMD -0.42, 95% confidence
interval -0.69 to -0.15; P = 0.002) and medication requirements [SMD -0.43
(-0.63, -0.23); P = 0.00003] following immunotherapy. Subgroup analyses failed to
identify a disproportionate benefit of treatment according to the allergen
administered. There was no significant reduction in symptoms and medication
scores in those studies involving only children but total numbers of participants
was too small to make this a reliable conclusion. Increasing duration of
treatment does not clearly increase efficacy. The total dose of allergen
administered may be important but insufficient data was available to analyse this
factor.

Publication Types: 
    Meta-Analysis
    Review

PMID: 15575924 [PubMed - indexed for MEDLINE]

845: Neuropeptides. 2004 Dec;38(6):351-8.

Chlorine inhalation produces nasal airflow limitation in allergic rhinitic
subjects without evidence of neuropeptide release.

Shusterman D, Balmes J, Murphy MA, Tai CF, Baraniuk J.

Upper Airway Biology Laboratory, University of California, San Francisco, Box
0843, San Francisco, CA 94143, USA. dennis3@u.washington.edu

BACKGROUND: Seasonal allergic rhinitic (SAR) subjects are more physiologically
reactive to airborne irritants than non-rhinitic (NR) subjects; however the
mechanism underlying this difference is unclear. OBJECTIVE: We sought to
determine whether irritant-induced nasal airflow limitation involves neuropeptide
release into nasal lining fluid, and if so, whether such release occurs
differentially by rhinitic status. METHODS: Eight SAR and 8 NR subjects were
exposed to 1.0 ppm chlorine and filtered air in random order during separate
visits; exposures were via nasal mask and lasted 15 min. Rhinomanometry was
performed before, immediately post-, and 15 min post-exposure. Following a
minimum of 2 weeks' time, exposures and symptom reporting were repeated with
nasal lavage pre- and post-exposure. Neuropeptides (substance P, cacitonin
gene-related protein, vasoactive intestinal peptide, and neuropeptide Y) as well 
as markers of plasma leakage (albumin and urea) and glandular secretion (lysozyme
and 7F10-mucin) were measured using standard methods. RESULTS: Cl(2) provocation 
significantly increased nasal airway resistance in SAR but not NR subjects
(p<0.05). Neuropeptide levels in nasal lavage fluid, on the other hand, were
unaffected, with the exception of a paradoxical increase in vasoactive intestinal
peptide in non-rhinitic controls post-Cl(2) provocation. CONCLUSIONS:
Irritant-induced nasal airflow limitation is more pronounced among SAR than NR
subjects. We could not, however, demonstrate a role for neuropeptide release in
the nasal congestive response of SAR subjects.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15567471 [PubMed - indexed for MEDLINE]

846: Asian Pac J Allergy Immunol. 2004 Jun-Sep;22(2-3):69-79.

Development of a health-related quality of life questionnaire for Thai patients
with rhinoconjunctivitis.

Bunnag C, Leurmarnkul W, Jareoncharsri P, Ungkanont K, Tunsuriyawong P,
Kosrirukvongs P, Sriussadaporn P, Musiksukont S, Kosawanon S, Chairojkanjana K.

Department of Otolaryngology, Faculty of Medicine, Siriraj Hospital, Mahidol
University, Thailand.

The objective of this study was to develop a disease-specific questionnaire for
patients with rhinoconjunctivitis. All patients were recruited at the Out-Patient
Clinic at Siriraj Hospital. Related topics were gathered from several sources,
and a list of 63 items was produced. In phase I, the first version of the
questionnaire was completed by 363 patients. Forty-eight items were identified by
clinical impact analysis during the item removal process, two more questions were
then added, giving a total of 50. Two hundred and forty-three patients completed 
the second version questionnaire in phase II. The average time taken to complete 
the questionnaire was 6.38 minutes. The item removal process in phase II was
achieved by a multi-step process. There were 36 items in the third version
questionnaire which consisted of six dimensions and two independent items as
follows: symptoms (17 items), physical functioning (3 items), role limitations (3
items), sleep (3 items), social functioning (3 items), emotions (5 items),
general health (1 item), and absenteeism (1 item). The scores of each item ranged
from 1 to 5; a lower score indicating a better quality of life. Data from the
selected 36 items was extracted to test the validity and reliability of the final
version. The floor and ceiling effects of the scores for each dimension were low.
Multitrait multi-item analysis was conducted to examine construct validity. The
scaling success of convergent and divergent validity was 100% and 94%,
respectively. Internal consistency determined by Cronbach's alpha coefficient,
was satisfactory (0.79-0.87). The study indicates that the questionnaire is
suitable for use in clinical settings. While the test results are encouraging,
further work needs to be done on the test-retest reliability and on
responsiveness.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15565942 [PubMed - indexed for MEDLINE]

847: Int Arch Allergy Immunol. 2004 Dec;135(4):336-42. Epub 2004 Nov 24.

The allergic march in pollinosis: natural history and therapeutic implications.

Marogna M, Falagiani P, Bruno M, Massolo A, Riva G.

Pneumology Unit, Cuasso al Monte, Macchi Hospital Foundation, Varese, Italy.
maurizio_marogna@libero.it

BACKGROUND: That specific immunotherapy (SIT) can slow the march of allergy has
been confirmed in controlled clinical trials. However, an assessment of its
effects in everyday life, in a large cohort of patients, might provide further
useful information. METHODS: This observational study comprised 3,643 patients
allergic to pollens; 1,620 with pure allergic rhinitis or rhinitis and
intermittent or mild-persistent bronchial asthma, responding poorly to standard
pharmacological therapy (SPT), were treated for 3 years with SPT alone (pure
rhinitis, n = 890), or combined with continuous SIT (rhinitis and asthma, n =
730). Symptom/drug scores were recorded, respiratory function and skin tests were
done, and methacholine challenge was scheduled at the beginning and end of the
study. A series of 2,023 patients with pure rhinitis, responsive to SPT, were
asked to 'self-medicate' as needed, serving as a control group to check the
incidence of asthma. RESULTS: The incidence of rhinitis-asthma co-morbidity was
highest in the self-medication group (50.8%). Persistent rhinitis was associated 
with asthma more often than the intermittent form, regardless of the severity of 
the symptoms that led to progression to asthma in patients with intermittent
rhinitis. Treatment with SIT combined with SPT always slowed the allergic march
which, however, was not influenced by drugs alone. CONCLUSIONS: In routine
clinical practice, SIT is effective in preventing the allergic march. Patients
with persistent rhinitis, who are at greatest risk of progression to asthma,
appear to be the most logical candidates. 2004 S. Karger AG, Basel.

Publication Types: 
    Comparative Study

PMID: 15564776 [PubMed - indexed for MEDLINE]

848: Int Arch Allergy Immunol. 2004 Dec;135(4):332-5. Epub 2004 Nov 24.

Efficacy of injection immunotherapy with ragweed and birch pollen in elderly
patients.

Asero R.

Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italia.
r.asero@libero.it

BACKGROUND: The role of specific immunotherapy (SIT) in elderly allergic patients
is still debated. OBJECTIVE: The aim of this study was to assess whether SIT is
associated with a better control of symptoms and a better quality of life also in
older allergic patients. METHODS: The effect of injection SIT was assessed in 39 
patients [age >54 years, median 59; 29 patients (74%) with asthma, otherwise
healthy] monosensitized to birch (n = 20) and ragweed (n = 19). Thirty-three
younger subjects [age <50 years, median 35; 26 patients (79%) with asthma,
otherwise healthy] monosensitized to birch (n = 10) and ragweed (n = 23), and 37 
subjects >54 years old (25 males/12 females; age 55-79 years, median 59 years)
monosensitized to birch (n = 18) and ragweed (n = 19) who refused to undergo SIT 
were enrolled as positive and negative controls, respectively. All groups had a
disease duration <10 years; the disease was inadequately controlled with standard
drug therapies in all cases. SIT was carried out using the same extracts and was 
administered using a perennial schedule both in patients and controls. Seasonal
therapies were the same in all groups and were not changed after SIT was started.
After 1-5 years of SIT, patients and controls were asked to quantify symptom
reduction on a visual analogue scale: reductions >50% were considered
significant. Moreover, the use of cetirizine and/or salbutamol as an adjunct to
standard therapies during the last pollen season was assessed as an objective
measure of SIT outcome. RESULTS: 37/39 (95%) patients versus 32/33 (97%) controls
submitted to SIT reported a symptom reduction >50% after 1-5 years of SIT
(nonsignificant). The median clinical efficacy of SIT was 80% in both groups
(nonsignificant). 27/37 controls not submitted to SIT did not report any change
in symptom severity at the follow-up visits, whereas 10/37 reported a more severe
disease (4 subjects reported the appearance of seasonal asthma) (p < 0.001 vs.
patients submitted to SIT). Patients used less frequently cetirizine (p < 0.001) 
and/or salbutamol (p < 0.05) than controls not submitted to SIT. CONCLUSION:
Injection SIT can be considered an effective therapeutic option in otherwise
healthy elderly patients with a short disease duration whose symptoms cannot be
adequately controlled by drug therapies alone. 2004 S. Karger AG, Basel.

PMID: 15564775 [PubMed - indexed for MEDLINE]

849: Ann Allergy Asthma Immunol. 2004 Nov;93(5):452-9.

Addition of ibuprofen to pseudoephedrine and chlorpheniramine in the treatment of
seasonal allergic rhinitis.

Meltzer EO, Berman GD, Corren J, Pedinoff AJ, Doyle G, Waksman JA, Butkerait P,
Cooper SA, Berlin RG, Wason S.

Allergy & Asthma Medical Group & Research Center, San Diego, California, USA.

BACKGROUND: Patients with seasonal allergic rhinitis experience many nasal and
concomitant nonnasal symptoms. Many patients also experience headaches and facial
pain, pressure, or discomfort. Standard over-the-counter therapy with
antihistamines and nasal decongestants often does not completely relieve all
symptoms associated with allergic rhinitis. OBJECTIVE: To establish the
contribution of ibuprofen when used with pseudoephedrine and chlorpheniramine, a 
standard over-the-counter regimen, to relieve the symptoms of seasonal allergic
rhinitis. METHODS: In this 7-day, multicenter, randomized, placebo-controlled,
double-blind, double-dummy, parallel-group trial, qualified subjects were
randomly assigned to 1 of 4 treatment groups that received combined
ibuprofen/pseudoephedrine/chlorpheniramine (200/30/2 mg or 400/60/4 mg), combined
pseudoephedrine/chlorpheniramine (30/2 mg), or placebo. Therapy began when the
subject experienced a minimum of moderate allergy-associated pain, and it
continued 3 times a day for 7 consecutive days. RESULTS: Mean pain intensity
reduction in both ibuprofen/pseudoephedrine/chlorpheniramine treatment groups was
40% greater than in the placebo group and 33% greater than in the
pseudoephedrine/chlorpheniramine treatment group (P < .001). Mean changes from
baseline in total and nonpain symptom scores for both
ibuprofen/pseudoephedrine/chlorpheniramine doses were significantly greater than 
for placebo (P < .001) and pseudoephedrine/chlorpheniramine (P < .001-.05) but
were not different from each other. Ibuprofen enhanced the chlorpheniramine and
pseudoephedrine effects, resulting in incremental 33% to 34% pain relief and 17% 
to 22% allergy symptom relief compared with pseudoephedrine/chlorpheniramine.
CONCLUSIONS: In both doses of the triple combination, ibuprofen added to the
effects of chlorpheniramine and pseudoephedrine, resulting in superior relief of 
pain and all nonpain allergy symptoms compared with
pseudoephedrine/chlorpheniramine treatment. Furthermore, the superior efficacy of
the lower dose of the triple combination allowed for a decrease in the incidence 
of adverse effects.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15562884 [PubMed - indexed for MEDLINE]

850: Ann Allergy Asthma Immunol. 2004 Nov;93(5):431-8.

Comment in:
    Ann Allergy Asthma Immunol. 2004 Nov;93(5):407-8.

Protective effect of montelukast on lower and upper respiratory tract responses
to short-term cat allergen exposure.

Perry TT, Corren J, Philip G, Kim EH, Conover-Walker MK, Malice MP, Massaad R,
Dass SB, Reiss TF, Wood RA.

Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins
University School of Medicine, Baltimore, Maryland 21287, USA.

BACKGROUND: Challenge with short-term exposure to airborne cat allergen in
sensitized patients produces pulmonary function changes and rhinitis symptoms.
OBJECTIVE: To determine the benefit of montelukast, 10 mg, for patients with
concomitant asthma and allergic rhinitis as demonstrated by protection against
both lower and upper airway responses to cat allergen challenge. METHODS: This
randomized, crossover study treated patients with montelukast vs placebo during
two 2-week, double-blind treatment periods, separated by a 1-week washout period.
After each treatment period, patients underwent a 60-minute or less exposure to
high levels of airborne cat allergen. Lower and upper airway responses were
measured by spirometry and symptom scores. RESULTS: Of 52 patients with data from
both treatment arms, 79% of patients taking montelukast and 67% taking placebo
were exposed to the full 60-minute allergen challenge. Montelukast provided
significant (P < or = .001) protection against allergen challenge in the lower
airway coprimary end point of area under the curve during challenge (AUC0-60min) 
for percentage decrease in forced expiratory volume in 1 second: mean of 10.5%
per hour and 14.7% per hour for montelukast and placebo, respectively. Although
the effect on the overall nasal symptoms score (NSS) coprimary end point of
AUC0-60min was not statistically significance (P = .12), nasal congestion during 
the challenge and NSS during recovery showed statistically significant (P = .048)
protection by montelukast. Additional analyses of simultaneous lower and upper
airway responses showed that more patients taking montelukast (22, 43%) vs
placebo (13, 26%) were protected from both asthma and rhinitis (P = .02), with an
odds ratio of 2.24 (95% CI, 1.16-4.32) in favor of montelukast. CONCLUSIONS:
Montelukast has a protective effect against both lower and upper airway responses
during exposure to high levels of cat allergen.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15562881 [PubMed - indexed for MEDLINE]

851: Ann Allergy Asthma Immunol. 2004 Nov;93(5):425-30.

Comment in:
    Ann Allergy Asthma Immunol. 2004 Nov;93(5):405-6.

Canadian trial of sublingual swallow immunotherapy for ragweed
rhinoconjunctivitis.

Bowen T, Greenbaum J, Charbonneau Y, Hebert J, Filderman R, Sussman G, Del Carpio
J, Gold M, Keith P, Moote W, Cecchetto S, Cecchetto O, Sharp D, Broutin O, André 
C.

Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
tbowen@pol.net

BACKGROUND: Sublingual swallow immunotherapy has been increasingly recognized as 
a safe and efficacious alternative to parenteral specific immunotherapy.
OBJECTIVE: To determine the safety and efficacy of sublingual swallow
immunotherapy ragweed allergen extract for rhinoconjunctivitis treatment starting
just before and continuing through the ragweed pollen season. METHODS: This
randomized, double-blind, placebo-controlled study was performed in children and 
adults with a documented history of allergic rhinoconjunctivitis during ragweed
season at 9 Canadian allergy centers. Active treatment was standardized extract
of ragweed allergen administered as sublingual swallow drops at increasing doses 
starting shortly before the pollen season and maintenance doses continued daily
during the season. Primary efficacy variables were symptom and medication scores,
and secondary variables included global evaluation of efficacy and immunologic
measurements. RESULTS: Eighty-three patients were included in the safety
analysis; 76 patients were included in the intent-to-treat analysis. Nine placebo
recipients and 1 treatment recipient withdrew for lack of efficacy (P = .004).
Nine patients in the treatment group withdrew because of adverse events, none
serious (P = .003). Investigator evaluation of efficacy showed that significantly
more patients improved and fewer deteriorated in the treatment group vs the
placebo group (P = .047). Ragweed IgE and IgG4 levels increased significantly in 
treatment recipients vs placebo users (P < .001). Sneezing and nasal pruritus
approached significant improvement in the treatment group vs the placebo group (P
= .09 and .06, respectively). Quebec City experienced low pollen counts.
Excluding Quebec City, significant improvement was seen for these 2 symptoms (P =
.04). CONCLUSION: Sublingual swallow immunotherapy seems to be safe and
efficacious for ragweed rhinoconjunctivitis even when started immediately before 
the ragweed pollen season.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15562880 [PubMed - indexed for MEDLINE]

852: Arzneimittelforschung. 2004;54(10):666-72.

Clinical study of the therapeutic efficacy and safety of emedastine difumarate
versus cetirizine in the treatment of seasonal allergic rhinitis.

Horak F, Stübner P, Zieglmayer R, Kavina A, Corrado ME, Assandri A, Mion A.

Ear-Nose-Throat University Clinic, Vienna (Austria). f.horak@vienna.at

OBJECTIVE: The therapeutic efficacy and tolerability of emedastine difumarate
(CAS 87233-62-3) in male and female Caucasian patients with seasonal allergic
rhinitis as compared to cetirizine (CAS 83881-51-0) was evaluated. METHODS: The
study was designed as a double-blind, randomised, parallel groups comparison of
two antihistamines administered by oral route (emedastine 4 mg o.d. versus
cetirizine 10 mg o.d.) in a population of 120 patients suffering from grass
pollen allergic rhinitis. The duration of the treatment period was 14 days.
Primary efficacy variable was a total symptoms score (including among symptoms
nasal congestion, sneezing, rhinorrhea, nasal/throat/palate itching, eye itching 
and lacrimation) evaluated after 14 days of treatment vs. baseline value. Safety 
was assessed on routine laboratory assays and recording vital signs and adverse
events (AEs). RESULTS: The between-group difference in primary efficacy variable 
averaged over the 2-week treatment period was not statistically significant.
Results clearly showed that no significant difference exists between the two
treatments as far as total symptoms score evaluated after 14 days of treatment
vs. baseline values are concerned. Therefore, the efficacy profiles of the study 
medications are overlapping. The pattern and incidence of AEs was similar in both
treatment groups. The most frequent AEs with both compounds were related to the
CNS, headache being the most reported one. In particular, this study seems to
disclose a slighter tendency to drowsiness with emedastine than with cetirizine. 
CONCLUSIONS: Both drugs under investigation in this trial appear to be effective 
for relieving the symptoms of seasonal allergic rhinitis in Caucasian adult
patients. The results demonstrate that emedastine 4 mg o.d. is comparable in
efficacy to cetirizine 10 mg once daily in the symptomatic management of seasonal
allergic rhinitis. Moreover, based on the results of this study, emedastine can
be considered a safe and well-tolerated drug and its safety profile seems to
resemble that of cetirizine.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Randomized Controlled Trial

PMID: 15553106 [PubMed - indexed for MEDLINE]

853: Arzneimittelforschung. 2004;54(10):660-5.

Clinical study of the therapeutic efficacy and safety of emedastine difumarate
versus terfenadine in the treatment of seasonal allergic rhinitis.

Corrado ME, Radicioni MM, Hartwig J, Assandri A, Oldeman HG, Mion A.

CROSS SA, Arzo, TI (Switzerland). croalliance@croalliance.com

OBJECTIVE: Emedastine is a new H1-receptor antagonist endowed with potent and
selective antihistamine activity. The aim of this study was to evaluate the
therapeutic efficacy and tolerability of emedastine difumarate (CAS 87233-62-3)
in Caucasian patients in the treatment of seasonal allergic rhinitis as compared 
to terfenadine (CAS 50679-08-8). METHODS: A total of 130 patients suffering from 
grass pollen allergic rhinitis were randomly assigned to 14 days treatment with
either emedastine difumarate (2 mg b.i.d.) or terfenadine (60 mg b.i.d.) in a
double-blind, randomised, crossover design. Primary efficacy parameter was a
Total Severity Symptom Score, including among symptoms nasal congestion,
sneezing, rhinorrhea, nasal/throat/palate itching, eye itching and lacrimation.
Safety was assessed on routine laboratory tests and recording vital signs and
adverse events (AEs). RESULTS: Emedastine 2 mg b.i.d. was significantly more
effective than terfenadine 60 mg b.i.d. in reducing Total Symptom Severity Score 
(p = 0.0258). This statistical significant difference was also obtained in
controlling sneezing and rhinorrhea (p = 0.003). Moreover, both the physician and
patients indicated emedastine as the preferred therapy (p < 0.01). Forty-seven
drug related AEs were reported for emedastine (= 51.07 %) and 53 for terfenadine 
(64.15 %), most of them involving the CNS. CONCLUSION: The results of study show 
that emedastine difumarate is more effective than terfenadine in the symptomatic 
management of seasonal allergic rhinitis and is particularly active in
controlling the main nasal symptoms, such as sneezing and rhinorrhea; it is safe 
and well tolerated in this therapeutic indication, while related AEs are less if 
compared to those displayed by terfenadine.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Randomized Controlled Trial

PMID: 15553105 [PubMed - indexed for MEDLINE]

854: J Investig Allergol Clin Immunol. 2004;14(3):238-43.

Airborne plane-tree (Platanus hispanica) pollen distribution in the city of
Córdoba, South-western Spain, and possible implications on pollen allergy.

Alcázar P, Cariñanos P, De Castro C, Guerra F, Moreno C, Dominguez-Vilches E,
Galán C.

Department of Plant Biology (Botany), University of Córdoba, Spain.
bv2pimur@uco.es

Plane-trees are widely grown in Spain as ornaments. This taxon releases large
amounts of pollen into the air and this pollen type seems to have proved
implications on pollinosis. The aim of this study was to analyse airborne
Platanus pollen content in the air of C6rdoba (South-western Spain) over the last
10 years, and its distribution in different areas of the city, as well as to
consider possible implications regarding pollen allergies. Results revealed that 
Platanus pollen concentrations have been at their highest over the last 5 years. 
Within the city, the lowest pollen concentrations were in Northern areas of the
city. Nevertheless, concentrations high enough to be of risk are reached over the
whole city. All the patients studied presented symptoms during the Platanus
pollen season. We can therefore conclude that plane pollen presents a risk for
the whole city although symptoms are more intense and persistent in districts
with a higher number of plane-trees. Platanus allergy is a particular problem for
city-dwellers, where these trees are commonly used as ornamentals.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15552719 [PubMed - indexed for MEDLINE]

855: Ann Allergy Asthma Immunol. 2004 Oct;93(4):345-50.

Patient preferences for sensory attributes of intranasal corticosteroids and
willingness to adhere to prescribed therapy for allergic rhinitis: a conjoint
analysis.

Mahadevia PJ, Shah S, Leibman C, Kleinman L, O'Dowd L.

MEDTAP International Inc, Bethesda, Maryland, USA.

BACKGROUND: Sensory attributes of intranasal corticosteroid (INS) products vary. 
OBJECTIVE: To evaluate patient preferences for INS sensory attributes and the
degree to which attributes influence patients' willingness to adhere to therapy. 
METHODS: We conducted a cross-sectional study with 120 individuals across 4 US
allergy/immunology clinics. Respondents chose between pairs of hypothetical INSs 
differing in sensory attribute composition. We measured the strength of
preferences for 6 sensory attributes (smell, taste, aftertaste, throat rundown,
nose runout, and feel of spray in nose or throat). Preferences were measured for 
3 intensity levels of each sensory attribute (eg, no taste, weak taste, and
strong taste). Other outcomes included an importance score for each sensory
attribute and patients' willingness to adhere to therapy with an INS with the
lowest intensity levels of each sensory attribute vs one with moderate intensity 
levels. RESULTS: Preferences decreased with increasing intensity levels of each
sensory attribute. Aftertaste was the most important attribute in 28% of
patients, taste in 19%, throat rundown in 18%, nose runout in 12%, smell in 11%, 
and feel of spray in 7%. If instructed to take an INS daily for 3 months, 77% of 
patients stated that they would definitely be able to follow their physician's
advice (willingness to adhere) if given one containing the lowest level of each
sensory attribute vs 4% if given one having moderate levels (P < .01).
CONCLUSIONS: Patient preferences are inversely related to increasing intensity
levels of sensory attributes and affect patients' willingness to adhere to
therapy. Application of patient preferences when selecting INSs could improve
adherence.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15521370 [PubMed - indexed for MEDLINE]

856: Biopharm Drug Dispos. 2004 Dec;25(9):373-87.

The utility of mixed-effects covariate analysis in rapid selection of doses in
pediatric subjects: a case study with fexofenadine hydrochloride.

Krishna R, Krishnaswami S, Kittner B, Sankoh AJ, Jensen BK.

Aventis Drug Innovation & Approval, Bridgewater, NJ, USA.
rajesh_krishna@merck.com

Fexofenadine hydrochloride is a non-sedating antihistamine that is used in the
treatment of symptoms associated with seasonal allergic rhinitis and chronic
idiopathic urticaria. A pooled analysis of pharmacokinetic data from children 6
months to 12 years of age and adults was conducted to identify the dose(s) in
children that produce exposures comparable to those in adults for the treatment
of seasonal allergic rhinitis. The pharmacokinetic parameter database included
peak and overall exposure data from 269 treatment exposures from 136 adult
subjects, and 90 treatment exposures from 77 pediatric allergic rhinitis
patients. The data were pooled and analysed using NONMEM software, version 5.0. A
covariate model based on body weight and age and a power function model based on 
body weight were identified as appropriate models to describe the variability in 
fexofenadine oral clearance and peak concentration, respectively. Individual oral
clearance estimates were on average 44%, 36% and 61% lower in children 6 to 12
years (n=14), 2 to 5 years (n=21), and 6 months to 2 years (n=42), respectively, 
compared with adults. Trial simulations (n=100) were carried out based on the
final pharmacostatistical models and parameter estimates to identify the
appropriate dose(s) in children relative to the marketed dose of 60 mg
fexofenadine hydrochloride in adults. The trials were designed as crossover
studies in 18 subjects comprising various potential dosing regimens with and
without weight stratification. Pharmacokinetic parameter variability was assumed 
to have a log-normal distribution. Individual weights and ages were simulated
using mean (SD) estimates derived from the studies used in this analysis and
proportional measurement/model mis-specification errors derived from the analysis
were incorporated into the simulation. The results indicated that a 30 mg dose of
fexofenadine hydrochloride administered to children 1 to 12 years of age and
weighing >10.5 kg and a 15 mg dose administered to children 6 months and older
and weighing <or=10.5 kg produces exposures similar to those seen with the 60 mg 
dose in adults. copyright (c) 2004 John Wiley & Sons, Ltd.

PMID: 15517550 [PubMed - indexed for MEDLINE]

857: Eur Respir J. 2004 Nov;24(5):758-64.

Prevalence and rate of diagnosis of allergic rhinitis in Europe.

Bauchau V, Durham SR.

UCB Pharma SA, R&D, Clinical Epidemiology and Outcomes Research, Chemin du
Foriest, B-1420, Braine-l'Alleud, Belgium. vincent.bauchau@ucb-group.com

To measure the prevalence of allergic rhinitis among European adults and the
proportion of undiagnosed subjects, a two-step, cross-sectional, population-based
survey in Belgium, France, Germany, Italy, Spain, and the UK was undertaken. Step
one of the study involved screening for allergic rhinitis by telephone interview,
based on history of symptoms and/or self-awareness of the condition. Step two
undertook confirmation of allergic rhinitis in a subset of the subjects screened 
positive; this was performed by a clinical diagnosis conducted in three to five
clinical centres per country, including specific immunoglobulin E tests and a
disease-specific questionnaire. A total of 9,646 telephone interviews were
conducted between February and April 2001. Self-awareness of allergic rhinitis
was reported by 19% of the subjects. Physician-based diagnosis of allergic
rhinitis was reported by 13% of the subjects. In step two, 725 clinical
assessments were conducted between May and August 2001. A total of 411 of
patients, who underwent step two, had investigator-confirmed allergic rhinitis.
Among patients with investigator-confirmed allergic rhinitis, 45% had not
reported a previous diagnosis by a physician. Prevalence of subjects with
clinically confirmable allergic rhinitis estimated by combining step one and step
two data ranged from 17% in Italy to 29% in Belgium with an overall value of 23%.
This large-scale study confirms that allergic rhinitis has a high prevalence in
western Europe and is frequently undiagnosed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15516669 [PubMed - indexed for MEDLINE]

858: Eur Respir J. 2004 Nov;24(5):750-7.

Eosinophil degranulation status in allergic rhinitis: observations before and
during seasonal allergen exposure.

Ahlstrom-Emanuelsson CA, Greiff L, Andersson M, Persson CG, Erjefält JS.

Department of Otorhinolaryngology, Head and Neck Surgery, Lund University
Hospital, 221 84 Lund, Sweden.

Despite the fact that extensive degranulation is a likely prerequisite for a
pathogenic role of eosinophils, little is known about the degranulation status of
these cells in eosinophilic conditions. The present study of the ultrastructure
of tissue eosinophils explores eosinophil degranulation in allergic rhinitis
before and during seasonal allergen exposure. A total of 23 patients scored
symptoms q.d., prior to and during the pollen season. The numbers of mucosal
eosinophils and their degranulation status were determined in nasal biopsies.
Furthermore, nasal lavage fluid levels of eosinophil cationic protein (ECP) and
alpha2-macroglobulin were assessed as indices of eosinophil activity and plasma
exudation, respectively. Seasonal allergen exposure was associated with increased
nasal symptoms, increased lavage fluid levels of ECP and alpha2-macroglobulin,
and increased numbers of tissue eosinophils. In the tissue, transmission electron
microscopy revealed a moderate piecemeal degranulation already prior to the
season (mean+/-sd 37+/-2.7% altered granules). Seasonal allergen exposure
increased this degranulation (87+/-1.8%), and produced local areas with extensive
deposition of granule proteins. The degree of eosinophil degranulation correlated
with levels of ECP in lavage fluids obtained at histamine challenge. In
conclusion, this study demonstrated that the nasal mucosa in allergic rhinitis
features moderately degranulated eosinophils already at nonsymptomatic baseline
conditions. In association with the development of symptomatic seasonal allergic 
rhinitis, the tissue deposition of eosinophil granule proteins is dramatically
elevated through increased eosinophil numbers, together with markedly augmented
degranulation of individual cells.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15516668 [PubMed - indexed for MEDLINE]

859: Adv Ther. 2004 May-Jun;21(3):162-72.

Psychometric validation of a patient-reported sensory perception and preference
instrument: the Sensory Perceptions Questionnaire.

Lennox RD, Fowler I, Gore M, Jones MK, Pethick N, O'Dowd L.

Psychometric Technologies, Hillsborough, NC 27278, USA.

This study evaluated the psychometric properties of content validity, construct
validity, and test-retest reliability of a 23-item Sensory Perceptions
Questionnaire (SPQ) used to survey sensory perceptions of intranasal
corticosteroid sprays. Two patient cohorts (men and women aged > or =18 years who
had at least a 1-year history of allergic rhinitis and had been using a
corticosteroid nasal spray) were enrolled. The content validity and construct
validity of the SPQ questions were evaluated using a cognitive debriefing method 
after cohort 1 (n=15) completed the SPQ. Test-retest reliability (assessed with
intraclass correlation coefficients [ICCs] of the SPQ questions) was evaluated in
cohort 2 (n=50), after they answered a Web-based version of the SPQ on two
occasions, each separated by 7 days. In cohort 1, 7 of 15 patients believed all
relevant sensory perceptions were addressed in the questionnaire. Although 8
patients mentioned at least 1 sensory perception that was not addressed, only 4
sensory perceptions were mentioned by more than 1 patient, and none was mentioned
reliably by more than 2 patients. Those 4 sensory perceptions not addressed in
the SPQ were all intentionally excluded, because they were potential symptoms of 
rhinitis or adverse events associated with intranasal corticosteroid spray use.
Patients regarded the questions as straightforward, nonburdensome, and
nonthreatening, signs suggesting the questions were not likely to challenge the
construct validity of the SPQ. The responses to 2 questions (one in which
patients were asked to indicate whether they were pleased or displeased overall
with a particular spray; the other to indicate their overall product preference) 
were somewhat influenced by the effectiveness of the sprays. Results of
test-retest reliability (cohort 2) showed both high (>0.8) and low (<0.7) ICCs. A
high degree of correspondence between the 2 administrations produced a low
between-patient variance, which likely resulted in lower ICCs. The SPQ adequately
represents the sensory attributes reported by patients regarding intranasal
corticosteroid spray use and, overall, is a valid measure of patient preference
based on sensory perception.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15509132 [PubMed - indexed for MEDLINE]

860: Rev Panam Salud Publica. 2004 Sep;16(3):193-8.

Smoking at home is strongly associated with symptoms of asthma and rhinitis in
children of primary school age in Trinidad and Tobago.

Monteil MA, Joseph G, Chang Kit C, Wheeler G, Antoine RM.

University of the West Indies, Faculty of Medical Sciences-St. Augustine Campus, 
Champs Fleurs, Trinidad. mmonteil@tstt.net.tt

OBJECTIVE: To compare, in the twin-island republic of Trinidad and Tobago, the
prevalence of symptoms of asthma and rhinitis among children of primary school
age who are exposed to household environmental tobacco smoke with the prevalence 
of these symptoms in their colleagues without this exposure. METHODS: Between
September and December 2002, questionnaires based on the instrument developed for
the International Study of Asthma and Allergies in Childhood (ISAAC) were
distributed, via the children in their schools, to parents of 6,611 Year 2 pupils
(typically 6 years old) or Year 3 pupils (typically 7 years old) in 106 randomly 
selected schools in Trinidad and Tobago (5,511 pupils on Trinidad and 1,100
pupils on Tobago). We added to the standard ISAAC questionnaires two questions,
one on household smoking and one on the ethnicity of the children. RESULTS: A
total of 3 170 completed questionnaires were suitable for further analysis (2,618
from Trinidad and 552 from Tobago). On Trinidad 782 of the children (29.9%) lived
in homes where one or both parents smoked, and 513 (19.6%) had other relatives in
the household who smoked. On Tobago 94 of the pupils (17.0%) had parents who
smoked, and 84 (15.4%) came from homes where other residents smoked. Parental
smoking was significantly associated with wheezing (odds ratio (OR): 1.43; 95%
confidence interval (CI): 1.11-1.83), exercise-induced wheezing (OR: 2.12; 95%
CI: 1.59-2.82), nocturnal coughing (OR: 1.64; 95% CI: 1.37-1.97), and symptoms of
rhinitis (OR: 1.35; 95% CI: 1.10-1.65) in the last 12 months as well as a history
of hay fever/sinus problems (OR: 1.39; 95% CI: 1.11-1.74). Smoking in the home by
adult residents other than parents was also significantly associated with all of 
these symptoms as well as a history of asthma (OR: 1.49; 95% CI: 1.13-1.97). In
terms of ethnic differences, parental smoking was most prevalent in the homes of 
South Asian students, while smoking by other adults in the home occurred most
commonly in the households of pupils of mixed race. CONCLUSIONS: Even in Trinidad
and Tobago, which is a tropical environment where more time is spent outdoors and
homes have more open ventilation than in temperate climates, environmental
tobacco smoke exposure is closely associated with an increased prevalence of
symptoms of asthma and rhinitis in primary-school-aged children.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15507187 [PubMed - indexed for MEDLINE]

861: Allergy. 2004 Dec;59(12):1285-93.

A prospective, randomized, double-blind, placebo-controlled multi-centre study on
the efficacy and safety of sublingual immunotherapy (SLIT) in children with
seasonal allergic rhinoconjunctivitis to grass pollen.

Rolinck-Werninghaus C, Wolf H, Liebke C, Baars JC, Lange J, Kopp MV, Hammermann
J, Leupold W, Bartels P, Gruebl A, Bauer CP, Schnitker J, Wahn U, Niggemann B.

Department of Pediatric Pneumology and Immunology, Charitè, Berlin, Germany.

BACKGROUND: Especially in childhood, sublingual immunotherapy (SLIT) could offer 
advantages over subcutaneous therapy. However, limited data on its efficacy is
available. METHODS: In four German centres 97 children (age 3-14 years) with
allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective,
double-blind trial comparing SLIT (Pangramin SLIT; ALK-SCHERAX, 0.5 microg major 
allergens, three times per week, 32 months) with placebo. Primary endpoint was a 
multiple symptom-medication score for changes in seasonal diary entries between
the first and third year of the study (SLIT n=39; placebo n=38). RESULTS: The
multiple symptom-medication score was significantly reduced by SLIT to 77.3% of
the placebo group (P=0.0498). The subsequent analysis of the single endpoints did
not reveal significant differences for symptom scores in favour of SLIT (85.1% of
placebo group; P=0.22). However, the medication score improved significantly
(67.1% of placebo group; P=0.0025). Furthermore, secondary endpoints assessing in
vivo immune responses did not differ significantly between the groups. However,
retrospective analysis showed some inhomogeneity for clinical and in vitro
parameters at the beginning of the study. Allergic side effects with possible
relation to the study drug were reported in both groups (SLIT 49%, placebo 27%,
P=0.026). CONCLUSION: Our study indicates that SLIT had a positive effect on the 
reduction of a multiple symptom-medication score, mainly by significantly
reducing rescue medication use, but had no significant effect on symptoms alone
in children with rhinoconjunctivitis to grass pollen compared with a placebo.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 15507097 [PubMed - indexed for MEDLINE]

862: Am J Rhinol. 2004 Jul-Aug;18(4):227-32.

Pulmonary arterial pressure in children with allergic rhinitis.

Reisli I, Oran B, Baspinar O, Baysal T, Karaaslan S.

Department of Pediatrics, Meram Medical Faculty, University of Selcuk, Konya,
Turkey.

BACKGROUND: Chronic upper airway obstruction may lead to increased pulmonary
arterial pressure in childhood. Allergic rhinitis is one of the frequent causes
of upper airway obstruction by nasal blockage. The aims of the study were to
evaluate the pulmonary arterial pressures in children with allergic rhinitis and 
the effect of topical corticosteroid therapy. METHODS: Forty-nine children
composed of 27 subjects with seasonal and 22 subjects with perennial allergic
rhinitis were enrolled in this study. The pulmonary arterial pressures were
measured by using Doppler echocardiography. RESULTS: The pretreatment pulmonary
arterial systolic, mean, and diastolic pressures of study group were
significantly higher than in healthy controls (p < 0.05). The pulmonary arterial 
systolic and mean pressures of the patient group significantly decreased at the
end of study (p < 0.05), whereas the decrease of the diastolic pressure was not
statistically significant (p > 0.05) after the treatment of a topical
corticosteroid, mometasone furoate (100 microg per day), for 8 weeks. CONCLUSION:
Our results showed that children with allergic rhinitis have higher pulmonary
arterial pressure levels compared with healthy controls and that increased
pulmonary arterial pressure levels due to allergic rhinitis are reversible by
using nasal topical corticosteroids. Further studies are needed to determine the 
clinical aspect of increased pulmonary arterial pressure.

PMID: 15490569 [PubMed - indexed for MEDLINE]

863: Ital J Anat Embryol. 2004 Apr-Jun;109(2):115-22.

Interferon-alpha affects the tumour necrosis factor-alpha content of mast cells
in human nasal mucosa. A pilot study in allergic patients.

Riccardi-Arbi R, Bacci S, Romagnoli P, Rucci L.

Department of Anatomy, Histology, and Forensic Medicine, Sect. E. Allara,
University of Florence, Italy.

Human nasal mucosal mast cells contain and secrete tumour necrosis factor
(TNF)-alpha, which in turn can stimulate histamine secretion by these cells.
Interferon (IFN)-alpha can inhibit TNF-alpha secretion by mast cells in vitro. We
have addressed the interrelationships between IFN-alpha and the content in
TNF-alpha and number of mast cells in vivo, in the human nasal mucosa. Biopsies
were taken from two healthy control patients, two allergic patients and two more 
allergic patients treated topically with IFN-alpha for two weeks; biopsies from
the last two patients were taken both before and after stimulation with the
specific allergen. Mast cells were counted upon tagging with rhodaminated avidin 
and by indirect immunofluorescence for TNF-alpha. Data were subjected to analysis
of variance. Mast cell numbers were significantly lower in all allergic patients 
than in controls (P<0.001). Upon IFN-alpha treatment, TNF-alpha positive mast
cells were less than in allergic, untreated patients and the opposite was true
for TNF-alpha negative mast cells (p<0.05). Allergen challenge caused selective, 
significant decrease only in the number of TNF-alpha negative mast cells
(p<0.05). The results suggest that upon topical IFN-alpha treatment: (1) mast
cells stores of TNF-alpha in the nasal mucosa of allergic patients are decreased;
and (2) only TNF-alpha negative cells degranulate in response to allergen
challenge. Therefore, one may expect that such a treatment reduces the TNF-alpha 
burden to the mucosa in these patients.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15481160 [PubMed - indexed for MEDLINE]

864: J Allergy Clin Immunol. 2004 Oct;114(4):851-7.

Comment in:
    Evid Based Nurs. 2005 Apr;8(2):44.

Coseasonal sublingual immunotherapy reduces the development of asthma in children
with allergic rhinoconjunctivitis.

Novembre E, Galli E, Landi F, Caffarelli C, Pifferi M, De Marco E, Burastero SE, 
Calori G, Benetti L, Bonazza P, Puccinelli P, Parmiani S, Bernardini R, Vierucci 
A.

Research Centre, Hospital "San Pietro Fatebenefratelli," AFaR, Rome.

BACKGROUND: We wondered whether short-term coseasonal sublingual immunotherapy
(SLIT) can reduce the development of asthma in children with hay fever in an open
randomized study. OBJECTIVE: We sought to determine whether SLIT is as effective 
as subcutaneous immunotherapy in reducing hay fever symptoms and the development 
of asthma in children with hay fever. METHODS: One hundred thirteen children aged
5 to 14 years (mean age, 7.7 years) with hay fever limited to grass pollen and no
other clinically important allergies were randomized in an open study involving 6
Italian pediatric allergy centers to receive specific SLIT for 3 years or
standard symptomatic therapy. All of the subjects had hay fever symptoms, but at 
the time of study entry, none reported seasonal asthma with more than 3 episodes 
per season. Symptomatic treatment was limited to cetirizine, loratadine, nasal
budesonide, and salbutamol on demand. The hay fever and asthma symptoms were
quantified clinically. RESULTS: The actively treated children used less
medication in the second and third years of therapy, and their symptom scores
tended to be lower. From the second year of immunotherapy, subjective evaluation 
of overall allergy symptoms was favorable in the actively treated children.
Development of asthma after 3 years was 3.8 times more frequent (95% confidence
limits, 1.5-10.0) in the control subjects. CONCLUSIONS: Three years of coseasonal
SLIT improves seasonal allergic rhinitis symptoms and reduces the development of 
seasonal asthma in children with hay fever.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 15480326 [PubMed - indexed for MEDLINE]

865: J Allergy Clin Immunol. 2004 Oct;114(4):838-44.

Levocetirizine improves quality of life and reduces costs in long-term management
of persistent allergic rhinitis.

Bachert C, Bousquet J, Canonica GW, Durham SR, Klimek L, Mullol J, Van
Cauwenberge PB, Van Hammée G; XPERT Study Group.

Department of Oto-Rhino-Laryngology, University Hospital, Ghent, Belgium.
Claus.Bachert@ugent.be

BACKGROUND: Allergic Rhinitis and its Impact on Asthma in collaboration with the 
World Health Organization initiative reclassified allergic rhinitis, like asthma,
by duration and severity. The Xyzal in Persistent Rhinitis Trial is the first
large, long-term clinical trial studying patients with persistent rhinitis as
defined by Allergic Rhinitis and its Impact on Asthma. OBJECTIVES: Two primary
objectives were defined: comparison of the Rhinoconjunctivitis Quality of Life
Questionnaire overall score and Total 5 Symptoms Score (rhinorrhea, sneezing,
nasal congestion, and nasal and ocular pruritus) over a period of 4 weeks between
levocetirizine 5 mg and placebo. Secondary endpoints included similar evaluations
at 1 week and 3, 4.5, and 6 months, summary scores for a general health status
questionnaire (Medical Outcomes Survey Short Form 36), a pharmacoeconomic
assessment, comorbidities, and a safety evaluation. METHODS: The Xyzal in
Persistent Rhinitis Trial was a 6-month double-blind, placebo-controlled,
multicenter, multinational trial in 551 patients. Adults with persistent rhinitis
sensitized to both grass pollen and house dust mite were randomized to receive
levocetirizine 5 mg/d or placebo. RESULTS: A total of 421 patients completed the 
full study. Levocetirizine significantly improved both the Rhinoconjunctivitis
Quality of Life Questionnaire overall score and the Total 5 Symptoms Score from
week 1 to 6 months (all P values <.001). Medical Outcomes Survey Short Form 36
summary scores were also improved in the levocetirizine group compared with the
placebo group. Treatment cessation because of lack of effect, comorbidities, and 
overall costs of disease, and comorbidities per working patient per month (160.27
vs 108.18) were lower in the levocetirizine group. CONCLUSION: Levocetirizine was
shown to improve quality of life and symptoms and to decrease the overall costs
of the disease over the 6-month treatment period.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15480324 [PubMed - indexed for MEDLINE]

866: J Allergy Clin Immunol. 2004 Oct;114(4):831-7.

Randomized controlled trial of high-dose sublingual immunotherapy to treat
seasonal allergic rhinitis.

Smith H, White P, Annila I, Poole J, Andre C, Frew A.

Wessex Research Network, Primary Medical Care, University of Southampton, United 
Kingdom.

BACKGROUND: Seasonal allergic rhinitis is common and troublesome. Sublingual
immunotherapy (SLIT) has been proposed as an alternative to injection
immunotherapy and might offer some advantages if it were effective and practical 
in a community setting. OBJECTIVES: To assess the efficacy and side-effect
profile of SLIT in patients with summer hay fever uncontrolled on current
standard medication. To assess the feasibility of delivering SLIT in a United
Kingdom general practice setting. METHODS: Double-blind, placebo-controlled study
in 186 patients with severe summer hay fever identified from 16 United Kingdom
general practices. After a baseline year to ensure balanced groups, subjects were
randomized, and SLIT was given for 1 or 2 years and compared with placebo. The
principal outcome measure was symptoms as recorded on diary cards. Secondary
criteria were skin and conjunctival reactivity, allergen-specific IgE and IgG 4 ,
and the frequency and severity of adverse effects. RESULTS: One hundred
thirty-six subjects completed the study. After 1 year, no significant differences
were found between actively treated subjects and the placebo group. After the
second year of therapy, subjects who had received 2 years treatment were 6.8
times more likely to show a reduction in nose running (P <.001) and 2.4 times
more likely to have reduced sneezing (P <.05) compared with subjects in the
placebo group. Benefits for nasal blockage were found at the peak pollen season
and were similar in both actively treated groups. CONCLUSION: Sublingual
immunotherapy can be given successfully and safely in the community. High-dose
SLIT has beneficial effects on nasal symptoms during the peak pollen season in
patients with severe seasonal allergic rhinitis. At least 2 years of treatment
with SLIT is required to show a benefit.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15480323 [PubMed - indexed for MEDLINE]

867: Clin Exp Allergy. 2004 Oct;34(10):1649-54.

Desloratadine partially inhibits the augmented bacterial responses in the sinuses
of allergic and infected mice.

Kirtsreesakul V, Blair C, Yu X, Thompson K, Naclerio RM.

Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, The
University of Chicago, Chicago, IL 60637, USA.

BACKGROUND: Allergic rhinitis (AR) is considered a major predisposing factor for 
the development of acute bacterial rhinosinusitis. How AR augments a bacterial
infection is unknown. OBJECTIVE: Our purpose in this study was to test whether an
H1 receptor antagonist, desloratadine, could reduce the augmented effect of an
ongoing allergic reaction on acute bacterial rhinosinusitis. METHODS: Three
groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected
and allergic mice treated with desloratadine, (2) infected and allergic mice
treated with placebo, and (3) infected mice. A fourth group of uninfected,
non-sensitized mice served as a control for the cellular changes. BALB/c mice
were sensitized by two intraperitoneal injections of OVA given 8 days apart. One 
day after the second injection, the mice were nasally exposed daily to 6% OVA
(the groups treated with desloratadine or placebo) or phosphate-buffered saline
(PBS) (the infection-only group) for 5 days. After the second OVA exposure, the
mice were intranasally inoculated with Streptococcus pneumoniae. Desloratadine or
placebo was given daily throughout the OVA exposure period. Nasal allergic
symptoms were observed by counting of nasal rubbing and sneezing for 10 min after
OVA or PBS nasal challenge. On day 5 post-infection, nasal lavage culture was
done, and the inflammatory cells in the sinuses were evaluated by flow cytometry.
RESULTS: Mice that were made allergic, infected, and treated with placebo showed 
more organisms and phagocytes than did only infect mice. They also manifested
allergic nasal symptoms and eosinophil influx into the sinuses. Desloratadine
treatment during allergen exposure reduced allergic symptoms and reduced
sinonasal infection (P<0.05). There tended to be less myeloid cell and neutrophil
influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in
the placebo-treated group. CONCLUSION: Desloratadine treatment during nasal
challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting
that histamine via an H1 receptor plays a role in the augmented infection in mice
with an ongoing allergic reaction.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15479283 [PubMed - indexed for MEDLINE]

868: Ann Allergy Asthma Immunol. 2004 Sep;93(3):259-64.

Comparison of objective and subjective measurements of cough frequency in
patients with seasonal allergic rhinitis.

Krahnke J, Gentile D, Angelini B, Danzig M, Skoner D.

Department of Pediatrics, Allegheny General Hospital, Pittsburgh, Pennsylvania
15212, USA.

BACKGROUND: Cough is a frequent complaint of patients with a variety of
respiratory disorders, including seasonal allergic rhinitis (SAR), and it is
often evaluated subjectively to determine disease status and response to
treatment. However, it is not known whether subjective reports of cough from
patients with SAR are accurate. OBJECTIVE: To compare a novel objective
measurement with subjective reports of cough frequency in a subset of 28 patients
(aged > or = 12 years) with active SAR who were enrolled in a large, multicenter 
trial examining the efficacy of an active treatment for SAR. METHODS: In this
supplemental pilot study, subjective data were collected on a diary card and
objective data were collected using home-based telemetry. Three 24-hour recording
sessions were conducted with each patient: 2 consecutive baseline sessions (day 1
and day 2) and 1 session after randomization to placebo or active cough treatment
(day 3). RESULTS: Strong correlations existed between cough frequency data for
days 1 and 2 (Spearman correlation coefficient = 0.91; P < .001) and between
subjective and objective data for days 1, 2, and 3 (daytime greater than
nighttime) (Spearman correlation coefficient = 0.51; P < .001). CONCLUSION: These
results have implications for the design and interpretation of results from
clinical trials that evaluate cough frequency as a treatment outcome.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15478386 [PubMed - indexed for MEDLINE]

869: Curr Allergy Asthma Rep. 2004 Nov;4(6):439-46.

Evidence-based strategies for treatment of allergic rhinitis.

Portnoy JM, Van Osdol T, Williams PB.

Section of Allergy, Asthma, and Immunology, Children's Mercy Hospital, 2401
Gillham Road, Kansas City, MO 64108, USA. jportnoy@cmh.edu

In this review, an evidence-based medicine approach to diagnosis and treatment
for allergic rhinitis is reviewed. We performed a search of the medical
literature for randomized, placebo-controlled trials of nonsedating
antihistamines, intranasal corticosteroids, montelukast, azelastine, allergen
immunotherapy, and anti-IgE. The mean numbers needed to treat were: nonsedating
antihistamines--15.2; nasal corticosteroids--4.4; montelukast--14.3;
azelastine--5.0; allergen immunotherapy--4.6; and anti-IgE--12.4. Treatment
thresholds for use were: antihistamines--23%; nasal corticosteroids--8%;
azelastine--16%; montelukast--8%; anti-IgE--50%; and immunotherapy--25%. When
used appropriately, this information could become very useful for clinicians,
particularly if cost, convenience, and other indirect factors can be included.

Publication Types: 
    Review

PMID: 15462709 [PubMed - indexed for MEDLINE]

870: Curr Med Res Opin. 2004 Oct;20(10):1549-58.

The effect of montelukast on rhinitis symptoms in patients with asthma and
seasonal allergic rhinitis.

Philip G, Nayak AS, Berger WE, Leynadier F, Vrijens F, Dass SB, Reiss TF.

Merck Research Laboratories, Rahway, NJ, USA.

OBJECTIVE: The objective of this study was to evaluate montelukast 10 mg daily as
treatment for allergic rhinitis in patients with symptomatic allergic rhinitis
and active asthma during the allergy season. METHODS: This was a multicenter
study of 831 patients (ages 15 years-85 years) with seasonal allergen
sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma.
Following a single-blind, placebo run-in period of 3 days-5 days, patients were
randomized to oral montelukast 10 mg (n = 415) or placebo (n = 416) daily during 
the 2-week, double-blind, active-treatment period. MAIN OUTCOME MEASURES: The
primary endpoint was Daily Rhinitis Symptoms score, average of Daytime Nasal
Symptoms and Nighttime Symptoms, as self-rated by patients on a 0-3 scale on
daily diaries. RESULTS: Montelukast reduced the Daily Rhinitis Symptoms score:
difference between montelukast and placebo in mean change from baseline was -0.12
[95% CI -0.18, -0.06; p < or = 0.001]. Similar improvements were seen in Daytime 
Nasal Symptoms (-0.14 [-0.21, -0.07; p < or = 0.001]) and Nighttime Symptoms
(-0.10 [-0.16, -0.04; p < or = 0.001]). Improvements (p < 0.05) were seen in
Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AR
by Patient and by Physician, and Rhinoconjunctivitis Quality of Life. In
exploratory analyses, improvement in rhinitis symptoms was numerically (though
not statistically) larger in patients with greater levels of asthma at study
start. Montelukast provided benefit in the Global Evaluations of Asthma by
Patient and by Physician: mean differences were -0.24 [-0.41, -0.06; p = 0.008]
and -0.17 [-0.33, -0.01; p = 0.037]. Similarly, as-needed beta-agonist use
(puffs/day) was reduced with montelukast (p < or = 0.005). CONCLUSION:
Montelukast provides significant relief from symptoms of seasonal allergic
rhinitis, while also conferring a benefit for asthma, in patients with both
allergic rhinitis and asthma.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15462688 [PubMed - indexed for MEDLINE]

871: Allergy. 2004 Nov;59(11):1224-8.

Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in
allergic rhinitis.

Polosa R, Li Gotti F, Mangano G, Paolino G, Mastruzzo C, Vancheri C, Lisitano N, 
Crimi N.

Istituto di Malattie Apparato Respiratorio, University of Catania, Catania,
Italy.

BACKGROUND: Bronchial hyperresponsiveness (BHR) and airway inflammation are
frequently associated with allergic rhinitis, and may be important risk factors
for the development of asthma. Specific immunotherapy (SIT) reduces symptom in
subjects with allergic rhinitis, but the mechanisms are not clear. AIMS OF THE
STUDY: To assess the effect of Parietaria-SIT on asthma progression, rhinitic
symptoms, BHR, and eosinophilic inflammation. METHODS: Nonasthmatic subjects with
seasonal rhinitis were randomly assigned to receive Parietaria pollen vaccine (n 
= 15) or matched placebo (n = 15). Data on symptoms and medication score, BHR to 
methacholine, eosinophilia in sputum were collected throughout the 3-year study. 
RESULTS: By the end of the study, in the placebo group, symptoms and medication
scores significantly increased by a median (interquartile range) of 121% (15-280)
and 263% (0-4400) respectively (P < 0.01), whereas no significant difference was 
observed in the SIT group. We found no significant changes in sputum eosinophils 
and BHR to methacholine in both groups throughout the study. Nine of 29
participants developed asthma symptoms during the study; of these, only two
subjects (14%) in the SIT-treated group (P = 0.056). CONCLUSIONS: Parietaria-SIT 
reduces symptom and rescue medication scores, but no changes in BHR to
methacholine or sputum eosinophilia were observed. Moreover, Parietaria-SIT
appears to prevent the natural progression of allergic rhinitis to asthma,
suggesting that SIT should be considered earlier in the management of subjects
with allergic rhinitis. Copyright 2004 Blackwell Munksgaard

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15461606 [PubMed - indexed for MEDLINE]

872: Allergol Immunopathol (Madr). 2004 Sep-Oct;32(5):271-7.

Tolerance and short-term effect of a cluster schedule with pollen-extracts
quantified in mass-units.

Guardia P, Moreno C, Justicia JL, Conde J, Cimarra M, Díaz M, Guerra F,
Martínez-Cócera C, Gonzalo-Garijo MA, Pérez-Calderón R, González-Quevedo T,
Sánchez-Cano M, Vigaray J, Acero S, Blanco R, Martín S, de la Torre F.

Hospital Clínico Universitario Virgen Macarena, Seville, Spain.

We performed a prospective, multicenter study to assess the tolerance and
possible short-term effects of allergen vaccines administered according to a
cluster schedule in the months immediately preceding the onset of the pollen
season.The study was carried out in eight centers and included 191 patients
(children and adults) with allergic respiratory disease due to sensitization to
olive tree and/or grass pollen. Of these, 34 patients acted as controls and the
remaining patients received immunotherapy administered in the initiation phase
according to a cluster schedule of eight doses injected on four visits. After 3
months of treatment, significant differences were found between the two groups in
medication consumption (antihistamines in drops and oral formulations: p = 0.045 
and p = 0.001, respectively; short-acting beta2-agonist treatments: p = 0.004)
and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014,
respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon 
[IFN-gamma], and tumor necrosis factor [TNF-alpha]) was determined before the
start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5
and 10 (Th2 profile) decreased while those of IL-2, IFN-gamma, and TNF-alpha (Th1
profile) decreased. These differences were more marked in the active group than
in the control group but were not statistically significant. No severe adverse
effects were recorded. This study shows that the schedule tested had an
acceptable tolerance profile and produced significant changes in symptom and
medication scores after a few months of treatment. A double-blind,
placebo-controlled study is needed to confirm these results.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Multicenter Study

PMID: 15456623 [PubMed - indexed for MEDLINE]

873: Arch Dis Child. 2004 Oct;89(10):917-21.

Association of parental eczema, hayfever, and asthma with atopic dermatitis in
infancy: birth cohort study.

Wadonda-Kabondo N, Sterne JA, Golding J, Kennedy CT, Archer CB, Dunnill MG;
ALSPAC Study Team.

Department of Child Health, University of Bristol, Bristol, UK.

OBJECTIVE: To evaluate the association of parental history of atopic disease with
childhood atopic dermatitis, and to examine the relative strength of associations
with maternal and paternal disease. DESIGN: Mothers were recruited to the Avon
longitudinal study of parents and children (ALSPAC) from the eighth week of
pregnancy. Before parturition, both parents were asked, separately, to report
their lifetime history of eczema, asthma, and hayfever. Parents reported symptoms
of atopic dermatitis in their children at ages 6, 18, 30, and 42 months. RESULTS:
Of 8530 children with complete information on rash at ages 6, 18, 30, and 42
months, 7969 had complete information on maternal atopic disease and 5658 on
maternal and paternal atopic disease. There was a strong association between
parental eczema and childhood atopic dermatitis: odds ratio 1.69 (95% confidence 
interval, 1.47 to 1.95) for maternal eczema only, 1.74 (1.44 to 2.09) for
paternal eczema only, and 2.72 (2.09 to 3.53) for eczema in both parents.
Associations with parental asthma or hayfever were attenuated after controlling
for parental eczema. There was no evidence that associations with maternal atopy 
were stronger than with paternal. CONCLUSIONS: Associations between parents'
atopic disease and the risk of atopic dermatitis in offspring vary according to
the type of atopic disease in the parents, but not according to parental sex.
These results are at variance with previous studies reporting stronger
associations with maternal than paternal atopy, and suggest that there is no
"parent-of-origin" effect in atopic dermatitis. Parental eczema may be a better
marker than parental asthma/hayfever in predisposing to childhood eczema.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15383434 [PubMed - indexed for MEDLINE]

874: Drugs Exp Clin Res. 2004;30(3):99-109.

Antioxidant properties of Aller-7, a novel polyherbal formulation for allergic
rhinitis.

D'Souza P, Amit A, Saxena VS, Bagchi D, Bagchi M, Stohs SJ.

Natural Remedies Research Center, Bangalore, India.

Allergic rhinitis, a frequently occurring immunological disorder affecting men,
women and children worldwide, is a state of hypersensitivity that occurs when the
body overreacts to a substance such as pollen, mold, mites or dust. Allergic
rhinitis exerts inflammatory response and irritation of the nasal mucosal
membranes leading to sneezing; stuffy/runny nose; nasal congestion; and itchy,
watery and swollen eyes. A novel, safe polyherbal formulation (Aller-7/NR-A2) has
been developed for the treatment of allergic rhinitis using a unique combination 
of extracts from seven medicinal plants including Phyllanthus emblica, Terminalia
chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale
and Piper longum. In this study, the antioxidant efficacy of Aller-7 was
investigated by various assays including hydroxyl radical scavenging assay,
superoxide anion scavenging assay, 1,1-diphenyl-2-picryl hydrazyl (DPPH) and
2,2-azinobis-ethyl-benzothiozoline-sulphonic acid diammonium salt (ABTS) radical 
scavenging assays. The protective effect of Aller-7 on free radical-induced lysis
of red blood cells and inhibition of nitric oxide release by Aller-7 in
lipopolysaccharide-stimulated murine macrophages were determined. Aller-7
exhibited concentration-dependent scavenging activities toward biochemically
generated hydroxyl radicals (IC50 741.73 microg/ml); superoxide anion (IC50 24.65
microg/ml by phenazine methosulfate-nicotinamide adenine dinucleotide [PMS-NADH] 
assay and IC50 4.27 microg/ml by riboflavin/nitroblue tetrazolium [NBT] light
assay), nitric oxide (IC50 16.34 microg/ml); 1,1-diphenyl-2-picryl hydrazyl
(DPPH) radical (IC50 5.62 microg/ml); and
2,2-azinobis-ethyl-benzothiozoline-sulphonic acid diammonium salt (ABTS) radical 
(IC50 7.35 microg/ml). Aller-7 inhibited free radical-induced hemolysis in the
concentration range of 20-80 microg/ml. Aller-7 also significantly inhibited
nitric oxide release from lipopolysaccharide-stimulated murine macrophages. These
results demonstrate that Aller-7 is a potent scavenger of free radicals and that 
it may serve.

Publication Types: 
    Comparative Study

PMID: 15366786 [PubMed - indexed for MEDLINE]

875: Otolaryngol Head Neck Surg. 2004 Sep;131(3):225-31.

Evaluation of patients' preferences for triamcinolone acetonide aqueous,
fluticasone propionate, and mometasone furoate nasal sprays in patients with
allergic rhinitis.

Stokes M, Amorosi SL, Thompson D, Dupclay L, Garcia J, Georges G.

Innovus Research Inc., Medford, MA, USA.

OBJECTIVE: To compare product attributes, preferences, and expected compliance
associated with triamcinolone acetonide aqueous (TAA-AQ), fluticasone propionate 
(FP), and mometasone furoate (MF) nasal sprays in patients with allergic
rhinitis. STUDY DESIGN AND SETTING: Data from 2 randomized, double-blind
crossover studies with identical design were pooled (N = 215). Patients completed
a 14-item sensory attributes questionnaire immediately after each product, and
stated their preference and expected compliance with a prescription after
receiving all products. RESULTS: Compared with FP and MF, TAA-AQ was associated
with significantly less odor and greater liking of odor ( P < 0.001); and less
taste, less dryness of nose/throat, less aftertaste, and greater overall liking (
P < 0.05). Significantly more patients preferred most a prescription of TAA-AQ
(50.0%) versus FP (25.0%; P < 0.001) and MF (25.0%; P < 0.001), and would
"definitely comply" with TAA-AQ (62.5%) versus FP (49.0%; P < 0.01) and MF
(51.0%; P < 0.01). CONCLUSION: TAA-AQ was associated with significantly more
positive sensory attributes, higher preference, and better expected compliance
than FP and MF. SIGNIFICANCE: Patients' preferences for the sensory attributes of
an intranasal corticosteroid may affect adherence to treatment.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15365540 [PubMed - indexed for MEDLINE]

876: Pharmacoeconomics. 2004;22(14):929-42.

Cost-benefit analysis of first-generation antihistamines in the treatment of
allergic rhinitis.

Sullivan PW, Follin SL, Nichol MB.

Pharmaceutical Outcomes Research Program, University of Colorado School of
Pharmacy, Denver, Colorado 80262, USA. Patrick.Sullivan@UCHSC.edu

BACKGROUND: The majority of individuals with allergic rhinitis in the US take
first-generation antihistamines (FGAs). Although FGAs have been proven effective 
in alleviating allergic rhinitis symptoms, they have been associated with an
increased risk of motor vehicle, aviation and occupational injuries and deaths,
reduced productivity and impaired learning. OBJECTIVE: The objective of this
analysis was to quantify the total costs and benefits of FGA use in the US from
the societal perspective. METHODS: We used a decision-analytic model to quantify 
the annual societal costs and benefits of treatment with FGAs compared with the
hypothetical alternative of no treatment for the population of individuals with
allergic rhinitis and taking FGAs in the US in 2001. The benefit associated with 
FGA use was estimated using the willingness-to-pay framework and projected to the
US population using published estimates of the prevalence of allergic rhinitis.
The costs of FGA-associated sedation included lost productivity and the direct
and indirect cost of unintentional injuries (including motor vehicle,
occupational, public and home injuries and fatalities). The incidence of injuries
and fatalities associated with FGA use was estimated using the risk of injury
attributable to the sedentary effects of FGAs in the allergic rhinitis
population. To evaluate uncertainty in the model assumptions, a probabilistic
sensitivity analysis was conducted using Bayesian second-order Monte Carlo
simulation. Costs and benefits are expressed in 2001 US dollars, using a 3%
discount rate. RESULTS: Based on current utilisation, the total societal benefit 
(95% credible interval) associated with the use of FGAs for the treatment of
allergic rhinitis was US 7.7 billion dollars (US 1.3 billion dollars to US 21
billion dollars). The societal cost of purchasing FGAs was only US 697 million
dollars. However, the societal cost of FGA-associated sedation was US 11.3
billion dollars (US 2.4 billion dollars to US 50.8 billion dollars). The annual
societal net benefit of FGA use for the treatment of allergic rhinitis in the US 
was -US4.2 billion dollars (-US 36 billion dollars to +US 0.296 billion dollars).
The net benefit was negative in 97% of the 10,000 Monte Carlo simulations.
CONCLUSIONS: The societal benefits of FGA use in alleviating the symptoms of
allergic rhinitis are significant. However, based on the assumptions, probability
distributions and parameter estimate ranges used in the current model, it is very
likely that the costs associated with sedation exceed the benefits of FGA use in 
the US. The cost of FGA-associated sedation is comparable to estimates of the
cost of all medical care expenditures on respiratory conditions in the US (US
12.1 billion dollars to US 31.3 billion dollars) [1996 values] and provides
compelling evidence of the economic burden of sedation associated with FGA use.

Publication Types: 
    Comparative Study

PMID: 15362929 [PubMed - indexed for MEDLINE]

877: Allergy. 2004 Oct;59(10):1063-7.

The association of hepatitis A and Helicobacter pylori with sensitization to
common allergens, asthma and hay fever in a population of young British adults.

Jarvis D, Luczynska C, Chinn S, Burney P.

Department of Public Health Sciences, Kings College London (Guys' Campus),
London, UK.

BACKGROUND: A negative association of oro-faecally spread infection with
serological markers of sensitization and allergic disease has been reported.
METHOD: Previous infection with hepatitis A and Helicobacter pylori was assessed 
in a community-based sample of young British adults and associations with
serum-specific IgE to environmental allergens, asthma-like symptoms and hay fever
were examined. RESULTS: There was no association of previous infection with
hepatitis A or H. pylori with wheeze or hay fever. There was no evidence of an
association of infection with either agent and sensitization except for the
isolated finding of a lower prevalence of sensitization to grass in those with
IgG antibodies to H. pylori (OR 0.65, 95% CI 0.43-0.99). This association did not
explain the negative association of family size with sensitization to grass.
CONCLUSION: In this population, there was no evidence that infection with
hepatitis A or H. pylori was associated with lower levels of IgE sensitization,
asthma or hay fever except for an isolated finding of a negative association of
H. pylori infection with sensitization to grass.

PMID: 15355464 [PubMed - indexed for MEDLINE]

878: Clin Exp Allergy. 2004 Sep;34(9):1438-43.

Comment in:
    Clin Exp Allergy. 2004 Sep;34(9):1333-5.

A survey of the quality of information leaflets on hayfever available from
general practices and community pharmacies.

White P, Smith H, Webley F, Frew A.

Nightingale Surgery, Romsey, UK.

BACKGROUND: Hayfever affects at least one in 10 people. The majority of hayfever 
is managed in the community setting where the management options are
pharmaceutical and behavioural. Hayfever medications are available over the
counter and on prescription from the general practitioner. Patient information
leaflets are published to augment the advice given and to promote
self-management, but these leaflets have rarely been subjected to critical
review. OBJECTIVE: To assess the quality of patient information leaflets written 
for people with hayfever and available from general practices and from community 
pharmacists. METHOD: A structured review of patient information leaflets about
hayfever. During the peak grass pollen season copies of all leaflets available
were collected from a random sample of community pharmacists and general
practices in Wessex. The characteristics of the leaflet were recorded and the
contents and presentation of each one was reviewed using the British Medical
Association patient information appraisal system. Readability was assessed using 
the Simple Measure of Gobbledegook (SMOG). Two allergy-accredited specialists
assessed each leaflet for accuracy. RESULTS: During the peak pollen season no
leaflets were available in 30% of the Community Pharmacists and 23% general
practices. In total, 38 different leaflets were identified. All the leaflets
reviewed were written for adults. Forty-seven percent of the leaflets had no
publication date and one-third of those dated were at least 5 years old. In
general the leaflets scored highly on issues of presentation, but less than half 
contained information on the full range of management and treatment options, many
being biased towards a single or limited range of interventions. Seventy-nine
percent leaflets were produced or sponsored by pharmaceutical companies and gave 
prominence to their own products. All the leaflets had readability scores
requiring at least secondary education (SMOG score equal or greater than 9). At
least one factual inaccuracy was identified in four-fifths of leaflets.
CONCLUSION: A large number of leaflets are published for people with hayfever,
but they are of variable quality and not accessible to all patients because of
limited distribution or high readability scores. If all patients are to benefit
from written information the authors and publishers of leaflets need to follow
published recommendations, especially with respect to content and readability. In
the absence of a national public health information strategy or a body that
systematically vets patient information materials, clinicians must pay attention 
to the quality of information provided for or obtained elsewhere by their
patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15347378 [PubMed - indexed for MEDLINE]

879: Clin Exp Allergy. 2004 Sep;34(9):1415-21.

Prevalence of sensitization to Artemisia allergens Art v 1, Art v 3 and Art v 60 
kDa. Cross-reactivity among Art v 3 and other relevant lipid-transfer protein
allergens.

Lombardero M, García-Sellés FJ, Polo F, Jimeno L, Chamorro MJ, García-Casado G,
Sánchez-Monge R, Díaz-Perales A, Salcedo G, Barber D.

Dept. I+D, ALK-Abelló SA, Madrid, Spain. manuel.lombardero@es.alk-abello.com

BACKGROUND: Artemisia vulgaris is a widespread weed in the Mediterranean area and
several allergens have been detected in its pollen. One of them, Art v 3, belongs
to the lipid-transfer protein (LTP) family and its prevalence in
Artemisia-sensitized patients or its relationship with other LTP allergens is not
clear. OBJECTIVE: To assess the pattern of sensitization to an array of mugwort
allergens in a Mediterranean population, and to study the cross-reactivity of Art
v 3 with Pru p 3 and Par j 1, relevant LTP allergens in the area. METHODS: Skin
prick test was performed with whole extracts (A. vulgaris, Parietaria judaica and
peach) and pure natural allergens Art v 1, Art v 3, Art v 60 kDa and Par j 1 in
24 mugwort-allergic patients from a Mediterranean area. In vitro assays included 
measurement of specific IgE and ELISA inhibition among LTP allergens. RESULTS:
The three Artemisia allergens elicited a positive skin response in 70-80% of the 
patients. Seven patients were clearly sensitized to Par j 1 and 11 to Pru p 3.
There was no correlation between Par j 1 and Pru p 3 sensitization, but a highly 
significant correlation was found between peach extract and Art v 3 as regards
the skin response. No IgE cross-reactivity was observed between Art v 3/Par j 1
or Pru p 3/Par j 1. In contrast, Art v 3 significantly inhibited the binding to
Pru p 3 of IgE from three patients' sera out of six studied, but Pru p 3 was not 
able to inhibit the IgE binding to Art v 3. CONCLUSION: Art v 3 is a major
mugwort allergen and in some patients with IgE to both Art v 3 and Pru p 3, Art v
3 behaves as the primary sensitizing agent.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15347375 [PubMed - indexed for MEDLINE]

880: Clin Exp Allergy. 2004 Sep;34(9):1373-8.

Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated
human peripheral blood mononuclear cells.

Wilcock LK, Francis JN, Durham SR.

Upper Respiratory Medicine, Imperial College, National Heart and Lung Institute, 
London, UK.

BACKGROUND: Aluminium hydroxide (alum) is a commonly used adjuvant for specific
immunotherapy of allergic diseases. While alum is traditionally associated with
murine Th2 sensitization, little is known about its effects on secondary allergic
responses in humans. METHODS: We investigated the in vitro effects of alum on
peripheral blood mononuclear cells (PBMC) from atopic donors. PBMC from 18 grass 
pollen-sensitive rhinitic subjects were stimulated with Phleum pratense (Phl p)
in the presence or absence of alum. After 6 days culture, cytokine production was
measured by ELISA and T cell proliferation by radiolabelled thymidine
incorporation. The effect of alum on the expression of human leucocyte antigen
and CD80/CD86 on cultured antigen-presenting cells was assessed by flow
cytometry. RESULTS: PBMC cultured with Phl p and alum showed a significant
decrease in both IL-5 and IL-13 production compared with allergen alone (P<0.005 
and P<0.001, respectively), but no change in IFN-gamma or IL-12 production or
proliferative responses. These alum-induced changes in T helper (Th)2 cytokine
production were unaffected by the addition of neutralizing antibodies to IL-4 or 
IL-12. Culture of PBMC with alum induced increased expression of CD86 (P=0.004)
and HLA (P=0.01) on monocytes while the expression of CD80 was decreased
(P=0.02). SUMMARY: Alum down-regulates allergen-driven Th2 cytokine responses
while Th1 cytokines are unaffected. These data confirm that alum is a useful
adjuvant for inclusion in allergen immunotherapy vaccines.

PMID: 15347369 [PubMed - indexed for MEDLINE]

881: Respir Med. 2004 Sep;98(9):826-31.

Comment in:
    Respir Med. 2005 Jul;99(7):929; author reply 930.

Bronchial hyperreactivity and spirometric impairment in patients with seasonal
allergic rhinitis.

Ciprandi G, Cirillo I, Tosca MA, Vizzaccaro A.

Dipartimento Regionale Testa-Collo, Padiglione Specialità (piano terzo), Ospedale
San Martino, Largo R. Benzi 10, Genoa 16132, Italy. gio.cip@libero.it

We previously demonstrated in a group of patients with perennial allergic
rhinitis alone, impairment of spirometric parameters and high percentage of
bronchial hyperreactivity (BHR). Thus, the present study aimed at evaluating a
group of subjects suffering from seasonal allergic rhinitis alone to investigate 
the presence of spirometric impairment and BHR both during and outside the pollen
season. METHODS: One-hundred rhinitics sensitized to pollen allergens only were
evaluated during and outside the pollen season. Spirometry and methacholine
bronchial challenge were performed. RESULTS: Four rhinitics showed impaired
values of FEV1 without referred symptoms of asthma during the pollen season. FEF 
25-75 values were impaired in 17 rhinitics during the pollen season and in 11
rhinitics outside the pollen season (P<0.05). Fifty-four patients showed positive
methacholine bronchial challenge both during and outside the pollen season.
PD20/FEV1 methacholine was lower during the pollen season than outside (P<0.05). 
In BHR positive patients, reduced values of FVC (P<0.05), FEV1 (P<0.05), and FEF 
25-75 (P<0.01) were significantly demonstrated in comparison with BHR negative
rhinitics. There was a relationship between BHR degree and FEF 25-75 values only 
during the pollen season (P<0.001). CONCLUSIONS: This study evidences that an
impairment of spirometric parameters may be observed also in patients with
seasonal allergic rhinitis alone during the pollen season. A high percentage of
these patients had BHR. A close relationship between upper and lower airways is
confirmed also in the model of pollen allergy. Thus, a careful evaluation of
lower airways should be performed also in those patients with seasonal allergic
rhinitis alone.

PMID: 15338793 [PubMed - indexed for MEDLINE]

882: Eur Ann Allergy Clin Immunol. 2004 Jun;36(6):237-40.

Cetirizine reduces cytokines and inflammatory cells in children with perennial
allergic rhinitis.

Ciprandi G, Tosca MA, Milanese M, Ricca V.

Allergy and ENT Division, Head Neck Dpt., San Martino Hospital, Genoa.

Cetirizine has been demonstrated able of reducing nasal inflammatory infiltration
in children with allergic rhinitis and cytokine production in in vitro studies.
The aim of this double-blind, placebo-controlled, and randomized study was to
evaluate cytokine pattern and inflammatory cells in children with perennial
allergic rhinitis, before and after treatment with cetirizine or placebo. Twenty 
children with perennial allergic rhinitis were evaluated, 13 males and 7 females 
(mean age 13.4 years). Inflammatory cells and cytokines were evaluated by
scraping and nasal lavage, before and after 2-weeks administration of cetirizine 
or placebo. IL4 and IL8 were measured by immunoassay and inflammatory cells were 
counted by conventional staining. Cetirizine treatment induced a significant
decrease of IL4 (p<0.01) and IL8 levels (p=0.01). A significant reduction of the 
inflammatory cells was detected in actively-treated children, both concerning
neutrophils and eosinophils (p<0.01). Moreover, cetirizine significantly reduced 
nasal obstruction score (p=0.007). This study shows the cetirizine effectiveness 
in exerting anti-inflammatory activity by modulating cytokine pattern and by
reducing inflammatory infiltration in children with perennial allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15329007 [PubMed - indexed for MEDLINE]

883: Ann Allergy Asthma Immunol. 2004 Aug;93(2):154-9.

Efficacy of azelastine nasal spray in seasonal allergic rhinitis patients who
remain symptomatic after treatment with fexofenadine.

LaForce CF, Corren J, Wheeler WJ, Berger WE; Rhinitis Study Group.

Carolina Allergy and Asthma Consultants, Raleigh, North Carolina 27607, USA.
claforce@nccr.com

BACKGROUND: Currently available oral second-generation antihistamines do not
provide adequate symptom relief for many allergy patients. OBJECTIVE: To
determine the ability of azelastine nasal spray to improve rhinitis symptoms in
patients with seasonal allergic rhinitis who remained symptomatic after treatment
with fexofenadine. METHODS: This was a multicenter, randomized, double-blind,
placebo-controlled, 2-week study in patients with moderate-to-severe seasonal
allergic rhinitis. The study began with a 1-week, open-label lead-in period,
during which patients received fexofenadine, 60 mg twice daily. Patients who
improved less than 25% to 33% with fexofenadine were randomized to treatment with
(1) azelastine nasal spray, 2 sprays per nostril twice daily; (2) azelastine
nasal spray, 2 sprays per nostril twice daily, plus fexofenadine, 60 mg twice
daily; or (3) placebo (saline) nasal spray and placebo capsules twice daily. The 
primary efficacy variable was the change from baseline to day 14 in the total
nasal symptom score (TNSS), consisting of runny nose, sneezing, itchy nose, and
nasal congestion symptom scores. RESULTS: A total of 334 patients who remained
symptomatic after treatment with fexofenadine were included in the efficacy
analysis. After 2 weeks of treatment, azelastine nasal spray (P = .007) and
azelastine nasal spray plus fexofenadine (P = .003) significantly improved the
TNSS compared with placebo. Azelastine nasal spray monotherapy was as effective
as the combination of azelastine nasal spray plus fexofenadine as measured by the
TNSS and individual symptoms of the TNSS. CONCLUSIONS: Azelastine nasal spray is 
effective monotherapy for patients who remain symptomatic after treatment with
fexofenadine and should be considered in the initial management of patients with 
seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15328675 [PubMed - indexed for MEDLINE]

884: Immunol Lett. 2004 Aug 15;95(1):37-44.

Absence of interleukin-3 does not affect the severity of local and systemic
anaphylaxis but does enhance eosinophil infiltration in a mouse model of allergic
peritonitis.

Neel NF, Creasy BM, Rankin JN, Pierce EM, McCoy ME, Daner RH, Fowler JA, Daniel
JC, Lantz CS.

Department of Biology, James Madison University, Harrisonburg, VA 22807, USA.

Interleukin-3 (IL-3), which is derived from T cells and other sources, can
promote the differentiation, proliferation, and migration of mast cells,
basophils, and eosinophils. However, little is known about the ability of IL-3 to
regulate the function of these cells in IgE-dependent and -independent allergic
responses in vivo. Therefore, we sought to investigate the extent to which
endogenously produced IL-3 can influence mast cell secretory function, the
expression of local and systemic anaphylactic responses, and ragweed-induced
eosinophilic peritonitis. We found that peritoneal mast cells from IL-3 deficient
(IL-3 -/-) mice released less serotonin following challenge with low doses of
anti-IgE antibody or antigen ex vivo than do cells isolated from corresponding
wild-type (IL-3 +/+) mice. Both IL-3 -/- and +/+ mice expressed equivalent
IgE-dependent passive cutaneous anaphylaxis responses following challenge with
specific antigen and exhibited equivalent active systemic anaphylaxis responses
to ovalbumin as assessed by changes in body temperature, death rates, total IgE
production, and histamine release. In contrast, ragweed allergen immunization and
peritoneal allergen challenge resulted in eosinophil recruitment that was greater
in IL-3 -/- mice than in IL-3 +/+ mice. Our data demonstrates that IL-3 does not 
appear to be essential for local or systemic anaphylaxis. However, IL-3
production in vivo was found to enhance the mediator release from freshly
isolated peritoneal mast cells stimulated ex vivo, and, unexpectedly, to inhibit 
the accumulation of eosinophils associated with a ragweed-induced allergic
peritonitis model.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15325796 [PubMed - indexed for MEDLINE]

885: Drugs Today (Barc). 2004 May;40(5):415-21.

Levocetirizine: a new selective H1 receptor antagonist for use in allergic
disorders.

Day JH, Ellis AK, Rafeiro E.

Division of Allergy and Immunology, Kingston General Hospital, Kingston, Ontario,
Canada. dayj@kgh.kari.net

Levocetirizine is the active R-enantiomer of cetirizine and represents a new
second-generation histamine H(1) antagonist. It has a high affinity and
selectivity for H(1) receptors. Comparative studies have shown evidence of
superior H(1) receptor binding affinity over its racemate, cetirizine.
Levocetirizine has a favorable pharmacokinetic profile; it is rapidly and
extensively absorbed, minimally metabolized, and has a lower volume of
distribution (V(d)) than some other second-generation antihistamines. A number of
studies using the histamine-induced wheal and flare model have repeatedly
demonstrated marked suppressive effects for levocetirizine. Levocetirizine has
also been found to be effective in relieving symptoms of seasonal and perennial
allergic rhinitis, including nasal congestion, and its side effects are minor.
(c) 2004 Prous Science. All rights reserved.

Publication Types: 
    Review

PMID: 15319796 [PubMed - indexed for MEDLINE]

886: Ann Ital Med Int. 2004 Apr-Jun;19(2):98-108.

Comment in:
    Ann Ital Med Int. 2004 Apr-Jun;19(2):79-80.

A randomized, controlled study of specific immunotherapy in monosensitized
subjects with seasonal rhinitis: effect on bronchial hyperresponsiveness, sputum 
inflammatory markers and development of asthma symptoms.

Crimi N, Li Gotti F, Mangano G, Paolino G, Mastruzzo C, Vancheri C, Lisitano N,
Polosa R.

Istituto di Malattie dell'Apparato Respiratorio, Università degli Studi di
Catania.

Allergic rhinitis is often associated with bronchial hyperresponsiveness (BHR)
and airway inflammation, and it seems to be an important risk factor for the
development of asthma. Specific immunotherapy (SIT) reduces symptoms and
medication requirements in subjects with allergic rhinitis, but the mechanisms by
which SIT promotes these beneficial effects are less clear. We have investigated 
the effects of Parietaria-SIT on rhinitis symptoms, BHR to inhaled methacholine, 
eosinophilic inflammation and cytokine production (interferon gamma and
interleukin-4) in the sputum. The effect on asthma progression was also examined.
Thirty non-asthmatic subjects with seasonal rhinitis and monosensitized to
Parietaria judaica participated in a randomized, double-blind,
placebo-controlled, parallel group study. Participants were randomly assigned to 
receive injections of a Parietaria pollen vaccine (n = 15) or matched placebo
injections (n = 15) in a rapid updosing cluster regimen for 7 weeks, followed by 
monthly injections for 34 months. Throughout the 3-year study we collected data
on symptoms and medication score, airway responsiveness to methacholine,
eosinophilia and soluble cytokines in sputum, followed by a complete evaluation
of the clinical course of atopy. Hay fever symptom and medication scores were
well controlled by SIT. By the end of the study, in the placebo group, symptom
and medication scores significantly increased by a median (interquartile range)
of 121% (15-280%) and 263% (0-4400%) respectively (p < 0.01), whereas no
significant difference was observed in the SIT group. We found no significant
changes in the sputum parameters and methacholine PC15 values in both groups
throughout the study. By the end of the investigation, a total of 9 out of 29
participants developed asthma symptoms; of these, seven (47%) belonged to the
placebo group, whereas only 2 (14%) to the SIT-treated group (p = 0.056). In
conclusion, Parietaria-SIT is effective in controlling hay fever symptoms and
rescue medications, but no changes in the BHR to methacholine or sputum
eosinophilia were observed. Moreover, Parietaria-SIT appears to prevent the
natural progression of allergic rhinitis to asthma, suggesting that SIT should be
considered earlier in the management of this condition.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15317270 [PubMed - indexed for MEDLINE]

887: J Allergy Clin Immunol. 2004 Aug;114(2):316-20.

Heparin attenuates symptoms and mast cell degranulation induced by AMP nasal
provocation.

Zeng D, Prosperini G, Russo C, Spicuzza L, Cacciola RR, Di Maria GU, Polosa R.

Department of Drug Research and Pharmacological Sciences, CV Therapeutics, Inc,
Palo Alto, Italy.

BACKGROUND: Previous studies have shown that inhaled heparin attenuated the
airway responses to allergen, exercise, and AMP bronchial provocation, possibly
through an inhibition of mast cell activation. OBJECTIVE: The aim of this study
was to provide the evidence of in vivo inhibition of human mast cell activation
by heparin in a noninvasive model. METHODS: Nine atopic and 6 nonatopic subjects 
received placebo and unfractionated heparin sodium (5000 IU/mL) 15 minutes before
an AMP nasal provocation in a double-blind crossover study design. The nasal
lavage was collected from these subjects before or 3, 5, 15, or 30 minutes after 
the AMP nasal challenge, and concentrations of histamine and tryptase in the
nasal lavage were measured. RESULTS: AMP nasal provocation produced considerable 
sneezing and induced a transient increase in histamine and tryptase release, with
peak values achieved at 3 to 5 minutes after the challenge in all atopic
subjects. Compared with placebo, inhaled heparin significantly attenuated the
release of histamine and tryptase induced by AMP challenge (P=.012 and.004,
respectively). Moreover, the AMP-induced sneezing was also inhibited by
pretreatment with heparin (P=.016). In nonatopic subjects, AMP did not induce a
significant increase in histamine and tryptase release on placebo-treated or
heparin-treated days. CONCLUSION: These data suggest that AMP nasal provocation
and AMP bronchial provocation cause mast cell mediator release in a similar
fashion. In addition, the data support the hypothesis that inhaled heparin plays 
a protective role against AMP provocation by inhibition of mast cell activation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15316509 [PubMed - indexed for MEDLINE]

888: Int Arch Allergy Immunol. 2004 Sep;135(1):40-3. Epub 2004 Aug 13.

Association of single nucleotide polymorphisms in the eosinophil peroxidase gene 
with Japanese cedar pollinosis.

Nakamura H, Higashikawa F, Miyagawa K, Nobukuni Y, Endo T, Imai T, Ozasa K,
Motohashi Y, Matsuzaki I, Sasahara S, Hatta K, Ogino K, Eboshida A.

Department of Environmental Medicine, Kochi University School of Medicine,
Kohasu, Okoh-cho, Nankoku 783-8505, Japan. hiro-n@po.incl.ne.jp

BACKGROUND: Japanese cedar pollinosis is the most common form of hay fever in
spring in Japan. We have previously demonstrated that single nucleotide
polymorphism Pro358Leu of exon 7 in the eosinophil peroxidase (EPO) gene is
associated with cedar pollinosis, although the association has not been confirmed
by analysis of the whole gene in a different population. METHODS: We sequenced
all exons of the EPO gene in 60 children with pollinosis and their parents using 
the PCR-restriction fragment length polymorphism method. RESULTS: We found 8
polymorphisms, Ile40Met, Gln122His, Arg202Arg (A660G), Asn303Asn (C909T),
Arg326Pro, Arg326His, Pro358Leu, and Asn572Ty, in the EPO gene. As a result of
the transmission disequilibrium test, we recognized significant transmissions of 
202Arg (660G) in exon 6 in addition to 358Leu of exon 7 in the EPO gene of
affected children. CONCLUSIONS: Our results might indicate that polymorphisms of 
the EPO gene are associated with Japanese cedar pollinosis. Copyright 2004 S.
Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15316147 [PubMed - indexed for MEDLINE]

889: Acta Biomed. 2004 Apr;75(1):22-5.

Effectiveness of intranasal corticosteroids.

Grzincich G, Capra L, Cammarata MG, Spaggiari C, Pisi G.

Department of Pediatrics, University of Parma, Italy.

Intranasal corticosteroids (IC) are most commonly prescribed to treat allergic
rhinitis (perennial and seasonal). There are now many IC available to treat
rhinitis, all effective on nasal obstruction, rhinorrhea, sneezing, itching and
post-nasal drip. IC are superior to oral antihistamines for the relief of all
nasal symptoms; however, antihistamines are first line therapy if allergic
conjunctivitis coexists. At present the data do not support the use of IC in the 
management of otitis media with effusion (OME), nasal polyposis and sinusitis,
but when topical IC are administered together with antibiotic therapy they
facilitate a more rapid improvement of symptoms.

PMID: 15315083 [PubMed - indexed for MEDLINE]

890: Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14677-82. Epub 2004 Aug 13.

Vaccination with genetically engineered allergens prevents progression of
allergic disease.

Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Valent P, Reisinger J,
Pelzmann M, Hayek B, Kronqvist M, Gafvelin G, Grönlund H, Purohit A, Suck R,
Fiebig H, Cromwell O, Pauli G, van Hage-Hamsten M, Valenta R.

Department of Otorhinolaryngology, Vienna General Hospital, University of Vienna,
1090 Vienna, Austria.

IgE-mediated allergy affects >25% of the population in industrialized countries. 
Repeated contact with the disease-eliciting allergens induces rises of
allergen-specific IgE Abs and progression of the disease to more severe
manifestations. Our study uses a type of vaccine that is based on genetically
modified allergen derivatives to treat allergic patients. We developed
hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by
genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a 
double-blind, placebo-controlled study. Active treatment induced protective IgG
Abs that inhibited allergen-induced release of inflammatory mediators. We also
observed a reduction of cutaneous sensitivity as well as an improvement of
symptoms in actively treated patients. Most important, rises of allergen-specific
IgE induced by seasonal birch pollen exposure were significantly reduced in
vaccinated patients. Vaccination with genetically engineered allergen derivatives
is a therapy for allergy that not only ameliorates allergic reactions but also
reduces the IgE production underlying the disease.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15310844 [PubMed - indexed for MEDLINE]

891: Clin Exp Allergy. 2004 Aug;34(8):1192-201.

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese
cedar pollen.

Cheng L, Enomoto T, Hirota T, Shimizu M, Takahashi N, Akahoshi M, Matsuda A, Dake
Y, Doi S, Enomoto K, Yamasaki A, Fukuda S, Mao XQ, Hopkin JM, Tamari M, Shirakawa
T.

Department of Health Promotion and Human Behaviour, Kyoto University Graduate
School of Public Health, Kyoto, Japan.

BACKGROUND: A recent report provided evidence that a disintegrin and
metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel
susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, 
there has been no investigation of the genetic role of ADAM33 variants in nasal
allergy. OBJECTIVE: The purpose of this study was to test the association between
ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common
seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control
association study among a Japanese population, involving 95 adult individuals
with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide
polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. 
RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and
12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were 
strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele
frequencies) and most of the SNPs were in linkage disequilibrium with each other.
A higher frequency of the common alleles of these SNPs was noted for the subjects
with JCPsis in comparison with healthy controls. We also identified a haplotype
associated with the disease susceptibility. In addition, associations were found 
between ADAM33 polymorphisms and various cedar pollinosis phenotypes including
clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE
levels in sera, but not total serum IgE levels. CONCLUSION: These results
indicate that polymorphisms in the ADAM33 gene are associated with susceptibility
to allergic rhinitis due to Japanese cedar pollen, but the functional
relationship still needs clarification.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15298558 [PubMed - indexed for MEDLINE]

892: J Manag Care Pharm. 2004 Jul-Aug;10(4):310-7.

Allergic rhinitis, asthma, and rhinosinusitis: diseases of the integrated airway.

Meltzer EO, Szwarcberg J, Pill MW.

Allergy and Asthma Medical Group and Research Center, University of California at
San Diego, San Diego, CA 92123, USA. eomeltzer@aol.com

OBJECTIVE: To review data supporting the integrated airway hypothesis. Allergic
rhinitis, rhinosinusitis, and asthma are common conditions associated with
significant morbidity and health care costs. A theory has been developed
suggesting that these conditions may be manifestations of an inflammatory process
within a continuous airway rather than fully separate diseases. Based on this
theory, the presence of upper airway symptoms may negatively influence the
natural course of lower airway disease. Controlling upper airway inflammation and
symptoms among asthma patients may help improve health and economic outcomes.
SUMMARY: Further clarifying and understanding the relationship between diseases
of the upper and lower respiratory tracts is important because of the prevalence 
of allergic rhinitis, rhinosinusitis, and asthma and the resulting burden on
patients and the health care system. Recent progress in understanding the biology
of airway disease has identified inflammation as playing a critical and
integrating role in these diseases; however, other important questions remain,
including factors that determine the clinical phenotype in allergic airway
disorders and optimal treatment approaches. CONCLUSIONS: Several recent studies
have suggested that allergic rhinitis, rhinosinusitis, and asthma may be
manifestations of a common underlying pathology, but there are many unanswered
questions. More studies are needed to better define all the underlying pathologic
mechanisms as well as treatments to optimize outcomes for patients with allergic 
rhinitis, rhinosinusitis, and asthma. Copyright 2004 Academy of Managed Care
Pharmacy

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15298529 [PubMed - indexed for MEDLINE]

893: Allergy. 2004 Sep;59(9):973-9.

The co-seasonal application of anti-IgE after preseasonal specific immunotherapy 
decreases ocular and nasal symptom scores and rescue medication use in grass
pollen allergic children.

Rolinck-Werninghaus C, Hamelmann E, Keil T, Kulig M, Koetz K, Gerstner B, Kuehr
J, Zielen S, Schauer U, Kamin W, Von Berg A, Hammermann J, Weinkauf B, Weidinger 
G, Stenglein S, Wahn U; Omalizumab Rhinitis Study Group.

Charité, Pediatric Pneumology and Immunology, Berlin, Germany.

BACKGROUND: Specific immunotherapy (SIT) and treatment with anti-immunoglobulin
(Ig)E antibody are complementary approaches to treat allergic
rhinoconjunctivitis, which may be used for single or combined treatment.
OBJECTIVE: A randomized, double-blind, placebo-controlled trial was conducted to 
compare the efficacy of single and combined treatment with SIT and anti-IgE
(Omalizumab) in reducing symptom severity and rescue medication use. METHODS: A
total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis
aged 6-17 years were analysed during the grass pollen season. Group A (SITbirch +
placebo) served as a reference group obtaining no effective treatment for grass
pollen allergy. Group B received anti-IgE monotherapy during grass pollen season,
group C SIT grass pollen monotherapy, and group D the combined treatment of SIT
and Omalizumab. RESULTS: Preseasonal treatment with grass pollen SIT alone
compared with SIT with the nonrelated allergen did not reduce symptoms or rescue 
medication use. Anti-IgE monotherapy significantly diminished rescue medication
use and number of symptomatic days. The combined treatment with SIT and anti-IgE 
showed superior efficacy on symptom severity compared with anti-IgE alone.
CONCLUSIONS: Co-seasonal Omalizumab therapy showed considerable effects in
children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab 
was clinically superior to each treatment alone during the first year of
observation.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 15291906 [PubMed - indexed for MEDLINE]

894: Allergy. 2004 Sep;59(9):953-60.

Acupuncture and Chinese herbal medicine in the treatment of patients with
seasonal allergic rhinitis: a randomized-controlled clinical trial.

Brinkhaus B, Hummelsberger J, Kohnen R, Seufert J, Hempen CH, Leonhardy H, Nögel 
R, Joos S, Hahn E, Schuppan D.

Department of Medicine I, Friedrich-Alexander-University of Erlangen-Nuremberg,
Erlangen Germany.

BACKGROUND: Patients with allergic rhinitis (AR) increasingly use complementary
medicine. The aim of this study was to determine whether traditional Chinese
therapy is efficacious in patients suffering from seasonal AR. METHODS: Fifty-two
patients between the ages of 20 and 58 who had typical symptoms of seasonal AR
were assigned randomly and in a blinded fashion to (i) an active treatment group 
which received a semi-standardized treatment of acupuncture and Chinese herbal
medicine, and (ii) a control group which received acupuncture applied to
non-acupuncture points in addition to a non-specific Chinese herbal formula. All 
patients received acupuncture treatment once per week and the respective Chinese 
herbal formula as a decoction three times daily for a total of 6 weeks.
Assessments were performed before, during, and 1 week after treatment. The change
in severity of hay fever symptoms was the primary outcome measured on a visual
analogue scale (VAS). RESULTS: Compared with patients in the control group,
patients in the active treatment group showed a significant after-treatment
improvement on the VAS (P = 0.006) and Rhinitis Quality of Life Questionnaire (P 
= 0.015). Improvement on the Global Assessment of Change Scale was noted in 85%
of active treatment group participants vs 40% in the control group (P = 0.048).
No differences between the two groups could be detected with the Allergic
Rhinitis Symptom Questionnaire. Both treatments were well-tolerated. CONCLUSIONS:
The results of this study suggest that traditional Chinese therapy may be an
efficacious and safe treatment option for patients with seasonal AR.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15291903 [PubMed - indexed for MEDLINE]

895: Arh Hig Rada Toksikol. 2004 Jun;55(2-3):197-204.

Exercise and allergic diseases.

Klepac-Pulanić T, Macan J, Plavec D, Kanceljak-Macan B.

Institute for Medical Research and Occupational Health, Zagreb, Croatia.
tajana.pulanic@hi.hinet.hr

The aim of this study was to compare exercise-induced bronchial reaction between 
healthy control subjects and subjects with allergic rhinitis (AR) and allergic
asthma (AA). It included 16 controls, 16 subjects with AR and 19 subjects with
AA. A skin prick test, pulmonary function test, histamine challenge test and
exercise challenge test (ECT) were performed in all subjects. Bronchial reaction 
to exercise was expressed as the fall index FEV1 (%), AUC(0-30) (min x %), and
fall index FEF(25-75) (%). After ECT, subjects with AA had a significantly
greater bronchial reaction to exercise than subjects with AR and controls
(respective fall index FEV1 8.4, 2.9, and 2.4%, P=0.0083; AUC(0-30) 127.7, 29.6, 
and 33.1 min x %, P=0.025; and fall index FEF(25-75) 14.6, 0.06, and 1.9%,
P<0.001). No difference was found between subjects with AR and controls. In
conclusion, ECT induced a significantly greater bronchial reaction in patients
with AA and bronchial hyperreactivity to histamine than in patients with AR and
bronchial normoreactivity to histamine and controls. This difference was not
found between subjects with AR and controls.

PMID: 15285469 [PubMed - indexed for MEDLINE]

896: Arh Hig Rada Toksikol. 2004 Jun;55(2-3):147-54.

Hypersensitivity to pollen allergens on the Adriatic coast.

Cvitanović S, Znaor L, Perisić D, Grbić D.

Department of Pulmonary Diseases, Clinical Hospital of Split, Split, Croatia.
slavicacvitanović@hotmail.com

This paper describes a study of air concentrations of pollens and a calendar of
pollination around the town of Split on the Croatian Adriatic in 1994. High
pollen concentrations of Parietaria officinalis dominated during the year (up to 
20% from April to June) followed by the pollens of Pistacia lentiscus, Olea
europaea, Pinus halepensis, Juniperus oxycedrus, Acacia baileyana, Artemisia
vulgaris, Ambrosia elatior and Cistus monspeliensis. In 1994-95, skin prick tests
using commercially available standard inhalation allergens and specially prepared
pollen allergens were performed on 3,500 patients with allergic respiratory
symptoms. About 30% were allergic to standard pollen allergens (mixed grass
pollen, mixed tree pollen, Parietaria officinalis and Pittosporum tobira).
Hypersensitivity to more than one allergen was found in 45% of patients, whereas 
15% did not react to any of the standard allergens. Additional testing with newly
prepared individual allergens (P. lentiscus, O. europaea, P. halepensis, A.
baileyana, C. monspeliensis, A. vulgaris, A. elatior) revealed hypersensitivity
in a number of patients, but 36% showed no reaction. This finding suggests that
further studies of this kind are needed for additional identification, isolation,
and characterisation of pollen allergens that are present in the Adriatic coast.

PMID: 15285462 [PubMed - indexed for MEDLINE]

897: Ann Allergy Asthma Immunol. 2004 Jul;93(1):61-7.

Effect of budesonide aqueous nasal spray on hypothalamic-pituitary-adrenal axis
function in children with allergic rhinitis.

Kim KT, Rabinovitch N, Uryniak T, Simpson B, O'Dowd L, Casty F.

Allergy, Asthma & Respiratory Care Medical Center, Long Beach, California 90806, 
USA. drkkim@wcctrials.com

BACKGROUND: Intranasal corticosteroids are safe and effective for treating
allergic rhinitis in adults. Since children may receive more systemic
corticosteroid on a dose-per-weight basis than adults, the safety of
corticosteroid therapy in pediatric patients is an important issue. OBJECTIVE: To
determine the effects of treatment with budesonide aqueous nasal spray using the 
recommended once-daily dose for adults and children 6 years and older on
hypothalamic-pituitary-adrenal (HPA) axis function in pediatric patients with
allergic rhinitis. METHODS: In a 6-week, multicenter, double-blind,
placebo-controlled study, 78 patients aged 2 to 5 years with allergic rhinitis
were treated with budesonide aqueous nasal spray (64 microg/d) or placebo. Mean
change in morning plasma cortisol levels from baseline to study end 0, 30, and 60
minutes after low-dose (10-microg) cosyntropin stimulation and mean change in the
difference from 0 to 30 minutes and from 0 to 60 minutes after cosyntropin
stimulation were used to evaluate HPA axis function. RESULTS: Mean change from
baseline to study end in plasma cortisol levels 0, 30, and 60 minutes after
cosyntropin stimulation and the difference from 0 to 30 minutes and from 0 to 60 
minutes were not significantly different between the treatment and placebo groups
(P > .05 for all). At the end of the study, 3 budesonide aqueous nasal spray and 
6 placebo patients were classified as having subnormal HPA axis function. The
safety and tolerability profile of budesonide aqueous nasal spray was comparable 
to that of placebo. CONCLUSIONS: Administration of budesonide aqueous nasal spray
for 6 weeks was well tolerated and safe and had no measurable suppressive effects
on HPA axis function in patients aged 2 to 5 years with allergic rhinitis.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15281473 [PubMed - indexed for MEDLINE]

898: Ann Allergy Asthma Immunol. 2004 Jul;93(1):56-60.

Effects of butterbur treatment in intermittent allergic rhinitis: a
placebo-controlled evaluation.

Gray RD, Haggart K, Lee DK, Cull S, Lipworth BJ.

Asthma & Allergy Research Group, Ninewells Hospital & Medical School, University 
of Dundee, Dundee, Scotland.

BACKGROUND: Butterbur (Petasites hybridus) contains the active ingredient
petasin, which exhibits antileukotriene and antihistamine activity. Previous
studies of intermittent allergic rhinitis (IAR) have demonstrated a comparable
response to butterbur compared with a histamine H1-receptor antagonist on the
36-Item Short-Form Health Survey quality-of-life score. However, there has been
no placebo-controlled study of the effects of butterbur use on objective and
subjective outcomes in IAR. OBJECTIVE: To evaluate the effects of treatment with 
butterbur vs placebo on objective and subjective outcomes in IAR. METHODS: A
double-blind, placebo-controlled, crossover study was carried out during the
grass pollen season in Tayside, Scotland. Thirty-five patients (14 men and 21
women) with IAR received butterbur, 50 mg twice daily, or placebo for 2 weeks.
Domiciliary measurements were taken in the morning and evening for peak nasal
inspiratory flow (PNIF) (the primary outcome variable), nasal and eye symptoms,
and rhinoconjunctivitis-specific quality-of-life score. RESULTS: Butterbur
treatment had no significant effect on PNIF, total nasal symptom score, eye
symptom score, or quality of life compared with placebo use. Mean (SEM) morning
and evening PNIF values were 107 (6) and 114 (6) L/min, respectively, for
butterbur vs 105 (6) and 117 (6) L/min for placebo. Mean (SEM) morning and
evening total nasal symptom scores (maximum total score, 12) were 3.4 (0.4) and
3.5 (0.4), respectively, for butterbur vs 3.7 (0.3) and 3.8 (0.4) for placebo.
CONCLUSIONS: There was no significant clinical efficacy of butterbur use vs
placebo use on objective and subjective outcomes in IAR. Further studies are now 
indicated to investigate the use of butterbur in persistent allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15281472 [PubMed - indexed for MEDLINE]

899: Clin Exp Immunol. 2004 Aug;137(2):366-72.

Nasal mucosa in natural colds: effects of allergic rhinitis and susceptibility to
recurrent sinusitis.

Alho OP, Karttunen R, Karttunen TJ.

Department of Otorhinolaryngology, University of Oulu, Finland. opalho@cc.oulu.fi

The mechanisms of virus-induced airway hyperresponsiveness in asthma and allergy 
and the failure of host defence in patients suffering from secondary airway
infections are still largely unknown. The aim of this study was to examine
whether the presence of allergic rhinitis or susceptibility to recurrent
sinusitis affects the structural and cellular changes in nasal mucosa during
natural colds and convalescence. We compared the mucosal changes in biopsy
samples during acute natural colds (days 2-4 of illness) and convalescence (3
weeks later) in patients with allergic rhinitis (n = 9), patients with
susceptibility to sinusitis (n = 19) and healthy controls (n = 20). We saw
similarly increased numbers of mucosal T and B lymphocytes and mast cells and
increased vascular density during the acute colds compared to convalescence in
all the three groups. The allergic subjects had elevated levels of eosinophils in
the acute phase (P = 0.03), and the allergic and sinusitis-prone subjects had
elevated levels of epithelial T cells (P = 0.04) and low levels of mast cells (P 
= 0.005) in convalescence compared to the control group. The sinusitis-prone
subjects lacked intraepithelial cytotoxic cells in convalescence. In the allergic
subjects, the reticular basement membrane was thicker in the acute phase compared
to the convalescence (P = 0.05). These results suggest that various cells of the 
airways, including inflammatory and structural cells, are involved during viral
respiratory infections in subjects with allergic rhinitis. The small numbers of
mast cells and cytotoxic lymphocytes in the sinusitis-prone subjects may be
related to their susceptibility to bacterial complications.

PMID: 15270854 [PubMed - indexed for MEDLINE]

900: Acta Otolaryngol. 2004 Jun;124(5):616-20.

A role for neutrophils in intermittent allergic rhinitis.

Fransson M, Benson M, Wennergren G, Cardell LO.

Department of Otorhinolaryngology, Malmö University Hospital, Malmö, Sweden.
mattias.fransson@oron.mas.lu.se

OBJECTIVE: In patients with intermittent allergic rhinitis, allergen challenge
may induce both early- and late-phase responses. The aim of this study was to
examine the correlation between inflammatory cells in the nasal lavage fluid and 
clinical parameters following pollen challenge. MATERIAL AND METHODS: Nasal
lavage fluids were obtained from 29 patients with intermittent allergic rhinitis 
before and 1 and 6 h after allergen provocation, representing the control, early 
and late phases, respectively. Symptom and rhinoscopic scores were registered on 
the same occasions. Inflammatory cells were determined in the nasal fluid.
RESULTS: The early phase was characterized by increased symptom scores,
rhinoscopic signs of oedema and secretion and neutrophilia. In the late phase,
symptom scores had diminished, but the signs of ongoing secretion remained. Both 
the total nasal symptom score and the secretion score correlated with the number 
of neutrophils in lavage fluids at 1 h. The eosinophil count did not increase
during the early or late phases. CONCLUSION: A single allergen provocation
induces an early-phase response dominated by neutrophils, with secretion being
the only clinical sign remaining during the late phase. The increase in
neutrophil numbers correlated with the registration of secretory symptoms. The
presented data indicate a role for neutrophils in intermittent allergic rhinitis 
and their relation with secretory parameters makes it intriguing to speculate
that neutrophils may function as promoters of nasal secretion.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15267182 [PubMed - indexed for MEDLINE]

901: J Asthma. 2004;41(3):311-7.

Incidence and prevalence of asthma and allergic rhinitis: a cohort study of
Finnish adolescents.

Huurre TM, Aro HM, Jaakkola JJ.

Department of Mental Health and Alcohol Research, National Public Health
Institute, Helsinki, Finland. taina.huurre@ktl.fi

Only limited data are available about the incidence of asthma and allergic
rhinitis based on prospective longitudinal studies throughout childhood into
adult life. The main purpose of the study was to estimate the incidence rate of
asthma and allergic rhinitis from birth to early adulthood. We also estimated the
prevalences of these diseases at 16, 22, and 32 years of age. The data were drawn
from a follow-up survey of a Finnish urban age cohort (1967 birth cohort, N =
2269) from age 16 to age 32 years. All data were based on self-report. The
prevalence of asthma from age 16 to age 32 years changed from 3.0% to 5.0% (males
from 3.3% to 4.9%; females from 2.7% to 5.1%); and that of allergic rhinitis from
17.5% to 26.0% (males from 18.7% to 27.8%; females 16.2% to 24.5%), respectively.
The overall incidence rate of asthma was approximately 2.1 new cases per 1000
person-years (95% CI = 1.6-2.8). There was a tendency for boys to have a higher
incidence rate of asthma than girls in childhood before 16 years of age: gender
difference was reversed from period 17 to 22 years of age. In early adulthood
(23-32 years), incidence rates were equal in both sexes. The incidence rate for
allergic rhinitis in males was 13.4 per 1000 person-years (95% CI- 11.8-14.8),
slightly greater than in females, 11.4 (95% CI = 10.1-12.8). Among both genders, 
the highest incidence rate of allergic rhinitis was between 17 and 22 years. Our 
study adds to the limited knowledge on the incidence rates of asthma and allergic
rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15260464 [PubMed - indexed for MEDLINE]

902: Clin Exp Allergy. 2004 Jul;34(7):1105-10.

Phenotypic alteration of neuropeptide-containing nerve fibres in seasonal
intermittent allergic rhinitis.

Heppt W, Dinh QT, Cryer A, Zweng M, Noga O, Peiser C, Melvan M, Witt C, Fischer
A, Groneberg DA.

Department of Otorhinolaryngology, Karlsruhe Teaching Hospital, University of
Freiburg, Karlsruhe, Germany.

BACKGROUND: Allergic rhinitis (AR) is the most common allergic disease affecting 
the respiratory tract. Next to inflammatory changes, the airway innervation plays
an important modulatory role in the pathogenesis of the disease. OBJECTIVE: To
examine the participation of different neuropeptides in the human nasal mucosa of
intermittent (seasonal) AR tissues in the allergic season. METHODS:
Immunohistochemistry for substance P (SP), calcitonin gene-related peptide
(CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY)
was related to the characterization of inflammatory cells in tissues of patients 
with seasonal AR (n=18). RESULTS: While there was a significant increase in the
number of eosinophils present if compared with a control group, no changes
occurred in mast cell numbers. Immunostaining was abundantly found in different
nerve fibre populations of both groups. SP expression was significantly increased
in mucosal nerve fibres of patients with intermittent (seasonal) AR. Also,
significantly increased numbers of VIP- and NPY-immunoreactive nerve fibres were 
found in biopsies of rhinitis patients in comparison with sections of normal
human nasal mucosa. In contrast, CGRP expression did not change significantly.
CONCLUSION: The increase of neuropeptide expression in mucosal nerve fibres
indicates a major role of the autonomous mucosal innervation in the
pathophysiology of intermittent (seasonal) AR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15248857 [PubMed - indexed for MEDLINE]

903: Clin Exp Allergy. 2004 Jul;34(7):1079-85.

Effect of anti-immunoglobulin E on nasal inflammation in patients with seasonal
allergic rhinoconjunctivitis.

Bez C, Schubert R, Kopp M, Ersfeld Y, Rosewich M, Kuehr J, Kamin W, Berg AV, Wahu
U, Zielen S.

University Children's Hospital, Frankfurt, Germany.

BACKGROUND: Binding of allergens to IgE on mast cells and basophils causes
release of inflammatory mediators in nasal secretions. OBJECTIVE: The combined
effect of specific immunotherapy (SIT) and omalizumab, a humanized monoclonal
anti-IgE antibody, on release of eosinophilic cationic protein (ECP), tryptase,
IL-6, and IL-8 in nasal secretion was evaluated. METHODS: Two hundred and twenty 
five children (aged 6-17 years) with a history of seasonal allergic
rhinoconjunctivitis induced by birch and grass pollen were randomized into four
groups: either birch- or grass-pollen SIT in combination with either anti-IgE or 
placebo. Complete sets of nasal secretion samples before treatment Visit 1 (V1), 
during birch- (V2) and grass (V3)-pollen season and after the pollen season (V4) 
were collected from 53 patients. RESULTS: A significant reduction in tryptase
only was seen in the anti-IgE-treated group at V2 (P<0.05) and V4 (P<0.05)
compared with the placebo group. During the pollen season, patients with placebo 
showed an increase of ECP compared with baseline (V2: +30.3 microg/L; V3: +134.2 
microg/L, P< 0.005; V4: +79.0 microg/L, P< 0.05), and stable levels of tryptase, 
IL-6 and IL-8. Treatment with anti-IgE resulted in stable ECP values and a
significant decrease of tryptase compared with V1 (baseline): V2: -80.0 microg/L 
(P< 0.05); V3: -56.3 microg/L, which persisted after the pollen season with V4:
-71.6 microg/L (P< 0.05). After the pollen season, a decrease of IL-6 was
observed in both groups (V4 placebo group: -37.5 ng/L; V4 anti-IgE group: -42.9
ng/L, P< 0.01). CONCLUSION: The combination of SIT and anti-IgE is associated
with prevention of nasal ECP increase and decreased tryptase levels in nasal
secretions.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15248853 [PubMed - indexed for MEDLINE]

904: Ann Allergy Asthma Immunol. 2004 Jun;92(6):654-8.

Effect of vitamin E supplementation on the regular treatment of seasonal allergic
rhinitis.

Shahar E, Hassoun G, Pollack S.

Institute of Allergy, Clinical Immunology, and AIDS, Rambam Medical Center,
Haifa, Israel. ed_shahar@rambam.health.gov.il

BACKGROUND: Vitamin E supplementation is widely used in clinical practice for the
prevention and treatment of different medical conditions. Evidence from basic
science studies suggests that vitamin E may reduce immune allergic responses.
However, only a few clinical studies of the effect of vitamin E on allergic
conditions have been performed in patients with atopic dermatitis and asthma, and
none have been performed in patients with allergic rhinitis. OBJECTIVE: To
determine the effect of high-dose vitamin E supplementation in combination with
the usual ("real-life") treatment on the symptoms of seasonal allergic rhinitis
during the pollen season. METHODS: In a double-blind, placebo-controlled,
randomized study, 112 patients with documented hay fever received either vitamin 
E (800 mg/d) or placebo in addition to their regular antiallergic treatment
during the pollen season. Patients recorded their daily nasal and eye symptoms
and their daily need for other medications to control allergic symptoms. RESULTS:
Although no effect was observed on ocular symptoms, nasal symptom scores were
lower in patients who received vitamin E supplementation during the hay fever
season. However, there was no reduction in the percentage of days with serious
symptoms or in the percentage of days that medications were used to control
allergic symptoms during the pollen season. CONCLUSIONS: Vitamin E
supplementation may be a valuable addition to the treatment of patients with
seasonal allergic rhinitis. However, further clinical and basic science studies
are needed to determine its real value.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15237767 [PubMed - indexed for MEDLINE]

905: Int J Pediatr Otorhinolaryngol. 2004 Aug;68(8):1007-15.

Comment in:
    Int J Pediatr Otorhinolaryngol. 2005 May;69(5):721; author reply 723-4.

Effect of intranasal triamcinolone acetonide on bronchial hyper-responsiveness in
children with seasonal allergic rhinitis and comparison of perceptional nasal
obstruction with acoustic rhinometric assessment.

Oztürk F, Türktaş I, Asal K, Ileri F, Münevver Pinar N.

Department of Pediatrics, Division of Pediatric Allergy and Asthma, Gazi
University Faculty of Medicine, Ankara, Turkey. fozturk@omu.edu.tr

OBJECTIVE: Many patients with allergic rhinitis (AR) have bronchial
hyper-responsiveness (BHR), and seasonal variation of BHR has been demonstrated
in these patients. We aimed to investigate how BHR in children with seasonal AR
is modified by triamcinolone acetonide aqueous nasal spray (TANS) therapy during 
the pollen season. A secondary aim was to assess the efficacy of TANS on nasal
congestion by acoustic rhinometry and symptom scores. METHODS: A total of 34
children aged 7-18 years with grass pollen-induced AR and 18 age and sex-matched 
healthy controls were included in study. The patients were divided into the
following two subgroups: 22 patients who had AR only; and 12 patients who had AR 
and asthma. All of them had a baseline BHR (PC20FEV1 methacholine < 8mg/ml). All 
patients received 220 microg TANS once daily for 4 weeks following a 1-week
run-in period. Nasal patency was measured by acoustic rhinometry and patients
recorded their nasal obstruction scores in a diary. RESULTS: There was no
significant difference at baseline pulmonary function test parameters between the
patients and the healthy control children. None of the control subjects had BHR. 
Asthmatic children with AR had significantly reduced baseline PC20FEV1 when
compared with the AR only group [mean +/- S.E.M., (1.60 +/- 0.57 mg/ml versus
2.93 +/- 0.42 mg/ml, P = 0.021)]. The mean PC20FEV1 values increased slightly at 
the end of treatment in both group (from 1.60 +/- 0.57 mg/ml to 3.25 +/- 1.11 and
from 2.93 +/- 0.42 mg/ml to 3.93 +/- 1.41 mg/ml), but the change was not
statistically significant. TANS produced substantial symptomatic recovery in
nasal obstruction according to patients' daily diary assessments, and
significantly improved all objective acoustic rhinometry parameters. CONCLUSIONS:
Once-daily intranasal TANS 220 microg effectively controlled nasal obstruction in
children with seasonal AR according to subjective and objective assessments, and 
blocked the increase in BHR to methacholine after high-load natural pollen
exposure. There was no correlation between patients' own subjective assessment of
nasal obstruction and objective acoustic rhinometric assessment.

PMID: 15236886 [PubMed - indexed for MEDLINE]

906: Ann Agric Environ Med. 2004;11(1):35-44.

Environmental factors affecting the start of pollen season and concentrations of 
airborne Alnus pollen in two localities of Galicia (NW Spain).

Rodriguez-Rajo FJ, Dopazo A, Jato V.

Dr. F. Javier Rodriguez Rajo, University of Vigo, Sciences Faculty of Ourense,
Department of Plant Biology and Soil Sciences, Ourense 32004, Spain.
javirajo@uvigo.es

Alnus pollen is an early component of the annual atmospheric aerosol of the
north-west regions of Spain, which causes the first occurrence of allergic
symptoms. Seasonal and intra-daily variation of Alnus pollination, and the
influence that main meteorological parameters exert, was studied in this paper.
Monitoring was carried out from 1993-2002, by using two Lanzoni VPPS 2000
volumetric samplers. Once the atmospheric behaviour of this pollen had been
identified, the final objective was to elaborate predictive models to determine
the onset of the Alnus pollen season and its concentrations during the
pollination period in two localities of north-west Spain (Santiago and Ourense). 
Winter chilling required to overcome the bud-dormancy period was similar in both 
cities, with around 800 Chilling Hours (C.H.) and 5.5 degrees C threshold
temperature. Calculation of heat requirement for bud growth was carried out with 
maximum temperature, with around 50 Growth Degree Days (G.D.D. degrees C) needed,
with 6 degrees C threshold temperature. Data from 2002 were used in order to
determine the real validity of the models. This year was not taken into account
to establish the aforementioned models. The variation between the predicted start
of the pollen season and the observed season was smallest in Ourense. Verifying
the proposed models for predicting daily mean concentrations of Alnus pollen
during the pollen season shows that the predicted curves fits the observed
variations of daily mean concentrations.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15236496 [PubMed - indexed for MEDLINE]

907: Allergy. 2004 Aug;59(8):857-62.

Lower prevalence of reported asthma in adolescents with symptoms of rhinitis that
received neonatal BCG.

da Cunha SS, Cruz AA, Dourado I, Barreto ML, Ferreira LD, Rodrigues LC.

Infectious Disease Epidemiology Unit, Department of Infectious and Tropical
Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London
WC1E 7HT, UK.

BACKGROUND: BCG is a vaccine used against tuberculosis and leprosy and is an
immunostimulant that primes T(H)1 lymphocytes to produce cytokines that
antagonize atopy both in animal models and in man. Considering that atopy is the 
main risk factor for asthma, one can hypothesize that vaccination inducing T(H)1 
responses, such as BCG, can be protective against asthma. METHODS: OBJECTIVE: To 
estimate the association between neonatal BCG vaccination and prevalence of
asthma among adolescents. STUDY DESIGN: Cross-sectional study with schoolchildren
aged 12-16 years. The presence of a scar compatible with BCG was used as a
surrogate of neonatal vaccination. A self administered structured questionnaire
was prepared based on that used by the International Study of Asthma and
Allergies in Childhood. The prevalence of asthma was categorized according to the
report of lifetime wheeze, lifetime asthma, lifetime asthma among those referring
allergy and among those referring allergy and sneezing. RESULTS: Neonatal BCG
vaccination was not associated with the overall prevalence of reported wheezing
or asthma. However, in the subgroup reporting current allergy and sneezing,
neonatal BCG was associated with a 37% reduction of prevalence of lifetime
asthma. CONCLUSIONS: In the population we surveyed, neonatal BCG scar was
associated with a reduction in the risk of asthma only in individuals with a past
history suggestive of allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15230819 [PubMed - indexed for MEDLINE]

908: J Manag Care Pharm. 2004 May-Jun;10(3):226-33.

Comment in:
    J Manag Care Pharm. 2004 May-Jun;10(3):266, 269-70.

Effects of an increase in prescription copayment on utilization of low-sedating
antihistamines and nasal steroids.

Meissner BL, Moore WM, Shinogle JA, Reeder CE, Little JM.

College of Pharmacy, Department of Pharmaceutical and Health Outcomes Sciences,
University of South Carolina, 1425 Richland St., Columbia, SC 29201, USA.
meissner@cop.sc.edu

BACKGROUND: Health plans are using 3-tier copayment designs and other methods to 
control utilization that shifts drug costs to plan members. There is a need to
determine the effects of increased member cost sharing on drug utilization and
drug costs. OBJECTIVE: To assess the impact of a 10 US dollars increase in
prescription copayment in a public employer health plan for 2 classes of drugs
used for allergic rhinitis. METHODS: Changes in the number of prescriptions
dispensed for 2 therapeutic classes.low-sedating antihistamines (LSAs) and nasal 
steroids (NSs).were examined 1 year prior to and 1 year after copayment increase.
Relative price effects were measured as arc price elasticity, the ratio of the
percent change in prescription utilization over the percent change in price, an
indicator of how responsive patients are to the copayment increase. RESULTS: Of
8,643 continuously enrolled health plan beneficiaries, 2,150 patients (24.8%)
received at least 1 NS or LSA during the 2-year period of the study, from January
1, 1998, through December 31, 1999. An average 10 US dollars increase in
copayment per prescription was associated with no statistically significant
change in utilization of combined LSA and NS prescriptions, 2.89 per patient in
1998 and 2.94 in 1999 (P = 0.597). Health plan costs for study drugs, unadjusted 
for inflation, decreased by 16.3% from 86.86 US dollars per patient in 1998 to
72.68 US dollars in 1999 (P = 0.004). Health plan costs per patient per month
(PPPM) for all drugs for the 2,150 allergic rhinitis patients decreased by 13%
from 41.33 US dollars PPPM in 1998 to 35.93 US dollars in 1999 (P<0.001), and
health plan drug costs for all 8,643 members decreased by 13% from 14.93 US
dollars per member per month (PMPM) in 1998 to 12.99 US dollars in 1999
(P<0.001). The actual average copayment increase was 7.23 US dollars (a 41%
increase) for LSAs, which was associated with a 14.8% increase in utilization of 
LSAs and an 11.8% increase in the number of patients using LSAs; the number of
LSA prescriptions per patient per year was unchanged at 2.68 in 1999 versus 2.61 
in 1998 (P = 0.429). The actual average copayment increase was 10.98 US dollars
(71%) for NSs, which was associated with an 11.3% decrease in utilization of NSs 
and a 10.2% decrease in the number of users of nasals steroids in 1999; the
number of nasal steroid prescriptions per patient per year was unchanged at 2.05 
in 1999 versus 2.07 in 1998 (P =.842). The combined utilization of LSA and NS
prescriptions increased by 8.9% following the increase in copayments for these 2 
therapeutically interchangeable drugs for allergic rhinitis. LSA prescriptions
were less elastic, with an unadjusted arc elasticity of 0.39, while nasal steroid
prescriptions were more responsive to the copayment change, with an unadjusted
arc elasticity of.0.22. CONCLUSIONS: An average 10 US dollars increase in patient
cost sharing per prescription (46.9% copayment increase) was associated with an
increase in combined utilization of 2 drug classes used for allergic rhinitis
(LSAs and NSs) but no change in the number of prescriptions per patient. Health
plan costs decreased significantly for allergic rhinitis drugs, all drugs used by
allergic rhinitis patients, and all drugs used by continuously enrolled health
plan members. NSs exhibited a greater arc price elasticity compared with
low-sedating oral antihistamines.

PMID: 15228372 [PubMed - indexed for MEDLINE]

909: Rhinology. 2004 Jun;42(2):85-91.

Phospholipase A2 mRNA expression in the nasal mucosa of healthy subjects and
patients with seasonal allergic rhinitis.

Lindbom J, Ljungman AG, Irander K, Lindahl M, Tagesson C.

Department of Molecular and Clinical Medicine, Division of Occupational and
Environmental Medicine, University of Linkôping, S-581 85 Linkôping, Sweden.
Johli@imk.liu.se

Phospholipase A2 (PLA2) is a family of enzymes that play different role(s) in
inflammation, but their importance in seasonal allergic rhinitis (SAR) has not
been clarified. Here, we determined the levels of messenger ribonucleic acid
(mRNA) for different PLA2 types in the nasal mucosa of SAR patients (n = 6) and
healthy controls (n = 5). Nasal brush samples were taken both during pollen
season, when the symptoms of the patients were severe, and off-season, when the
patients were free of symptoms. We found that PLA2 IB, IIA, IID, IIE, IIF, III,
IVA, IVB, IVC, VIA, VIB, VIIA, VIIB, VIIIA, VIIIB, X, XII and XIII were all
expressed in each subject at both occasions. The mRNA levels of PLA2 VIIA
(platelet-activating factor (PAF) acetylhydrolase) were lower in SAR patients
than controls, both during pollen season (p = 0.03) and off season (p = 0.03).
These findings demonstrate that a large number of PLA2 types are expressed in the
nasal mucosa, regardless of whether there is ongoing allergic inflammation or
not. The observation that PAF acetylhydrolase mRNA expression in the nasal mucosa
is lower in SAR patients than in healthy subjects suggests the possibility that
impaired ability to inactivate PAF might be of importance in SAR. Further studies
are required to clarify whether the decreased PAF acetylhydrolase mRNA expression
in SAR is accompanied by decreased enzyme activity and whether aberrations in PAF
acetylhydrolase are present in infectious rhinitis patients as well.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15224635 [PubMed - indexed for MEDLINE]

910: Rhinology. 2004 Jun;42(2):81-4.

Partial laser turbinectomy: two year outcomes in patients with allergic and
non-allergic rhinitis.

Sandhu AS, Temple RH, Timms MS.

Department of Otorhinolaryngology, Blackburn Royal Infirmary, Blackburn,
Lancashire BB2 3LR, England. kaz.sandhu@virgin.net

OBJECTIVE: The aim was to compare two year outcomes of partial laser turbinectomy
in patients with allergic and non-allergic rhinitis with respect to nasal
obstruction symptom scores and nasal peak inspiratory flow rates (nPIFR). This
has not been reported previously. METHOD: Fifty-four patients underwent partial
laser turbinectomy (28 with allergic rhinitis, 26 with non-allergic rhinitis).
NPIFR was measured preoperatively, at 3 months and two years postoperatively. A
symptom score questionnaire was also completed. RESULTS: Both allergic and
non-allergic patients showed a significant improvement in symptom scores and
nPIER at three months (n = 54). The improvement in allergic patients was greater.
In the 31 patients seen at two years, there was still a significant improvement
in median symptom scores but no such improvement in median nPIFR. In allergic
patients (n = 18) at two years, there was no significant improvement in symptom
and nPIFR scores. Non-allergic patients (n = 13), however, did show sustained
significant improvement in these scores (p < 0.05). Eighty-seven percent (26/31) 
considered the operation successful and would recommend it to others.
CONCLUSIONS: Non-allergic patients derive a more sustained improvement in the
medium term compared to allergic individuals when undergoing partial laser
turbinectomy. The improvement in symptom scores in the group as a whole was still
significant.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15224634 [PubMed - indexed for MEDLINE]

911: Rhinology. 2004 Jun;42(2):49-56.

Allergic rhinitis: aetiology, predisposing and risk factors.

Jones N.

Department of Otorhinolaryngology, Head and Neck Surgery, Queen's Medical Centre,
University Hospital, Nottingham NG7 2UH, United Kingdom.
nick.jones@nottingham.ac.uk

The reason for examining the predisposing and risk factors that affect the
prevalence of allergic rhinitis is to help understand its cause and prevent its
occurrence particularly in the light of the marked increase that is taking place 
in the prevalence of this condition. The epidemiology in different population
groups and studying patient's family histories may give us clues about what
factors predispose people to developing allergic rhinitis. Furthermore we can
gain a better understanding of the disease mechanisms from the histological and
molecular tissue studies that relate to allergic rhinitis.

Publication Types: 
    Review

PMID: 15224629 [PubMed - indexed for MEDLINE]

912: Pediatr Allergy Immunol. 2004 Jun;15(3):253-60.

Safety and efficacy of oral fexofenadine in children with seasonal allergic
rhinitis--a pooled analysis of three studies.

Meltzer EO, Scheinmann P, Rosado Pinto JE, Bachert C, Hedlin G, Wahn U, Finn AF
Jr, Ruuth E.

Allergy and Asthma Medical Group and Research Center, San Diego, CA, USA.
eomeltzer@aol.com

Allergic rhinitis is one of the most common clinical conditions in children;
however, data regarding the safety of antihistamines in children with seasonal
allergic rhinitis are limiting. To evaluate the safety and efficacy of
fexofenadine in children with seasonal allergic rhinitis, data were pooled from
three, double-blind, randomized, placebo-controlled, parallel-group, 2-week
trials in children (6-11 year) with seasonal allergic rhinitis. All studies
assessed fexofenadine HCl 30 mg b.i.d.; two studies included fexofenadine HCl at 
15 and 60 mg b.i.d. Patients (and investigators) reported any adverse events
during the trial. Physical examinations, including measurements of vital signs
and laboratory tests, were performed. Efficacy assessments (total symptom score
and individual symptom scores) were evaluated. Exposure to fexofenadine HCl 30 mg
b.i.d. and to any fexofenadine dose exceeded 10,000 and 17,000 patient days,
respectively. Incidences of adverse events, and discontinuations because of
adverse events, were low and similar across treatment groups. In the placebo
group, 24.4% of subjects reported adverse events compared with 24.1% for
fexofenadine HCl 30 mg b.i.d., and 28.4% for all fexofenadine-treated groups. The
most common adverse event overall was headache (4.3% placebo; 5.8% fexofenadine
HCl 30 mg b.i.d.; and 7.2% any fexofenadine doses). Treatment-related adverse
events were similar across treatment groups with no sedative effects.
Fexofenadine HCl 30 mg b.i.d. was significantly superior to placebo in reducing
the total symptom score and all individual seasonal allergic rhinitis symptoms,
including nasal congestion (p < 0.05). Fexofenadine, at doses of up to 60 mg
b.i.d., is safe and non-sedating, and fexofenadine HCl 30 mg b.i.d. effectively
reduces all seasonal allergic rhinitis symptoms in children aged 6-11 years.
Copyright 2004 Blackwell Munksgaard

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15209959 [PubMed - indexed for MEDLINE]

913: Curr Med Res Opin. 2004 Jun;20(6):891-902.

A direct comparison of the efficacy of antihistamines in SAR and PAR: randomised,
placebo-controlled studies with levocetirizine and loratadine using an
environmental exposure unit - the Vienna Challenge Chamber (VCC).

Stübner P, Zieglmayer R, Horak F.

ENT University Clinic Vienna, Austria. petra.stuebner@akh-wien.ac.at

OBJECTIVE: The Vienna Challenge Chamber (VCC) is an established method for the
controlled exposure of patients to specific allergens, used to make valid
comparisons between antihistamines. The aim of the significantly more than
loratadine at all time two placebo-controlled, randomised studies reported here
was to compare the efficacy and safety of levocetirizine 5 mg od and loratadine
10 mg od in subjects suffering from seasonal allergic rhinitis (SAR) or perennial
allergic rhinitis (PAR). Subjects and methods: During each study period, SAR and 
PAR subjects were exposed to grass pollen or house-dust mite allergens,
respectively for 6 h on 2 consecutive days in the VCC. Each day, medications were
administered 2 h after the start of the challenge; with a washout of at least 5
days between each period. The main criterion for evaluation of efficacy was the
major symptom complex (MSC) for SAR and the complex symptom score (CSS) for PAR. 
RESULTS: The pattern of patients' response was similar in SAR and PAR. Both
levocetirizine and loratadine were superior to placebo in alleviating SAR and PAR
symptoms at all time intervals evaluated during the two study days.
Levocetirizine decreased the mean MSC score intervals in SAR subjects, with the
most marked difference observed on day 2 (p = 0.002). In PAR patients, although
with borderline significance (p = 0.08), levocetirizine decreased the mean CSS
more than loratadine. Levocetirizine appeared to have a faster onset of action
than loratadine in SAR (45 min versus 1 h 15 min) and PAR (1 h versus 1 h 30
min). However, these apparent differences were not tested for statistical
significance. Both medications were well tolerated and no treatment-related
adverse events were reported. This level of antihistamine efficacy was maintained
regardless of whether the subjects' rhinitis was seasonal or perennial.
CONCLUSION: This study demonstrated that levocetirizine is superior to loratadine
in improving symptoms in SAR and that there is a similar trend in PAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15200748 [PubMed - indexed for MEDLINE]

914: Clin Exp Allergy. 2004 Jun;34(6):958-64.

Levocetirizine improves nasal obstruction and modulates cytokine pattern in
patients with seasonal allergic rhinitis: a pilot study.

Ciprandi G, Cirillo I, Vizzaccaro A, Tosca MA.

Allergologia, Ospedale San Martino, Genoa, Italy. gio.cip@libero.it

BACKGROUND: Allergic rhinitis is characterized by an IgE-dependent inflammation. 
Nasal obstruction is related to allergic inflammation. Some antihistamines have
been demonstrated to be capable of improving this nasal symptom. OBJECTIVE: The
aim of this pilot study was to evaluate nasal symptoms, nasal airflow,
inflammatory cells, and cytokine pattern in patients with seasonal allergic
rhinitis (SAR), before and after treatment with levocetirizine, desloratadine, or
placebo. METHODS: Thirty patients with SAR were evaluated, 27 males and three
females (mean age 26.9+/-5.4 years). All of them received levocetirizine (5
mg/day), desloratadine (5 mg/day), or placebo for 2 weeks. The study was
double-blind, parallel-group, placebo-controlled, and randomized. Total symptom
score (TSS) (including: rhinorrhea, nasal itching, sneezing, and nasal
obstruction) was assessed before and after treatment. Rhinomanometry, nasal
lavage, and nasal scraping were performed in all subjects before and after
treatment. Inflammatory cells were counted by conventional staining; IL-4 and
IL-8 were measured by immunoassay on fluids recovered from nasal lavage. RESULTS:
Levocetirizine treatment induced significant symptom relief (P=0.0009) and
improved nasal airflow (P=0.038). Desloratadine also relieved TSS (P=0.01), but
did not affect nasal airflow. Levocetirizine significantly reduced eosinophils
(P=0.029), neutrophils (P=0.005), IL-4 (P=0.041), and IL-8 (P=0.02), whereas
desloratadine diminished IL-4 only (P=0.044). Placebo treatment did not
significantly affect any evaluated parameters. CONCLUSIONS: This pilot study
demonstrates the effectiveness of levocetirizine in: (i) relieving nasal
symptoms, (ii) improving nasal airflow, (iii) reducing leucocyte infiltration,
and (iv) diminishing cytokine levels. These findings are the first evidence of
the effectiveness of levocetirizine in SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15196286 [PubMed - indexed for MEDLINE]

915: Clin Exp Allergy. 2004 Jun;34(6):952-7.

Treatment with intranasal fluticasone propionate significantly improves ocular
symptoms in patients with seasonal allergic rhinitis.

Bernstein DI, Levy AL, Hampel FC, Baidoo CA, Cook CK, Philpot EE, Rickard KA.

Division of Immunology-Allergy and Bernstein Clinical Research Center, Inc.,
University of Cincinnati, Cincinnati, OH 45267, USA. bernstdd@ucmail.uc.edu

BACKGROUND: If monotherapy with an intranasal corticosteroid can alleviate both
nasal and ocular symptoms of allergic rhinitis, treatment may be simplified and
costs may be reduced. OBJECTIVE: The purpose of this study was to evaluate the
efficacy of once-daily fluticasone propionate (FP) aqueous nasal spray 200 microg
compared with vehicle placebo and oral loratadine (LOR) 10 mg in reducing ocular 
symptoms associated with seasonal allergic rhinitis. METHODS: A total of 471
patients received vehicle placebo, LOR, or FP in this multi-centre, double-blind,
double-dummy, randomized study. Patients were > or =12 years old with a history
of seasonal allergic rhinitis and a positive skin test for a relevant allergen.
During the baseline and treatment periods, patients rated the severity of eye
itching, tearing, and redness via visual analogue scales that ranged from 0 (no
symptoms) to 100 (most severe symptoms). The three ocular ratings were added to
derive the total ocular symptom score (TOSS). Patients with a TOSS > or =120 on
at least 4 of the 7 days before the randomization visit were enrolled. The
primary outcome was the difference between FP and vehicle placebo in the mean
change from baseline in the reflective TOSS overall (averaged over the 28-day
treatment period). A difference between FP and vehicle placebo of 25.5 was
considered clinically significant. RESULTS: The overall mean change from baseline
in the TOSS was significantly greater in the FP group compared with vehicle
placebo (clinically significant difference of 28.8; P<0.001) and compared with
LOR (difference of 16.2; P=0.028). Overall mean (SEM) changes were -59.9 (5.4)
for the placebo group, -72.5 (5.4) for the LOR group, and -88.7 (5.3) for the FP 
group. The FP treatment group also showed significantly greater overall mean
changes in ocular itching, tearing, and redness compared with vehicle placebo
(P<0.001) and compared with LOR (P< or =0.045). CONCLUSION: Patients treated with
intranasal FP had clinically and statistically significant decreases in ocular
symptom scores compared with vehicle placebo. Data also suggest that FP reduced
ocular symptoms more than or comparable with oral LOR. Patients experiencing
ocular symptoms associated with allergic rhinitis may benefit from monotherapy
with intranasal FP.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15196285 [PubMed - indexed for MEDLINE]

916: Clin Exp Allergy. 2004 Jun;34(6):945-51.

Effect of glucocorticosteroids on tumour necrosis factor-alpha-induced
intercellular adhesion molecule-1 expression in cultured primary human nasal
epithelial cells.

Shirasaki H, Watanabe K, Kanaizumi E, Sato J, Konno N, Narita S, Himi T.

Department of Otolaryngology, Sapporo Medical University, Sapporo, Japan.
puchibe@spa.att.ne.jp

OBJECTIVE: In order to confirm the direct effect of glucocorticosteroids on
epithelial intercellular adhesion molecule-1 (ICAM-1) expression, we examined
ICAM-1 expression on primary cultured human nasal epithelial cells (HNECs) at
both protein and mRNA levels. MATERIAL AND METHODS: HNECs were stimulated with
recombinant human TNF-alpha (20 pg/mL-20 ng/mL) for specified time periods (0,
12, 24, and 48 h) and ICAM-1 mRNA and the soluble ICAM-1 (sICAM-1) concentrations
were measured by quantitative RT-PCR and ELISA, respectively. We also evaluated
surface expression of ICAM-1 by flow cytometry 48 h after stimulation and
determined the effect of dexamethasone (DEX) on TNF-alpha-induced ICAM-1
expression. RESULTS: Significant increases in ICAM-1 gene expression in HNECs
were initially detected at 24 h, peaking at 48 h after the stimulation. The
TNF-mediated-ICAM-1 mRNA and ICAM-1 surface expression at 48 h was significantly 
inhibited by co-incubation with human recombinant soluble TNF receptor I.
Similarly, TNF-alpha-induced release sICAM-1 occurred in a time- and
concentration-dependent manner. DEX 10(-6) M attenuated the TNF-alpha-induced
ICAM-1 expression at mRNA and protein levels. CONCLUSIONS: Our finding suggests a
potential role for topical steroids in allergic rhinitis in suppressing
inflammatory reactions in the nasal mucosa by regulating ICAM-1 expression on
nasal epithelium.

PMID: 15196284 [PubMed - indexed for MEDLINE]

917: Clin Exp Allergy. 2004 Jun;34(6):897-903.

Characteristics of patients with seasonal allergic rhinitis and concomitant
asthma.

Bousquet J, Boushey HA, Busse WW, Canonica GW, Durham SR, Irvin CG, Karpel JP,
Van Cauwenberge P, Chen R, Iezzoni DG, Harris AG.

Montpellier University/INSERM, Montpellier, France. bousquet@montp.inserm.fr

BACKGROUND: Allergic rhinitis and asthma often co-exist and appear to produce a
continuum of airway disease, but whether the clinical characteristics of asthma
in patients with seasonal rhinitis differ from those of persistent asthma has not
been examined. OBJECTIVE: The aim of this retrospective study was to characterize
the clinical features of patients with seasonal allergic rhinitis with
concomitant asthma and to compare them with those in patients with persistent
asthma. METHODS: The patient populations for this study were derived from nine
prospective, placebo-controlled planned clinical trials of similar design. Six
studies (958 patients) enrolled patients with seasonal allergic rhinitis and
concomitant asthma; three (607 patients) involved patients with persistent
asthma. In all studies, patients were excluded from oral corticosteroid therapy
in the preceding 3 months, and from inhaled corticosteroids in the preceding
month. RESULTS: Patients with seasonal rhinitis and asthma had a significantly
(P<0.001) higher total asthma symptom score than those with persistent asthma. In
particular, cough was three times more severe. The need for beta(2)-agonist as a 
rescue medication and the ratio of forced expiratory volume in 1 s/forced vital
capacity (FVC) were similar in the two groups whereas forced expiratory fraction 
25-75%/FVC was significantly (P<0.02) reduced in the persistent asthmatics.
Asthma and nasal symptom severity scores were correlated in patients with
seasonal rhinitis and asthma (P<0.0001). CONCLUSIONS: Patients with seasonal
allergic rhinitis and concomitant asthma appear to differ from those with
persistent asthma. A prospective study should be designed to discover whether
patients with seasonal rhinitis and asthma may represent a distinct nosological
entity, 'allergic airway disease'.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15196277 [PubMed - indexed for MEDLINE]

918: Clin Exp Allergy. 2004 Jun;34(6):891-6.

Airway function and nasal inflammation in seasonal allergic rhinitis and asthma.

Ciprandi G, Cirillo I, Vizzaccaro A, Milanese M, Tosca MA.

Ospedale San Martino, Genoa, Italy. gio.cip@libero.it

BACKGROUND: Allergic rhinitis (AR) and asthma are frequently associated and
characterized by a Th2-dependent inflammation. Nasal and bronchial obstruction
may be objectively measured. OBJECTIVE: The aim of this study was to evaluate the
relationships among upper and lower airway function and nasal inflammation in
subjects with seasonal allergic rhinitis (SAR) and asthma. METHODS: Twenty
out-patients (12 males and eight females, mean age: 23.4+3.6 years) with SAR and 
asthma were evaluated during the pollen season. All of them showed a
moderate-severe grade of nasal obstruction. Total symptom score, rhinomanometry, 
spirometry, nasal lavage, and nasal scraping were obtained in all subjects.
Eosinophils were counted by conventional staining; IL-4 and IFN-gamma were
measured by immunoassay on fluids recovered from nasal lavage. RESULTS:
Functional parameters, i.e. nasal airflow and forced expiratory volume in 1 s
(FEV(1)), were correlated with nasal eosinophils (R(2)>0.83, P<0.001).
Inflammatory parameters, i.e. eosinophils were correlated with immunological
parameters, i.e. IL-4 and IFN-gamma levels (R(2)=0.93, P<0.001). Nasal symptoms
were correlated with nasal airflow (rho=-0.71, P< or =0.01) and eosinophils
(rho=0.72, P<0.01). Nasal airflow was correlated with FEV(1) (r=0.89, P<0.0001). 
CONCLUSIONS: This study demonstrates the close connection between Th2 cytokines
and eosinophil infiltration in the nose. There is also clear evidence concerning 
the relationships between eosinophils infiltration and cytokines levels. Nasal
eosinophils can be regarded as the most important predictors of upper and lower
airway functions. These findings constitute first evidence of a relationship
among nasal Th2-related inflammation and nasal and bronchial airflow in patients 
with SAR and asthma.

PMID: 15196276 [PubMed - indexed for MEDLINE]

919: Drugs Today (Barc). 2004 Apr;40(4):367-76.

Omalizumab: an effective anti-IgE treatment for allergic asthma and rhinitis.

Casale TB; Prous Science.

Medical Information Department, Prous Science, Provença 388, 08025 Barcelona,
Spain. support@prous.com

IgE plays a crucial role in the pathophysiology of asthma and allergic rhinitis. 
Omalizumab is a humanized anti-IgE monoclonal antibody that binds to free IgE and
prevents its binding to specific receptors on the surface of cells, thus
preventing the release of immune mediators. Treatment with omalizumab in patients
with asthma or allergic rhinitis results in a rapid and pronounced decrease in
serum IgE levels that is correlated with an improvement in the severity of
symptoms and in the quality of life of patients. Omalizumab has a good safety
profile, with only mild to intermediate drug-related adverse events. (c) 2004
Prous Science. All rights reserved.

Publication Types: 
    Review

PMID: 15190389 [PubMed - indexed for MEDLINE]

920: Clin Ther. 2004 Apr;26(4):473-92.

Once-daily budesonide aqueous nasal spray for allergic rhinitis: a review.

Stanaland BE.

Division of Allergy and Immunology, University of South Florida Health Sciences
Center, Tampa, Florida, USA. allerguy@aol.com

BACKGROUND: Allergic rhinitis (AR) is a highly prevalent inflammatory condition
with substantial direct and indirect costs. Intranasal corticosteroids are
recommended as first-line therapy for moderate to severe persistent AR.
Intranasal budesonide is effective and well tolerated; budesonide aqueous nasal
spray (BANS) offers several advantages of potential importance to patients,
including once-daily dosing at a low volume of spray in a formulation that is
free of chlorofluorocarbon propellants, alcohol, benzalkonium chloride, and
scents. OBJECTIVE: This article reviews the findings of randomized, blinded
studies assessing the efficacy, safety profile, quality-of-life effects, patient 
preference, and cost-effectiveness of once-daily BANS in the treatment of AR.
METHODS: A MEDLINE search (1966-April 2003) was conducted to identify potentially
relevant English-language articles. Pertinent abstracts from recent allergy
society meetings were also identified. The search strategy employed the medical
subject heading terms budesonide, intranasal corticosteroid, or nasal steroid and
allergic rhinitis. Selected studies were randomized, controlled clinical trials
of once-daily BANS in patients with AR. RESULTS: Based on the results of
randomized, double-blind, controlled trials, once-daily BANS is an effective
treatment for both seasonal and perennial AR at doses as low as 64 microg (one
32-microg spray per nostril). BANS was well tolerated in these studies, with an
adverse-event profile similar to that of placebo, and caused no clinically
meaningful suppression of hypothalamic-pituitary-adrenal axis function at doses
4-fold higher than the recommended starting dose. Once-daily administration of
BANS 64 microg was similar in efficacy to mometasone furoate nasal spray 200
microg once daily; comparable doses of BANS and fluticasone propionate nasal
spray (FPNS) were similar in efficacy as well. Based on specific sensory
attributes, patients preferred BANS to FPNS at the recommended once-daily
starting doses. BANS was associated with more days of treatment per prescription 
at a lower cost per day compared with other intranasal corticosteroids.
CONCLUSIONS: Based on the studies reviewed, BANS administered once daily is an
effective and well-tolerated treatment for seasonal and perennial AR in both
children and adults. Due to its sensory attributes, efficacy, safety profile, and
relatively low cost, BANS may help improve patient adherence.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15189745 [PubMed - indexed for MEDLINE]

921: Allergy. 2004 Jul;59(7):781-5.

Does my partner cause my allergy?

Schäfer T, Merkl J, Klemm E, Wichmann HE, Ring J; KORA Study Group.

Department of Social Medicine, Medical University Schleswig-Holstein, Lübeck,
Germany.

BACKGROUND: The study of partners can help to understand the impact of
environmental influences on the development of allergies. We aimed to test the
hypothesis that subjects whose partners have hay fever are at increased risk for 
the same disease and that the risk increases with the time subjects live together
with an affected partner. METHODS: A nested unmatched case-control study was
performed in a random sample of 4261 inhabitants, aged 25-74 years, of the City
of Augsburg, Germany, and two adjacent counties. Using standardized
computer-assisted face-to-face interviews, we determined the risk of
doctor-diagnosed hay fever in subjects who lived together with a partner having
the same disease as opposed to subjects living with an unaffected partner.
Furthermore, the risk of doctor-diagnosed hay fever depending on the time the
subjects had lived together with an affected partner was calculated. RESULTS:
After adjustment for age, sex, parental predisposition and social status, the
risk of hay fever was more than double in subjects who lived together with a
partner having the same disease (odds ratio, OR(adj.), 2.41; 95% confidence
interval, CI, 1.48-3.92). If subjects lived together with an affected partner,
the risk of developing the disease increased with the time the partners lived
together (1-11 years, OR 1; 12-23 years, OR 1.8; 24-35 years, OR 7.4; 36-54
years, OR 13.7). CONCLUSION: The risk of developing hay fever is significantly
elevated in subjects who live together with a partner having the same disease.
The risk further increases with the time the partners live together. This points 
to important shared environmental influences or behaviours and raises
speculations on a transmissible cause.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15180767 [PubMed - indexed for MEDLINE]

922: Allergy. 2004 Jul;59(7):766-71.

Rupatadine 10 mg and ebastine 10 mg in seasonal allergic rhinitis: a comparison
study.

Guadaño EM, Serra-Batlles J, Meseguer J, Castillo JA, De Molina M, Valero A,
Picado C; Rupatadine Study Group.

Hospital Sant Pere Claver, Barcelona, Spain.

BACKGROUND: The aim of this study is to establish the efficacy and safety of
rupatadine vs ebastine and placebo in the treatment of seasonal allergic rhinitis
(SAR). Rupatadine is a new second generation H(1)-antihistamine with once-daily
dosing that may provide better control of symptoms than the currently used
H(1)-receptor blockers because of its dual pharmacological profile (anti-PAF and 
anti-H(1)). METHODS: In a multicentre study, 250 patients with SAR were included 
in a double-blind, randomized, parallel-group and placebo-controlled study.
Patients received either rupatadine 10 mg, ebastine 10 mg or placebo once daily
for 2 weeks. The main efficacy outcome was based on the patient's record of
severity of nasal symptoms (sneezing, nasal itching, runny nose and nasal
obstruction) and nonnasal symptoms (conjunctival itching, tearing and pharyngeal 
itching). The daily total symptom score (DTSS) was the mean of the DSS recorded
for each of the seven symptoms assessed, and the mean DTSS (mDTSS) was the mean
of the DTSS values for each study day. RESULTS: Significant differences in mDTSS 
were detected between rupatadine and placebo (33% lower for rupatadine group; P =
0.005) after 2 weeks of treatment. The TSS for rupatadine were 22% lower than for
ebastine, although the differences were not statistically significant. No serious
adverse events were reported during the study period. CONCLUSIONS: Rupatadine 10 
mg once daily was clearly superior to placebo in alleviating the symptoms of SAR 
over a 2-week period. In comparison with ebastine, rupatadine shows a trend
towards a better profile as regard several secondary efficacy variables.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15180765 [PubMed - indexed for MEDLINE]

923: Curr Med Chem. 2004 Jun;11(11):1403-21.

Efficacy, chemistry and pharmacology of chinese herbal medicine for allergic
rhinitis.

Xue CC, Hügel HM, Li CG, Story DF.

The RMIT Chinese Medicine Research Group, Faculty of Life Sciences, RMIT
University, Bundoora, Vic. 3083, Australia. charlie.xue@rmit.edu.au

An extensive literature search identified six randomized controlled clinical
trials in which the efficacy of Chinese herbal medicine had been investigated for
the treatment of allergic rhinitis. Although four of these trials had
methodological flaws, the therapeutic outcomes of all six have been reviewed. One
of two trials considered to be of high quality was concerned with the treatment
of seasonal allergic rhinitis and the other with perennial allergic rhinitis. It 
is considered that all six studies demonstrated various degrees of alleviation of
the symptoms of allergic rhinitis. No serious side effects were reported in any
of the trials. A number of the herbs in the Chinese herbal formulae used in the
trials, and/or their constituent compounds have been reported to possess
anti-allergic, anti-inflammatory or immune modulation activity. Such actions
include inhibition of the release or action of mast cell mediators such as
histamine, inhibition of inflammation induced by chemical agents, and modulation 
of serum IgE levels or of lymphocyte and/or macrophage activity. An aqueous,
unresolved extract of the herbal formula used in one of the six trials has been
reported to exhibit a range of pharmacological actions relevant to the treatment 
of allergic rhinitis. Essential oils, lignans, flavonoids and saponins are
chemical classes that are frequently represented in individual herbs of the six
Chinese herbal formulae used in the trials. The chemical structures
characterising these classes of compound and the pharmacological actions of these
and other constituents of the herbs, relevant to allergic rhinitis, have been
reviewed.

Publication Types: 
    Comparative Study

PMID: 15180574 [PubMed - indexed for MEDLINE]

924: Eur Ann Allergy Clin Immunol. 2004 Apr;36(4):146-50.

Mizolastine and fexofenadine modulate cytokine pattern after nasal allergen
challenge.

Ciprandi G, Cirillo I, Vizzaccaro A.

San Martino Hospital, Genoa, Italy.

Allergen specific nasal challenge (ASNC) is an optimal model to study the
pathophysiological mechanisms sustaining allergic inflammation, particularly the 
cytokine pattern. Antihistamines have been accepted as a highly effective therapy
for allergic rhinitis. The aim of this double blind, randomised, placebo
controlled study was the evaluation of symptoms and cytokines, during the early
phase, after a single dose of mizolastine (10 mg), fexofenadine (120 mg) or
placebo, using the model of ASNC. A total of 30 patients with allergic rhinitis
underwent nasal challenge 6 hours after treatment. The following parameters were 
evaluated 30 minutes after ASNC (i.e. early phase): nasal symptoms (rhinorrhea,
itching, sneezing, obstruction), and cytokine pattern, including IL1, IL6, and
TNFalpha. Mizolastine was associated with early phase reduction of: i) clinical
symptoms (p < 0.03), ii) cyotkine levels of IL1 (p = 0.003), IL6 (p < 0.007), and
TNF_ (p < 0.003) in comparison with placebo group. Fexofenadine significantly
inhibited IL6 (p < 0.004) and TNFalpha (p < 0.004) levels in comparison with
placebo. The present findings demonstrate that mizolastine exerts a significant
effect on early phase events, reducing symptoms and pro-inflammatory cytokines.
Fexofenadine reduces TNFalpha and IL6 levels only. These effects appear to be
clinical relevant for mizolastine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15180356 [PubMed - indexed for MEDLINE]

925: Int Arch Allergy Immunol. 2004 Jul;134(3):227-32. Epub 2004 Jun 1.

Altered levels of the soluble IL-1, IL-4 and TNF receptors, as well as the IL-1
receptor antagonist, in intermittent allergic rhinitis.

Benson M, Wennergren G, Fransson M, Cardell LO.

Laboratory for Clinical and Experimental Allergology, Department of
Oto-Rhino-Laryngology, Malmö University Hospital, Lund University, Malmö, Sweden.
mikael.benson@vgregion.se

BACKGROUND: The effects of cytokines are modulated by soluble cytokine receptors 
(SCR) and receptor antagonists. Therefore, allergic disease may depend on altered
proportions between cytokines, their SCR and receptor antagonists, rather than
absolute changes in cytokine levels. Little is known about SCR in intermittent
allergic rhinitis (IAR). OBJECTIVE: To examine the concentrations of SCR, i.e.
sIL-1R2, sIL-4R, sIL-6R and sTNFR1, as well as the interleukin-1 receptor
antagonist (IL-1Ra) in nasal fluids from allergen-challenged patients with IAR
and healthy controls. METHODS: 30 patients with birch- or grass-pollen-induced
IAR and 30 healthy controls were studied. In the patients nasal fluids were
obtained before as well as 1 and 6 h after allergen provocation. RESULTS: Both
symptom scores and rhinoscopic signs of rhinitis increased in the patients after 
allergen challenge. Comparisons between patients and controls showed that sIL-4R 
was lower in patients before and 1 and 6 h after provocation. IL-1Ra was lower
before and 1 h after provocation. In addition, lower concentrations of sTNFR1
were found in patients after 1 h, while sIL-1R2 concentrations were higher after 
1 h. Comparisons of patients before and after challenge showed that IL-1Ra and
sTNFR1 decreased after 1 h, while sIL-1R2 increased. No significant differences
were found compared to 6 h. sIL-6R did not significantly differ between the study
groups. CONCLUSIONS: After allergen challenge, significant changes in the nasal
fluid levels of IL-1Ra, sIL-1R2 and sTNFR1 were found. By contrast, sIL-4R
remained at lower levels than in controls both before and after challenge. Since 
sIL-4R modulates IgE synthesis, this may play a role in the pathogenesis of IAR. 
Copyright 2004 S. Karger AG, Basel

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15178892 [PubMed - indexed for MEDLINE]

926: Allergy Asthma Proc. 2004 Mar-Apr;25(2):107-13.

Direct cost assessments in subjects with seasonal allergic rhinitis living in
Ankara, Turkey.

Celik G, Mungan D, Abadoğlu O, Pinar NM, Misirligil Z.

Department of Chest Diseases, Ankara University School of Medicine, Cebeci
Hospital, Ankara, Turkey.

The characteristics of seasonal allergic rhinitis (SAR) including the severity at
initial presentation and cost estimates are not established for Turkey. The aim
of this study was to document the clinical features and direct cost of subjects
with SAR when diagnosed and followed according to international treatment
guidelines and to determine the effectiveness of treatment in relation to the
regional pollen count in our country. The clinical features of SAR were
determined cross-sectionally in 175 patients living in Ankara, Turkey. The direct
medical cost analysis obtained by a symptom-medication score method was performed
prospectively in a subgroup of patients evaluated at the beginning of the pollen 
season (n = 37). Airborne Gramineae pollen grains were counted also in the same
period. SAR was mild in 12.6% of cases, moderate in 51.4% of cases, and severe in
36% of cases. Regional pollen counts were correlated with the number of patient
visits and the initial severity of SAR. Mean cost of SAR per person without a
comorbid disorder during a Gramineae pollen season for Ankara was 79.0 +/- 3.3
dollars, where it reached a mean of 138.60 +/- 0.5 dollars in the presence of
asthma and/or conjunctivitis. No difference was observed among disease severity
groups by means of total direct cost (p > 0.05). Regional pollen counts influence
the initial severity of SAR in our country. Appropriate treatment seemed to
induce effective symptom control. Hence, education of both public and primary
care physicians about the international guidelines might provide better
cost-effective management of SAR.

PMID: 15176495 [PubMed - indexed for MEDLINE]

927: Allergy Asthma Proc. 2004 Mar-Apr;25(2):81-3.

Onset of action for the relief of allergic rhinitis symptoms with
second-generation antihistamines.

Greisner WA 3rd.

Allergy and Asthma Associates of the Bluegrass, Lexington, Kentucky, USA.

Onset of action for relief of allergic rhinitis symptoms is of clinical
significance to both the physician and the patient. Using either subjective or
objective methods, the onset of action after a single, oral dose of an
antihistamine can be measured. Multicenter studies, outdoor studies, and pollen
challenge systems have been used to measure the onset of action. A literature
search from 1985 to May 2002 was performed. All published, randomized,
placebo-controlled clinical studies pertaining to the onset of action for relief 
of allergic rhinitis symptoms after a single, oral dose of a second-generation
antihistamine (not combined with a decongestant) including cetirizine,
desloratadine, fexofenadine, and loratadine, were reviewed. The onset of action
for cetirizine ranged from 59 minutes to 2 hours and 6 minutes and for loratadine
onset of action ranged from 1 hour and 42 minutes to none identified during the
duration of the study. Cetirizine had a shorter onset of action than loratadine
for all comparisons. Fexofenadine had an onset of action within 60 minutes. The
literature search did not reveal any published onset of action studies for
desloratadine. The onset of action for a given second-generation antihistamine
depends on how it is defined and subsequently measured.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15176489 [PubMed - indexed for MEDLINE]

928: Int J Immunopathol Pharmacol. 2004 May-Aug;17(2):201-8.

Do tryptase, ECP and specific IgE measurement by nasal incubation increase the
specific nasal provocation test sensitivity?

Bellussi L, Marcucci F, Sensi LG, Passali GC, Lauriello M, Passali FM, Giannuzzi 
AL, Passali D.

ENT Dept, University of Siena, Italy.

The specific Nasal Provocation Test (sNPT) is a third level diagnostic tool.
Fitted to reproduce natural exposure condition to pick the responsible allergen
for nasal symptoms out, it is applied when prick test and RAST responses are
doubtful. SNPT results have been evaluated measuring nasal resistance (anterior
rhinomanometry) and nasal symptoms (clinical score), reaching 50% of sensitivity.
This study focused on the determination of allergic response markers, triggered
by nasal challenge: tryptase levels in the nose, specific IgE and ECP (Eosinophil
Cationic Protein). The aim was to increase sNPT sensitivity. Twenty patients
suffering from allergic rhinitis and 16 age-matched-nonallergic subjects were
enrolled in the study. Tryptase, specific IgE and ECP were determined in nasal
mucosa applying a new method, based on in situ incubation, before and after sNPT.
The latter was performed following a standardized method. Tryptase levels
increased in 13 patients (65%), were unchanged in four patients (20%), and
slightly decreased in three patients (15%). The increase recorded was significant
in mite allergic patients (p=0.005), but not significant (p> 0.05) in pollen
allergic patients. ECP values increased in 13 patients (65%), were unchanged in
two patients (10%), and highly decreased in five patients (25%). ECP increase was
not significant (p> 0.05). Specific IgE levels increased in seven patients (35%),
were unchanged in 11 patients (55%) and decreased in two patients (10%). The IgE 
increase was significant in pollen-allergic patients (p<0.05), while it was not
significant in mite-allergic patients (p>0.05). Tryptase, ECP, and specific IgE
were not detected in the control group. The data obtained showed a positive sNPT 
response in 12 patients (60%). Comparing our results with those derived from
classical-parameter employment, we gathered an improvement of 10%. On the basis
of the usual parameters, in fact, we recorded 50% positivity, while the use of
mediators provided an additional 10% improvement in sNPT sensitivity: taking
together the usual parameters and nasal allergic mediators values, we reached an 
sNPT over-all sensitivity of 85%.

PMID: 15171821 [PubMed - indexed for MEDLINE]

929: J Investig Allergol Clin Immunol. 2004;14(1):56-63.

A randomized, double-blind, placebo-controlled study comparing the efficacy and
safety of ebastine (20 mg and 10 mg) to loratadine 10 mg once daily in the
treatment of seasonal allergic rhinitis.

Hampel F Jr, Howland W 3rd, Van Bavel J, Ratner P.

Central Texas Health Research, New Braunfels, TX, USA. fchampel@aol.com

Few randomized studies have compared the H1-receptor antagonists loratadine and
ebastine in seasonal allergic rhinitis (SAR) patients. The objective of this
study was to compare the efficacy and safety of ebastine 20 mg (E20), ebastine 10
mg (E10), loratadine 10 mg (L10), and placebo (P), once daily, in controlling
symptoms of SAR over a 4-week period. This was a double-blind,
placebo-controlled, randomized, parallel-group study. Efficacy was assessed in
749 patients (12 to 70 years old) by SAR symptom scores (nasal discharge,
congestion, itching, sneezing, and total eye symptoms) entered on diary cards
every morning and every evening over the previous 12 hours (reflective score) and
at the time of recording (snapshot score). The E20 group showed greater
reductions from baseline compared with the L10 group in 2 daily reflective
composite scores (nasal index [with or without congestion]) and in all 4 daily
snapshot composite scores. E10 and L10 groups showed no significant differences
in either the daily reflective or snapshot scores overall although E10 showed a
greater improvement of nasal discharge snapshot score than L10. The efficacy of
E20 at controlling the symptoms of SAR was well sustained during the fourth week 
of treatment, with significant differences over placebo in 22/36 total rhinitis
symptom scores, followed by E10 (6/36), whereas L10 showed no differences (0/36).
Patient and physician global evaluations at the final visit were not
statistically significant for any treatment group compared with placebo. There
was no significant difference among all groups in the number of patients who
reported adverse events. In conclusion, ebastine 20 mg given once daily for 4
weeks in the treatment of SAR showed larger mean reductions from baseline in most
rhinitis symptoms scores than loratadine 10 mg. Sustained efficacy was most
frequently observed with ebastine 20 mg over placebo, whereas loratadine 10 mg
did not provide a statistically significant improvement in any individual or
composite symptom score at the end of the fourth week. Both ebastine 20 and 10 mg
were well tolerated and proved safe in the treatment of SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15160443 [PubMed - indexed for MEDLINE]

930: J Investig Allergol Clin Immunol. 2004;14(1):34-40.

A randomized, double-blind, parallel-group study, comparing the efficacy and
safety of rupatadine (20 and 10 mg), a new PAF and H1 receptor-specific histamine
antagonist, to loratadine 10 mg in the treatment of seasonal allergic rhinitis.

Saint-Martin F, Dumur JP, Pérez I, Izquierdo I; French Rupatadine-Rhinitis Study 
Group.

Clinical Research Unit, Research Centre, J. Uriach & Cía S.A., Barcelona, Spain.

BACKGROUND: The main objective of this randomized, double-blind, parallel-group, 
comparative study was to assess the efficacy and safety of rupatadine 10 mg (R10)
and 20 mg (R20) administered once-daily for two weeks compared with those of
loratadine 10 mg (L10) in the treatment of seasonal allergic rhinitis (SAR).
METHODS: A total of 339 SAR patients were randomized to receive R20 (111
patients), R10 (112 patients) or L10 (116 patients). The main efficacy variable
was the mean total daily symptom score (mTDSS) based on the daily subjective
assessment of the severity of rhinitis symptoms--rhinorrhea, sneezing, nasal
itching, nasal obstruction, conjunctival itching, tearing and pharyngeal
itching--recorded by patients. RESULTS: The mTDSS was significantly lower in the 
groups treated with R20 (0.80 +/- 0.46) and R10 (0.85 +/- 0.52) than in the group
treated with L10 (0.92 +/- 0.51) by protocol analysis (p = 0.03) but not by
intention-to-treat analysis. The secondary variables used to assess efficacy
(mDSS, DSSmax, CSS and TCSS) also showed significantly milder symptoms in
patients treated with R20 and R10, particularly in sneezing and nasal itching.
All treatments were well tolerated and no serious adverse events were recorded.
Headache was the most frequent non-serious adverse event, and these did not show 
significant differences between treatments at similar dose levels. Somnolence was
more frequent in R20 than in the other two groups. CONCLUSIONS: The present
results suggest that rupatadine 10 mg a day may be a valuable and safe
alternative for the symptomatic treatment of seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15160440 [PubMed - indexed for MEDLINE]

931: Am J Chin Med. 2004;32(1):105-15.

The effect of acupuncture on allergic rhinitis: a randomized controlled clinical 
trial.

Magnusson AL, Svensson RE, Leirvik C, Gunnarsson RK.

Bollebygd's Primary Health Care Center, Bollebygd, Sweden.
anna-lena.magnusson@vgregion.se

Allergic rhinitis is a common health problem usually treated with drug therapy.
Some patients experience side effects of drug therapy while others fear the use
of drugs. Acupuncture is an interesting alternative to traditional treatment. The
few studies evaluating acupuncture indicate a possible clinical effect on
allergic rhinitis. This study compared active versus sham acupuncture in 40
consecutive patients with a history of allergic rhinitis and a positive skin
test. Patients were randomized and assessed prior to treatment and then
reassessed after 12 months. Improvements in symptoms using visual analogue
scales, reduction in skin test reactions and levels of specific immunoglobin E
(IgE) were used to compare the effect of treatment. For one allergen, mugwort, a 
greater reduction in levels of specific IgE (p = 0.019, 0.039) and skin test
reaction (p = 0.004) was seen in the group receiving active acupuncture compared 
to the group receiving sham acupuncture. However, this finding might be an
artifact. No differences in clinical symptoms were seen between active versus
sham acupuncture, thus the conclusion being that the effect of acupuncture on
allergic rhinitis should be further evaluated in larger randomized studies.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15154290 [PubMed - indexed for MEDLINE]

932: Clin Exp Allergy. 2004 May;34(5):770-8.

Roles of major oligosaccharides on Cry j 1 in human immunoglobulin E and T cell
responses.

Okano M, Kimura Y, Kino K, Michigami Y, Sakamoto S, Sugata Y, Maeda M, Matsuda F,
Kimura M, Ogawa T, Nishizaki K.

Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate
School of Medicine and Dentistry, Okayama, Japan. mokano@cc.okayama-u.ac.jp

BACKGROUND: We have demonstrated that carbohydrates in Cry j 1, the major
allergen of Cryptomeria japonica pollen, play a major role in promoting Cry j
1-specific Th2 response. However, little is known as to whether the carbohydrates
directly participate in allergic responses. OBJECTIVE: We sought to determine
whether Cry j 1-related oligosaccharides function as IgE and/or T cell epitopes. 
In addition, the regulatory effect of Cry j 1-related oligosaccharide on Cry j
1-specific T cell responses was investigated. METHODS: Two monovalent
oligosaccharides largely found on Cry j 1,
Manalpha1-6(Manalpha1-3)(Xylbeta1-2)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc
(M3FX), and
GlcNAcbeta1-2Manalpha1-6(GlcNAcbeta1-2Manalpha1-3)(Xylbeta1-2)Manbeta1-4GlcNAcbet
a1-4(Fucalpha1-3)GlcNAc (GN2M3FX) were prepared.
Manalpha1-2Manalpha1-6(Manalpha1-2Manalpha1-3)Manalpha1-6(Manalpha1-2Manalpha1-2M
analpha1-3)Manbeta1-4GlcNAcbeta1-4GlcNAc (M9A) was used as control. Competitive
inhibition ELISA for Cry j 1-specific IgE was performed using these
oligosaccharides as inhibitors. In addition, T cell lines specific for Cry j 1 or
purified protein derivative of Mycobacterium tubecurosis (PPD) were established, 
and cellular responses against these oligosaccharides were investigated in the
presence or absence of the respective antigens. RESULTS: Overall, neither M3FX
nor GN2M3FX displayed inhibitory effect on the binding between IgE and Cry j 1.
In addition, M3FX did not by itself stimulate Cry j 1 or PPD-specific T cells.
However, M3FX significantly inhibited Cry j 1-induced proliferation and IL-4
production in Cry j 1-specific T cells. Such an inhibitory effect was not seen in
PPD-specific T cell responses. CONCLUSION: These results suggest that Cry j
1-related oligosaccharides are not major epitopes for IgE or T cells. However,
these oligosaccharides have a novel potential to inhibit Cry j 1-specific T cell 
responses selectively.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15144470 [PubMed - indexed for MEDLINE]

933: Clin Exp Allergy. 2004 May;34(5):731-5.

Topical treatment with aqueous solutions of rofleponide palmitate and budesonide 
in a pollen-season model of allergic rhinitis.

Ahlström-Emanuelsson C, Andersson M, Persson C, Schrewelius C, Greiff L.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital,
Lund, Sweden.

BACKGROUND: Rofleponide palmitate is an esterified glucocorticosteroid pro-drug
with a promising pre-clinical profile designed to deliver topical airway
treatment for allergic rhinitis and asthma in a novel manner. Thus, the
rofleponide palmitate pro-drug is designed to provide topical exposure of the
mucosa to the inactive lipophilic drug, which would be locally metabolized to the
more hydrophilic and readily cleared drug rofleponide. OBJECTIVE: To examine
whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow
(PIF) in a pollen-season model of allergic rhinitis and to compare any such
effects with those of another glucocorticosteroid (i.e., budesonide). METHODS:
During the pollen-free season, 40 patients with strictly seasonal allergic
rhinitis received topical nasal spray treatment with an aqueous solution of
rofleponide palmitate 400 microg and an aqueous solution of budesonide 128 microg
once daily for 10 days in a double-blind, placebo-controlled, and crossover
study. After 3 days of drug treatment, individualized allergen challenges were
given once daily for 7 days while the treatment continued. The washout periods
between each of the challenge series were 2 weeks. Nasal symptoms and PIF were
recorded in the morning and evening, as well as 10 and 20 min after each allergen
challenge. The mean recordings obtained during the last 3 days of the
allergen-challenge series, when symptoms were established and when the treatment 
had lasted for 8-10 days, were used in the analysis. RESULTS: Both active
treatments reduced nasal symptoms and improved nasal PIF compared with placebo
(P<0.01-0.001). There was no overall difference in efficacy between rofleponide
palmitate 400 microg and budesonide 128 microg. CONCLUSIONS: Topical treatment
with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and
improves nasal PIF in allergic rhinitis. The overall efficacy of 400 microg of
rofleponide palmitate is similar to that of 128 microg of budesonide in the
pollen-season model used in this study.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15144464 [PubMed - indexed for MEDLINE]

934: Saudi Med J. 2004 May;25(5):621-4.

Examination of the distribution of mast cells in the nasal mucosa of patients
with seasonal allergic rhinitis.

Kilinc N, Cureoglu S, Oktay F.

Department of Pathology, Dicle University Medical School, Diyarbakir, Turkey.
nhl@dic.edu.tr

OBJECTIVE: It is known that mast cells play an important role in pathogenesis of 
allergic rhinitis. In this study, we investigated the distribution of mast cells 
in the nasal mucosa of patients with seasonal allergic rhinitis during the
pollen-season. METHODS: This study was carried out at the Faculty of Medicine,
Dicle University, Turkey, during the grass-pollen season between, March and July 
in 2002. Twenty patients with seasonal allergic rhinitis (12 females and 8 males)
and 20 healthy (10 females and 10 males) non-allergic controls were examined for 
the distribution and abundance of mast cells in nasal biopsies. Biopsies were
performed in all patients and controls, once during natural provocation in the
spring and were taken from the lower edge of the inferior turbinate using a
forceps. The samples of nasal mucosa were fixed in 10% neutral buffered
formaline, stained with 0.5% aqueous toluidine blue and hematoxylin and eosin
were examined under a light microscope. RESULTS: Mast cells were observed in the 
nasal mucosa obtained from 12 patients (60%) and 5 patients (25%) controls cases 
(p=0.025). It was found out that intrapitelial mast cells are present in nasal
mucosa samples of patients with SAR (seasonal allergic rhinitis) but not in the
epithelium of non-allergic controls. CONCLUSION: The number of submucosal mast
cells has considerably increased in the nasal mucosa samples of patients with
SAR. Besides this, these cells are determined in great amounts in non-allergic
individuals.

PMID: 15138530 [PubMed - indexed for MEDLINE]

935: Otolaryngol Head Neck Surg. 2004 May;130(5):617-29.

Influences of allergic rhinitis on sleep.

Ferguson BJ.

Division of Sino-Nasal Disorders and Allergy, University of Pittsburgh Medical
Center, Pennsylvania, USA. fergusonbj@upmc.edu

BACKGROUND: Allergic rhinitis is classically characterized by sneezing, pruritus,
rhinorrhea, and nasal congestion. These symptoms can lead to impaired nocturnal
sleep, and this impairment results in daytime fatigue and somnolence, reducing
both learning and work efficiency and decreasing quality of life. STUDY DESIGN:
In addition, the mediators of AR, including histamine, leukotrienes, cytokines,
and prostaglandins, may play a role in sleep regulation and, thus, may be
directly involved in this impairment independent of nasal obstruction. Recumbency
and/or diurnal variation augments turbinate swelling, causing nasal blockage
during nocturnal sleep. Medications directed toward reversal of nasal congestion 
often concomitantly work through suppression of inflammatory mediators and
constitute the primary therapy for sleep disturbance associated with allergic
rhinitis. Some pharmaceutical interventions that reduce nasal congestion have
adverse effects on sleep. Decongestants effectively reduce nasal congestion but
frequently produce stimulatory effects and even insomnia. Antihistamines reduce
sneezing and pruritus, but are less effective in relieving congestion. Earlier,
"first-generation" antihistamines are associated with significant sedation. They 
also have anticholinergic properties, which can cause dry mouth and make mouth
breathing even more uncomfortable in the allergic individual with nasal
obstruction. The absence of anticholinergic properties in second-generation,
largely nonsedating antihistamines limits their efficacy in rhinorrhea.
Azelastine, a topical antihistamine, significantly reduces rhinorrhea and
congestion and improves subjective sleep quality, but is also associated with
increased sedation. Intranasal corticosteroids and oral leukotriene receptor
antagonists effectively reduce rhinorrhea, congestion, and inflammatory
mediators. CONCLUSIONS: The efficacy of these medications at improving subjective
sleep quality has been established through multiple randomized, double-blind,
placebo-controlled clinical trials.

Publication Types: 
    Review

PMID: 15138430 [PubMed - indexed for MEDLINE]

936: Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):171-6.

Quality of life scales in allergic rhinitis.

Kremer B.

Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty of
University of Maastricht, The Netherlands. bkr@skno.azm.nl

PURPOSE OF REVIEW: The recent literature on types, development, validation,
indications, and limitations of quality of life scales in allergic rhinitis is
reviewed. This review does not report clinical trials that included quality of
life as an outcome. RECENT FINDINGS: Today, quality of life measurement is
standard in allergic rhinitis. Different disease-specific and generic
questionnaires are very well validated and established. Recent research concerns 
the development or adaptation of questionnaires for specific purposes or
populations. Other research focuses on the registration of concomitant illnesses,
especially of asthma, taking the model of rhinitis and asthma as 'one airway
disease' into account. Recently, the first questionnaire for rhinitis and asthma 
was presented. Furthermore, attempts have been made to improve the registration
of other local or systemic concomitant illnesses, the sensitivity to rapid
changes in the patient's condition, and the objectivity of quality of life
scales. SUMMARY: Allergic rhinitis is associated with significant impairments of 
quality of life. Disease-specific quality of life scales offer a better
registration of changes in disease-related problems, whereas generic scales allow
for a comparison between different disorders and patient populations. Different
versions of quality of life scales have been validated for different purposes.
Careful selection of quality of life scales is becoming more and more important. 
The registration of comorbid conditions and of psychological factors influencing 
quality of life measurement remains a central problem. For research, the
combination of disease-specific and generic quality of life scales may offer new 
perspectives; for clinical use, patient-friendly scales should be used.

Publication Types: 
    Review

PMID: 15126937 [PubMed - indexed for MEDLINE]

937: Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):159-63.

Mediators of inflammation in the early and the late phase of allergic rhinitis.

Hansen I, Klimek L, Mösges R, Hörmann K.

ENT Department, Mannheim University Hospital, Germany.

PURPOSE OF REVIEW: This review provides the reader with an overview of the early 
and the late phase of the immediate allergic reaction. Furthermore, recent
publications are presented that could reveal important new insights into the
mechanisms of allergic inflammation. RECENT FINDINGS: Recent work on the possible
roles of nerve growth factor, nitric oxide synthases, several CC chemokines and
other mediators is presented. SUMMARY: Allergic rhinitis is characterized by the 
clinical symptoms of sneezing, itching, rhinorrhea, and nasal congestion.
Frequently, these are accompanied by eye, ear and throat symptoms or postnasal
drip. The symptoms arise as a result of inflammation induced by IgE-mediated
immune response to a specific allergen. Inflammatory mediators are released and
cells are activated and recruited to the mucosa. In this review, early and late
phase responses of the allergic type I reaction are described, including the
different cell types and mediators involved. Special attention is paid to new
inflammatory processes to provide the reader with recent information.

Publication Types: 
    Review

PMID: 15126935 [PubMed - indexed for MEDLINE]

938: Auris Nasus Larynx. 2004 Jun;31(2):135-9.

Measurement of quality of life during different clinical phases of Japanese cedar
pollinosis.

Nishiike S, Ogino S, Irifune M, Arimoto H, Sakaguchi Y, Takeda M, Baba K, Miyake 
Y, Harada T.

Department of Otolaryngology, Suita Municipal Hospital, 2-13-20 Katayama-cho,
Suita, Osaka 564-0082, Japan. nishiike@concerto.plala.or.jp

OBJECTIVE: To assess Quality of Life (QOL) scores in patients with Japanese cedar
(Cryptomeria japonica, CJ) pollinosis. METHODS: QOL was measured intraseasonally 
and extraseasonally in patients (n = 69) using the Medical Outcomes Study
Short-Form Health Survey, and compared with healthy control subjects (n = 50).
The differences in intraseasonal QOL scores between short and long disease
duration groups were studied. The relation of intraseasonal QOL scores to nose
symptoms was evaluated using Spearman's rank correlation. RESULTS: Significant
decrease was observed in two of eight QOL items in intraseasonal measurements of 
patients. These QOL impairments improved extraseasonally. Scores for emotional
problems in patients with long disease duration were less impaired than those
with short disease duration. QOL scores in patients correlated poorly with the
severity of nasal symptom. CONCLUSIONS: This is the first study to report QOL
impairment in CJ pollinosis. Based on the findings long disease duration may
improve emotional problems, and the correlation between disease severity and QOL 
is low.

PMID: 15121222 [PubMed - indexed for MEDLINE]

939: Ann Allergy Asthma Immunol. 2004 Apr;92(4):438-45.

Comment in:
    Ann Allergy Asthma Immunol. 2004 Aug;93(2):206; author reply 206-7.

Effect of nasal triamcinolone acetonide on seasonal variations of bronchial
hyperresponsiveness and bronchial inflammation in nonasthmatic children with
seasonal allergic rhinitis.

Orhan F, Sekerel BE, Adalioglu G, Pinar M, Tuncer A.

Faculty of Medicine, Department of Pediatric Allergy, Hacettepe University,
Ankara, Turkey.

BACKGROUND: Recent evidence suggests that patients with allergic rhinitis have
lower airway inflammation and a higher prevalence of bronchial
hyperresponsiveness (BHR) regardless of asthma. OBJECTIVE: To investigate markers
of lower airway inflammation in nonasthmatic children with seasonal allergic
rhinitis (SAR) before and during pollen season and the effect of nasal
triamcinolone acetonide on seasonal variations in these parameters. METHODS:
Thirty-two nonasthmatic children with SAR in response to grass and/or weed
pollens were recruited and separated into 2 groups. Group 1 was treated with
triamcinolone acetonide (220 microg once daily) for 6 weeks, and group 2 received
no intranasal corticosteroid treatment. Bronchial responsiveness to methacholine 
[concentration that caused a decrease in forced expiratory volume in 1 second of 
20% (PC20)], eosinophil counts in sputum and peripheral blood, and eosinophil
cationic protein (ECP) levels in sputum and serum were measured before and during
grass pollen season. RESULTS: Twenty-eight patients completed the study. During
the pollen season, methacholine PC20 significantly decreased in both groups when 
compared with the corresponding preseasonal values (P = .01 and P = .003,
respectively). The mean percentage of sputum eosinophils increased significantly 
during the pollen season compared with preseasonal values in group 1 and group 2 
(12.7% +/- 2.1% vs 16.5% +/- 2.1%, P = .007, and 11.0% +/- 2.0% vs 20.2% +/-
1.4%, P = .003, respectively). Median [interquartile ranges (IQR)] sputum ECP
levels were significantly higher during the pollen season when compared with the 
preseasonal values in group 1 and group 2 [7.5 microg/L (3.5-36.0 microg/L) vs
35.5 microg/L (13.0-71.7 microg/L), P = .04, and 18.0 microg/L (6.0-36.0
microg/L) vs 69.0 microg/L (39.0-195.0 microg/L), P = .003, respectively], as
were the serum ECP levels [6.0 microg/L (2.0-13.0 microg/L) vs 19.0 microg/L
(14.0-43.5 microg/L), P = .004, and 6.0 microg/L (3.0-7.0 microg/L) vs 18.0
microg/L (6.0-36.0 microg/L), P = .001, respectively]. Although the mean number
of eosinophils in blood increased during the pollen season in both groups, it was
only significant in group 2 (70.0 +/- 20.0 vs 161.6 +/- 29.0, P = .02).
CONCLUSIONS: Although prophylactic nasal corticosteroid treatment provides
significant reduction of nasal symptoms and rescue antihistamine use, there is no
significant prevention in the seasonal increase of bronchial inflammation and
methacholine BHR.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 15104196 [PubMed - indexed for MEDLINE]

940: J Allergy Clin Immunol. 2004 Apr;113(4):663-8.

Changes in daytime sleepiness, quality of life, and objective sleep patterns in
seasonal allergic rhinitis: a controlled clinical trial.

Stuck BA, Czajkowski J, Hagner AE, Klimek L, Verse T, Hörmann K, Maurer JT.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital
Mannheim, 68135 Mannheim, Germany.

BACKGROUND: It has long been assumed that allergic rhinitis leads to daytime
sleepiness and a deterioration of nocturnal sleep, yet systematic studies have
only been rarely conducted in this field. OBJECTIVE: The aim of the present study
was to investigate the effects of seasonal allergic rhinitis on subjective and
objective sleep patterns, quality of life, and daytime sleepiness in otherwise
healthy subjects in comparison with nonallergic volunteers. METHODS: Twenty-five 
patients with seasonal allergic rhinitis and 25 healthy volunteers were enrolled 
in this prospective, controlled clinical trial. Daytime sleepiness and quality of
life were assessed with the help of questionnaires (Epworth Sleepiness Scale,
SF-36); 2 consecutive nights of fully attended polysomnography were performed
before and during the pollen season of 2002. RESULTS: Statistically significant
differences between groups were found in respect to changes in daytime sleepiness
and selected parameters of quality of life. Impairment of daytime sleepiness and 
quality of life were related to the severity of the disease. Statistically
significant differences were also found for selected parameters of the sleep
studies, although the changes were only minimal, and all values were within
normal ranges. CONCLUSION: Seasonal allergic rhinitis leads to increased daytime 
sleepiness, as well as to an impairment of quality of life, depending on the
severity of the disease. Objective measurements revealed a statistically
significant influence of seasonal allergic rhinitis on selected sleep parameters,
but changes were not of clinical relevance. Daytime sleepiness seems to be
related to the condition itself rather than to an impairment of nocturnal sleep.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15100670 [PubMed - indexed for MEDLINE]

941: Am J Med Sci. 2004 Mar;327(3):127-38.

Clinical implications of the allergic rhinitis-asthma link.

Casale TB, Dykewicz MS.

Department of Medicine, Creighton University, Omaha, Nebraska, USA.
tbcasale@creighton.edu

A possible link between allergic rhinitis (AR) and allergic asthma has long been 
a subject of debate. Surveys report that up to 78% of asthma patients have AR and
38% of patients with AR have asthma. Evidence points to a causal or coincidental 
relation between these upper and lower airway diseases. Various agents used to
manage one entity have shown benefit in treating the other. The 2001 Allergic
Rhinitis and Its Impact on Asthma guidelines call for patients with either
condition to be assessed for the other. Medical therapy for AR or asthma should
be chosen with awareness of the probable coexistence of these diseases. We
present the case for and against the united airway theory proposed to explain the
association between these diseases. The roles of various therapies for dually
afflicted patients are evaluated, including topical corticosteroids,
antihistamines, leukotriene modifiers, anti-immunoglobulin E monoclonal antibody,
theophylline, and immunotherapy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15090751 [PubMed - indexed for MEDLINE]

942: Allergol Immunopathol (Madr). 2004 Mar-Apr;32(2):69-75.

Non-occupational allergy caused by the pine processionary caterpillar
(Thaumetopoea pityocampa).

Fuentes Aparicio V, de Barrio Fernández M, Rubio Sotés M, Rodríguez Paredes A,
Martínez Molero MI, Zapatero Remón L, Bartolomé Zavala B.

Allergy, General Hospital Universitary Gregorio Marañón. Madrid. Spain.
victoriafuente@terra.es

Contact with the pine processionary caterpillar induces dermatitis, usually
located in exposed areas, and, less frequently, ocular lesions through a
toxic-irritative mechanism. Recently, the existence of an immediate
hypersensitivity mechanism has been demonstrated, mainly in occupationally
exposed patients. OBJECTIVE: To present four patients who experienced allergic
reactions (urticaria-angioedema and rhinitis-asthma) after non-occupational
exposure to pine processionary caterpillar. PATIENTS AND METHODS: The four
patients underwent allergy testing through skin prick tests (SPT), specific IgE
detection and SDS-PAGE immunoblotting. One patient also underwent a specific
bronchial challenge test with the pine processionary antigen. RESULTS: In all
patients, both SPT with the caterpillar extract and specific IgE were positive.
Western blotting showed several IgE-binding bands with molecular mass values
ranging from 18 to 107 kDa. A shift in the electrophoretic mobility of some of
the relevant allergens occurred under the presence of a reductive agent (beta
-mercaptoethanol). The specific bronchial challenge test with pine processionary 
antigen performed in one of the patients also produced positive results.
CONCLUSIONS: The results of this study show an immunologic IgE-mediated immediate
hypersensitivity mechanism in these reactions. The processionary caterpillar's
airborne urticating hairs or spicules should be considered, at least in some
locations, not only as contact and occupational allergens, but also as seasonal
aeroallergens.

Publication Types: 
    Case Reports

PMID: 15087093 [PubMed - indexed for MEDLINE]

943: Allergol Immunopathol (Madr). 2004 Mar-Apr;32(2):59-63.

The prevalence of allergic asthma and rhinitis in children of Polichni,
Thessaloniki.

Sichletidis L, Chloros D, Tsiotsios I, Gioulekas D, Kyriazis G, Spyratos D,
Charalambidou O, Goutsikas S.

Pulmonary Clinic, Aristotle University of Thessaloniki, Greece. Laboratory for
the Investigation of Environmental Diseases. aravinou@compulink.gr

AIM: To define the prevalence of asthma and rhinitis in primary school children
in the Polichni Municipality of the city of Thessaloniki. METHODS AND RESULTS:
The parents of 2005 students living in the area of Polichni completed a
questionnaire for the detection of pulmonary disease in childhood. Of 493
children who gave positive answers to the questions about allergies, asthma and
rhinitis, 203 were excluded after an interview with the parents, because they
suffered from either atopic dermatitis or drug allergy or had normal lgE levels. 
Of the remaining children, 290 were further examined: methacholine test was
positive in 109, exercise test was positive in 67, nasal provocation test with
histamine was positive in 244, and rhinodilation test with tramazoline was
positive in 206. Skin prick tests were positive in 142 children (90 to
grass-cereal pollen, 66 to acarea and 59 to Parietaria officinalis). CONCLUSIONS:
We found that 168 children suffered from rhinitis, 84 from both asthma and
rhinitis concurrently and 38 from asthma alone. Only 37 % of the parents knew
that their children suffered from asthma, while even fewer (32 %) knew that their
children had rhinitis. The prevalence of asthma was 6.1 % and that of rhinitis
was 12.6 % among children aged 9-12 years in the area of Polichni, Thessaloniki. 
Childhood rhinitis and asthma seem to be frequently underdiagnosed and
undertreated.

PMID: 15087091 [PubMed - indexed for MEDLINE]

944: Allergy. 2004 May;59(5):498-504.

Efficacy of sublingual swallow immunotherapy in children with severe grass pollen
allergic symptoms: a double-blind placebo-controlled study.

Bufe A, Ziegler-Kirbach E, Stoeckmann E, Heidemann P, Gehlhar K, Holland-Letz T, 
Braun W.

Experimental Pneumology, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1,
Bochum, Germany.

BACKGROUND: Local application of allergen extracts in specific immunotherapy is
accompanied by increased compliance and significantly reduced side effects.
However, efficacy of local immunotherapy in children has yet not been
sufficiently demonstrated. This study was performed to determine clinical
efficacy of high dose sublingual swallow immunotherapy (SLIT) by a double-blind
placebo-controlled study in children with grass pollen allergy using high dose
allergen extracts. METHODS: A total of 161 children with seasonal
rhinoconjunctivitis of which, 68 had also asthma symptoms were enrolled in a
multicenter double-blind placebo-controlled study for 1 year and treated on a
daily basis with sublingually applied allergen drops. After 1 year all children
were given treatment for another 2 years in an open-controlled setting. Symptom
scores and medication were assessed during the pollen seasons with structured
interviews. Applied allergen dosage, compliance, and side effects were documented
by daily diary cards. Primary endpoint was a clinical index (CI) combining
symptom scores with medication index. Titrated skin prick tests (SPT) and
specific antibody measurements were performed each year. RESULTS: Combining
symptom with medication scores to CI was highly reliable (reliability coefficient
= 0.89, standard error = 9.6%). Allergen-specific IgE- and IgG-subclass
antibodies increased significantly in patients treated with SLIT indicating an
activation of the immune response induced by the locally applied grass pollen
extract. SPT reactivity did not change during therapy. After 1 year of SLIT in
the original design we observed no significant difference in the CI between
treatment and placebo analyzing all patients included in the study per intention 
to treat and per protocol. However, subgroup analysis in a repeated measures
model revealed that patients with SLIT and severe symptoms before the beginning
of treatment (CI > mean/ > 1.51) showed a significant improvement of clinical
symptoms after 3 years. CONCLUSION: In this study SLIT was accompanied by a
significant placebo effect. Efficacy of treatment could only be seen in children 
with severe clinical symptoms and this became clinically marked after 3 years of 
therapy.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15080830 [PubMed - indexed for MEDLINE]

945: Eur Respir J. 2004 Mar;23(3):407-13.

Comment in:
    Eur Respir J. 2004 Mar;23(3):359-60.

No further increase in asthma, hay fever and atopic sensitisation in adolescents 
living in Switzerland.

Braun-Fahrländer C, Gassner M, Grize L, Takken-Sahli K, Neu U, Stricker T,
Varonier HS, Wüthrich B, Sennhauser FH; Swiss Study on Childhood Allergy and
Respiratory symptoms; Air Pollution (SCARPOL) team.

Institute of Social and Preventive Medicine, University of Basel, Basel,
Switzerland. C.Braun@unibas.ch

Prevalence rates of childhood asthma and allergy have been on the increase for
several decades. The present study investigated whether this trend continued
during the 1990s in adolescents living in Switzerland. Between 1992 and 2000, the
change in prevalence of specific immunoglobulin E to aeroallergens, asthma
symptoms and hay fever symptoms assessed by parents' and students' answers to the
International Study of Asthma and Allergies in Childhood questions was
investigated using three cross-sectional surveys. In total 1,324 (74.9%), 1,668
(80.6%) and 1,250 (73.9%) adolescents participated. Prevalence rates of asthma
and current asthmatic symptoms remained constant, irrespective of whether the
assessment was based on parental questionnaires or the student's self-completed
written or video questionnaires (students' report of current wheeze 8.8, 7.3, and
8.3%). Similarly, no further increase was observed for reported hay fever rates
and allergic sensitisation rates (positive multiscreen allergy test, SX1-test:
34.6, 38.9, and 35.6%, respectively). Although time trends in the occurrence of a
series of known risk factors were recorded, none of these factors had a
significant impact on asthma and allergy prevalence over time. No further
increase in asthma and allergy rates occurred during the 1990s in adolescents
living in Switzerland. However, to adequately assess the trend a longer period of
observation is needed.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15065830 [PubMed - indexed for MEDLINE]

946: Eur Ann Allergy Clin Immunol. 2004 Feb;36(2):67-70, 72.

Antihistamines added to an antileukotriene in treating seasonal allergic
rhinitis: histamine and leukotriene antagonism.

Ciprandi G, Tosca MA, Milanese M, Schenone G, Ricca V.

Allergy & ENT Unit, Head-Neck Dpt., San Martino Hospital, Genoa, Italy.

Cysteinyl leukotrienes (CysLTs) are a key element of allergic inflammation. Thus,
the antagonism of CysLTs appears a potential target of allergic rhinitis
management. Antileukotrienes and antihistamines combined showed a synergistic
effect in treating seasonal allergic rhinitis (SAR). This double blind, parallel 
group, randomized study aimed at evaluating the clinical and anti-inflammatory
effects exerted by two combinations of antihistamine plus antileukotriene in
patients with SAR and mild intermittent asthma. Thirty patients were treated with
montelukast added to cetirizine (M-C group) or desloratadine (M-D group) for 2
weeks. The visits, including spirometry, nasal scraping and lavage, were
performed in all subjects before and directly after the treatment. Evaluation
parameters were: i) nasal symptoms, ii) number of eosinophils and neutrophils,
and iii) IL5 and IL8 levels. Both combinations significantly reduced: nasal
symptoms (p<0.001), eosinophils and neutrophils (p<0.001), IL5 (p<0.001 for M-C
groupand p<0.01 for M-D group), and IL8 levels (p<0.001 for M-C group and p<0.05 
for M-D group). M-C combination reduced more significantly than M-D combination: 
nasal symptoms (p<0.01), inflammatory cells (p<0.01), and cytokines (p<0.01). The
present study demonstrates that these antileukotriene-antihistamine combinations 
are effective in relieving nasal symptoms in SAR. Moreover, these combinations
exert additional anti-inflammatory activity as provided by reduction of
inflammatory infiltrate and cytokine levels. Finally, cetirizine might exert more
beneficial activity than desloratadine when added to montelukast.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15061398 [PubMed - indexed for MEDLINE]

947: Biol Pharm Bull. 2004 Apr;27(4):554-8.

Preventive and curative effects of Gyokuheifu-san, a formula of traditional
Chinese medicine, on allergic rhinitis induced with Japanese cedar pollens in
guinea pig.

Makino T, Ito Y, Sasaki SY, Fujimura Y, Kano Y.

Department of Kampo Medicinal Science, Hokkaido College of Pharmacy, 7-1
Katsuraoka, Otaru 047-0264, Japan. makino@hokuyakudai.ac.jp

Gyokuheifu-san (GHS; Jade Windscreen Powder in English, Yupingfeng-san in
Chinese) is an herbal formula in traditional Chinese medicine that consolidates
the superficial resistance to protect from invasion by external pathogenic
influences. We evaluated the preventive and curative effects of GHS on allergic
rhinitis induced by Japanese cedar pollens in guinea pigs, since the pollen can
be considered one of external pathogens indicated by GHS. Guinea pigs were
sensitized by intranasal instillation of cedar pollen extract with alum twice a
day for 7 d, and the animals were then forced to inhale the pollens for challenge
once a week for 5 weeks. We administered GHS once a day for 2 weeks in the period
of sensitization to evaluate its preventive effect, or for 2 weeks from the 2nd
to the 4th week of pollen inhalation, once pollinosis had begun, to evaluate its 
curative effect on allergic rhinitis. GHS significantly suppressed the frequency 
of sneezing induced by pollens and tended to reduce nose-scratching behavior
after ceasing its administration in both designs of medicinal treatment.
Tranilast, which is an anti-allergic drug we used as a positive control, could
not suppress these rhinitic symptoms. GHS appears to have non-symptomatic and
non-allopathic effects on allergic rhinitis. Our results suggest that traditional
medicines have their own characteristics different from modern medicines, and the
original pharmacological experiments are important to evaluate traditional
medicines scientifically.

PMID: 15056865 [PubMed - indexed for MEDLINE]

948: Curr Allergy Asthma Rep. 2004 May;4(3):237-44.

Omalizumab and the treatment of allergic rhinitis.

Kaliner MA.

Institute for Allergy and Asthma, 11160 Veirs Mill Road, Suite 414, Wheaton, MD
20902, USA. makaliner@aol.com

Anti-IgE therapy affects mechanisms in the allergic response that are
IgE-dependent or IgE-mediated and common to both allergic asthma and allergic
rhinitis. Clinical trials of omalizumab in the treatment of patients with
allergic rhinitis or comorbid allergic rhinitis and moderate to severe allergic
asthma have recorded significant reductions in symptom severity scores of both
conditions. This novel therapy has increased the knowledge base concerning
IgE-mediated allergic responses, and, in keeping with its actions established in 
the treatment of asthma, appears to be useful in the treatment of moderate to
severe allergic rhinitis, as well.

Publication Types: 
    Review

PMID: 15056407 [PubMed - indexed for MEDLINE]

949: Int J Clin Pract. 2004 Feb;58(2):109-18.

Comparative clinical efficacy, onset and duration of action of levocetirizine and
desloratadine for symptoms of seasonal allergic rhinitis in subjects evaluated in
the Environmental Exposure Unit (EEU).

Day JH, Briscoe MP, Rafeiro E, Ratz JD.

Division of Allergy and Immunology, Kingston General Hospital, Kingston, Ontario,
Canada. dayj@kgh.kari.net

The Environmental Exposure Unit, an indoor pollen challenge system to test
anti-allergic medications, was used to compare the onset and duration of action
and the efficacy of levocetirizine and desloratadine, two recently developed
H1-antagonists. In this double-blind, placebo-controlled, parallel-group study,
qualified subjects were randomised to once-daily levocetirizine 5 mg (n = 141),
desloratadine 5 mg (n = 140) or placebo (n = 92) and exposed to ragweed pollen on
two consecutive days (7 h and 6 h). Symptoms were self-rated every 30 min. On
both days, levocetirizine produced a greater improvement in the major symptom
complex score (primary efficacy variable) than desloratadine (p = 0.015); both
were better than placebo (p < 0.001). Levocetirizine acted earlier (1 h vs. 3 h) 
and produced greater symptom relief at 24 h than desloratadine (p = 0.003).
Levocetirizine also alleviated nasal obstruction better than desloratadine (p =
0.007) on day 1; and better than placebo (p = 0.014) after the second dose on day
2, which was not observed with desloratadine. Levocetirizine and desloratadine
were safe and well tolerated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15055856 [PubMed - indexed for MEDLINE]

950: Allergy Asthma Proc. 2004 Jan-Feb;25(1):53-8.

Triamcinolone acetonide and fluticasone propionate aqueous nasal sprays
significantly improve nasal airflow in patients with seasonal allergic rhinitis.

Meltzer EO, Gallet CL, Jalowayski AA, Garcia J, Diener P, Liao Y, Georges G.

Allergy and Asthma Medical Group and Research Center, San Diego, California
92123, USA.

Domiciliary measurement of nasal peak inspiratory flow rate (nPIFR) provides a
simple, noninvasive, objective assessment of nasal patency and may be useful for 
determining the effectiveness of therapeutic interventions. This randomized,
parallel-group, investigator-blind study compared the effects of triamcinolone
acetonide aqueous nasal spray (TAA AQ), 220 microg everyday (n = 19), and
fluticasone propionate (FP AQ), 200 microg everyday (n = 20), for 21 days on
nasal airflow in patients with seasonal allergic rhinitis (SAR), using
domiciliary nPIFR. Patients had a > or = 2-year history of springtime SAR and
positive epicutaneous or intradermal test to grass, tree pollen, or outdoor
molds. nPIFR was measured three times each morning (before dosing) and at bedtime
using an In-Check nPIF meter. All measurements were recorded on diary cards, and 
the best of the three measurements was used for data analysis. There were no
significant demographic differences between treatment groups at baseline.
Baseline nPIFR (+/- SE) was 106.5 L/minute (+/- 51.2) and 97.7 L/minute (+/-
45.0) in the TAA AQ and FP AQ groups, respectively (p = 0.5733). Model-based
estimation of mean change from baseline with TAA AQ and FP AQ at the end of the
study were 21.72 (+/- 6.04) and 16.48 (+/- 5.73), respectively. Both treatment
groups showed an approximately 20% improvement in nPIFR versus baseline (p =
0.0002 and p = 0.0069 for TAA AQ and FP AQ, respectively), with no statistical
difference between treatments. Weekly mean nPIFR scores indicated progressive
improvement in nasal airflow with both treatments. Both TAA AQ and FP AQ were
effective for improving nasal airflow as indicated by increases in nPIFR in
patients with SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15055563 [PubMed - indexed for MEDLINE]

951: Int Arch Allergy Immunol. 2004 May;134(1):34-40. Epub 2004 Mar 25.

Nasal obstruction in patients with seasonal allergic rhinitis: relationships
between allergic inflammation and nasal airflow.

Ciprandi G, Cirillo I, Vizzaccaro A, Milanese M, Tosca MA.

Ospedale San Martino, Genoa, Italy. gio.cip@libero.it

BACKGROUND: Nasal obstruction is a typical symptom of allergic rhinitis. Allergic
rhinitis is characterized by a Th2-dependent inflammation. The aim of this study 
was to evaluate the possible relationships between allergic inflammation,
including inflammatory cells and cytokine pattern, and nasal airflow in patients 
with nasal obstruction due to seasonal allergic rhinitis. METHODS: Fifty patients
(31 males and 19 females, mean age 31.9 +/- 4.8 years) with seasonal allergic
rhinitis were evaluated during the pollen season. All of them had moderate to
severe nasal obstruction. Total symptom score, rhinomanometry, nasal lavage, and 
nasal scraping were assessed in all subjects. Inflammatory cells were counted by 
conventional staining; IL-4, IL-5, IL-8, and IFNgamma were measured by
immunoassay on fluids recovered from nasal lavage. RESULTS: Significant positive 
relationships were demonstrated between eosinophil infiltration and IL-4 levels
(p < 0.0001), eosinophils and IL-5 levels (p < 0.0001), and eosinophils and IL-8 
levels (p < 0.0001). Significant negative relationships were demonstrated between
eosinophil infiltration and IFNgamma levels (p < 0.0001) and eosinophil
infiltration and nasal airflow (p < 0.001). CONCLUSIONS: This study demonstrates 
the close connection between Th2 cytokines and eosinophil infiltration. In
addition, there is clear evidence concerning the relationship between eosinophil 
infiltration and nasal airflow. These findings constitute first evidence of the
relationship between nasal airflow impairment and Th2-related inflammation in
seasonal allergic rhinitis. Copyright 2004 S. Karger AG, Basel

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 15051938 [PubMed - indexed for MEDLINE]

952: Ann Allergy Asthma Immunol. 2004 Mar;92(3):367-73.

Montelukast for treating fall allergic rhinitis: effect of pollen exposure in 3
studies.

Chervinsky P, Philip G, Malice MP, Bardelas J, Nayak A, Marchal JL, van Adelsberg
J, Bousquet J, Tozzi CA, Reiss TF.

New England Research Center, North Dartmouth, Massachusetts, USA.

BACKGROUND: Montelukast, a potent leukotriene receptor antagonist, is an
effective therapy for symptoms of seasonal allergic rhinitis, a disease governed 
by patients' individual sensitivity and exposure to relevant allergens.
OBJECTIVE: To evaluate the relationship of montelukast treatment effect vs pollen
exposure in studies conducted during 3 consecutive fall allergy seasons. METHOD: 
A combined analysis of these multicenter, randomized, double-blind,
parallel-group studies was performed; 1 of the 3 studies is presented for the
first time in this article. After a placebo run-in period, 1,862 symptomatic
patients were randomly assigned to receive either a 10-mg montelukast tablet (n =
929) or placebo (n = 933) once daily for 2 weeks. Pollen exposure was summarized 
by mean daily weed pollen count. The interaction between treatment effect and
pollen exposure was evaluated on the primary efficacy endpoint and daytime nasal 
symptom score, as rated by patients; also evaluated was the influence of the
timing of the 2-week treatment period relative to the peak of the weed pollen
season. RESULTS: Montelukast significantly improved daytime nasal symptoms score 
and individual scores of congestion, rhinorrhea, itching, and sneezing compared
with placebo. There was a significant interaction (P < .043) between treatment
effect and weed pollen exposure; a larger treatment effect was noted in patients 
exposed to higher pollen counts. An interaction between treatment effect and
timing of treatment in relation to peak pollen season was suggested. CONCLUSIONS:
Montelukast significantly improved daytime nasal symptoms score in patients with 
seasonal allergic rhinitis, and the effect was greater in patients exposed to
higher pollen levels.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15049402 [PubMed - indexed for MEDLINE]

953: Ann Allergy Asthma Immunol. 2004 Mar;92(3):344-9.

Comparison of the effects of fluticasone propionate aqueous nasal spray and
loratadine on daytime alertness and performance in children with seasonal
allergic rhinitis.

Bender BG, Milgrom H.

Department of Pediatrics, National Jewish Medical and Research Center, Denver,
Colorado 80206, USA. benderb@njc.org

BACKGROUND: Concern has been directed at the relative sedating properties of
lipophilic and lipophobic antihistamines, but few studies have sought to
determine the comparative benefit of seasonal allergic rhinitis (SAR) treatments 
in controlling symptoms and consequently improving alertness. OBJECTIVE: To
compare the relative contributions of fluticasone propionate aqueous nasal spray 
and loratadine in enhancing daytime performance in 8- to 17-year-old children.
METHODS: All participants had a documented history of SAR, positive response to a
skin prick (wheal 3-mm greater than negative control or equal to the positive
control) for seasonal aeroallergens, and clinically identifiable symptoms at the 
time of randomization. Following confirmation during baseline of current SAR
symptoms, participants were randomized to 1 of the 2 treatments and returned 2
weeks later for evaluation of symptom control, quality of life, attention,
reaction time, and memory. RESULTS: Children in the fluticasone propionate
aqueous nasal spray group but not the loratadine group demonstrated improvement
in nasal symptoms, nasal quality of life score, and composite verbal memory. No
differences were identified on any scores from the Conners Continuous Performance
Test. CONCLUSIONS: Treatments that most effectively control SAR symptoms are also
likely to provide the greatest benefit to children whose daytime functioning,
including their capacity to learn at school, is compromised by their illness.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15049399 [PubMed - indexed for MEDLINE]

954: J Manag Care Pharm. 2004 Mar-Apr;10(2):115-21.

Evaluation of the utilization patterns of leukotriene modifiers in a large
managed care health plan.

Lakomski PG, Chitre M.

Excellus Health Plan, Inc., 344 South Warren St., Syracuse, NY 13202, USA.
paul.lakomski@flrx.com

OBJECTIVE: To assess the utilization of leukotriene modifiers (LM) relative to
national guidelines and to investigate possible emergency room utilization
differences for LMs as monotherapy versus inhaled corticosteroid (ICS)
monotherapy or combination ICS and LM therapy. METHODS: The utilization of
leukotriene modifiers (montelukast sodium, zafirlukast, and zileuton), concurrent
inhaled steroids (beclomethasone, budesonide, flunisolide, fluticasone, and
triamcinolone), beta-agonists (albuterol, bitolterol, formoterol, isoetharine,
levalbuterol, metaproterenol, pirbuterol, salmeterol, and terbutaline) and
low-sedating antihistamines ([LSAs] cetirizine, desloratadine, fexofenadine, and 
loratadine) were assessed from the drug claims database of a large health insurer
for dates of service for the 12-month period from September 1, 2001, through
August 31, 2002. New-start LM patients were identified as having no previous LM
drug claim within a 180-day look-back period from the first date of fill for the 
LM. Claims were stratified into age cohorts of.under 16 years. and.16 years and
older. Emergency room (ER) claims for patients utilizing LMs, ICSs, and patients 
on both LM and ICS were retrieved for analysis from the medical claims database
for the same 12-month study period. RESULTS: More than 89% of new LM starts had
no history of an ICS in the claims database. Overall, 61% of all (new and
existing) LM patients did not have a claim for an ICS in their drug claims
profile during the study period. An estimated 25% of LM utilization was not for
asthma. No differences in ER utilization were found between ICS users and LM
users; however, the ER utilization rate (0.090 ER visits per patient per year)
was lower with combination therapy compared with monotherapy with ICS (0.110 ER
visits per patient per year, P = 0.001) or LM (0.119 emergency room visits per
patient per year, P<0.001). CONCLUSIONS: The majority of LM use in this health
plan was initial monotherapy, contrary to national treatment guidelines for
asthma. At the time of the study, the apparent off-label use of LM for allergic
rhinitis was significant for this health plan.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15032560 [PubMed - indexed for MEDLINE]

955: Int Arch Allergy Immunol. 2004 Apr;133(4):371-9. Epub 2004 Mar 17.

Efficacy and safety of ebastine 20 mg compared to loratadine 10 mg once daily in 
the treatment of seasonal allergic rhinitis: a randomized, double-blind,
placebo-controlled study.

Ratner P, Hampel F Jr, Van Bavel J, Howland W 3rd.

Sylvana Research, San Antonio, TX 78229, USA. phratner@swbell.net

BACKGROUND: Few randomized studies have compared loratadine to ebastine in the
symptomatic treatment of seasonal allergic rhinitis (SAR) patients. METHODS: This
double-blind, placebo-controlled, randomized, parallel-group, comparative trial
compared the efficacy and safety of ebastine 20 mg (E20), loratadine 10 mg (L10) 
and placebo (P), administered once daily, in the control of SAR symptoms over a
2-week period. An additional 2-week treatment period was included in order to
check sustained efficacy and tolerability. RESULTS: A total of 703 patients were 
enrolled: 282 patients in the E20 group, 279 in the L10 group and 142 in the P
group. E20 showed a greater decrease from baseline in the main efficacy variable 
(mean daily reflective total symptom score) than L10 (p = 0.0018) or P (p =
0.0024), whereas the difference between L10 and P was not significant. Moreover, 
reductions from baseline in all composite/individual daily reflective rhinitis
symptom scores were significantly larger in patients receiving E20 than in
patients receiving L10 or P. Most significant differences between E20 and L10 or 
P were maintained after 4 weeks of treatment. Overall, all treatments were safe
and well tolerated. There was no significant difference in the percentage of
patients who reported one or more adverse events (AEs) between the groups, and
most AEs were mild to moderate (89.9%). CONCLUSIONS: E20 given once daily for 2
weeks was more effective in the treatment of SAR symptoms than L10 or P. E20 also
showed a sustained efficacy after 4 weeks of treatment, and overall was well
tolerated and proved safe. Copyright 2004 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 15031611 [PubMed - indexed for MEDLINE]

956: Curr Med Res Opin. 2004 Mar;20(3):305-17.

Economic impact and quality-of-life burden of allergic rhinitis.

Schoenwetter WF, Dupclay L Jr, Appajosyula S, Botteman MF, Pashos CL.

Park Nicollet Clinic, St. Louis Park, MN 55416, USA. schoe012@tc.umn.edu

Allergic rhinitis can be a debilitating condition which, if untreated, can result
in considerable health-related and economic consequences. A review of the
published literature was conducted, with quantitative/qualitative analysis as
appropriate, to explore the direct, indirect, and hidden costs of allergic
rhinitis, as well as the quality-of-life burdens that the disease presents to
patients and to the healthcare system. Lack of treatment, undertreatment, or
nonadherence to treatment in allergic rhinitis were seen to increase direct and
indirect costs, reinforcing the need for patient education and for physicians to 
implement existing evidence-based guidelines for prevention and treatment. It was
concluded that greater awareness of the total economic burden of allergic
rhinitis should encourage appropriate intervention and ultimately ensure
clinically favorable and cost-effective outcomes.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15025839 [PubMed - indexed for MEDLINE]

957: Br J Clin Pharmacol. 2004 Apr;57(4):402-11.

Retrospective population pharmacokinetic analysis of cetirizine in children aged 
6 months to 12 years.

Pitsiu M, Hussein Z, Majid O, Aarons L, de Longueville M, Stockis A.

Medeval Ltd, Manchester, UK.

AIMS: To evaluate retrospectively the population pharmacokinetics of cetirizine, 
a second-generation antihistamine, in children. METHODS: Data were pooled from
six clinical trials, in which cetirizine was administered orally in various
formulations and in single and multiple dosage regimens. The population consisted
of 112 children (33 female and 79 male) aged 6 months to 12 years. A
one-compartment open model with first-order absorption and elimination was fitted
to the plasma concentration-time profiles using nonlinear mixed effects modelling
with first-order estimation. RESULTS: A linear association was found between
apparent clearance (CL/F) and age with the former increasing by 0.12 l h(-1) per 
year. The intercept of the relationship was slightly lower for female children
(0.59 vs. 0.77 l h(-1) in male). The population estimate of CL/F for an average
age of 7 years was 1.61 and 1.43 l h(-1) for male and female children,
respectively. A linear association was found between apparent volume of
distribution (V/F) and age with the former increasing by 1.4 l year(-1), with an 
intercept of 4.0 l. The population estimate of V/F for an average age of 7 years 
was 13.9 l. The magnitudes of interpatient variability were 35.6% for CL/F and
19.7% for V/F. The magnitude of residual variability in cetirizine concentrations
was 26.9%. CONCLUSIONS: Population analysis predicts a linear increase in
cetirizine CL/F and V/F with age, with CL/F being slightly lower in female
children, relative to males of the same age. However, this gender difference
probably has no clinical consequences. Since V/F increased more rapidly with age 
than CL/F, a nonlinear increase in half-life was seen, from < 4 h in infants to
near the adult value at 12 years of age. The current recommended dosing regimens 
that younger children should receive lower but more frequent doses, are confirmed
by the present analysis.

Publication Types: 
    Multicenter Study

PMID: 15025737 [PubMed - indexed for MEDLINE]

958: Expert Opin Pharmacother. 2004 Mar;5(3):679-86.

A review of montelukast in the treatment of asthma and allergic rhinitis.

Nayak A.

Department of Pediatrics, University of Illinois College of Medicine, Peoria,
Illinois 61603, USA. DrNayak@asthma2.com

Montelukast sodium (Singulair, Merck) is a selective and orally-active
leukotriene-receptor antagonist (LTRA) that inhibits the cysteinyl leukotriene 1 
(CysLT1) receptor. Montelukast is an effective and well-tolerated preventative
treatment for asthma and allergic rhinitis in adults and children. The upper and 
lower airway show similar inflammatory responses to allergen challenge.
Leukotrienes are inflammatory mediators that are known as the slow-reacting
substance of anaphylaxis produced by a number of cell types including mast cells,
eosinophils, basophils, macrophages and monocytes. Synthesis of these mediators
results from the cleavage of arachidonic acid in cell membranes and they exert
their biological effects by binding and activating specific receptors. This
occurs in a series of events that lead to contraction of the human airway smooth 
muscle, chemotaxis and increased vascular permeability. These effects have led to
their important role in the diseases of asthma and allergic rhinitis. As these
agents lead to the production of symptoms in patients that are asthmatic or
allergic, the use of LTRAs, particularly montelukast, may seem appropriate.
Clinical trials have shown that montelukast is effective and safe in the
treatment of patients with asthma, allergic rhinitis or both diseases.

Publication Types: 
    Review

PMID: 15013935 [PubMed - indexed for MEDLINE]

959: J Allergy Clin Immunol. 2004 Mar;113(3):415-9.

Rhinitis therapy and the prevention of hospital care for asthma: a case-control
study.

Corren J, Manning BE, Thompson SF, Hennessy S, Strom BL.

Allergy Research Foundation, Los Angeles, CA 90025, USA.

BACKGROUND: Although clinical trials have demonstrated that rhinitis therapy
improves subjective and objective measures of asthma, it is uncertain whether
treatment of allergic rhinitis significantly affects the frequency of asthma
exacerbations. OBJECTIVE: The objective of this study was to determine whether
treatment with intranasal corticosteroids and/or second-generation antihistamines
is associated with changes in rates of asthma exacerbations resulting in
emergency room visits and/or hospitalizations in patients with asthma and
allergic rhinitis. METHODS: This was a nested, case-control study. RESULTS:
Treatment with either nasal corticosteroids or second-generation antihistamines
was associated with a lower risk of asthma-related emergency room treatment and
hospitalization (adjusted odds ratio [OR], 0.51; 95% CI, 0.34 to 0.77 and 0.34,
0.18 to 0.62, respectively). Patients who used nasal corticosteroids had a
significantly lower risk of both asthma-related emergency room treatment and
hospitalization (adjusted OR, 0.75; 95% CI, 0.62 to 0.91 and 0.56, 0.42 to 0.76, 
respectively), whereas there was a trend toward lower risk of emergency room
treatment and hospitalization in patients who used second-generation
antihistamines (adjusted OR, 0.88; 95% CI, 0.62 to 1.26 and 0.68, 0.40 to 1.14,
respectively). Combined treatment with both medications was associated with a
further lowering of the risk of both emergency room treatment and hospitalization
(adjusted OR, 0.37; 95% CI, 0.19 to 0.73 and 0.22, 0.07 to 0.63). CONCLUSIONS: In
patients with asthma, treatment of concomitant allergic rhinitis was associated
with significant reductions in risk of emergency room treatment and
hospitalization for asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15007339 [PubMed - indexed for MEDLINE]

960: Allergy. 2004 Apr;59(4):461-4.

Disease perception and social behaviour in persistent rhinitis: a comparison
between patients with allergic and nonallergic rhinitis.

Rydén O, Andersson B, Andersson M.

Department of Psychology, Lund University, Lund, Sweden.

BACKGROUND: Although the understanding of the pathophysiology and pharmacology of
rhinitis has increased within recent years, few studies have examined the impact 
of rhinitis on patients' behaviour. AIM: To compare perennial allergic rhinitis
(PAR) and perennial nonallergic rhinitis (PNR) in terms of patients' perception
of their disease and its psychosocial concomitants. METHODS: Thirty-one PAR
patients and 32 PNR patients responded to a standard symptom list and were
interviewed in-depth regarding their complaints and the impact of rhinitis on
their daily lives. RESULTS: PAR and PNR patients reported similar somatic and
psychosocial complaints. In both disease groups the adverse effects of rhinitis
were reported to be substantially limiting, particularly in social contacts, the 
impact appearing to be more severe in the women. CONCLUSION: Rhinitis has a
severe impact on the daily lives of patients, women reporting more severe
psychosocial effects. Disease perception and social adjustment appear to not
depend appreciably on whether or not an objective diagnosis of rhinitis can be
established.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15005772 [PubMed - indexed for MEDLINE]

961: Allergy. 2004 Apr;59(4):415-20.

Improvements in simulated real-world relevant performance for patients with
seasonal allergic rhinitis: impact of desloratadine.

Satish U, Streufert S, Dewan M, Voort SV.

Department of Psychiatry and Behavioral Science, SUNY Upstate Medical University,
Syracuse, NY 13210, USA.

BACKGROUND: Seasonal allergic rhinitis (SAR) diminishes task performance and
decreases quality of life. Antihistamines are frequently used to treat the
symptoms of SAR. First generation antihistamines often have their own detrimental
effects upon human functioning while second generation antihistamines appear to
have fewer or no undesirable side-effects. OBJECTIVE: This study evaluated the
impact of desloratadine on simulated real-world performance demands in
individuals suffering from SAR. METHODS: This was a randomized, double-blind,
cross-over study where asymptomatic participants were treated with placebo and
symptomatic participants were treated with desloratadine or placebo. They then
participated in a real-world equivalent task performance simulation that assessed
information processing capacity at multiple levels of task difficulty ranging
from easy to difficult decision-making tasks. RESULTS: Desloratadine either
completely restored performance to the level of the asymptomatic placebo control 
or improved performance in six of the nine performance categories, where it had
been diminished by the presence of SAR. CONCLUSIONS: These findings suggest that 
treatment with desloratadine has considerable beneficial effects on work place
performance when individuals suffer from SAR.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15005765 [PubMed - indexed for MEDLINE]

962: Clin Exp Allergy. 2004 Mar;34(3):429-36.

VH gene usage in immunoglobulin E responses of seasonal rhinitis patients
allergic to grass pollen is oligoclonal and antigen driven.

Davies JM, O'Hehir RE.

Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, 
Commercial Road, Melbourne, Vic 3004, Australia. Janet.Davies@med.monash.edu.au

BACKGROUND: IgE is the pivotal-specific effector molecule of allergic reactions
yet it remains unclear whether the elevated production of IgE in atopic
individuals is due to superantigen activation of B cell populations, increased
antibody class switching to IgE or oligoclonal allergen-driven IgE responses.
OBJECTIVES: To increase our understanding of the mechanisms driving IgE responses
in allergic disease we examined immunoglobulin variable regions of IgE heavy
chain transcripts from three patients with seasonal rhinitis due to grass pollen 
allergy. METHODS: Variable domain of heavy chain-epsilon constant domain 1 cDNAs 
were amplified from peripheral blood using a two-step semi-nested PCR, cloned and
sequenced. RESULTS: The VH gene family usage in subject A was broadly based, but 
there were two clusters of sequences using genes VH 3-9 and 3-11 with unusually
low levels of somatic mutations, 0-3%. Subject B repeatedly used VH 1-69 and
subject C repeatedly used VH 1-02, 1-46 and 5a genes. Most clones were highly
mutated being only 86-95% homologous to their germline VH gene counterparts and
somatic mutations were more abundant at the complementarity determining rather
than framework regions. Multiple sequence alignment revealed both repeated use of
particular VH genes as well as clonal relatedness among clusters of IgE
transcripts. CONCLUSION: In contrast to previous studies we observed no preferred
VH gene common to IgE transcripts of the three subjects allergic to grass pollen.
Moreover, most of the VH gene characteristics of the IgE transcripts were
consistent with oligoclonal antigen-driven IgE responses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15005737 [PubMed - indexed for MEDLINE]

963: Clin Exp Allergy. 2004 Mar;34(3):420-8.

A double-blind, placebo-controlled birch allergy vaccination study: inhibition of
CD23-mediated serum-immunoglobulin E-facilitated allergen presentation.

van Neerven RJ, Arvidsson M, Ipsen H, Sparholt SH, Rak S, Würtzen PA.

ALK-Abelló, Bøge Alle, Hørsholm, Denmark.

BACKGROUND: The clinical efficacy of specific allergy vaccination (SAV),
previously called specific immunotherapy is well documented. The working
mechanism of this treatment is not completely known at present. Allergen-specific
CD4+ T lymphocytes are activated at extremely low allergen concentrations in vivo
possibly as a result of serum IgE-facilitated allergen presentation (S-FAP).
Previously, we have shown that this process can be inhibited by long-term birch
SAV sera. METHODS: In the present study, we have analysed sera from
birch-allergic patients in a randomized double-blind, placebo-controlled clinical
trial for their ability to mediate S-FAP. Birch-specific IgE levels were not
changed after SAV. Bet v 1-specific IgE levels, however, were significantly
decreased (P<0.05) and Bet v 1-specific IgG4 levels were strongly increased after
SAV (P<0.001). None of these changes were observed in the placebo group. When the
sera were tested for their ability to induce S-FAP, a complete abrogation of this
effect was noted in the sera from patients receiving active treatment (P<0.001), 
but not in the control group. This inhibition of S-FAP seemed to be associated
with the reduction in the ratio between Bet v 1-specific IgE and IgG4 antibodies 
in serum, but a clear correlation could not be demonstrated. CONCLUSION: In
conclusion, the present study clearly shows that SAV leads to an inhibition of
the S-FAP needed to obtain optimal T cell activation at the low allergen
concentrations present in vivo. This novel mechanism may explain the increased
allergen threshold levels found in allergen provocation tests and the reduction
of late-phase reactions observed after SAV.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15005736 [PubMed - indexed for MEDLINE]

964: Clin Exp Allergy. 2004 Mar;34(3):413-9.

Comment in:
    Clin Exp Allergy. 2004 Mar;34(3):328-31.

Increased expression of allergen-induced in vitro interleukin-10 and
interleukin-18 mRNA in peripheral blood mononuclear cells of allergic rhinitis
patients after specific immunotherapy.

Savolainen J, Laaksonen K, Rantio-Lehtimäki A, Terho EO.

Department of Pulmonary Diseases and Clinical Allergology, University of Turku,
Turku, Finland. johannes.Savolainen@utu.fi

BACKGROUND: During specific pollen immunotherapy (SIT) there is a local mucosal
shift from Th2- to Th1- type cytokine predominance, with IL-12 having a major
role in this shift. IL-10-induced tolerance is supposed to be a key phenomenon in
venom immunotherapy (VIT). However, the role of Th1-promoting cytokines, on the
one hand, and the role of regulatory cytokines, on the other hand, have not been 
studied in parallel during SIT. OBJECTIVE: This study was undertaken to analyse
the allergen-induced in vitro mRNA expression of Th1-type effector cytokine IL-18
and regulatory cytokines IL-10 and TGF-beta during SIT in peripheral blood
mononuclear cells (PBMC) of allergic rhinitis (AR) patients. METHODS: Thirty
patients with AR undergoing pollen SIT and 10 patients with AR who were not
treated with SIT were included in the study. The symptoms and medications were
registered post-seasonally before the beginning of SIT and after 1 year of
therapy. PBMC samples were collected and stimulated with pollen allergen extract 
prior to the treatment, at the maintenance phase in 12 patients and after 1 year 
of the treatment. The cytokine mRNA expression was assessed using kinetic
real-time RT-PCR (TaqMan). RESULTS: There was a clear increase in the treated AR 
patients, in comparison with untreated AR patients, in the expression of both
IL-10 (mean change from baseline (SEM): 3.1 (0.8) vs. -0.3 (0.3), P<0.002,
Mann-Whitney U-test) and IL-18 (2.7 (0.9) vs. -0.2 (0.6), P<0.03) mRNA after 1
year. The clearest increase in IL-10 mRNA expression was seen in patients who did
not benefit at all (6.0 (2.3), P<0.001 vs. untreated) and the least increase in
patients that had the greatest reduction of symptoms (0.8 (0.6), n.s. vs.
untreated) at 1 year. The clearest increase in IL-18 mRNA expression was seen in 
patients with moderate outcome (3.4 (1.6), P<0.04 vs. untreated). In intermediate
samples, taken when the maintenance dose was reached, the peak expression of
allergen-induced IL-10 mRNA was associated with the most favourable outcome of
SIT (P=0.01, Fisher exact test). A similar trend was seen in IL-18 mRNA
expression. CONCLUSIONS: The results suggest that an early and transient increase
in allergen-specific IL-10 and IL-18 mRNA expression in PBMC is essential for the
therapeutic outcome after 1 year of SIT.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15005735 [PubMed - indexed for MEDLINE]

965: Clin Exp Allergy. 2004 Mar;34(3):346-53.

Association of polymorphisms in Th1, Th2 cytokine genes with hayfever and atopy
in a subsample of EPIC-Heidelberg.

Nieters A, Linseisen J, Becker N.

Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg,
Germany.

BACKGROUND: Hayfever is determined by an interaction of environmental and genetic
factors and biologically characterized by an imbalanced T helper cell 1 (Th1) and
Th2 immune response and elevated IgE levels against inhalant allergens.
Indications exist that polymorphisms in cytokine genes involved in the regulation
of the Th1/Th2 balance may contribute to the allergic phenotype. OBJECTIVE: We
investigate whether polymorphisms in genes directly or indirectly involved in
Th1, Th2 immune response are associated with hayfever and elevated IgE levels
against inhalant allergens. METHODS: From a subsample of the European Prospective
Investigation into Cancer and Nutrition-Heidelberg, 322 subjects with hayfever
and 322 age- and sex-matched non-allergic controls were selected and genotypes
determined for 15 polymorphisms in 13 genes. Plasma IgE against inhalant
allergens was measured via CAPSX1 (Phadiatop) test. We computed odds ratios (ORs)
by logistic regression, tests on group differences of IgE-levels in dependence
upon genotype and tests for trend by means of non-parametric methods. RESULTS: We
found decreased OR for hayfever (OR=0.60, 95%CI=0.4-0.9) and sensitization to
inhalant antigens (OR=0.5, 95%CI=0.4-0.8) in heterozygotes of the IL-6 -174 G/C
polymorphism. Homozygotes of the G-allele in IL-2 -330 T/G were at increased risk
of hayfever (OR=2.6, 95%CI=1.3-5.2). Moreover, we found indications for
differences in IgE levels against inhalant allergens in dependence upon genotypes
of polymorphisms in IL-4R, IL-6, IL-13, and IL-18. CONCLUSION: Our data suggest
an association of genetic variants in IL-6 and IL-2 with hayfever, confirm a role
of polymorphisms in IL-4R, IL-13, and IL-18 for the elevated IgE phenotype, and
add IL-6 to the list of candidate genes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15005726 [PubMed - indexed for MEDLINE]

966: Pediatr Allergy Immunol. 2004 Feb;15(1):72-8.

Increasing prevalence of allergic rhinitis but not asthma among children in Hong 
Kong from 1995 to 2001 (Phase 3 International Study of Asthma and Allergies in
Childhood).

Lee SL, Wong W, Lau YL.

Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The
University of Hong Kong, Hong Kong SAR, China.

There is a worldwide belief that the prevalence of asthma and other allergic
diseases is increasing but the measures used in many studies are susceptible to
systematic errors. We examined the trend of asthma, allergic rhinitis and eczema 
prevalence in school children aged 6-7 years in Hong Kong from 1995 to 2001 using
standardized ISAAC methodology. There were 4448 and 3618 children participating
in 2001 and 1995, respectively. The prevalence of life-time rhinitis (42.4% vs.
38.9%, p < 0.01), current rhinitis (37.4% vs. 35.1%, p < 0.03), current
rhinoconjunctivitis (17.2 vs. 13.6%, p < 0.01) and life-time eczema (30.7% vs.
28.1%, p = 0.01) increased significantly. There was no significant change in
prevalence of life-time asthma, life-time wheeze and current wheeze albeit a
significant increase in severe asthma symptoms. We investigated a number of
potential risk factors including sex, family history of atopy, sibship size,
birth weight, respiratory tract infections, pet ownership and exposure to tobacco
smoke. However, the increases in prevalence of rhinitis and eczema could not be
entirely explained by the change of prevalence of these risk factors. The odds
ratio OR for the study period remained significantly associated with current
rhinitis (OR 1.31, 95% confidence intervals CI 1.17-1.46), current
rhinoconjunctivitis (OR 1.63, 95% CI 1.41-1.87) and life-time eczema (OR 1.30,
95% CI 1.16-1.45) after adjustment for these confounding variables using logistic
regression model. Further study is warranted to elucidate the factors
contributing to the observable change in the prevalence of rhinitis in our
population.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 14998385 [PubMed - indexed for MEDLINE]

967: Clin Ther. 2004 Jan;26(1):35-47.

Efficacy and tolerability of ophthalmic epinastine assessed using the
conjunctival antigen challenge model in patients with a history of allergic
conjunctivitis.

Abelson MB, Gomes P, Crampton HJ, Schiffman RM, Bradford RR, Whitcup SM.

Ophthalmic Research Associates, North Andover, USA.

BACKGROUND: Epinastine hydrochloride is a nonsedating antihistamine with a high
affinity for histamine H(1) receptors, together with mast cell-stabilizing and
anti-inflammatory activities. OBJECTIVE: The aim of this study was to assess the 
efficacy and tolerability of topically administered ophthalmic epinastine using
the conjunctival antigen challenge (CAC) model in patients with a history of
allergic conjunctivitis. METHODS: This prospective, single-center, randomized,
double-masked, vehicle-controlled, Phase III clinical trial was conducted at the 
Ophthalmic Research Associates study center (North Andover, Massachusetts) from
November 2000 to January 2001. Eligible participants were asymptomatic but had a 
history of allergic conjunctivitis and had positive CAC reactions at the initial 
screening (week 0) and at a confirmation visit (week 1). Patients were randomly
assigned by eye to receive epinastine hydrochloride 0.05% ophthalmic solution in 
1 eye and vehicle in the contralateral eye. Each eye received 1 drop of study
medication 15 minutes before antigen application (onset challenge; week 3) or 8
hours before antigen application (duration challenge; week 5). Primary end points
were ocular itching and conjunctival hyperemia. Itching was recorded 3, 5, and 10
minutes after antigen challenge. Hyperemia was recorded 5, 10, and 20 minutes
after antigen challenge, as were secondary end points, which included eyelid
swelling, episcleral and ciliary hyperemia, chemosis, tearing, and ocular mucous 
discharge. Tolerability was assessed by patient interview and slit-lamp
biomicroscopy. RESULTS: Sixty-seven patients (37 females, 30 males; mean [SD]
age, 38.4 [14.2] years [range, 12-67 years]) were included in the study. Mean
severity scores for the following signs and symptoms were significantly lower
with epinastine compared with vehicle at all time points after onset and duration
challenges: ocular itching (P<0.001); eyelid swelling (P<0.001); conjunctival (
P<0.001), episcleral ( P<0.001), and ciliary hyperemia (P<0.001); and chemosis
(P<or=0.009). The percentage of eyes with tearing was significantly lower with
epinastine compared with vehicle at all time points (P<or=0.021), except at 5
minutes after the duration challenge. Adverse events (AEs), reported for 7.5%
(5/67) of patients, included only symptoms of upper respiratory tract infection. 
No ocular or treatment-related AEs were reported. CONCLUSIONS: In this CAC model,
multiple signs and symptoms of allergic conjunctivitis were significantly reduced
by instillation of epinastine compared with vehicle. Epinastine showed prompt
onset (3 minutes) and long duration of action (>or=8 hours). The tolerability of 
epinastine was similar to that of vehicle.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Randomized Controlled Trial

PMID: 14996516 [PubMed - indexed for MEDLINE]

968: Clin Ther. 2004 Jan;26(1):29-34.

Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, 
parallel-group, active- and vehicle-controlled environmental trial in patients
with seasonal allergic conjunctivitis.

Whitcup SM, Bradford R, Lue J, Schiffman RM, Abelson MB.

Allergan, Inc, Irvine, California 92623-9534, USA.

BACKGROUND: Epinastine hydrochloride is an antihistamine with mast
cell-stabilizing and anti-inflammatory activity. OBJECTIVE: The aim of this study
was to assess the efficacy and tolerability of ophthalmic epinastine in patients 
with seasonal allergic conjunctivitis (SAC) exposed to environmental allergens.
METHODS: This randomized (age-stratified), double-masked, parallel-group, active-
and vehicle-controlled, environmental, Phase III clinical trial was conducted at 
6 ophthalmology clinics in the United States. Patients aged >or=9 years diagnosed
with SAC and who had a positive reaction in a conjunctival allergen challenge
were enrolled. Patients were randomly assigned in a 2:2:1 ratio to receive 1
drop/eye BID of epinastine hydrochloride 0.05% ophthalmic solution, levocabastine
hydrochloride 0.05% ophthalmic suspension, or vehicle of epinastine,
respectively, for 8 weeks. The primary end point was ocular itching, and
secondary end points included ocular hyperemia, chemosis, ocular mucous discharge
(all assessed on a 5-point scale), eyelid swelling (assessed on a 4-point scale),
and tearing (present or absent). Efficacy analyses used assessments from the two 
1-week periods with the highest pollen counts. For tolerability assessment
slit-lamp biomicroscopy and visual acuity examinations were conducted at each
study visit (weeks 0, 2, 4, 6, and 8). RESULTS: Two-hundred ninety-eight patients
(159 females, 139 males; mean [SD] age, 32.7 [14.6] years [range, 9-71 years])
entered the study; 118 received epinastine, 118 received levocabastine, and 62
received vehicle. Epinastine-treated patients reported significantly less ocular 
itching than those receiving vehicle (P=0.045); scores for hyperemia were similar
between these 2 groups. Ocular itching and hyperemia scores were similar between 
the epinastine and levocabastine groups. No clinically or statistically
significant between-group differences were seen in slit-lamp biomicroscopy
findings, changes in visual acuity from baseline, or the incidence of
treatment-related adverse effects. CONCLUSIONS: In this study of patients with
SAC, ophthalmic epinastine instilled twice daily was more effective than vehicle 
for the control of ocular itching and was similar in efficacy to levocabastine
for control of ocular itching and hyperemia. Epinastine was well tolerated.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 14996515 [PubMed - indexed for MEDLINE]

969: Otolaryngol Head Neck Surg. 2004 Feb;130(2):192-6.

Association between HLA class II locus and the susceptibility to Artemisia
pollen-induced allergic rhinitis in Chinese population.

Wang M, Xing ZM, Yu DL, Yan Z, Yu LS.

Department of ENT, People's Hospital, Peking University, Beijing, People's
Republic of China.

OBJECTIVE: The aim of the study was to determine whether susceptibility or
resistance to Artemisia pollen-induced allergic rhinitis was associated with HLA 
class II DQA1, DQB1 loci.Study design and setting Forty-one subjects with
allergic rhinitis and 41 healthy controls from Beijing were genotyped at HLA
class II DQA1, DQB1 alleles by polymerase chain reaction amplification with
sequence-specific primers-based technique. RESULTS: The allele frequencies of
HLA-DQA1*0201, DQB1*0602 were lower in patients with allergic rhinitis compared
with the controls (24.39% versus 46.34%, P = 0.038; 4.88% versus 26.83%, P =
0.007), and the frequency of DQA1*0302 was higher among patients than the
controls (58.54% versus 14.63%, P = 0.00004, Pc = 0.0004). CONCLUSION AND
SIGNIFICANCE: HLA-DQA1 and -DQB1 genes may be involved in the development of
Artemisia pollen-induced allergic rhinitis. HLA-DQA1*0201, DQB1*0602 alleles may 
be a protective factor and DQA1*0302 may be a susceptible factor for Artemisia
pollen-induced allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14990915 [PubMed - indexed for MEDLINE]

970: Ann Allergy Asthma Immunol. 2004 Feb;92(2):262-7.

Salsola pollen as a predominant cause of respiratory allergies in Kuwait.

Al-Dowaisan A, Fakim N, Khan MR, Arifhodzic N, Panicker R, Hanoon A, Khan I.

Al-Rashid Centre for Allergic Diseases, Ministry of Health, Sulaibikhat, Kuwait.

BACKGROUND: Respiratory allergies are common in Kuwait, and the role of certain
allergens has been previously documented. OBJECTIVE: To evaluate the results of
skin prick tests to a range of allergens that were considered relevant to the
vegetation surveys and aerobiological studies performed in Kuwait. METHOD: New
patients attending our center during August 2002 to February 2003 with asthma or 
allergic rhinitis underwent skin prick tests to a battery of allergens. RESULTS: 
A total of 451 patients aged 5 to 60 years (mean age, 29.5 years) were tested. Of
these patients, 403 (89.4%) had a positive test result to at least one allergen
and were considered allergic. A total of 76.7% of the allergic patients had a
positive reaction to Salsola pollen, with a mean wheal diameter of 8.25 mm
(median, 8 mm). Chenopodium album was positive in 57.6% and Bermuda grass was
positive in 38.2% of the allergic cases. Indoor allergens seemed to play a lesser
role than pollens: Dermatophagoides pteronyssinus was positive in only 37.5%, and
American and German cockroaches were positive in 33.2% and 22.3%, respectively.
All the allergens other than Salsola elicited a mean wheal diameter of less than 
6.25 mm (median, < or = 6 mm). CONCLUSIONS: Indoor allergens seem to play a
lesser role in respiratory allergies in Kuwait. Most allergic patients become
sensitized to pollens; the strongest and most frequent reaction is from Salsola
pollen. Salsola imbricata is found growing extensively in most areas of the
country, flowering mainly in autumn, when the most common pollen is of the
Chenopod-Amaranth type and when most patients with seasonal allergic rhinitis
become symptomatic.

PMID: 14989397 [PubMed - indexed for MEDLINE]

971: Ann Allergy Asthma Immunol. 2004 Feb;92(2):255-61.

Triamcinolone acetonide aqueous nasal spray improves nocturnal rhinitis-related
quality of life in patients treated in a primary care setting: the Quality of
Sleep in Allergic Rhinitis study.

Mintz M, Garcia J, Diener P, Liao Y, Dupclay L, Georges G.

Eastern Vascular Associates, Denville, New Jersey, USA.

BACKGROUND: Sleep disturbances due to allergic rhinitis can contribute to daytime
fatigue, impair mood, and decrease daytime functioning. OBJECTIVE: To measure
allergic rhinitis patients' nocturnal rhinitis-related quality of life using a
new, validated disease-specific instrument, the Nocturnal Rhinoconjunctivitis
Quality of Life Questionnaire (NRQLQ). METHODS: This open-label study was
conducted in a primary care setting. Adult patients with seasonal or perennial
allergic rhinitis rated nocturnal rhinitis-related quality of life using the
NRQLQ and sleep disturbances using the Pittsburgh Sleep Quality Index (PSQI) at
baseline and after 3 weeks of treatment with triamcinolone acetonide aqueous
nasal spray (TAA AQ), 220 microg/d. Changes from baseline in overall and
individual domain scores for both the NRQLQ and PSQI were evaluated using t tests
for paired differences. RESULTS: The majority of the patients (N = 651) were
female (58%), were white (85%), and shared a bed with a partner (63%). Mean +/-
SD patient age was 45.7 +/- 15.5 years. TAA AQ treatment was associated with
significant improvements in overall NRQLQ score (mean +/- SD change, -1.5 +/-
1.3; P < .001) and in individual domain scores (P < .001 for sleep problems,
symptoms during sleep, symptoms upon waking in morning, and practical problems). 
Similarly, overall and individual PSQI domain scores were statistically
significantly improved (P < .001). There were strong correlations between NRQLQ
and PSQI scores (all comparisons P < .001). CONCLUSIONS: Treatment with TAA AQ
for 3 weeks resulted in statistically significant improvements in nocturnal
rhinitis-related quality of life and sleep quality in allergic rhinitis patients 
treated in a primary care setting.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 14989396 [PubMed - indexed for MEDLINE]

972: J Investig Allergol Clin Immunol. 2003;13(4):252-8.

Pulmonary function parameters in patients with allergic rhinitis.

Bavbek S, Saryal S, Karabiyikoglu G, Misirligil Z.

Department of Allergic Diseases, Ankara University Medical School, Turkey.
bavbek@medicine.ankara.edu.tr

Rhinitis patients may have abnormal airway function as demonstrated by an
obstruction in large or small airways and increased bronchial reactivity to
inhaled nonspecific provocating agents. The nonspecific bronchial hyperreactivity
(BHR) is particularly important in patients with rhinitis because they are more
prone to develop asthma. However, the factors associated with BHR in rhinitis
patients have not yet been explained. Therefore, we performed this study to
determine the differences in airflow rates, and bronchial and nasal resistance
between nonasthmatic rhinitis patients with or without BHR, and to evaluate the
relationship between these parameters and bronchial reactivity to methacholine. A
total of 66 patients with allergic rhinitis but not asthma were selected for the 
study and divided into two groups; Group 1 (40 patients with allergic rhinitis
and negative mechacholine provocation test) and Group 2 (26 patients with
allergic rhinitis and positive methacholine provocation test). Pulmonary function
tests, methacholine provocation tests, anterior rhinomanometry, and skin prick
tests were performed on the patients. The study groups were homogeneous with
regard to gender, age, duration of illness, and smoking ratio. Expiratory airflow
parameters including FVC, FEV1, PEFR, and FEF25 were similar in both groups,
however FEV1/FVC, FEF25-75, FEF50, and FEF75 were significantly lower in Group 2.
Additionally, sRaw was significantly higher in Group 2 and negatively correlated 
with the expiratory airflow parameters for small airways. Total nasal resistance 
was not different between the groups. There was no correlation between nasal
resistance and BHR to methacholine or airway resistance. The present study
suggests that nonasthmatic rhinitis patients with BHR may have mild but
significant changes in the small airways. Clinical and functional follow-up of
these patients should assess the long-term consequences of these parameters and
their clinical importance.

PMID: 14989114 [PubMed - indexed for MEDLINE]

973: J Investig Allergol Clin Immunol. 2003;13(4):228-31.

Symptomatic relief after grass nasal immunotherapy: lasting efficacy after 4-5
years.

Andri L, Falagiani P.

Lofarma SpA, Milan, Italy.

Twenty-two patients with rhinoconjunctivitis from grass pollen allergy, who were 
initially recruited for a one-year open clinical trial with local nasal
immunotherapy (LNIT), continued the treatment for 2 or 3 more years. Three to
four years after the end of treatment, they were reapproached and agreed to
complete a questionnaire to evaluate their symptoms and rescue medications during
the grass-pollen season. Twelve patients (54.6%) were almost free of symptoms,
six patients (27.3%) complained of only minor symptoms, and four (18.1%) still
had substantial symptoms. The median score for cumulative symptoms 4-5 years
after stopping LNIT (112.5 points) was lower than before LNIT (291.6 points) and 
after the one-year clinical trial (138.2 points). The present observational study
confirms the validity of LNIT as an alternative to conventional subcutaneous
immunotherapy.

PMID: 14989110 [PubMed - indexed for MEDLINE]

974: Clin Exp Allergy. 2004 Feb;34(2):259-67.

Erratum in:
    Clin Exp Allergy. 2004 Aug;34(8):1329.

Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in 
mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and
cetirizine plus montelukast for seasonal allergic rhinitis.

Di Lorenzo G, Pacor ML, Pellitteri ME, Morici G, Di Gregoli A, Lo Bianco C, Ditta
V, Martinelli N, Candore G, Mansueto P, Rini GB, Corrocher R, Caruso C.

Dipartimento di Medicina Clinica e delle Patologie Emergenti, Università di
Palermo, Italy.

BACKGROUND: Corticosteroids are considered to be particularly effective in
reducing nasal congestion and are therefore recommended as first-line treatment
in allergic rhinitis patients with moderate to severe and/or persistent symptoms.
OBJECTIVE: We compared the clinical efficacy of fluticasone propionate aqueous
nasal spray (FPANS) 200 microg given once daily, administered in mono-therapy or 
combined therapy with a H1 receptor antagonist (cetirizine, CTZ) or with a
leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus
MSK in the treatment of patients affected by allergic rhinitis to Parietaria
during natural pollen exposure. In addition, we examined the effect of the
treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal
lavage performed at beginning of season, during season and at the end of the
season. METHODS: One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6)
with a history of moderate to severe Parietaria pollen-induced seasonal allergic 
rhinitis were selected. A randomized, double-blind, double dummy, placebo
(PLA)-controlled, parallel-group study design was used. Patients were treated
FPANS 200 microg once daily (n=20) or with FPANS 200 microg once daily, plus CTZ 
(10 mg) in the morning (n=20), or with FPANS 200 microg once daily, plus MSK (10 
mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the
evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores 
of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage.
RESULTS: All treatments showed significant differences (P<0.001) compared with
PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores.
Concerning nasal congestion on waking and daily only the groups treated with
FPANS in mono-therapy or in combined therapy showed significant differences
compared with PLA. Comparing the group treated with FPANS alone and the groups
treated with FPANS plus CTZ, we found significant differences for total symptom
score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus
CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003).
Finally, there were significant differences between the group treated with FPANS 
and the group treated with CTZ plus MSK for total symptom score (P=0.009), for
nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also
the comparisons between the group treated with FPANS plus CTZ and the group
treated with CTZ plus MSK demonstrated significant differences (P<0.001) for
total symptom, for nasal congestion on waking and for nasal congestion on daily, 
for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the
comparison between the group treated with FPANS plus MSK and the group treated
with CTZ plus MSK we found significant differences for total symptom score
(P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on
daily (P<0.001). No other differences were observed between the groups.
Concerning blood eosinophil counts, significant differences were found between
the treatments with FPANS in mono-therapy or in combined therapy with PLA group
during and at the end of the season (P=0.0003 and P<0.0001, respectively).
Concerning eosinophils and ECP in nasal lavage, all treatments showed significant
differences (P<0.001) compared with PLA. Besides, there were significant
differences (P<0.001) between the groups treated with FPANS alone or in combined 
therapy and the group treated with CTZ plus MSK. CONCLUSION: The results of this 
comparative study demonstrate that FPANS is highly effective for treating
patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus 
MSK in combined therapy. In addition, the regular combined therapy of FPANS plus 
CTZ or plus MSK would not seem to offer substantial advantage with respect to
FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14987306 [PubMed - indexed for MEDLINE]

975: Am J Med. 2004 Mar 1;116(5):338-44.

Comment in:
    ACP J Club. 2004 Sep-Oct;141(2):45.

Leukotriene receptor antagonists for allergic rhinitis: a systematic review and
meta-analysis.

Wilson AM, O'Byrne PM, Parameswaran K.

Firestone Institute for Respiratory Health, St. Joseph's Healthcare, and
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

PURPOSE: To compare the clinical efficacy of leukotriene receptor antagonists
with that of placebo, antihistamines, and nasal corticosteroids in patients with 
allergic rhinitis or nasal polyposis. METHODS: We performed a systematic review
and meta-analysis of randomized controlled trials of the effectiveness of
leukotriene receptor antagonists in patients with rhinitis. Composite daily
rhinitis symptom scores (as a percentage of the maximum score) and
rhinitis-specific quality of life (unit scores ranging from 0 to 6) were pooled
after assessing heterogeneity among studies. The pooled estimates were expressed 
as weighted mean differences between treatments in a random-effects model. We
considered a difference of 10% in nasal score and 0.6 units in quality-of-life
score to be clinically relevant. RESULTS: Of the 196 citations, 11 studies on
seasonal allergic rhinitis were used in the analysis: eight evaluating
leukotriene receptor antagonists alone or in combination with other treatments
versus placebo or other treatments (n = 3924) and three evaluating leukotriene
receptor antagonists plus an antihistamine (n = 80). Leukotriene receptor
antagonists reduced mean daily rhinitis symptom scores (in absolute terms) 5%
(95% confidence interval [CI]: 3% to 7%) more than did placebo. However,
antihistamines improved the nasal symptoms score 2% (95% CI: 0% to 4%) more than 
did leukotriene receptor antagonists, and nasal corticosteroids improved the
score 12% (95% CI: 5% to 18%) more than did leukotriene antagonists. Leukotriene 
receptor antagonists significantly improved rhinoconjunctivitis quality of life
by 0.3 units (95% CI: 0.24 to 0.36 units) when compared with placebo. There were 
no randomized controlled trials evaluating the effect of leukotriene receptor
antagonists on perennial allergic rhinitis or polyposis. CONCLUSION: Leukotriene 
receptor antagonists are modestly better than placebo, as effective as
antihistamines, but less effective than nasal corticosteroids in improving
symptoms and quality of life in patients with seasonal allergic rhinitis.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 14984820 [PubMed - indexed for MEDLINE]

976: Eur J Clin Invest. 2004 Jan;34(1):67-73.

Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal
allergic rhinitis.

Tillmann HC, Stuck BA, Feuring M, Rossol-Haseroth K, Tran BM, Lösel R, Schmidt
BM, Hörmann K, Wehling M, Schultz A.

Institute of Clinical Pharmacology, University of Heidelberg, Mannheim, Germany.

BACKGROUND: Glucocorticosteroids are effective in the treatment of allergic
rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and
itching. The time course of symptomatic relief for allergic rhinitis by steroids 
has not been examined in detail to date, although the onset of steroid action is 
one of the main discriminations between genomic and nongenomic actions of
steroids. We therefore investigated the time course of subjective and objective
measures of nasal affection after steroid administration in patients with
allergic rhinitis following specific allergen challenge. METHODS: Six female and 
18 male volunteers (median age 26 years) with a history of allergic rhinitis but 
currently free of symptoms were included in this randomized, placebo-controlled, 
double-blind, three-period crossover study. A single dose of either betamethasone
(60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min
after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal
itching and nasal obstruction were assessed using a standardized visual analogue 
scale. In addition, nasal airflow was measured by anterior rhinomanometry.
RESULTS: Nasal itching was markedly reduced following either of the two steroids 
within 10 min after administration of study drug. Itching was depressed by 38%
following betamethasone (P<0.05) and by 18% following methylprednisolone (P=0.07)
compared with placebo. Nasal airflow and nasal obstruction were not significantly
altered by steroids during the first 2 h of the study. However, after 150 min,
nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone 
(P<0.05) compared with placebo. After 240 min, nasal airflow was increased by 20%
following betamethasone (P<0.05) and by 19% following methylprednisolone. Nasal
obstruction was also beneficially affected by both steroids 150 and 240 min after
administration compared with placebo (P<0.05 for both time points following
betamethasone). CONCLUSION: This study for the first time shows rapid in vivo
effects of external glucocorticosteroids in humans. Itching, a
pathophysiologically complex sensation, is favourably influenced by steroids
within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed
mechanisms can be derived from this study, steroid interaction with receptors in 
the central nervous system may play an important role in mediating this effect.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14984440 [PubMed - indexed for MEDLINE]

977: Allergy. 2004 Mar;59(3):320-6.

Association between nasal and bronchial symptoms in subjects with persistent
allergic rhinitis.

Downie SR, Andersson M, Rimmer J, Leuppi JD, Xuan W, Akerlund A, Peat JK, Salome 
CM.

Woolcock Institute of Medical Research, Camperdown, Sydney, Australia.

BACKGROUND: The association between nasal and bronchial symptoms, and the course 
of bronchial responsiveness and airway inflammation in house dust mite sensitive 
persistent rhinitis over a prolonged time period has not been thoroughly
explored. OBJECTIVE: To determine if nasal symptoms were associated with
bronchial symptoms in persistent rhinitic subjects, and to assess their bronchial
responsiveness and airway inflammation in comparison to nonrhinitic, nonatopic
controls. The additional impact of pollen sensitivity on the lower airways in
rhinitic subjects was also addressed. METHODS: Rhinitics and controls answered
telephone symptom questionnaires once every 2 weeks for 1 year. Every 3 months,
exhaled nitric oxide (eNO) and bronchial responsiveness to histamine were
measured. RESULTS: Thirty-seven rhinitics and 19 controls completed the study.
High nasal symptom scores in rhinitic subjects were associated with bronchial
symptoms (OR = 1.7, 95% CI 1.2-2.5). Bronchial hyper-responsiveness was present
in 32.4% of rhinitic subjects on at least one clinical visit during the year.
Pollen allergy caused seasonal variation in eNO (P = 0.03). CONCLUSION: In
persistent rhinitic subjects, high nasal symptom scores were associated with
bronchial symptoms, and many subjects experienced bronchial hyper-responsiveness 
during the year. Persistent rhinitic subjects were more at risk than healthy
adults of bronchial symptoms and airway inflammation, which are likely risk
factors for asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14982515 [PubMed - indexed for MEDLINE]

978: Allergy. 2004 Mar;59(3):315-9.

Management of allergic rhinitis: a common part of practice in primary care
clinics.

Wang DY, Chan A, Smith JD.

Department of Otolaryngology, National University of Singapore, Singapore.

BACKGROUND: Allergic rhinitis (AR) is an extremely common disease worldwide and
one of the top-ten reasons for a visit to primary care clinics. This study aimed 
to investigate the understanding of current guidelines and concepts of management
for AR among general practitioners (GPs) in Singapore. METHODS: A postal
questionnaire was designed to survey the dispensing practice and understanding of
current guidelines in the management of AR among Singapore GPs. RESULTS: Two
hundred GPs completed the questionnaire. AR was estimated to be 10-40% of total
patient visits in 50% of the primary care clinics surveyed. There was no
significant difference in diagnosis and management of AR among GPs practicing
solo, as a group or in polyclinics. The use of allergy tests (skin or in vitro
tests) was <50%. Most physicians understood correctly the efficacy, side-effects,
and cost effectiveness of first and newer generation H1-antihistamines and nasal 
glucocorticosteroids. However, first generation H1-antihistamines and oral/nasal 
decongestants are commonly used to reduce the cost of medication and to achieve
quick relief from nasal obstruction. CONCLUSION: Management of allergic rhinitis 
is common in primary care clinics. Quick symptomatic relief with low-cost
medications is a major concern for GPs in the management of AR, as it will affect
a patient's compliance and perception of efficacy. However, inappropriate use of 
decongestants and other nonevidence-based therapies should not be recommended.
Implementing the current evidence-based international guidelines for AR needs to 
be improved.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14982514 [PubMed - indexed for MEDLINE]

979: Allergy. 2004 Mar;59(3):306-14.

The role of climate on the geographic variability of asthma, allergic rhinitis
and respiratory symptoms: results from the Italian study of asthma in young
adults.

Zanolin ME, Pattaro C, Corsico A, Bugiani M, Carrozzi L, Casali L, Dallari R,
Ferrari M, Marinoni A, Migliore E, Olivieri M, Pirina P, Verlato G, Villani S,
Marco R; ISAYA Study Group.

Unit of Epidemiology and Medical Statistics, University of Verona, Verona, Italy.

BACKGROUND: Variations in the prevalence of respiratory symptoms according to
geo-climatic factors could provide important clues to the knowledge of the
aetiology of asthma. METHODS: Geo-climatic variations in the prevalence of
current asthma, allergic rhinitis and chronic cough, and phlegm were assessed on 
a random sample of 18 873 subjects (response rate = 72.7%) from different
climatic regions of Italy. An ecological analysis, supported by robust
statistical methods, was employed to investigate potential trends. RESULTS: The
prevalence of all symptoms was significantly heterogeneous throughout the
peninsula. Only asthma-like symptoms showed a north-south trend: the prevalence
increased at a decreasing latitude [odds ratio (OR) varies from 0.92 to 0.96, P <
0.05], at a decreasing distance from the sea (OR: 0.90-0.93 for 30 km distance, P
< 0.05), at higher annual mean temperatures (OR: 1.11-1.14, P < 0.05) and at
smaller annual temperature ranges (OR: 0.94-0.95, P < 0.05). Of the geo-climatic 
variables considered, temperature range had the greatest influence on most
asthma-like symptoms. No association was found between geo-climatic variables and
allergic rhinitis or chronic cough and phlegm. CONCLUSIONS: Asthma prevalence
seems to be significantly affected by climate as asthma-like symptoms were more
common in central-southern Italy, with a Mediterranean climate, than in areas
with a continental climate (northern Italy).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14982513 [PubMed - indexed for MEDLINE]

980: Allergy. 2004 Mar;59(3):280-8.

Comment in:
    Allergy. 2004 Mar;59(3):276-9.

Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic
rhinitis: influence on clinical symptoms and nasal allergic inflammation.

Kurowski M, Kuna P, Górski P.

Division of Pneumonology and Allergology, Department of Medicine, Medical
University of Łódź, Łódź, Poland.

BACKGROUND: The aim of our study was to investigate effects of 6-week
pretreatment of seasonal allergic rhinitis (AR) with cetirizine, and montelukast,
alone and in combination. Antihistamine/antileukotriene treatment is effective in
AR. Antihistamines may prevent AR symptoms while prophylactic activity of
antileukotrienes remains unclear. METHODS: Sixty AR patients, aged 18-35 years,
were randomized to receive placebo, montelukast only, cetirizine only, or
montelukast plus cetirizine, 6 weeks prior and 6 weeks after the beginning of
grass pollen season. Mean self-recorded in-season symptom scores and mean weekly 
all-symptom scores were analyzed. In 31 patients, nasal lavages were performed
before treatment, and at the end of the study, i.e. 12 weeks after the treatment 
initiation. Eosinophil and basophil counts, eosinophil cationic protein (ECP),
and mast cell tryptase (MCT) levels were evaluated in lavage samples. RESULTS:
Combined montelukast/cetirizine pretreatment significantly reduced in-season
symptom score for sneezing, eye itching, nasal itching, rhinorrhea, and
congestion. Montelukast plus cetirizine were more effective than cetirizine alone
in preventing eye itching, rhinorrhea, and nasal itching. Moreover, combined
pretreatment with montelukast and cetirizine delayed appearance of AR symptoms.
Eosinophil nasal lavage fluid counts were significantly increased during pollen
season in placebo and montelukast-only groups. No differences were observed in
basophil counts. The in-season ECP level was significantly increased in all
groups except montelukast-plus-cetirizine group. In-season MCT levels were not
increased. CONCLUSION: Combined antihistamine and antileukotriene treatment
started 6 weeks before the pollen season is effective in preventing AR symptoms
and reduces allergic inflammation in nasal mucosa during natural allergen
exposure.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14982509 [PubMed - indexed for MEDLINE]

981: J Immunol. 2004 Mar 1;172(5):3252-9.

Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and
blocking IgG activity.

Nouri-Aria KT, Wachholz PA, Francis JN, Jacobson MR, Walker SM, Wilcock LK,
Staple SQ, Aalberse RC, Till SJ, Durham SR.

Upper Respiratory Medicine, Imperial College London, National Heart and Lung
Institute, London, United Kingdom.

T regulatory cells and IL-10 have been implicated in the mechanism of
immunotherapy in patients with systemic anaphylaxis following bee stings. We
studied the role of IL-10 in the induction of clinical, cellular, and humoral
tolerance during immunotherapy for local mucosal allergy in subjects with
seasonal pollinosis. Local and systemic IL-10 responses and serum Ab
concentrations were measured before/after a double-blind trial of grass pollen
(Phleum pratense, Phl P) immunotherapy. We observed local increases in IL-10
mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy, but only 
during the pollen season. IL-10 protein-positive cells were also increased and
correlated with IL-10 mRNA(+) cells. These changes were not observed in
placebo-treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA
signals were colocalized to CD3(+) T cells and CD68(+) macrophages, respectively,
whereas only 1-2% of total CD3(+) cells and 4% of macrophages expressed IL-10.
Following immunotherapy, peripheral T cells cultured in the presence of grass
pollen extract also produced IL-10. Immunotherapy resulted in blunting of
seasonal increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold
increases in Phl p 5-specific IgG, and 100-fold increases in Phl p 5-specific
IgG4. Post-immunotherapy serum exhibited inhibitory activity, which coeluted with
IgG4, and blocked IgE-facilitated binding of allergen-IgE complexes to B cells.
Both the increases in IgG and the IgG "blocking" activity correlated with the
patients' overall assessment of improvement. Thus, grass pollen immunotherapy may
induce allergen-specific, IL-10-dependent "protective" IgG4 responses.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14978133 [PubMed - indexed for MEDLINE]

982: Int Arch Allergy Immunol. 2004 Mar;133(3):267-75. Epub 2004 Feb 17.

Suppressive activity of fexofenadine hydrochloride on thymus- and
activation-regulated chemokine production from human peripheral blood leukocytes 
in response to antigenic stimulation in vitro.

Asano K, Kanai K, Suzaki H.

Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
asanok@med.showa-u.ac.jp

BACKGROUND: Thymus- and activation-regulated chemokine (TARC) is accepted as
being an important molecule in the development and maintenance of allergic
diseases. However, there is little information about the influence of
antiallergic agents on TARC production after allergen challenge. The aim of this 
study is to examine the influence of fexofenadine hydrochloride (FEX), an
H1-receptor antagonist, on TARC production from human peripheral blood leukocytes
(PBL) using an in vitro cell culture technique. METHODS: PBL prepared from donors
with pollinosis were cultured with either Japanese cedar pollen allergen, Cry j
1, or interleukin (IL)-4 in the presence of various doses of FEX for 6 days.
Levels of TARC and the T cell cytokines IL-4 and interferon (IFN)-gamma in
culture supernatants were examined by ELISA. RESULTS: FEX did not affect PBL
proliferation induced by Cry j 1 stimulation, even when 500 ng/ml of the agent,
twice the therapeutic blood levels, was added to cell cultures as assessed by
measuring 3H-thymidine incorporation into DNA. On the other hand, FEX at 250
ng/ml (but not 125 ng/ml), similar to therapeutic blood levels, significantly
inhibited the ability of PBL to produce IL-4 (but not IFN-gamma), which was
enhanced by Cry j 1 stimulation. FEX at concentrations of more than 250 ng/ml
also exerted a suppressive effect on TARC production from PBL in response to Cry 
j 1 and IL-4 stimulation in vitro. CONCLUSION: This inhibitory action of FEX may 
be partially responsible for the attenuating effect of the agent on allergic
diseases. Copyright 2004 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14976396 [PubMed - indexed for MEDLINE]

983: Phytomedicine. 2004 Jan;11(1):36-42.

Characteristics, clinical effect profile and tolerability of a nasal spray
preparation of Artemisia abrotanum L. for allergic rhinitis.

Remberg P, Björk L, Hedner T, Sterner O.

Department of Organic and Bioorganic Chemistry, Lund University, Lund, Sweden.

A nasal spray formulation containing an extract of Artemisia abrotanum L. was
developed for therapeutic use in patients with allergic rhinitis and other upper 
airway disorders. The nasal spray preparation used contains a mixture of
essential oils (4 mg/ml) and flavonols (2.5 microg/ml), of which some components 
have been shown to possess antiinflammatory, expectorant, spasmolytic as well as 
antiseptic and antimicrobial activities. The most important constituents in the
essential oil fraction of the preparation are 1,8-cineole, linalool and davanone,
while the flavonol fraction contains centauredin, casticin and quercetin
dimethyl-ethers. No trace of thujon was observed in the essential oil of the
Artemisia abrotanum L. genotype "Tycho" used for the manufacture of the nasal
spray preparation. In 12 patients with diagnoses of allergic rhinitis, allergic
conjunctivitis and/or bronchial obstructive disease, the nasal spray was given
immediately after the appearance of characteristic allergic nasal symptoms. In 10
of the 12 patients, allergic rhinitis with nasal congestion, sneezing and
rhinorrhea was dominant. After administration of the nasal spray, all patients
experienced a rapid and significant symptom relief of nasal symptoms, comparable 
to the effect of antihistamine and chromoglicate preparations which several of
the patients had used previously. The effect was present within 5 minutes after
the administration and lasted for several hours. In 7 of the 10 rhinitis patients
with concomitant symptoms of allergic conjunctivitis, a significant subjective
relief of eye symptoms was also experienced. In 3 of the 6 patients who had a
history of characteristic symptoms of endogenous, exogenous or exercise induced
bronchial obstructive disease, there was a bronchial symptom relief by the nasal 
spray preparation which was experienced as rapid and clinically significant. It
is concluded from the present proof of concept study, that a nasal spray
formulation containing an extract characterised by a mixture of essential oils
and flavonols from the Artemisia abrotanum L. genotype "Tycho", appears to be
clinically useful and suitable for the prophylactic and therapeutic management of
patients with allergic rhinitis and adjuvant symptoms.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 14971719 [PubMed - indexed for MEDLINE]

984: J Otolaryngol. 2003 Dec;32(6):388-93.

Role of microbial toxins in the induction of glucocorticoid receptor beta
expression in an explant model of rhinosinusitis.

Fakhri S, Christodoulopoulos P, Tulic M, Fukakusa M, Frenkiel S, Leung DY, Hamid 
QA.

Department of Otolaryngology, McGill University, Montreal, Quebec.

BACKGROUND: Glucocorticoids (GCs) are the most potent agents currently available 
for relieving the symptoms of chronic rhinosinusitis. The pathogenesis and
molecular basis of GC insensitivity in allergic rhinosinusitis are unknown.
Studies done on patients with GC-insensitive asthma demonstrated an
overexpression of GC receptor beta (GRbeta), an abnormal splice variant and an
endogenous inhibitor of the classic GC receptor alpha. The mechanisms that induce
the overexpression of GRbeta remain poorly understood. OBJECTIVE: To study the
role of Staphylococcus-derived enterotoxin in inducing GRbeta in a human explant 
model of rhinosinusitis. METHODS: Nasal tissue was obtained from inferior
turbinates of nonatopic and ragweed-sensitive patients. Tissue samples from
nonatopic patients were incubated in the presence and absence of superantigen
(SAg) of staphylococcal enterotoxin. In addition, tissue samples from
ragweed-sensitive patients were incubated with and without ragweed allergen in
the presence or absence of SAg. The expression of GRbeta was assessed by
immunocytochemistry using a specific polyclonal antibody to GRbeta. RESULTS: SAg 
increased the expression of GRbeta in both atopic and nonatopic tissue. The
highest increase in the expression of GRbeta occurred when atopic nasal tissue
was incubated with both ragweed and SAg. CONCLUSION: SAg-induced GRbeta is an
important modulator of steroid sensitivity in chronic rhinosinusitis.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 14967085 [PubMed - indexed for MEDLINE]

985: J Allergy Clin Immunol. 2004 Feb;113(2):297-302.

Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on
basophils.

Lin H, Boesel KM, Griffith DT, Prussin C, Foster B, Romero FA, Townley R, Casale 
TB.

Division of Allergy/Immunology, Department of Medicine, Creighton University,
Omaha, Neb, USA.

BACKGROUND: Omalizumab is a monoclonal anti-IgE antibody that is effective for
the treatment of allergic respiratory disorders; however, its onset of action is 
unknown. OBJECTIVE: This study was designed to determine the onset of action of
omalizumab through the use of a challenge model to determine time-dependent
inhibition of ragweed-induced changes in nasal volume as well as correlate the
kinetics of omalizumab-induced decreases in serum free IgE and FcepsilonRI
receptors on basophils. METHODS: We conducted a 6-week, randomized, double-blind,
placebo-controlled study of 24 rhinitic patients with ragweed allergy. After
PD(30) ragweed nasal allergen challenge, patients received either omalizumab,
approximately 0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were
rechallenged with ragweed PD(30) dose biweekly. FcepsilonRI expression on blood
basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days
after treatment. IgE levels were measured at baseline and on days 3, 28, and 42. 
RESULTS: Mean IgE levels decreased by 96% (P <.001) from baseline within 3 days
in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was
decreased to 20.4% at 7 to 14 days (P <.001) and 12.2% at 35 to 42 days (P <.001)
for the omalizumab group. There was a median decrease in basophil FcepsilonRI
expression of 73% (P <.001) in the omalizumab group, with maximum inhibition
occurring within 14 days of treatment. No significant changes in IgE levels,
nasal allergen challenge responses, or basophil FcepsilonRI expression were
observed throughout the study in the placebo group. CONCLUSIONS: Our study showed
that the onset of action by omalizumab in blunting ragweed-induced nasal
responses is within 2 weeks, and this response was associated with 2 putative
mechanisms of action: decreased serum free IgE and decreased FcepsilonRI receptor
expression on immune effector cells.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14767445 [PubMed - indexed for MEDLINE]

986: J Allergy Clin Immunol. 2004 Feb;113(2):235-41.

Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases 
the nasal inflammatory response.

Tulic MK, Fiset PO, Christodoulopoulos P, Vaillancourt P, Desrosiers M, Lavigne
F, Eiden J, Hamid Q.

Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.

BACKGROUND: Amb a 1-immunostimulatory phosphorothioate oligonucleotide conjugate 
(AIC) is a novel immunotherapeutic compound consisting of purified Amb a 1 from
short ragweed proteins covalently linked to an immunostimulatory phosphorothioate
oligodeoxyribonucleotide. In sensitized animals AIC can stimulate an Amb a
1-specific T(H)1 response and decrease pulmonary reactivity to ragweed challenge.
Clinical trials have documented reduced allergic response to AIC in comparison
with licensed ragweed extract. OBJECTIVES: We sought to determine the in vivo
effect of short-course immunotherapy with AIC on eosinophilia and cytokine mRNA
expression in the nasal mucosa of ragweed-sensitive patients. METHODS:
Ragweed-sensitive patients with allergic rhinitis were treated with 6 escalating 
doses of AIC (0.06-12 microg, n = 28) or placebo (n = 29) at weekly intervals
immediately before the 2001 ragweed season. Symptom scores and medication use
were recorded for the 2001 and 2002 ragweed seasons for all patients. A subset of
patients (12 receiving AIC and 7 receiving placebo) consented to have nasal
biopsy specimens taken before immunization and before and after the first ragweed
season. The preseason and postseason biopsy specimens were taken 24 hours after
ragweed allergen challenge and compared with the initial unchallenged biopsy
specimen to assess cytokine and inflammatory cell responses by using
immunocytochemistry and in situ hybridization. RESULTS: AIC was safe and well
tolerated by all patients. There was no difference between the AIC and placebo
groups in the number of allergen-induced major basic protein-, IL-4-, IL-5-, or
IFN-gamma-positive cells in the mucosa in the first weeks after AIC immunization.
On rechallenge and rebiopsy after the end of the 2001 ragweed season, however,
AIC-treated patients had a significantly reduced increase in eosinophils and IL-4
mRNA-positive cells and an increased number of IFN-gamma mRNA-positive cells
compared with placebo-treated patients. No difference between treatment groups
was observed in symptom scores or medication use during the first ragweed season.
During the second ragweed season, however, there was a significant decrease in
chest symptoms and a trend toward reduced nasal symptoms in the AIC-treated
group. CONCLUSION: Short-course immunotherapy with AIC can modify the response of
nasal mucosa to allergen challenge by increasing T(H)1 cytokine production and
decreasing T(H)2 cytokine production and eosinophilia. This modification was not 
immediate but was observed 4 to 5 months after completion of immunotherapy and
seasonal ragweed-pollen exposure. The T-cell subset shift after immunization and 
seasonal exposure was followed by evidence of clinical efficacy in the second
ragweed season without additional AIC immunizations.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14767435 [PubMed - indexed for MEDLINE]

987: Int Arch Allergy Immunol. 2004 Feb;133(2):164-7. Epub 2004 Feb 5.

The seasonal variation in allergic rhinitis and its correlation with outdoor
allergens in Kuwait.

Behbehani N, Arifhodzic N, Al-Mousawi M, Marafie S, Ashkanani L, Moussa M,
Al-Duwaisan A.

Department of Medicine, Kuwait University, Kuwait. nasser_beh@hsc.kuniv.edu.kw

BACKGROUND: Allergic rhinitis (AR) is the most common allergic problem in Kuwait.
Most of the patients who have either AR or asthma are referred to the Al-Rashed
Allergy Center. OBJECTIVE: To determine if there is a seasonal variation in AR in
Kuwait and to correlate it with the daily pollen count. METHODS: Information
about the new patients referred to the center over a 5-year study period
(1996-2000) was extracted from the center's records. The daily pollen count in
Kuwait city was obtained from the Air Biology Laboratory. RESULTS: There was a
significant seasonal variation with a bimodal increase in the number of patients 
with AR referred to the center. The main peak in the number of patients occurred 
in September-October, and there was a smaller peak in April-May. The mean number 
+/- SD of new patients per month over the 5-year period varied from 87 +/- 32 for
December to 367 +/- 104 for September. Similarly, the average daily pollen count 
varied from 3.7 +/- 1.0 pollens per mm3 in January to 124 +/- 92 in October.
There was high correlation between the number of new AR patients and the average 
total pollen count (Pearson correlation, r=0.77, p<0.001), as well as with
Chenopodiaceae and Amaranthaceae (weed) pollens (r=0.75, p<0.001), while there
was no correlation between the number of new patients and either tree or grass
pollens. CONCLUSION: Seasonal AR occurs during two periods in Kuwait, i.e.
September-October and April-May, with September-October being the main season.
The rise in AR during late summer in Kuwait is mainly associated with the
pollination of Chenopodiaceae species. Copyright 2004 S. Karger AG, Basel

PMID: 14764943 [PubMed - indexed for MEDLINE]

988: Ann Allergy Asthma Immunol. 2004 Jan;92(1):73-9.

Comparison of the combinations of fexofenadine-pseudoephedrine and
loratadine-montelukast in the treatment of seasonal allergic rhinitis.

Moinuddin R, deTineo M, Maleckar B, Naclerio RM, Baroody FM.

Section of Otolaryngology-Head and Neck Surgery, The Pritzker School of Medicine,
The University of Chicago, Chicago, Illinois 60637, USA.

BACKGROUND: Antihistamine-decongestant combinations are used routinely for the
treatment of seasonal allergic rhinitis. Recently, the combination of an
antihistamine and a leukotriene receptor antagonist has been shown to be
efficacious. OBJECTIVE: To compare the 2 combinations in the treatment of
seasonal allergic rhinitis. METHODS: This was a randomized, double-blind,
double-dummy, parallel study in which patients with seasonal allergic rhinitis
received either fexofenadine, 60 mg, and pseudoephedrine, 120 mg, twice daily, or
loratadine, 10 mg, and montelukast, 10 mg, once daily, for 2 weeks. The
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was completed at the
beginning and end of the study. Patients recorded nasal symptoms and measured
nasal peak inspiratory flow (NPIF) twice daily. Baseline measurements were
obtained before initiation of treatment. RESULTS: Compared with baseline, both
treatments resulted in statistically and clinically meaningful reductions of
overall and individual RQLQ domain scores (P < .01) except for the sleep domain, 
for which only loratadine-montelukast led to significant improvement. There was a
significant reduction in total symptoms (P < or = .05) compared with baseline on 
most treatment days in patients receiving both combinations. When the change from
baseline was analyzed, there were no statistically significant differences in
total symptoms between fexofenadine-pseudoephedrine and loratadine-montelukast
(median, -28.5 vs -22.5; P = .33). There was a significant improvement in NPIF
from baseline on all treatment days in both groups (P < .05), with no significant
difference between treatments. CONCLUSIONS: Fexofenadine-pseudoephedrine and
loratadine-montelukast have comparable efficacy in improving symptoms, RQLQ
scores, and nasal obstruction in seasonal allergic rhinitis. The lack of
improvement in sleep in the fexofenadine-pseudoephedrine group is probably
related to insomnia, a known adverse effect of pseudoephedrine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14756468 [PubMed - indexed for MEDLINE]

989: Ann Allergy Asthma Immunol. 2004 Jan;92(1):25-31.

Comment in:
    Ann Allergy Asthma Immunol. 2004 Jan;92(1):1-2.

Clinical efficacy of microencapsulated timothy grass pollen extract in
grass-allergic individuals.

TePas EC, Hoyte EG, McIntire JJ, Umetsu DT.

Division of Immunology and Allergy, Department of Pediatrics, Stanford
University, Stanford, California, USA. etepas@partners.org

BACKGROUND: Conventional allergen immunotherapy is clinically effective in
reducing the symptoms of allergic rhinitis and asthma. It differs from other
pharmacotherapies in that it can induce long-term clinical remission of these
diseases. However, it requires years of treatment and is associated with serious 
allergic reactions. OBJECTIVE: To evaluate the safety, clinical efficacy, and
immunologic mechanisms of immunotherapy with an oral, microencapsulated form of
timothy grass allergen. METHODS: In this double-blind, placebo-controlled study, 
24 patients aged 19 to 55 years with grass pollen allergy were randomized to
receive either microencapsulated timothy grass pollen extract or placebo once a
day for 10 weeks. The dose of study drug was doubled weekly. Safety was evaluated
through weekly visits, daily symptom diaries, and routine laboratory tests.
Efficacy was evaluated by comparing medication use and symptoms scores during
peak grass pollen season before and after treatment. Allergen-specific T-cell
responses, cytokine production, and IgG, IgE, and skin reactivity were measured
to evaluate immunologic mechanisms. RESULTS: Eleven of 12 patients in the active 
treatment group had a decrease in the combined medication and symptom score, but 
only 4 of 10 patients in the placebo group had a decrease in scores. The
proliferative response to timothy grass was reduced by at least 30% in 9 of the
12 grass-treated patients, but only 3 of 11 placebo patients had a proliferative 
response reduction. Timothy grass-induced interleukin-5 messenger RNA was reduced
in the active group, but not in the placebo group. There were no significant
changes in either group in IgG, IgE, and skin reactivity. CONCLUSIONS: Oral
immunotherapy with microencapsulated allergen induces a form of immunologic
tolerance to the allergen and is a safe, efficient, and effective method of
allergen immunotherapy.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14756461 [PubMed - indexed for MEDLINE]

990: Pharmacotherapy. 2004 Jan;24(1):26-32.

Effect of fluticasone propionate nasal spray on bioavailability of intranasal
hydromorphone hydrochloride in patients with allergic rhinitis.

Davis GA, Rudy AC, Archer SM, Wermeling DP, McNamara PJ.

Division of Pharmacy Practice and Science, College of Pharmacy, University of
Kentucky, Lexington 40536-0293, USA. gadavi00@email.uky.edu

STUDY OBJECTIVE: To investigate the effect of the nasal corticosteroid
fluticasone propionate on the bioavailability and pharmacokinetics of single-dose
intranasal hydromorphone hydrochloride in patients with allergic rhinitis.
DESIGN: Randomized, three-way, crossover pharmacokinetic study. SETTING:
University clinical research unit. PATIENTS: Twelve patients with allergic
rhinitis. INTERVENTION: Hydromorphone hydrochloride 2.0 mg was administered by
intravenous infusion (treatment A), intranasal spray without allergic rhinitis
treatment (treatment B), and intranasal spray after 6 days of fluticasone
propionate (treatment C). Blood samples were collected serially from 0-16 hours. 
MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters were determined by
noncompartmental methods. An analysis of variance (ANOVA) model was used for
statistical analysis. Mean (% coefficient of variation) absolute bioavailability 
of intranasal hydromorphone was 51.9% (28.2) and 46.9% (30.3) in patients with
allergic rhinitis with and without treatment with fluticasone propionate,
respectively. Mean maximum concentration (Cmax) values were 3.02 and 3.56 ng/ml, 
respectively. No statistical differences in Cmax and area under the concentration
versus time curve were detected between intranasal treatments. Bioavailability
values for both intranasal treatments were lower than those in healthy volunteers
(57%). Median time to Cmax (Tmax) values were significantly different (p=0.02)
for treatments B and C (15 and 30 min, respectively) using rank-transformed Tmax 
for ANOVA. Adverse effects were consistent with known effects of hydromorphone
administered by other routes, with the exception of bad taste after intranasal
administration. CONCLUSION: Hydromorphone was rapidly absorbed after nasal
administration, with maximum concentrations occurring for most subjects within 30
minutes. Allergic rhinitis may affect pain management strategies for intranasal
hydromorphone, with a delay in onset of action for patients treated with
fluticasone propionate.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14740785 [PubMed - indexed for MEDLINE]

991: J Pharmacol Sci. 2003 Dec;93(4):437-45.

Acquired nasal hyperresponsiveness aggravates antigen-induced rhinitis in the
guinea pig.

Mizutani N, Nabe T, Takenaka H, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, Yamaguchi, Japan.

Whether a state of nasal hyperresponsiveness influences antigen-induced biphasic 
nasal blockage and sneezing were examined using a guinea pig model of allergic
rhinitis. Sensitized animals were challenged with an antigen, Japanese cedar
pollen, once every week. Before the 13th challenge, the animals were randomly
divided into 2 groups, and then the 13th challenge was performed (Groups A-0 and 
B-0). The 14th challenge was done on day 2 (Group A-2) and on day 7 (Group B-7)
after the 13th challenge, on which nasal hyperresponsiveness was present and
absent, respectively. Biphasic nasal blockage and sneezing after the challenge in
Group A-2 were more severe than those in Group A-0, while those of Group B-7 were
almost the same as those of Group B-0. An anti-histaminic, mepyramine, inhibited 
sneezing but not the biphasic nasal blockage in Group B-7. A cysteinyl
leukotriene (CysLT) antagonist, pranlukast, suppressed the late nasal blockage
but not the early blockage and sneezing in Group B-7. In contrast, in Group A-2, 
mepyramine significantly attenuated not only sneezing but also the early nasal
blockage. Pranlukast significantly inhibited both nasal blockage and sneezing in 
Group A-2. In conclusion, nasal hyperresponsiveness aggravated the
antigen-induced nasal responses, to which histamine and CysLTs considerably
contributed.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14737014 [PubMed - indexed for MEDLINE]

992: Clin Exp Allergy. 2004 Jan;34(1):123-30.

Cytokine production in peripheral blood cells during and outside the pollen
season in birch-allergic patients and non-allergic controls.

Wosinska-Becler K, Plewako H, Håkansson L, Rak S.

Asthma and Allergy Research Group, Department of Respiratory Medicine and
Allergology, Sahlgrenska University Hospital, Göteborg, Sweden.

BACKGROUND: The naturally occurring pollen season permits observation of the
kinetic changes in the process of allergic inflammation. We examined cytokine
production in peripheral blood (PB) T cells and monocytes obtained from
birch-allergic patients both during and outside the pollen season. METHODS: PB
from 16 patients and six healthy controls was obtained during the alder pollen
season, at the beginning and the peak of the birch pollen season and outside the 
pollen season. Mononuclear cells (MNC) were stimulated with allergen and
polyclonal activators. For flow cytometric analysis, MNC were stained with
monoclonal antibodies (MoAbs) against the cell surface markers CD3, CD8, CD14 and
the intracellular cytokines IL-4, IL-5, IL-10, IL-12, IL-13, granulocyte
macrophage-colony stimulating factor (GM-CSF) and IFN-gamma. RESULTS: In allergic
patients, significant increases in clinical symptoms, use of medication,
eosinophil numbers and birch-specific IgE were found during the pollen season. In
vitro allergen stimulation increased the number of GM-CSF+ monocytes (P<0.01) and
this increase was dependent on allergen exposure. The IL-4/IFN-gamma ratio rose
(P<0.001) at the peak of birch pollen season and the ratio correlated with
symptom scores during the birch season. In the CD4+ cell population, the numbers 
of GM-CSF+ cells were higher throughout the alder and birch seasons compared with
outside the pollen season (P<0.05). No such changes were seen in the healthy
controls. CONCLUSIONS: The main finding of our study was the increased percentage
of GM-CSF+ monocytes in atopic subjects compared with healthy controls. In
allergic patients, natural seasonal pollen exposure resulted in increased numbers
of GM-CSF+ cells among both monocytes and CD4+ T cells. We have also shown that a
seasonal change in Th2/Th1 cytokine ratio requires an adequate and prolonged
allergen stimulation that is seen late in the pollen season.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14720272 [PubMed - indexed for MEDLINE]

993: J Manag Care Pharm. 2004 Jan;10(1 Suppl):S9-13.

Cost efficiency of intranasal corticosteroid prescribing patterns in the
management of allergic rhinitis.

Reissman D, Price T, Leibman CW.

Rxperts, Irvine, CA 92618, USA.debi@rxperts.net

BACKGROUND: Effective treatment of seasonal or perennial allergic rhinitis often 
requires use of topical intranasal corticosteroids (INSs). Despite differences in
recommended starting dosages, the 4 leading INSs by market share are packaged in 
bottles containing 120 metered-dose sprays. OBJECTIVE: To determine the relative 
prescribed dosages of the leading INSs and compare economic differences resulting
from these prescribing behaviors. METHODS: The IMS National Disease and
Therapeutic Index (NDTI) was used to identify prescribing habits for the 4
leading INSs: fluticasone propionate nasal spray (FPNS), mometasone furoate
aqueous nasal spray (MFNS), triamcinolone acetonide aqueous nasal spray (TANS),
and budesonide aqueous nasal spray (BANS). The NDTI uses a national, randomly
drawn, 2-stage stratified clustersampling methodology. Physicians are sampled
during the first stage, with 2 workdays per month subsampled from each physician 
in the second stage. Each physician reports on all patient contacts during the 2 
consecutive days, offering a continuing compilation of statistical information
about patterns and treatment of disease encountered by office-based physicians.
In a given month, the NDTI reports on 1180 unique physicians. RESULTS: From
January 1, 2002, to December 31, 2002, 58% of prescriptions for FPNS were for 4
sprays daily with 37% for 2 sprays daily, MFNS: 44% for 4 sprays and 52% for 2,
TANS: 65% for 4 sprays and 31% for 2, and BANS: 29% for 4 sprays and 68% for 2.
These equated to mean prescribed daily dosages of 3.47 sprays per day for FPNS,
3.33 for MFNS, 3.50 for TANS, and 2.73 for BANS. Because each INS is packaged in 
a bottle with 120 metered-dose sprays, the differences in dosage offer varying
days of supply per unit filled. BANS offered the most days of treatment (44
days), followed by MFNS (38 days) and FPNS and TANS (means of 35 and 34 days,
respectively) per single prescription filled. Cost per day of treatment was
calculated by multiplying the prescribed dosage with the average wholesale price 
of the products. BANS had the lowest cost per day of treatment at US dollars
1.54, with each other INS costing at least an additional US dollars 0.26 daily
(MFNS US dollars 1.80; FPNS US dollars 1.88; TANS US dollars 1.97). CONCLUSION:
Based on physician prescribing patterns of INSs from the NDTI database, BANS
offers more days of treatment at a lower cost per day than other leading INSs.

PMID: 14720101 [PubMed - indexed for MEDLINE]

994: J Manag Care Pharm. 2004 Jan;10(1 Suppl):S3-8.

Evaluating the efficiency of treatment in the allergic rhinitis market.

Lee TA, Divers CH, Leibman CW.

Midwest Center for Health Services and Policy Research, Hines VA Hospital, Hines,
IL 60141, USA. Debi@rxperts.net

BACKGROUND: In the present era of increasing health care expenditures, economic
comparisons of therapeutic products play an important role in ensuring that
limited health care resources are used appropriately. OBJECTIVE: To provide a
model for the comparative analysis of alternative treatments, in terms of both
cost and efficacy, in allergic rhinitis that will provide decision makers in a
managed care environment an additional tool to help maximize health care benefit 
per dollar spent. We also review current treatments in the allergic rhinitis
market and their impact on cost, availability, and utilization. SUMMARY: Efficacy
estimates were derived from published reviews, meta-analyses, and guidelines, and
cost data are based on average wholesale prices. Our results indicate that when
cost and efficacy data are plotted on a cost-effectiveness plane, the intranasal 
corticosteroids appear to be the most efficient use of health care resources.
Moreover, budesonide aqueous nasal spray was found to be the most efficient
treatment for allergic rhinitis when compared with 3 other leading intranasal
corticosteroids used at their recommended starting doses, the
less-sedating/nonsedating antihistamines, and a leukotriene receptor antagonist. 
CONCLUSION: Evaluating products on an efficiency frontier platform, which
integrates both the effectiveness and cost of products, will allow health plan
decision makers to ensure the appropriate allocation of health care resources.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14720100 [PubMed - indexed for MEDLINE]

995: Am J Respir Med. 2003;2(1):55-65.

Comparison of intranasal corticosteroids and antihistamines in allergic rhinitis:
a review of randomized, controlled trials.

Nielsen LP, Dahl R.

Department of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark.
lpn@dadlnet.dk

For several years there has been discussion of whether first-line pharmacological
treatment of allergic rhinitis should be antihistamines or intranasal
corticosteroids. No well documented, clinically relevant differences seem to
exist for individual nonsedating antihistamines in the treatment of allergic
rhinitis. Likewise, the current body of literature does not seem to favor any
specific intranasal corticosteroid. When comparing efficacy of antihistamines and
intranasal corticosteroids in allergic rhinitis, present data favor intranasal
corticosteroids. Interestingly, data do not support antihistamines as superior in
treating conjunctivitis associated with allergic rhinitis. Safety data from
comparative studies in allergic rhinitis do not indicate differences between
antihistamines and intranasal corticosteroids. Combining antihistamines and
intranasal corticosteroids in the treatment of allergic rhinitis does not provide
additional beneficial effects to intranasal corticosteroids alone. Considering
present data, intranasal corticosteroids seem to offer superior relief in
allergic rhinitis, when compared with antihistamines.

Publication Types: 
    Comparative Study
    Review

PMID: 14720022 [PubMed - indexed for MEDLINE]

996: Hypertens Res. 2003 Dec;26(12):961-3.

Relation between blood pressure and rhinitis in a Japanese adolescent population.

Saito I, Mori M, Shibata H, Hirose H, Tsujioka M, Kawabe H.

Health Center, Keio University, Tokyo, Japan. saito@hc.cc.keio.ac.jp

Recent studies have reported an association between systolic blood pressure (BP) 
and rhinitis. The prevalence of allergic rhinitis is 20% to 30% in Japan. The
present cross-sectional study was performed to assess the relation between BP and
allergic rhinitis in a sample of 2,292 male adolescent high school students who
attended the annual school health examination. Of the 2,292 students (mean age,
16 years), 26.6% were considered to have allergic rhinitis based on their
responses to a questionnaire, 25.1% were diagnosed with allergic rhinitis by an
otolaryngologist, and 12.6% were consistently diagnosed with allergic rhinitis by
both questionnaire and an otolaryngologist. There was no difference in systolic
BP between subjects with and without allergic rhinitis. Diastolic BP, however,
was higher in subjects without allergic rhinitis than in those with allergic
rhinitis as diagnosed by questionnaire alone or by both questionnaire and an
otolaryngologist. When the subjects were divided into three BP categories
(normal, high normal, and hypertension) according to the criteria in the JSH
2000, the rates of allergic rhinitis were similar in the three BP categories.
These findings do not confirm a relation between allergic rhinitis and systolic
BP.

PMID: 14717338 [PubMed - indexed for MEDLINE]

997: Acta Otolaryngol. 2003 Dec;123(9):1060-3.

Comment in:
    Acta Otolaryngol. 2004 Dec;124(10):1240.

Effect of botulinum toxin type A on nasal symptoms in patients with allergic
rhinitis: a double-blind, placebo-controlled clinical trial.

Unal M, Sevim S, Doğu O, Vayisoğlu Y, Kanik A.

Department of Otorhinolaryngology, Mersin University School of Medicine, Mersin, 
Turkey. muunal@hotmail.com

OBJECTIVE: To investigate the possible beneficial effects of botulinum toxin type
A (BTX-A) on nasal symptoms in patients with allergic rhinitis (AR). MATERIAL AND
METHODS: Thirty-four patients (21 females, 13 males; mean age 28 years) were
included in the study. AR was diagnosed by means of history, clinical examination
and skin prick test. Patients were randomly divided into 3 subgroups a follows:
in Group A, 20 units of BTX-A was injected into each nasal cavity (total 40
units); in Group B, 30 units of BTX-A was injected into each nasal cavity (total 
60 units); and in Group C, 2 ml of isotonic saline was injected as placebo. The
symptoms of AR (rhinorrhea, nasal obstruction, sneezing, itching) were scored by 
the patient on a six-point scale (from 0 to 5). All of the patients were followed
up at Weeks 1, 2, 4, 6 and 8; at each visit an anterior rhinoscopic examination
was done and symptom scores were recorded. RESULTS: There was no statistically
significant difference between Groups A and B in terms of average symptom scores.
Rhinorrhea, nasal obstruction and sneezing scores in Groups A and B were
significantly better than those in Group C at all time points. Although itching
scores were significantly lower at Weeks 1 and 2, there was no difference in the 
Week 4, 6 and 8 scores in Groups A and B. When total symptom scores were
evaluated, the results for Groups A and B were similar but significantly better
than those for Group C. CONCLUSION: In selected cases, injection of 40 units of
BTX-A into the turbinates, as a single agent, may help the symptomatic control of
AR for up to 8 weeks.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 14710908 [PubMed - indexed for MEDLINE]

998: Drugs Exp Clin Res. 2003;29(3):107-15.

Mast cell stabilization, lipoxygenase inhibition, hyaluronidase inhibition,
antihistaminic and antispasmodic activities of Aller-7, a novel botanical
formulation for allergic rhinitis.

Amit A, Saxena VS, Pratibha N, D'Souza P, Bagchi M, Bagchi D, Stohs SJ.

Natural Remedies Research Center, Bangalore, India.

Allergic rhinitis, also known as hay fever, rose fever or summer catarrh, is a
major challenge to health professionals. A large number of the world's
population, including approximately 40 million Americans, suffers from allergic
rhinitis. A novel, botanical formulation (Aller-7) has been developed for the
treatment of allergic rhinitis using a combination of extracts from seven
medicinal plants, including Phyllanthus emblica, Terminalia chebula, T.
bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and P. longum,
which have a proven history of efficacy and health benefits. The clinical
manifestations of allergy are due to a number of mediators that are released from
mast cells. The effect of Aller-7 on rat mesenteric mast cell degranulation was
studied by incubating different concentrations of Aller-7 and challenging them
with a degranulating agent, compound 48/80. The inhibitory activity of Aller-7
was determined against lipoxygenase and hyaluronidase, the key enzymes involved
in the initiation and maintenance of inflammatory responses. Furthermore, most of
these manifestations are due to histamine, which causes vasodilatation,
increasing capillary permeability and leading to bronchoconstriction. Hence, the 
antihistaminic activity of Aller-7 was determined is isolated guinea pig ileum
substrate using cetirizine as a positive control. The antispasmodic effect of
Aller-7 on contractions of guinea pig tracheal chain was determined using
papaverine and cetirizine as controls. Aller-7 exhibited potent activity in all
these in vitro models tested, thus demonstrating the novel anti-allergic
potential of Aller-7.

Publication Types: 
    Comparative Study

PMID: 14708456 [PubMed - indexed for MEDLINE]

999: Ann Otol Rhinol Laryngol. 2003 Dec;112(12):1043-9.

Carbon dioxide laser vaporization of the inferior turbinate for allergic
rhinitis: short-term results.

Imamura S, Honda H.

Department of Otorhinolaryngology, Suwa Central Hospital, Chino City, Japan.

Carbon dioxide laser vaporization of the turbinate has recently become accepted
as a common treatment for allergic rhinitis. Usually, only a single procedure is 
applied to minimize trauma. However, repeated procedures on separate days are
often required to achieve an adequate effect. Therefore, we attempted a new
method of vaporization and evaluated the outcome, and also tried to determine
which patients have good indications for laser treatment. To widely and deeply
vaporize the inferior turbinate, we repeated the procedure 3 times in 1 session
after removing the carbon coating from the previous vaporization under nasal
endoscopic observation. After the procedure, most patients experienced complete
nasal obstruction for 2 or 3 days, but there was no intraoperative or
postoperative bleeding or severe pain. All patients obtained improvement of their
chief complaints and were satisfied 2 months after the operation. In particular, 
60% of the patients were completely relieved of refractory nasal obstruction.
Most patients were more satisfied with the effects than are those treated by the 
usual methods. Completely successful cases (improvement in all symptoms and
complete satisfaction obtained) were selected and were compared with other cases.
Favorable prognostic factors are more severe complaints, longer symptomatic
periods, stronger allergic reactions, and worse nasal resistance and its greater 
improvement with administration of decongestant nasal drops. This method may be
especially accepted by patients with severe complaints, in particular nasal
obstruction, who do not experience enough relief with conservative therapies or
have enough time to make frequent visits to an outpatient clinic over a period of
several weeks.

PMID: 14703108 [PubMed - indexed for MEDLINE]

1000: Thorax. 2004 Jan;59(1):11-5.

Comment in:
    Thorax. 2004 Jun;59(6):541.

Early prescriptions of antibiotics and the risk of allergic disease in adults: a 
cohort study.

Cullinan P, Harris J, Mills P, Moffat S, White C, Figg J, Moon A, Newman Taylor
AJ.

Department of Occupational and Environmental Medicine, Imperial College School of
Medicine at the National Heart and Lung Institute, London, UK.
p.cullinan@ic.ac.uk

BACKGROUND: It is frequently asserted that antibiotic prescriptions in childhood 
are associated with the development of allergic disease, especially asthma. A
study was undertaken to establish the direction of this relationship. METHODS: A 
retrospective cohort study of 746 adults was performed in three general
practices. Antibiotic prescriptions in the first 5 years of life, collected from 
contemporary medical records, were related to self-reports of asthma and hay
fever and the results of skin prick testing with common aeroallergens. RESULTS:
There was no relationship between early antibiotic prescription and atopy, either
for all antibiotic use (OR 1.01) or for antibiotics prescribed at different ages.
The significant associations between prescriptions at ages 4 and 5 and hay fever 
(OR 1.23 and 1.16, respectively) were explained by coexisting asthma.
Relationships between antibiotic use and asthma (allergic or otherwise) were
statistically significant and strengthened with increasing age of prescription,
but were largely confined to antibiotics prescribed for lower respiratory
symptoms. CONCLUSIONS: The reported associations between childhood antibiotic use
and asthma are most plausibly explained by "reverse causation"--the tendency for 
prescriptions to be written for the early manifestations of pre-existing asthma.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 14694239 [PubMed - indexed for MEDLINE]

1001: Allergy. 2004 Jan;59(1):45-53.

Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific
immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy
study.

Khinchi MS, Poulsen LK, Carat F, André C, Hansen AB, Malling HJ.

Allergy Clinic, National University Hospital, Copenhagen, Denmark.

BACKGROUND: Both sublingual allergen-specific immunotherapy (SLIT) and
subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only
few comparative studies have been performed. OBJECTIVE: To investigate the
clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with
placebo and to evaluate the relative clinical efficacy in relation to systemic
side-effects. METHODS: A 3-year randomized, placebo-controlled, double-blind,
double-dummy study including 71 adult birch pollen hay fever patients treated for
two consecutive years after a baseline year. Allocation to treatment groups was
based on disease severity in the baseline season, gender and age. RESULTS:
Clinical efficacy was estimated in 58 patients completing the first treatment
year by subtracting baseline data and by calculating the ratio first treatment
season vs baseline. SLIT diminished the median disease severity to one-half and
SCIT to one-third of placebo treatment. No statistical significant difference
between the two groups was observed. Both for symptoms and medication scores
actively treated patients showed statistically significant and clinical relevant 
efficacy compared with placebo. SLIT treatment only resulted in local mild
side-effects, while SCIT resulted in few serious systemic side-effects.
CONCLUSION: Based on the limited number of patients the clinical efficacy of SLIT
was not statistically different from SCIT, and both treatments are clinically
effective compared with placebo in the treatment of birch pollen
rhinoconjunctivitis. The lack of significant difference between the two
treatments does not indicate equivalent efficacy, but to detect minor differences
necessitates investigation of larger groups. Due to the advantageous safety
profile SLIT may be favored.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14674933 [PubMed - indexed for MEDLINE]

1002: Adv Ther. 2003 Jul-Aug;20(4):213-9.

Use of cellulose powder for the treatment of seasonal allergic rhinitis.

Josling P, Steadman S.

Herbal Health Centre, Battle, UK.

This study was designed to determine whether a unique cellulose powder extract
could prevent the classic hay fever attack from occurring among volunteers who
have suffered for some years. Nasaleze enhances nasal mucus, which allows the
filtration of allergens, to ensure that only clean air reaches the lungs. One
hundred two volunteers were recruited and, using a simple 5-point scoring system 
to grade their general well-being and severity of any hay fever attacks, the
overall average score was 3.85, indicating that Nasaleze was able to control hay 
fever very well. Rapid relief of symptoms was also demonstrated, sometimes within
minutes after inhalation. Overall, 77% of volunteers reported a significant
reduction in the number of challenges throughout the study period and most graded
Nasaleze as more effective and reported fewer side effects than with a wide range
of chemical treatments.

Publication Types: 
    Clinical Trial

PMID: 14669817 [PubMed - indexed for MEDLINE]

1003: Int J Pediatr Otorhinolaryngol. 2003 Dec;67 Suppl 1:S205-8.

Evaluation of CD25, CD152, Fas-ligand expression in the adenoids of allergic and 
non-allergic children: a pilot study.

Zakrzewska A, Kobos J, Gryczyńska D.

Department of Pediatric Otolaryngology, Medical University of Lodz, Sporna 36/50,
91-738 Lodz, Poland.

BACKGROUND: The nasal mucosa is the initial site in the upper airways of the host
defence against antigen challenge. The lymphatic structure closest to the nasal
mucosa is the adenoid. Apoptotic cell death is an important mechanism for
maintaining homeostasis in the immune system, and for regulating the fates of
lymphocytes following encounters with self and foreign antigens. This process
regulates the population of lymphocytes in peripheral lymphoid organs following
exposure to various allergens. OBJECTIVES: The objectives of this study were to
find evidence for the hypothesis that the development of allergic illness depends
on allergic sensitisation in the adenoid. METHODS: In this study, cellular
infiltrates in the adenoids of 12 allergic and 13 non-allergic children were
evaluated. The number of positive cells for CD4, CD8, CD25, CD152, and Fas-ligand
were determined using immunohistochemical stainings and imaging analysis
techniques. RESULTS: There was found a higher expression of CD25, CD152 and
Fas-ligand in small, activated lymphocytes, especially in the interfollicular
area of allergic patients than in the control group. The expression of FasL in
activated lymphocytes, as well as in macrophages, was observed. Statistical
analysis has shown a significant correlation between expression of CD152 and
allergic disease, and a more intense correlation between CD25, CD152 and
Fas-ligand and allergic disease. There was no statistically important divergence 
in the CD4/CD8 ratio in different samples.

PMID: 14662196 [PubMed - indexed for MEDLINE]

1004: Int J Pediatr Otorhinolaryngol. 2003 Dec;67 Suppl 1:S201-4.

Recent advances in the treatment of rhinitis and rhinosinusitis.

Scadding GK.

Royal National TNE Hospital, Grays Inn Road, London WC1 X8D, UK.
g.scadding@ucl.ac.uk

Current rhinitis treatment is unsatisfactory for many patients, possibly because 
monotherapy is employed, without regard to the major presenting symptom.
Recognition of the impact of rhinitis on quality of life and on associated
disorders such as asthma has led to the development of guidelines, use of which
has been shown to improve symptom control and quality of life compared to
unguided therapy. The role of antihistamines, topical corticosteroids and
anti-leukotrienes is discussed.

PMID: 14662195 [PubMed - indexed for MEDLINE]

1005: Ear Nose Throat J. 2003 Nov;82(11):881-7.

Improved immunotherapy with a rapid allergen vaccination schedule: a study of 137
patients.

Smits W, Inglefield JT, Letz K, Lee R, Craig TJ.

Allergy and Asthma Center, 7230 Engle Rd., Suite 300, Fort Wayne, IN 46804-2234, 
USA. wlsmits@aol.com

Rapid allergen vaccination (RAV) is the updated term for what was previously
called rush immunotherapy and rapid desensitization. RAV offers several
advantages over traditional immunotherapy--that is, conventional allergen
vaccination (CAV)--in terms of faster efficacy, better compliance, and
cost-effectiveness. We used a 3-hour RAV protocol to treat 137 allergy patients. 
All patients were premedicated with either prednisone or prednisolone and an H1
antihistamine. Following the RAV procedure, all patients resumed a CAV schedule. 
Only six patients (4.4%) experienced a mild systemic reaction to RAV, and five
(3.6%) experienced a mild systemic reaction to CAV 14 to 77 days later. All six
patients who reacted to RAV quickly responded to treatment--in most cases,
subcutaneous epinephrine and/or nebulized albuterol--and were sent home after a
short period of observation. Compliance rates at 3, 6, and 12 months were 96.4,
94.2, and 75.9%, respectively, which is an improvement over rates previously
reported for patients undergoing CAV therapy. We conclude that the 3-hour RAV
protocol can be safely and successfully administered. Patients who undergo RAV
are more compliant with their subsequent CAV regimen than are patients who do not
undergo RAV because signs of clinical efficacy manifest almost immediately and
because RAV is associated with substantially lower rates of systemic reactions.
Moreover, RAV is associated with less morbidity and less expense. Our findings
should encourage physicians who treat allergy patients to give further
consideration to using RAV.

PMID: 14661440 [PubMed - indexed for MEDLINE]

1006: Hong Kong Med J. 2003 Dec;9(6):427-34.

Effect of adding a Chinese herbal preparation to acupuncture for seasonal
allergic rhinitis: randomised double-blind controlled trial.

Xue CC, Thien FC, Zhang JJ, Yang W, Da Costa C, Li CG.

RMIT Chinese Medicine Research Group, RMIT University, Bundoora West Campus,
Bundoora, Victoria 3083, Australia. charlie.xue@rmit.edu.au

OBJECTIVE: To assess whether the addition of a Chinese herbal medicine formula to
acupuncture affects the severity of symptoms and quality-of-life scores among
patients with seasonal allergic rhinitis. DESIGN: Randomised double-blind
placebo-controlled trial. SETTING: University teaching and research clinic,
Australia. PARTICIPANTS: Sixty-five patients with seasonal allergic rhinitis, who
were recruited through public media. INTERVENTION: Between July and December
1999, patients received acupuncture twice a week for 8 weeks plus either a
Chinese herbal drug formula (n=33) or placebo (n=32) at a dosage of four
capsules, three times daily. MAIN OUTCOME MEASURES: The severity of nasal and
non-nasal symptoms on a five-point scale, as assessed by both patients and an
ear, nose, and throat specialist, and quality-of-life scores as measured by the
Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire. RESULTS:
Sixty-one patients completed the study (31 in the intervention group and 30 in
the control group). After 8 weeks, no significant difference was found between
the two groups in the severity of nasal and non-nasal symptoms and in the
Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire scores.
Intention-to-treat analysis of categorical variables showed moderate-to-marked
improvement rates of 72.7% and 81.2% for intervention and control groups,
respectively. Six patients reported mild adverse events-three from each of the
study groups. CONCLUSION: The Chinese herbal formulation under investigation did 
not provide additional symptomatic relief or improvement in quality-of-life
scores among patients with seasonal allergic rhinitis who were receiving
acupuncture.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14660810 [PubMed - indexed for MEDLINE]

1007: J Allergy Clin Immunol. 2003 Dec;112(6):1147-54.

Omalizumab treatment downregulates dendritic cell FcepsilonRI expression.

Prussin C, Griffith DT, Boesel KM, Lin H, Foster B, Casale TB.

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, MD, USA.

BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells that
express FcepsilonRI, the high-affinity IgE receptor. Although the downregulation 
of basophil FcepsilonRI during anti-IgE therapy with omalizumab is well
documented, its effect on FcepsilonRI expression by DCs has not been reported.
OBJECTIVE: We hypothesized that IgE regulates surface FcepsilonRI expression by
DCs in vivo and that, consequently, anti-IgE therapy decreases FcepsilonRI
expression by DCs. METHODS: In a randomized, double-blind, placebo-controlled
clinical trial 24 subjects (16 receiving omalizumab and 8 receiving placebo) with
seasonal allergic rhinitis received the study drug on days 0 and 28. Serial blood
samples drawn on days 0, 7, 14, 28, and 42 were analyzed for precursor DC1 (pDC1)
and pDC2 surface expression of FcepsilonRIalpha by using flow cytometry. RESULTS:
Omalizumab caused a significant decrease in surface FcepsilonRI expression at all
time points examined in both the pDC1 and pDC2 subsets. No significant change was
seen with placebo. The maximum decrease in FcepsilonRI expression in the
omalizumab group was 52% and 83%, respectively, for the pDC1 and pDC2 subsets.
The decrease in FcepsilonRI expression by both pDC subsets correlated with the
decrease in serum-free IgE and was of a similar magnitude to that found in
basophils. A 10-fold decrease in IgE corresponded to a 42% and 54% decrease in
surface FcepsilonRI expression by the pDC1 and pDC2 subsets, respectively.
CONCLUSION: These results demonstrate that anti-IgE therapy causes a rapid
decrease in DC surface FcepsilonRI expression and establish that IgE is an
important regulator of FcepsilonRI expression by DCs.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14657874 [PubMed - indexed for MEDLINE]

1008: J Allergy Clin Immunol. 2003 Dec;112(6):1127-31.

High contribution contrast between the genes of eosinophil peroxidase and IL-4
receptor alpha-chain in Japanese cedar pollinosis.

Nakamura H, Miyagawa K, Ogino K, Endo T, Imai T, Ozasa K, Motohashi Y, Matsuzaki 
I, Sasahara S, Hatta K, Eboshida A.

Department of Environmental Medicine, Kochi Medical School, Nankoku, Japan.

BACKGROUND: Japanese cedar pollinosis is the most common form of hayfever in
Japan in spring and has remarkably increased since 1960. OBJECTIVE: We sought to 
clarify the candidate genes for cedar pollinosis using a case-control study.
METHODS: After diagnosing 351 subjects on the basis of an intradermal test, nasal
provocation test, and questionnaire regarding nasal and conjunctival symptoms, we
determined the blood-specific IgE values and genotypes of eosinophil peroxidase
(EPO) and interleukin-4 receptor alpha-chain (IL4RA) in 145 patients with
pollinosis and 206 healthy subjects, including 75 healthy subjects with higher
specific IgE values. RESULTS: We found significant differences in the frequencies
of Pro358Leu in EPO and of Ile50Val and Glu375Ala in IL4RA between patients and
healthy subjects. There was a significantly higher frequency of 358Leu in EPO in 
patients than in healthy subjects showing a higher specific IgE value. In
contrast, we recognized significant changes in the prevalence of Ile50Val and
Glu375Ala in IL4RA in healthy subjects with a normal IgE value compared with
those in healthy subjects with a higher specific IgE value. The relationship
between EPO polymorphisms and the onset of symptoms was exactly opposite that for
IL4RA. CONCLUSIONS: These results suggest that Pro358Leu in EPO is strongly
involved in the development of cedar pollinosis. Ile50Val and Glu375Ala in IL4RA 
seem to be related to cedar pollen sensitization. Subjects with Ile50 or Glu375
might develop cedar pollinosis with increased exposure to cedar pollen.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14657871 [PubMed - indexed for MEDLINE]

1009: Clin Exp Allergy. 2003 Dec;33(12):1667-74.

Erratum in:
    Clin Exp Allergy. 2004 Feb;34(2):322.

Validation of an environmental exposure unit for controlled human inhalation
studies with grass pollen in patients with seasonal allergic rhinitis.

Krug N, Hohlfeld JM, Larbig M, Buckendahl A, Badorrek P, Geldmacher H, Behnke W, 
Dunkhorst W, Windt H, Loedding B, Luettig B, Koch W.

Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany. 
krug@item.fraunhofer.de

BACKGROUND: There is an increasing need for allergen inhalation systems to
perform basic clinical research and test anti-allergic drugs under
well-controlled conditions. This requires stability of environmental conditions
like temperature and humidity, as well as allergen concentration and reproducible
induction of allergic symptoms. OBJECTIVE: The aim of this study was to validate 
an environmental exposure unit for controlled human pollen inhalation studies in 
participants with seasonal allergic rhinitis. METHODS: Temperature, relative
humidity, and air flow rate were kept constant with an air conditioning system.
Pollen atmosphere was generated using a specially designed feeding system and
monitored online by laser counter and offline using rotating rod samplers.
Efficacy (total nasal symptom score, nasal air flow rate, nasal secretion) and
safety (lung function) parameters were evaluated at different pollen
concentrations and repeated allergen challenges. RESULTS: Temperature, humidity, 
and air flow rate in the environmental exposure unit remained constant within a
range of <2%. The spatial distribution and the temporal stability of the pollen
concentration varied only slightly over 4 h (+/-10% and <4%, respectively).
Dose-dependent induction of allergic rhinitis symptoms, reduction in nasal air
flow rate, and increase in nasal secretion were observed over time. These effects
were reproducible from day to day. Lung function remained clinically normal at
all concentrations and from day to day. CONCLUSIONS: Thus, pollen exposure in the
environmental exposure unit is an effective, reproducible, safe, and suitable
method for single-centre clinical studies on the efficacy of anti-allergic
treatment or basic clinical research.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 14656353 [PubMed - indexed for MEDLINE]

1010: Clin Exp Allergy. 2003 Dec;33(12):1641-7.

Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in
children allergic to Parietaria pollen treated with inhaled fluticasone
propionate.

Pajno GB, Vita D, Parmiani S, Caminiti L, La Grutta S, Barberio G.

Paediatric Clinic, Messina Polyclinic Hospital, Messina University, Messina,
Italy. Giovanni.Pajno@unime.it

BACKGROUND: Immunotherapy is a recognized treatment for allergic respiratory
diseases. OBJECTIVE: To study the usefulness of immunotherapy in combination with
optimal pharmacological therapy. METHODS: Thirty-eight children (8-14 years)
suffering from seasonal asthma+/-rhinoconjunctivitis due to Parietaria poorly
controlled by anti-allergic drugs treatment were selected. After randomization
according to a double-blind placebo-controlled design they received active
sublingual immunotherapy (15 children) or placebo (15 children) for 13 months
combined with inhaled fluticasone twice a day during the pollen season. Eight
children were taken as control, whereas all patients were instructed to take
symptomatic drugs on need. Early and late skin response to the allergen were
assessed in all patients before and after treatment. Drug and symptom scores, as 
well as visual analogue scores (VASs) and Parietaria pollen counts were assessed 
during the pollen season. RESULTS: Groups were well balanced for age, gender,
early and late skin response before treatment. Four children dropped out, in one 
case in relationship with active sublingual immunotherapy (SLIT) administration. 
Chest and nose symptoms, as well as drug scores and VASs were significantly
better in both the active or placebo SLIT+fluticasone (S+F) as compared to the
control group (P between <0.001 and 0.043). Eye symptoms were significantly
better in the active S+F group as compared to control (P=0.025). The VASs were
significantly better in the active S+F group as compared to the placebo S+F group
(P=0.037). The early skin response decreased significantly in the active S+F
group (P<0.001), whereas the late skin response changed significantly in all
groups, with an increase in the placebo+fluticasone group (P=0.019) and in the
control group (P=0.037) and a decrease (P<0.0001) in the active S+F group.
CONCLUSION: The clinical efficacy of S+F is equal to that of fluticasone alone,
but the addition of SLIT has effects also on non-bronchial symptoms.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 14656349 [PubMed - indexed for MEDLINE]

1011: Eur Ann Allergy Clin Immunol. 2003 Oct;35(8):300-5.

The pattern of indoor and outdoor respiratory allergens in asthmatic adult
patients in a humid and desert newly developed country.

Sattar HA, Mobayed H, al-Mohammed AA, Ibrahim AS, Jufairi AA, Balamurugan P, Mary
VP, Bener A.

BACKGROUND: Studies have shown that allergens are very important sensitizing
agents in patients with asthma. Respiratory disorders such as asthma and allergic
rhinitis are common in the State of Qatar. OBJECTIVE: To characterize the most
frequent indoor and outdoor respiratory allergens involved in bronchial asthma
and allergic rhinitis in the State of Qatar. DESIGN: A hospital-based prospective
study conducted. SETTING: Allergy Laboratory at the Hamad General Hospital and
Hamad Medical Corporation, Doha, State of Qatar. PATIENTS: Adult patients over 12
years of age diagnosed with bronchial asthma and/or allergic rhinitis who were
referred for allergy skin pick test. 1106 adult patients recruited with
respiratory diseases of suspected allergic origin who attended Allergy Clinic at 
the Hamad General Hospital, during three years from January 2001 to April 2003.
Total of 1106 whom 607 were females (54.9%) and 499 were males (45.1%) and their 
mean was age 30 years (12-48). METHODS: Skin Prick Test [SPT] was performed on
1106 patients for common allergens whom The blood sample was taken for measuring 
specific IgE concentration. RESULTS: There were 1106 patients studied and 569
patients (51.4%) had positive skin prick test. All patients expressed clinical
allergy, 464 patients (52%) had asthma and rhinitis, 286 patients (32%) had
rhinitis alone and 137 patients (15%) had asthma alone. The population sample had
a higher prevalence of diagnosed asthma among females (32.7%) than in males
(29.8%) and also skin conditions such as eczema, pruritus, and urticaria higher
in females (9.1%%) than males (7.0%). Similarly, males had higher prevalence of
allergic rhinitis (86.0%) than in females. There were 318 (55.9%) patients whose 
asthma developed before they were 10 years old. The percentage of asthmatic
patients with a positive family history of asthma was 44%. The most common
allergens detected in order of frequency were Dermatophagoides Pteronyssimus (Der
p l) in 248 patients (41.6%), Dermatophagoides Farinae (Der f l) in 220 patients 
(36.9%), Cockroach allergen (Bla g l) in 192 patients (32.2%). The study showed
that females are more exposed to pollen, grasses and tress, but males are mostly 
exposed to mites and insects. Furthermore, Molds and Yeast were common among
males. CONCLUSION: In conclusion, the frequency of indoor and outdoor allergens
in state of Qatar, based on skin prick test study showed the dominance of house
dust mites, pollen, grasses which are more or less same to other countries with
similar and even with different climate. Reduced exposure to these agents will
help control raising severity of these disease.

Publication Types: 
    Comparative Study

PMID: 14653049 [PubMed - indexed for MEDLINE]

1012: Inflamm Res. 2003 Nov;52(11):477-9.

Platelet activity measured by plasma levels of beta-thromboglobulin and platelet 
factor 4 in seasonal allergic rhinitis during natural pollen exposure.

Kasperska-Zajac A, Rogala B.

Clinical Department of Internal Diseases, Allergology and Clinical Immunology,
Medical University of Silesia, ul. 3-go Maja 13-15, 41-800, Zabrze, Poland.
kaspp@plusnet.pl

BACKGROUND: Upon activation, platelets release mediators with potent inflammatory
properties in IgE-mediated immune responses. Moreover, the atopic state leads
towards functional abnormalities of these cells. OBJECTIVE: The aim of our study 
was to examine the degree of activation of circulating platelets in patients with
seasonal allergic rhinitis (SAR) during the symptomatic period, to improve the
understanding of platelet function in atopy. Subjects and Method: Plasma levels
of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) - specific markers 
of platelet activation were measured by enzyme-linked immunoassay in 20 patients 
suffering from SAR and in 15 healthy, nonatopic subjects. RESULTS: There were no 
significant differences in peripheral blood platelet numbers and plasma levels of
beta-TG and PF4 in SAR patients when compared with control subjects. CONCLUSION: 
It seems that increased in vivo platelet activity, assessed by measuring plasma
beta-TG and PF4, may not occur during allergic inflammation that is associated
with SAR.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14652682 [PubMed - indexed for MEDLINE]

1013: Br J Clin Pharmacol. 2003 Nov;56(5):562-8.

Erratum in:
    Br J Clin Pharmacol. 2004 Jan;57(1):117.

Comment in:
    Br J Clin Pharmacol. 2004 Sep;58(3):340-1.

Ultramolecular homeopathy has no observable clinical effects. A randomized,
double-blind, placebo-controlled proving trial of Belladonna 30C.

Brien S, Lewith G, Bryant T.

Complementary Medicine Research Unit, University of Southampton, Royal South
Hants Hospital, Brintons Terrace, Southampton SO14 0YG, UK. s.brien@soton.ac.uk

AIMS: To investigate if ultramolecular homeopathy has any clinical effects. This 
was assessed using the proving of the homeopathic remedy Belladonna given at an
ultramolecular dose (30C), as a model. A proving states that when a homeopathic
remedy is given to a healthy person, they will experience symptomatic effects
specific to that remedy. If ultramolecular doses are clinically active, the
Belladonna 30C group should experience more true Belladonna proving symptoms than
the placebo group. METHODS: Healthy subjects (n = 253), aged 18-30 years, took
part in this double-blind, randomized placebo-controlled study. Total study
duration was 4 weeks. Subjects were randomized before 1 week placebo run-in. They
received 2 weeks of treatment intervention (Belladonna 30C or placebo) and were
followed up for 1 week. Subjects recorded any symptoms experienced during the
total study period on a daily basis using a structured questionnaire. Symptom
diaries were analysed blind to determine if each subject had proved or not (based
on predefined criteria). The main outcome was the proportion of subjects who had 
proved in each treatment group. RESULTS: No significant group differences in
proving rates were observed [Belladonna provers N = 14 (13.9%); placebo provers N
= 15 (14.3%); mean difference -0.4%, 95% confidence interval -9.3, 10.1] based on
intention to treat analysis. Primary outcome was not affected by seasonality or
the individual's attitude to complementary medicine. CONCLUSION: Ultramolecular
homeopathy had no observable clinical effects.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14651731 [PubMed - indexed for MEDLINE]

1014: Int Arch Allergy Immunol. 2003 Nov;132(3):268-76.

Increase in serum levels of autoantibodies after attack of seasonal allergic
rhinitis in patients with Graves' disease.

Takeoka K, Hidaka Y, Hanada H, Nomura T, Tanaka S, Takano T, Amino N.

Department of Laboratory Medicine, Osaka University Graduate School of Medicine, 
Osaka, Japan.

BACKGROUND: The prevalence of allergic disease is increasing worldwide, but its
influence on the clinical course of autoimmune diseases is unknown. OBJECTIVE:
The purpose of this study was to assess the effect of seasonal allergic rhinitis 
on the clinical course of Graves' disease, which has been considered a
Th2-dominant autoimmune disease. METHODS: Ten patients with Graves' disease, who 
were considered to be in a state of remission or near remission, were serially
examined for 18 months starting from August. Five of them had seasonal allergic
rhinitis due to Japanese cedar pollen, and the remaining patients had no such
allergic disorders. Peripheral eosinophil counts, serum concentrations of
cedar-pollen-specific IgE, anti-TSH-receptor antibody, anti-thyroid-peroxidase
antibody and antithyroglobulin antibody were assessed at 2- to 4-month intervals.
Serum thyroid hormones and TSH levels were also measured to evaluate disease
activity. RESULTS: All patients with pollinosis had attacks of allergic rhinitis 
caused by cedar pollen in early March. Subsequently, peripheral eosinophil
counts, pollen-specific IgE activity and serum levels of anti-thyroid-peroxidase 
and antithyroglobulin autoantibodies markedly increased. Serum levels of
anti-TSH-receptor antibody increased in 3 patients in association with an
increase in serum thyroid hormones but were always negative in 2 patients. The
control patients without pollinosis showed no consistent change of these
parameters. CONCLUSIONS: Seasonal allergic rhinitis aggravated the clinical
course of Graves' disease and induced an increase in serum antithyroid
autoantibody concentrations as well as an increase in pollen-specific IgE
concentration. These data suggest that environmental antigens induce not only
local allergic reactions, but also stimulate thyroid immune reactions toward Th2 
proliferation, and finally aggravate Th2-dependent autoimmune thyroid disease.
Copyright 2003 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14646389 [PubMed - indexed for MEDLINE]

1015: Int Arch Allergy Immunol. 2003 Nov;132(3):258-62.

Safety of subcutaneous specific immunotherapy with pollen allergen extracts for
respiratory allergy.

Arifhodzic N, Behbehani N, Duwaisan AR, Al-Mosawi M, Khan M.

Al Rashed Allergy Centre, Kuwait University, Safat, Kuwait.

BACKGROUND: Specific immunotherapy (SIT) is a well-documented treatment for
respiratory allergy. However, the major risk of SIT is the development of
systemic anaphylactic reactions. OBJECTIVES: To evaluate the safety of SIT given 
by subcutaneous route for 3 years to patients with seasonal allergic rhinitis
(AR) with or without asthma. METHODS: A prospective open-label study of
immunotherapy (Chenopodium album, Bermuda grass, or both) in 181 consecutive
patients with AR with or without asthma. After an initial dose-escalation phase, 
a maintenance dose of 0.5 ml of 100,000 PNU/ml was administered monthly for 3
years. The occurrence and severity of systemic reaction (SR) and local reaction
was recorded and graded according to the WHO position paper. RESULTS: Of 181
patients enrolled, 57 (31%) did not complete the study (53 due to poor compliance
and 4 due to systemic side effects). All 4 patients who developed SR had asthma
and all the SR occurred during the dose- escalation phase. Three patients had
moderate SR (grade 2), while 1 patient had severe reaction (grade 3). Three of
the SR occurred within the first 20 min after injection and 1 SR occurred 2 h
after injection. None of the reactions were life threatening and were managed
easily. Total rhinitis symptom score decreased from 11.8 at baseline to 7.46 at
the end of treatment (p<0.001). The size of the skin prick test reaction to the
main sensitising allergen was reduced from 7.48 +/- 2.26 mm at baseline to 5.60
+/- 2.18 mm at the end of treatment, p<001. CONCLUSION: If a strict protocol is
used, SIT is safe in AR patients with or without mild asthma and may result in
significant subjective and objective improvement. Copyright 2003 S. Karger AG,
Basel

PMID: 14646387 [PubMed - indexed for MEDLINE]

1016: Pediatr Allergy Immunol. 2003 Oct;14(5):401-4.

Urinary leukotriene E4 levels in children with allergic rhinitis treated with
specific immunotherapy and anti-IgE (Omalizumab).

Kopp MV, Mayatepek E, Engels E, Brauburger J, Riedinger F, Ihorst G, Wahn U,
Kuehr J.

University Children Hospital, Freiburg, Germany. Kopp@kikli.ukl.uni-freiburg.de

Recently, we were able to demonstrate that Omalizumab, a humanized monoclonal
anti-IgE antibody, reduces in vitro leukotriene (LT) release of peripheral
leukocytes stimulated with allergen in children with allergic rhinitis undergoing
allergen immunotherapy. The aim of this study was to investigate the effect of
anti-IgE in combination with specific immunotherapy (SIT) on urinary leukotriene 
E4 (LTE4) levels. Children and adolescents with sensitization to birch and grass 
pollens and suffering from seasonal allergic rhinitis were included in a phase
III, placebo-controlled, multicenter clinical study. Within the four-arm study,
patients were randomized to receive SIT for either birch or grass pollen and to
receive either subcutaneous anti-IgE or placebo for 24 weeks during the pollen
season. From a total population of 225 children, we collected three urine samples
in a subgroup of 19 children [n = 12 boys (63%); mean age 11.8 years; range
7.2-17.5 years; Group A (n = 10): SIT (grass or birch) + anti-IgE; Group B (n =
9): SIT (grass or birch) + placebo]. Urine samples were collected before, during 
and at the end of treatment. Endogenous urinary LTE4 was separated by
high-performance liquid chromatography (HPLC) and determined by enzyme
immunoassay with a specific antibody. No differences in urinary LTE4
concentrations were observed between the anti-IgE and the placebo groups before
(A: 35.2; B: 36.5 nmol/mol creatinine), during (A: 27.0; B: 29.3) and after
treatment (A: 28.9; B: 26.5 nmol/mol creatinine). We conclude that urinary LTE4
levels are not helpful in monitoring patients treated with anti-IgE and SIT.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14641611 [PubMed - indexed for MEDLINE]

1017: J Investig Allergol Clin Immunol. 2003;13(3):145-8.

Double-blind, placebo-controlled study with sublingual immunotherapy in children 
with seasonal allergic rhinitis to grass pollen.

Wüthrich B, Bucher Ch, Jörg W, Bircher A, Eng P, Schneider Y, Schnyder F,
Eigenmann P, Senti G.

Allergy Unit, Department of Dermatology, University Hospital, Zurich,
Switzerland. wuethric@derm.unizh.ch

Sublingual immunotherapy (SLIT) has been recognized as a viable alternative to
subcutaneous immunotherapy for respiratory allergies both in adults and children,
but clinical documentation about safety and efficacy in children is still poor.
The purpose of this study was to assess the efficacy and tolerance of SLIT in
children who are sensitized to grass pollen. METHODS: Children with a clinical
history of intermittent rhinoconjunctivitis, with or without mild asthma and
positive skin prick tests to grass pollen, were selected to participate in a
2-year double-blind, placebo-controlled study with SLIT, using a grass extract
(ALK-Abellò). RESULTS: 22 children were analyzed at the end of the study. No
relevant side effects occurred in the active group. A statistically significant
difference (p = 0.05; Mann-Whitney test) in favor of the active group (n = 10)
could be shown for drug consumption during the second year, as well as a
significant improvement as compared to the first year of SLIT (p = 0.05; Wilcoxon
test). CONCLUSIONS: Despite the small number of patients, our data suggest that
SLIT with a grass pollen extract is well tolerated in children and is able to
significantly reduce drug consumption during the second year of treatment.
Studies in larger groups of children sensitized to both grass and tree pollens
are needed to definitively assess the role of SLIT in intermittent, seasonal
rhinitis and pollen asthma.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14635462 [PubMed - indexed for MEDLINE]

1018: Asian Pac J Allergy Immunol. 2003 Jun;21(2):75-8.

Rhinosinusitis among the patients with perennial or seasonal allergic rhinitis.

Yariktas M, Doner F, Demirci M.

Department of Otorhinolaryngology, Süleyman Demirel University, School of
Medicine, Isparta, Turkey.

Although no hypothesis is universally accepted, allergic rhinitis (AR) may play
an important role in the occurrence of rhinosinusitis. This study was carried out
to investigate the frequency and severity of rhinosinusitis among patients with
seasonal or perennial AR. This study included 73 patients with AR. Findings
related to rhinosinusitis of these patients were demonstrated by computed
tomography (CT), and were scored according to the Lund-Mackay CT scan staging
system. Fifty-two of the 73 patients (71.2%) were shown to have findings of
rhinosinusitis. Of these 52, twenty-four patients (77.4%) had perennial AR and 28
(66.7%) patients had seasonal AR. The mean total CT staging score of
rhinosinusitis was 4.2 +/- 3.2 in patients with perennial AR and 2.6 +/- 1.3 in
patients with seasonal AR. Although the frequency of rhinosinusitis among
patients with perennial AR was higher than among seasonal ones, this was
statistically insignificant (p = 0.32). But CT staging scores of rhinosinusitis
among the patients with perennial AR were significantly higher than among the
seasonal AR group (p = 0.014). Although there was no significant difference
between the frequency of rhinosinusitis of seasonal and perennial AR, the
severity of rhinosinusitis was more severe in cases with perennial AR, in this
study. Early management of an allergic disease is essential if its long-term
consequences are to be prevented or minimized.

Publication Types: 
    Comparative Study

PMID: 14629123 [PubMed - indexed for MEDLINE]

1019: Prescrire Int. 2003 Oct;12(67):171-2.

Levocetirizine: new preparation. Me-too: simply the active enantiomer of
cetirizine.

[No authors listed]

Levocetirizine is the active enantiomer of cetirizine. According to the only
available comparative trial in patients with seasonal allergic rhinitis, 5 mg
levocetirizine is equivalent to 10 mg cetirizine.

Publication Types: 
    Comparative Study

PMID: 14619884 [PubMed - indexed for MEDLINE]

1020: Allergy Asthma Proc. 2003 Sep-Oct;24(5):331-7.

The efficacy of intranasal fluticasone propionate in the relief of ocular
symptoms associated with seasonal allergic rhinitis.

DeWester J, Philpot EE, Westlund RE, Cook CK, Rickard KA.

DeWester, Duggan, and DeWester Family Medicine, 8921 Southpointe Drive, Suite B1,
Indianapolis, IN 46227, USA.

Intranasal corticosteroids have been shown to decrease ocular symptoms associated
with allergic rhinitis as well as nasal symptoms. The primary objective of this
retrospective analysis was to evaluate the efficacy of fluticasone propionate
(FP) aqueous nasal spray in the treatment of ocular symptoms in patients with
seasonal allergic rhinitis (SAR). We pooled efficacy data from seven multicenter,
randomized, double-blind, placebo-controlled studies of similar design. Each
study evaluated the efficacy of intranasal FP, 200 micrograms, given once daily
in the treatment of nasal and ocular symptoms associated with SAR. At baseline
and after 7 and 14 days of treatment, clinicians rated the severity of four
individual ocular symptoms (itching, tearing, redness, and puffiness) via visual 
analog scales of 0-100, where 0 = no symptoms and 100 = worst symptoms. The four 
ratings were added to form the total ocular symptom score (TOSS). Patients rated 
the overall severity of their ocular symptoms (all symptoms evaluated with a
single score) daily on diary cards in a similar fashion. The primary outcome was 
the mean change from baseline in the clinician-rated TOSS. A between-group
difference of 25 points in the mean change from baseline TOSS by day 14 was
considered clinically relevant. The FP group had greater mean changes from
baseline in the TOSS and in all four individual symptom scores compared with
placebo at days 7 and 14. At day 7, mean decreases from baseline in the TOSS were
76.0 points for the FP group and 50.9 points for the placebo group (p < 0.001), a
difference between groups of 25.1. At day 14, mean decreases from baseline in the
TOSS were 91.8 points for the FP group and 60.2 points for the placebo group (p <
0.001), a difference between groups of 31.6. Consistent with the clinician-rated 
data, patient-rated data showed a significantly greater reduction in the overall 
ocular symptom score for the FP group compared with placebo for both weeks 1 and 
2 (p < 0.001). Intranasal FP provides safe and effective relief of ocular
symptoms associated with SAR. Patients with allergic rhinitis who also have
ocular symptoms as a component of their disease may benefit from intranasal FP
monotherapy without the addition of topical ophthalmologic agents or oral
antihistamines. Such an approach may have advantages regarding compliance and
cost-effectiveness of treatment.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 14619333 [PubMed - indexed for MEDLINE]

1021: Allergy Asthma Proc. 2003 Sep-Oct;24(5):323-9.

Tolerability of retreatment with omalizumab, a recombinant humanized monoclonal
anti-IgE antibody, during a second ragweed pollen season in patients with
seasonal allergic rhinitis.

Nayak A, Casale T, Miller SD, Condemi J, McAlary M, Fowler-Taylor A, Della Cioppa
G, Gupta N.

Sneeze, Wheeze & Itch Associates, 2010 Jacobssen Drive, Normal, IL 61761, USA.

Two randomized, placebo-controlled, double-blind studies have shown clinical
benefit with omalizumab (Xolair), a recombinant humanized monoclonal
anti-immunoglobulin E (IgE) antibody, at a dose of 300 mg every 3 or 4 weeks in
patients with seasonal allergic rhinitis. The present open-label, 12-week study
was designed to assess the safety and tolerability of retreatment with omalizumab
in 287 patients previously treated with this agent in one of the latter studies. 
Omalizumab, 300 mg, was administered subcutaneously every 4 weeks (three
injections) to patients with IgE levels < or = 150 IU/mL (n = 182) and every 3
weeks (four injections) to patients with IgE levels > 150 IU/mL (n = 105) at
screening before retreatment. Reported adverse events were monitored and blood
samples were analyzed for laboratory safety (hematology and serum chemistry) and 
IgE levels. Urinalysis also was completed as part of the laboratory safety
evaluation. The overall incidence and pattern of adverse events were similar to
those reported in the primary study. There were no severe or serious adverse
events related to omalizumab treatment and no anti-omalizumab antibodies were
detected in any patient. Two patients withdrew from treatment because of adverse 
events (skin rash and nausea; facial erythema and edema) related to study
treatment. Free IgE levels decreased to the levels associated with symptom
reduction in the core study. In summary, retreatment during a second pollen
season with omalizumab, 300 mg every 3 or 4 weeks, was well tolerated and was not
associated with any significant immunologic reactions.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 14619332 [PubMed - indexed for MEDLINE]

1022: Clin Exp Allergy. 2003 Nov;33(11):1518-25.

Early-life exposure to antibacterials and the subsequent development of hayfever 
in childhood in the UK: case-control studies using the General Practice Research 
Database and the Doctors' Independent Network.

Bremner SA, Carey IM, DeWilde S, Richards N, Maier WC, Hilton SR, Strachan DP,
Cook DG.

Department of Community Health Sciences, St George's Hospital Medical School,
London, UK.

BACKGROUND : Theoretically, antibacterial agents in early life might influence
allergic sensitization in two ways: (i) as an indicator of infectious illness,
they might be expected to protect against allergy; (ii) alternatively they might 
increase the risk through effects on the commensal bowel flora. Epidemiological
evidence linking the prescription of antibacterial agents in early life to the
subsequent development of hayfever is conflicting. OBJECTIVE : To establish
definitively whether an association exists between early-life antibacterial
exposure and childhood hayfever diagnosis. METHODS : Nested case-control studies 
were based on birth cohorts of children identified within two large UK general
practice databases of electronic patient records. One hundred and sixteen
thousand and four hundred and ninety-three children from 605 general practices
were identified as being continuously registered from birth to at least age 5
years. Seven thousand and ninety-eight cases were diagnosed with hayfever after
the age of 2 years. One control per case was matched for practice, birth month,
sex and still being registered on case diagnosis date. Odds ratios were derived
from conditional logistic regressions within each database followed by pooling
using a fixed-effect model. RESULTS : The pooled odds ratio for hayfever was
1.11, 95% CI (1.03-1.20) if exposed to antibacterials in the first year of life, 
1.35 (1.25-1.46) in year 2 and 1.47 (1.37-1.59) in year 3. Adjusting for
consultation frequency reduced these odds ratios to 0.92, 1.05 and 1.10,
respectively. There was no evidence that broader spectrum antibacterials,
exposure in any specific month of year 1 or in the grass pollen season influenced
the risk of hayfever. CONCLUSION : These data exclude any important effect of
antibacterial exposure in infancy on subsequent hayfever risk. Associations
reported in earlier studies have likely been exaggerated through publication bias
and by lack of control for the tendency of some families to consult frequently
for a range of conditions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14616863 [PubMed - indexed for MEDLINE]

1023: Allergy. 2003 Dec;58(12):1277-84.

The influence of the dietary intake of fatty acids and antioxidants on hay fever 
in adults.

Nagel G, Nieters A, Becker N, Linseisen J.

Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg,
Germany.

BACKGROUND: The objective of the investigation was to explore in a prospective
study the associations between dietary intake of fatty acids, antioxidants and
hay fever manifestation in adulthood. METHODS: Three hundred and thirty-four hay 
fever cases with adult onset of clinical symptoms from the European Prospective
Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort were identified 
during follow-up and matched with 1336 controls. Dietary intake data were
obtained by means of validated food frequency questionnaires. The influence of
dietary fatty acid and vitamin intake on hay fever risk was estimated by means of
unconditional logistic regression. RESULTS: High intake of oleic acid was
positively associated with hay fever [odds ratio (OR): 2.86, 95% confidence
intervals (95% CI): 1.22-6.70], whereas high intake of eicosapentaenoic acid was 
inversely related to hay fever (OR: 0.45, 95% CI: 0.22-0.93). Furthermore, high
beta-carotene intake increased the risk of hay fever (OR: 1.69, 95% CI:
1.09-2.63) while increasing intake of vitamin E was a protective factor (OR:
0.38, 95% CI: 0.17-0.85). In grouped analyses, the effects of beta-carotene and
vitamin E were mainly observed among women and ex-/current-smokers; in these
subgroups, linoleic acid increased the risk of hay fever. CONCLUSIONS: In
conclusion, the present results provide further evidence that dietary factors
might affect the risk of clinical manifestation of hay fever. However, the
effects in smokers and women may suggest different biological mechanisms for the 
investigated nutrients, which need further research.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 14616103 [PubMed - indexed for MEDLINE]

1024: Allergy. 2003 Dec;58(12):1268-76.

Erratum in:
    Allergy. 2004 Mar;59(3):357.

Montelukast improves symptoms of seasonal allergic rhinitis over a 4-week
treatment period.

van Adelsberg J, Philip G, Pedinoff AJ, Meltzer EO, Ratner PH, Menten J, Reiss
TF; Montelukast Fall Rhinitis Study Group.

Merck Research Laboratories, Rahway, NJ, USA.

BACKGROUND: Proinflammatory mediators such as the cysteinyl leukotrienes are
important in the pathophysiology of allergic rhinitis. This study evaluated the
efficacy and tolerability of montelukast, a cysteinyl leukotriene receptor
antagonist, given once daily in the morning for treatment of seasonal (fall)
allergic rhinitis for 4 weeks. METHODS: This was a randomized, double-blind trial
with a placebo run-in and a 4-week treatment period. Patients (n = 1079) with a
history of allergic rhinitis and a positive skin test to seasonal pollen
allergens were assigned to placebo, montelukast 10 mg, or loratadine 10 mg.
Symptoms were assessed with a daily diary. RESULTS: Montelukast was more
effective than placebo in improving scores for the primary endpoint of daytime
nasal symptoms (P = 0.003) and the secondary endpoints of night-time, composite, 
and daytime eye symptoms, patient's and physician's global evaluations of
allergic rhinitis, and rhinoconjunctivitis quality-of-life (P </= 0.006). The
positive control loratadine also improved scores for the primary endpoint (P </= 
0.001) and the majority of the secondary endpoints (P < 0.03). When analyzed by
week, the treatment effect of montelukast was more persistent than loratadine
over all 4 weeks of treatment. CONCLUSION: Montelukast provided effective relief 
of seasonal allergic rhinitis symptoms when given once daily in the morning,
showed significant and sustained improvement in symptoms of allergic rhinitis
over 4 weeks of treatment, and was well-tolerated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14616102 [PubMed - indexed for MEDLINE]

1025: Ann Allergy Asthma Immunol. 2003 Oct;91(4):375-85.

A comparison of the effect of diphenhydramine and desloratadine on vigilance and 
cognitive function during treatment of ragweed-induced allergic rhinitis.

Wilken JA, Kane RL, Ellis AK, Rafeiro E, Briscoe MP, Sullivan CL, Day JH.

Department of Psychology, Veterans Affairs Medical Center, Washington, DC 20422, 
USA. jeffrey.wilken@med.va.gov

BACKGROUND: Decrements in cognitive performance are associated with the use of
sedating antihistamines. Most, but not all, second-generation antihistamines have
been found to be nonsedating. OBJECTIVE: To examine the central nervous system
(CNS) profile of a new second-generation antihistamine, desloratadine. METHODS:
Subjects with ragweed-induced allergic rhinitis (aged 18-60 years) who
demonstrated a predetermined severity of symptoms after priming with ragweed
pollen in the Environmental Exposure Unit were randomized to receive a single
dose of desloratadine, 5 mg; diphenhydramine, 50 mg; or placebo. A comprehensive 
battery of repeatable, automated neuropsychological tests was administered to
subjects before treatment (symptomatic baseline) and 90 minutes after taking
study medication. RESULTS: Both desloratadine (P = .04) and diphenhydramine (P < 
.01) alleviated the symptoms of allergic rhinitis compared with placebo, but
treatment with diphenhydramine was associated with clinically meaningful
decrements on all vigilance parameters (P < .05 for desloratadine-diphenhydramine
contrasts). Also, subjects treated with diphenhydramine performed significantly
worse than subjects given desloratadine or placebo across all cognitive domains
evaluated. Most effect sizes for the mean desloratadine and diphenhydramine
differences were between 0.4 and 0.8 (moderate to high). Stanford Sleepiness
Scale scores also indicated significantly more somnolence with diphenhydramine vs
desloratadine or placebo (P < .001). There were no significant differences on any
of the cognitive parameters between subjects treated with desloratadine and those
given placebo. CONCLUSIONS: Desloratadine improved ragweed-induced allergic
rhinitis symptoms without adversely affecting performance. Diphenhydramine
improved allergic rhinitis symptoms but caused significant decrements in
vigilance and cognitive functioning. Thus, efficacy of antihistamine treatment
must be balanced against the associated effects on CNS functioning.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14582817 [PubMed - indexed for MEDLINE]

1026: Ann Allergy Asthma Immunol. 2003 Oct;91(4):354-61.

Comment in:
    Ann Allergy Asthma Immunol. 2003 Oct;91(4):324-5.

Fexofenadine hydrochloride, 180 mg, exhibits equivalent efficacy to cetirizine,
10 mg, with less drowsiness in patients with moderate-to-severe seasonal allergic
rhinitis.

Hampel F, Ratner P, Mansfield L, Meeves S, Liao Y, Georges G.

Central Texas Health Research, New Braunfels, Texas 78130, USA. fchampel@aol.com

BACKGROUND: Previous studies have shown that fexofenadine and cetirizine
effectively relieve symptoms of seasonal allergic rhinitis (SAR). OBJECTIVE: To
compare the effects of fexofenadine hydrochloride, 180 mg, and cetirizine, 10 mg,
on symptoms, drowsiness, and motivation in patients with moderate-to-severe SAR. 
METHODS: In this 2-week multicenter, double-blind, randomized study, 495 subjects
with moderate-to-severe SAR received once-daily fexofenadine hydrochloride, 180
mg, or cetirizine, 10 mg, without regard to food intake. Daily 12-hour reflective
(AM, PM) and instantaneous (AM) individual symptoms and total symptom score (TSS)
were evaluated. Drowsiness and motivation were recorded daily using visual analog
scale at 7 AM, 10 AM, and 3 PM. RESULTS: Between-treatment differences in
reduction from baseline in AM instantaneous and 24-hour reflective TSS were -0.18
[95% confidence interval (CI), -0.55 to 0.20) and -0.22 (95% CI, -0.59 to 0.15), 
respectively. Since CIs for reduction in TSS between treatments fell within a 0.7
margin (defined a priori), treatments were considered statistically equivalent.
Patients receiving fexofenadine experienced significantly less overall drowsiness
vs baseline than those receiving cetirizine [-2.33 (95% CI, -3.80 to 0.86) vs
0.37 (95% CI, -1.10 to 1.84), P = .0110]. There was a trend toward greater
improvements in overall motivation with fexofenadine compared with cetirizine
[-2.36 (95% CI, -3.83 to 0.90) vs -0.30 (95% CI, -1.76 to 1.17), P = .0504].
CONCLUSIONS: Once-daily fexofenadine hydrochloride, 180 mg, given for 2 weeks
caused statistically and clinically equivalent improvement in symptoms and
significantly less drowsiness va baseline, compared with cetirizine, 10 mg, in
patients with moderate-to-severe SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14582814 [PubMed - indexed for MEDLINE]

1027: Rhinology. 2003 Sep;41(3):159-66.

Effects of dimethindene maleate nasal spray on the quality of life in seasonal
allergic rhinitis.

Kirchhoff CH, Kremer B, Haaf-von Below S, Kyrein HJ, Mösges R.

Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical
School, Boston, USA.

OBJECTIVE: To determine if the H1-receptor antagonist dimethindene maleate (DMM),
topically applied, is able to improve the quality of life (QoL) in patients with 
seasonal allergic rhinitis better than placebo. METHODS: The study was a
multi-centre, randomised, placebo-controlled, double-blinded phase III trial
including 157 patients. Two parallel groups received either DMM nasal spray or
placebo for 2 weeks. Patients answered 5 QoL questionnaires (Rhinoconjunctivitis 
QoL Questionnaire (LQ-AR), Munich Life Dimension List (MLDL), Profile of Mood
States (POMS), 2 Visual Analogue Scales (VAS-QoL, VAS-GES)) on days 1, 4, 8, and 
15. RESULTS: QoL improved significantly in all scales and groups. Statistically
significant differences between groups were achieved in the sub-scales LQ-AR Eye 
Symptoms and Daily Activities, MLDL Total, POMS Depression and Energy, VAS-QoL
and VAS-General Health. All differences favoured the DMM group and were present
initially but disappeared in visit 4, except MLDL Total and POMS Energy. Almost
all other scores had a better tendency of DMM. CONCLUSION: A significant
improvement of QoL was found in both groups. Only weak differences between groups
(in favour of DMM) were found. There are several reasons explaining this outcome,
mainly the rainy weather during the study period (mean weather index 10-20% less 
sunny than in previous seasons).

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial

PMID: 14579656 [PubMed - indexed for MEDLINE]

1028: Allergol Immunopathol (Madr). 2003 Sep-Oct;31(5):270-7.

Efficacy and tolerability of short-term specific immunotherapy with pollen
allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and
adolescents.

Drachenberg KJ, Heinzkill M, Urban E, Woroniecki SR.

Bencard Allergie GmbH, Munich, Germany.

BACKGROUND: Specific immunotherapy (SIT) with pollen allergoids formulated with
the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant,
Corixa) has shown good efficacy and tolerability in the treatment of pollen
allergies in adults. The aim of this study was to evaluate this treatment in
children and adolescents aged 6-17 years old who were sensitive to grass/rye or
tree pollens. METHODS: An open, multicenter study was performed using 90 children
and adolescents. The patients received four subcutaneous injections of grass/rye 
(n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing
MPL adjuvant. Efficacy was measured by symptom and medication scoring, skin prick
test reactivity and IgG/IgE antibody responses. Tolerability was monitored by
recording adverse events. RESULTS: Both grass/rye and tree pollen treatment
groups showed significant reductions in symptom scores and anti-allergic
medication use compared with the previous pollen seasons (p < 0.01 in all cases).
After therapy, skin prick test reactivity was significantly reduced in both
groups and pollen-specific IgG was significantly increased in both groups whereas
little change was apparent in pollen-specific IgE. Overall tolerability was
similar to results obtained in previous studies in adults. CONCLUSION: Short-term
SIT using four injections of grass/rye or tree pollen allergoids adsorbed to
L-tyrosine and with MPL adjuvant was shown to be effective with good
tolerability. The treatment compared favorably with previous studies in adults.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study

PMID: 14572416 [PubMed - indexed for MEDLINE]

1029: ORL J Otorhinolaryngol Relat Spec. 2003 Jul-Aug;65(4):202-5.

Local pathogenic bacteria in allergic rhinitis: a novel concept of its
pathogenesis.

Glück U, Gebbers JO.

ENT Unit, Division of Occupational Medicine, Suva Swiss National Accident
Insurance Institute, Luzern, Switzerland. u_gluck@yahoo.com

BACKGROUND: It is still unclear to what extent microorganisms are involved in the
pathogenesis of allergic rhinitis. OBJECTIVE: Therefore, we examined the mucosal 
colonization with potential pathogenic bacteria (PPB) of the nasal cavity in
allergic and nonallergic subjects. METHODS: In an open prospective study of 389
office workers (297 men, mean age 42.5 years, and 92 women, mean age 36.7 years),
bacterial swabs were taken selectively from both nasal cavities. Standard skin
tests for various aeroallergens and negative control tests were conducted in
parallel in these subjects. RESULTS: In the 389 subjects, we found positive skin 
tests in 58 (15%); 37 of these revealed a high level of sensitivity, whilst the
other 21 persons had low to moderate levels. Ninety percent of the 58 sensitive
persons had PPB in their nasal cavity while only 36% (119) of the remaining 331
subjects with negative skin tests were shown to have PPB in nasal cultures (p <
0.001). Sixty-four percent of the sensitized subjects with PPB were found to have
more than 2 PPB species and a positive correlation with the intensity of the skin
reaction. In contrast, only 18% (22) of the 119 nonallergic test persons with PPB
had more than 1 PPB species. CONCLUSIONS: This finding of an unusually high
frequency of nasal PPB in subjects with positive skin tests to aeroallergens may 
indicate an involvement of PPB in the pathogenesis of allergic rhinitis. Yet,
further data are still lacking to support this novel concept. Copyright 2003 S.
Karger AG, Basel

PMID: 14564093 [PubMed - indexed for MEDLINE]

1030: Curr Drug Targets Inflamm Allergy. 2002 Sep;1(3):215-20.

Treatment of allergic rhinitis: H1-antihistamines and intranasal steroids.

Wang DY.

Department of Otolaryngology, National University of Singapore. entwdy@nus.edu.sg

Allergic rhinitis is charterized as an inflammatory disease of the nasal mucosa. 
In clinical practice, H(1)-antihistamines and topical corticosteroids are most
commonly used pharmacological agents for the treatment of allergic rhinitis. The 
beneficial effects of steroids depend upon their long-term anti-inflammatory
effect rather than upon direct receptor antagonism. This is different to
H(1)-antihistamines, which block both neural and vascular H(1) receptors and have
a clinical effect on symptoms such as nasal itching, sneezing, and rhinorrhea.
H(1)-antihistamines are rapidly absorbed and most of them are metabolized by the 
hepatic cytochrome P system and begin to reduce nasal symptoms (itching and
sneezing) within one hour. Understanding of both the efficacy and the
pharmacological properties of these commonly used drugs in the treatment of nasal
allergic inflammation and its related nasal symptoms is very important. From a
clinical viewpoint, it will provide a useful guideline for an appropriate use of 
these drugs.

Publication Types: 
    Review

PMID: 14561186 [PubMed - indexed for MEDLINE]

1031: Thyroid. 2003 Aug;13(8):811-4.

Association of seasonal allergic rhinitis is high in Graves' disease and low in
painless thyroiditis.

Amino N, Hidaka Y, Takano T, Izumi Y, Tatsumi KI, Nakata Y.

Department of Laboratory Medicine, Osaka University Graduate School of Medicine, 
Suita, Osaka, Japan. namino@labo.med.osaka-u.ac.jp

Hashimoto's thyroiditis is thought to be a T-helper cell type 1 (TH1)-dependent
disease, but it is not clear whether Graves' disease is T-helper cell type 2
(TH2)-predominant or not. TH1-predominant diseases are infrequently and
TH2-predominant diseases are frequently associated with allergic diseases. We
examined the prevalence of seasonal allergic rhinitis to Japanese cedar pollen, a
typical TH2-associated disease, in patients with Graves' disease (n = 126),
painless thyroiditis (n = 46) and Hashimoto's thyroiditis (n = 88), and compared 
them to healthy controls (n = 766). Gender and age distribution were not
different among patient groups and healthy controls, except for the higher age of
patients with Hashimoto's thyroiditis. The prevalence of seasonal allergic
rhinitis was significantly high in patients with Graves' disease (42.9%, p <
0.05) and low in patients with painless thyroiditis (13.0%, p < 0.01) but was not
different in patients with Hashimoto's thyroiditis (26.1%) compared to that of
healthy controls (32.6%). When patients with painless thyroiditis were included
in Hashimoto's thyroiditis group, the prevalence of seasonal allergic rhinitis
was 21.6% and significantly different from that of healthy controls (p < 0.05).
These data indicate that Graves' disease is TH2 predominant and painless
thyroiditis is a TH1-predominant disease. Our findings suggest that the shift
from TH2 toward TH1 immunogenesis may be important for achieving earlier
remission of Graves' disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14558923 [PubMed - indexed for MEDLINE]

1032: Int Arch Allergy Immunol. 2003 Sep;132(1):76-81.

Dissimilarity between seasonal changes in airway responsiveness to
adenosine-5'-monophosphate and methacholine in patients with grass pollen
allergic rhinitis: relation to induced sputum.

Beier J, Beeh KM, Kornmann O, Morankic E, Ritter N, Buhl R.

Pulmonary Department, Internal Medicine, University Hospital, Mainz, Germany.
j.beier@3-med.klinik.uni-mainz.de

BACKGROUND: In patients with allergic rhinitis, bronchial hyperresponsiveness
(BHR) and airway inflammation may increase during pollen exposure. BHR can be
assessed by adenosine-5'-monophosphate (AMP) or methacholine challenge. It has
been suggested that BHR to AMP is more closely related to airway inflammation
than BHR to methacholine. Seasonal allergic rhinitis offers a dynamic model to
study changes in BHR and airway inflammation during natural allergen exposure.
METHODS: We measured BHR [provocative concentration causing a 20% fall (PC(20))
in forced expiratory volume in 1 s (FEV(1))] to AMP and methacholine, and induced
sputum cells in 16 rhinitis patients before and during the 2001 grass pollen
season. RESULTS: There was a decrease in PC(20) methacholine during pollen
exposure (geometric mean PC(20) from 3.22 to 1.73 mg/ml, p = 0.0023), whereas no 
reduction was observed for PC(20) AMP (p = 0.11). There was no increase in sputum
eosinophils [pre: 0.69% (95% confidence interval 0.22-2.07); during: 1.85 (0.55- 
5.6), p = 0.31]. Although the correlation of log PC(20) methacholine and log
PC(20) AMP at baseline was good (r = 0.76, p = 0.001), individual seasonal
changes (doubling concentrations) in PC(20) methacholine were not correlated with
changes in PC(20) AMP (rho = 0.21, p = 0.44). There was no correlation between
baseline log PC(20) methacholine or seasonal changes in PC(20) methacholine and
sputum eosinophils (p > 0.12, all correlations). In contrast, there was a
significant correlation between seasonal changes in PC(20) AMP and changes in
sputum eosinophils (rho = -0.59, p = 0.025). CONCLUSIONS: These data show
dissimilarity between seasonal changes in PC(20) AMP and methacholine in patients
with seasonal allergic rhinitis. Moreover, PC(20) AMP seems to be more closely
related to sputum eosinophils than PC(20) methacholine. The clinical significance
of this discrepancy is unclear. Copyright 2003 S. Karger AG, Basel

PMID: 14555861 [PubMed - indexed for MEDLINE]

1033: Ann Allergy Asthma Immunol. 2003 Sep;91(3):258-62.

Histamine skin test reactivity following single and multiple doses of azelastine 
nasal spray in patients with seasonal allergic rhinitis.

Pearlman DS, Grossman J, Meltzer EO.

Colorado Allergy & Asthma Centers, PC, Denver, Colorado 80230, USA.
ds.pearlman@coloradoallergy.com

OBJECTIVE: To determine whether azelastine nasal spray suppresses the dermal
response to epicutaneous histamine in allergic patients and the duration of
suppression after azelastine use is discontinued. METHODS: Seventy-eight patients
with seasonal allergic rhinitis were entered into this randomized, double-blind, 
parallel-group, placebo-controlled study. Patients received either azelastine
nasal spray (2 sprays per nostril twice daily) or placebo nasal spray for 14
days. Skin tests were performed 5 hours after the first dose of study drugs to
determine the effect of a single dose of azelastine nasal spray on the
wheal-and-flare response to histamine. At the end of the 14-day treatment period,
skin tests were performed 5 hours after the last dose of study drugs and at
24-hour intervals thereafter, until each patient's wheal-and-flare response to
histamine (1.0 and 5.0 mg/mL) returned to within 20% of baseline values. RESULTS:
A single dose of azelastine nasal spray did not significantly alter the
wheal-and-flare response to histamine. The wheal response was within 20% of the
baseline value in 82% and 88% (1.0 and 5.0 mg/mL of histamine, respectively) of
the patients 5 hours after discontinuing 14 days of treatment with azelastine
nasal spray. Wheal responses were within 20% of baseline values 48 hours after
treatment was discontinued, whereas flare responses returned to within 20% of
baseline within 48 hours in 92% of the patients. CONCLUSIONS: Azelastine nasal
spray should be discontinued for at least 48 hours before beginning allergy skin 
test procedures.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14533657 [PubMed - indexed for MEDLINE]

1034: Altern Ther Health Med. 2003 Sep-Oct;9(5):80-7.

Treatment for seasonal allergic rhinitis by Chinese herbal medicine: a randomized
placebo controlled trial.

Xue CC, Thien FC, Zhang JJ, Da Costa C, Li CG.

RMIT Chinese Medicine Research Group, RMIT University, Bundoora West Campus,
Bundoora, Australia.

CONTEXT: Chinese herbal medicine (CHM) is widely used to treat seasonal allergic 
rhinitis (SAR), however, evidence of efficacy is lacking. OBJECTIVE: To evaluate 
the efficacy of a Chinese herbal formulation for the treatment of SAR. DESIGN:
Randomized, double blind, placebo controlled trial. SETTING: RMIT Chinese
Medicine Clinic. PATIENTS: 55 patients with seasonal allergic rhinitis (active
28, placebo 27). INTERVENTIONS: CHM extract capsule (containing 18 herbs) or
placebo, given daily for 8 weeks. MAIN OUTCOME MEASURES: The primary measure of
efficacy were changes in severity of nasal and non-nasal symptoms using a Five
Point Scale (FPS) measured by both patients and the practitioner. The secondary
measure was the change in score for the domains measured in the
Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire (RQLQ) assessed by
patients. RESULTS: Forty-nine patients completed the study (active 24, placebo
25). After eight weeks, the severity of nasal symptoms and non-nasal symptoms
were significantly less in the active treatment group than in the control group, 
both for measurements made by patients and those by the practitioner. Comparison 
of active and placebo treatment groups RQLQ scores also indicated significant
beneficial effects of treatment (end point Section 1: P < 0.05; Section 2: P <
0.01). Intention-to-treat analyses of categorical items showed moderate to marked
improvement rates were 60.7% and 29.6% for active and placebo respectively.
Eleven patients reported mild adverse events including 1 withdrawn from the
trial. CONCLUSIONS: This CHM formulation appears to offer symptomatic relief and 
improvement of quality of life for some patients with seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 14526714 [PubMed - indexed for MEDLINE]

1035: J Huazhong Univ Sci Technolog Med Sci. 2003;23(3):310-2.

Expression of HSP70 in peripheral lymphocytes of the patients with allergic
rhinitis.

Liu L, Xiao C, Zhang M, Cheng L, Wang E, Wu T.

Department of Otorhinolaryngology, Tongji Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan 430030.

The expression levels of heat shock protein 70 (HSP70) from peripheral
lymphocytes of the patients with allergic rhinitis (AR) and the clinical
implication were investigated. In the morning, 3 ml of fasting venous blood was
taken out. The lymphocytes were isolated by using Ficoll-Hypaque and the
expression of HSP70 in the lymphocytes was detected by using Western blot. In the
AR patients the HSP70 level (41.49 +/- 15.77 integrated optical density, IOD)
were significantly higher than that in the control group (23.89 +/- 10.13 IOD, P 
< 0.05). Western blot demonstrated that HSP70 bands in AR patients were more
intensive than those in the control group. It was concluded that the elevated
HSP70 level in peripheral lymphocytes of the AR patients might contribute to the 
development of AR.

PMID: 14526444 [PubMed - indexed for MEDLINE]

1036: Bull Hist Med. 2003 Fall;77(3):600-35.

Hay fever holiday: health, leisure, and place in Gilded-Age America.

Mitman G.

By the 1880s hay fever (also called June Cold, Rose Cold, hay asthma, hay cold,
or autumnal catarrh) had become the pride of America's leisure class. In
mid-August each year, thousands of sufferers fled to the White Mountains of New
Hampshire, to the Adirondacks in upper New York State, to the shores of the Great
Lakes, or to the Colorado plateau, hoping to escape the dreaded seasonal symptoms
of watery eyes, flowing nose, sneezing fits, and attacks of asthma, which many
regarded as the price of urban wealth and education. Through a focus on the White
Mountains as America's most fashionable hay fever resort in the late nineteenth
century, this essay explores the embodied local geography of hay fever as a
disease. The sufferers found in the White Mountains physical relief, but also a
place whose history affirmed their social identity and shaped their relationship 
to the natural environment. And, they, in turn, became active agents in shaping
the geography of place: in the very material relationships of daily life, in the 
social contours of the region, and in the symbolic space that nature inhabited.
In the consumption of nature for health and pleasure, this article suggests, lies
an important, yet relatively unexplored, source for understanding changing
perceptions of environment and place and the impact of health on the local and
regional transformation of the North American landscape.

Publication Types: 
    Historical Article

PMID: 14523262 [PubMed - indexed for MEDLINE]

1037: Clin Exp Allergy. 2003 Oct;33(10):1439-42.

Primary sensitization to sweet bell pepper pollen in greenhouse workers with
occupational allergy.

Vermeulen AM, Groenewoud GC, de Jong NW, de Groot H, Gerth van Wijk R, van
Toorenenbergen AW.

Department of Clinical Chemistry, University Hospital Rotterdam, Rotterdam, The
Netherlands.

BACKGROUND: In a previous investigation, a high prevalence of allergy to sweet
bell pepper pollen was found among exposed horticulture workers. Allergy to
plant-derived food is often the consequence of primary sensitization to common
pollen allergens. OBJECTIVE: We therefore investigated the cross-reactivity
between sweet bell pepper pollen and pollen from grass, birch or mugwort. METHOD:
We selected 10 sera from greenhouse workers who had, besides specific IgE against
sweet bell pepper pollen, also IgE to grass, birch or mugwort pollen.
Cross-reactivity was tested by the inhibition of IgE binding to solid-phase
coupled sweet bell pepper pollen extract. The 10 sera were also analysed for IgE 
binding to sweet bell pepper pollen by immunoblotting. RESULTS: With these sera, 
no or small inhibition of IgE binding to sweet bell pepper pollen extract was
observed with grass, birch and mugwort pollen. With immunoblotting, major
IgE-binding structures were seen at 14, 29 and 69 kDa in sweet bell pepper pollen
extract. CONCLUSION: The results of our study demonstrate that sweet bell pepper 
pollen contains allergens that have no or limited cross-reactivity with common
pollen allergens. With sera from the 10 patients tested, sensitization to sweet
bell pepper pollen was not the consequence of primary sensitization to common
pollen allergens.

PMID: 14519152 [PubMed - indexed for MEDLINE]

1038: Clin Exp Allergy. 2003 Oct;33(10):1380-8.

Expression of cysteinyl leukotriene synthetic and signalling proteins in
inflammatory cells in active seasonal allergic rhinitis.

Figueroa DJ, Borish L, Baramki D, Philip G, Austin CP, Evans JF.

Department of Neuroscience, Merck Research Laboratories, West Point, PA 19468,
USA. david_figueroa@merck.com

BACKGROUND: Cysteinyl leukotrienes (CysLTs) are bioactive lipids that have been
shown to contribute to allergic and inflammatory diseases. Eosinophils and mast
cells have the capacity to produce large amounts of CysLTs after allergic or
non-allergic stimulation. Molecular identification of both the synthetic and
signalling proteins in the CysLT pathway allows the investigation of expression
of the CysLT enzymes and receptors in active allergic rhinitis. OBJECTIVE: We
examined the expression of the proteins involved in the synthesis of CysLTs and
the cysteinyl leukotriene-1 (CysLT1) and cysteinyl leukotriene-2 (CysLT2)
receptors in inflammatory cells from patients with active seasonal allergic
rhinitis. METHODS: Nasal lavage samples were obtained from patients during active
seasonal allergic rhinitis. Specific cellular immunocytochemical techniques were 
used to detect the cysteinyl leukotriene synthetic proteins, namely
5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and leukotriene
C4 synthase (LTC4S). In situ hybridization and immunocytochemical techniques were
used to identify the mRNA and proteins for the CysLT1 and CysLT2 receptors.
RESULTS: 5-LO, FLAP and LTC4S, and the CysLT1 and CysLT2 receptors were expressed
in the majority of eosinophils and in subsets of mast cells and mononuclear
cells. 5-LO, FLAP and the CysLT1 receptor, but not LTC4S or the CysLT2 receptor, 
were expressed in a subset of nasal neutrophils. CONCLUSIONS: Our study
demonstrates the presence of CysLT pathway proteins in key allergic and
inflammatory cells from the upper airway of patients with active seasonal
allergic rhinitis. Our expression data highlight the potential of CysLT-modifying
agents to treat both upper and lower airway symptoms in patients suffering from
allergic rhinitis and asthma.

PMID: 14519144 [PubMed - indexed for MEDLINE]

1039: Inhal Toxicol. 2003 Oct;15(12):1179-89.

Influence of age, gender, and allergy status on nasal reactivity to inhaled
chlorine.

Shusterman D, Murphy MA, Balmes J.

Department of Medicine, University of California, San Francisco, California, USA.
dennis@itsa.ucsf.edu

Upper-respiratory-tract symptoms (nasal irritation, congestion and rhinorrhea)
are prevalent complaints in so-called "problem buildings." In epidemiologic
studies, symptom reporting is associated with selected subject characteristics,
including younger age, female gender, and the presence of allergic rhinitis. The 
physiologic correlates of these differential reporting patterns, however, are
largely unknown. Using dilute chlorine gas as a model upper-respiratory-tract
irritant, we studied 52 otherwise healthy volunteers in a sample stratified on
age (18-69 yr), gender, and allergy status. In a single-blinded crossover study, 
subjects had their nasal airway resistance measured preexposure, immediately
postexposure, and 15 min postexposure to both filtered air and chlorine (1.0 ppm 
in air) for 15 min. Allergic rhinitic subjects showed a significantly greater net
(chlorine minus air) congestive response at 15 min postexposure than did
nonrhinitic controls (p <.01). Advancing age also predicted a greater response
immediately post-exposure (p <.01). No gender effect was observed. Significant
interindividual variability was evident in the nasal congestive response to
irritant (chlorine) provocation. The rhinitis effect was consistent with prior
observations, whereas the effect of advancing age was opposite to that
hypothesized.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 14515221 [PubMed - indexed for MEDLINE]

1040: Clin Ther. 2003 Aug;25(8):2198-214.

Two multicenter, randomized, single-blind, single-dose, crossover studies of
specific sensory attributes of budesonide aqueous nasal spray and fluticasone
propionate nasal spray.

Shah SR, Miller C, Pethick N, Uryniak T, Jones MK, O'Dowd L.

Allergy and Asthma Consultants of NJ-PA, PC, Collegeville, Pennsylvania 19426,
USA.

BACKGROUND: Intranasal corticosteroids are effective for the treatment of
allergic rhinitis. Sensory attributes associated with these sprays may affect
patient preference and adherence to treatment regimens. OBJECTIVES: These 2
studies compared patients' perceptions of and preferences for specific sensory
attributes of budesonide aqueous nasal spray (BANS) and fluticasone propionate
nasal spray (FPNS). METHODS: In 2 multicenter, randomized, single-blind
(patient), single-dose, 2-period, 1-day crossover studies, adults with mild to
moderate allergic rhinitis received single doses of BANS (one 32-pg spray per
nostril in both studies, 64-microg total dose) and FPNS (two 50-microg sprays per
nostril in study 1, 200-pg total dose; one 50-microg spray per nostril in study
2, 100-microg total dose). Study 1 compared the once-daily recommended starting
doses of BANS and FPNS, and study 2 compared BANS with half the once-daily
recommended dose of FPNS to balance the number of actuations for delivery of
study drug. Patients completed the 23-item Sensory Perceptions Questionnaire and 
indicated their product preference (if any). RESULTS: A total of 110 women and 71
men in study 1 and 136 women and 54 men in study 2 were randomized to treatment. 
None had previously used BANS or FPNS. In both studies, fewer patients perceived 
scent or taste (both P < 0.001 in both studies), forceful spray (P < 0.001 in
both studies), and a wet feel in both the nose and throat (study 1, P < 0.004;
study 2, P < 0.002) with BANS than with FPNS. In addition, more patients in both 
studies liked the spray force (study 1, P < 0.01; study 2, P < 0.001) and
moisture content in the throat (study 1, P < 0.001; study 2, P < 0.006) of BANS
and indicated a greater overall satisfaction with the sensory features of BANS
than those of FPNS (study 1, P < 0.001; study 2, P < 0.015). In analyses that
included all responding patients, 54.4% of patients in study 1 preferred BANS and
37.8% preferred FPNS (P < 0.022). In study 2, 47.4% preferred BANS and 41.1%
preferred FPNS (not significant). Of the 92.2% of patients in study 1 and 88.4%
in study 2 who specified a product preference, 59.0% preferred BANS and 41.0%
preferred FPNS in study 1 (P = 0.021), and 53.6% preferred BANS and 46.4%
preferred FPNS in study 2 (not significant). CONCLUSIONS: On the basis of
perceptions of specific sensory attributes reported after 1 administration in
these 2 studies, BANS was rated as more pleasing and preferred over the
recommended QD starting dose of FPNS, and was also rated as more pleasing than
half the QD recommended starting dose of FPNS.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14512128 [PubMed - indexed for MEDLINE]

1041: Ear Nose Throat J. 2003 Aug;82(8):592-7.

The effect of topical fluticasone on nasal nitric oxide levels in a patient with 
allergic rhinitis.

Vural C, Gungor A.

Sisli Etfal Training and Research Hospital, Istanbul, Turkey.

Nitric oxide (NO) in exhaled breath is produced primarily by the upper
respiratory airway mucosa. The nasal output of this gas is increased in patients 
with allergic rhinitis. We performed a study on a 41-year-old nonsmoking male
volunteer with allergic rhinitis to investigate the effect of fluticasone nasal
spray on nasal NO output (VNO). A total of 28 nasal NO measurements from both
nostrils were taken during the 2-month period of June and July 2002. During the
second half of the study period (treatment phase), the patient took fluticasone
in doses of 100 micrograms per nostril once a day. During the treatment phase,
nasal NO measurements were taken 10 days after the initiation of treatment. In
addition, we also recorded the patient's nasal symptom scores and the grass
pollen counts in the greater Pittsburgh area. The patient's mean VNO was 989.9
nl/min prior to treatment and 787.7 nl/min following treatment--a statistically
significant 20.4% decrease (p < 0.01). The findings of our study support the
observation that topical nasal steroid treatment decreases NO production in
sinonasal mucosa.

Publication Types: 
    Case Reports

PMID: 14503095 [PubMed - indexed for MEDLINE]

1042: Am J Respir Crit Care Med. 2003 Nov 15;168(10):1243-5. Epub 2003 Sep 18.

Rhinitis and blood pressure in adults.

Heinrich J, Topp R, Brasche S.

GSF-Institute of Epidemiology, PO Box 1129, D-85758 Neuherberg, Germany.
joachim.heinrich@gsf.de

Recently, a study of 330 adults reported increased systolic blood pressure and
higher hypertension rates in men with rhinitis. We replicated this study using
data from a population-based sample of 896 subjects participating in the European
Respiratory Health Survey and in a study on "Monitoring of Trends and
Determinants of Cardiovascular Diseases" in Erfurt, Germany. Rhinitis was
assessed by questionnaire, blood pressure was measured using a standardized
method, and subjects were asked about current use of any high blood pressure
medication. After adjustment for age, body mass index, and smoking, neither
average systolic (p = 0.17) nor diastolic blood pressure (p = 0.60) was
statistically significantly different between men with and without rhinitis. The 
adjusted prevalence rate of hypertension was also not different between males
with and without rhinitis (p = 0.25). In addition, no statistically significant
associations between rhinitis and blood pressure were seen in women. We could not
confirm the conclusion of the previous study that men with rhinitis need special 
attention for blood pressure control.

PMID: 14500262 [PubMed - indexed for MEDLINE]

1043: Clin Exp Immunol. 2003 Oct;134(1):78-85.

Methods for the in vitro determination of an individual disposition towards TH1- 
or TH2-reactivity by the application of appropriate stimulatory antigens.

Barth H, Berg PA, Klein R.

Department of Internal Medicine II, University of Tübingen, Germany.

In this study we performed several methods for the determination of cytokines
(RT-PCR for the demonstration of cytokine mRNA and flow cytometry for the
analysis of intracellular cytokines) and compared them with a recently
established test system stimulating peripheral blood mononuclear cells (PBMC)
with TH1- and TH2-relevant recall antigens and analysing type 1 and type 2
cytokines by ELISA. Aim of the study was therefore to evaluate the reliability of
TH1/TH2 cytokine profiles in two individuals with different types of an
allergic/atopic disposition: one of them showed a strong TH1/type 1-mediated
tuberculin-reaction (subject A), the other (subject B) revealed elevated
IgE-levels and eosinophil counts (TH2/type 2-mediated). PBMC were incubated with 
the type 1-antigen purified protein derivative (PPD) and the type 2-antigen
tetanus-toxoid (TT) for seven days. From the comparison of ELISA with RT-PCR and 
flow cytometry-analysis it became evident that all three methods allowed the
definition of subject A as a 'type 1-responder'. Subject B showed a pure type
2-response in the ELISA method; PCR and flow cytometry analysis revealed the
simultaneous production of type 1- and type 2-cytokines resulting in a mixed type
1/type 2-profile. Active immunization of subject A with TT at the end of the
observation period of 12 months resulted in a transient shift from type 1- to a
mixed type 1/type 2-profile (simultaneous PPD-induced IFN-gamma- and TT-induced
IL-5 production). From this pilot study based on clear cut clinical criteria
concerning either a humoral or cellular immunological reactivity towards
allergens/antigens it is suggested that the determination of type 1/type
2-cytokines by ELISA in supernatants of PBMC stimulated with type 1/type
2-relevant antigens is a useful approach for a better classification of 'type1-' 
or 'type 2-responder'.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 12974758 [PubMed - indexed for MEDLINE]

1044: Eur J Epidemiol. 2003;18(8):755-61.

Comment in:
    Eur J Epidemiol. 2003;18(8):739-41.

Pregnancy complications and the risk of asthma among Norwegians born between 1967
and 1993.

Nafstad P, Samuelsen SO, Irgens LM, Bjerkedal T.

Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
per.nafstad@fhi.no

BACKGROUND: Fetal life events may affect the development of the immune and/or
respiratory system and increase the risk of asthma and allergic diseases. The
objective of this study was to test the hypothesis that pregnancy complications
are associated with the risk of developing asthma in the off-spring. METHODS: The
study population comprised Norwegian live births 1967-1993 (n = 1,548,429)
linking the Medical Birth Registry of Norway (MBRN) (exposure variables) and the 
National Insurance Administration Register (NIAR) (outcome variables), which
covers all Norwegians. The MBRN variables included pregnancy complications,
pregnancy outcomes and diseases of the mother. The NIAR provided data on all
Norwegians who had received cash benefit for treatment of asthma from 1967 to
1996 (n = 5938, 3.9/1000 persons). RESULTS: In multiple logistic regression
analysis, pregnancy complications (International Classification of Diseases
(ICD)-8-codes: 630-634) were associated with the risk of asthma (odds ratio 1.82,
95% confidence interval: 1.67-1.98). This was also the case if analyses were
performed in different strata according to year of birth, plurality, maternal
atopy, geographical district of birth, and maternal education. CONCLUSIONS:
Pregnancy complications may represent risk factors for the development of asthma 
in the offspring or express early signs of increased risk for developing the
disease.

Publication Types: 
    Comparative Study

PMID: 12974550 [PubMed - indexed for MEDLINE]

1045: Eur J Pharmacol. 2003 Aug 29;476(3):239-47.

Effects of TAK-427 on acute nasal symptoms and nasal obstruction in guinea pig
model of experimental allergic rhinitis.

Fukuda S, Midoro K, Gyoten M, Kawano Y, Ashida Y, Nabe T, Kohno S, Nagaya H.

Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, 2-17-85,
Juso-Honmachi, Yodogawa, Osaka 532-8686, Japan. Fukuda_Shigeru@takeda.co.jp

TAK-427
(2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino]imidazo[1,2-b]pyridazin-2-y
l]-2-methylpropionic acid dihydrate) is a novel anti-allergic agent that has both
histamine H1-receptor antagonist and anti-inflammatory activities. In this study,
we evaluated the efficacy of TAK-427 on acute nasal responses and nasal
obstruction using various guinea pig models of allergic rhinitis. TAK-427
inhibited the histamine-induced nasal reactions with an ID50 value of 0.633
mg/kg, p.o. TAK-427 (0.1-10 mg/kg, p.o.) and most histamine H1-receptor
antagonists tested inhibited the increase in intranasal pressure, nasal
hypersecretion, sneezing and nasal itching caused by a single antigen challenge
in sensitized guinea pigs. In addition, TAK-427 (0.3, 30 mg/kg, p.o.)
significantly inhibited the development of nasal obstruction when sensitized
guinea pigs were repeatedly challenged via inhalation with Japanese cedar pollen,
whereas the histamine H1-receptor antagonist, azelastine (1 mg/kg, p.o.), and
ketotifen (1 mg/kg, p.o.) were without effect. These results suggest that TAK-427
might not only suppress acute nasal symptoms but also ameliorate nasal
obstruction via the effects other than those as a histamine H1-receptor
antagonist.

Publication Types: 
    Comparative Study

PMID: 12969771 [PubMed - indexed for MEDLINE]

1046: Eur J Pharmacol. 2003 Aug 29;476(3):229-37.

Kinins are involved in the development of allergic nasal hyperresponsiveness in
guinea pigs.

Sugahara S, Nabe T, Mizutani N, Takenaka H, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi,
Misasagi, Yamashina, Kyoto 607-8414, Japan.

We evaluated roles of kinins in allergen-induced nasal blockage and sneezing, and
development of nasal hyperresponsiveness to leukotriene D4 in a Japanese cedar
pollen-induced allergic rhinitis model of guinea pigs. Sensitised guinea pigs
were repeatedly challenged by pollen inhalation once every week. Neither a
bradykinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin nor a bradykinin B2 
receptor antagonist, icatibant suppressed allergen-induced sneezing and nasal
blockage. However, development of nasal hyperresponsiveness to leukotriene D4 was
significantly suppressed by them. The amount of bradykinin in nasal cavity lavage
fluid was immediately increased after the challenge. In non-sensitised animals,
hyperresponsiveness to leukotriene D4 was developed by a bradykinin B2 receptor
agonist, bradykinin, but not by a bradykinin B1 receptor agonist,
des-Arg10-kallidin, while in the sensitised-challenged animal, both agonists
developed hyperresponsiveness. In conclusion, the nasal hyperresponsiveness
appeared to be induced by kinins produced in response to the antigen challenge
through activation of not only bradykinin B2 but also B1 receptors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12969770 [PubMed - indexed for MEDLINE]

1047: Drug Saf. 2003;26(12):863-93.

Safety and tolerability profiles of intranasal antihistamines and intranasal
corticosteroids in the treatment of allergic rhinitis.

Salib RJ, Howarth PH.

Respiratory Cell and Molecular Biology, Faculty of Medicine, Southampton General 
Hospital, Southampton, United Kingdom. rjs4@soton.ac.uk

Intranasal corticosteroids and intranasal antihistamines are efficacious topical 
therapies in the treatment of allergic rhinitis. This review addresses their
relative roles in the management of this disease, focusing on their safety and
tolerability profiles. The intranasal route of administration delivers drug
directly to the target organ, thereby minimising the potential for the systemic
adverse effects that may be evident with oral therapy. Furthermore, the topical
route of delivery enables the use of lower doses of medication. Such therapies,
predominantly available as aqueous formulations following the ban of
chlorofluorocarbon propellants, have minimal local adverse effects. Intranasal
application of therapy can induce sneezing in the hyper-reactive nose, and
transient local irritation has been described with certain formulations.
Intranasal administration of corticosteroids is associated with minor nose
bleeding in a small proportion of recipients. This effect has been attributed to 
the vasoconstrictor activity of the corticosteroid molecules, and is considered
to account for the very rare occurrence of nasal septal perforation. Nasal biopsy
studies do not show any detrimental structural effects within the nasal mucosa
with long-term administration of intranasal corticosteroids. Much attention has
focused on the systemic safety of intranasal application. When administered at
standard recommended therapeutic dosage, the intranasal antihistamines do not
cause significant sedation or impairment of psychomotor function, effects that
would be evident when these agents are administered orally at a therapeutically
relevant dosage. The systemic bioavailability of intranasal corticosteroids
varies from <1% to up to 40-50% and influences the risk of systemic adverse
effects. Because the dose delivered topically is small, this is not a major
consideration, and extensive studies have not identified significant effects on
the hypothalamic-pituitary-adrenal axis with continued treatment. A small effect 
on growth has been reported in one study in children receiving a standard dosage 
over 1 year, however. This has not been found in prospective studies with the
intranasal corticosteroids that have low systemic bioavailability and therefore
the judicious choice of intranasal formulation, particularly if there is
concurrent corticosteroid inhalation for asthma, is prudent. There is no evidence
that such considerations are relevant to shorter-term use, such as in
intermittent or seasonal disease. Intranasal therapy, which represents a major
mode of drug delivery in allergic rhinitis, thus has a very favourable
benefit/risk ratio and is the preferred route of administration for
corticosteroids in the treatment of this disease, as well as an important option 
for antihistaminic therapy, particularly if rapid symptom relief is required.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12959630 [PubMed - indexed for MEDLINE]

1048: Otolaryngol Head Neck Surg. 2003 Sep;129(3):199-203.

The effects of montelukast on intradermal wheal and flare.

Hill SL 3rd, Krouse JH.

Department of Otolaryngology-Head and Neck Surgery, Wayne State University,
Detroit, Michigan 48201, USA.

OBJECTIVE: We sought to determine the effect of montelukast, a leukotriene
receptor antagonist, on intradermal skin testing.Study design and setting We
conducted a prospective, randomized, double-blind, placebo-controlled study in a 
university setting. METHODS: After a 1-week washout of allergy pharmacotherapy,
intradermal skin testing was performed on 23 atopic subjects. Whealing size was
measured 20 minutes after injection. Subjects then began a 1-week regimen of
daily loratadine, montelukast, or placebo. At 1 week, subjects again underwent
intradermal skin testing. The change in wheal size was then calculated from
baseline. RESULTS: A significant difference (P < 0.05) between the montelukast
and loratadine groups in suppression of intradermal whealing at 1 week was
observed. No significant difference was noted between the montelukast and placebo
subjects. CONCLUSIONS: Montelukast demonstrated no significant suppression of
skin whealing after antigen challenge over placebo. SIGNIFICANCE: Montelukast
does not need to be discontinued before intradermal allergy testing.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12958567 [PubMed - indexed for MEDLINE]

1049: Ann Allergy Asthma Immunol. 2003 Aug;91(2):205-11.

Comment in:
    Ann Allergy Asthma Immunol. 2004 Jul;93(1):104; author reply 104.

Efficacy of azelastine nasal spray in patients with an unsatisfactory response to
loratadine.

Berger WE, White MV; Rhinitis Study Group.

Southern California Research Center, Mission Viejo, California 92691, USA.
weberger@uci.edu

OBJECTIVE: To evaluate the effectiveness and safety of azelastine nasal spray,
desloratadine, and the combination of azelastine nasal spray plus loratadine
compared with placebo in patients with seasonal allergic rhinitis who had an
unsatisfactory response to loratadine. METHODS: This was a 2-week, multicenter,
placebo-controlled, randomized, double-blind study in patients with
moderate-to-severe symptoms of seasonal allergic rhinitis. Following a 1-week,
open-label lead-in period, during which the patients received loratadine 10 mg
daily, those patients who met the symptom qualification criteria (<25% to 33%
improvement taking loratadine) were randomized to treatment with azelastine nasal
spray 2 sprays per nostril, twice daily, azelastine nasal spray 2 sprays per
nostril, twice daily, plus loratadine 10 mg daily, desloratadine 5 mg daily plus 
placebo (saline) nasal spray, or placebo (saline) nasal spray/placebo capsules.
The primary efficacy variable was the change from baseline to day 14 in the total
nasal symptom score, consisting of runny nose, sneezing, itchy nose, and nasal
congestion symptom scores recorded twice daily (AM and PM) in patient diary
cards. RESULTS: A total of 428 patients with an unsatisfactory response to
loratadine completed the double-blind treatment period. After 2 weeks of
treatment, azelastine nasal spray (P < 0.001), azelastine nasal spray plus
loratadine (P < 0.001), and desloratadine (P = 0.039) significantly improved the 
total nasal symptom score compared with placebo. CONCLUSIONS: Azelastine nasal
spray is an effective treatment for patients with seasonal allergic rhinitis who 
do not respond to loratadine and is an alternative to switching to another oral
antihistamine or to using multiple antihistamines.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12952117 [PubMed - indexed for MEDLINE]

1050: Chem Immunol Allergy. 2003;82:119-26.

The WHO ARIA (allergic rhinitis and its impact on asthma) initiative.

Bachert C, van Cauwenberge P.

Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium.
claus.bachert@rug.ac.be

The ARIA working group, in collaboration with the WHO in Geneva, recently
published a state-of-the-art review and recommendations derived from it on the
link between rhinitis and asthma. Rhinitis is the most frequent manifestation of 
allergic disease in humans and is often linked to other atopic diseases such as
food allergy, atopic dermatitis or asthma, and may furthermore have an impact on 
the sinuses. ARIA focuses on one of the most important of the mentioned issues,
the link between upper and lower airways in allergic disease. To facilitate
understanding between the otorhinolaryngologist and the pulmonologist, the
classification of rhinitis has been adapted to that of asthma, and the terms
'intermittent' and 'persistent' allergic rhinitis have been introduced. Elaborate
guidelines for the diagnosis and assessment of the severity of disease are
provided, and detailed recommendations for the management of rhinitis and asthma 
are suggested with a special focus on specific immunotherapy.

PMID: 12947998 [PubMed - indexed for MEDLINE]

1051: Chem Immunol Allergy. 2003;82:89-98.

Nasal application of immunotherapy.

Ascione E, De Lucia A, Imperiali M, Varricchio A, Motta G.

ENT Institute, Second University of Naples, Naples, Italy.

BACKGROUND: In patients with allergic rhinitis local nasal immunotherapy (LNIT)
appears to offer considerable advantages over other hyposensitization methods.
The aim of our study was to obtain further confirmation of the validity of LNIT. 
METHODS: A randomized, double-blind, placebo-controlled study of LNIT in patients
allergic to Parietaria and Dermathophagoides was performed. Patients were
evaluated, before and after treatment, with symptom and medication scores,
specific nasal provocation tests, anterior rhinomanometry and mucociliary
clearance time. RESULTS: Compared to placebo the clinical efficacy of LNIT was
confirmed by a reduction of clinical symptoms and drug intake. In the active
group the reduction of allergen-specific nasal reactivity was significant. No
local or systemic side effects were observed. CONCLUSIONS: The clinical efficacy 
of LNIT suggests that this therapy is effective in the prophylaxis of allergic
rhinitis. Finally, there is no conflict between LNIT and drug treatment.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12947995 [PubMed - indexed for MEDLINE]

1052: Clin Ther. 2003 Jul;25(7):1988-2005.

A placebo-controlled comparison of ketotifen fumarate and nedocromil sodium
ophthalmic solutions for the prevention of ocular itching with the conjunctival
allergen challenge model.

Greiner JV, Minno G.

Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
02114, USA. greiner@vision.eri.harvard.edu

BACKGROUND: Ketotifen fumarate 0.025% ophthalmic solution and nedocromil sodium
2.0% ophthalmic solution are 2 topical antiallergic medications with different
modes of action and efficacy profiles. Both solutions are indicated for ocular
itching associated with allergic conjunctivitis. OBJECTIVE: This study compared
the efficacy, safety, and comfort of ketotifen fumarate 0.025% ophthalmic
solution and nedocromil sodium 2.0% ophthalmic solution for the prevention of
ocular itching, using the conjunctival allergen challenge (CAC) model. METHODS:
This was a single-center, double-masked, contralateral, randomized, placebo- and 
active-controlled CAC clinical trial. Subjects aged >10 years with a history of
allergic hypersensitivity who responded to the CAC at screening visits 1 and 2
qualified for randomization at visit 3. At visit 3 (day 21) and visit 4 (day 35),
subjects received 1 of 3 treatments: ketotifen, nedocromil, or placebo
(artificial tears), randomized by eye. Allergen challenges were conducted at 5
minutes posttreatment dose (visit 3) and 12 hours posttreatment dose (visit 4).
At each visit, subjects evaluated their ocular itching every 30 seconds for 20
minutes. At visit 4, subjects evaluated the comfort of the medication immediately
after instillation, at 30 seconds after instillation, and at l, 2, 5, and 10
minutes after instillation. The subjects were also queried about overall eyedrop 
comfort by choosing from descriptive terms and about overall eyedrop preference
based on comfort and perceived efficacy. RESULTS: Eighty-five subjects were
screened for this study. Fifty-nine (28 males, 31 females; mean age, 38.7 years) 
qualified and were randomized to receive study medications. Ketotifen-treated
eyes experienced significantly less ocular itching induced by CAC than
nedocromil-treated eyes and those that received placebo at both the 5-minute and 
12-hour posttreatment allergen challenges (all P < 0.05). Nedocromil-treated eyes
showed no statistical or clinical differences from placebo at any time point.
Ketotifen-treated eyes showed no differences in comfort from those that received 
placebo but were significantly more comfortable than nedocromil-treated eyes at
1, 2, 5, and 10 minutes after instillation (all P < 0.05). On the basis of
comfort and subjective efficacy, 60% of subjects preferred ketotifen, 21%
preferred nedocromil, and 19% preferred placebo. CONCLUSION: Ketotifen was
significantly more effective and comfortable than nedocromil at both 5 minutes
and 12 hours after administration in this CAC model.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12946546 [PubMed - indexed for MEDLINE]

1053: Clin Ther. 2003 Jul;25(7):1975-87.

Comparison of ketotifen fumarate ophthalmic solution alone, desloratadine alone, 
and their combination for inhibition of the signs and symptoms of seasonal
allergic rhinoconjunctivitis in the conjunctival allergen challenge model: a
double-masked, placebo- and active-controlled trial.

Crampton HJ.

Ophthalmic Research Associates, North Andover, Massachusetts, USA.

BACKGROUND: Ketotifen fumarate is a topical antiallergic combination mast-cell
stabilizer and antihistamine indicated for the temporary prevention of ocular
itching due to allergic conjunctivitis. Desloratadine is a systemic antihistamine
indicated for the treatment of seasonal and perennial allergic rhinitis.
OBJECTIVE: The purpose of this study was to compare the efficacy of ketotifen
0.025% ophthalmic solution instilled in the eye, desloratadine 5-mg tablets taken
orally, and their combination for prevention of the signs and symptoms of
allergic rhinoconjunctivitis, as induced by the conjunctival allergen challenge
(CAC) model. METHODS: This was a randomized, double-masked, placebo- and
active-controlled, single-center clinical trial. At visit l, the dose of allergen
necessary to elicit a qualifying allergic reaction was determined for subjects
meeting the entry criteria. At visit 2, the allergen dose determined at visit 1
was confirmed, and all subjects who had a qualifying ocular and nasal allergic
reaction were randomized to 1 of 3 treatment groups: ketotifen ophthalmic
solution and placebo tablet, desloratadine tablet and placebo eyedrop, or
ketotifen and desloratadine. Subjects were instructed to instill 1 drop into each
eye twice daily and take 1 tablet with water once daily at the same time as the
morning eyedrop for approximately 4 weeks. At visit 3, subjects brought in their 
medication and were given 1 drop of the eyedrop bilaterally and 1 tablet with
water. Bilateral CAC was performed 2 hours after administration of medication.
Using standardized scales, subjects rated ocular itching at 3, 5, and 7 minutes
after CAC; ocular tearing and eyelid swelling at 10, 15, and 20 minutes after
CAC; and nasal signs and symptoms (sneezing, rhinorrhea and postnasal drip,
pruritus, and nasal congestion) at 10, 20, 30, 40, and 50 minutes after CAC. The 
investigator graded ocular redness and chemosis at 10, 15, and 20 minutes after
CAC. At all visits, subjects were offered an anti-allergy eyedrop to relieve any 
immediate ocular discomfort caused by CAC. RESULTS: One hundred two subjects were
screened-82 (55 women, 27 men; mean age, 42.8 years [range, 21-70 years]) were
randomized to treatment, and 80 completed the study. Subjects in the group that
received ketotifen (n = 27) and the group that received ketotifen with
desloratadine (n = 26) had significantly lower mean itching scores compared with 
those in the group that received desloratadine alone (n = 27) at all time points 
(P </= 0.05). Total ocular redness, calculated by summing the mean redness scores
for each of the 3 vessel beds, was significantly lower in the ketotifen group
than in the other treatment groups at most time points (P </= 0.05). All
treatments attenuated nasal symptoms; no statistically significant differences
were noted between treatment groups, with the exception of the 50-minute time
point, at which combination treatment was significantly more effective than
ketotifen alone (P </= 0.05). The proportion of subjects who requested relief
drops after CAC was significantly lower in both the ketotifen alone and
combination treatment groups compared with the desloratadine alone group (P =
0.004). CONCLUSIONS: Ketotifen ophthalmic solution significantly decreased the
signs and symptoms of ocular and nasal allergic rhinoconjunctivitis. The addition
of ketotifen to the oral desloratadine regimen improved the overall antiallergic 
efficacy of both medications.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12946545 [PubMed - indexed for MEDLINE]

1054: Acta Clin Belg. 2003 May-Jun;58(3):178-82.

Is the prevalence of specific IgE to classical inhalant aeroallergens among
patients with respiratory allergy changing? Evidence from two surveys 15 years
apart.

Stevens WJ, Ebo DG, Hagendorens MM, Bridts CH, De Clerck LS.

Departement Immunologie, Allergologie en Reumatologie, Universiteit Antwerpen
(UA), Universiteitsplein 1, B 2610 Antwerpen, België. immuno@uia.ua.ac.be

OBJECTIVE: The aim of this study was to evaluate the relative frequencies of
sensitisation to four common inhalant allergens in two atopic populations
suffering from asthma and/or rhinitis. One had been studied in the period of 1975
till 1979, and a second population was evaluated between 1992 and 1995. DATA
SOURCES: At both time periods patients with inhalant allergy and visiting our
outpatient clinic were included. Quantification of IgE to Dermatophagoides
pteronyssinus, birch, timothy grass, and mugwort was performed via the Phadebas
RAST technique (Pharmacia, Brussels, Belgium). RESULTS: In patients suffering
from respiratory allergy the frequency of birch pollen sensitisation
significantly increased from 13% in the period 1975-1979 to 34% in the period
1992-1995. In contrast, the frequency of house dust mite, timothy grass pollen,
and mugwort pollen sensitisation remained almost unchanged. The increase was not 
associated with an increase in the birch pollen count. CONCLUSION: Birch pollen
hypersensitivity has almost tripled among atopic subjects during the last 2
decades. The exact mechanisms for this increase remain to be evaluated.

Publication Types: 
    Comparative Study

PMID: 12945477 [PubMed - indexed for MEDLINE]

1055: Drugs Today (Barc). 2003 Jun;39(6):451-68.

Rupatadine: a new selective histamine H1 receptor and platelet-activating factor 
(PAF) antagonist. A review of pharmacological profile and clinical management of 
allergic rhinitis.

Izquierdo I, Merlos M, García-Rafanell J.

Research and Development Scientific Area, J. Uriach and Cia., Barcelona, Spain.
clin-izquierdo@uriach.com

Rupatadine is a new agent for the management of diseases with allergic
inflammatory conditions, such as seasonal and perennial rhinitis. The
pharmacological profile of rupatadine offers particular benefits in terms of a
strong antagonist activity towards both histamine H1 receptors and
platelet-activating factor (PAF) receptors. Rupatadine has a rapid onset of
action, and its long-lasting effect (>24 h) permits once-daily dosing. Rupatadine
should not be used in combination with the cytochrome P450 inhibitors, such as
erythromycin or ketoconazole, due to an increase in AUC and Cmax for rupatadine, 
although no clinically relevant adverse events have been reported. In addition,
rupatadine, at the recommended dose of 10 mg, has been shown to be free of
sedative effects and not to cause significant changes in the corrected QT
interval in special populations, including the elderly, nor when coadministered
with erythromycin or ketoconazole. Preclinical data have also shown that
rupatadine and its main active metabolites did not interfere with cloned human
HERG channel and did not affect in vitro isolated dog Purkinje fibers at
concentrations at least 2000 times greater than those obtained with therapeutic
doses in humans. Rupatadine is clinically effective in relieving symptoms in
patients with seasonal and perennial allergic rhinitis. Newly published data on
its efficacy and safety suggest that this compound may improve the nasal and
non-nasal symptoms in comparison to other currently available second generation
H1 receptor antihistamines. 2003 Prous Science. All rights reserved.

Publication Types: 
    Comparative Study
    Review

PMID: 12944997 [PubMed - indexed for MEDLINE]

1056: Expert Opin Pharmacother. 2003 Sep;4(9):1579-91.

Features of mometasone furoate nasal spray and its utility in the management of
allergic rhinitis.

Schenkel E.

Valley Allergy and Asthma Treatment Center/Valley Clinical Research Center,
Easton, PA, USA. Eschenkelm@aol.com

Mometasone furoate aqueous nasal spray (NS; Nasonex, Schering Corporation), is a 
synthetic corticosteroid approved for the prophylaxis and treatment of seasonal
allergic rhinitis (SAR) and the treatment of perennial allergic rhinitis (PAR) in
patients >or= 12 years of age, and for the treatment of SAR and PAR in children
as young as 2 years of age. Studies demonstrate that mometasone furoate NS is a
potent, clinically effective and well-tolerated intranasal corticosteroid with
negligible systemic activity and which offers the convenience of once-daily
dosing.

Publication Types: 
    Review

PMID: 12943488 [PubMed - indexed for MEDLINE]

1057: J Investig Allergol Clin Immunol. 2002;12(4):263-71.

Immunotherapy with an extract of Olea europaea quantified in mass units.
Evaluation of the safety and efficacy after one year of treatment.

González P, Florido F, Sáenz de San Pedro B, de la Torre F, Rico P, Martín S.

Unidad de Alergia, Hospital General Ciudad de Jaén, Spain.

Sensitization to olive pollen is a frequent cause of rhinoconjunctivitis (RC) and
bronchial asthma (BA) in the region of Jaén (southern Spain), where this allergen
reaches atmospheric levels of almost 7000 grains/m3 during pollen season (May and
June) and produces high morbidity. Specific immunotherapy (SIT) has proven very
efficient in allergic RC and BA caused by grass pollen. Considering the
availability of a biologically standardized extract of Olea europaea, with its
major allergen quantified in mass units, we decided to investigate SIT with this 
extract in a group of rhinitic and/or asthmatic patients monosensitized to olive.
We studied tolerance, safety, and efficacy by comparison of the active group
(subjected to SIT) with a control group that did not receive SIT. A
hyposensitizing dose of Olea europaea extract was administered preseasonally,
establishing a maintenance dose 3.8 times higher than those administered in
conventional treatments. Eighty-three percent of the patients reached the
proposed maximal dose of 75 BU, equivalent to 45 micrograms Ole e 1, with a rate 
of 0.8% of systemic reactions. A significant decrease in cutaneous (p < 0.001)
and bronchial (p < 0.001) reactivity was observed in the active group, but not in
the control group. Also, a decrease in specific IgE and an increase in IgG1 and
IgG4 were found in the group of patients treated with SIT. Regarding clinical
evolution, the active group, but not the control group, experienced a clear
statistically significant improvement both in nasal (p < 0.05) and bronchial (p <
0.05) symptoms, in addition to a significant decrease in the consumption of
antihistamines (p < 0.05) and beta 2-agonists (p < 0.01). In conclusion, SIT with
olive extract proved to be safe and efficacious for the treatment of asthma and
rhinitis caused by this allergen.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12926186 [PubMed - indexed for MEDLINE]

1058: J Investig Allergol Clin Immunol. 2002;12(4):227-34.

Immunophenotypic characterization of peripheral B cells. During short-term
immunotherapy with tree pollen allergoid and the immunoadjuvant monophosphoryl
lipid A.

Röver AC, Reimann S, Zuberbier T, Worm M.

Department of Dermatology and Allergy, Charité, Humboldt University, Berlin.

The effects of immunotherapy (IT) on the activation and functions of B cells are 
not well described yet. We therefore measured the expression of several surface
markers on peripheral B cells during short-term IT. Twelve patients with seasonal
allergic rhinoconjunctivitis, sensitized to hazel, alder, and birch pollen proven
by positive history, skin test, sIgE, and nasal provocation test, were included
in the study. Eight patients received short-term IT with TA tree pollen and the
immunoadjuvant monophosphoryl Lipid A; 4 patients received a placebo suspension
containing 2% tyrosine. After separation of PBMCs, the expression of surface
molecules on peripheral B cells were analyzed by flow cytometry before the start 
of IT, before the 3rd injection, at the end of IT, and after the pollen season.
The expression of CD23, CD54, and HLA-DR-II on CD19+ B cells decreased during IT 
and then increased again after the pollen season. In the placebo group, the
expression of CD23, CD54, and HLA-DR-II remained unchanged during the first three
measurements. After the season, the expression of CD23, CD54 and HLA-DR-II
increased in both groups. CD86 expression was decreased during treatment in both 
groups. Although CD86 expression increased in both groups after the season, the
increase was more pronounced in the placebo group. No changes in the expression
of CD32, CD40, and HLA-ABC-I were registered during the study. The results show
that expression of CD23, CD54, and HLA-DR-II on peripheral B cells decreases
during IT, which indicates reduced B-cell activation. Whether these effects are a
result of direct allergen action on the B cells or whether they are mediated by T
cells and their clinical relevance remains to be elucidated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12926181 [PubMed - indexed for MEDLINE]

1059: J Otolaryngol. 2003 Jun;32(3):198-202.

Minnesota multiphasic personality inventory profile of patients with allergic
rhinitis.

Muluk NB, Oğuztürk O, Koç C, Ekici A.

Otolaryngology Department, Kirikkale University, Faculty of Medicine, Ankara,
Turkey.

The aim of this study was to investigate the relationship between allergic
rhinitis and personality traits in a nonpsychiatric population of proven allergic
status. Subjects were assigned to the allergic group (n = 29) and the nonallergic
group (n = 29) on the basis of the medical examination, allergic prick tests, and
self-reported allergic status. Analysis of Minnesota Multiphasic Personality
Inventory Profile (MMPI) profiles showed that male subjects with allergic
rhinitis had significantly higher scores on depression, paranoia, and social
introversion. Depression, hypochondriasis, and hysteria scores were significantly
higher in female subjects. It may be concluded that patients with allergic
rhinitis have poorer psychological function compared with the nonallergic
subjects.

PMID: 12921140 [PubMed - indexed for MEDLINE]

1060: BMC Fam Pract. 2003 Aug 13;4:10. Epub 2003 Aug 13.

Assessing satisfaction with desloratadine and fexofenadine in allergy patients
who report dissatisfaction with loratadine.

Glass DJ, Harper AS.

Zynx Life Sciences, Cerner Corporation, Beverly Hills, CA, USA. dglass@cerner.com

BACKGROUND: The FDA recently moved loratadine (Claritin) from prescription only
status to over-the-counter (OTC). In response to the availability of an OTC
non-sedating antihistamine, many managed care organizations are reevaluating
which if any prescription antihistamines should remain on formulary. From a
managed care perspective, determining which of the remaining prescription
antihistamines results in the greatest patient satisfaction with allergy
treatment would be informative. METHODS: We report on a weighted cross sectional 
survey (n = 10,023) delivered online to a sample of allergy sufferers in the U.S.
during the month of December 2002. Two segments were identified for analysis:
patient who were dissatisfied with loratadine and converted to desloratadine
(Clarinex; n = 61), and patients who were dissatisfied with loratadine and
converted to fexofenadine (Allegra; n = 211). The two segments were compared
along a series of measures that the literature suggests are related to treatment 
satisfaction. RESULTS: The survey found that two of the satisfaction measures
differentiated desloratadine converters from fexofenadine converters (p <.05):
mean sum of self-reported adverse events and nighttime awakening due to allergy
symptoms. For the remainder of satisfaction measures though, patients who were
dissatisfied with loratadine reported equal duration of coverage and satisfaction
with desloratadine as fexofenadine. When severity of disease was controlled for
in the analysis, a pattern emerged suggesting greater levels of satisfaction
amongst loratadine dissatisfied patients who converted to desloratadine. Point
estimates suggest a consistent pattern favoring desloratadine patient
satisfaction, with statistically significant results reported for sum of adverse 
effects, nighttime awakening due to symptoms, symptom severity just prior to the 
next dose, and overall satisfaction (p < 0.05). CONCLUSIONS: On average, patients
who were dissatisfied with loratadine reported equal or better satisfaction with 
desloratadine as fexofenadine. Patients with severe allergic rhinitis reported
greater satisfaction when converted from loratadine to desloratadine than
fexofenadine for select satisfaction measures. These results suggest that if
managed care intends to position prescription antihistamines as second line for
OTC loratadine treatment dissatisfaction, desloratadine is a useful treatment
alternative. These findings, while informative to formulary decision-makers, must
be interpreted with caution. Only through head-to-head controlled clinical trials
can differences in efficacy and safety be established.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12917016 [PubMed - indexed for MEDLINE]

1061: Clin Exp Allergy. 2003 Aug;33(8):1153-8.

In vitro and in vivo allergenicity of recombinant Bet v 1 compared to the
reactivity of natural birch pollen extract.

Tresch S, Holzmann D, Baumann S, Blaser K, Wüthrich B, Crameri R,
Schmid-Grendelmeier P.

Allergy Unit, Department of Dermatology, University Hospital of Zürich, Zürich,
Switzerland.

BACKGROUND : Diagnostic procedures using natural extracts show only limited
quantitative correlation between in vivo and in vitro results. Highly pure
recombinant allergens might show more predictive findings. OBJECTIVE : The aim of
this study was to compare natural birch pollen extract (BPE) and recombinant
Betula verrucosa (rBet v 1) for their diagnostic value comparing skin prick tests
(SPTS) and nasal provocation tests (NPTS) with specific IgE in the serum. METHODS
: Thirty-four patients allergic to birch pollen and five healthy controls were
investigated. SPT and NPT were performed with BPE and rBet v 1 at different
concentrations. Specific serum IgE was measured by the Pharmacia CAP system.
RESULTS : Commercial BPE and rBet v 1 (10 micro g/mL) were able to elicit similar
allergenic reactions in vivo and IgE binding in vitro. SPT reflects
immediate-type allergy as determined by NPT to a higher degree than specific IgE,
for both reagents. To cause allergic reactions in NPT, higher amounts of rBet v 1
were needed than for skin tests and the sensitivity was lower than with BPE.
CONCLUSION : rBet v 1 alone is sufficient for a reliable diagnosis of birch
pollen allergy in most patients and induces comparable skin test reactivity as
BPE, but less allergic reactions in nasal provocations.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12911792 [PubMed - indexed for MEDLINE]

1062: Clin Exp Allergy. 2003 Aug;33(8):1141-6.

Increased expression of surface activation markers on neutrophils following
migration into the nasal lumen.

Kinhult J, Egesten A, Benson M, Uddman R, Cardell LO.

Laboratory for Clinical and Experimental Allergy Research, Department of
Otorhinolaryngology Department of Medical Microbiology, Malmö University
Hospital, Malmö, Sweden.

BACKGROUND : The sequence of events following the recruitment of a free-flowing
neutrophil in the peripheral circulation, via adhesion, migration and release of 
mediators, to a neutrophil on the surface of the nasal epithelium is a
co-ordinated process. Little is known about the state of neutrophil activation
following this course of events. OBJECTIVES : To investigate the expression of
surface activation markers on neutrophils, reflecting activation during their
recruitment to the nose, and to see whether the inflammatory process during
allergic rhinitis influences this process. METHOD : Nine healthy controls and 12 
patients with grass pollen-induced intermittent allergic rhinitis were
investigated during the peak of the pollen season. The expression of CD11b, CD66b
and CD63 on the neutrophil cell surface, as a reflection of activation, was
analysed using flow cytometry. Neutrophils were derived from peripheral blood and
nasal lavage fluid. In addition, eosinophil cationic protein (ECP) and
myeloperoxidase (MPO) as well as L-, P- and E-selectins in the nasal lavage fluid
were analysed using RIA and ELISA, respectively. RESULTS : A marked increase in
the expression of all three CD markers on the neutrophil cell surface was noticed
following migration from the bloodstream to the surface of the nasal mucosa. At
the peak of the grass pollen season, the MPO levels increased, reflecting an
increase in the total number of nasal fluid neutrophils. In parallel, the
expression of CD11b was further augmented. The expression of the CDb11b was
reduced on neutrophils remaining in the circulation. In addition, the level of
L-selectin was reduced on neutrophils derived from the blood during allergic
inflammation. CONCLUSION : Neutrophils might become activated during their
transfer from the blood to the surface of the nasal mucosa, but these changes may
also be due to depletion of activated neutrophils in the blood via activated
endothelial/epithelial adhesion and chemoattractant measures. The increased
expression of surface activation markers during allergic rhinitis suggests roles 
for neutrophils in the inflammatory process.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12911790 [PubMed - indexed for MEDLINE]

1063: Expert Rev Vaccines. 2003 Feb;2(1):85-97.

Immunological mechanisms of specific immunotherapy with pollen vaccines:
implications for diagnostics and the development of improved vaccination
strategies.

Movérare R.

Pharmacia Diagnostics AB, Research and Development, Uppsala, Sweden.
robert.moverare@pharmacia.com

This review deals with specific immunotherapy performed with pollen vaccines.
Pollen allergens, the immunological mechanism of allergic inflammation and the
mechanisms behind successful specific immunotherapy treatment of seasonal pollen 
allergy shall be discussed. The different approaches to develop improved regimes 
for specific immunotherapy based on new diagnostic tools, improved pollen
vaccines and alternative routes for administration of the vaccines will be
highlighted. Diagnostic tools to select patients for specific immunotherapy and
for monitoring the treatment are quantitative measurements of allergen-specific
immunoglobulin E, G and G4 antibodies and component-resolved diagnostics based on
immunoglobulin E binding to individual allergenic components. Future pollen
vaccines may consist of hypoallergenic recombinant allergens and T-helper cell
type 1-inducing immunostimulatory adjuvants. Both sublingual and nasal
administration of pollen vaccines for specific immunotherapy may be used more in 
future.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12901600 [PubMed - indexed for MEDLINE]

1064: Expert Rev Vaccines. 2003 Feb;2(1):75-84.

Genetic engineering of pollen allergens for hayfever immunotherapy.

Bhalla PL.

Plant and Molecular Biology and Biotechnology Laboratory, Institute of Land and
Food Resources, The University of Melbourne, Parkville, Victoria, Australia.
premlb@unimelb.edu.au

Type I allergy is an immunoglobulin E-mediated disease, representing a major
health problem affecting more than 25% of the world's population. Grass, birch
and ragweed pollen are a major source of environmental allergen. Specific
immunotherapy is clinically proven to be an effective treatment for allergic
conditions that involve the administration of crude extracts prepared from
natural sources with potential life-threatening anaphylactic side effects. Recent
developments in the molecular biology of pollen allergens have made it possible
to design novel therapeutic approaches for improved and safer forms of specific
immunotherapy. Hypoallergenic forms of major allergens with reduced
immunoglobulin E epitopes have been produced using genetic engineering, whilst
preserving other characteristics of the molecule that are able to induce a
protective response. These modified forms are expected to make allergen-specific 
immunotherapy more widely used.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12901599 [PubMed - indexed for MEDLINE]

1065: J Allergy Clin Immunol. 2003 Aug;112(2):289-300.

Comment in:
    J Allergy Clin Immunol. 2003 Aug;112(2):263-4.

Pet-keeping in childhood and adult asthma and hay fever: European community
respiratory health survey.

Svanes C, Heinrich J, Jarvis D, Chinn S, Omenaas E, Gulsvik A, Künzli N, Burney
P.

Section of Respiratory Medicine, Institute of Medicine, University of Bergen and 
Department of Medicine, Haraldsplass Hospital, Bergen, Norway.

BACKGROUND: Whether pet-keeping early in life protects against or promotes
allergy remains unclear. OBJECTIVE: Our aim was to examine the effects of
childhood pet-keeping on adult allergic disease in a large international
population-based study, including information on sensitization, adult
pet-keeping, and pet prevalence in the populations. METHODS: We used information 
from structured interviews (n = 18,530) and specific IgE to common aeroallergens 
in blood samples (n = 13,932) from participants in the European Community
Respiratory Health Survey (ECRHS) to analyze the associations between keeping
pets and adult asthma and hay fever. RESULTS: Keeping cats in childhood was
associated with asthma only among atopic subjects, an association that varied
between centers (P =.002) and was stronger where cats where less common (< 40%
cats: odds ratio(wheeze) [OR(wheeze)] = 1.84, 95% CI = 1.31-2.57; 40%-60% cats:
OR(wheeze) = 1.33, 95% CI = 1.10-1.61; > or =60% cats: OR(wheeze) = 0.98, 95% CI 
= 0.73-1.33). Dogs owned in childhood or adulthood were associated with asthma
among nonatopic subjects (childhood: OR(wheeze) = 1.28, 95% CI = 1.13-1.46;
adulthood: OR(wheeze) = 1.31, 95% CI = 1.14-1.51; both: OR(wheeze) = 1.69, 95% CI
= 1.40-2.04). In atopic subjects, those who had owned dogs in childhood had less 
hay fever (OR = 0.85; 95% CI = 0.73-0.98) and no increased risk of asthma
(OR(wheeze) = 1.01, 95% CI = 0.87-1.17). Respiratory symptoms were more common in
subjects who had owned birds during childhood (OR(wheeze) = 1.12; 95% CI =
1.02-1.23) independent of sensitization. CONCLUSIONS: The effects of pet-keeping 
in childhood varied according to the type of pet, the allergic sensitization of
the individual, and the wider environmental exposure to allergen. Cats owned in
childhood were associated with more asthma in sensitized adults who grew up in
areas with a low community prevalence of cats. Dogs owned in childhood seemed to 
protect against adult allergic disease but promote nonallergic asthma.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12897734 [PubMed - indexed for MEDLINE]

1066: J Allergy Clin Immunol. 2003 Aug;112(2):252-62.

Allergic and nonallergic forms of atopic diseases.

Novak N, Bieber T.

Department of Dermatology, University of Bonn, Bonn, Germany.

Atopic dermatitis, allergic rhinitis, and asthma are atopic diseases that develop
on a complex genetic background, the so-called atopic diathesis. Although they
target different organs, in most patients they are characterized by the presence 
of elevated total serum IgE levels. However, a subgroup of atopic patients
exhibits normal IgE levels and mechanisms contributing to the so-called
"intrinsic" or "nonallergic form" have been the matter of intensive research work
in the last years. Because of the rapid advancements in the research field of
atopic diseases, it now becomes possible for the first time to delineate a new
disease classification of allergic and nonallergic subtypes of atopic diseases,
thereby bringing hope to the clinician for a more specific treatment approach for
each subgroup of these patients.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12897728 [PubMed - indexed for MEDLINE]

1067: BMJ. 2003 Aug 2;327(7409):251-4.

Comment in:
    BMJ. 2003 Nov 22;327(7425):1229.    BMJ. 2003 Nov 22;327(7425):1229.

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis:
double blind randomised controlled study.

Radcliffe MJ, Lewith GT, Turner RG, Prescott P, Church MK, Holgate ST.

School of Medicine, Infection Inflammation and Repair Research Division,
University of Southampton, Southampton General Hospital, Southampton SO16 6YD.
michael@radcliffe.net

OBJECTIVE: To assess the efficacy of enzyme potentiated desensitisation in the
treatment of severe summer hay fever poorly controlled by pharmacotherapy.
DESIGN: Double blind randomised placebo controlled parallel group study. SETTING:
Hospital in Hampshire. PARTICIPANTS: 183 participants aged between 18 and 64 with
a history of severe summer hay fever for at least two years; all were skin prick 
test positive to timothy grass pollen. 90 randomised to active treatment; 93
randomised to placebo. INTERVENTIONS: Active treatment: two injections of enzyme 
potentiated desensitisation, given between eight and 11 weeks apart, each
comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50
ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for
trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust
and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two 
injections of 0.05 ml buffered saline solution. MAIN OUTCOME MEASURES: Proportion
of problem-free days; global rhinoconjunctivitis quality of life scores assessed 
weekly during pollen season. RESULTS: The active treatment group and the placebo 
group did not differ in the proportion of problem-free days, quality of life
scores, symptom severity scores, change in quantitative skin prick provocation
threshold, or change in conjunctival provocation threshold. No clinically
significant adverse reactions occurred. CONCLUSIONS: Enzyme potentiated
desensitisation showed no treatment effect in this study.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12896934 [PubMed - indexed for MEDLINE]

1068: Ann Allergy Asthma Immunol. 2003 Jul;91(1):44-8.

Fluticasone propionate aqueous nasal spray improves nasal symptoms of seasonal
allergic rhinitis when used as needed (prn).

Dykewicz MS, Kaiser HB, Nathan RA, Goode-Sellers S, Cook CK, Witham LA, Philpot
EE, Rickard K.

Division of Allergy and Immunology, Department of Internal Medicine, St. Louis
University School of Medicine, St. Louis, Missouri 63104-1028, USA.
dykewicz@slu.edu

BACKGROUND: Few published clinical trials document the efficacy of intranasal
corticosteroids used as needed for treatment of seasonal allergic rhinitis.
OBJECTIVE: To evaluate the efficacy and safety of 4 weeks' treatment with
fluticasone propionate aqueous nasal spray 200 microg used as needed (FP200PRN)
in patients with seasonal allergic rhinitis. METHODS: A randomized, double-blind,
placebo-controlled study in 241 patients (> or = 12 years of age) with a positive
skin test result to a relevant fall allergen and who were symptomatic at
randomization. The primary endpoint was the mean change from baseline in total
nasal symptom score (TNSS; the sum of nasal congestion, rhinorrhea, sneezing, and
nasal itching, each rated on a 4-point scale from 0 = none to 3 = severe).
RESULTS: The mean percentage of days that patients used the study medications in 
the FP200PRN and placebo groups was 61.8% (SD = 30.4%) and 70.1% (SD = 28.3%),
respectively. Patients treated with FP200PRN had a significantly greater
reduction from baseline in TNSS compared with those treated with vehicle placebo 
(mean +/- SE = -2.02 +/- 0.18 vs -1.06 +/- 0.22, P < 0.001), representing a 91%
greater improvement with FP200PRN than vehicle placebo. The FP200PRN group also
had a significantly greater (P < 0.001) mean reduction in individual nasal
symptoms of rhinorrhea, sneezing, nasal itching, and nasal congestion compared
with placebo. FP200PRN was well tolerated, with an incidence of adverse events
comparable to vehicle placebo. CONCLUSIONS: FP200PRN in patients 12 years and
older is effective for treatment of nasal symptoms associated with seasonal
allergic rhinitis. It has a lower incidence of adverse events than typically
associated with regular once-daily use.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12877448 [PubMed - indexed for MEDLINE]

1069: Eur Ann Allergy Clin Immunol. 2003 Jun;35(6):204-7.

Prevalence and treatment of allergic rhinitis in Italian conscripts.

Cirillo I, Vizzaccaro A, Tosca MA, Milanese M, Ciprandi G.

I Medicine, Navy Hospital, La Spezia, Allergy & ENT Unit, Head-Neck Department,
San Martino Hospital, Genoa, Italy.

BACKGROUND: Previous surveys on Italian conscripts showed a low prevalence of
allergic rhinitis. This study investigated the prevalence and the treatment of
allergic rhinitis in the "conscript model" during a four-year period (1999-2002).
METHODS: 28,327 18-year old males were screened and referred to La Spezia
Military Navy Hospital for call-up visit. Detailed history, clinical examination,
skin prick test, spirometry, and metacholine challenge were performed in subjects
with suspected diagnosis of respiratory allergy. RESULTS: Allergic rhinitis was
diagnosed in 2,876 conscripts (10.15%). Most of them showed an association with
asthma (67.2%). Prevalence of allergic rhinitis increased five-fold in comparison
with a previous survey. Sneezing was the most common nasal symptom. The use of
antihistamines and intranasal corticosteroids increased significantly. However,
about one third of the rhinitis subjects did not receive any treatment at all.
CONCLUSIONS: Prevalence of allergic rhinitis in Italian conscripts has increased.
Treatment of allergic rhinitis was correctly based on antihistamines and
corticosteroids, but many rhinitis subjects remained still untreated.

PMID: 12872678 [PubMed - indexed for MEDLINE]

1070: Otolaryngol Head Neck Surg. 2003 Jul;129(1):16-23.

Triamcinolone acetonide aqueous nasal spray and fluticasone propionate are
equally effective for relief of nasal symptoms in patients with seasonal allergic
rhinitis.

Berger WE, Kaiser H, Gawchik SM, Tillinghast J, Woodworth TH, Dupclay L, Georges 
GC.

Southern California Research, Mission Viejo, USA. weberger@uci.edu

OBJECTIVE: We compared 220 microg daily intranasal aqueous triamcinolone
acetonide (TAA AQ) with 200 microg daily fluticasone propionate (FP) for relief
of seasonal allergic rhinitis symptoms.Study design and setting Randomized,
parallel-group, investigator-blind study included patients with symptomatic
seasonal allergic rhinitis. After a baseline period, TAA AQ or FP was taken for
about 21 days. Nasal symptom (discharge, stuffiness, itching, sneezing) severity 
was recorded twice daily; total nasal symptom score was calculated.
Health-related quality of life was assessed by Rhinoconjunctivitis Quality of
Life Questionnaire. RESULTS: Reductions in individual symptoms and total nasal
symptom score were statistically significant versus baseline and were equivalent 
between treatments: -3.15 +/- 0.19 with TAA AQ (n = 148) and approximately 3.17
+/- 0.18 with FP (n = 147) (95% confidence interval for the difference, -0.7391
to 0.3693). Clinically and statistically significant improvements in
Rhinoconjunctivitis Quality of Life Questionnaire scores were comparable.
CONCLUSION: TAA AQ and FP were equally efficacious in relieving seasonal allergic
rhinitis symptoms and improving health-related quality of life. SIGNIFICANCE:
Differences in molecular potency of intranasal steroids do not confer differences
in efficacy.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12869911 [PubMed - indexed for MEDLINE]

1071: Allergy Asthma Proc. 2003 May-Jun;24(3):203-10.

A comparison of once-daily triamcinolone acetonide aqueous and twice-daily
beclomethasone dipropionate aqueous nasal sprays in the treatment of seasonal
allergic rhinitis.

Lumry W, Hampel F, LaForce C, Kiechel F, el-Akkad T, Murray JJ.

AARA Research Center, 9900 N. Central Expressway, Suite 525, Dallas, Texas 75231,
USA. LumryMD@aol.com

Ragweed pollen is the most frequent cause of allergic rhinitis in the late
summer-fall in North America. The objectives of this multicenter, randomized,
single-blind study are to assess the efficacy and safety of triamcinolone
acetonide aqueous (TAA AQ) and beclomethasone dipropionate aqueous (BDP) in the
treatment of adult patients with seasonal ragweed-induced allergic rhinitis.
Patient's self-assessment of comfort with medication and health-related quality
of life were also assessed. A total of 152 patients were randomized to treatment 
with TAA AQ 200 micrograms once daily in the morning (n = 75) or BDP twice-daily 
336 micrograms/day (n = 77). Both treatments were shown to be effective in
alleviating the symptoms of allergic rhinitis, with no significant differences
between the two treatments in mean reduction from baseline of nasal stuffiness,
discharge, nasal index (sum of discharge, stuffiness, and sneezing), itching, and
total eye symptoms. There were no significant differences between treatments in
quality of life scores. However, TAA AQ was described by patients as having a
better taste and smell than aqueous BDP (p < or = 0.05). Both treatments were
well tolerated and associated with a similar incidence of adverse events. These
results show that both once-daily TAA AQ 220 micrograms and twice-daily BDP 336
micrograms are well tolerated and effective in the treatment of seasonal allergic
rhinitis. In addition, both treatments are equally as effective at improving
patient health-related quality of life. However, patients preferred the odor and 
taste of TAA AQ over BDP. It is likely that once-daily dosing and patient
preference for the sensory attributes of TAA AQ may enhance treatment compliance.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12866325 [PubMed - indexed for MEDLINE]

1072: Ear Nose Throat J. 2003 Jun;82(6):438-40.

Nasopharyngeal carcinoma and nasal allergy: any correlation?

Prepageran N, Lingham OR, Krishnan G, Jalaludin MA, Raman R.

Department of Otolaryngology, University of Malaya Medical Center, 50603 Kuala
Lumpur, Malaysia. prepageran@yahoo.com

Although it has been observed that nasal allergy is rarely seen in patients who
have nasopharyngeal carcinoma, to our knowledge, no actual study of such a lack
of association has been previously reported. To fill this void, we conducted a
pilot study to investigate any such inverse relationship. We conducted skin-prick
allergen tests on 22 patients with newly diagnosed but not-yet-treated
nasopharyngeal carcinoma. Combining these test results with findings on the
history and clinical examination, we concluded that only one of the 22 cancer
patients (4.5%) had allergic rhinitis. Our study also confirmed the validity of
using findings on the history, clinical examination, and skin-prick testing as a 
reliable means of diagnosing allergic rhinitis.

PMID: 12861869 [PubMed - indexed for MEDLINE]

1073: Value Health. 2003 Jul-Aug;6(4):448-56.

Seasonal versus perennial allergic rhinitis: drug and medical resource use
patterns.

Crown WH, Olufade A, Smith MW, Nathan R.

Outcomes Research and Econometrics, The MEDSTAT Group, Cambridge, MA 02140, USA. 
bill.crown@medstat.com

BACKGROUND: There are no published studies that have compared the medical costs
of patients with seasonal and perennial allergic rhinitis symptomatology.
OBJECTIVES: The objectives of this study were to develop an algorithm for
classifying patients into seasonal and perennial groups based on their patterns
of allergy medication use and then compare the epidemiology and economics of the 
two groups. METHODS: Data for the study were obtained from the 1996 to 1998
MarketScan databases containing linked inpatient, outpatient, and pharmaceutical 
claims for approximately 2 million covered lives annually. Patients were
classified into seasonal allergic rhinitis (SAR) or perennial allergic rhinitis
(PAR) groups based on their pattern of allergy medication use over the course of 
1 year and then compared using descriptive methods. RESULTS: Seventy-nine percent
of the total study sample (80534 allergy patients) was classified as SAR and 21% 
as PAR. PAR patients were found to have higher mean levels of allergy-related
outpatient payments (US dollars 568 vs. US dollars 471) and higher mean costs for
second-generation antihistamines (US dollars 552 vs. US dollars 162). PAR
patients also had higher levels of comorbidities (asthma, sinusitis, depression, 
and migraine), higher numbers of concomitant medications (multiple
second-generation antihistamines, nasal steroids, other antihistamines, asthma
medications, and ophthalmic decongestants), and more immunization encounters.
CONCLUSIONS: Approximately 21% of allergic rhinitis patients have perennial
symptoms as reflected in their patterns of medication use. Perennial patients
have significantly higher allergy-related health-care costs and rates of
comorbidities and greater use of concomitant medications. These distinct clinical
and resource use profiles may have implications for therapy choices in the
cost-effective management of perennial allergic rhinitis patients.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12859586 [PubMed - indexed for MEDLINE]

1074: Allergy. 2003 Aug;58(8):795-801.

The effect of recombinant interleukin-8 on eosinophils' and neutrophils'
migration in vivo and in vitro.

Bocheńska-Marciniak M, Kupczyk M, Górski P, Kuna P.

Department of Pneumonology and Allergology, Medical University of Lodz, Lodz,
Poland.

BACKGROUND: Interleukin-8 (IL-8) is a chemokine that causes chemotaxis of
neutrophils, eosinophils and lymphocytes in vitro; however, its role as a
chemoattractant in allergic inflammation is unclear. The objective of this study 
was to investigate the effect of nasal instillation of IL-8 on the influx of
inflammatory cells. METHODS: Twelve patients suffering from seasonal allergic
rhinitis hypersensitive to grass pollens, with average age 30.1 +/- 2.67 years
were challenged both with diluent for IL-8 and IL-8 on a subsequent day, in two
phases: before the pollen season (unprimed mucosa) and during the season (primed 
mucosa). The number of neutrophils, eosinophils and myeloperoxydase (MPO) levels 
in the nasal fluid collected after IL-8 or placebo challenge were determined.
RESULTS: Challenge with IL-8 of primed nasal mucosa induced a significant influx 
of neutrophils (29 x 10(4) cells/ml at 0.5 h, 251 x 10(4) at 2 h and 334 x 10(4) 
at 3 h). Number of eosinophils in comparison with diluent challenge was not
significant. There was no difference in MPO levels in the nasal lavage between
IL-8 and diluent challenge of unprimed and primed mucosa. We did not find the
relationship between MPO levels and the neutrophils number in the lavage (rank
Spearman factor, RS = 0.258, P = 0.42). CONCLUSION: We have demonstrated that
IL-8 causes influx of neutrophils but not eosinophils into nasal mucosa in vivo. 
MPO level seems to be of little value as a marker of neutrophil influx into nasal
mucosa.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12859561 [PubMed - indexed for MEDLINE]

1075: Allergy. 2003 Aug;58(8):767-71.

Subjects with allergic rhinitis show signs of more severely impaired paranasal
sinus functioning during viral colds than nonallergic subjects.

Alho OP, Karttunen TJ, Karttunen R, Tuokko H, Koskela M, Suramo I, Uhari M.

Department of Otorhinolaryngology, University of Oulu, Finland.

BACKGROUND: Viral cold is thought to be the major contributing factor in the
pathogenesis of sinusitis, as it causes ostiomeatal obstruction. The aim was to
evaluate whether paranasal sinus functioning during viral colds is similar in
subjects with and without allergic rhinitis. METHODS: Forty-eight volunteers were
examined during an early (2-4 days) natural cold and again 3 weeks later. The
examinations included computed tomography (CT) scans, nasal mucosal biopsies, and
viral and bacterial specimens. Subjects with positive skin prick tests and
persistent or intermittent rhinitis were considered to have allergic
immunoglobulin E (IgE)-mediated rhinitis. In addition, specific IgE antibodies to
staphylococcal enterotoxin B (SEB) were measured. RESULTS: Nine subjects (19%)
had allergic rhinitis. The allergic subjects were significantly more often IgE
sensitized to SEB than the nonallergic subjects (33%vs 3%, P = 0.02). Viral
etiology of the cold was identified in 32 (67%) subjects. The subjects with
allergic rhinitis had significantly higher CT scores compared with nonallergic
subjects during the colds (median (range) scores 16 (6-22) vs 6 (0-17), P =
0.004). In both groups, the median scores declined markedly during convalescence,
but the difference remained significant (P = 0.009). Among the allergic subjects,
those who were IgE sensitized to SEB tended to have the highest CT scores [median
(range) 16 (16-22)]. Total serum IgE and the nasal subepithelial eosinophil
counts correlated with the CT scores during the cold (rs = 0.38, P = 0.008 and rs
= 0.46, P = 0.001, respectively). CONCLUSIONS: Subjects with allergic
IgE-mediated rhinitis had more severe paranasal sinus changes in CT scans than
nonallergic subjects during viral colds. These changes indicate impaired sinus
functioning and may increase the risk of bacterial sinusitis.

PMID: 12859556 [PubMed - indexed for MEDLINE]

1076: Allergy. 2003 Aug;58(8):733-41.

Comment in:
    Allergy. 2003 Aug;58(8):724-6.

Implementation of guidelines for seasonal allergic rhinitis: a randomized
controlled trial.

Bousquet J, Lund VJ, van Cauwenberge P, Bremard-Oury C, Mounedji N, Stevens MT,
El-Akkad T.

Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Montpellier,
France.

BACKGROUND: Allergic rhinitis is a common disease altering quality of life. Its
treatment is well established and guidelines have been proposed. However, their
efficacy has never been tested. The aim of the study was to validate the
guidelines of the International Consensus on Rhinitis in the treatment of
seasonal allergic rhinitis. METHODS: A multicenter, multinational, open label,
parallel, randomized study compared two therapeutic strategies in seasonal
allergic rhinitis during a 3-week treatment. General practitioners were
randomized into two groups. In the first group of 224 patients, doctors followed 
guidelines from the International Consensus on Rhinitis. Depending on the
severity of nasal and ocular symptoms defined using visual analogue scales,
patients received ebastine (an oral antihistamine), triamcinolone acetonide (a
topical corticosteroid) and/or ophthalmic nedocromil sodium (a topical ocular
cromone). In the second group of 241 patients, general practitioners had a free
choice of treatment. The primary efficacy end points were quality of life
measured using the standardized rhinoconjunctivitis quality of life questionnaire
(RQLQ) and the symptom-medication scores assessed daily with an electronic dairy 
system. RESULTS: Adjusted mean total symptom scores over 21 days were 4.93 in the
guidelines strategy group compared with 7.48 in the free-choice treatment group
(P = 0.0001). Mean total scores in the RQLQ decreased by 2.19 in the guidelines
group compared with a decrease of 1.79 in the free-choice treatment group (P =
0.0001). At 21 days, the least square mean difference in improvement in overall
scores for RQLQ in the guidelines group compared with the free-choice treatment
group was 0.53, which was greater than the minimal important difference.
CONCLUSIONS: Patients with seasonal allergic rhinitis often present severe
symptoms which are not well recognized or controlled by physicians using their
own criteria of severity and treatment. Using a simple method for the evaluation 
of the severity and a simple therapeutic scheme based on International
Guidelines, patients with seasonal allergic rhinitis presented a significant
improvement by comparison with those receiving a non-standardized treatment.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12859551 [PubMed - indexed for MEDLINE]

1077: Allergy. 2003 Aug;58(8):691-706.

Links between rhinitis and asthma.

Bousquet J, Vignola AM, Demoly P.

Clinique des Maladies Respiratoires and INSERM U454, Hôpital Arnaud de
Villeneuve, CHU Montpellier, France.

There is compelling evidence of a close relationship between the upper and lower 
airways in asthma and rhinitis. Rhinitis is present in the majority of patients
with asthma, and a significant minority of patients with rhinitis have
concomitant asthma. Similarities between the two conditions occur in the nature
of the inflammation present in the target tissues. A common initiating step in
the inflammatory process of allergic airways disease is the presence of
immunoglobulin E providing an adaptor molecule between the offending allergen and
inflammatory cell activation and mediator release. Differences in the two
conditions arise largely from the structural differences between the nose and the
lungs. In an asthmatic, concomitant allergic rhinitis increases healthcare costs 
and further impairs quality of life. The presence of rhinitis should always be
investigated in children and young adults with asthma. Subjects with allergic
rhinitis have an increased risk of developing asthma and may form a suitable
population for secondary intervention to interrupt the 'allergic march'.

Publication Types: 
    Review

PMID: 12859545 [PubMed - indexed for MEDLINE]

1078: Clin Exp Allergy. 2003 Jul;33(7):882-6.

Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal
responsiveness in seasonal allergic rhinitis.

Lee DK, Carstairs IJ, Haggart K, Jackson CM, Currie GP, Lipworth BJ.

Asthma & Allergy Research Group, Ninewells Hospital & Medical School, University 
of Dundee, Dundee, Scotland, UK.

BACKGROUND: Butterbur (BB) or Petasites hybridus, a herbal remedy, exhibits in
vitro inhibition of cysteinyl leukotriene biosynthesis. However, no
placebo-controlled studies have been performed to evaluate the effectiveness of
BB on objective outcomes such as nasal provocation testing in seasonal allergic
rhinitis (SAR). METHODS: Twenty patients with grass-pollen-sensitized SAR were
randomized in a double-blind, cross-over manner to receive for 2 weeks either BB 
50 mg twice daily or placebo (PL) twice daily during the grass pollen season.
Nasal adenosine monophosphate (AMP) challenge (the primary outcome) was
administered as a single 400 mg/mL dose after each randomized treatment. RESULTS:
Spontaneous recovery following AMP challenge (area under the response time
profile curve as % x min+/-SEM) was significantly attenuated (P=0.028) with BB
(584+/-289) compared to PL (1438+/-240); mean difference: 854 (95% CI 95-1614),
and the maximum % peak nasal inspiratory flow reduction from baseline following
AMP challenge was significantly blunted (P=0.036) with BB (30+/-4) compared to PL
(43+/-5); mean difference: 13 (95% CI 1-25). CONCLUSIONS: BB exhibited protection
against AMP-induced nasal responsiveness during the grass pollen season in
sensitized patients. This is turn may explain its potential clinical efficacy in 
patients with SAR.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12859442 [PubMed - indexed for MEDLINE]

1079: Clin Exp Allergy. 2003 Jul;33(7):873-81.

Comment in:
    Clin Exp Allergy. 2003 Jul;33(7):855-8.

Monitoring of seasonal variability in bronchial hyper-responsiveness and sputum
cell counts in non-asthmatic subjects with rhinitis and effect of specific
immunotherapy.

Polosa R, Li Gotti F, Mangano G, Mastruzzo C, Pistorio MP, Crimi N.

Dipartimento di Medicina Interna e Specialistica, University of Catania, Catania,
Italy. rpolosa@hotmail.com

Bronchial hyper-responsiveness (BHR) is documented in a proportion of
non-asthmatic individuals with allergic rhinitis (NAAR) and reflects inflammatory
events in the lower airways. Natural exposure to allergens is known to modulate
BHR and the level of airway inflammation in asthma, but less consistently in
NAAR. Specific immunotherapy (SIT) attenuates symptoms possibly by reducing BHR
and airway inflammation. The influence of natural exposure to Parietaria pollen
on BHR and sputum cell counts of NAAR was investigated and the effect of
Parietaria SIT examined. Thirty NAAR, monosensitized to Parietaria judaica,
participated in a randomized, double-blind, placebo-controlled, parallel group
study of the effects of a Parietaria pollen vaccine on symptoms/medication score,
BHR to inhaled methacholine and adenosine 5'-monophosphate (AMP), and cell counts
in the sputum collected out of and during the pollen seasons for 36 months.
Seasonal variation in BHR to inhaled methacholine and AMP and changes in sputum
cell counts were documented. Changes were consistent for AMP, but not
methacholine, and invariably associated with modifications in sputum eosinophils 
and epithelial cells. The clinical efficacy of Parietaria SIT was associated with
a decline in the seasonal deterioration of BHR to AMP, whereas no significant
effect was observed on BHR to methacholine or sputum cell differentials.
Between-groups comparison of the seasonal changes in PC15 methacholine values and
sputum cell differentials calculated as the AUC were not statistically
significant, whereas a significant difference in PC15 AMP was demonstrated
throughout the study (P=0.029), the median (inter-quartile range) AUC values
being 2478.5 (1153.3-3600.0) and 1545.5 (755.3-1797.9) for the SIT- and
placebo-treated group, respectively. Bronchial airways of NAAR exhibit features
of active inflammation that deteriorate during natural allergen exposure,
particularly with regard to BHR to AMP. The clinical efficacy of Parietaria SIT
was exclusively associated with attenuation in seasonal worsening of PC15 AMP,
suggesting that AMP may be useful in monitoring changes in allergic inflammation 
of the airways.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12859441 [PubMed - indexed for MEDLINE]

1080: Respirology. 2003 Mar;8(1):69-76.

A relatively high prevalence and severity of asthma, allergic rhinitis and atopic
eczema in schoolchildren in the Sultanate of Oman.

Al-Riyami BM, Al-Rawas OA, Al-Riyami AA, Jasim LG, Mohammed AJ.

Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos
University, Muscat, Sultanate of Oman. bazdawi@squ.edu.om

OBJECTIVES: Although asthma, allergic rhinitis and eczema are among the most
common chronic diseases in children worldwide, there is very limited information 
about the burden of these conditions in Oman. The aim of this study was to
determine the prevalence and severity of symptoms of asthma, allergic rhinitis
and eczema in Omani schoolchildren using the International Study of Asthma and
Allergies in Childhood (ISAAC) Phase I questionnaire. METHODS: An Arabic version 
of the ISAAC Phase I questionnaire was completed by parents of 3893 children aged
6-7 years and self-completed by 3174 children aged 13-14 years, randomly selected
from a nationwide sample of public schools. RESULTS: The prevalence rates of
reported diagnoses of asthma, allergic rhinitis and eczema were higher in older
children (20.7%, 10.5% and 14.4% compared with 10.5%, 7.4% and 7.5%,
respectively, in young children). In young children, 277 were current wheezers
and of these 40.8% had sleep-disturbing wheeze at least once a week and 45.1% had
speech-limiting wheeze during the past year. Similarly, 283 older children were
current wheezers, and of these 30.0% had sleep-disturbing wheeze at least once a 
week and 37.5% had speech-limiting wheeze during the past year. Exercise-induced 
wheeze was higher in older children (19.2% vs 6.9%; P < 0.001). Allergic rhinitis
and eczema were also associated with significant sleep disturbance and limitation
of activity in both age groups. CONCLUSION: Allergic conditions in Omani
schoolchildren are common and associated with significant morbidity. Further
research is required to identify the local risk factors for allergy to allow
better understanding and management of these conditions.

Publication Types: 
    Comparative Study

PMID: 12856745 [PubMed - indexed for MEDLINE]

1081: Nurs Stand. 2003 Jun 18-24;17(40):47-52; quiz 54-5.

Comment in:
    Nurs Stand. 2003 Sep 17-23;18(1):20-1.

Management of allergic rhinitis.

Hopkinson K, Powell P.

Queens Medical Centre, Nottingham. kate.hopkinson@nottingham.ac.uk

Allergic rhinitis, including hay fever, can have a major effect on patients'
quality of life. This article outlines the assessment and management of this
common condition, which nurses are ideally placed to carry out.

Publication Types: 
    Review

PMID: 12854196 [PubMed - indexed for MEDLINE]

1082: Clin Ther. 2003 Mar;25(3):931-47.

A randomized, double-blind, parallel-group comparison of olopatadine 0.1%
ophthalmic solution versus placebo for controlling the signs and symptoms of
seasonal allergic conjunctivitis and rhinoconjunctivitis.

Abelson MB, Turner D.

Department of Ophthalmology, Harvard Medical School, Boston, USA.

BACKGROUND: The most common form of allergic ocular disease is seasonal allergic 
conjunctivitis, coinciding with the pollen season and generally associated with
rhinitis. Symptoms of allergic conjunctivitis include ocular itching, hyperemia, 
tearing, mucus production, foreign body sensation, chemosis, and lid edema.
Similarly, the primary symptoms of allergic rhinoconjunctivitis are nasal
itching, irritation, sneezing, watery rhinorrhea, and congestion combined with
ocular itching, tearing, and swelling. OBJECTIVE: This study compared olopatadine
0.1% ophthalmic solution with placebo eyedrops (over-the-counter artificial tear 
product), instilled in the eye, with regard to the prevention and relief of the
ocular and nasal symptoms of seasonal allergic conjunctivitis and
rhinoconjunctivitis. METHODS: This was a randomized, double-blind, parallel-group
study, conducted at 7 US centers, to instill either olopatadine 0.1% ophthalmic
solution or placebo eyedrops (artificial tears) in both eyes twice daily for 10
weeks. Patients were evaluated for efficacy (intent-to-treat) and safety. Only
patients with proven grass pollen allergy (dermal and conjunctival allergen
challenge tests) were selected; all patients were studied during the same period,
historically shown to be grass season; and grass pollen counts were obtained.
RESULTS: A total of 131 patients (64 olopatadine; 67 placebo) were assessed for
efficacy (intent-to-treat); 132 patients were assessed for safety. The mean (SD) 
age of participants was 38.53 (11.61) years (range, 18 to 87 years), and 58.0%
were women (76/131), with no significant differences between groups for age or
sex. In the olopatadine group, 1.6% of patients were black (1/64), compared with 
14.9% of the placebo group (10/67) (P = 0.005). Mean scores of ocular itching and
hyperemia were lower at all assessment times with olopatadine than placebo. The
difference was statistically significant (P < 0.05) for itching on days 7, 14,
35, 63, and 70, and for hyperemia on days 14, 28, 42, and 63, after correction
for multiplicity. Linear regression slopes predicting ocular itching and
hyperemia from the pollen count were significantly lower (P < 0.003 and P <
0.035, respectively) with olopatadine than with placebo. Similar results were
obtained for rhinorrhea, sneezing, and nasal itching (P < 0.006, P < 0.012, and P
< 0.034, respectively). With placebo, the proportion of patients with frequent
ocular itching and hyperemia increased as a function of pollen level; however,
with olopatadine, the proportions remained low and virtually constant.
CONCLUSION: In the population studied, olopatadine 0.1% ophthalmic solution
controlled ocular and nasal symptoms of allergic conjunctivitis and
rhinocojunctivitis and was well tolerated when administered twice daily for 10
weeks.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12852709 [PubMed - indexed for MEDLINE]

1083: J Allergy Clin Immunol. 2003 Jul;112(1):134-40.

TNF-alpha contributes to the development of allergic rhinitis in mice.

Iwasaki M, Saito K, Takemura M, Sekikawa K, Fujii H, Yamada Y, Wada H, Mizuta K, 
Seishima M, Ito Y.

Department of Otorhinolaryngology, Gifu University School of Medicine, Gifu.

BACKGROUND: Allergic rhinitis is an inflammation involving T(H)2-type cytokine
production, with pathologic eosinophil infiltration in the nasal mucosa. Although
TNF-alpha is thought to be a pro-inflammatory cytokine, the relationship between 
TNF-alpha and allergic rhinitis has not been clarified. OBJECTIVES: The role of
TNF-alpha in a murine model of ovalbumin (OVA)-sensitized allergic rhinitis was
investigated by using mice deficient in the gene encoding TNF-alpha
(TNF-alpha(-/-) mice). METHODS: Both wild-type (TNF-alpha(+/+)) and
TNF-alpha(-/-) mice were sensitized with OVA by means of intraperitoneal
injection. They were then challenged with intranasal OVA, and various allergic
responses were assessed. RESULTS: The production of OVA-specific IgE in the serum
(P <.05) and the frequency of sneezes (P <.05) and nasal rubs (P <.05) decreased 
significantly in TNF-alpha(-/-) mice after OVA sensitization compared with that
in TNF-alpha(+/+) mice (P <.05). The mRNA expression of IL-4, IL-10, and eotaxin 
in nasal mucosa in TNF-alpha(-/-) mice was also significantly suppressed compared
with that in TNF-alpha(+/+) mice after OVA sensitization (P <.05). Furthermore,
the expression of both endothelial-leukocyte adhesion molecule 1 and vascular
cell adhesion molecule 1 mRNA in the nasal mucosa was significantly suppressed (P
<.05), although intercellular adhesion molecule 1 mRNA expression did not
decrease significantly in TNF-alpha(-/-) mice compared with that in
TNF-alpha(+/+) mice after OVA sensitization. In addition, the effect of TNF-alpha
on endothelial-leukocyte adhesion molecule 1 and vascular cell adhesion molecule 
1 expression by means of Western blot analysis was compatible with the mRNA
results. Pathologically, eosinophil infiltration in nasal mucosa was
significantly restricted in TNF-alpha(-/-) mice compared with in TNF-alpha(+/+)
mice after OVA sensitization (P <.05). CONCLUSION: TNF-alpha is necessary for
antigen-specific IgE production and for the induction of T(H)2-type cytokines and
chemokines. Furthermore, TNF-alpha might be important for the expression of
adhesion molecules to recruit eosinophils to the allergic inflammatory site. We
conclude that the lack of TNF-alpha inhibited the development of allergic
rhinitis.

PMID: 12847490 [PubMed - indexed for MEDLINE]

1084: Curr Med Res Opin. 2003;19(4):313-20.

Comparison of the efficacy and tolerability of topically administered azelastine,
sodium cromoglycate and placebo in the treatment of seasonal allergic
conjunctivitis and rhino-conjunctivitis.

James IG, Campbell LM, Harrison JM, Fell PJ, Ellers-Lenz B, Petzold U.

Southbank Surgery, Glasgow, UK.

Objective and setting: Azelastine (AZE) in a novel, eye drop, formulation, was
compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in
the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a
multicentre, parallel group study. Research design: 144 subjects ranging in age
from 16 to 65 years participated. All had at least a 2-year history of seasonal
allergic conjunctivitis and were symptomatic at the time of inclusion.
Medications were administered topically either twice daily (AZE/PLA) or four
times daily (SCG) over a 2-week treatment period. Method and outcome measures:
Azelastine and placebo were compared double-blind; the comparison versus SCG was 
carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, 
foreign-body sensation, photophobia, soreness and discharge were scored on a
4-point severity scale. RESULTS: Results for the decrease of main conjunctivitis 
symptoms (itching, tearing and conjunctival redness) showed a marked effect for
both active treatments on day 3 with a sustained improvement on days 7 and 14. A 
clear response to treatment (an improvement of sum scores for day 3 of >/=3
points compared to baseline) occurred in 85.4% of azelastine-treated patients,
83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response
rates for both active treatments were statistically superior to those for placebo
(azelastine p = 0.005; sodium cromoglycate p = 0.007). Global assessment of
efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of
sodium cromoglycate patients and 66.3% of placebo-treated patients. The most
frequent adverse effects were transient application site reactions which tended
to disappear with increasing duration of treatment, and, less frequently, taste
perversion. CONCLUSION: The results of this study indicate that the therapeutic
use of azelastine eye drops in patients with seasonal allergic conjunctivitis or 
rhino-conjunctivitis can be recommended.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12841924 [PubMed - indexed for MEDLINE]

1085: Nurs Times. 2003 Jun 10-16;99(23):60-1.

Management of allergic rhinitis.

Walker S.

National Respiratory Training Centre, Warwick.

Rhinitis is characterised by the presence of two or more of the following
symptoms: nasal blockage, sneezing, rhinorrhoea (a persistent watery mucous
discharge from the nose) and nasal itching which last for an hour or more on most
days. Allergy is the commonest cause of chronic symptoms. Patients with allergic 
rhinitis often have a clear relationship between symptoms and allergen exposure, 
for example, during the tree/grass pollen season. Viral or bacterial infection is
the commonest acute cause of symptoms and is usually self-limiting.

Publication Types: 
    Review

PMID: 12838652 [PubMed - indexed for MEDLINE]

1086: Curr Opin Investig Drugs. 2003 May;4(5):603-7.

AIC. Dynavax.

Bohle B.

Department of Pathophysiology, Division of Immunopathology, University of Vienna,
AKH-EBO 3Q, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
barbara.bohle@akh-wien.ac.at

Dynavax is developing Amb a 1 immunostimulatory oligodeoxynucleotide-conjugate
(AIC) as a potential immunotherapy for ragweed-induced seasonal allergy. By May
2001, phase II/III trials were underway in Canada and the US, and by March 2002, 
phase II trials were underway in France. In October 2002, Dynavax expected to
commence a phase III trial in 2003.

Publication Types: 
    Review

PMID: 12833657 [PubMed - indexed for MEDLINE]

1087: Allergy. 2003 Jul;58(7):672-5.

Validation of the classification of ARIA (allergic rhinitis and its impact on
asthma).

Demoly P, Allaert FA, Lecasble M, Bousquet J; PRAGMA.

Unité d'Explorations des Allergies, Service des Maladies Respiratoires, INSERM,
Hôpital Arnaud de Villeneuve, Montpellier Cedex, France.

BACKGROUND: Allergic rhinitis is commonly divided into seasonal and perennial
rhinitis. The recent Allergic Rhinitis and its Impact on Asthma (ARIA) workshop
proposes to replace these terms by intermittent vs persistent rhinitis. METHODS: 
In order to test the new ARIA classification against the classical one used in
medical practice in France, we designed two cross-sectional surveys: (i) a spring
survey, where 1321 general practitioners enrolled 3026 patients consulting for
seasonal allergic rhinitis and (ii) an autumn-winter survey, where 1346 doctors
enrolled 3507 patients for perennial allergic rhinitis. Both doctors and patients
filled out a specific questionnaire on allergic rhinitis. RESULTS: Focusing on
the number of days per week and consecutive weeks per year, the patients
described the duration of their symptoms (based on an auto-questionnaire). About 
43.7% of the patients, classified by their doctor as seasonal, did in fact have
persistent rhinitis, whereas 44.6% classified as perennial had intermittent
rhinitis. CONCLUSIONS: The proposal of the ARIA expert panel defining the
chronology of allergic rhinitis as number of days per week and consecutive weeks 
per year is likely to change daily physician practice.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 12823130 [PubMed - indexed for MEDLINE]

1088: Br J Clin Pharmacol. 2003 Jun;55(6):639-42.

Erratum in:
    Br J Clin Pharmacol. 2004 Feb;57(2):227.

The effects of histamine and leukotriene receptor antagonism on nasal mannitol
challenge in allergic rhinitis.

Lee DK, Haggart K, Currie GP, Anderson SD, Lipworth BJ.

Asthma & Allergy Research Group, Department of Clinical Pharmacology and
Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Dundee
DD1 9SY, UK.

AIMS: It is unclear as to which mediators are involved in mediating the response 
to nasal mannitol challenge, a novel osmotic stimulus. METHODS: A double-blind,
randomized, placebo-controlled, crossover design was employed. Nine patients with
allergic rhinitis were randomized to receive a single-dose of desloratadine 5 mg,
montelukast 10 mg or placebo, and underwent nasal mannitol challenges with nasal 
peak inspiratory flow recordings over 60 min. The change in peak nasal
inspiratory flow was calculated as percentage change from baseline as the peak
response and area under the time-response curve (AUC). RESULTS: Desloratadine and
montelukast conferred a significant degree of protection compared to placebo for 
peak and AUC response, but there were no significant differences between the two 
drugs. For the peak response as percentage fall, the mean difference (95% CI) vs 
placebo was 27.7 (8.0, 47.4)% for desloratadine and 17.6 (1.9, 33.3)% for
montelukast. CONCLUSIONS: Our results suggest that histamine and
cysteinyl-leukotrienes are involved in mediating the response to nasal mannitol
in allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12814463 [PubMed - indexed for MEDLINE]

1089: Int Arch Allergy Immunol. 2003 Jun;131(2):111-8.

A double-blind placebo-controlled evaluation of sublingual immunotherapy with a
standardized ragweed extract in patients with seasonal rhinitis. Evidence for a
dose-response relationship.

André C, Perrin-Fayolle M, Grosclaude M, Couturier P, Basset D, Cornillon J,
Piperno D, Girodet B, Sanchez R, Vallon C, Bellier P, Nasr M.

Département Scientifique et Médical, Stallergènes S.A., Antony, France.
candre@stallergenes.fr

BACKGROUND: There is a growing consensus on the benefits of sublingual-swallow
immunotherapy in the treatment of allergic diseases. METHODS: This randomized,
double-blind placebo-controlled study was undertaken to assess the efficacy and
safety of sublingual immunotherapy with standardized ragweed pollen extract
tablets, in patients with an allergic rhinitis. A total of 110 outpatients were
randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable
for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a
28-day progression phase, the patients received a maintenance treatment during
6.5 months. Efficacy variables included a global assessment of efficacy (patient/
investigator), symptoms and medication scores as well as the frequency of asthma 
attacks. RESULTS: In the active treatment group, 43 patients completed the study,
versus 49 on placebo. During the whole period of pollination, the difference
favoring immunotherapy was highly significant for the global assessment by the
patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were
reported more often in the active treatment but mild or moderate, and they abated
after dose adjustment. A subgroup analysis of those patients receiving the
highest dose of immunotherapy (3 tablets 3 times a week) showed a highly
significant response for rhinitis and conjunctivitis total scores by comparison
to lower dosages. CONCLUSION: This study confirms the efficacy and safety of
sublingual immunotherapy and strongly suggests a dose-response relationship.
Copyright 2003 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12811019 [PubMed - indexed for MEDLINE]

1090: Cochrane Database Syst Rev. 2003;(2):CD002893.

Sublingual immunotherapy for allergic rhinitis.

Wilson DR, Torres LI, Durham SR.

Upper Respiratory Medicine, Imperial College School of Medicine at the National
Heart & Lung Institute, Dovehouse Street, London, UK, SW3 6LR. duncw
99@yahoo.co.uk

BACKGROUND: Allergic rhinitis is a common condition which, at its most severe,
can significantly impair quality of life despite optimal treatment with
antihistamines and topical nasal corticosteroids. Allergen injection
immunotherapy significantly reduces symptoms and medication requirements in
allergic rhinitis but its use is limited by the possibility of severe systemic
reactions. There has therefore been considerable interest in alternative routes
for delivery of allergen immunotherapy, particularly the sublingual route.
OBJECTIVES: To evaluate the efficacy of sublingual immunotherapy (SLIT), compared
with placebo, for reductions in symptoms and medication requirements. SEARCH
STRATEGY: The Cochrane Controlled Trials Register, MEDLINE (1966-2002), EMBASE
(1974-2002) and Scisearch were searched, up to September 2002, using the terms
(Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual).
SELECTION CRITERIA: All studies identified by the searches were assessed by the
reviewers to identify randomised controlled trials involving participants with
symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT 
or corresponding placebo. DATA COLLECTION AND ANALYSIS: Data from identified
studies were abstracted onto a standard extraction sheet and subsequently entered
into RevMan 4.1. Analysis was performed by the method of Standardised Mean
Differences (SMD) using a random effects model. P values <0.05 were considered
statistically significant. Subgroup analyses were performed according to the type
of allergen administered, the age of participants and the duration of treatment. 
MAIN RESULTS: Twenty two trials involving 979 patients were included. There were 
6 trials of SLIT for House Dust Mite allergy, 5 for Grass Pollen, 5 for
Parietaria, 2 for Olive and one each for, Ragweed, Cat, Tree and Cupressus. Four 
studies enrolled exclusively children. Seventeen studies administered the
allergen by sublingual drops subsequently swallowed, 3 by drops subsequently spat
out and 2 by sublingual tablets. Eight studies involved treatment for less than 6
months, 10 studies for 6-12 months and 4 studies for greater than 12 months. All 
included studies were double-blind placebo-controlled trials of parallel group
design. Concealment of treatment allocation was considered adequate in all
studies and the use of identical placebo preparations was almost universal. There
was significant heterogeneity, most likely due to widely differing scoring
systems between studies, for most comparisons. Overall there was a significant
reduction in both symptoms (SMD -0.34, 95% confidence interval -0.69 to -0.15;
p=0.002) and medication requirements (SMD -0.43 [-0.63, -0.23]; p=0.00003)
following immunotherapy. Subgroup analyses failed to identify a disproportionate 
benefit of treatment according to the allergen administered. There was no
significant reduction in symptoms and medication scores in those studies
involving only children but total numbers of participants were small, casting
doubt on the validity of the conclusion. Increasing duration of treatment does
not clearly increase efficacy. The total dose of allergen administered may be
important but insufficient data were available to analyse this factor. REVIEWER'S
CONCLUSIONS: SLIT is a safe treatment which significantly reduces symptoms and
medication requirements in allergic rhinitis. The size of this benefit compared
to that of other available therapies, particularly injection immunotherapy, is
not clear, having been assessed directly in very few studies. Further research is
required concentrating on optimising allergen dosage and patient selection.

Publication Types: 
    Meta-Analysis
    Review

PMID: 12804442 [PubMed - indexed for MEDLINE]

1091: Clin Exp Allergy. 2003 Jun;33(6):823-6.

Montelukast as an adjuvant to mainstay therapies in patients with seasonal
allergic rhinitis.

Topuz B, Ogmen GG.

Pamukkale University Medical Faculty, Otolaryngology Department, Denizli Turkey. 
obtopuz@yahoo.com

BACKGROUND: Drug selection for optimal treatment of allergic rhinitis may be
difficult and involve many diverse factors. OBJECTIVE: To evaluate montelukast,
in the treatment of patients with seasonal allergic rhinitis, as an adjuvant to
mainstay therapies, i.e., antihistamines and corticosteroids. METHODS: The study 
was a prospective, three-phased (per lasted 2 weeks) clinical trial. In phase I, 
patients were separated into two groups, based on the predominating symptoms: (1)
runners (patients with moderate to severe sneezing/itchy, watery nose/itchy,
watery eyes), and (2) blockers (patients with moderate to severe nasal
congestion). The runners received antihistamine loratidine 10 mg daily, and the
blockers received intranasal corticosteroid mometasone furoate 200 microg. In
phase II, if patients were dissatisfied with the initial treatment, they were
assigned to receive another study drug additionally. In phase III, for the
patients unsatisfied with the treatment of loratidine plus mometasone furoate,
montelukast 10 mg once daily was added. RESULTS: Of the 169 patients who entered 
phase I, 150 could be evaluated for treatment efficacy and safety. There were 108
runners and 42 blockers. Physicians' and patients' assessments indicated that in 
phase I 58 runners (60.0% of 50 runners) and 36 blockers (33.3% of six blockers) 
were satisfied with their therapy. In phase II, 30 runners (27.7%) and two
blockers (4.7%) were satisfied with the addition of other study drug. Totally
62.6% of patients were satisfied at the end of phase I, and 84.0% at the end of
phase II. Sixteen patients (66.6% of 24 patients) were satisfied with the
addition of montelukast to the previous two drugs (in total, 10.6% of patients). 
Fourteen patients (12.2%) treated with loratadine, and three patients (0.3%)
treated with mometasone, reported side-effect. CONCLUSION: The results of this
trial indicate that 10% of patients with seasonal allergic rhinitis may be
treated with the supplement of montelukast to mainstay therapy.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 12801319 [PubMed - indexed for MEDLINE]

1092: J Allergy Clin Immunol. 2003 Jun;111(6):1328-36.

Native Art v 1 and recombinant Art v 1 are able to induce humoral and T
cell-mediated in vitro and in vivo responses in mugwort allergy.

Schmid-Grendelmeier P, Holzmann D, Himly M, Weichel M, Tresch S, Rückert B, Menz 
G, Ferreira F, Blaser K, Wüthrich B, Crameri R.

Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.

BACKGROUND: Mugwort pollen is an important allergen source in hay fever and
pollen-related food allergy. Little is known about the clinical relevance of the 
major mugwort allergen Art v 1 and its importance in allergy. OBJECTIVE: In this 
study we aimed to investigate the allergenicity of mugwort extract compared with 
the allergenicity of native (n)Art v 1 and recombinant (r)Art v 1, one major
allergen of mugwort, in vivo and in vitro. METHODS: Thirty-two patients allergic 
to mugwort and 10 control subjects were investigated by means of skin prick and
nasal provocation testing with different concentrations of mugwort extract, nArt 
v 1, and rArt v 1. nArt v 1 was purified from aqueous mugwort extract, and rArt v
1 was cloned, expressed in Escherichia coli, and then purified. The in vitro
allergenicity was measured by means of ImmunoCAP, ELISA, ELISA-inhibition
experiments, and T-cell proliferation assays. RESULTS: nArt v 1 and rArt v 1 were
able to elicit positive in vivo and in vitro reactions. The IgE-binding capacity,
as determined by means of ELISA, was slightly higher for nArt v 1 than for rArt v
1, and both allergens were able to induce T-cell proliferation in sensitized
patients. However, rArt v 1 elicited a reduced response in skin and nasal
provocation tests compared with nArt v 1. Compared with mugwort extract, both
nArt v 1 and rArt v 1 showed lower sensitivity in patients with mugwort allergy
in vivo. CONCLUSIONS: Art v 1, either in its native or recombinant form, is able 
to induce allergic reactions in patients with mugwort allergy. rArt v 1 induced
comparable humoral and cell-mediated responses in vitro but showed reduced in
vivo allergenicity compared with biochemically purified nArt v 1.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12789236 [PubMed - indexed for MEDLINE]

1093: J Allergy Clin Immunol. 2003 Jun;111(6):1255-61.

Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy.

Francis JN, Till SJ, Durham SR.

Upper Respiratory Medicine, National Heart and Lung Institute, Imperial College, 
Dovehouse Street, London SW3 6LY, UK.

BACKGROUND: Immunotherapy involves the modulation of allergen-specific T-cell
responses, either T(H)2-to-T(H)1 immune deviation or, in bee venom-treated
patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing
CD4+CD25+ regulatory T cells have emerged as potential mediators of immune
tolerance in numerous murine models of immunopathology. OBJECTIVE: The aim of
this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in 
the response to grass pollen immunotherapy. METHODS: PBMCs were isolated from
patients after 1 year of grass pollen immunotherapy and from matched untreated
atopic and healthy control subjects. After 6 days of in vitro stimulation with
Phleum pratense, production of IL-10, IL-5, IL-4, and IFN-gamma and proliferation
and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for 
a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed
for intracellular IL-10 by means of flow cytometry. RESULTS: Patients undergoing 
immunotherapy produced significantly more IL-10 than atopic control subjects
(patients undergoing immunotherapy, 116 +/- 21 pg/mL [n = 11]; atopic patients,
30 +/- 5 pg/mL [n = 11]; P <.001), and the number of CD4+CD25+ cells identified
after allergen stimulation was also greater in the immunotherapy group. The
numbers of CD4+CD25+ T cells correlated positively with activation as measured by
proliferation in both of the control groups but not in the immunotherapy group.
Moreover, only T cells from patients undergoing immunotherapy were positive for
intracellular IL-10, and these were almost exclusively CD4+CD25+ cells.
CONCLUSION: Grass pollen immunotherapy results in a population of circulating T
cells that express the IL-10(+) CD4+CD25+ phenotype in response to allergen
restimulation.

Publication Types: 
    Clinical Trial

PMID: 12789226 [PubMed - indexed for MEDLINE]

1094: J Allergy Clin Immunol. 2003 Jun;111(6):1232-8.

Is the prevalence of adult asthma and allergic rhinitis still increasing? Results
of an Italian study.

Verlato G, Corsico A, Villani S, Cerveri I, Migliore E, Accordini S, Carolei A,
Piccioni P, Bugiani M, Lo Cascio V, Marinoni A, Poli A, de Marco R.

Unit of Epidemiology and Medical Statistics, Department of Medicine and Public
Health, Istituti Biologici 2, Strada le Grazie 8, 37134 University of Verona,
Verona, Italy.

BACKGROUND: The prevalence of asthma and allergic rhinitis has increased
worldwide during the 1970s and 1980s. OBJECTIVE: This study was aimed at
evaluating whether the increasing trend in prevalence persisted during the 1990s 
in the young adult Italian population. METHODS: In 1998 to 2000 a screening
questionnaire was sent by mail to a general population sample aged 20 to 44
years; nonresponders were contacted again first by mail and then by phone,
achieving a final response rate of 78.1% (6876 of 8800). Prevalence estimates,
adjusted to correct for nonresponse bias, were compared with those recorded in
Italy in 1991 to 1993 during the European Community Respiratory Health Survey,
when response rate had been slightly higher (87.6%). Temporal variations in
symptom prevalence were analyzed by a logistic regression model, controlling for 
sex, age, site of residence (urban vs suburban areas), season of response,
response rate, and type of contact (mail vs phone). RESULTS: The prevalence of
asthma attacks did not vary significantly from 1991 to 1993 (3.6%) to 1998 to
2000 (3.2%) (P =.188). The prevalence of asthma-like symptoms (wheezing, chest
tightness, shortness of breath) tended to decrease in the age classes of 32.5 to 
45 years, while increasing in the youngest age class (20 to 26 years). A
clear-cut increase from 15.4% to 18.3% was observed for the prevalence of
allergic rhinitis (P <.001), whereas the proportion of people under antiasthmatic
treatment increased in suburban areas but not in urban areas (interaction
time-site of residence, P <.001). CONCLUSION: Asthma prevalence has not increased
during the last decade in Italy. The persistence of an increasing trend in
allergic rhinitis prevalence deserves attention.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12789222 [PubMed - indexed for MEDLINE]

1095: J Allergy Clin Immunol. 2003 Jun;111(6):1171-83; quiz 1184.

Rhinitis and asthma: evidence for respiratory system integration.

Togias A.

Divisions of Clinical Immunology and Respiratory, Department of Medicine, Johns
Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD
21224, USA.

The vast majority of patients with asthma have rhinitis, and rhinitis is a major 
independent risk factor for asthma in cross-sectional and longitudinal studies.
The relationships between rhinitis and asthma can be viewed under the concept
that the 2 conditions are manifestations of one syndrome, the chronic allergic
respiratory syndrome, in 2 parts of the respiratory tract. At the low end of the 
syndrome's severity spectrum, rhinitis appears to be the sole manifestation,
although pathologic abnormalities in the lower airways are already present. At
the higher end, rhinitis is worse, and the lower airways disease becomes
clinically evident. Once manifested, the 2 conditions track in parallel in terms 
of severity. This parallel relationship is influenced by many interactions
between the nasal and the lower airways: some interactions stem from the fact
that the nasal passages play a major homeostatic role by conditioning inhaled
air, but perhaps even more important is the bidirectional interaction that
results from the systemic inflammation that is produced after local allergic
reactions. Successful management of the chronic allergic respiratory syndrome
requires an integrated view of the airways and an understanding of their
interactions.

Publication Types: 
    Review

PMID: 12789212 [PubMed - indexed for MEDLINE]

1096: Eur J Immunol. 2003 Jun;33(6):1667-76.

Prevention of allergen-specific IgE production and suppression of an established 
Th2-type response by immunization with DNA encoding hypoallergenic allergen
derivatives of Bet v 1, the major birch-pollen allergen.

Hochreiter R, Stepanoska T, Ferreira F, Valenta R, Vrtala S, Thalhamer J, Hartl
A.

Institute of Chemistry and Biochemistry, University of Salzburg, Austria.

In atopic patients, programming towards a preferential Th2 immunity leads to IgE 
antibody production and cellular Th2 immunity against otherwise harmless
antigens. We report the development of prophylactic and therapeutic DNA vaccines 
for the major birch-pollen allergen, Bet v 1. We constructed three DNA vaccines, 
coding for the complete cDNA, coding for two hypoallergenic fragments or coding
for a hypoallergenic Bet v 1 mutant. The protective effect was studied in mice
pretreated by intradermal DNA injections, then sensitized with Bet v 1 protein.
Mice pretreated with any of the three Bet v 1-specific DNA vaccines were
protected against allergic sensitization to Bet v 1. Protection was characterized
by a lack of Bet v 1-specific IgE production, a lack of basophil activation and
an enhanced IFN-gamma expression. DNA vaccines with wild-type Bet v 1 induced
strong Bet v 1-specific antibody responses whereas DNA vaccines with
hypoallergenic Bet v 1 derivatives induced no (fragments) or only transient
(mutant) Bet v 1-specific antibody responses. A therapeutic approach with the
fragment-DNA vaccine reduced IgE production and stimulated a sustained Th1
cytokine milieu. Our results demonstrate that DNA vaccines with hypoallergenic
forms of the allergen specifically protect against sensitization and suppress
established Th2-type responses. This concept may be applied for the development
of safe and specific DNA vaccines for the prophylaxis and therapy of allergic
diseases.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 12778485 [PubMed - indexed for MEDLINE]

1097: Ann Allergy Asthma Immunol. 2003 May;90(5):536-42.

Comment in:
    Ann Allergy Asthma Immunol. 2003 May;90(5):466-8.

Fluticasone propionate aqueous nasal spray provided significantly greater
improvement in daytime and nighttime nasal symptoms of seasonal allergic rhinitis
compared with montelukast.

Ratner PH, Howland WC 3rd, Arastu R, Philpot EE, Klein KC, Baidoo CA, Faris MA,
Rickard KA.

Sylvana Research Associates, San Antonio, Texas, USA.

BACKGROUND: The safety and efficacy of intranasal corticosteroids for the
treatment of allergic rhinitis is well documented in the literature.
Additionally, an expert panel has concluded that intranasal corticosteroids are
the first line of therapy when obstruction is a major component of rhinitis.
Montelukast is a leukotriene receptor antagonist recently approved for the
treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: This randomized,
double-blind, double-dummy, parallel-group study was conducted to compare the
effectiveness of a 15-day course of intranasal fluticasone propionate 200 microg,
once daily (FP200QD), to oral montelukast 10 mg, once daily (MON10QD), in
relieving daytime and nighttime nasal symptoms associated with SAR. METHODS: The 
intent-to-treat (ITT) analysis population consisted of 705 eligible males and
females (> or = 15 years) with SAR randomized to either FP200QD (N = 353) or
MON10QD (N = 352). The primary efficacy endpoint was the mean change from
baseline in subject-rated daytime total nasal symptom scores (the sum of four
individual scores: nasal congestion, itching, rhinorrhea, and sneezing),
evaluated via visual analog scales, and averaged over weeks 1 to 2. Secondary
endpoints included the four daytime individual nasal symptom scores, the
nighttime total, and individual nasal symptom scores (each evaluated on a
four-point scale from 0 to 3). RESULTS: Statistically significant differences
favoring FP200QD over MON10QD were observed for the mean change from baseline in 
daytime total nasal symptom scores (P < 0.001), daytime individual nasal symptom 
scores (P < 0.001), nighttime total (P < 0.001), and all individual nasal symptom
scores (P < or = 0.002) over the 15-day treatment period. FP200QD and MON10QD
were both well tolerated. CONCLUSIONS: The results of this well controlled study 
demonstrated that FP200QD was consistently superior to MON10QD with regard to
every efficacy endpoint evaluated, including daytime and nighttime nasal
congestion, in subjects with SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12775135 [PubMed - indexed for MEDLINE]

1098: Eur Respir J. 2003 Apr;21(4):652-7.

Chlorine inhalation produces nasal congestion in allergic rhinitics without mast 
cell degranulation.

Shusterman D, Balmes J, Avila PC, Murphy MA, Matovinovic E.

Dept of Medicine, University of California, San Francisco, CA, USA.
dennis@itsa.ucsf.edu

Seasonal allergic rhinitic (SAR) subjects are more sensitive to nasal irritants
than nonrhinitic (NR) subjects; however, the mechanism underlying this difference
is unclear. This study sought to determine whether irritant-induced nasal
congestion involves mast cell degranulation. Eight SAR and eight NR subjects were
exposed to both 1.0 parts per million chlorine and filtered air in separate
visits; exposures were via nasal mask and lasted 15 min. Rhinomanometry was
performed before, immediately after and 15 min after exposure. Following > or = 2
weeks, exposures and symptom reporting were repeated with nasal lavage, rather
than rhinomanometry, pre- and postexposure. A separate substudy using rye grass
antigen provided a positive control. Mast cell tryptase was measured in nasal
lavage fluid from both substudies using an automated fluoroenzyme immunoassay.
Chlorine provocation significantly increased nasal airway resistance in SAR but
not NR subjects. Conversely, tryptase levels in nasal lavage fluid were
unaffected. Nasal allergen challenge significantly increased both nasal
obstruction and nasal lavage tryptase in SAR subjects. Irritant-induced nasal
congestion is more pronounced among seasonal allergic rhinitic than nonrhinitic
subjects. However, unlike nasal allergen challenge, the mechanism of response to 
chlorine does not appear to involve mast cell degranulation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 12762352 [PubMed - indexed for MEDLINE]

1099: Arch Otolaryngol Head Neck Surg. 2003 May;129(5):557-62.

Fluticasone nasal spray and the combination of loratadine and montelukast in
seasonal allergic rhinitis.

Saengpanich S, deTineo M, Naclerio RM, Baroody FM.

Section of Otolaryngology--Head and Neck Surgery, The Pritzker School of
Medicine, The University of Chicago, Chicago, Ill, USA.

OBJECTIVE: To compare the effectiveness of an intranasal steroid treatment with
that of the combination of a histamine1 receptor antagonist and a leukotriene D
receptor antagonist in the treatment of seasonal allergic rhinitis. DESIGN: A
2-week, parallel, randomized, double-blind, double-dummy study with rolling
enrollment. SETTING: Tertiary care medical center.Subjects A total of 63 adults
with a 2-year history of ragweed sensitivity in the Chicago, Ill, area and a
positive skin-prick reaction to ragweed pollen.Intervention Subjects were
randomized to receive either 100 micro g of fluticasone propionate aqueous nasal 
spray in each nostril or 10 mg of loratadine and 10 mg of montelukast sodium by
mouth once daily in the evening for 2 weeks. At visits 1 and 2, subjects
completed a quality-of-life questionnaire and underwent nasal lavage to determine
total eosinophil count and eosinophil cationic protein (ECP) measurements. Daily 
symptom diaries were kept for 2 weeks. MAIN OUTCOME MEASURES: Questionnaire
answers, daily nasal symptom scores, eosinophil counts, and ECP levels. RESULTS: 
Median total nasal symptom scores were lower in the fluticasone group (4.5 vs 6),
but the difference was not statistically significant. The questionnaire answers
showed dramatic improvement in overall and individual domains for both groups
(P<.01 vs visit 1) with significantly greater reduction in nasal symptoms in the 
fluticasone group (P<.05). Eosinophil counts and ECP levels were significantly
reduced in the fluticasone group. CONCLUSION: Both treatments provided clinically
meaningful responses, but the overall results favored fluticasone propionate.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12759270 [PubMed - indexed for MEDLINE]

1100: Allergy. 2003 Jun;58(6):481-5.

Comparison of the effects of desloratadine 5-mg daily and placebo on nasal
airflow and seasonal allergic rhinitis symptoms induced by grass pollen exposure.

Horak F, Stübner P, Zieglmeyer R, Harris AG.

ENT-Universitätsklinik, Vienna, Austria.

BACKGROUND: Nasal congestion is a chronic symptom of seasonal allergic rhinitis
(SAR) that is often difficult to treat with antihistamines. Desloratadine, a new,
potent, H1-receptor antagonist has been shown to decrease nasal congestion in
clinical trials and to maintain nasal airflow in response to grass pollen
exposure. We compared the effects of desloratadine 5 mg and placebo on nasal
airflow, nasal secretion weights and SAR symptoms, including nasal congestion, in
patients exposed to grass pollen in an environmental exposure unit. METHODS:
Forty-six grass pollen allergic SAR patients received desloratadine or placebo
for 7 days, followed by a 10-day washout, and then crossed over to the other
treatment for 7 days. A 6-h allergen exposure was performed at the end of each
treatment period. RESULTS: Desloratadine was significantly superior to placebo in
maintaining nasal airflow (P <or= 0.014) and lessening the increase in nasal
secretion weights (P < 0.001) throughout allergen exposure. SAR symptom scores,
including nasal congestion, were significantly less with desloratadine than
placebo (P <or= 0.001). Desloratadine was well tolerated. CONCLUSIONS: This study
confirms that, compared with placebo, desloratadine can maintain nasal airflow
and reduce nasal secretion weights and the severity of SAR symptoms, including
nasal congestion, in SAR patients exposed to grass pollen allergen.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12757447 [PubMed - indexed for MEDLINE]

1101: Allergy. 2003 Jun;58(6):476-80.

Nasal blockage and urinary leukotriene E4 concentration in patients with seasonal
allergic rhinitis.

Higashi N, Taniguchi M, Mita H, Ishii T, Akiyama K.

Clinical Research Center, National Sagamihara Hospital, Kanagawa, Japan.

BACKGROUND: Cysteinyl-leukotrienes have been reported to have a primary role in
the induction of nasal blockage of allergic rhinitis. However, there has been
little experimental evidence that substantiates the relationship between nasal
blockage severity and urinary leukotriene E4 (U-LTE4) concentration in patients
with seasonal allergic rhinitis (SAR). METHODS: The concentrations of urinary
mediators in 20 SAR patients were measured using an enzyme immunoassay to
determine the relationship between nasal blockage severity and U-LTE4
concentration in patients with SAR. RESULTS: The basal U-LTE4 concentration was
significantly higher in SAR patients with severe nasal blockage than in those
with mild nasal blockage and in healthy control subjects. Although U-LTE4
concentrationwas significantly higher in patients with both asthma and SAR than
in SAR patients with mild nasal blockage, no significant difference in the U-LTE4
concentration between patients with both asthma and SAR and SAR patients with
severe nasal blockage was found. There was a significant correlation between
U-LTE4 and urinary 9alpha11beta-prostoglandin F2 (9alpha11betaPGF2)
concentrations (rs = 0.51, P = 0.02) in SAR patients. CONCLUSIONS: Although
specific sites and cells of cysteinyl-leukotriene biosynthesis could not be
determined in this study, severe nasal blockage is associated with the increased 
excretion level of U-LTE4.

PMID: 12757446 [PubMed - indexed for MEDLINE]

1102: Allergy. 2003 Jun;58(6):472-5.

Epidermal growth factor receptor - but not histamine receptor - is upregulated in
seasonal allergic rhinitis.

Matovinovic E, Solberg O, Shusterman D.

Division of Occupational and Environmental Medicine, University of California,
San Francisco, CA, USA.

BACKGROUND: We were interested in exploring the molecular mechanisms underlying
the observed difference in histamine (H) responsiveness between seasonal allergic
rhinitic (SAR) and nonrhinitic (NR) subjects. We hypothesized that SAR subjects
express higher nasal mucosal histamine receptor 1 (H1R) and 2 (H2R) levels than
do NR subjects. In addition, we examined expression of genes involved in
regulating the glandular response, including epidermal growth factor (EGF), EGF
receptor (EGFR), and mucins (Muc5Ac and Muc5B). METHODS: Fourteen subjects, seven
SAR and seven NR, were provoked during pollen season with doubling doses of H
(0.125-8.0 mg/ml). Nasal airway resistance (NAR) was measured by active posterior
rhinomanometry. Provocation was halted when NAR exceeded 150% of baseline. Prior 
to provocation, nasal scrapings were obtained and mRNA quantified using two-step 
real-time PCR. RESULTS: The mean PD50 (concentration of H producing a 50%
increase in NAR) was significantly lower in the SAR than NR group (0.36 vs 1.32
mg/ml; P < 0.05). The ratio of relative gene copy numbers between the SAR and NR 
groups were as follows: H1R, 0.85 (P = 0.52); H2R, 0.67 (P = 0.35); EGF, 1.02 (P 
= 0.93), and EGFR, 103.5 (P < 0.05). CONCLUSIONS: There were no significant
differences in H1R or H2R mRNA levels between SAR and NR subjects in-season,
despite observed differences in H reactivity. SAR subjects, however, did show a
significant elevation in EGFR expression, consistent with the observation of
mucus hypersecretion in allergic rhinitis.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12757445 [PubMed - indexed for MEDLINE]

1103: Otolaryngol Head Neck Surg. 2003 May;128(5):616-31.

Allergic rhinitis: broader disease effects and implications for management.

Baroody FM.

Section of Otolaryngology and Head and Neck Surgery, Pritzker School of Medicine,
The University of Chicago, Illinois, USA. fbaroody@surgery.bsd.uchicago.edu

Allergic rhinitis is a burdensome disease for a significant part of the
population in both adults and children. Poorly controlled allergic rhinitis can
trigger exacerbations of asthma, sinusitis, and otitis media, diseases with which
it shares common pathophysiologic elements. Consequently, early diagnosis and
treatment should be a priority for patients and physicians, not only to control
the symptoms of allergic rhinitis but also to improve the management of
associated diseases. Several pharmacologic therapies can be considered in an
armamentarium that includes antihistamines (intranasal and systemic), intranasal 
cromolyn, intranasal anticholinergic agents, intranasal steroids, systemic
steroids, immunotherapy, and, most recently, leukotriene receptor antagonists.
Often, combinations of these treatments are used to maximize control of
refractory symptoms.

Publication Types: 
    Review

PMID: 12748554 [PubMed - indexed for MEDLINE]

1104: J Allergy Clin Immunol. 2003 May;111(5):S835-42.

Comment in:
    J Allergy Clin Immunol. 2003 Dec;112(6):1246; author reply 1246-7.

First do no harm: managing antihistamine impairment in patients with allergic
rhinitis.

Casale TB, Blaiss MS, Gelfand E, Gilmore T, Harvey PD, Hindmarch I, Simons FE,
Spangler DL, Szefler SJ, Terndrup TE, Waldman SA, Weiler J, Wong DF;
Antihistamine Impairment Roundtable.

Creighton University, School of Medicine, Omaha, NE 68131, USA.
fbcasale@creighton.edu

Antihistamines are effective medications that have been used for decades in the
management of allergic rhinitis; however, they may be administered or selected in
an inappropriate fashion and may be the source of drug-related morbidity. Our
objective is to present relevant background information and an expert consensus
statement on the use of antihistamines in treatment of allergic rhinitis. In July
2002, 14 experts in allergy, clinical immunology, pharmacology, and impairment
assessment were invited to participate in a roundtable conference to present
current concepts and develop a consensus statement on the clinical management of 
allergic rhinitis with antihistamines. Many of the antihistamines used to treat
allergic rhinitis, as well as the disease itself, may produce sedation,
impairment, and reduced quality of life. Allergic rhinitis is more appropriately 
managed with the relatively nonimpairing second-generation antihistamines (eg,
loratadine, desloratadine, cetirizine, and fexofenadine), because older agents
(eg, diphenhydramine, chlorpheniramine, and brompheniramine) produce sedation and
impairment and worsen sleep architecture. Although there is some debate
surrounding the varying degrees of efficacy of second-generation antihistamines, 
it is known that some agents may produce varying levels of drowsiness or
impairment, especially at higher than recommended doses. The differences with
regard to safety among the second-generation antihistamines are smaller than are 
the differences between the first and second generations. A nonsedating,
nonimpairing (even at higher than recommended doses), second-generation
antihistamine is preferred for all patients, particularly those with a higher
risk for the development of adverse effects. We recommend that primary care and
specialist physicians, nurse practitioners, physician assistants, pharmacists,
and all other health professionals involved in the diagnosis and treatment of
allergic rhinitis follow this consensus document and share this information with 
patients for whom antihistamine therapy is recommended. In addition, further
epidemiologic studies on the effects of antihistamines should be performed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12743547 [PubMed - indexed for MEDLINE]

1105: Pharmacol Res. 2003 Jun;47(6):541-7.

Effects of zafirlukast on bronchial asthma and allergic rhinitis.

Piatti G, Ceriotti L, Cavallaro G, Ambrosetti U, Mantovani M, Pistone A, Centanni
S.

Institute of Respiratory Diseases, Ospedale Maggiore di Milano, IRCCS, University
of Milan, Milan, Italy. gioia.piatti@unimi.it

Asthma and allergic rhinitis are common conditions, occurring with increasing
prevalence and frequently coexist. In both conditions histamine and cysteinil
leukotrienes are important pathogenic inflammatory mediators.We evaluated the
effects of the leukotriene receptor antagonist zafirlukast, 20mg administered
twice daily for 2 weeks, in patients with allergic rhinitis and bronchial asthma 
during the grass pollen season.Patients underwent skin prick testing, spirometry,
rhinomanometry, mucus transport test with saccharine, nasal epithelial brushing
to study ciliary beat and, finally, nasal lavage.Thirty-five subjects completed
the study. At the end of the study period, zafirlukast significantly reduced
asthma and rhinitis symptoms (P< or =0.05); FEV(1) values were unchanged
(P=0.10), whereas nasal resistances showed a decrease following treatment
(P=0.01). Ciliary beat frequency (CBF) also improved (P=0.00), although
mucociliary transport showed no improvement (P=0.87). The number of eosinophils
in nasal lavage fluid decreased (P=0.00) while that of neutrophils was unchanged 
(P=0.09).These positive effects suggest that zafirlukast may be usefully employed
in the treatment of both bronchial asthma, as previously demonstrated, and
allergic rhinitis.

Publication Types: 
    Clinical Trial

PMID: 12742009 [PubMed - indexed for MEDLINE]

1106: Int Arch Allergy Immunol. 2003 Apr;130(4):307-13.

Comparative effects of desloratadine versus montelukast on asthma symptoms and
use of beta 2-agonists in patients with seasonal allergic rhinitis and asthma.

Baena-Cagnani CE, Berger WE, DuBuske LM, Gurné SE, Stryszak P, Lorber R, Danzig
M.

Department of Paediatrics, Infantile Hospital, Santa Rosa, Cordoba, Argentina.
baena@powernet.net.ar

BACKGROUND: Asthma and seasonal allergic rhinitis (SAR) are recognized as
manifestations of a single airway disease. Desloratadine has demonstrated
efficacy in treating SAR symptoms, including nasal obstruction. METHODS: Safety
and efficacy of desloratadine and montelukast each were assessed in a
double-blind, placebo-controlled trial of patients with SAR and symptoms of
asthma, who were assigned randomly to once-daily treatment with desloratadine 5
mg, montelukast 10 mg, or placebo for 4 weeks. Change from baseline of AM/PM
reflective total asthma symptom severity scores (TASS), FEV(1), individual asthma
symptom scores, and beta(2)-agonist usage were assessed. RESULTS: Desloratadine
and montelukast each were associated with statistically significant reductions
from baseline in the mean TASS averaged over the 4-week period (p < or =0.022 vs.
placebo). Individual asthma symptom scores also improved significantly for both
therapies (p < or = 0.05). Patients treated with desloratadine or montelukast
demonstrated improvement from baseline in FEV(1) versus placebo; significant
improvement was seen in a subset of patients with baseline FEV(1) <80% of
predicted normal (both p < 0.05). Both active therapies significantly reduced
beta(2)-agonist use (both p < 0.01). Improvements for both therapies were
comparable for all efficacy parameters; they were tolerated well with adverse
event profiles similar to placebo. CONCLUSIONS: Asthma symptoms and
beta(2)-agonist were improved significantly in patients with concomitant SAR and 
asthma treated with desloratadine 5 mg as well as montelukast 10 mg once daily.
Both therapies significantly improved FEV(1) in a subset of patients with FEV(1) 
<80% of predicted normal at entry. Improvements in asthma symptoms were
comparable for both active treatment groups. Copyright 2003 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12740532 [PubMed - indexed for MEDLINE]

1107: Methods Find Exp Clin Pharmacol. 2003 Mar;25(2):111-5.

Efficacy of ebastine in the control of nasal congestion associated with allergic 
rhinitis.

Ratner P, Hampel F Jr, Gispert J.

Sylvana Research Associates, San Antonio, Texas, USA. phratner@swbell.net

Three similarly designed, multicenter, double-blind, randomized,
placebo-controlled, parallel-group comparative studies were carried out in the
United States in a total of 1,881 patients to evaluate the efficacy of ebastine
20 mg (E20), ebastine 10 mg (E10), loratadine 10 mg (L10), and placebo (P), all
given once daily, in controlling the symptoms of ragweed-induced rhinitis over a 
4-week treatment period. Efficacy was assessed, among other means, by nasal
congestion symptom scores entered by patients on diary cards in the morning and
before bedtime over the previous 12-h period (reflective score, R) and at the
time of recording (snapshot score, SS). Mean value of both morning and evening
score changes from baseline were analyzed in each study and for each treatment.
E20 was more effective than placebo in all studies, in both R and SS symptom
scores (6 of 6 scores), while E10 was effective in 4 of 6 scores (2 R and 2 SS). 
In contrast, L10 was effective in only 1 of 6 scores (1 R). In conclusion, the
comparative analysis of the results from these three trials shows that ebastine
is efficacious in the reduction of nasal congestion associated with seasonal
allergic rhinitis. This symptomatic effect of ebastine may be accounted for by
its ability to reduce inflammatory markers, as shown in preclinical studies, in
addition to its primary effect of antagonizing histamine H1 receptors.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12731456 [PubMed - indexed for MEDLINE]

1108: Ann Allergy Asthma Immunol. 2003 Apr;90(4):416-21.

Relief of cough and nasal symptoms associated with allergic rhinitis by
mometasone furoate nasal spray.

Gawchik S, Goldstein S, Prenner B, John A.

Asthma and Allergy Associates, Upland, Pennsylvania, USA. smgawchik@aol.com

BACKGROUND: Cough commonly occurs as a symptom of seasonal allergic rhinitis
(SAR), an inflammatory condition of the nasal mucous membranes that results in
rhinorrhea, nasal stuffiness/congestion, nasal itching, and sneezing. Mometasone 
furoate nasal spray (MFNS, Nasonex, Schering, Kenilworth, NJ), an
anti-inflammatory nasal corticosteroid, has been shown to be safe and effective
in reducing the nasal inflammation of SAR. OBJECTIVE: To examine the
effectiveness of MFNS in relieving SAR-associated cough, in addition to nasal
symptoms. METHODS: This was a multicenter, randomized, double-blind study.
Patients 12 years of age or older with > or = 1-year history of SAR symptoms,
positive skin test to a prevailing seasonal allergen, moderate nasal symptoms,
and moderate cough were treated for 14 days with MFNS 200 microg daily (n = 122) 
or placebo (n = 123). RESULTS: The group treated with MFNS showed significant
improvement in the daytime cough severity score at endpoint compared with placebo
(P = 0.049). Improvement in the nighttime cough severity score showed a trend in 
favor of MFNS treatment. Treatment with MFNS significantly improved total nasal
symptoms in both the daytime and nighttime compared with placebo at endpoint (P <
or = 0.017). Overall daytime symptom scores (cough + total nasal) improved
significantly compared with placebo at endpoint (P = 0.005). Overall nighttime
symptom scores improved significantly compared with placebo at endpoint (P =
0.028). Treatments were well tolerated, with no significant differences in the
incidence of adverse events. CONCLUSIONS: MFNS is effective and well tolerated in
the treatment of daytime cough associated with SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12722964 [PubMed - indexed for MEDLINE]

1109: Biol Psychol. 2003 Apr;63(1):1-14.

Salivary cortisol patterns and cognitive speed in major depression: a comparison 
with allergic rhinitis and healthy control subjects.

den Hartog HM, Nicolson NA, Derix MM, van Bemmel AL, Kremer B, Jolles J.

Department of Psychiatry and Neuropsychology, Institute of Brain and Behaviour,
Maastricht University, Brugakker 58-61, 3704 MX Zeist, The Netherlands.
hm.den.hartog@planet.nl

Few studies have investigated the relationship between cortisol and cognitive
functions other than memory in depression. This study investigated daily salivary
cortisol patterns (basal cortisol levels at 08:00, 16:00, and 21:00 h and
flatness of the diurnal curve) in relation to cognitive speed and memory.
Twenty-seven unmedicated outpatients with major depressive disorder (MDD) were
compared with 36 healthy controls and with 20 allergic rhinitis patients, to
determine whether effects should be ascribed to MDD or to more general
disease-related processes. MDD patients were characterised by a flatter diurnal
cortisol curve and by reduced cognitive speed. Flatter cortisol curves were
associated with cognitive slowness. However, this relationship is unlikely to be 
causal; after control for depressive symptoms and group membership, flatness of
the diurnal cortisol curve was no longer a significant predictor of cognitive
slowness. Thus, MDD and related depressive symptoms appeared to be independently 
associated with altered cortisol secretory patterns and with decrements in
cognitive speed.

Publication Types: 
    Comparative Study

PMID: 12706961 [PubMed - indexed for MEDLINE]

1110: J Allergy Clin Immunol. 2003 Apr;111(4):763-9.

Erratum in:
    J Allergy Clin Immunol. 2003 Dec;112(6):1202.    J Allergy Clin Immunol. 2003 Jul;112(1):71.

Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal 
allergic rhinitis.

Wahn U, Meltzer EO, Finn AF Jr, Kowalski ML, Decosta P, Hedlin G, Scheinmann P,
Bachert C, Rosado Pinto JE, Baena-Cagnani C, Potter P, Simons FE, Ruuth E.

Department of Pediatric Pneumology and Immunology, University Children's
Hospital, Berlin, Germany.

BACKGROUND: This is the first prospective, randomized, double-blind,
placebo-controlled study showing statistical improvement of an H(1)-antihistamine
in children with seasonal allergic rhinitis in all symptoms throughout the entire
treatment period. OBJECTIVE: This randomized, placebo-controlled, parallel-group,
double-blind study was performed to assess the efficacy and safety of
fexofenadine in children with seasonal allergic rhinitis. METHODS: This study was
conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged
6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n =
464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms
(sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery,
and/or red eyes; and nasal congestion) were assessed at baseline and then daily
at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each
total symptom score was the sum of all symptoms, excluding nasal congestion. The 
primary efficacy variable was the change from baseline in the average of the
daily 12-hour evening reflective total symptom scores throughout the double-blind
treatment. Safety was evaluated from adverse-event reporting, vital signs,
physical examinations, and clinical laboratory data at screening and study end
point. RESULTS: Fexofenadine was significantly superior to placebo in the primary
efficacy analysis (P </=.0001). Individual symptom scores showed statistically
significant superiority compared with placebo (P <.05), including nasal
congestion in the evening reflective assessment (P <.05). There was no
significant difference in adverse events between fexofenadine and placebo, either
overall or by causality. CONCLUSION: The efficacy and safety of the
H(1)-antihistamine fexofenadine has been confirmed in this multicenter,
multinational study of children aged 6 to 11 years with seasonal allergic
rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12704355 [PubMed - indexed for MEDLINE]

1111: Thyroid. 2003 Feb;13(2):129-32.

Comment in:
    Thyroid. 2003 Feb;13(2):127-8.

Increased serum concentration of eosinophil-derived neurotoxin in patients with
Graves' disease.

Hidaka Y, Kimura M, Izumi Y, Takano T, Tatsumi KI, Amino N.

Department of Laboratory Medicine, Osaka University Graduate School of Medicine, 
Suita, Osaka, Japan. hidaka@hp-lab.med.osaka-u.ac.jp

Eosinophil-derived neurotoxin (EDN) is released after activation and stimulation 
of eosinophils in allergic disease, which is a T(H)2-predominant condition. We
previously reported that Graves' thyrotoxicosis develops or relapses after an
attack of allergic rhinitis. In this study, to confirm the relation between
Graves' disease and the allergic condition, we determined the serum level of EDN 
in 30 untreated patients with Graves' disease, 50 patients with Hashimoto's
thyroiditis, and 39 normal controls. Compared to the serum level in normal
subjects (30.1 +/- 15.6 ng/mL), EDN was increased in untreated patients with
Graves' disease (52.4 +/- 27.6 ng/mL), but not in patients with Hashimoto's
thyroiditis (thyrotoxic, 30.9 +/- 13.4 ng/mL; euthyroid, 30.0 +/- 11.9 ng/mL;
hypothyroid, 23.4 +/- 10.2 ng/mL). A significant correlation was observed between
the EDN level and the serum activity of thyrotropin (TSH) receptor antibody (r = 
0.541, p < 0.0001). These data suggest that the allergic condition is closely
related to Graves' disease and that a T(H)2-type immune response is crucial in
the pathogenesis of Graves' disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12699586 [PubMed - indexed for MEDLINE]

1112: Clin Exp Allergy. 2003 Apr;33(4):496-500.

Retrospective assessment of seasonal allergic symptoms: over-rating but useful.

Bodtger U, Poulsen LK, Malling HJ.

Allergy Clinic, National University Hospital, Copenhagen, Denmark. ub-all@rh.dk

BACKGROUND: The history of the severity of seasonal allergic symptoms is often
obtained post-seasonally as a retrospective assessment. Correct rating is
essential when determining the efficacy of pharmaceutical treatment, indications 
for allergen-specific immunotherapy (SIT), or inclusion into controlled clinical 
studies. OBJECTIVES: To investigate the agreement between in- and post-seasonal
ratings of seasonal symptoms, and to investigate whether the effect of SIT could 
be detected retrospectively. MATERIAL AND METHODS: Thirty-five birch
pollen-allergic patients were allocated to SIT or placebo in a double-blind
study. Assessment of severity of symptoms from the nose, eyes and lungs were
performed daily during the season 2000, and post-seasonally 6 months after the
season in 1999 and 2000. A four-point verbal descriptor scale (VDS-4) was used at
all occasions. A mean in-seasonal symptom rating was calculated for four periods:
the day, the week and the 2 weeks with the highest symptoms score, and the
arithmetic season (the period covering the mid-90% of the accumulated pollen
count). In- and post-seasonal ratings were compared with Cohen's weighted kappa
(kappaw). RESULTS: Agreement between in-seasonal and retrospective ratings was
fair to moderate (kappaw: 0.30-0.60). Post-seasonal ratings were most related to 
symptoms experienced in the week with the highest symptom scores, and least
related to the arithmetic season. The post-seasonal ratings were significantly
skewed towards higher symptom scores than the mean of in-seasonal ratings in
periods >or= 2 weeks. Despite being comparable before intervention, only in the
SIT-treated group was a significant decrease in post-season ratings of severity
of rhinoconjunctivitis apparent (P < 0.05). Asthma scores were not reduced but
fewer patients in the SIT group reported lung symptoms (P < 0.001). CONCLUSION:
Post-seasonal assessment of seasonal allergic symptoms generally describes a
shorter period than the arithmetic season. Post-season assessment tends to
over-rate average symptom severity, but appears sufficiently sensitive to detect 
treatment efficacy.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12680866 [PubMed - indexed for MEDLINE]

1113: Clin Exp Allergy. 2003 Apr;33(4):475-82.

A single nasal allergen challenge increases induced sputum inflammatory markers
in non-asthmatic subjects with seasonal allergic rhinitis: correlation with
plasma interleukin-5.

Beeh KM, Beier J, Kornmann O, Meier C, Taeumer T, Buhl R.

Pulmonary Department, Internal Medicine, University Hospital Mainz, Mainz,
Germany. k.beeh@3-med.klinik.uni-mainz.de

BACKGROUND: Seasonal allergic rhinitis (SAR) is a risk factor for asthma in
affected individuals. Nasal allergic inflammation enhances bone-marrow eosinophil
production, mainly via IL-5, and rhinitis patients have increased airway
inflammation during the pollen season. OBJECTIVE: To assess the impact of nasal
allergy on sputum inflammatory markers. METHODS: In an open-labelled, randomized,
placebo-controlled cross-over study with 16 non-asthmatic SAR patients (median
age 25 years, 56% males), the effect of a single nasal allergen challenge
performed out of season on induced sputum inflammatory parameters was evaluated. 
SAR patients were identified by history, skin-prick test and specific IgE. All
patients had normal lung function/bronchial hyper-responsiveness out of season
and a negative asthma/wheezing history. Sputum cells and supernatant levels of
ECP, sICAM, IL-5 and IL-10, and plasma levels of IL-5 and ECP, were measured
before and 24 h after nasal allergen challenge. After a washout period of at
least 4 weeks, the procedure was repeated with placebo challenge (diluent).
RESULTS: Nasal allergen challenge led to an increase in sputum ECP (pre = 60 +/- 
12, post = 212 +/- 63 micro g/L, P = 0.02 vs. placebo), and sICAM (4.8 +/- 2.7 to
6.5 +/- 2.9 ng/mL, P = 0.02 vs. placebo), whereas IL-10 decreased after
provocation (44 +/- 11 to 29 +/- 6 pg/mL, P = 0.06 vs. placebo). Sputum IL-5 was 
undetectable in all patients. The absolute number of blood and sputum eosinophils
did not change significantly after allergen or placebo challenge (P > 0.07, both 
comparisons). Plasma levels of IL-5 increased after allergen challenge (8.7 +/-
2.9 to 14.5 +/- 3.9 pg/mL, P = 0.001), and the increase in plasma IL-5 was
positively correlated with the rise in sputum ECP in a subgroup of 'responders'
(n = 12, r = 0.71, P = 0.01). CONCLUSIONS: A single nasal allergen challenge in
SAR patients increased markers of allergic inflammation in the lower respiratory 
tract, possibly via pronounced activation of inflammatory cells through
circulating immediate-type reaction cytokines like IL-5. These findings may
provide additional explanatory data for the high susceptibility of SAR patients
to incident asthma.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12680863 [PubMed - indexed for MEDLINE]

1114: Chest. 2003 Apr;123(4):993-7.

Comment in:
    Chest. 2003 Apr;123(4):971-3.

Effect of cigarette smoking on airway responsiveness to adenosine
5'-monophosphate in subjects with allergic rhinitis.

Prieto L, Gutiérrez V, Uixera S, Bertó JM.

Sección de Alergología and Universidad de Valencia, Spain. prieto_jes@gva.es

STUDY OBJECTIVES: The objective of this study was to determine differences in
airway responsiveness to adenosine 5'-monophosphate (AMP) between smokers and
nonsmokers with allergic rhinitis. METHODS: A total of 41 adults with allergic
rhinitis (16 smokers and 25 nonsmokers) were challenged with increasing
concentrations of methacholine and AMP. Airflow was assessed after each
concentration, and the response to each bronchoconstrictor agent was measured by 
the provocative concentration required to produce a 20% fall in FEV(1) (PC(20)). 
RESULTS: The geometric mean PC(20) AMP values were significantly lower in smokers
than in nonsmokers: 72.4 mg/mL (95% confidence interval [CI], 33.9 to 154.9) vs
204.2 mg/mL (95% CI, 120.2 to 346.7) [p = 0.021]. The proportion of subjects with
bronchoconstriction in response to AMP was higher in smokers (12 of 16 subjects) 
than in nonsmokers (7 of 25 subjects) [p = 0.005]. CONCLUSIONS: We conclude that 
smokers with allergic rhinitis have a greater AMP sensitivity than nonsmokers.

PMID: 12684285 [PubMed - indexed for MEDLINE]

1115: Paediatr Perinat Epidemiol. 2003 Apr;17(2):212-20.

Atopic manifestations, breast-feeding protection and the adverse effect of DDE.

Karmaus W, Davis S, Chen Q, Kuehr J, Kruse H.

Department of Epidemiology, Michigan State University, East Lansing, MI 48823,
USA. karmaus@msu.edu

Despite the numerous studies on the possible protective effect of breast feeding 
against the onset of atopic manifestations during childhood, this issue remains
controversial. As part of an environmental epidemiological study, we investigated
whether different blood concentrations of dichlorodiphenyl-dichloroethylene (DDE)
modified the protective effect of breast feeding against atopic manifestations in
338 children. DDE concentration, duration of breast feeding and manifestation of 
atopic disorders were measured in 1994-95 at age 7-8 years. Information gathered 
on asthma, atopic eczema and hay fever was based on questionnaire data. We
measured the total serum concentration of immunoglobulin E (IgE) and specific IgE
levels against inhalant allergens. In 1997, we also determined bronchial
hyper-reactivity with a hypertonic saline challenge test. To estimate odds ratios
from our cross-sectional analysis, we applied logistic regressions, controlling
for confounders. Breast feeding had a protective effect on the two asthma
variables (e.g.> 12 weeks breast feeding for doctor-diagnosed asthma, OR = 0.32
[95% CI 0.11, 0.87]; for 'ever' asthma, OR = 0.13 [95% CI 0.02, 0.68]), but not
on bronchial hyper-reactivity, hay fever, atopic eczema or the two IgE variables.
The protective effect became stronger in children with DDE blood levels below the
median of 0.29 micro g/L (e.g. doctor-diagnosed asthma,> 12 weeks breast feeding,
OR = 0.24 [95% CI 0.06, 0.95]). Also, for specific IgE against inhalant
allergens, the association gained statistical significance. For children with a
DDE concentration of 0.29 micro g/L and higher, breast feeding did not show a
significant protective effect. Our results suggest that contaminants such as DDE 
may modify the protective effect and may have contributed to inconsistent
findings on the protective effect of breast feeding in previous studies. We
recommend determining levels of breast milk contaminants in children when
assessing the impact of breast feeding on atopic manifestations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12675789 [PubMed - indexed for MEDLINE]

1116: Pediatr Allergy Immunol. 2003 Apr;14(2):140-3.

Comment in:
    Pediatr Allergy Immunol. 2004 Apr;15(2):190.

Hypersaline nasal irrigation in children with symptomatic seasonal allergic
rhinitis: a randomized study.

Garavello W, Romagnoli M, Sordo L, Gaini RM, Di Berardino C, Angrisano A.

Department of Otorhinolaryngology, D.N.T.B., University of Milano Bicocca,
Milano, Italy. wer_g@yahoo.it

Recent evidence suggests that nasal irrigation with hypertonic saline may be
useful as an adjunctive treatment modality in the management of many sinonasal
diseases. However, no previous studies have investigated the efficacy of this
regimen in the prevention of seasonal allergic rhinitis-related symptoms in the
pediatric patient. Twenty children with seasonal allergic rhinitis to Parietaria 
were enrolled in the study. Ten children were randomized to receive three-times
daily nasal irrigation with hypertonic saline for the entire pollen season, which
had lasted 6 weeks. Ten patients were allocated to receive no nasal irrigation
and were used as controls. A mean daily rhinitis score based on the presence of
nasal itching, rhinorrea, nasal obstruction and sneezing was calculated for each 
week of the pollen season. Moreover, patients were allowed to use oral
antihistamines when required and the mean number of drug assumption per week was 
also calculated. In patients allocated to nasal irrigation, the mean daily
rhinitis score was reduced during 5 weeks of the study period. This reduction was
statistically significantly different in the 3th, 4th and 5th week of therapy.
Moreover, a decreased consumption of oral antihistamines was observed in these
patients. This effect became evident after the second week of treatment and
resulted in statistically significant differences during the 3th, 4th and 6th
week. This study supports the use of nasal irrigation with hypertonic saline in
the pediatric patient with seasonal allergic rhinitis during the pollen season.
This treatment was tolerable, inexpensive and effective.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12675761 [PubMed - indexed for MEDLINE]

1117: Pediatr Allergy Immunol. 2003 Apr;14(2):120-9.

Hay fever and predictive value of prick test and specific IgE antibodies: a
prospective study in children.

Schäfer T, Hoelscher B, Adam H, Ring J, Wichmann HE, Heinrich J.

Department of Social Medicine, Medical University Lüebeck, Lüebeck, Germany.
torsten.schaefer@sozmed.mu-luebeck.de

Little is known from population-based studies in children about the diagnostic
values of allergen-specific IgE antibodies (RAST) and skin prick test (SPT) with 
respect to hay fever. We aimed to determine and compare the diagnostic values of 
SPT and RAST to aeroallergens with respect to the incidence of hay fever cases in
schoolchildren at different cut-off points. A prospective cohort study was
performed on 1100 school children (5-7 and 8-10 years). Information on a doctor's
diagnosis of hay fever was obtained by questionnaire and allergic sensitization
to grass and birch pollen, cat, and Dermatophagoides pteronyssinus were measured 
using SPT and RAST between September 1992 and July 1993. Thirty-eight children
give a history of hay fever (3.5%) in 1992/93 and additionally 37 cases occurred 
until 1996. Allergic sensitization was present in 17.9% (SPT), 30.2% (RAST) and
more frequent in children with a history of hay fever (SPT: OR 11.7, 5.5-24.7;
RAST: OR 10.6, 4.3-26.4). This difference was most pronounced for sensitization
to pollen allergens. The sensitivity, specificity, positive and negative
predictive values (PPV, NPV) for SPT and RAST were 65.6, 83.7, 11.9, 98.6 and
79.3, 71.6, 9.3, 99.0, respectively, with differences for specificity being
significant (p < 0.001). Whereas NPV were equally high for SPT (99.2) and RAST
(99.3), the incidence of hay fever cases were predicted rather poorly though
somewhat better by SPT than by RAST (PPV 16.7 vs. 9.8; p < 0.001) initially. With
increasing cut-off point for RAST reactivity, the PPV increased and reached 25.0 
at 17.5 kU/l, whereas the NPV decreased to 97.9, which was lower than that of SPT
reactivity (p < 0.01). At the cut-off point of 1.5 kU/l almost identical
predictive values for SPT and RAST were obtained. SPT and RAST perform better in 
the negative than positive prediction of hay fever cases in epidemiological
studies. Differences in the predictive capabilities depend on the chosen cut-off 
point for RAST reactivity.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12675758 [PubMed - indexed for MEDLINE]

1118: Pediatr Allergy Immunol. 2003 Apr;14(2):100-5.

Natural exposure to Alternaria spores induces allergic rhinitis symptoms in
sensitized children.

Andersson M, Downs S, Mitakakis T, Leuppi J, Marks G.

Department of Otorhinolaryngology, University Hospital, Lund, Sweden.
Morgan.Andersson@onh.lu.se

Allergic rhinitis is associated with exposure to inhaled allergens. Allergic
sensitization to the fungus Alternaria is common, especially in warm climates,
but the relevance of sensitization to Alternaria in the generation of rhinitis
has not been elucidated. The aim of this study was to determine whether natural
exposure to Alternaria induces rhinoconjuctivitis symptoms in
Alternaria-sensitized children. Symptoms of rhinoconjuctivitis in 132 atopic
(measured by skin prick tests) children (aged 7-12 years) in inland New South
Wales Australia were measured using parent-completed questionnaires in summer and
winter 1998. Airborne concentrations of Alternaria spores and grass pollen were
measured throughout the study period using a Burkard volumetric trap. The
relation between airborne concentrations of Alternaria spores and symptoms of
rhinoconjunctivitis was examined using Wilcoxon's matched pairs signed ranked
test and generalized estimating equations. The proportion of children atopic to
Alternaria reporting symptoms of rhinitis was significantly higher in the summer,
when airborne concentrations of Alternaria were high, than in the winter, when
airborne concentrations were low (66.2% vs. 38.2% for nasal symptoms at night, p 
= 0.0001, 70.6% vs. 51.52% for nasal symptoms during the day, p = 0.02). The
proportion of children using anti-allergic treatment was also higher in summer
than in winter (anti-allergic medication for the nose 39.7% vs. 17.7%, p =
0.0003). A strong correlation between airborne concentrations of grass pollen and
Alternaria was found (R = 0.94, p < 0.001). However, when all children atopic to 
ryegrass were excluded from the analyses, significant associations between
symptoms and season remained. We conclude that exposure to Alternaria spores may 
be an important cause of allergic rhinoconjunctivitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12675755 [PubMed - indexed for MEDLINE]

1119: Curr Allergy Asthma Rep. 2003 May;3(3):266-72.

Preformed enzymes in mast cell granules and their potential role in allergic
rhinitis.

Parikh SA, Cho SH, Oh CK.

UCLA School of Medicine, Harbor-UCLA Medical Center, Bldg. N-25, 1000 W. Carson
Street, Torrance, CA 90509, USA.

Mast cells not only function as effector cells but also influence nearly every
other cell involved in causing allergic rhinitis. Mast cell-derived mediators
such as histamine, bradykinin, tryptase, and the arachidonic acid derivatives
produce the symptoms of the early-phase reaction of allergic rhinitis and also
attract and activate other leukocytes involved in the late-phase reaction. In
addition, activated mast cells are known to secrete a number of cytokines, both
preformed and newly synthesized, that can modulate T- and B-cell function,
propagate the early- and late-phase reactions, and contribute to tissue
remodeling. Most currently available therapies work by antagonizing the mediators
secreted by mast cells and other leukocytes. With the possible exception of
immunotherapy, these therapies do not provide long-term protection against
allergic disorders. Exciting new developments in gene-based therapies seem
promising in both reducing and reversing the development of allergic rhinitis.

Publication Types: 
    Review

PMID: 12662477 [PubMed - indexed for MEDLINE]

1120: Curr Allergy Asthma Rep. 2003 May;3(3):238-48.

Airway hypersecretion in allergic rhinitis and asthma: new pharmacotherapy.

Rogers DF.

Thoracic Medicine, National Heart & Lung Institute, Imperial College, Dovehouse
St, London SW3 6LY, UK. duncan.rogers@imperial.ac.uk

Mucus hypersecretion is a prominent feature of allergic rhinitis and asthma.
Biologic targets for suppression of hypersecretion range from the inflammatory
cells that initiate airway inflammation, to specific cellular elements such as
calcium-activated chloride (CLCA) channels, epidermal growth factor receptor
tyrosine kinase, and antiapoptotic factors (eg, Bcl-2). Identification of these
targets is driving development of new pharmacotherapeutic compounds. Aside from
specific instances in which a single mediator has a major impact on
hypersecretion--for example, histamine in rhinitis--it is likely that compounds
with broad-spectrum anti-inflammatory activity are more effective than compounds 
with restricted activity. However, certain highly specific targets, such as CLCA 
channels, seem to be intimately associated with development of a hypersecretory
phenotype. Data from clinical trials with blockers of these targets are awaited
with great interest, not only for disease management but also to determine the
clinical benefit of selective inhibition of airway hypersecretion.

Publication Types: 
    Review

PMID: 12662474 [PubMed - indexed for MEDLINE]

1121: Curr Allergy Asthma Rep. 2003 May;3(3):232-7.

Relationships between atopy and bacterial infections.

Mucha SM, Baroody FM.

Section of Otolaryngology-Head and Neck Surgery, The Pritzker School of Medicine,
The University of Chicago, 5841 S. Maryland Ave, MC 1035, Chicago, IL 60637, USA.

Atopy in its most common forms (asthma, allergic rhinitis, and atopic dermatitis)
has a significant impact on society in terms of health care costs and quality of 
life. Aside from having significant morbidity from these diseases, patients with 
atopy have also been noted to have a high incidence of comorbidities, including
bacterial infections such as otitis media and sinusitis. In this paper, current
evidence is reviewed that supports the close associations among allergic rhinitis
and the two commonly diagnosed bacterial diseases, otitis media and sinusitis.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 12662473 [PubMed - indexed for MEDLINE]

1122: Curr Allergy Asthma Rep. 2003 May;3(3):204-9.

Immunotherapy for rhinitis.

Malling HJ.

Allergy Clinic 4222, National University Hospital, Blegdamsvej 9, 2100
Copenhagen, Denmark. all-unit@rh.dk

Allergen-specific immunotherapy in the treatment of allergic rhinitis has a
well-documented clinical efficacy that indicates a statistically significant and 
clinically relevant reduction in symptom scores and the need for pharmacotherapy.
The clinical efficacy of recently published studies is equivalent to or superior 
to the effect of standard anti-allergic drugs. Additional advantages are related 
to a downregulation of the allergic phenotype with the additional induction of a 
Th1 cytokine profile. The immunoregulatory capacity and the global downregulation
of the allergic inflammation in mucous membranes might be important factors in
the capacity to ensure long-term clinical efficacy (after termination of
treatment) and the preventive capacity of immunotherapy in reducing the
progression of rhinitis to asthma as well as deflowering the development of new
sensitizations. Subcutaneous immunotherapy is optimal in severe allergic rhinitis
with signs of bronchial hyperreactivity; however, sublingual immunotherapy might 
be an option for patients with milder disease.

Publication Types: 
    Review

PMID: 12662468 [PubMed - indexed for MEDLINE]

1123: Clin Exp Immunol. 2003 Apr;132(1):76-80.

Evaluation of CD4+ T cells proliferating to grass pollen in seasonal allergic
subjects by flow cytometry.

Rimaniol AC, Garcia G, Till SJ, Capel F, Gras G, Balabanian K, Emilie D, Humbert 
M.

Service de Pneumologie UPRES EA2705, INSERM U 31, Institut Paris-Sud sur les
Cytokines, Hôpital Antoine Béclère, Assistance Publique Hôpitaux de Paris,
Université Paris-Sud, Clamart, France.

Our objective was to characterize T-cell responses to Phleum pratense in grass
pollen allergic individuals and healthy controls using the fluorescent dye PKH26.
Peripheral blood mononuclear cells were stimulated with P. pratense, or with
recall antigens, and CD3+/CD4+ and CD3+/CD8+ T-cells that had proliferated were
analysed by flow cytometry. In the presence of P. pratense CD4+/CD3+ T-cells
proliferated more in grass pollen sensitive atopic patients than in nonallergic
controls or in nongrass pollen sensitive atopic subjects. PPD and TT recall
antigens elicited uniformly high proliferation in all T-cell subsets. Only half
of pollen sensitive patients also had an increased proliferation of CD3+/CD8+
T-cells in response to P. pratense. We determined precursor frequency of CD4+ T
cells in the original population that responded to P. pratense and found values
ranging from 1 x 10-3 to 0.6 x 10-1, in the same range as those measured for PPD 
and TT. In conclusion, grass pollen sensitive atopic patients show enhanced CD4+ 
T-cell reactivity to P. pratense, and this could be related to the presence of
elevated numbers of circulating allergen-specific CD4+ T cells. This flow
cytometric method should allow the identification of other phenotypic markers
such as intracellular cytokines in allergen specific responding CD4+ T cells.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12653839 [PubMed - indexed for MEDLINE]

1124: Clin Exp Allergy. 2002 Dec;32(12):1728-33.

Concentrations of exhaled nitric oxide in asthmatics and subjects with allergic
rhinitis sensitized to the same pollen allergen.

Prieto L, Gutiérrez V, Uixera S, Bruno L.

Sección de Alergología, Hospital Universitario Dr Peset, Valencia, Spain.
prieto_jes@gva.es

BACKGROUND: Some studies have reported that the levels of exhaled nitric oxide
(ENO) in asthmatics are similar to those in subjects with allergic rhinitis, and 
it has been postulated that atopic status might be the determinant of enhanced
nitric oxide production in asthma. OBJECTIVES: The aim of this study was to
determine differences in ENO levels between asthmatics and subjects with allergic
rhinitis sensitized to the same allergen, and to correlate these levels with
airway responsiveness. METHODS: Nineteen patients with asthma and 18 subjects
with allergic rhinitis monosensitized to Parietaria pollen were enrolled in the
study. ENO values and airway responsiveness to methacholine and adenosine
5'-monophosphate (AMP) were measured during the pollen season. The response to
each bronchoconstrictor agent was measured by the provocative concentration
required to produce a 20% fall in FEV1 (PC20). ENO was measured with the
single-exhalation method. RESULTS: The geometric mean (95% confidence interval)
ENO values were significantly higher in asthmatics than in subjects with allergic
rhinitis: 72.4p.p.b. (54.9-93.3p.p.b) vs. 44.7p.p.b. (30.9-64.6p.p.b., P = 0.03).
In asthmatics, a significant correlation was found between ENO and PC20 AMP
values (p = -0.57, P=0.02), whereas no correlation was detected between ENO and
PC20 methacholine (p = -0.35, P = 0.14). CONCLUSIONS: Our results suggest that
atopy is not the only determinant of increased ENO levels detected in subjects
with asthma, and that responsiveness to AMP may be a more sensitive marker for
assessing airway inflammation in asthma compared to methacholine.

Publication Types: 
    Comparative Study

PMID: 12653163 [PubMed - indexed for MEDLINE]

1125: Allergol Immunopathol (Madr). 2003 Mar-Apr;31(2):91-3.

A case of anaphylaxis due to rose pollen ingestion.

Karakaya G, Kalyoncu AF.

Hacettepe University. School of Medicine. Dept. of Chest Diseases. Adult Allergy 
Unit. Ankara. Turkey. gkarakay@hacettepe.edu.tr

BACKGROUND: Recent publications have demonstrated that in Güneykent (Turkey), a
rose-cultivating area, some workers experience various allergic reactions due to 
contact with rose or its pollen. CASE REPORT: A 47-year-old man, originally from 
Güneykent although he no longer lived there, suffered perennial rhinitis, asthma 
and rhinoconjunctivitis in spring related to sensitization to dust mites and
various pollens, respectively. On several occasions, he had presented oral and
cutaneous symptoms and angioedema due to contact with rose or intake of honey or 
other products. Finally, he had an anaphylactic reaction on drinking dew
collected in the tulips of a rose that possibly contained rose pollen. METHODS:
Specific IgE was evaluated with Rosa rugosa extract and was 30.3 IU (class IV).
Sensitization to other pollens and to mites was also confirmed. Oral provocation 
test was not deemed ethical. CONCLUSION: This may be the first reported case of
anaphylactic reaction due to rose pollen ingestion.

Publication Types: 
    Case Reports

PMID: 12646125 [PubMed - indexed for MEDLINE]

1126: Allergol Immunopathol (Madr). 2003 Mar-Apr;31(2):77-82.

Single-course specific immunotherapy with mixed pollen allergoids: results of a
multi-centre study.

Drachenberg KJ, Pröll S, Urban E, Woroniecki SR.

Bencard Allergie GmbH, Munich, Germany.

BACKGROUND: A short-term immunotherapy vaccine for the treatment of pollen
allergy has been developed utilising L-tyrosine adsorbed allergoids. The reduced 
number of injections could provide advantages over long-term therapy schedules.
This would improve compliance and support application of specific immunotherapy
(SIT) to a greater extent. We report a multicenter study to evaluate the efficacy
and safety of this treatment in a clinical practice setting. METHODS: Patients (n
= 1808) with a diagnosis of sensitivities to various pollens and symptoms of
allergic asthma and/or allergic rhinitis and/or allergic conjunctivitis were
selected. The vaccine formulation was made up according to individual
sensitivities and contained L-tyrosine adsorbed allergoids. The patients were
treated with a 3-injection initial course followed by a 3-injection maintenance
course. Efficacy was measured by consumption of symptomatic anti-allergic
medication compared with that in the previous season and by physician assessment 
using a 5-point scale. All adverse events were recorded. RESULTS: Efficacy was
demonstrated by a considerable decrease in regular and frequent use of medication
compared with that in the previous season (p < 0.001). In addition, in 80 % of
the patients, the physician's assessment was either "good" or "very good". These 
outcomes were unaffected by the closeness of the treatment course to the onset of
the pollen season. Tolerability was good and most local and systemic reactions
were mild. CONCLUSIONS: The treatment of pollen-allergic patients with a
short-term SIT using a 6-injection pollen allergoid/L-tyrosine vaccine in a
clinical practice setting provided a high level of efficacy with a low incidence 
of mainly mild adverse events.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 12646122 [PubMed - indexed for MEDLINE]

1127: Allergol Immunopathol (Madr). 2003 Mar-Apr;31(2):63-9.

Clinical efficacy and safety of a depigmented and glutaraldehyde polymerized
therapeutic vaccine of Parietaria judaica.

García-Sellés J, Pascual A, Funes E, Pagán JA, López JD, Negro JM, Hernández J.

Hospital Virgen de la Arrixaca. Murcia. Spain. jhernandezg@meditex.es

BACKGROUND: The inhalation of Parietaria judaica pollen is a common cause of
allergic respiratory diseases in the Mediterranean area. The objective of this
study was to investigate the safety and clinical efficacy of a chemically
modified (depigmented and glutaraldehyde-polymerized) vaccine of Parietaria
judaica. METHODS AND RESULTS: Thirty patients with a well-documented clinical
history of seasonal rhinitis and clinical sensitivity to Parietaria judaica
pollen were included in a randomized trial during 12 months. The study was
conducted following good clinical practices and appropriate consent forms were
signed. Patients were divided into 2 groups of 15 individuals; group A received
the modified extract and group C did not receive specific immunotherapy. Any
adverse event was recorded to assess safety. Symptom scores, symptomatic
medication use and the results of specific nasal challenges (before and after 12 
months of treatment) were recorded to evaluate clinical efficacy. The treatment
schedule consisted of an incremental phase of 5 injections and a maintenance
dosage of 0.5 ml per month. Each patient received 14 injections during this
period. All the patients completed the trial and no adverse reactions related to 
immunotherapy were recorded. A significant difference (p < 0.001) in symptom
scores and overall use of symptomatic medication was observed between the two
groups, being both scores lower in group A. No significant differences in nasal
sensitivity existed before treatment among the 2 groups. However, after 12
months, a significant difference (p < 0.05) was observed only in group A
patients, who showed a significant improvement in specific nasal challenges.
CONCLUSIONS: Immunotherapy with depigmented and glutaraldehyde-polymerized
extract of Parietaria judaica pollen is safe and effective to treat patients with
allergic rhinitis and clinical sensitivity to this pollen.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12646120 [PubMed - indexed for MEDLINE]

1128: J Allergy Clin Immunol. 2003 Mar;111(3):484-90.

A questionnaire to measure quality of life in adults with nocturnal allergic
rhinoconjunctivitis.

Juniper EF, Rohrbaugh T, Meltzer EO.

Department of Clinical Epidemiology and Biostatistics, McMaster University,
Hamilton, Ontario, Canada.

BACKGROUND: Many patients with rhinoconjunctivitis experience symptoms at night
and these interfere with getting a good night's sleep. OBJECTIVE: The aim of this
study was to develop the Nocturnal Rhinoconjunctivitis Quality of Life
Questionnaire (NRQLQ) to measure the functional problems that are most
troublesome to patients with nocturnal allergic rhinoconjunctivitis (NAR).
METHODS: After generating a list of 256 potentially important items, 132 patients
with NAR identified the items that were most troublesome. The top scoring 16
items are included in the NRQLQ in four domains (sleep problems, symptoms during 
sleep time, symptoms on waking and practical problems). The NRQLQ asks patients
to recall their experiences during the previous week and score each item on a
7-point scale. RESULTS: One hundred and six patients with NAR participated in a 3
week validation study. This showed the NRQLQ to have good reliability (ICC =
0.87) and responsiveness (responsiveness index = 0.93). For both cross-sectional 
and longitudinal construct validity correlations between the NRQLQ and other
measures of health status were close to a priori predictions. CONCLUSIONS: The
NRQLQ has strong evaluative and discriminative measurement properties and can be 
used with confidence in both clinical practice and clinical trials to measure the
functional impairments that are most troublesome to patients with nocturnal
allergic rhinoconjunctivitis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 12642826 [PubMed - indexed for MEDLINE]

1129: Microbiol Immunol. 2003;47(1):101-3.

Individuals exhibiting conspicuous nevi (lentigo simplex) are resistant to
allergic rhinitis/conjunctivitis (pollinosis), but those who do not show
increased susceptibility to pollinosis.

Awaya A, Watanabe K, Kato S.

Japan Science and Technology Corporation, Tachikawa, Tokyo 190-0012, Japan.
awaya@home.email.ne.jp

We investigated 115 individuals in Tokyo from two groups of persons with
conspicuous nevi on the head, neck, and arms, etc. (nevus-positive group) and
persons who do not exhibit such nevi (nevi-negative group) interviewing them to
determine whether they suffered from allergic rhinitis/conjunctivitis
(pollinosis) and examining them for the presence and extent of nevi. There was a 
distinct correlation: only 5 persons among 85 individuals of the nevus-positive
group suffered from pollinosis, and all 30 people in the nevus-negative group had
pollinosis. Thus, individuals exhibiting conspicuous nevi are resistant to
pollinosis, but those who do not show increased susceptibility to pollinosis.

PMID: 12636259 [PubMed - indexed for MEDLINE]

1130: Cytokine. 2002 Dec 21;20(6):268-73.

Increased expression of Vascular Endothelial Growth Factor-A in seasonal allergic
rhinitis.

Benson M, Carlsson B, Carlsson LM, Wennergren G, Cardell LO.

Laboratory for Clinical and Experimental Allergology, Department of
Oto-Rhino-Laryngology, Malmö University Hospital, Malmö, Sweden.
Mikael.benson@pediat.gu.se

Increased vascular dilatation and permeability characterize allergic rhinitis. In
this study oligonucleotide microarrays (Affymetrix HuGe95A) were used to identify
differentially expressed vasoactive genes in nasal biopsies from 23 patients with
symptomatic seasonal allergic rhinitis (SAR) and 12 healthy controls. RNA was
extracted from the biopsies and pooled in three patient and three control pools. 
Out of 12,626 analysed transcripts, 39 were higher and 81 lower in the patients. 
Of these transcripts two have vasoactive effects: Vascular Endothelial Growth
Factor-A (VEGF-A) and the Beta-1-Adrenergic Receptor. Both were higher in
patients than in controls. The mean +/- SEM expression levels in arbitrary units 
of VEGF-A were 130 +/- 123 in the patients and 59 +/- 53 in the controls. The
fold ratio in expression levels between patients/controls was 2.2. The
corresponding values for the beta-1-adrenergic receptor were 129 +/- 123 in the
patients and 40 +/- 31 in the controls. The fold ratio between patient/controls
was 3.2. The role of VEGF-A was assessed by determining VEGF-A concentrations in 
nasal fluids from another 30 patients with SAR before and after allergen
provocation. VEGF-A increased from 124.3 +/- 30.2 to 163.2 +/- 37.8 pg/ml after
challenge, P < 0.05. In summary, oligonucleotide microarray analysis of nasal
biopsies and protein analyses of nasal fluids indicate that VEGF-A may be an
important mediator in SAR. Copyright 2003 Elsevier Science Ltd.

PMID: 12633568 [PubMed - indexed for MEDLINE]

1131: Am J Respir Crit Care Med. 2003 Jun 1;167(11):1504-8. Epub 2003 Mar 5.

Neural expression and increased lavage fluid levels of secretoneurin in seasonal 
allergic rhinitis.

Korsgren M, Erjefält JS, Hinterholzl J, Fischer-Colbrie R, Emanuelsson CA,
Andersson M, Persson CG, Mackay-Sim A, Sundler F, Greiff L.

Department of Clinical Pharmacology, University Hospital, SE-221 85 Lund, Sweden.
magnus.korsgren@klinfarm.lu.se

Secretoneurin is a neuropeptide potentially involved in migration of eosinophils,
monocytes, and dendritic cells. Whether secretoneurin is present in the human
airway mucosa and whether it is released at ongoing allergic airway inflammation 
is currently unknown. In patients with allergic rhinitis, we have explored the
occurrence of secretoneurin in nasal mucosal biopsies and lavage fluids before
and during natural allergen exposure. Immunohistochemical analysis revealed an
abundance of nerves displaying secretoneurin immunoreactivity, which were
distributed predominantly around blood vessels and submucosal glands. A majority 
of nerve fibers containing vesicular acetylcholine transporter, tyrosine
hydroxylase, calcitonin gene-related peptide, and vasoactive intestinal peptide
were also secretoneurin-immunoreactive, indicating a localization of
secretoneurin in cholinergic, adrenergic, and sensory nerves. Lavage fluid levels
of secretoneurin were increased at allergen exposure (p < 0.01-0.05). Levels of
secretoneurin did not correlate with eosinophil cationic protein (rho = 0.1, p = 
0.7). We conclude that secretoneurin has a widespread occurrence in nasal mucosal
nerves of patients with seasonal allergic rhinitis and that increased nasal
lavage fluid levels of secretoneurin may characterize ongoing allergen exposure. 
These data favor a role of secretoneurin in the local traffic of immune cells in 
human airway mucosa.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12626352 [PubMed - indexed for MEDLINE]

1132: Acta Otolaryngol. 2003 Jan;123(1):75-80.

Prevalence of self-reported allergic and non-allergic rhinitis symptoms in
Stockholm: relation to age, gender, olfactory sense and smoking.

Olsson P, Berglind N, Bellander T, Stjärne P.

Department of Otorhinolaryngology, Huddinge University Hospital, Stockholm,
Sweden. petter.olsson@ent.hs.sll.se

OBJECTIVE: To estimate the prevalence of isolated self-reported allergic and
non-allergic rhinitis symptoms in an adult population and to explore the
relations to age, gender, olfaction and smoking habits. MATERIAL AND METHODS:
Self-judged health and environmental exposures were investigated by means of a
questionnaire survey administered to a stratified random sample of 15,000 adults 
in Stockholm County. RESULTS: A total of 10,670 individuals were included in the 
analysis, corresponding to a response rate of 73%. The results revealed a high
prevalence of self-reported non-allergic rhinitis, 19%, almost as high as the
prevalence of self-reported allergic rhinoconjunctivitis, 24%. In contrast to
current clinical opinion, we did not find a significant increase in the
prevalence of non-allergic symptoms with increased age. There were no
statistically significant gender differences in the prevalence of either allergic
or non-allergic symptoms. A reduced sense of smell was twice as common in the
non-allergic group, 23%, as in the healthy population. The prevalence of rhinitis
symptoms differed according to smoking habits. CONCLUSION: Both self-reported
allergic rhinitis symptoms and non-allergic nasal symptoms are frequent in the
population sample. Self-reported non-allergic nasal symptoms seem to occur
independent of age and reduced olfactory sense is a common complaint among these 
subjects. The prevalence of self-reported allergic and non-allergic nasal
symptoms did not differ much between men and women or between individuals with
different smoking habits.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12625578 [PubMed - indexed for MEDLINE]

1133: Clin Exp Allergy. 2003 Mar;33(3):351-8.

The health-related quality of life effects of once-daily cetirizine HCl in
patients with seasonal allergic rhinitis: a randomized double-blind,
placebo-controlled trial.

Noonan MJ, Raphael GD, Nayak A, Greos L, Olufade AO, Leidy NK, Champan D, Kramer 
B.

Allergy Associates, PC, 545 NE 47th Street, Suite 310, Portland, OR 97213, USA.
allergy1@asthma-research.com

BACKGROUND: Seasonal allergic rhinitis (SAR) is characterized by subjectively
irritating symptoms that can have a substantial impact on the patient's
health-related quality of life (HRQL), adversely affecting physical and social or
work activity, interpersonal relationships, and general psychological well-being.
The objective of this study was to test the effect of cetirizine HCl 10 mg once
daily on the HRQL of adult patients 18-65 years of age with SAR, concurrently
assessing safety and efficacy. METHODS: Randomized double-blind,
placebo-controlled, parallel group trial conducted during the 1999 spring SAR
season at 19 centers in the US. Following a 1-week placebo run-in period,
qualified patients were randomized to cetirizine 10 mg, or placebo once daily for
a 2-week treatment period. Change in Rhinoconjunctivitis Quality of Life
Questionnaire (RQLQ) and Total Symptom Severity Complex (TSSC) scores from
baseline were the primary outcomes of interest. RESULTS: Of the 611 patients
enrolled, 403 (66%) were randomized. Cetirizine-treated patients reported
significantly greater improvement in overall HRQL (P < 0.001) and in each of the 
seven domains of the RQLQ at all time-points (P < 0.05 to < 0.001) than the
placebo group. They also experienced significantly greater symptom relief (P <
0.001) and were more satisfied with treatment (65% vs. 44%) compared to the
placebo group. Correlations between symptomatic relief and overall HRQL
improvement were moderate to strong and statistically significant (r = 0.49-0.68,
P < 0.01). CONCLUSIONS: Results of this study are consistent with previous
investigations, suggesting cetirizine HCl 10 mg taken once daily in the morning
offers symptomatic relief that improves the HRQL of adults suffering from SAR.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12614450 [PubMed - indexed for MEDLINE]

1134: Pediatr Allergy Immunol. 2003 Feb;14(1):60-5.

Steroid-sensitive indices of airway inflammation in children with seasonal
allergic rhinitis.

Meyer P, Andersson M, Persson CG, Greiff L.

Department of Pediatrics, University Hospital, Lund, Sweden.

Previous studies involving adults have demonstrated that airway
glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic
rhinitis. This study explores the possibility that plasma exudation, exudative
responsiveness, and the occurrence of eosinophil activity-related proteins are
glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a
placebo-controlled, parallel-group design effects of nasal budesonide (64 microg 
per nasal cavity b.i.d) were determined in children with seasonal allergic
rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein
(ECP), and alpha2-macroglobulin, indicating plasma exudation, were determined,
the latter with and without challenge with topical histamine. Nasal lavage fluid 
levels of alpha2-macroglobulin and ECP increased significantly during the pollen 
season, and the acute plasma exudation response to histamine was significantly
greater during than outside the season. There was a trend towards a seasonal
increase in nasal lavage fluid levels of eotaxin. Budesonide significantly
inhibited the seasonal increase in alpha2-macroglobulin as well as the exudative 
hyperresponsiveness to histamine. Any tendency of increases in mucosal output of 
eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude
that mucosal exudation of plasma, as a global sign of active inflammatory
processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in
children. Exudative hyperresponsiveness, potentially caused by several weeks of
mucosal inflammation, emerges as a significant feature of allergic rhinitis in
children, and its development is prevented by local treatment with a
glucocorticosteroid drug. The seasonal increase in ECP and the trend for an
increase in eotaxin were absent in the glucocorticosteroid-treated subjects.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12603713 [PubMed - indexed for MEDLINE]

1135: Ann Allergy Asthma Immunol. 2003 Feb;90(2):214-22.

Randomized controlled trial evaluating the clinical benefit of montelukast for
treating spring seasonal allergic rhinitis.

van Adelsberg J, Philip G, LaForce CF, Weinstein SF, Menten J, Malice MP, Reiss
TF; Montelukast Spring Rhinitis Investigator Group.

Merck & Co. Inc. Rahway, New Jersey, USA. janet_vanadelsberg@merck.com

BACKGROUND: Symptoms of allergic rhinitis are mediated in part by cysteinyl
leukotrienes. OBJECTIVE: To evaluate the clinical benefit of montelukast, a
cysteinyl leukotriene receptor antagonist, administered once daily for treating
seasonal allergic rhinitis. METHODS: This multicenter, randomized, double-blind, 
placebo- and active-controlled study enrolled 1,214 healthy, nonsmoking
outpatients aged 15 to 85 years with spring allergic rhinitis, positive skin test
to a spring allergen, and predefined daytime nasal symptoms. After a 3- to 5-day 
placebo run-in period, patients were randomly assigned to treatment with
montelukast 10 mg (n = 522), loratadine 10 mg (n = 171), or placebo (n = 521)
once daily at bedtime for 2 weeks. During the run-in and treatment periods,
symptoms were evaluated in a daily diary using a 0 (best) to 3 (worst) scale.
RESULTS: Baseline characteristics of randomized patients were clinically similar 
in the three treatment groups. Montelukast was significantly more effective than 
placebo (P = 0.003) in improving the daytime nasal symptoms score (difference in 
least square means, -0.09; 95% confidence interval, -0.16, -0.03) averaged over 2
weeks of therapy. The treatment effect of montelukast was significantly greater
(P < 0.05), relative to placebo, for all secondary endpoints, including nighttime
symptoms and daytime eye symptoms, patient and physician global evaluations of
allergic rhinitis, and rhinoconjunctivitis quality of life. Loratadine, which
served as a positive control, was significantly more effective than placebo for
most endpoints, validating the study results. Both montelukast and loratadine
were well tolerated. CONCLUSION: Therapy with montelukast significantly improves 
assessments of symptom severity as well as quality-of-life parameters for
patients with seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12602669 [PubMed - indexed for MEDLINE]

1136: J Allergy Clin Immunol. 2003 Feb;111(2):313-20.

Effect of nasal triamcinolone acetonide on lower airway inflammatory markers in
patients with allergic rhinitis.

Sandrini A, Ferreira IM, Jardim JR, Zamel N, Chapman KR.

Asthma and Airway Centre of the Toronto Western Hospital, University Health
Network, Division of Respiratory Medicine, University of Toronto, 399 Bathurst
Street, Toronto, Ontario M5T 2S8, Canada.

BACKGROUND: Allergic rhinitis (AR) and asthma are commonly associated, and
similar underlying inflammatory processes link both diseases. AR, even in the
absence of asthma, is associated with increased levels of exhaled nitric oxide
(ENO) and hydrogen peroxide (H(2)O(2)) in exhaled breath condensate, 2
noninvasive markers of lower airway inflammation. OBJECTIVE: We sought to
evaluate the effect of treatment with the nasal steroid triamcinolone acetonide
on ENO and exhaled H(2)O(2) in subjects with AR. METHODS: We allocated 23
subjects in a randomized, double-blind, parallel-controlled fashion to 4-week
treatment with triamcinolone acetonide (220 microg/d) or matching placebo.
RESULTS: ENO levels were greater in the subgroup with concomitant asthma (16/23
subjects) and decreased significantly with triamcinolone acetonide treatment in
this subgroup of patients in comparison with patients receiving placebo. Breath
condensate levels of H(2)O(2) were higher in patients with AR without asthma than
in those with asthma but decreased significantly with triamcinolone acetonide
treatment in both subgroups. No changes were observed in bronchial
hyperresponsiveness, nasal and asthma symptoms, or peak expiratory flow with
active treatment or placebo. CONCLUSION: We conclude that treatment of AR with
triamcinolone acetonide results in decrease of 2 noninvasive markers of lower
airway inflammation, ENO and H(2)O(2), supporting that upper and lower airway
inflammation should be seen as a continuum in subjects with AR with and without
asthma. ENO might be a more specific marker of the lower airway inflammation
present in asthma.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12589351 [PubMed - indexed for MEDLINE]

1137: J Allergy Clin Immunol. 2003 Feb;111(2):296-300.

Direct costs of allergic rhinitis in the United States: estimates from the 1996
Medical Expenditure Panel Survey.

Law AW, Reed SD, Sundy JS, Schulman KA.

Center for Clinical and Genetic Economics, Duke Clinical Research Institute,
Durham, NC 27715, USA.

BACKGROUND: Previous estimates of the cost of allergic rhinitis predate the
substantial increase in the use of second-generation antihistamines and
intranasal corticosteroids. OBJECTIVE: We sought to update estimates of the
direct costs of allergic rhinitis in the United States and to estimate
prescription medication expenditures by type of insurance coverage. METHODS: Data
from the 1996 Medical Expenditure Panel Survey were used in a cross-sectional
analysis of resource use and costs. RESULTS: Approximately 7.7% of the population
are estimated to have had allergic rhinitis in 1996. The total direct medical
cost of allergic rhinitis was estimated at $3.4 billion, with the majority
attributable to prescription medications (46.6%) and outpatient visits (51.9%).
Fifty-one percent of the prescription medication expenditures were for
second-generation antihistamines, 25% for intranasal corticosteroids, and 5% for 
first-generation antihistamines. Fifty-eight percent of patients with allergic
rhinitis received 1 or more prescription drugs for its treatment during the study
year. Among these patients, mean prescription expenditures were $131 (95% CI,
$119-$143), of which $50 (95% CI, $43-$56) were paid out of pocket. The mean
prescription medication expenditure was $103 (95% CI, $70-$136) for persons with 
Medicaid, $155 (95% CI, $140-$169) for private insurance, $213 (95% CI, $0-$521) 
for other insurance, and $69 (95% CI, $57-$80) for no prescription drug
insurance. CONCLUSION: The direct costs of allergic rhinitis have increased
substantially since the introduction of second-generation antihistamines and
intranasal corticosteroids, especially costs attributable to prescription
medications. Individuals with no insurance coverage have higher total
out-of-pocket prescription expenditures than those with coverage.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12589348 [PubMed - indexed for MEDLINE]

1138: Clin Exp Allergy. 2003 Feb;33(2):211-7.

Analysis of sequential immunoglobulin E-binding epitope of Japanese cedar pollen 
allergen (Cry j 2) in humans, monkeys and mice.

Tamura Y, Kawaguchi J, Serizawa N, Hirahara K, Shiraishi A, Nigi H, Taniguchi Y, 
Toda M, Inouye S, Takemori T, Sakaguchi M.

Department of Immunology, National Institute of Infectious Diseases, Tokyo,
Japan.

BACKGROUND: Japanese cedar (Cryptomeria japonica; CJ) pollinosis has been
reported to occur naturally in Japanese monkeys (Macaca fuscata) as well as in
humans. Most human patients and monkeys with pollinosis have specific IgE for Cry
j 2, a major allergen of CJ pollen. OBJECTIVE: The main purpose of this study was
to identify IgE B cell epitopes of Cry j 2 using a synthetic peptide in humans,
monkeys and mice. METHODS: We synthesized 38 overlapping peptides that span the
entire length of Cry j 2. We examined the B cell epitopes of Cry j 2 that are
recognized by IgE in the sera of human patients and monkeys with pollinosis and
immunized mice using synthetic peptides of Cry j 2. We also examined the reaction
of Cry j 2-specific mouse monoclonal IgG antibodies to the peptides. Furthermore,
we conducted a histamine release assay with leucocytes from a pollinosis patient 
using human serum albumin (HSA) conjugated with the peptides as a B cell epitope.
RESULTS: We found that 16 of the 20 pollinosis patients who had specific IgE to
Cry j 2 also exhibited IgE reaction with some Cry j 2 peptides. Of these 16
patients, 10 exhibited IgE reaction with Cry j 2 peptide no. 13
(121GQCKWVNGREICNDRDRPTA140). Five of the seven monkeys with CJ pollinosis
exhibited a reaction with peptide no. 13. Furthermore, IgE in mice immunized with
Cry j 2 and two mouse monoclonal IgG antibodies reacted with peptide no. 13.
Peptide no. 13-conjugated HSA showed the release of histamine from basophils.
Furthermore, to determine the minimum epitope in peptide no. 13, we conducted an 
enzyme-linked immunosorbent assay inhibition test. The core of the epitope in
humans, monkeys and mice was 124KWVNGREI131. CONCLUSION: We found that
124KWVNGREI131 is an important B cell epitope recognized by IgE in humans,
monkeys and mice.

PMID: 12580914 [PubMed - indexed for MEDLINE]

1139: Int Arch Allergy Immunol. 2003 Jan;130(1):60-5.

Positive effects of a fresh air filtration system on hay fever symptoms.

Brehler R, Kütting B, Biel K, Luger T.

Department of Dermatology, UKM, Münster, Germany. r.brehler@uni-muenster.de

BACKGROUND: Avoidance of allergen exposure is the basic preventive measure in
reducing symptoms of immediate-type allergies. As room air cleaners were found to
have no benefic effect on general health, their use has not been recommended. The
purpose of this study was to evaluate the effect of a fresh air filtration system
installed in the bedrooms of non-air-conditioned homes on hay fever symptoms.
METHODS: In a placebo-controlled, double-blind, two-period, crossover study, we
investigated the effectiveness of a fresh air filtration system installed in the 
bedrooms of volunteers suffering from hay fever. RESULTS: Volunteers only
suffering from pollinosis reported an improvement of their allergy symptoms. We
observed a significant decrease in nighttime hay fever symptoms and an increase
in morning peak expiratory flow rates (PEFR). No effects were recognized in
volunteers who additionally had perennial allergy. CONCLUSION: Based upon these
results, the installation of fresh air filtration systems in bedrooms should be
recommended for patients suffering from hay fever. Copyright 2003 S. Karger AG,
Basel

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12576736 [PubMed - indexed for MEDLINE]

1140: Int Arch Allergy Immunol. 2003 Jan;130(1):51-9.

Comparison of conjunctival and nasal provocation test in allergic rhinitis to
house dust mite.

Riechelmann H, Epple B, Gropper G.

Department of Otorhinolaryngology, University of Ulm, Germany.
herbert.riechelmann@medizin.uni-ulm.de

BACKGROUND: Nasal allergen provocation tests (NPTs) are useful in confirming the 
diagnosis of allergic rhinitis, if data obtained by clinical history, skin tests 
and specific IgE determinations are not conclusive. Since NPTs are laborious,
conjunctival provocation tests (CPTs) appear as an attractive alternative. The
concordance of CPTs and NPTs with house dust mite allergen extract in sensitized 
and nonsensitized subjects should be evaluated. METHODS: 50 otherwise healthy
subjects with self-reported house dust mite allergy and positive skin prick tests
and serum specific IgE to Dermatophagoides pteronyssinus and 45 sex- and
age-matched healthy controls without allergic symptoms were included. For NPTs,
100 microl allergen extract [10,000 allergy units (AU/ml)] were applied to the
less congested nasal cavity. A clinical symptom score and active anterior
rhinomanometry were employed to assess the response. For CPTs, 50 microl
low-concentrated D. pteronyssinus extract (1,000 AU/ml), and if negative, 50
microl normally concentrated extract (10,000 AU/ml) were applied to the lower
conjunctival sac. The response was assessed employing clinical symptom scores.
RESULTS: NPTs and CPTs yielded concordant results in 90% of the subjects
successfully tested (Cohen's kappa = 0.78, p < 0.0001). The diagnostic efficacy
of the CPT, with the NPT as the reference method, was 89%, whether or not
conjunctival symptoms had been reported in addition to rhinitis symptoms. Both
techniques were judged almost equally uncomfortable. CONCLUSION: CPTs are an
acceptable alternative to NPTs in patients with allergic rhinitis to house dust
mite, even if they have no conjunctival symptoms. Copyright 2003 S. Karger AG,
Basel

Publication Types: 
    Comparative Study

PMID: 12576735 [PubMed - indexed for MEDLINE]

1141: Allergol Immunopathol (Madr). 2003 Jan-Feb;31(1):31-43.

Erratum in:
    Allergol Immunopathol (Madr). 2003 May-Jun;31(3):114.

A pre-seasonal birch/hazel sublingual immunotherapy can improve the outcome of
grass pollen injective treatment in bisensitized individuals. A case-referent,
two-year controlled study.

Cirla AM, Cirla PE, Parmiani S, Pecora S.

Istituti Ospitalieri, Center for Environmental Allergy, Cremona, Italy.

BACKGROUND: The study tests the hypothesis of a reduction of priming due to tree 
allergy in patients sensitised to both birch/hazel and grass pollen undergoing an
associated preseasonal Sublingual/Injective immunotherapy. METHODS: 36 out of 49 
bisensitized candidates were pair-matched into 18 case-referent couples. During
two years all patients were administered preseasonal grass-SIT and one patient in
each couple received also birch/hazel-SLIT. Diary cards were fulfilled for three 
consecutive grass pollen seasons. Specific Nasal Provocation Test (NPT) for grass
and aspecific bronchial challenge were done; sera were analyzed for specific IgE 
and IgG. RESULTS: During the peak of the grass pollen season both groups showed a
significant improvement in total symptom-score. Conjunctivitis and cough improved
significantly more in patients with associated therapies. While antihistamine
score decreased significantly in both groups, antiasthmatics did only in the
SLIT-SIT group. The follow-up documented a significant increase in grass- and
birch-specific IgG and a decrease in grass-specific IgE. Grass-NPT threshold was 
clearly higher in SLIT-SIT-group (p = 0.01) and only in this group PD20
methacholine improved significantly (p < 0.05). CONCLUSIONS: Combined
birch/hazel-SLIT and grass-SIT are safe and improve clinical outcomes of SIT
alone in young bisensitized patients. Priming reduction is supported by specific 
NPT and bronchial hyperresponsiveness.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12573207 [PubMed - indexed for MEDLINE]

1142: Eur Respir J. 2003 Jan;21(1):116-22.

Cost of illness of atopic asthma and seasonal allergic rhinitis in Germany: 1-yr 
retrospective study.

Schramm B, Ehlken B, Smala A, Quednau K, Berger K, Nowak D.

MERG Medical Economics Research Group, Munich, Germany.
Barbara.Schramm@merg-munich.de

The purpose of this study was to evaluate the cost of illness of
moderate-to-severe atopic asthma and/or seasonal allergic rhinitis (SAR) in
Germany from the perspective of third-party payers (TPP) and patients.
Five-hundred patients (276 children/adolescents) with moderate-to-severe asthma
and/or SAR were included in this cross-sectional study. Information was collected
using a specific patient questionnaire and the abstraction of patient records.
Overall, annual costs per patient increased with the severity of atopic asthma
and if it was associated with SAR. The average annual cost of SAR was Euro1,089
per child/adolescent and Euro1,543 per adult. Annual costs of severe asthma plus 
SAR increased to Euro7,928 per child/adolescent and to Euro9,287 per adult. For
TPPs, the main cost drivers were medication, hospitalisation, and rehabilitation.
The most significant costs for patients were household modifications. For
children/adolescents, 60-78% of the expenditures were direct costs, while in
adults, 58% of expenditures were indirect costs. It was also observed that
patients with moderate and severe asthma used inhaled corticosteroids less
frequently than recommended by treatment guidelines. In summary, the total cost
for patients increases with the severity of atopic asthma and/or seasonal
allergic rhinitis and indirect costs represent a large proportion of the total
cost.

PMID: 12570119 [PubMed - indexed for MEDLINE]

1143: Ann Pharmacother. 2003 Feb;37(2):237-46; quiz 313-6.

Erratum in:
    Ann Pharmacother. 2003 Mar;37(3):454.

Desloratadine: a nonsedating antihistamine.

Limon L, Kockler DR.

Department of Pharmacy Services, Virginia Commonwealth University Health System, 
Medical College of Virginia Hospitals and Physicians, Richmond, VA 23298-0042,
USA. llimon@hsc.vcu.edu

OBJECTIVE: To review information on desloratadine, a nonsedating antihistamine.
DATA SOURCES: An English-language MEDLINE search was conducted (1966-July 2002). 
References of identified articles were subsequently reviewed for additional data.
Schering Corporation provided unpublished information. STUDY SELECTION/DATA
EXTRACTION: Articles and abstracts pertaining to desloratadine were considered
for inclusion, with emphasis on randomized, placebo-controlled, double-blind
trials. DATA SYNTHESIS: Desloratadine is approved for the treatment of symptoms
associated with seasonal allergic rhinitis (SAR), perennial allergic rhinitis
(PAR), and chronic idiopathic urticaria (CIU) in patients aged > or =12 years. In
placebo-controlled trials, desloratadine demonstrated superior efficacy as a
once-daily treatment of SAR, PAR, and CIU. Data suggest that desloratadine has
antiinflammatory and decongestant activity. CONCLUSIONS: Desloratadine appears to
be a "me-too" agent, with no major differences compared with other
second-generation antihistamines.

Publication Types: 
    Review

PMID: 12549956 [PubMed - indexed for MEDLINE]

1144: J Appl Physiol. 2003 May;94(5):1821-8. Epub 2003 Jan 24.

Canine model of nasal congestion and allergic rhinitis.

Tiniakov RL, Tiniakova OP, McLeod RL, Hey JA, Yeates DB.

University of Illinois at Chicago, and Veterans Affairs Chicago Health Care
System, Chicago, Illinois 60612, USA.

The ragweed- and histamine-induced decreases in nasal patency in cohorts of
ragweed-sensitized and nonsensitized dogs were assessed. The volume of nasal
airways (V(NA)) was assessed by acoustic rhinometry and resistance to airflow
(R(NA)) by anterior rhinomanometry. Histamine delivered to the nasal passages of 
five dogs caused a rapid and prolonged increase in R(NA) (0.75 +/- 0.26 to 3.56
+/- 0.50 cmH(2)O. l(-1). min), an effect that was reversed by intranasal delivery
of aerosolized phenylephrine. Ragweed challenge in five ragweed-sensitized dogs
increased R(NA) from 0.16 +/- 0.02 to 0.53 +/- 0.07 cmH(2)O. l(-1). min and
decreased V(NA) from 12.5 +/- 1.9 to 3.9 +/- 0.3 cm(3), whereas administration of
saline aerosol neither increased R(NA) nor decreased V(NA). Prior administration 
of d-pseudoephedrine (30 mg po) attenuated the ragweed-induced increase in R(NA) 
and decrease in V(NA). Ragweed challenge changed neither R(NA) nor V(NA) in four 
nonsensitized dogs. Mediator-induced nasal congestion and allergen-induced
allergic rhinitis in ragweed-sensitized dogs, which exhibit symptoms similar to
human disease, can be used in the evaluation of safety and efficacy of
antiallergic activity of potential drugs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12547842 [PubMed - indexed for MEDLINE]

1145: Ann Allergy Asthma Immunol. 2003 Jan;90(1):79-86.

Efficacy and safety of clemastine-pseudoephedrine-acetaminophen versus
pseudoephedrine-acetaminophen in the treatment of seasonal allergic rhinitis in a
1-day, placebo-controlled park study.

Meltzer EO, Casale TB, Gold MS, O'Connor R, Reitberg D, del Rio E, Weiler JM,
Weiler K.

Allergy and Asthma Medical Group and Research Center, San Diego, California, USA.

BACKGROUND: Allergic rhinitis afflicts more than 40 million people in the United 
States and is a leading cause of reduced productivity at work and in school.
Patients with allergic rhinitis have a wide range of symptoms that are often
treated with oral combination products that contain antihistamines,
decongestants, and analgesics. OBJECTIVE: To evaluate the onset of action and the
extent of efficacy and safety of a combination (CPA) of clemastine (0.68 mg),
pseudoephedrine (60 mg), and acetaminophen (1,000 mg) versus a combination (PA)
of pseudoephedrine and acetaminophen versus placebo in the treatment of seasonal 
allergic rhinitis (SAR). The primary goal was to evaluate the benefit of adding
clemastine to the PA combination product to treat the symptoms of SAR. METHOD: A 
1-day, multicenter, double-blind, double-dummy, randomized, parallel-group park
study was organized, and medication was given at 9:00 AM and 3:00 PM. RESULTS: A 
total of 298 subjects participated at two outdoor facilities. The primary
efficacy outcome was the major symptom complex score averaged over the period of 
2 to 5 hours after each dose. Mean absolute and percentage reduction in major
symptom complex averaged over the period of 2 to 5 hours in the CPA group was
significantly superior to those of either the PA (P < 0.01) or placebo (P < 0.03)
groups. Somnolence, fatigue, and nausea were the most common volunteered adverse 
events; only somnolence was significantly greater after CPA than after either PA 
or placebo. CONCLUSIONS: Treatment with CPA was safe and highly effective in
reducing symptoms associated with SAR. It was more effective than either PA or
placebo over most of the postdose observation period.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12546342 [PubMed - indexed for MEDLINE]

1146: Auris Nasus Larynx. 2003 Feb;30 Suppl:S61-8.

Effect of fexofenadine hydrochloride on cedar pollinosis.

Miyabe S, Koizuka I, Ochi K, Tanaka K, Kuroda H, Takatsu M, Kinoshita H, Sugiyama
Y.

Department of Otolaryngology, St. Marianna University School of Medicine, 2-16-1,
Sugao, Miyamae-ku, 216-8511, Kawasaki City, Japan. s2miyabe@marianna-u.ac.jp

OBJECTIVE: To investigate the therapeutic efficacy of fexofenadine hydrochloride 
(Allegra(R) tablets), an antihistaminic launched in 2001, in patients with cedar 
pollinosis by dividing them into two groups for comparison, i.e. the
early-treatment group in which treatment was started before the initial day of
the pollen scattering, and the therapeutic-treatment group in which treatment was
started after the initial day of the pollen scattering. METHODS: Early-treatment 
group: patients who visited the hospital before the initial day of cedar pollen
scattering were orally given one tablet of the drug twice daily.
Therapeutic-treatment group: patients who visited the hospital after the initial 
day of cedar pollen scattering were orally given one tablet of the drug twice
daily. The total number of cases in which the efficacy evaluation was possible
was 37 cases (19 cases of the early-treatment group and 18 cases of the
therapeutic-treatment group) after application of exclusion criteria. RESULTS:
The useful rate of moderately effective or better against sneeze was 90% in the
early-treatment group, and 78% in the therapeutic-treatment group, and there was 
a significant difference between both groups. The degree of satisfaction in the
early-treatment group was 3.8 points, and 4.2 points in the therapeutic-treatment
group, and the therapeutic-treatment group showed a higher score, but there was
no significant difference between both groups. As adverse reaction, there was
only one case of mild dizziness (2.7%), and no other adverse reactions such as
sleepiness were observed. CONCLUSIONS: It was suggested that fexofenadine
hydrochloride administered in patients with cedar pollinosis from before
substantial pollen scattering might control their symptoms to mild ones, and
might control worsening of their symptoms after the substantial pollen
scattering, and, therefore, the drug was considered to be useful in early
therapy.

Publication Types: 
    Clinical Trial

PMID: 12543163 [PubMed - indexed for MEDLINE]

1147: J Allergy Clin Immunol. 2003 Jan;111(1):51-6.

Mode of delivery and risk of allergic rhinitis and asthma.

Bager P, Melbye M, Rostgaard K, Benn CS, Westergaard T.

Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens 
Serum Institut, Copenhagen, Denmark.

BACKGROUND: It has been hypothesized that cesarean section might increase the
risk of developing allergic disease by depriving the fetus and newborn of
exposure to maternal microflora. Furthermore, it has been suggested that
complicated modes of delivery might be associated with an increased risk of
asthma. OBJECTIVE: The purpose of this investigation was to study whether
cesarean section and other complicated modes of delivery are associated with an
increased risk of allergic rhinitis or asthma. METHODS: Information on
self-reported allergic rhinitis, asthma ever, current asthma, and occupation was 
obtained from 9722 singleton women born in Denmark during the period 1973-1977
who participated in a national cohort study during the period 1997-2001. For
these women, information was available on mode of delivery (spontaneous delivery,
cesarean section, vacuum extraction, or other complicated mode of delivery, such 
as rotation/traction or use of forceps), gestational age, birth weight, and
length at birth from the Danish Medical Birth Register. Information on parity and
maternal age was obtained from the Danish Civil Registration System. RESULTS: The
odds ratios (ORs) of allergic rhinitis were 1.16 (95% CI, 0.90-1.49) for cesarean
section and 1.06 (95% CI, 0.85-1.32) for other complicated modes of delivery in
comparison with spontaneous delivery. The corresponding ORs of asthma ever were
1.33 (95% CI, 1.02-1.74) and 1.18 (95% CI, 0.94-1.49) for cesarean section and
other complicated modes of delivery, respectively, and the ORs of current asthma 
were 1.22 (95% CI, 0.87-1.73) and 1.26 (95% CI, 0.94-1.68), respectively, in
comparison with spontaneous delivery. CONCLUSIONS: Our findings do not support
the hypothesis that cesarean section or other complicated modes of delivery are
associated with the development of allergic rhinitis. However, there might be a
positive association with development of asthma--in particular, for cesarean
section--that was not explained by gestational age, birth weight, ponderal index,
smallness for gestational age, parity, maternal age, or occupation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12532096 [PubMed - indexed for MEDLINE]

1148: J Investig Allergol Clin Immunol. 2002;12(3):204-10.

Psychological status of patients with seasonal and perennial allergic rhinitis.

Bavbek S, Kumbasar H, Tuğcu H, Misirligil Z.

Ankara University, Medical School, Department of Allergy, Ankara, Turkey.
bavbek@medicine.ankara.edu.tr

There has been a tendency among some clinicians to underestimate the
psychological problems of patients with rhinitis. This study assesses the
psychological status of allergic rhinitis patients and the influence of type,
duration, and severity of rhinitis on the psychiatric evaluation. Forty-one
patients with seasonal and perennial allergic rhinitis and 36 healthy control
subjects were enrolled in the study. All patients and control subjects were
studied through psychological interviews and several psychological tests such as 
Symptom Checklist-90 (SCL-90), Courtauld Emotional Control Scale, the McMaster
Family Assessment Device, and the Satisfaction with Life Scale. Statistically
significant differences between patients and controls were observed in all
subscales of the SCL-90, particularly in somatization, depression, and general
symptom index subscales. Differences between groups were not significant for the 
other psychological tests. Additionally, differences between seasonal and
perennial allergic rhinitis patients were not significant in all questionnaires. 
Total symptom scores of rhinitis were positively correlated with general symptom 
index, somatization, interpersonal relationship difficulties subgroups of the
SCL-90, whereas negatively correlated with the scores of satisfaction with the
life scale. Patients with allergic rhinitis--regardless of type of rhinitis--may 
develop a group of psychological complaints related to symptom severity. Since
the recognition of specific psychiatric disorders can have therapeutic
importance, further studies focusing on the associations of these disorders and
allergic rhinitis should be conducted.

PMID: 12530120 [PubMed - indexed for MEDLINE]

1149: Allergy Asthma Proc. 2002 Nov-Dec;23(6):391-8.

Comprehensive evaluation of cetirizine in the management of seasonal allergic
rhinitis: impact on symptoms, quality of life, productivity, and activity
impairment.

Murray JJ, Nathan RA, Bronsky EA, Olufade AO, Chapman D, Kramer B.

Vanderbilt University, Asthma Sinus, Allergy Program, 2611 West End Ave. #120,
Nashville, TN 37203, USA.

Improvement in patient daily functioning and well-being resulting from
disease-related symptom relief is increasingly viewed as a clinically relevant
therapeutic outcome. The objective of this study was to evaluate the
health-related quality of life (HRQL) effects, safety and efficacy of cetirizine 
in the treatment of seasonal allergic rhinitis, and impact on self-reported
work/school-related productivity and activity impairment (WPAI). This was a
double-blind, placebo-controlled, parallel-group study. Adult patients (n = 865) 
were randomized to daily treatment for 2 weeks with cetirizine or placebo.
Patient disease-specific HRQL and WPAI were assessed at baseline and weeks 1 and 
2 of treatment using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
and Allergy-Specific Work Productivity and Activity Impairment (WPAI-AS)
Instrument, respectively. Treatment with cetirizine resulted in greater (p <
0.001) improvement in overall RQLQ and individual domain scores (activities,
sleep, non-nose/eye symptoms, practical problems, nasal symptoms, eye symptoms,
emotional), as compared with placebo. Cetirizine therapy produced a 28.9% mean
reduction in total symptom severity complex (TSSC) score versus 12.7% with
placebo at study end. Work/school productivity and activity impairment were
significantly (p < 0.001) decreased from baseline for cetirizine-treated patients
compared with placebo. The incidence of treatment-related side effects was
similar between groups. Cetirizine provides safe and effective symptomatic relief
in adults with SAR while significantly improving HRQL and providing a positive
impact on work/school-related productivity and activity impairment. These results
provide a more comprehensive assessment of cetirizine, indicating that its
benefits extend beyond conventional measures of clinical outcome.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12528605 [PubMed - indexed for MEDLINE]

1150: Rhinology. 2002 Dec;40(4):211-4.

Treating allergic rhinitis in the athlete.

Keleş N.

Department of ORL, Istanbul Faculty of Medicine, Istanbul University, Capa,
Istanbul, Turkey. nkeles@e-kolay.net

Allergic rhinitis may affect athletes like any other member of society. It is a
major problem for the atopic athlete. Either perennial or seasonal, it may cause 
problems with nasal function depending upon the type and quantity of allergen
exposure. Moreover, exposure to irritants, chemicals and air pollutants may
exacerbate allergic rhinitis. In this patient group, special diagnostic and
particularly therapeutic considerations are warranted for the disease. Treatment 
of the athlete should be based on two important principles: no medication given
should be on any list of doping products and no medication used should affect the
athlete's performance. Antihistamines, topical cromolyn, and topical steroids may
be used to control allergic rhinitis without violating 'anti-doping' regulations.

Publication Types: 
    Review

PMID: 12526250 [PubMed - indexed for MEDLINE]

1151: Am J Med. 2002 Dec 16;113 Suppl 9A:17S-24S.

Treatment of allergic rhinitis.

Rosenwasser LJ.

National Jewish Medical and Research Center and the University of Colorado Health
Science Center, Denver, Colorado 80206, USA. rosenwasser@njc.org

Allergic rhinitis, a common and often debilitating disease marked by rhinorrhea, 
nasal congestion, nasal itching, and sneezing, is on the increase worldwide.
Treatment involves allergen avoidance, pharmacotherapy, and, in selected cases,
immunotherapy. This overview describes the characteristics, pathogenesis, and
diagnosis of allergic rhinitis. The major contributing allergens of seasonal and 
perennial allergic rhinitis are identified. Pharmacotherapy is described within
the context of treatment guidelines developed by the major asthma and allergy
professional organizations. Oral H1 antihistamines are first-line therapy for
mild-to-moderate allergic rhinitis. The newer, nonsedating agents are recommended
over first-generation antihistamines. Some of the newer oral antihistamines, such
as cetirizine, desloratadine, and fexofenadine, have been shown to relieve the
symptom of nasal congestion. Intranasal steroids are first-line therapy for
patients with more severe symptoms.

Publication Types: 
    Review

PMID: 12517578 [PubMed - indexed for MEDLINE]

1152: Am J Med. 2002 Dec 16;113 Suppl 9A:8S-16S.

Treatment of allergic asthma.

Lin H, Casale TB.

Division of Allergy/Immunology, Department of Medicine, Creighton University,
Omaha, Nebraska, USA.

Asthma is a chronic inflammatory disorder of the airways that causes recurrent
episodes of wheezing, breathlessness, chest tightness, and coughing, particularly
at night or in the early morning. The airway inflammation also increases
bronchial hyperresponsiveness to a variety of stimuli. After evaluation that
includes spirometry, patients with intermittent asthma are treated with a
short-acting bronchodilator on an as-needed basis. Patients with persistent
asthma should receive inhaled corticosteroids as first-line anti-inflammatory
therapy and long-acting inhaled beta(2)-agonists as preferred adjunctive therapy.
Leukotriene modifiers can be used as maintenance therapy in patients with mild
persistent asthma, or added to the regimen of patients with moderate or severe
persistent asthma. In patients with asthma and concomitant allergic rhinitis,
antihistamines may be useful as adjunctive therapy.

Publication Types: 
    Review

PMID: 12517577 [PubMed - indexed for MEDLINE]

1153: Clin Ther. 2002 Nov;24(11):1800-8.

A comparison of the relative clinical efficacy of a single dose of ketotifen
fumarate 0.025% ophthalmic solution versus placebo in inhibiting the signs and
symptoms of allergic rhinoconjunctivitis as induced by the conjunctival allergen 
challenge model.

Crampton HJ.

Ophthalmic Research Associates, North Andover, Massachusetts, USA.

BACKGROUND: Ketotifen fumarate 0.025% ophthalmic solution is an antiallergic
treatment currently available in the United States. It is indicated for the
temporary prevention of ocular itching due to allergic conjunctivitis. OBJECTIVE:
The purpose of this study was to determine the relative efficacy of ketotifen
when applied topically to the eye, compared with placebo, in the treatment of
nasal signs and symptoms of allergic rhinoconjunctivitis as induced by the
conjunctival allergen challenge (CAC) model. METHODS: This was a randomized,
double-blind, parallel-group, single-center clinical study using the CAC model.
Patients aged > or = 18 years, able to follow the study instructions, willing to 
avoid disallowed medications, and having a history of rhinoconjunctivitis and a
positive skin test were eligible. At visit 1, the dose of allergen necessary to
achieve a qualifying reaction was determined using bilateral ocular instillation 
of allergen to eligible patients. At visit 2, the allergen dose determined at
visit 1 was confirmed, and all patients attaining a qualifying nasal reaction
continued in the study. At visit 3, each patient was randomized to receive 1 drop
of ketotifen bilaterally in the eyes or 1 drop of placebo bilaterally. Fifteen
minutes after instillation of the study medication, bilateral CAC was performed. 
Patients rated nasal symptoms (sneezing, rhinorrhea and postnasal drip, nasal
pruritus, palatal pruritus, and nasal congestion) on standardized scales at 10,
20, and 30 minutes after CAC. RESULTS: Thirty-two patients (16 men, 16 women;
mean age, 45 years [range, 28-70 years]) were randomized to treatment and
completed the study. Nineteen patients received ketotifen and 13 received
placebo. Nasal symptom scores in ketotifen-treated patients were statistically
and clinically significantly fewer than in those treated with placebo at all time
points (mean baseline corrected total nasal score: 10 minutes, P = 0.010; 20
minutes, P = 0.025; 30 minutes, P = 0.006). CONCLUSION: In this study, topical
ketotifen fumarate 0.025% ophthalmic solution, when dosed ocularly, offered
protecdon against the nasal signs and symptoms of acute allergic
rhinoconjunctival reaction as induced by the CAC model.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12501875 [PubMed - indexed for MEDLINE]

1154: Allergy. 2002;57 Suppl 75:25-8.

Impact and modulation of nasal obstruction.

Horak F.

Ear, Nose, and Throat Clinic, Vienna, Austria.

Nasal obstruction, the leading symptom of allergic rhinitis, results from the
combined activity of early- and late-phase allergic reactions. Desloratadine
inhibits both early- and late-phase inflammatory mediators in vitro. Thus,
double-blind, placebo-controlled, randomized, crossover trials were conducted to 
assess the efficacy of desloratadine against nasal obstruction, measured
objectively and subjectively, during controlled exposure of patients with
seasonal allergic rhinitis to allergen. Positive results were obtained in three
single-dose studies; desloratadine 5 mg resulted in a greater improvement from
baseline than did placebo in the total symptom score and the nasal obstruction
symptom score (P </= 0.02). Desloratadine was more effective than placebo in a
multiple-dose study; desloratadine 5 mg was given once daily for 7 days, and a
6-h allergen challenge was administered at the end of treatment compared with
placebo. Desloratadine treatment was associated with less deterioration from
baseline in the mean nasal airflow (P < 0.05) and in the mean severity score for 
the symptom of nasal obstruction (P < 0.03). Desloratadine significantly reduces 
the severity of nasal obstruction in patients with seasonal allergic rhinitis.

Publication Types: 
    Review

PMID: 12492726 [PubMed - indexed for MEDLINE]

1155: J Korean Med Sci. 2002 Dec;17(6):761-4.

Nasal eosinophilic inflammation contributes to bronchial hyperresponsiveness in
patients with allergic rhinitis.

Jang AS.

Department of Internal Medicine, Cheju National University College of Medicine,
Jeju, Korea. jas877@cheju.ac.kr

There are increasing evidences that allergic rhinitis (AR) may influence the
clinical course of asthma. We conducted methacholine challenge test and nasal
eosinophils on nasal smear to patients with allergic rhinitis in order to
investigate the mechanism of connecting upper and lower airway inflammation in 35
patients with AR during exacerbation. The methacholine concentration causing a
20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness
(BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients 
had normal pulmonary function. Significant differences in BHR were detected in
the comparison of patients with cough or postnasal drip and without cough or
postnasal drip. There were significant differences of PC20 between patients with 
cough or postnasal drip and those without cough or postnasal drip (3.41+/-3.59
mg/mL vs 10.2+/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in
patients with seasonal AR than in patients with perennial AR with exacerbation
(472.5+/-132.5 IU/L vs. 389.0+/-70.9 IU/L, p<0.05). Nasal eosinophils were
closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that
nasal eosinophilic inflammation might contribute to BHR in patients with AR.

PMID: 12482998 [PubMed - indexed for MEDLINE]

1156: Allergy Asthma Proc. 2002 Sep-Oct;23(5):325-30.

Efficacy of once-daily desloratadine/pseudoephedrine for relief of nasal
congestion.

Schenkel E, Corren J, Murray JJ.

Valley Clinical Research Center, 3729 Easton-Nazareth Highway, Suite 202, Easton,
PA 18045, USA.

The majority of patients with seasonal allergic rhinitis (SAR) suffer from nasal 
congestion. Desloratadine, a nonsedating H1-receptor antagonist, has given
decongestant relief to patients with mild-to-moderate nasal congestion associated
with SAR. The following study was undertaken to show that a once-daily
formulation of desloratadine/pseudoephedrine would provide greater decongestant
relief to patients experiencing moderate-to-severe nasal congestion compared with
component monotherapy. A total of 1018 patients were assigned randomly to receive
desloratadine/pseudoephedrine (5 mg/240 mg), desloratdine (5 mg), or
pseudoephedrine (240 mg) daily for 15 days. Over the 15-day study period,
patients receiving desloratadine/pseudoephedrine combination tablets had a
significant reduction in mean A.M./P.M. reflective nasal congestion scores
compared with patients receiving desloratadine or pseudoephedrine (p < 0.01);
this reduction reached significance by day 2. Desloratadine/pseudoephedrine
combination tablets also produced a greater reduction in A.M. instantaneous nasal
congestion scores compared with component monotherapy (p < 0.01), indicating not 
only superior efficacy but also a full 24-hour effect. Desloratadine monotherapy 
reduced all mean nasal congestion scores to a similar degree as compared with
pseudoephedrine monotherapy (p = NS). No unusual or unexpected adverse events
were reported in any group. It was concluded that desloratadine/pseudoephedrine
offers additional benefit to patients with moderate-to-severe SAR-associated
nasal congestion compared with pseudoephedrine therapy alone.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12476542 [PubMed - indexed for MEDLINE]

1157: Allergy Asthma Proc. 2002 Sep-Oct;23(5):303-10.

On the association between date of birth and pollen sensitization: is age an
effect modifier?

Guerra S, Sherrill DL, Cottini M, Michetti G, Allegra L.

Institute of Respiratory Diseases, IRCCS Policlinico Hospital, University of
Milan, 20122 Milan, Italy. sguerra@resp-sci.arizona.edu

An association between date of birth and development of allergy has been proposed
by prior research. Yet, the presence of a dose-response relationship or any
potential effect modification for this association has not been widely studied.
The aims of our study were to investigate whether an association between birth
during pollen season and symptomatic sensitization to pollens exists, whether
this association is stronger for patients with high rather than low allergic
reactivity to pollens, and whether this association is modified by the age of the
patients. Among 3318 asthmatic and/or rhinitic outpatients, we selected 805
patients sensitized exclusively to pollens (78 with low reactivity [LR] and 727
with high reactivity [HR]) and 629 patients with negative skin-prick tests (SPT) 
(control group). The association between being born during pollen season
(February-July) and each of the pollen reactivity levels was assessed by
estimating the odds ratios (OR). HR pollinosis patients were more likely than SPT
negative patients of being born in February-July (OR 1.38, 95% Confidence
Intervals (CI) 1.11-1.71). The likelihood of having been born in pollen season
significantly increased across the levels of reactivity to pollens (HR > LR > SPT
negative). These findings were valid only among patients with an early onset of
symptoms. Although the OR for being born in pollen season was 1.91 (95% CI
1.32-2.77) for HR pollinosis patients with onset of symptoms < or = 15 years, it 
was 1.13 (95% CI 0.87-1.48) for those with later onset of symptoms (test of
homogeneity: p = 0.026). Our results suggest that the exposure to allergenic
pollens in the first months of life increases the risk of developing clinically
relevant sensitization to them, particularly in the first 15 years of life.

PMID: 12476539 [PubMed - indexed for MEDLINE]

1158: Clin Pediatr (Phila). 2002 Nov-Dec;41(9):687-96.

The health-related quality of life effects of once-daily cetirizine HCl syrup in 
children with seasonal allergic rhinitis.

Gillman SA, Blatter M, Condemi JJ, Collins M, Olufade AO, Leidy NK, Chapman D,
Kramer B.

CHOC Pediatric Subspecialty Faculty, Division of Allergy and Immunology,
Children's Hospital of Orange County, Orange, CA 92868, USA.

Seasonal allergic rhinitis (SAR) can adversely impact children's physical,
psychological, and social functioning and well-being, that is, their
health-related quality of life (HRQL). This study assessed HRQL in children 6 to 
11 years treated with cetirizine HCl syrup, while concurrently assessing
symptomatic relief and safety. In an open-label, non-comparative study, 544
children from 124 centers in the United States were instructed to take cetirizine
HCl syrup (10 cc of 1 mg/mL) each evening for 4 weeks. Children experienced
statistically significant improvements in HRQL with significant reductions in
mean symptom score (p < 0.001) during the treatment period. Results were
consistent across age groups (6-7, 8-9, 10-11 years). These results suggest that 
the symptomatic relief and tolerability profile of cetirizine HC1 syrup daily
translates into improvements in the HRQL of children with SAR. This 4-week open
label study is among the first to evaluate the effect of antihistamine treatment 
on HRQL outcomes in children.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12462319 [PubMed - indexed for MEDLINE]

1159: Arch Dis Child. 2002 Dec;87(6):478-81.

Breast feeding and allergic diseases in infants-a prospective birth cohort study.

Kull I, Wickman M, Lilja G, Nordvall SL, Pershagen G.

Department of Environmental Health, Stockholm County Council, Stockholm, Sweden.

AIMS: To investigate the effect of breast feeding on allergic disease in infants 
up to 2 years of age. METHODS: A birth cohort of 4089 infants was followed
prospectively in Stockholm, Sweden. Information about various exposures was
obtained by parental questionnaires when the infants were 2 months old, and about
allergic symptoms and feeding at 1 and 2 years of age. Duration of exclusive and 
partial breast feeding was assessed separately. Symptom related definitions of
various allergic diseases were used. Odds ratios (OR) and 95% confidence
intervals (CI) were estimated in a multiple logistic regression model.
Adjustments were made for potential confounders. RESULTS: Children exclusively
breast fed during four months or more exhibited less asthma (7.7% v 12%, OR(adj) 
= 0.7, 95% CI 0.5 to 0.8), less atopic dermatitis (24% v 27%, OR(adj) = 0.8, 95% 
CI 0.7 to 1.0), and less suspected allergic rhinitis (6.5% v 9%, OR(adj) = 0.7,
95% CI 0.5 to 1.0) by 2 years of age. There was a significant risk reduction for 
asthma related to partial breast feeding during six months or more (OR(adj) =
0.7, 95% CI 0.5 to 0.9). Three or more of five possible allergic
disorders-asthma, suspected allergic rhinitis, atopic dermatitis, food allergy
related symptoms, and suspected allergic respiratory symptoms after exposure to
pets or pollen-were found in 6.5% of the children. Exclusive breast feeding
prevented children from having multiple allergic disease (OR(adj) = 0.7, 95% CI
0.5 to 0.9) during the first two years of life. CONCLUSION: Exclusive breast
feeding seems to have a preventive effect on the early development of allergic
disease-that is, asthma, atopic dermatitis, and suspected allergic rhinitis, up
to 2 years of age. This protective effect was also evident for multiple allergic 
disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12456543 [PubMed - indexed for MEDLINE]

1160: Ann Allergy Asthma Immunol. 2002 Nov;89(5):503-12.

Rhinitis (allergic and nonallergic) in an atopic pediatric referral population in
the grasslands of inland South Africa.

Mercer MJ, van der Linde GP, Joubert G.

Department of Paediatrics and Child Health, University of the Orange Free State, 
Bloemfontein, South Africa. househam@shisas.com

BACKGROUND: Allergic rhinitis is a common condition, which causes considerable
morbidity. South African data are scarce. OBJECTIVE: We sought to describe
allergic rhinitis in atopic children in inland South Africa. METHODS: An
observational, descriptive study of rhinitis occurring in 771 new patients seen
consecutively by a single observer at a referral pediatric allergy clinic
(Universitas Hospital, Bloemfontein) over an 8 1/2-year period (August 1984 to
March 1993) was carried out. A detailed questionnaire was used to record clinical
data. Chest and sinus x-rays, skin prick testing, and radioallergosorbent test
were performed, and serum immunoglobulin E levels were determined. Response to
drug treatment regimens was recorded at subsequent followup visits. RESULTS:
Significant rhinitis was reported in 78.1% of patients, and mild intermittent
rhinitis was reported in 21.4%. Male to female ratio was 1.6:1. Median age at
onset of rhinitis symptoms was 6 months (range 0 months to 12 years), with 30.1% 
experiencing symptoms from birth. Rhinitis was chronic in 61.3%, although 53.5%
reported seasonal variation. More children with rhinitis were born in midsummer
than during other seasons, although this did not reach statistical significance
(P = 0.46). Breast-feeding had no protective effect, and parental smoking and
household pets were not found to be risk factors. Family history was positive for
allergic rhinitis in 88% of patients. Exposure to dust, weather changes, strong
odors, pets, pollens, and tobacco smoke were the most common trigger factors.
Sinus x-ray findings associated poorly with clinical findings. The most common
allergens identified were grass pollen, tree pollen, and cat. Oral antihistamines
provided good symptomatic relief in 62.9% of patients who used them. Intranasal
corticosteroids provided good relief in 78.0% of those who used them, and
ketotifen provided relief in 54.4% of those who used it. CONCLUSIONS: Rhinitis is
a common manifestation of allergy in the population studied. Onset occurs early
in childhood. A family history of allergy is a risk factor for the development of
the condition, and grass pollen is the most common allergen involved. Special
investigations are of limited value. Appropriate treatment is very effective.

PMID: 12452210 [PubMed - indexed for MEDLINE]

1161: Ann Allergy Asthma Immunol. 2002 Nov;89(5):485-91.

Safety and efficacy of desloratadine 5 mg in asthma patients with seasonal
allergic rhinitis and nasal congestion.

Berger WE, Schenkel EJ, Mansfield LE; Desloratadine Study Group.

Southern California Research, Mission Viejo, California 92691, USA.
weberger@uci.edu

BACKGROUND: Antihistamines relieve most seasonal allergic rhinitis (SAR)
symptoms, with the exception of nasal congestion, which is often the most
troublesome symptom for patients. A nonsedating antihistamine that significantly 
decreases nasal congestion and improves symptoms of seasonal allergic asthma
would be a significant advance in therapy. OBJECTIVES: To evaluate the safety and
efficacy of desloratadine 5 mg in patients experiencing moderate SAR, nasal
congestion, and symptoms of seasonal allergic asthma. METHODS: This 4-week,
multicenter, parallel-group, double-blind study evaluated desloratadine treatment
(5 mg once daily) versus placebo in 331 subjects with SAR and mild seasonal
allergic asthma. Subjects evaluated SAR and asthma symptoms twice daily,
recording 12-hour reflective and instantaneous severity evaluation scores. The
primary efficacy parameter was the difference from baseline in AM/PM reflective
total symptom scores. Changes in individual SAR and asthma symptoms were also
analyzed. RESULTS: Compared with placebo, desloratadine significantly reduced
mean AM/PM reflective total symptom scores for SAR, beginning with the first dose
(P < 0.001) and continuing throughout days 1 to 15 (-4.90 vs -2.98; P < 0.001)
and days 1 to 29 (-5.47 vs -3.73; P < 0.001). Desloratadine significantly
decreased AM/PM reflective total asthma symptom scores for days 1 to 15 (P =
0.023) and AM/PM reflective nasal congestion scores over days 1 to 15 and days 1 
to 29 (P = 0.006 and P = 0.014, respectively). Desloratadine was safe and well
tolerated; adverse events were similar to placebo overall. CONCLUSIONS:
Desloratadine provided significant relief from the signs and symptoms of SAR,
including nasal congestion. In this patient population, symptoms of seasonal
allergic asthma also improved.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12452207 [PubMed - indexed for MEDLINE]

1162: Ann Allergy Asthma Immunol. 2002 Nov;89(5):479-84.

Intranasal corticosteroids versus topical H1 receptor antagonists for the
treatment of allergic rhinitis: a systematic review with meta-analysis.

Yáñez A, Rodrigo GJ.

Servicio de Alergia e Inmunología Clínica, Hospital Aeronáutico Central, Buenos
Aires, Argentina.

OBJECTIVE: We performed a systematic review of randomized, controlled trials to
determine whether intranasal corticosteroids offered an advantage over topical
antihistamines in the treatment of allergic rhinitis. DATA SOURCES: We searched
for studies using MEDLINE, Embase, Cinahi, and Cochrane databases, pharmaceutical
companies, and references of included trials. STUDY SELECTION: Criteria for
considering trials included: 1) published randomized controlled trials; 2)
single- or double-blind studies; and 3) presence of one of the following clinical
outcomes: nasal symptoms, eye symptoms, global symptoms evaluation of quality of 
life and side effects. RESULTS: Nine studies including 648 subjects (mean age
30.4 years, range 13 to 73) with allergic rhinitis were selected. Intranasal
corticosteroids produced significantly greater reduction of total nasal symptoms 
(standardized mean difference -0.36, 95% confidence interval -0.57 to -0.14),
sneezing (-0.41, -0.57 to -0.24), rhinorrhea (-0.47, -0.64 to -0.29), itching
(-0.38, -0.56 to -0.19), and nasal blockage (-0.86, -1.07 to -0.64) than did
topical antihistamines. There was no significant difference between treatments
for ocular symptoms (-0.07, -0.27 to 0.12). The effects on sneezing, rhinorrhea, 
itching, and ocular symptoms were significantly heterogeneous between studies.
Other outcomes (total nasal symptom score and nasal blockage) were homogeneous
between studies. Subgroup and sensitivity analysis suggested that most of the
heterogeneity of outcomes could be explained on the basis of the methodologic
quality of studies. CONCLUSIONS: Intranasal corticosteroids produced greater
relief of nasal symptoms than did topical antihistamines (topical H1 receptor
antagonists). However, there was no difference in the relief of the ocular
symptoms.

Publication Types: 
    Meta-Analysis
    Review

PMID: 12452206 [PubMed - indexed for MEDLINE]

1163: Ann Allergy Asthma Immunol. 2002 Nov;89(5):457-62.

Comment in:
    Ann Allergy Asthma Immunol. 2002 Nov;89(5):435-6.

Health care costs of allergic rhinitis-associated conditions vary with allergy
season.

Crystal-Peters J, Neslusan CA, Smith MW, Togias A.

The MEDSTAT Group, Washington, DC 20008, USA. jodi.peters@medstat.com

BACKGROUND: Studies have documented how allergic respiratory symptoms vary with
allergen levels, but the impact of allergen levels on health care expenditures
for allergy-related conditions has never been shown using actual data on outdoor 
allergen levels. Evidence linking respiratory allergy to comorbid conditions has 
also been scanty. OBJECTIVE: To investigate the link between respiratory allergy 
and presumably associated conditions by documenting seasonal patterns in their
severity and co-occurrence, and to suggest a plan for future research. METHODS: A
retrospective, cross-sectional analysis of medical claims data from 1995 to 1996 
were linked to monthly data from federal counting stations on outdoor allergen
levels. Participants were employed persons and their dependents, living within 15
miles of an allergen-counting station, continuously enrolled in a health plan for
1995 and 1996, and identified through medical claims data as having asthma,
allergic rhinitis (AR), migraines, sinusitis, tonsillitis, otitis media,
depression, or anxiety disorder. RESULTS: All conditions studied were more likely
to occur during allergy season than during nonallergy season. For persons with
health care claims for a condition of interest in both seasons, total health care
costs during allergy season were significantly higher than during nonallergy
season. Predicted condition-related expenditures were higher in allergy season
for every condition even after controlling for the effect of AR. CONCLUSION:
Allergy effects appear to extend beyond AR symptoms. Other conditions may be
affected by outdoor allergen levels even in the absence of AR symptoms, implying 
that these conditions may be etiologically related to allergy, irrespective of
their co-existence with allergic rhinitis, further implying that allergic
sensitization can independently affect different parts of the respiratory tract
as well as the brain.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12452202 [PubMed - indexed for MEDLINE]

1164: Am J Respir Crit Care Med. 2003 Feb 15;167(4):538-43. Epub 2002 Nov 21.

Comment in:
    Am J Respir Crit Care Med. 2004 Feb 1;169(3):428.    Am J Respir Crit Care Med. 2004 Jan 15;169(2):318; author reply 319.    Am J Respir Crit Care Med. 2004 Jan 15;169(2):318; author reply 319.

Rhinitis is associated with increased systolic blood pressure in men: a
population-based study.

Kony S, Zureik M, Neukirch C, Leynaert B, Vervloet D, Neukirch F.

Unit 408, Respiratory Diseases Epidemiology, National Institute of Health and
Medical Research (INSERM), Paris, France.

An association between impaired lower respiratory function and cardiovascular
risk factors, such as hypertension, is often reported but it is unknown whether
there is a relationship between upper airway disorders and cardiovascular risk
factors, despite evidence that upper and lower respiratory tract disorders are
closely linked. Our objective was to assess whether rhinitis is associated with
arterial blood pressure and hypertension. In a population-based study of 330
adults aged 28-56 years, as part of the European Community Respiratory Health
Survey, rhinitis was assessed by means of a questionnaire, and cardiovascular
data were obtained using a questionnaire and by measuring blood pressure.
Systolic blood pressure (SBP) was higher in men with rhinitis than in men without
rhinitis (130.6 +/- 12.7 mm Hg versus 123.5 +/- 13.9 mm Hg; p = 0.002), and it
was still the case after adjustment for cardiovascular and respiratory
confounding factors. Hypertension was more frequent in men with rhinitis than in 
men without rhinitis, even after multivariate adjustment (odds ratio = 2.6, 95%
confidence interval = [1.14-5.91]). The observation of SBP levels according to
whether men have no rhinitis, seasonal rhinitis, or perennial rhinitis was
compatible with a dose-response relationship (p for trend = 0.02). In conclusion,
rhinitis is strongly associated with SBP and hypertension in men. Blood pressure 
should be regularly checked in men with rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12446269 [PubMed - indexed for MEDLINE]

1165: J Invest Dermatol. 2002 Nov;119(5):1059-64.

Inhibition of IgE production by the imidazoquinoline resiquimod in nonallergic
and allergic donors.

Frotscher B, Anton K, Worm M.

Department of Dermatology and Allergy, Charité, Campus Virchow Klinikum, Humboldt
Universität zu Berlin, Germany.

The aim of this study was to examine whether the immune modulator resiquimod,
which belongs like imiquimod to the imidazoquinolines, is capable of influencing 
IgE synthesis. Peripheral blood mono-nuclear cells from normal donors and
patients with atopic dermatitis and with seasonal allergic rhinitis were analyzed
in the presence of resiquimod, anti-CD40+interleukin-4 stimulation for induction 
of IgE, and anti-CD40+interleukin-4 in the presence of resiquimod, respectively. 
Our data show that spontaneous IgE production was inhibited in the presence of
resiquimod, which was strongest at 10 ng per ml in both groups of allergic
patients. Inhibition of IgE production after anti-CD40+interleukin-4 stimulation 
in the presence of resiquimod (10 ng per ml) was comparable between all the
groups. In normal donors median inhibition of IgE synthesis was 93%, in seasonal 
allergic rhinitis patients 77%, and in patients with atopic dermatitis 72%. In
order to rule out antiproliferative effects of resiquimod, which might influence 
IgE production, we also studied proliferation of peripheral blood mononuclear
cells from normal donors, which remained unchanged in the presence of resiquimod 
at 0.1-10 ng per ml but was inhibited at 100 or 1000 ng per ml. In search of
possible mechanisms responsible for the observed inhibition of IgE production, we
analyzed the expression and production of molecules that are known to modulate
IgE production, namely CD23 and interferon-gamma. CD23 expression on B cells was 
lower in the presence of resiquimod (10 ng per ml) in anti-CD40+interleukin-4
stimulated cells, whereas interferon-gamma was strongly induced (4-6-fold) by
resiquimod (10 ng per ml). Furthermore, by using neutralizing interferon-gamma
monoclonal antibodies, we show that inhibition of IgE production occurred in an
interferon-gamma-dependent manner. Taken together our results show that
resiquimod is a potent modulator of IgE production in vitro in normal but also in
allergic donors.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 12445193 [PubMed - indexed for MEDLINE]

1166: Curr Med Res Opin. 2002;18(6):332-7.

The use of antihistamines in safety-critical jobs: a meeting report.

Mohler SR, Nicholson A, Harvey P, Miura Y, Meeves SG.

Wright State University Medical School, Good Samaritan Hospital and Health
Center, Dayton, OH 45406, USA. stanley.mohler@wright.edu

The use of sedating agents by aircrew and those with safety-critical occupations 
has raised serious concern and has been extensively debated for several years.
This meeting report summarizes the findings of an international panel of experts 
in aerospace medicine and allergic rhinitis who were brought together to discuss 
issues related to the use of antihistamines, in particular the selective,
H1-receptor antagonist fexofenadine, in pilots. The presentations covered a wide 
range of topics including methods for accurately assessing sedation and
impairment, and the validity of laboratory testing versus simulator assessments. 
The panel also examined data on sedation and impairment levels with currently
available antihistamines and assessed the impact of these data on their use by
pilots and aircrew. It was the consensus of the meeting that fexofenadine can be 
safely recommended for use in individuals involved in skilled activities, such as
pilots, without the concern of sedation above recommended therapeutic doses.

Publication Types: 
    Congresses

PMID: 12442879 [PubMed - indexed for MEDLINE]

1167: Pharmacotherapy. 2002 Nov;22(11):1458-67.

Intranasal corticosteroids for allergic rhinitis.

Trangsrud AJ, Whitaker AL, Small RE.

Department of Pharmacy Practice, College of Pharmacy, Midwestern University,
Glendale, Illinois, USA.

Intranasal corticosteroids are accepted as safe and effective first-line therapy 
for allergic rhinitis. Several intranasal corticosteroids are available:
beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate,
mometasone furoate, and triamcinolone acetonide. All are efficacious in treating 
seasonal allergic rhinitis and as prophylaxis for perennial allergic rhinitis. In
general, they relieve nasal congestion and itching, rhinorrhea, and sneezing that
occur in the early and late phases of allergic response, with studies showing
almost complete prevention of late-phase symptoms. The rationale for topical
intranasal corticosteroids in the treatment of allergic rhinitis is that adequate
drug concentrations can be achieved at receptor sites in the nasal mucosa. This
leads to symptom control and reduces the risk of systemic adverse effects.
Adverse reactions usually are limited to the nasal mucosa, such as dryness,
burning and stinging, and sneezing, together with headache and epistaxis in 5-10%
of patients regardless of formulation or compound. Differences among agents are
limited to potency, patient preference, dosing regimens, and delivery, device and
vehicle.

Publication Types: 
    Review

PMID: 12432972 [PubMed - indexed for MEDLINE]

1168: J Infect. 2002 Nov;45(4):227-32.

Effects of rhinovirus-induced common colds on granulocyte activity in allergic
rhinitis.

Greiff L, Venge P, Andersson M, Enander I, Linden M, Myint S, Persson CG.

Department of Otorhinolaryngology, University Hospital, S-221 85 Lund, Sweden.
lennart.greiff@skane.se

OBJECTIVE: To explore the activities of mast cells, eosinophils, and neutrophils 
in patients with allergic rhinitis developing common colds and increased
responsiveness to allergen following nasal rhinovirus inoculation. METHODS: We
have revisited a nasal lavage material obtained from 17 patients who were
successfully inoculated with rhinovirus outside the pollen season and received
nasal allergen challenges before and after inoculation. We have examined indices 
of mast cell activity (tryptase), eosinophil degranulation (eosinophil
peroxidase; EPO), and neutrophil activation (myeloperoxidase; MPO). RESULTS:
Allergen challenges performed before rhinovirus inoculation increased the nasal
output of EPO. Notably, this response was significantly greater after rhinovirus 
inoculation (cf. before inoculation). The output of MPO was also increased
following allergen challenge after, but not before, rhinovirus inoculation. Nasal
lavage fluid levels of tryptase were increased following allergen challenge
similarly before and after rhinovirus inoculation. Also, the viral infection did 
not affect the baseline levels of tryptase. CONCLUSIONS: The present data
demonstrate that rhinovirus infections activate both eosinophils and neutrophils,
but that they may not affect mast cell activity. We suggest that common colds in 
part through stimulation of granulocyte activity potentiate the airway
inflammation in allergic diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12423609 [PubMed - indexed for MEDLINE]

1169: Respir Med. 2002 Nov;96(11):927-33.

Natural allergen exposure does not diminish the sensitivity of cytokine
production to glucocorticosteroids in blood cells of seasonal allergic asthma and
rhinitis patients.

Larsson S, Hansson L, Greiff L, Löfdahl CG, Persson CG, Broberg P, Linden M.

Department of Respiratory Medicine, Lund University Hospital, Sweden.
susannelarsson.lund@telia.com

Glucocorticosteroid (GCS) inhibition of cytokine production is a major
anti-inflammatory mechanism. However, increased production of pro-inflammatory
cytokines during allergic airway inflammation has been proposed to reduce GCS
effects. This study aimed to investigate whether allergic airway inflammation due
to natural allergen exposure might decrease the sensitivity of
granulocyte-macrophage colony-stimulating factor (GM-CSF) production to GCS in
blood cells. Blood samples were collected from patients with seasonal allergic
asthma (n = 10) and rhinitis (n = 8) and healthy subjects (n = 9), before,
during, and after the birch pollen season. Whole blood cultures were stimulated
with LPS (10 ng/ml) and treated with budesonide (10(-11)-10(-7) M) for 20 h.
GM-CSF levels were analysed using immunoassay. Birch pollen exposure did not
alter LPS-stimulated GM-CSF production, although disease symptoms and blood
eosinophils increased in the patients. There were no significant differences in
budesonide inhibition of GM-CSF production by blood cells of asthma and rhinitis 
patients compared with cells of healthy subjects before, during or after the
birch pollen season and no change in response to allergen exposure. A
concentration of 1 nM budesonide inhibited GM-CSF production by more than 50% at 
all time points. In conclusion, natural allergen exposure did not reduce the
sensitivity of GM-CSF production to GCS inhibition in blood cells of seasonal
allergic asthma and rhinitis patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12418591 [PubMed - indexed for MEDLINE]

1170: J Allergy Clin Immunol. 2002 Nov;110(5):728-35.

The effect of anti-IgE treatment on in vitro leukotriene release in children with
seasonal allergic rhinitis.

Kopp MV, Brauburger J, Riedinger F, Beischer D, Ihorst G, Kamin W, Zielen S, Bez,
Friedrichs F, Von Berg A, Gerhold K, Hamelmann E, Hultsch, Kuehr J.

University Children's Hospital, Freiburg, Germany.

BACKGROUND: Binding of allergens with IgE to the IgE receptors on mast cells and 
basophils results in the release of inflammatory mediators as sulfidoleukotrienes
(SLTs), triggering allergic cascades that result in allergic symptoms, such as
asthma and rhinitis. OBJECTIVE: We sought to investigate whether anti-IgE
(Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific 
immunotherapy (SIT) affects the leukotriene pathway. METHODS: Ninety-two children
(age range, 6-17 years) with sensitization to birch and grass pollens and with
seasonal allergic rhinitis were included in a phase III, placebo- controlled,
multicenter clinical study. All subjects were randomized to one of 4 treatment
groups. Two groups subcutaneously received birch SIT and 2 groups received grass 
SIT for at least 14 weeks before the start of the birch pollen season. After 12
weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary
clinical efficacy variable was symptom load (ie, the sum of daily symptom
severity score and rescue medication score during pollen season). Blood samples
taken at baseline and at the end of study treatment after the grass pollen season
were used for separation of leukocytes in this substudy. After in vitro
stimulation of the blood cells with grass and birch pollen allergens, SLT release
(LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. RESULTS:
Before the study treatment, SLT release to birch and grass pollen exposure did
not differ significantly among the 4 groups. Under treatment with anti-IgE +
SIT-grass (n = 23), a lower symptom load occurred during the pollen season
compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both
groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end 
of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE
plus birch SIT, resulted in significantly lower SLT release after stimulation
with the corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207
ng/L [1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L
[384-6587 ng/L], P =.001; 2489 ng/L [1-5670 ng/L], P =.001). In addition,
treatment with anti-IgE was also followed by significantly lower SLT releases to 
the allergens unrelated to SIT (grass SIT: 300 ng/L [1-2432 ng/L] in response to 
birch allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen)
in comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P =.001; birch
SIT: 2792 ng/L [154-5839 ng/L], P =.04]. CONCLUSION: Anti-IgE therapy reduces
leukotriene release of peripheral leukocytes stimulated with allergen in children
with allergic rhinitis undergoing allergen immunotherapy independent of the type 
of SIT allergen used.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12417881 [PubMed - indexed for MEDLINE]

1171: Thorax. 2002 Nov;57(11):945-50.

Early exposure to children in family and day care as related to adult asthma and 
hay fever: results from the European Community Respiratory Health Survey.

Svanes C, Jarvis D, Chinn S, Omenaas E, Gulsvik A, Burney P; European Community
Respiratory Health Survey.

Department of Thoracic Medicine, University of Bergen, 5021 Bergen, Norway.
cecilie.svanes@haraldsplass.no

BACKGROUND: The literature indicates that early exposure to children in the
family and to day care permanently influences the development of allergic
disease. A study was undertaken to examine the associations of family size and
day care with adult asthma and hay fever and to determine whether these
associations are mediated through specific IgE production and whether they vary
with allergic predisposition. METHODS: 18,530 subjects aged 20-44 years from 36
areas predominantly in the market economies participated in the European
Community Respiratory Health Survey and provided information through
interviewer-led questionnaires. 13,932 subjects gave blood samples for
measurement of specific IgE. RESULTS: Hay fever was less common in subjects with 
many siblings (OR=0.92; 95% CI 0.90 to 0.95 per sib). There was a U-shaped
relationship between asthma and number of siblings (quadratic effect of siblings,
pwheeze=0.014, pFEV(1)=0.016). In subjects without siblings but exposed to
children in day care, hay fever was less common (OR=0.76; 95% CI 0.60 to 0.98)
and asthma symptoms were more common (ORwheeze=1.48; 95% CI 1.12 to 1.95).
Adjustment for specific IgEs did not alter these associations. The inverse
association of hay fever with siblings was found in sensitised subjects (OR=0.89;
95% CI 0.84 to 0.94) and in those with parental allergy (OR=0.91; 95% CI 0.85 to 
0.97), but not in subjects without such a predisposition (OR=1.02; 95% CI 0.97 to
1.09). CONCLUSION: Subjects exposed to many children at home or in day care
experienced less hay fever and more asthma in adulthood. Microbial challenge
through children may contribute to a non-allergic immunological development
giving less hay fever but more airways infections predisposing to asthma. These
effects were not mediated through production of specific IgE. The protective
effect of siblings on hay fever was particularly strong in those with an allergic
predisposition.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12403876 [PubMed - indexed for MEDLINE]

1172: J Environ Monit. 2002 Oct;4(5):734-8.

Pollen allergy related to the area of residence in the city of Córdoba,
south-west Spain.

Cariñanos P, Sánchez-Mesa JA, Prieto-Baena JC, Lopez A, Guerra F, Moreno C,
Dominguez E, Galan C.

Department of Plant Biology, University of Córdoba, Spain.

The aim of this study was to analyse the relationship between the distribution of
hay-fever patients in the city of Córdoba, south-western Iberian Peninsula, and
the specific atmospheric biological content originating from local sources. Four 
different districts were established in the metropolitan area of the city,
according to vegetational and urbanistic characteristics. Air samples were taken 
in each area using portable Hirst-type samplers (Lanzoni VPPS 1000) and the
spectrum of biological content was defined. Patients attending the Allergy Unit
at Córdoba Teaching Hospital in 2000 with allergic rhinitis and/or asthma, and
displaying a positive reaction to aeroallergen extracts, were distributed within 
the areas as a function of their district of residence. Aerobiological results
revealed differences in pollen content between areas, in terms of both quantity
and number of pollen types recorded. These differences were largely due to
proximity to rural areas, prevalence of pollen from typically urban species and
the possible effect of urban architecture as a barrier to the dispersal/
concentration of particles and other pollutants. Patients were not uniformly
distributed within the city. The majority lived in districts in which pollen from
rural species was mixed with pollen from ornamentals. Patients living in
typically urban districts displayed a higher prevalence of allergy to pollen from
ornamentals. It is concluded that a high degree of exposure to the same
environment may influence the development of sensitisation to the particular
pollen load associated with that area.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12400923 [PubMed - indexed for MEDLINE]

1173: Mediators Inflamm. 2002 Aug;11(4):225-33.

Increased apoptosis of peripheral blood mononuclear cells in patients with
perennial allergic asthma/rhinitis: relation to serum markers of apoptosis.

Grzegorczyk J, Kowalski ML, Pilat A, Iwaszkiewicz J.

Department of Clinical Immunology and Allergy, Faculty of Medicine, Medical
University of Lodz, 251 Pomorska Street, 92-213 Lodz, Poland.
ngrzegor@csk.am.lodz.pl

BACKGROUND: The goal of our study was to examine spontaneous and stimulated
apoptosis of peripheral blood MNC from allergic patients, sensitized to Der p I
antigen as compared to cells from non-atopic subjects. Furthermore we aimed to
investigate which populations of mononuclear cells (lymphocytes, monocytes)
undergo the apoptosis and to determine relations between apoptosis and serum
levels of sFas/APO-1, ICE/caspase-1 or TNF-alpha. METHODS: The study included 17 
patients with perennial, allergic asthma and/or allergic rhinitis [6 male and 11 
female; mean age 29,5 years; (range 15-49)]. Apoptosis was assessed by
fluorescence technique and confirmed by flow-cytometric method and DNA ladder.
Serum levels of sFas, ICE/caspase-1 or TNF-alpha were determined by immunoassays 
(ELISA). RESULTS: Apoptotic index of unfractionated mononuclear cells (MNC) and
lymphocytes (but not monocytes) were significantly higher in allergic patients as
compared to non-allergic subjects after 48 and 72 hours of culture (p<0.05).
Incubation of cells with ConA (10 microg/ml) resulted in a significant increase
in the proportion of apoptotic cells in all populations once the apoptotic index 
for MNC and lymphocytes (but not monocytes) was again significantly higher in
allergic as compared to non-allergic subjects after 24, 48 and 72 hour of
culture. In allergic patients, mean serum sFas level, was significantly lower
then in non-allergic group (mean value 624.8 pg/ml +/- 25.67 versus 802.0 pg/ml
+/- 31.91; p = 0.003) and in both groups sFas level correlated inversely with
apoptosis of MNC. The mean ICE/caspase-1 concentration was significantly higher
in sera of allergic patients as compared to non-allergic group (mean value 27.71 
pg/ml +/- 3.79 vs 23.54 pg/ml respectively; p<0.01). ICE/caspase-1 levels in
allergic patients correlated with apoptotic index of mononuclear cells (r = 0.57;
p<0.001). CONCLUSIONS: An increased spontaneous and mitogen-induced apoptosis of 
MNC from peripheral blood of atopic patients as well as different serum levels of
sFas and ICE/caspase-1 correlating with apoptosis, suggest different regulation
of apoptotic process in peripheral blood mononuclear cells of patients with
allergic asthma and/or rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12396474 [PubMed - indexed for MEDLINE]

1174: Clin J Sport Med. 2002 Sep;12(5):296-300.

Effects of intranasal budesonide on symptoms, quality of life, and performance in
elite athletes with allergic rhinoconjunctivitis.

Katelaris CH, Carrozzi FM, Burke TV, Byth K.

Institute of Immunology and Allergy Research, Westmead Hospital, Sydney,
Australia. chk@allergyimmunol.com.au

OBJECTIVE: To assess change in symptoms, quality of life (QOL), and performance
ability before, during, and after treatment with budesonide in a group of Olympic
and Paralympic athletes with seasonal allergic rhinoconjunctivitis (SAR/C).
DESIGN: Because budesonide has already been proven to be an effective and
well-tolerated treatment of SAR/C(1), an open-label treatment format was used.
SETTING: The study was community-based with participating athletes preparing for 
Olympic competition. PARTICIPANTS: Olympic and Paralympic athletes were screened 
for the presence of SAR/C using history and positive skin test results for pollen
allergens. INTERVENTIONS: All were offered treatment with intranasal budesonide, 
applied to each nostril, once daily for eight weeks. OUTCOME MEASUREMENTS:
Symptom and medication diaries were completed before treatment and after 4 and 8 
weeks of treatment. Similarly, Quality of Life (QOL) was measured with the
Rhinoconjunctivitis Quality of Life Questionnaire. As a secondary outcome
measure, the ability to train and compete was assessed using a performance diary.
RESULTS: Of the 236 athletes eligible for the study, 145 (61%) agreed to
participate. Forty-six percent of the athletes who were dispensed treatment did
not return questionnaires. For those returning questionnaires, scores between
baseline (week 0) and weeks 4 and 8 were calculated for total symptoms, QOL, and 
performance scores. There were statistically significant improvements in
symptoms, QOL, and performance scores in athletes who used intranasal budesonide.
CONCLUSION: SAR/C is a common condition and has demonstrable negative effects on 
athletes. Better education of coaches and athletes is necessary to ensure that
the condition is correctly diagnosed and treated, with safe, effective, permitted
medication.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12394202 [PubMed - indexed for MEDLINE]

1175: Control Clin Trials. 2002 Oct;23(5):469-80.

The use of handheld computers in clinical trials.

Koop A, Mösges R.

Institute for Medical Statistics, Informatics, and Epidemiology, University of
Cologne, Cologne, Germany. Andreas.Koop@medizin@uni-koeln.de

A recently completed, randomized, double-blind placebo-controlled clinical trial 
is presented in which Palm handheld computers were used as a substitute for
normal paper-based patient diaries. In this nasal provocation study, a common
antihistamine approved for the treatment of seasonal allergic rhinitis was tested
against placebo for evidence of additional properties. In addition to their
medical examinations, the 12 study volunteers rated subjective complaints in a
diary program on 4 examination days, for a duration of 4.5 hours every 15 minutes
at each visit. This resulted in 903 data sets consisting of five questions each, 
or 4515 data points total. In this study the use of handheld computers resulted
in an increase in data quality and shortened the time needed to close the
database. Moreover, the benefit of electronic reminders for protocol compliance
is clearly demonstrated. Our findings support the results found in the literature
we reviewed. For more than 16 years, mobile computers have been supporting the
implementation of clinical trials. Our review of 27 articles out of more than 100
clinical trials in which mobile computers have been used elaborates on the
advantages and problems of this technology. We give a comprehensive overview of
the various technologies as used in different settings, and then discuss the
methodology of using mobile devices in comparison to traditional methods, the
considerations that need to be made and things to be avoided in order to conduct 
a successful clinical trial with mobile tools. We conclude that mobile devices
are very useful in most cases, especially when design and software validation
aspects have been taken into account. Copyright 2002 Elsevier Science Inc.

Publication Types: 
    Clinical Trial
    Comparative Study
    Evaluation Studies
    Randomized Controlled Trial

PMID: 12392861 [PubMed - indexed for MEDLINE]

1176: Ann Allergy Asthma Immunol. 2002 Oct;89(4):413-8.

Desloratadine reduces allergen challenge-induced mucinous secretion and plasma
exudation in allergic rhinitis.

Greiff L, Persson CG, Andersson M.

Department of Otorhinolaryngology, University Hospital, Lund, Sweden.
lennart.greiff@skane.se

BACKGROUND: Rhinorrhea is a key symptom of allergic rhinitis and this disease
feature is reduced by antihistamine treatment. The nasal output of fluid in
allergic rhinitis is associated with luminal appearance of bioactive molecules
emanating from the microcirculation as well as the secretory apparatus.
OBJECTIVE: In the present study, we examined the effects of antihistamine
treatment on nasal symptoms and output of mucinous secretions and plasma.
METHODS: Desloratadine (5 mg) was administered orally once daily for 5 days in a 
placebo-controlled, crossover design to 24 patients with allergic rhinitis. Nasal
challenges with diluent and allergen (100 to 10,000 SQ-U) were carried out on day
5 of the treatment. The nasal mucosa was lavaged with saline, and symptoms were
scored 10 minutes after each allergen challenge and 1 to 4 hours after the
challenge series. Nasal lavage fluid levels of fucose and alpha2-macroglobulin
were determined as indices of mucinous secretion and plasma exudation,
respectively. RESULTS: The allergen challenges produced nasal symptoms, including
rhinorrhea, and increased nasal output of fucose and alpha2-macroglobulin.
Desloratadine reduced the nasal symptoms (P < 0.05 to 0.001) and output of fucose
(P < 0.05 at 100 and 1,000 SQ-U) and alpha2-macroglobulin (P < 0.05 at 1,000
SQ-U). In both treatment groups, symptoms and nasal lavage fluid levels of fucose
and alpha2-macroglobulin returned toward prechallenge levels 1 to 4 hours after
the allergen challenge series. CONCLUSION: We conclude that the antihistamine
desloratadine, in addition to a symptom-reducing effect, also reduces acute
allergen challenge-induced mucinous secretion and plasma exudation in allergic
rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12392387 [PubMed - indexed for MEDLINE]

1177: Ann Allergy Asthma Immunol. 2002 Oct;89(4):372-80.

Comment in:
    Ann Allergy Asthma Immunol. 2002 Oct;89(4):344-5.

Decrements in vigilance and cognitive functioning associated with ragweed-induced
allergic rhinitis.

Wilken JA, Berkowitz R, Kane R.

Department of Psychology Veterans Affairs Medical Center, Washington, DC 20422,
USA. jeffrey.wilken@med.va.gov

BACKGROUND AND OBJECTIVE: The adverse effects of untreated seasonal allergic
rhinitis (AR) on performance in the workplace, school, and home are poorly
understood. To delineate more clearly the impact and consequences of the disease 
on performance, the effect of symptomatic AR on vigilance and a wide range of
cognitive functions was investigated. METHODS: A battery of automated
neuropsychological tests was administered to asymptomatic adult subjects with
histories of AR. Subjects were randomized to either a symptomatic or to an
asymptomatic group. Subjects in the symptomatic group were exposed to ragweed
pollen in a controlled exposure setting until they demonstrated predetermined
severities of AR symptoms. Subjects in the asymptomatic group were not exposed to
ragweed pollen in the environmental unit and retained a minimum symptom profile. 
The battery of cognitive measures was re-administered to both groups. RESULTS: AR
had major adverse impacts on measures of vigilance. Further, AR adversely
affected a broad range of cognitive functions. Specifically, subjects with AR
symptoms demonstrated longer response times and decreased efficiency on measures 
of working memory, psychomotor speed, reasoning/computation, and divided
attention as compared with asymptomatic subjects. CONCLUSIONS: In addition to
decreased vigilance, AR was associated with decrements in speed and efficiency
across several cognitive domains. This is similar to findings in research on
medications and medical conditions that cause sedation. Findings may represent a 
link between AR and poor productivity/personal safety among AR sufferers. This
suggests that these results have implications with regard to public health.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12392381 [PubMed - indexed for MEDLINE]

1178: J Occup Environ Med. 2002 Oct;44(10):924-9.

Innervation of human nasal mucosa in environmentally triggered hyperreflectoric
rhinitis.

Heppt W, Peiser C, Cryer A, Dinh QT, Zweng M, Witt C, Fischer A, Groneberg DA.

Department of Otorhinolaryngology, Karlsruhe Teaching Hospital, University of
Freiburg, Karlsruhe, Germany.

Hyperreflectoric rhinitis is related to an unspecific hyperreactivity probably
caused by chemical irritants. As a major modulatory role may be attributed to the
mucosal innervation, the present study was carried out to examine possible
changes in the nasal mucosa innervation. Immunohistochemistry for the
neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related
peptide (CGRP), substance P (SP) and neuropeptide tyrosine (NPY) revealed
abundant staining of nerve fibers. Neuropeptide-contents in mucosal nerves was
then quantitatively assessed and significant increases were found for SP (3.00
+/- 0.37 vs. 1.64 +/- 0.34 control group staining intensity) and VIP (2.33 +/-
0.42 vs. 0.82 +/- 0.33). In conclusion, these findings demonstrated differences
in human nasal mucosa innervation between nonrhinitic and hyperreflectoric
rhinitic subjects and provide evidence for a modulatory participation of
neuropeptide-specific subpopulations of nerve fibers in hyperreflectoric
rhinitis.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12391771 [PubMed - indexed for MEDLINE]

1179: Clin Otolaryngol Allied Sci. 2002 Oct;27(5):352-8.

More siblings, less hay fever: more evidence.

Marshall AH, Owen V, Jones NS.

Department of Otorhinolaryngology and Head and Neck Surgery, Queen's Medical
Centre, Nottingham, UK.

The prevalence of allergic rhinitis is increasing. Many authors have noted the
prevalence of hay fever is less in children from large families and the 'hygiene 
hypothesis' has been suggested as an explanation. We looked at the association of
sibling number and other variables on the prevalence of hay fever and perennial
rhinitis. From 26100 households selected at random, 34362 questionnaires were
returned from individuals over 14 years of age; 19.3% had symptoms of hay fever
and a further 6.0% had symptoms of perennial rhinitis. A logistic regression
analysis showed that for individuals with two or more siblings, the odds of
suffering from hay fever are less than the odds for people with no siblings and
that these odds decrease as the number of siblings increases. This effect was not
found in subjects with perennial rhinitis. This study adds weight to the 'hygiene
hypothesis'.

PMID: 12383296 [PubMed - indexed for MEDLINE]

1180: Clin Exp Allergy. 2002 Oct;32(10):1504-9.

Effects of fexofenadine and desloratadine on subjective and objective measures of
nasal congestion in seasonal allergic rhinitis.

Wilson AM, Haggart K, Sims EJ, Lipworth BJ.

Asthma & Allergy Research Group, Ninewells Hospital & Medical School, University 
of Dundee, Dundee, UK.

BACKGROUND: In vitro studies have shown much higher H1-receptor antagonist
potency with desloratadine (DL) compared to fexofenadine (FEX), although it is
unclear whether this has any clinical relevance on disease control parameters in 
seasonal allergic rhinitis (SAR), especially for nasal congestion. OBJECTIVE: To 
compare the relative efficacy between presently recommended doses of DL and FEX
on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in
SAR. METHODS: Forty-nine patients with SAR were randomized into a double-blind,
placebo-controlled cross-over study during the grass pollen season, comparing 2
weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the
morning. There was a 7-10 day placebo run-in and washout prior to each randomized
treatment. Measurements were made in the morning (AM) and in the evening (PM) for
PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM
values were used for analysis. RESULTS: There were significant (P < 0.05)
improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage,
nasal irritation, and total nasal symptoms, but not nasal discharge or eye
symptoms. There were no significant differences between active treatments. Values
for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI
for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean 
difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal
symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for
DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 
0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and
nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3),
respectively. CONCLUSIONS: Recommended once daily doses of fexofenadine and
desloratadine were equally effective in improving nasal peak flow and nasal
symptoms in SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12372132 [PubMed - indexed for MEDLINE]

1181: Clin Exp Allergy. 2002 Oct;32(10):1476-83.

Are Ca2+-binding motifs involved in the immunoglobin E-binding of allergens?
Olive pollen allergens as model of study.

Ledesma A, González E, Pascual CY, Quiralte J, Villalba M, Rodríguez R.

Departmento de Bioquímica y Biología Molecular, Facultad de Ciencias, Químicas,
Universidad Complutense, Madrid, Spain.

BACKGROUND: Several Ca2+-binding proteins, which possess EF-hand sites with a
high sequence similarity, have been found to be able to induce Type-I allergy.
OBJECTIVE: To study whether the common EF-hand sequential motifs can be involved 
in the IgE-reactivity of these proteins, thus being responsible of a degree of
cross-reactivity among different Ca2+-binding proteins. METHODS: Two olive pollen
allergens, Ole e 3 and Ole e 8, have been used in the study. Parvalbumin and
calmodulin were included in immunological analyses. Sera from patients allergic
to olive pollen, as well as Ole e 3- and Ole e 8-specific rabbit antisera were
used in indirect enzyme-linked immunosorbent assay (ELISA), ELISA inhibition
assays and immunoblotting. Conformational analyses (circular dichroism spectra
and thermal stability) and specific immunodetection assays were performed in the 
presence and the absence of Ca2+. Chemical breakdown and high-performance liquid 
chromatography (HPLC) was used to obtain fragments from Ole e 3 containing a
single EF-hand motif. RESULTS: Thirty-four (17%) and 16 (8.2%) out of 195 sera
from patients allergic to olive pollen contained specific IgE against Ole e 3 and
Ole e 8, respectively. The IgE-binding of 12 allergic sera diminished up to 22%
for Ole e 3 and to 82% for Ole e 8, when depleted Ca2+. A pool of these sera
recognized the two olive allergens and parvalbumin, but at very different extent.
Inhibition of the IgE-binding was only achieved between two olive allergens. No
structural relationships between Ole e 3 and Ole e 8 were established when
specific polyclonal antisera against both proteins were used. CONCLUSION: EF-hand
Ca2+-binding sites can not be considered as general allergenic motifs responsible
for the cross-reactivity between Ca2+-binding allergens. Different families of
Ca2+-binding allergens have specific epitopes that could be involved in the
cross-reactivity among members of the same family.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12372128 [PubMed - indexed for MEDLINE]

1182: J Clin Pharmacol. 2002 Oct;42(10):1097-104.

A double-blind, placebo-controlled study of the efficacy and safety of ebastine
20 mg once daily given with and without food in the treatment of seasonal
allergic rhinitis.

Frank H Jr, Gillen M, Rohatagi SS, Lim J, George G; Ebastine Study Group.

The efficacy and safety of ebastine 20 mg once daily given with and without food 
were compared in patients ages 12 to 70 years with seasonal allergic rhinitis
(SAR) caused by mountain cedar allergen. This double-blind, placebo-controlled
study was conducted at six centers in Texas. Efficacy and safety analyses were
performed on the intent-to-treat population, which comprised 652 patients; 540
patients completed the study. Following 2 weeks' treatment, no significant
differences (p > or = 0.91) were found between the ebastine with and without food
groups in the percentage change from baseline of daily "reflective" total
rhinitis symptom scores (i.e., patients' assessment of severity over the previous
12 h), but both ebastine groups exhibited significantly greater reductions versus
patients receiving placebo (p < 0.0001). There were also no significant
differences in the percentages of patients experiencing adverse events between
the ebastine with and without food groups. Mean steady-state plasma
concentrations of ebastine and its active metabolite carebastine were,
respectively, 5.5% (ns) and 15.1% (p < 0.05) higher when ebastine was given with 
food versus its administration without food. Overall, these results indicate that
in clinical practice, ebastine does not need to be administered with reference to
food.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12362923 [PubMed - indexed for MEDLINE]

1183: Rhinology. 2002 Sep;40(3):141-6.

Cholinergic blockade does not alter the nasal congestive response to irritant
provocation.

Shusterman D, Murphy MA, Walsh P, Balmes JR.

Division of Occupational and Environmental Medicine, University of California,
San Francisco, USA. dennis@itsa.ucsf.edu

OBJECTIVE: To understand the mechanism underlying the nasal congestive response
to irritant challenge. METHODS: We exposed 22 subjects--8 with seasonal allergic 
rhinitis (SAR), 6 with perennial allergic rhinitis (PAR), and 8 normals--to
chlorine (Cl2) gas (1.0 ppm x 15 min.) by nasal CPAP mask. Control exposures
(filtered air) were carried out on separate days, with counter-balancing of
exposure order. Nasal airway resistance (NAR) was measured in triplicate before
and after the provocation sequence using active posterior rhinomanometry. For
each subject, this experiment was repeated twice, after [double-blinded]
pre-treatment with: 1) ipratropium bromide (IB) 0.6% nasal spray, and 2) vehicle.
RESULTS: As a group, allergic rhinitics (SAR + PAR) showed greater [Cl2]
exposure-related increases in NAR than did normals on placebo (vehicle)
pretreatment days (p < 0.05). IB pre-treatment, however, did not have a
systematic effect on Cl2-induced congestion. CONCLUSION: Cholinergic mechanisms
do not appear to be responsible for the nasal congestive response to irritant
provocation.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12357714 [PubMed - indexed for MEDLINE]

1184: J Med Assoc Thai. 2002 Jun;85(6):722-7.

A comparative study of the side effects between pseudoephedrine in Loratadine
plus Pseudoephedrine Sulfate Repetabs Tables and loratadine + pseudoephedrine
tablet in treatment of allergic rhinitis in Thai patients.

Supiyaphun P, Chochaipanichnon L, Kerekhanjanarong V, Saengpanich S.

Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand.

The objective of the study was to evaluate the adverse reactions of Loratadine
plus Pseudoephedrine Sulfate Repetabs Tables (LTD+PSE Repetabs) (Loratadine 5 mg 
+ Pseudoephedrine 120 mg) twice daily with that of loratadine (5 mg) twice daily 
and pseudoephedrine (60 mg) quarter daily in the treatment of patients with
allergic rhinitis. The study was designed as an investigator-blind, parallel
group study. In this study, 56 patients were equally separated into 2 groups and 
treated for 14 days with either LTD+PSE Repetabs or loratadine + pseudoephedrine 
tablet. Both groups were comparable in age, gender, weight; baseline systolic
blood pressure, diastolic blood pressure and pulse rate. The change of systolic
blood pressure, diastolic blood pressure, and pulse rate did not reach clinical
significance throughout the study period. There was no significant difference in 
occurrences of insomnia, palpitation, mouth dryness and anxiety. However, the
incidence of patients with tremor at day 14 in the loratadine + pseudoephedrine
tablet group was significantly higher than the LTD+PSE Repetabs group (39% vs
10.7%, p-value = 0.03). Furthermore, one patient in the loratadine +
pseudoephedrine tablet group had to discontinue medication at day 7 due to
insomnia. In conclusion, LTD+PSE Repetabs is well tolerated and has fewer adverse
effects when compared to the loratadine + pseudoephedrine tablet.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12322847 [PubMed - indexed for MEDLINE]

1185: J Am Pharm Assoc (Wash). 2002 Sep-Oct;42(5 Suppl 1):S44-5.

Update on allergic rhinitis.

Delafuente JC, Cheigh NH.

Geriatric Programs, Virginia Commonwealth University School of Pharmacy,
Richmond, USA.

AR is an increasingly common inflammatory disorder. In patients with AR,
abnormalities in the immune response trigger inflammatory reactions to otherwise 
innocuous substances, such as pollen, mold, and house dust mites. An array of
environmental and pharmacologic options for AR is available, which should be
tailored to the patient's symptoms and lifestyle. Investigational immunotherapies
may prove valuable for patients who have an inadequate response to current
therapies or experience intolerable adverse events.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12296551 [PubMed - indexed for MEDLINE]

1186: Ann Allergy Asthma Immunol. 2002 Sep;89(3):316-8.

Recurrence of allergic rhinitis, previously alleviated with allergen
immunotherapy, after autologous bone marrow transplant.

Kelso JM.

Department of Internal Medicine, Naval Medical Center, San Diego, California
92134-1005, USA. jmkelso@nmcsd.med.navy.mil

BACKGROUND: Several associations between immunoglobulin E and bone marrow
transplantation (BMT) have been reported. OBJECTIVE: A patient whose allergic
rhinitis (AR) resolved after allergen immunotherapy (AIT) but recurred after the 
patient received an autologous BMT is reported. METHODS: Allergy skin tests were 
performed before AIT began and after 4 years of therapy. Skin tests were repeated
after a recurrence of symptoms 6 years later after an autologous BMT for breast
cancer. RESULTS: Six years of AIT led to a near complete resolution of AR
symptoms. Skin tests showed a marked reduction in reactivity to allergens in the 
AIT. After an additional 6-year symptom-free interval off AIT, symptoms returned 
after the BMT. Repeat skin tests showed a marked increase in reactivity.
CONCLUSIONS: Patients reconstituting their immune systems after autologous BMT
may have a recurrence of AR previously suppressed with AIT.

Publication Types: 
    Case Reports
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 12269654 [PubMed - indexed for MEDLINE]

1187: Ann Allergy Asthma Immunol. 2002 Sep;89(3):292-7.

Comment in:
    Ann Allergy Asthma Immunol. 2003 May;90(5):576; author reply 577.

Patient preferences and sensory comparisons of three intranasal corticosteroids
for the treatment of allergic rhinitis.

Bachert C, El-Akkad T.

Department of Ear, Nose, and Throat, University Hospital, Ghent, Belgium.
Claus.bachert@rug.ac.be

BACKGROUND: Although they have comparable safety and efficacy profiles, different
intranasal corticosteroids possess different sensory/chemical properties that can
be easily differentiated by patients, and which may influence their preference
and compliance. OBJECTIVE: We sought to compare patient assessments of sensory
attributes of three intranasal corticosteroid sprays: triamcinolone acetonide
aqueous (TAA), fluticasone propionate (FP), and mometasone furoate (MF). METHODS:
In a multicenter, randomized, double-blind, crossover study, 95 patients with
allergic rhinitis rated 14 sensory items (100-point scales), product preference, 
and likelihood of compliance with treatment. RESULTS: Immediately after
administration, compared with MF, TAA was rated as having significantly better
comfort during administration, less irritation, less odor strength, preferred
odor, more moistness of nose/throat, milder taste (all P < or = 0.001), and
preferred taste (P < or = 0.01). Compared with FP, TAA was rated as having
significantly less odor strength, preferred odor (both P < or = 0.001), more
moistness of nose/throat (P < or = 0.01), and milder taste (P < or = 0.05). Two
minutes after application, TAA was rated as having less aftertaste than FP (P <
or = 0.01) or MF (P < or = 0.001), and produced significantly less irritation (FP
P < or = 0.05; MF P < or = 0.01). Of patients, 54.7% said they would prefer a
prescription of TAA over one for MF (24.2%; P = 0.001) or FP (21.1%; P = 0.001). 
More patients indicated that they would be more compliant with treatment if given
the TAA prescription (67.4%) than if given a prescription with FP (54.7%) or MF
(49.5%). CONCLUSION: Several of the TAA sensory attributes were preferred over
those of MF and FP. Patient preference may play a role in enhancing treatment
compliance. Such findings indicate that TAA nasal spray may be a better choice
than MF or FP in the treatment of seasonal and perennial allergic rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12269650 [PubMed - indexed for MEDLINE]

1188: Int J Biometeorol. 2002 Sep;46(4):176-84. Epub 2002 Jun 20.

Phenological behaviour of Quercus in Ourense (NW Spain) and its relationship with
the atmospheric pollen season.

Jato V, Rodríguez-Rajo FJ, Méndez J, Aira MJ.

Department of Vegetal Biology and Soil Sciences, University of Vigo, Campus
Universitario, As Lagoas, 32004 Ourense, Spain. vjato@uvigo.es

Knowing the beginning of the pollen season is of particular importance to people 
allergic to a given pollen. Phenological studies in combination with
aerobiological studies enable us to observe the relationship between the
reproductive phenology of the species and their airborne pollen curves. They also
enable us to study the relationship between the release of pollen from anthers
and its presence in the atmosphere. The objectives of this study are (1) to
determine chill and heat requirements for different phenological phases in the
Quercus species present in Ourense (Spain), (2) to verify the synchronization
between the flowering event and the presence of Quercus pollen in the air, (3) to
select the best criterion for determining the onset of the pollen season
according to phenological data, and finally, (4) to obtain models enabling us to 
determine the onset of the pollen season. Pollen monitoring was carried out from 
1993 to 2001, by means of a 7-day Lanzoni VPPS pollen trap and, in order to
characterize the floral phenophase of different Quercus species, a sampling
method was applied from February to June 2001. We observed that climatic and
biotic factors can produce a delay in the onset of the pollen season.
Temperatures above 8 degrees C and between 6 degrees C to 8 degrees C are good
threshold temperatures for estimating chill and heat requirements respectively.
Medium-distance transportation of Quercus robur and Quercus pyrenaica pollen from
areas 10-30 km away influences the concentrations of Quercus pollen registered in
Ourense.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12242473 [PubMed - indexed for MEDLINE]

1189: Int J Biometeorol. 2002 Sep;46(4):159-70. Epub 2002 Jul 26.

Erratum in:
    Int J Biometeorol. 2003 Mar;47(2):113-5.

Responses in the start of Betula (birch) pollen seasons to recent changes in
spring temperatures across Europe.

Emberlin J, Detandt M, Gehrig R, Jaeger S, Nolard N, Rantio-Lehtimäki A.

National Pollen Research Unit, University College, Worcester WR2 6AJ, UK.
j.emberlin@worc.ac.uk

A shift in the timing of birch pollen seasons is important because it is well
known to be a significant aeroallergen, especially in NW Europe where it is a
notable cause of hay fever and pollen-related asthma. The research reported in
this paper aims to investigate temporal patterns in the start dates of Betula
(birch) pollen seasons at selected sites across Europe. In particular it
investigates relationships between the changes in start dates and changes in
spring temperatures over approximately the last 20 years. Daily birch pollen
counts were used from Kevo, Turku, London, Brussels, Zurich and Vienna, for the
core period from 1982 to 1999 and, in some cases, from 1970 to 2000. The sites
represent a range of biogeographical situations from just within the Arctic
Circle through to North West Maritime and Continental Europe. Pollen samples were
taken with Hirst-type volumetric spore traps. Weather data were obtained from the
sites nearest to the pollen traps. The timing of birch pollen seasons is known to
depend mostly on a non-linear balance between the winter chilling required to
break dormancy, and spring temperatures. Pollen start dates and monthly mean
temperatures for January through to May were compiled to 5-year running means to 
examine trends. The start dates for the next 10 years were calculated from
regression equations for each site, on the speculative basis that the current
trends would continue. The analyses show regional contrasts. Kevo shows a marked 
trend towards cooler springs and later starts. If this continues the mean start
date will become about 6 days later over the next 10 years. Turku exhibits cyclic
patterns in start dates. A current trend towards earlier starts is expected to
continue until 2007, followed by another fluctuation. London, Brussels, Zurich
and Vienna show very similar patterns in the trends towards earlier start dates. 
If the trend continues the mean start dates at these sites will advance by about 
6 days over the next 10 years. Following this work, amendments will be needed to 
pollen calendars and local predictive models. It will also be important to assess
the implications of earlier seasons for allergy sufferers.

PMID: 12242471 [PubMed - indexed for MEDLINE]

1190: Am J Respir Crit Care Med. 2002 Sep 15;166(6):827-32.

Comment in:
    Am J Respir Crit Care Med. 2003 Jun 1;167(11):1578; author reply 1578-9.

The importance of prenatal exposures on the development of allergic disease: a
birth cohort study using the West Midlands General Practice Database.

McKeever TM, Lewis SA, Smith C, Hubbard R.

Division of Respiratory Medicine, University of Nottingham, Nottingham, United
Kingdom. tricia.mckeever@nottingham.ac.uk

The etiology of allergic disease is not understood, but a decreased exposure to
infection may play an important role. There are few published data on the impact 
of change in microbial exposure during pregnancy on the child's risk of
developing allergic disease. Using a birth cohort of 24,690 children, derived
from the West Midlands General Practice Research Database, we investigated a
number of perinatal exposures on the incidence of asthma, eczema, and hay fever. 
Our findings suggest that exposure to antibiotics in utero is associated with an 
increased risk of asthma in a dose-related manner (more than two courses of
antibiotics compared with none adjusted hazard ratio [HR] 1.68; 95% confidence
interval [CI], 1.51-1.87), and similar associations are present for eczema
(adjusted HR 1.17; 95% CI, 1.06-1.29) and hay fever (adjusted HR 1.56; 95% CI,
1.22-2.01). Exposure to a range of infections in utero was also associated with a
small increased risk of developing allergic disease. Strong protective effects of
older siblings on the incidence of allergy are present within this cohort, but
previous pregnancies that did not result in a live birth were not protective. Our
findings suggest that exposure to antibiotics and to infections in utero is a
potentially important risk factor in the development of allergic disease.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12231492 [PubMed - indexed for MEDLINE]

1191: Chest. 2002 Sep;122(3):940-7.

Modifications of airway responsiveness to adenosine 5'-monophosphate and exhaled 
nitric oxide concentrations after the pollen season in subjects with
pollen-induced rhinitis.

Prieto L, Uixera S, Gutiérrez V, Bruno L.

Sección de Alergología (The NAOMI Project), Hospital Universitario Dr. Peset and 
Universidad de Valencia, Spain. prieto_jes@gva.es

STUDY OBJECTIVE:s: To determine the effect of cessation of exposure to pollen on 
airway responsiveness to adenosine 5'-monophosphate (AMP) in subjects with
pollen-induced rhinitis, and to explore the relationship between changes in
airway responsiveness and changes in exhaled nitric oxide (ENO) levels. STUDY
DESIGN: Subjects were studied during the pollen season and out of season.
SETTING: Specialist allergy unit in a university hospital. PATIENTS: Fourteen
subjects without asthma with pollen-induced rhinitis who showed
bronchoconstriction in response to methacholine and AMP during the pollen season 
and 10 healthy nonatopic control subjects. MEASUREMENTS AND RESULTS: In subjects 
with pollen-induced rhinitis, ENO concentrations, provocative concentration of
agonist causing a 20% fall in FEV(1) (PC(20)) methacholine, and PC(20) AMP were
determined during the pollen season and out of season. Healthy control subjects
were studied during the pollen season. In subjects with allergic rhinitis, PC(20)
AMP increased from a geometric mean of 79.4 mg/mL (95% confidence interval [CI], 
31.6 to 199.5 mg/mL) during the pollen season to 316.2 mg/mL (95% CI, 158.5 to
400.0 mg/mL) out of season (p = 0.004). The ENO concentrations decreased from
63.1 parts per billion (ppb) [95% CI, 50.1 to 79.4 ppb] during the pollen season 
to 30.2 ppb (95% CI, 23.4 to 38.0 ppb) out of season (p < 0.001). The ENO
concentrations out of pollen season were still significantly increased in
subjects with pollen-induced rhinitis when compared with healthy control
subjects. There was no relationship between individual changes in ENO levels and 
changes in either PC(20) methacholine or PC(20) AMP. CONCLUSIONS: In
pollen-sensitive subjects with allergic rhinitis, the cessation of exposure to
pollen is associated with a significant reduction of airway responsiveness to
inhaled AMP. However, no association was found between allergen-induced changes
in ENO values and in airway responsiveness to either direct or indirect
bronchoconstrictors. These findings suggest that modifications in ENO and in
airway responsiveness are the consequence of different alterations induced by
allergen exposure on the lower airways.

PMID: 12226036 [PubMed - indexed for MEDLINE]

1192: Chest. 2002 Sep;122(3):798-805.

Comment in:
    Chest. 2002 Sep;122(3):763-5.

Effect of salmeterol on seasonal changes in airway responsiveness and exhaled
nitric oxide in pollen-sensitive asthmatic subjects.

Prieto L, Gutiérrez V, Torres V, Uixera S, Marín J.

Sección de Alergología, Hospital Universitario Dr. Peset, Valencia, Spain.
prieto_jes@gva.es

OBJECTIVE: Using a model of natural allergen exposure, we examined the effect of 
regular treatment with salmeterol on allergen-induced changes in airway
responsiveness and exhaled nitric oxide (ENO). DESIGN: Double-blind, randomized, 
parallel-group study. SETTING: Specialist allergy unit in a university hospital. 
PATIENTS: Asthmatic patients sensitized to pollen allergens were randomly
allocated to monotherapy with salmeterol (n = 14) or placebo (n = 13).
INTERVENTIONS: Salmeterol, 25 micro g, and placebo inhalers, two puffs bid, for 6
weeks. MEASUREMENTS: Spirometry, the level of a provocative concentration of a
substance (methacholine) causing a 20% fall in FEV(1) (PC(20)), the PC(20) level 
for adenosine 5'-monophosphate (AMP), and ENO were measured before the pollen
season and were repeated at the height of the pollen season after 6 weeks of
treatment with salmeterol or placebo. RESULTS: The decrease in FEV(1) during the 
pollen season was significantly larger in the placebo group than in the
salmeterol group, the mean difference in the change between the groups being 0.20
L (95% confidence interval, 0.03 to 0.35; p = 0.047). Changes in PC(20) for
methacholine, PC(20) for AMP, and ENO levels were not significantly different
between treatment groups. However, a mean (+/- SEM) decrease in the PC(20) for
methacholine of -1.0 +/- 0.4 doubling concentrations was observed within the
placebo group (p = 0.03), whereas no significant changes were observed within the
salmeterol group. A significant decrease in PC(20) for AMP (doubling
concentrations) was observed within the placebo group (-2.1 +/- 0.6; p = 0.003)
and the salmeterol group (-1.5 +/- 0.4; p = 0.003). ENO concentrations increased 
significantly among the placebo and the salmeterol groups during natural pollen
exposure. CONCLUSION: These observations indicate that natural allergen exposure 
and the regular use of salmeterol are not associated with a greater increase in
ENO and airway responsiveness than allergen exposure alone.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12226016 [PubMed - indexed for MEDLINE]

1193: Arch Otolaryngol Head Neck Surg. 2002 Sep;128(9):1058-60.

Decrease of specific and total IgE levels in allergic patients after BCG
vaccination: preliminary report.

Cavallo GP, Elia M, Giordano D, Baldi C, Cammarota R.

Dipartimento di Fisiopatologia Clinica, I Clinica Otorinolaringoiatrica,
University of Turin, Via Genova No. 3, 10126 Turin, Italy. mt.eli@virgilio.it

BACKGROUND: A systemic reaction to mycobacteria biases the balance of T helper
cell types 1 and 2 toward T helper cell type 1. BCG vaccination mimics some
characteristics of mycobacterial infection. Children who have undergone
tuberculin conversion after BCG vaccination seem to be more likely to lose their 
atopic symptoms. Inhibition of both allergic response and airway hyperreactivity 
after vaccination for mycobacteria has been observed in animal experiments.
OBJECTIVE: To evaluate the effects that BCG vaccination has on the serological
status of allergic people. PARTICIPANTS AND METHODS: This study included 20
volunteers with a history of allergic rhinitis who were required to undergo BCG
vaccination by Italian law. Epicutaneous allergy testing with a panel of common
seasonal and perennial inhalational allergens and 2 blood withdrawals were
performed. The serum total IgE levels and the serum allergen-specific IgE levels 
of each individual were measured just before BCG vaccination and again 4 months
later. Total IgE levels were determined using the paper radioimmunosorbent test, 
and allergen-specific IgE levels were determined using the radioallergosorbent
test. RESULTS: Total IgE and allergen-specific IgE levels were significantly
decreased after BCG vaccination (P =.004 and P<.001, respectively). CONCLUSION:
BCG, an effective stimulus for cell-mediated immunity, deserves further study to 
evaluate its ability to modulate the immune response associated with allergic
rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12220212 [PubMed - indexed for MEDLINE]

1194: Int Arch Allergy Immunol. 2002 Aug;128(4):336-43.

Influence of natural exposure to pollens and domestic animals on airway
responsiveness and inflammation in sensitized non-asthmatic subjects.

Boulay ME, Boulet LP.

Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de
Pneumologie de l'Université Laval, Sainte-Foy, Québec, Canada.

BACKGROUND: Atopy may be a risk factor in the development of asthma. Indoor
allergens are considered to be more potent asthma inducers than outdoor ones such
as pollens. Lower airway inflammation may be present in non-asthmatic subjects
during natural exposure to relevant allergens and may eventually lead to the
development of asthma. AIMS: To document seasonal variation in lower airway
responsiveness and inflammation in sensitized non-asthmatic subjects, during
natural exposure to allergens, and to determine whether it is more marked in
those exposed to animals to which they are sensitized. METHODS: Twenty-two atopic
subjects were seen during and out of the pollen season. All (but the controls)
were sensitized to domestic animals, and to trees, grasses or ragweed. Eleven
were not exposed to animals at home and 8 were exposed. They were compared with 3
normal controls. A respiratory questionnaire was administered, allergy skin prick
tests, spirometry, methacholine challenge, blood and induced sputum with
differential cell counts were obtained during the pollen season for all subjects.
These tests were repeated out of the pollen season. RESULTS: Throughout the
study, none of the subjects had asthma symptoms. Mean PC(20) was significantly
lower in subjects exposed to animals compared with unexposed subjects or
controls, both during and out of the pollen season. In season, subjects exposed
to animals had significantly higher sputum eosinophil numbers than unexposed or
normal control subjects. CONCLUSIONS: Non-asthmatic atopic subjects show variable
degrees of airway responsiveness and inflammation. However, subjects exposed to
animals show higher airway eosinophilia, which may suggest they are at increased 
risk of developing airway hyperresponsiveness and asthma. Copyright 2002 S.
Karger AG, Basel

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12218372 [PubMed - indexed for MEDLINE]

1195: Int Arch Allergy Immunol. 2002 Aug;128(4):325-35.

Different IgE reactivity profiles in birch pollen-sensitive patients from six
European populations revealed by recombinant allergens: an imprint of local
sensitization.

Movérare R, Westritschnig K, Svensson M, Hayek B, Bende M, Pauli G, Sorva R,
Haahtela T, Valenta R, Elfman L.

Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala
University, Uppsala, Sweden. robert.moverare@pharmacia.com

BACKGROUND: Sensitivity to birch pollen allergens is a common feature among
European patients with seasonal pollen allergy. In this in vitro study, we
examined the specific serum IgE binding profiles to individual birch pollen
allergens in birch-sensitive patients from six European populations. METHODS: The
study included 242 patients from Finland, Sweden, Austria, France, Switzerland
and Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. Their
sera were analyzed for specific IgE reactivity to individual birch pollen
allergens (recombinant Bet v 1, Bet v 2 and Bet v 4) and natural birch pollen
extract using Pharmacia CAP System and immunoblotting. RESULTS: Almost all
Finnish, Swedish and Austrian sera contained IgE specific for Bet v 1 (>or=98%). 
Bet v 1-specific IgE antibodies were found in 90% of the French sera, and in 65
and 62% of the sera from Switzerland and Italy, respectively. Few Finnish (2%)
and Swedish (12%) patients had IgE to Bet v 2, while Bet v 2 reactivity was more 
common in the other populations (20-43%). Reactivity to Bet v 4 was rare in all
populations (5-11%) except for the Italian patients, in whom 3 of 11 sera were
positive (27%). The immunoblot results supported the specific IgE profiles
obtained with Pharmacia CAP System showing a broader IgE reactivity profile in
patients from central and southern Europe as compared to northern Europe.
CONCLUSION: Component-resolved allergy diagnosis with recombinant allergens
reveals that the IgE reactivity profiles to individual birch pollen allergens
vary between European populations. This observation may be explained by
sensitization to different allergen sources and will have an impact on
allergen-specific prevention and therapy strategies. Copyright 2002 S. Karger AG,
Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12218371 [PubMed - indexed for MEDLINE]

1196: Int Arch Allergy Immunol. 2002 Aug;128(4):271-9.

Allergies to cross-reactive plant proteins. Latex-fruit syndrome is comparable
with pollen-food allergy syndrome.

Yagami T.

Division of Medical Devices, National Institute of Health Sciences, Kamiyoga,
Setagaya-Ku, Tokyo, Japan. yagami@nihs.go.jp

Both latex-fruit syndrome and oral allergy syndrome concomitant with pollinosis
(pollen-food allergy syndrome) are considered to be caused by cross-reactivity
between sensitizers and symptom elicitors. The cross-reactive food allergens
relevant to these syndromes are mostly sensitive to heat and digestive enzymes.
Such a vulnerable antigen cannot sensitize people perorally but provokes allergic
reactions in already sensitized patients based on its cross-reactivity to the
corresponding sensitizer. These types of food allergens are often called
incomplete food allergens or nonsensitizing elicitors. Their features contrast
with those of complete food allergens that have the capacity for peroral
sensitization as well as symptom elicitation. Although highly antigenic and
cross-reactive, carbohydrate epitopes do not generally elicit allergic reactions 
and often disturb in vitro IgE tests. Recent research has revealed that some of
the cross-reactive allergens responsible for the two syndromes are proteins
related to the defense responses of higher plants. Plant defense-related proteins
are relatively conserved in the course of evolution and can supply cross-reactive
epitopes. It is important to note that various stresses can stimulate the
expression of these proteins, which implies that allergens increase in plants
under stressful conditions like severe growing situations and exposure to some
kinds of chemicals. Because defense-related proteins usually provide a plant with
resistance to stresses, varieties that are apt to intensively induce such
proteins are agriculturally valuable. Less toxic substances that cause crops to
express defensive proteins are being investigated as a new type of agrochemical. 
Moreover, some defense-related proteins are going to be constantly produced in
genetically modified plants. Even though these proteins can be useful
agriculturally, their allergenicity should be evaluated carefully. Copyright 2002
S. Karger AG, Basel

Publication Types: 
    Comparative Study
    Review

PMID: 12218365 [PubMed - indexed for MEDLINE]

1197: J Immunol Methods. 2002 Oct 15;268(2):189-95.

Measurement of changes in mRNA for IL-5 in noninvasive scrapings of nasal
epithelium taken from patients undergoing nasal allergen challenge.

Dreskin SC, Dale SN, Foster SM, Martin D, Buchmeier A, Nelson HS.

Department of Medicine, Division of Allergy, University of Colorado Health
Sciences Center, 4200 East Ninth Avenue, Campus box B164, Denver 80262, USA.
stephen.dreskin@uchsc.edu

Nasal allergen challenge of patients with allergic rhinitis results in increased 
numbers of inflammatory cells and increased production of pro-inflammatory
cytokines including interleukin 5 (IL-5). We report a sensitive, noninvasive
method to measure changes in the amount of mRNA for IL-5 in nasal epithelium and 
have used this method to detect alterations of IL-5 mRNA from patients undergoing
a nasal allergen challenge. Ten grass or ragweed allergic adults were challenged 
out of season with appropriate pollen extracts at sufficient dose to give a
rhinitis total symptom score of 5 on a scale of 12. After allergen exposure,
symptoms were recorded hourly. At 0, 3, and 6 h after allergen exposure, secreted
proteins were collected on filter paper strips and two superficial scrapings of
nasal epithelium were obtained. The scrapings of epithelium were immediately
immersed in 100 microl of RNAlater (Ambion, Austin, TX) and stored at 4 degrees C
for up to 1 month without loss of RNA quality. Total RNA was isolated and RT-PCR 
was performed. cDNA for IL-5 was then measured by real-time fluorescence
quantitative PCR with Pre-Developed TaqMan Assay Reagents (PE Biosystems, Foster 
City, CA). Sufficient RNA was isolated from eight subjects to measure IL-5 mRNA. 
Data were normalized for content of ribosomal RNA. The relative amount of cDNA
for IL-5 was calculated by comparison with internal standards prepared from
phytohemagluttinin-stimulated peripheral blood mononuclear cells. Messenger RNA
for IL-5 was increased 8.7+/-2.7-fold at 3 h (p<0.01) and 39.5+/-20.9-fold at 6 h
(p<0.01). Increased IL-5 mRNA levels at 6 h closely correlate with total symptom 
scores at 6 h (r=0.88; p=0.007). IL-5 protein was measured by ELISA in eluates
from the filter papers. At 6 h, there was increased IL-5 protein (7.7+/-2.8
ng/ml) compared with time zero (1.8+/-0.5 ng/ml) (p=0.02). The levels of IL-5
protein did not correlate significantly with the symptoms score or with changes
in the levels of IL-5 protein with IL-5 mRNA. These data show that changes in
IL-5 mRNA in patients with allergic rhinitis undergoing an allergen challenge
correlate with total symptom scores better than changes in IL-5 protein eluted
from filter paper. Furthermore, these changes can be measured quantitatively in
very small amounts of tissue.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12215387 [PubMed - indexed for MEDLINE]

1198: J Allergy Clin Immunol. 2002 Sep;110(3):381-7.

Hay fever and asthma in relation to markers of infection in the United States.

Matricardi PM, Rosmini F, Panetta V, Ferrigno L, Bonini S.

Institute of Neurobiology and Molecular Medicine, Consiglio Nazionale delle
Ricerche, Istituto Superiore di Sanità, Rome.

BACKGROUND: The hygiene hypothesis proposes that declining exposure to infections
is implicated in the rising trend of allergy and asthma. OBJECTIVE: We sought to 
test this hypothesis by examining the relationship of hay fever, asthma, and
atopic sensitization with markers of infection in a large general population
sample of the United States. METHODS: We analyzed the data of 33,994 US residents
recorded in a public database of a nationally representative cross-sectional
survey (Third National Health and Nutrition Examination Survey, 1988-1994). The
variables examined were sociodemographic information, lifetime diagnosis and age 
at first diagnosis of hay fever or asthma, current skin sensitization to 9
airborne allergens and peanut, and current serology for Toxoplasma gondii, herpes
simplex viruses type 1 and 2, and hepatitis A, B, and C viruses. RESULTS: Hay
fever (adjusted odds ratio, 0.27; 95% CI, 0.18-0.41; P <.001) and asthma
(adjusted odds ratio, 0.45; 95% CI, 0.31-0.66; P <.001) were less frequent in
subjects seropositive for hepatitis A virus (HAV), T gondii, and herpes simplex
virus 1 versus seronegative subjects after adjusting for age, sex, race, urban
residence, census region, family size, income, and education. Skin sensitization 
to peanut and to all the airborne allergens examined, except for cockroach, was
less frequent among HAV-seropositive versus HAV-seronegative subjects younger
than 40 years of age. The prevalence of hay fever and asthma diagnosed at or
before 18 years of age in HAV-seronegative subjects increased progressively from 
2.7% (95% CI, 0.7%-4.7%) and 0.4% (95% CI, 0.1%-1.6%), respectively, in cohorts
born before 1920 to 8.5% (95% CI, 7.3%-9.7%) and 5.8% (95% CI, 4.8%-6.8%),
respectively, in cohorts born in the 1960s, whereas they remained constant at
around 2% in all cohorts of HAV-seropositive subjects. CONCLUSION: In the United 
States serologic evidence of acquisition of certain infections, mainly food-borne
and orofecal infection, is associated with a lower probability of having hay
fever and asthma. Third National Health and Nutrition Examination Survey data
support the hypothesis that hygiene is a major factor contributing to the
increase in hay fever, asthma, and atopic sensitization in westernized countries.

PMID: 12209083 [PubMed - indexed for MEDLINE]

1199: Eur J Med Res. 2002 Aug 30;7(8):353-8.

Exhaled hydrogen peroxide, nitrite and nitric oxide in healthy children: decrease
of hydrogen peroxide by atmospheric nitric oxide.

Latzin P, Griese M.

Children's Hospital, Ludwig Maximilians-University of Munich, Germany.

Hydrogen peroxide (H2O2) and nitrite (NO2-) in exhaled breath condensate have
recently been suggested as non-invasive markers of airway inflammation. The goal 
of this study was to clarify the role of factors that may potentially influence
the measurement of H2O2 and nitrite and to look for possible correlations among
these inflammatory markers. H2O2 and nitrite values were assessed
fluorometrically in breath condensate of 102 healthy children (age 4-18 years)
and a detailed status of atopy (including history, lung function and skin prick
test) was taken in all children. To find out the role of atmospheric nitric
oxide, eNO and envNO were measured via chemiluminescence in association with the 
sampling of the breath condensate. Median (interquartile range) H2O2 was 0.51
(0.26 - 0.74) microM and nitrite was 3.3 (2.7 4.1) microM. A significant negative
correlation between H2O2 and envNO was observed (r = -0.50; p < 0.0001). ENO was 
independent of envNO at our envNO range up to 56 ppb. No further correlation was 
found. The inflammatory markers in exhaled breath condensate H2O2, nitrite and
eNO are not interrelated to each other in healthy children. Whereas eNO was not
dependent on envNO values, high envNO values must be taken into account when
measuring H2O2 in exhaled breath condensate.

PMID: 12204843 [PubMed - indexed for MEDLINE]

1200: Allergol Immunopathol (Madr). 2002 Jul-Aug;30(4):218-24.

Is Lolium pollen from an urban environment more allergenic than rural pollen?

Armentia A, Lombardero M, Callejo A, Barber D, Martín Gil FJ, Martín-Santos JM,
Vega JM, Arranz ML.

Allergy Section of Rio Hortega Hospital, Valladolid, Spain. jmartinsantos@nexo.es

BACKGROUND: Allergy to grass pollen is a highly prevalent allergic disease. Hay
fever is more predominant in urban than in rural areas, despite the increasingly 
smaller areas of surrounding grassland. The effect of vehicle exhaust pollutants,
mainly diesel particles, and other industrial sources of atmospheric pollution
leading to plant damage has been implicated in this phenomenon. OBJECTIVE: This
study compared the in vivo and in vitro allergenicity of pooled samples of Lolium
perenne grass pollen harvested from 10 different urban areas with that of samples
of the same pollen from 10 neighboring rural areas. METHODS: Lolium perenne
pollen from different parts of a city and from a nearby rural area was harvested 
in 1999 and 2000 during the peak pollination period. Protein composition was
compared by SDS-PAGE and in vivo and in vitro IgE-binding capacity was compared
by skin-prick tests, RAST-inhibition and measurement of the major allergen, Lol p
5. RESULTS: In the two years under study, urban samples contained approximately
twice the protein content of the rural samples. Biological activity and Lol p 5
content was higher in urban pollen than in rural pollen and showed differences in
the two years under study. CONCLUSIONS: The protein content and allergenicity of 
Lolium perenne pollen was higher in urban areas than in rural areas. These
differences might explain why allergy to grass pollen is more prevalent in urban 
areas. This finding should be taken into account in diagnosis, preventive
measures and specific immunotherapy.

Publication Types: 
    Comparative Study

PMID: 12199966 [PubMed - indexed for MEDLINE]

1201: Ann Allergy Asthma Immunol. 2002 Aug;89(2):159-65.

Establishing a model of seasonal allergic rhinitis and demonstrating
dose-response to a topical glucocorticosteroid.

Ahlström-Emanuelsson C, Persson CG, Svensson C, Andersson M, Hosszu Z, Akerlund
A, Greiff L.

Department of Otorhinolaryngology, Head & Neck Surgery, University Hospital,
Lund, Sweden.

BACKGROUND: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for
research purposes, there is a need for disease-like models of allergic rhinitis. 
In a preliminary study, involving 7 days' challenge with allergen, promising
symptom consistency was obtained and dose-response to a glucocorticosteroid
could, in part, be demonstrated. OBJECTIVE: To establish this model of seasonal
allergic rhinitis and test the hypothesis that mometasone furoate is more potent 
than budesonide as an antirhinitis drug. METHODS: Thirty-eight patients with
seasonal allergic rhinitis received treatment with spray-formulations of placebo,
budesonide 64 microg, budesonide 256 microg, and mometasone furoate 200 microg in
a double-blind, crossover design. After 3 days' treatment, individualized nasal
allergen-challenges were administered daily for 7 days while the treatment
continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. RESULTS:
During the last 3 days of allergen challenge without active treatment, consistent
around-the-clock symptoms were recorded and recordings during these days were
used in the analysis. With few exceptions the active treatments reduced nasal
symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused
dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF
recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256
microg produced greater improvement than mometasone furoate 200 microg for nasal 
PIF 10 minutes after allergen-challenge (P < 0.05). CONCLUSION: The present
allergen challenge method, producing consistent symptoms and nasal PIF data,
emerges as a model of seasonal allergic rhinitis well suited for exploring
potency and efficacy of drug intervention. The present data do not support the
view that mometasone furoate is a more potent antirhinitis drug than budesonide.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12197572 [PubMed - indexed for MEDLINE]

1202: Ann Pharmacother. 2002 Sep;36(9):1366-74.

Comment in:
    Ann Pharmacother. 2003 Jan;37(1):147.

Single-patient drug trial methodology for allergic rhinitis.

Reitberg DP, Del Rio E, Weiss SL, Rebell G, Zaias N.

Scientific Affairs, Opt-e-scrip, Inc., Morristown, NJ 07960-4455, USA.
donreitberg@opt-e-scrip.com

BACKGROUND: Historically, single-patient trials (SPTs) have been specifically
designed for each patient, requiring significant time and effort for execution.
There has been no previous attempt to standardize an SPT for routine commercial
availability. OBJECTIVE: To validate the use of an SPT method to discriminate
effectiveness and adverse events while comparing drugs/doses in patients with
allergic rhinitis. DESIGN: Double-blind, randomized, 4 paired-period,
multiple-crossover SPT. SETTING: Academic and commercial investigative sites.
PATIENTS: Thirty-six patients with allergic rhinitis were evaluated for the most 
appropriate treatment; 6 of these participated in 2 different SPTs.
INTERVENTIONS: Treatment of symptoms of allergic rhinitis by comparing either
loratadine with chlorpheniramine maleate or loratadine with placebo in a series
of SPTs. MEASUREMENTS: Effectiveness endpoints were selected from a modern, Food 
and Drug Administration (FDA)-approved new drug application. Expected adverse
events were directly solicited; unsolicited events were also recorded. Total
signs and symptoms cumulatively included sneezing, runny nose, itchy nose, teary 
eyes, and itchy eyes. Quality of life was measured by the most bothersome symptom
and the patient's global evaluation. RESULTS: Of 42 initiated SPTs, 40 (95%)
provided complete data and 1 (2%) provided partial data, resulting in 41 (98%)
evaluable tests. Thirty-one evaluable SPTs compared loratadine 10 mg/d with
chlorpheniramine maleate 12 mg twice daily, and 10 SPTs compared loratadine 10
mg/d with placebo. Four of 31 SPTs (13%) showed significant superiority for
loratadine over chlorpheniramine maleate and 5 of 31 (16%) for chlorpheniramine
maleate over loratadine. Twenty-two of 31 (71%) showed parity performance between
loratadine and chlorpheniramine maleate. Loratadine was significantly superior to
placebo in 3 of 10 trials (30%), consistent with rates found in 3 pivotal group
trials used for FDA approval (24%, 17%, and 0%). Sleepiness could be
discriminated for loratadine versus placebo and for chlorpheniramine maleate
versus loratadine. CONCLUSIONS: The allergic rhinitis SPT proved to be acceptable
to patients, feasible to administer, and reproducible. It can statistically
discriminate effectiveness and adverse events, serving as a useful, prognostic
tool in community practice.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12196053 [PubMed - indexed for MEDLINE]

1203: J Allergy Clin Immunol. 2002 Aug;110(2):310-7.

Hypersensitivity to mugwort (Artemisia vulgaris) in patients with peach allergy
is due to a common lipid transfer protein allergen and is often without clinical 
expression.

Pastorello EA, Pravettoni V, Farioli L, Rivolta F, Conti A, Ispano M, Fortunato
D, Bengtsson A, Bianchi M.

Allergy Center, 3rd Division of General Medicine, Ospedale Maggiore IRCCS, Via
Francesco Sforza 35, 20122 Milan, Italy.

BACKGROUND: The observation of mugwort-specific IgE antibodies in patients with
peach allergy suggests that mugwort sensitization might play a role in
sensitization to peach. OBJECTIVE: We sought to study the clinical manifestations
of mugwort hypersensitivity in patients with peach allergy, identify the common
allergens, and evaluate their IgE crossreactivity. METHODS: Patients with oral
allergy syndrome for peach and specific IgE antibodies to mugwort were
investigated for respiratory symptoms during the mugwort season. Peach and
mugwort allergens were identified by means of SDS-PAGE and IgE immunoblotting.
Immunoblotting inhibition experiments were done to study cross-reactivity between
peach and mugwort and other pollens. RESULTS: Seventeen patients were studied, 10
with no seasonal respiratory symptoms and 7 with clear late summer respiratory
symptoms. In IgE immunoblotting the 10 asymptomatic patients reacted only to a
9-kd allergen of both mugwort and peach, whereas the 7 patients with pollinosis
reacted to other allergens. Ten patients with mugwort allergy, no history of
allergy to peach, and negative results for peach-specific IgE antibodies were
also studied. The mugwort 9-kd protein was identified as a lipid transfer protein
(LTP) homologous to peach LTP. Immunoblotting inhibition showed that IgE binding 
to the peach 9-kd band was totally inhibited by 4 microg of peach LTP but only by
400 microg of mugwort LTP, whereas 4 microg of both mugwort and peach LTP totally
inhibited the mugwort immunoblotting. The results were similar with other
pollens. CONCLUSIONS: Patients sensitized only to the 9-kd LTP of mugwort do not 
present hay fever symptoms, and this sensitization is a consequence of the peach 
sensitization.

PMID: 12170274 [PubMed - indexed for MEDLINE]

1204: Allergy. 2002 Sep;57(9):825-30.

Up-regulation of IL-18 in allergic rhinitis.

Verhaeghe B, Gevaert P, Holtappels G, Lukat KF, Lange B, Van Cauwenberge P,
Bachert C.

Department of Otorhinolaryngology, Ghent University Hospital, Belgium.

BACKGROUND: This paper reports a study on the concentrations of the
pro-inflammatory cytokines IL-18 and IL-1beta in nasal secretions of allergic
rhinitis patients in relation to ECP and nasal symptoms. METHODS: We measured
IL-18 and IL-1beta concentrations using ELISA, and eosinophilic cationic protein 
(ECP) using the CAP system, in nasal secretions of 15 seasonal allergic rhinitis 
(SAR) patients at six visits throughout the pollen season. Pollen exposure, nasal
and ocular symptoms were monitored daily. Furthermore, we measured IL-18,
IL-1beta and ECP concentrations in nasal secretions of 19 controls and 20
symptomatic persistent allergic rhinitis (PAR) patients with house dust mite
allergy. RESULTS: In SAR, the increase of IL-18, IL-1beta and ECP paralleled the 
pollen flight with a time delay. IL-18 and IL-1beta significantly increased
during the pollen season compared to baseline, and differently from ECP, remained
elevated until 4 weeks after the season. In PAR, the concentrations of IL-18 and 
ECP, but not IL-1beta, were significantly higher compared to controls, with IL-18
concentrations also being significantly higher than in SAR. CONCLUSION: This is
the first study to demonstrate the up-regulation of IL-18 in nasal secretions in 
allergic rhinitis. The persistence of elevated IL-18 concentrations until after
the season and the high concentrations in PAR compared to SAR suggests its role
in persistent allergic inflammation.

PMID: 12169180 [PubMed - indexed for MEDLINE]

1205: Eur J Pharmacol. 2002 Aug 9;449(3):287-91.

Participation of chemical mediators other than histamine in nasal allergy signs: 
a study using mice lacking histamine H(1) receptors.

Kayasuga R, Sugimoto Y, Watanabe T, Kamei C.

Department of Pharmacology, Faculty of Pharmaceutical Science, Okayama
University, Okayama 700-8530, Okayama, Japan.

The purpose of this study was to investigate the involvement of chemical
mediators other than histamine in nasal allergic signs using histamine H(1)
receptor-deficient mice. In passively sensitized mice, antigen instillation into 
the nasal cavity induced significant increases in sneezing and nasal rubbing in
wild-type mice, but no such increases were observed in histamine H(1)
receptor-deficient mice. In actively sensitized mice, both sneezing and nasal
rubbing were also significantly increased in a dose-dependent manner in both
wild-type and histamine H(1) receptor-deficient mice. Histamine H(1) receptor
antagonists such as cetirizine and epinastine significantly inhibited
antigen-induced nasal allergic signs in wild-type mice, although the effects were
incomplete. In addition, the thromboxane A(2) receptor antagonist ramatroban also
inhibited these responses in wild-type mice. However, the leukotriene receptor
antagonist zafirlukast showed no effects in wild-type mice. These results
suggested that in the acute allergic model (passive sensitization), only
histamine H(1) receptors are related to nasal signs induced by antigen, whereas
in the chronic allergic model (active sensitization), both histamine H(1)
receptors and thromboxane A(2) receptors were involved in the responses.

PMID: 12167471 [PubMed - indexed for MEDLINE]

1206: Auris Nasus Larynx. 2002 Jul;29(3):261-6.

Birch-pollen sensitization in an area without atmospheric birch pollens.

Yamagiwa M, Hattori R, Ito Y, Yamamoto S, Kanba M, Tasaki T, Ueda K, Nishizumi T.

Department of Otolaryngology, Matsusaka Chuo Hospital, Kawaimachi Kobo 102,
Matsusaka, Mie 515-8566, Japan. miki@mch.miekosei.or.jp

OBJECTIVE: To clarify the incidence of individuals with a subclinical allergy to 
birch pollen and the possible allergic association between birch pollen and other
allergens in areas without atmospheric birch pollen. METHODS:
Birch-pollen-specific immunoglobulin E concentration in sera, together with those
for some other inhaled and ingested allergens, was measured in 409 male and 525
female patients (an average age of 58.6 years, born and raised in an area without
atmospheric birch pollen) with suspicious nose and/or throat allergies.
Concomitantly, types and concentrations of pollen grains in the regional air were
examined. RESULTS: Of 934 patients 13.2% showed birch-pollen-specific
immunoglobulin E although no birch pollens were observed in the atmospheric air. 
The rate was relatively low in comparison with those for clinically important
inhaled allergens in this area: 35.2% for Japanese cedar pollen, 24.7% for house 
dust and 23.2% for cypress pollen. Spearman's rank correlation analysis and
logistic regression analysis revealed that birch pollen correlated strongly with 
apple and some foodstuffs commonly ingested by all age groups (rho>0.6000, odds
ratio>27.191). CONCLUSIONS: A considerably large number of patients with a
subclinical allergy to birch pollen exist in an area without atmospheric birch
pollen. Measurement of specific immunoglobulin E to birch pollen is important
even in such areas for screening and diagnosing patients with oral allergy
syndrome.

PMID: 12167448 [PubMed - indexed for MEDLINE]

1207: Eur Respir J. 2002 Jul;20(1):92-9.

Comment in:
    Eur Respir J. 2003 Jan;21(1):197; author reply 197-8.

Exhaled carbon monoxide is not elevated in patients with asthma or cystic
fibrosis.

Zetterquist W, Marteus H, Johannesson M, Nordval SL, Ihre E, Lundberg JO, Alving 
K.

Dept of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
wilhelm.zetterquist@fyfa.ki.se

Increased levels of exhaled carbon monoxide (fractional concentration of CO in
expired gas (FE,CO)), measured with an electrochemical sensor, have been reported
in patients with inflammatory airway disorders, such as asthma, rhinitis and
cystic fibrosis. This study aimed to evaluate these findings by using a
fast-response nondisperse infrared (NDIR) analyser, and to compare these
measurements with the fractional concentration of nitric oxide in exhaled air
(FE,NO). Thirty-two steroid-naïve asthmatics, 24 steroid-treated asthmatics (16
patients with allergic rhinitis, nine patients with cystic fibrosis), and 30
nonsmoking healthy controls were included. CO measurements with the NDIR analyser
were performed simultaneously with nitric oxide (NO) analysis (chemiluminescence 
technique). After 15 s of breath-hold, single-breath exhalations over 10 s were
performed at two flow rates and end-tidal plateau concentrations were registered.
An electrochemical CO sensor was used independently with an exhalation to
residual volume, after a 15 s breath-hold. None of the two CO analysers gave a
significant increase in FE,CO in the groups of patients with inflammatory airway 
disorders compared to controls. FE,NO was significantly elevated in steroid-naïve
asthmatics and subjects with allergic rhinitis, but not in steroid-treated
asthmatics and subjects with cystic fibrosis. Reducing exhalation flow rate by
50% gave a two-fold increase in FE,NO, while FE,CO was unaffected. A significant 
increase was seen in FE.CO, but not in FE,NO, when comparing with and without a
10 s breath-hold. In conclusion, the fractional concentration of carbon monoxide 
in expired gas was not increased in any of the patient groups, while the
fractional concentration of nitric oxide in expired gas was significantly
elevated in patients with steroid-naïve asthma and allergic rhinitis. Moreover,
carbon monoxide was unaffected by flow rate but increased with breath-hold,
suggesting an origin in the alveoli rather than the conducting airways.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12166588 [PubMed - indexed for MEDLINE]

1208: Eur Respir J. 2002 Jul;20(1):79-85.

Association of asthma and total IgE levels with human leucocyte antigen-DR in
patients with grass allergy.

Woszczek G, Kowalski ML, Borowiec M.

Dept of Clinical Immunology and Allergy, University Medical School of Lodz,
Poland.

Exposure to grass pollens during the pollen season, reveals in sensitive patients
symptoms of allergic rhinitis, conjunctivitis and/or bronchial asthma. It is not 
well understood why, in some patients, only symptoms of rhinitis occur while in
others similar exposure causes symptoms of asthma and rhinitis. An association
study is reported here, where the possible contribution of human leucocyte
antigen (HLA)-DR gene polymorphisms to differential phenotypic expression of
symptoms in patients with grass-pollen allergy was determined. HLA-DR genotyping 
was performed by the polymerase chain reaction with the sequence-specific primers
method in 82 patients with symptoms of seasonal allergic rhinitis and/or
bronchial asthma and 52 healthy nonatopic control subjects. A significant
association was found between HLA-DRB1*02, B5* haplotype and asthma phenotype in 
patients with grass-pollen allergy when compared to patients with rhinitis only. 
Significantly higher total serum immunoglobulin E levels were observed in
patients with HLA-DRB1*01 alleles in comparison to patients without these
alleles. The data in this study suggest that human leucocyte antigen-DR locus, or
other genes in linkage disequilibrium, may play an important role in asthma
phenotype expression in patients with grass-pollen allergy as well as in
determining total immunoglobulin E levels in these patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12166586 [PubMed - indexed for MEDLINE]

1209: J Immunol. 2002 Aug 15;169(4):2054-60.

Up-regulation of functional kinin B1 receptors in allergic airway inflammation.

Christiansen SC, Eddleston J, Woessner KM, Chambers SS, Ye R, Pan ZK, Zuraw BL.

Department of Molecular and Experimental Medicine, The Scripps Research
Institute, La Jolla, CA 92037, USA.

B1 receptors are known to be induced during allergic airway inflammation in
animal models. However, little is known regarding in vivo B1 receptor expression 
in humans. We examined B1 receptor mRNA expression in nasal tissue samples from
allergic rhinitis and normal subjects. Allergic rhinitis subjects displayed
significantly higher expression of B1 receptor mRNA than did the normal subjects,
and nasal allergen challenge increased B1 receptor mRNA expression at 8 to 24 h
time points in allergic rhinitis subjects. No significant difference was found in
B2 receptor expression. To confirm B2 and B1 receptor functional activity,
subjects were challenged with kinin agonists. Nasal challenge with the B1
receptor ligand, Lys-des-Arg-bradykinin (BK), activated extracellular
signal-regulated kinase in allergic rhinitis, but not normal, subjects. Nasal
challenge with the B2 receptor ligand, BK, activated extracellular
signal-regulated kinase in both allergic rhinitis and normal subjects. The
consequences of B1 receptor activation were investigated using the human airway
epithelial cell lines A549 and BEAS-2B. We demonstrated that Lys-des-Arg-BK
activates the transcription factor AP-1. Taken together, these results show that 
functional B1 receptors are induced in the airway during allergic inflammation
and suggest that they participate in the regulation of gene expression.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12165532 [PubMed - indexed for MEDLINE]

1210: BMC Fam Pract. 2002 Aug 5;3:14.

24-hour efficacy of once-daily desloratadine therapy in patients with seasonal
allergic rhinitis [ISRCTN32042139].

Salmun LM, Lorber R.

Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
luis.salmun@spcorp.com

BACKGROUND: Early studies with desloratadine demonstrated efficacy in treating
seasonal allergic rhinitis (SAR). A dose-ranging study was conducted to
characterize its 24-hour efficacy in patients with SAR. METHODS: Patients (N =
1,026) were randomly assigned once-daily (QD) desloratadine (2.5, 5, 7.5, 10, or 
20 mg) for 2 weeks in a placebo-controlled, double-blind study. The end point of 
24-hour efficacy was assessed by the mean change from baseline in the average AM 
instantaneous total symptom score (TSS) over the treatment period. Day 2 data
were assessed for efficacy of desloratadine following the first dose. Other
efficacy variables included AM/PM previous total nasal and nonnasal symptom
scores and individual symptom scores. RESULTS: Desloratadine 5-20 mg was
significantly (P <.01) more effective than placebo in improving total AM
instantaneous TSS and AM/PM previous total nasal and nonnasal symptom scores.
This dosing range also was significantly (P <.01) more effective than placebo for
reducing AM instantaneous TSS beginning with the first dose; thus, demonstrating 
the full 24-hour efficacy of desloratadine. AM/PM previous scores for all
individual symptoms, including nasal congestion, were also significantly improved
versus placebo (P <.05) with desloratadine at 5, 7.5, and 20 mg. All treatments
were well tolerated. There were no clinically meaningful changes in
electrocardiogram parameters. CONCLUSION: Desloratadine 5-20 mg provided
significant 24-hour relief of SAR signs and symptoms. There were no statistically
significant differences between the 4 largest doses suggesting that desloratadine
5 mg QD offers the best therapeutic profile for patients with SAR.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12162793 [PubMed - indexed for MEDLINE]

1211: FASEB J. 2002 Aug;16(10):1301-3. Epub 2002 Jun 21.

Combination vaccines for the treatment of grass pollen allergy consisting of
genetically engineered hybrid molecules with increased immunogenicity.

Linhart B, Jahn-Schmid B, Verdino P, Keller W, Ebner C, Kraft D, Valenta R.

Department of Pathophysiology, Vienna General Hospital, AKH, University of
Vienna, Austria.

Most of the 400 million grass pollen-allergic patients worldwide are
co-sensitized to several unrelated grass pollen allergens. Based on frequent
co-sensitization patterns determined in 200 grass pollen-allergic patients, three
recombinant hybrid molecules were developed by polymerase chain reaction-based
mending of cDNAs coding for the major timothy grass pollen allergens (Phl p 1,
Phl p 2, Phl p 5, Phl p 6) for vaccination against grass pollen allergy. The
hybrids rP2-P6, rP6-P2, and rP5-P1 contained most of the epitopes of natural
grass pollen extract and induced stronger lymphoproliferative responses in
cultured mononuclear cells of grass pollen-allergic patients than did equimolar
mixtures of the individual allergens. Immunization of mice with the hybrids
yielded higher antibody titers than did immunization with the individual allergen
components or grass pollen extract, which suggests that the individual components
of the hybrids can serve as molecular scaffolds for each other to enhance their
immunogenicity. Antibodies induced with the hybrids in mice inhibited the binding
of grass pollen-allergic patients' immunoglobulin E to each of the individual
allergens and grass pollen extract and may thus represent protective antibodies. 
The principle of increasing the immunogenicity of antigens by engineering hybrids
thereof may be applied not only for the treatment of polysensitized allergic
patients but also for general vaccine development.

PMID: 12154002 [PubMed - indexed for MEDLINE]

1212: Laryngoscope. 2002 May;112(5):926-9.

An interpretation method for objective assessment of nasal congestion with
acoustic rhinometry.

Mamikoglu B, Houser SM, Corey JP.

Department of Surgery, University of Chicago Hospitals, Illinois, USA.

OBJECTIVES: Acoustic rhinometry is a relatively new modality for evaluating the
status of the nose. It assesses the geometry of the nasal cavity by analyzing
reflected sound waves. Despite its expanding use, there is no established
interpretation method. Our aims in the present descriptive study were to develop 
and test a protocol as a possible method to read these graphs for clinical use.
STUDY DESIGN: We formulated a reading protocol to grade the congestion state of
the nasal cavity. The percentile difference of cross-sectional area and volume
values between the baseline and decongested states were classified into five
categories based on normative values. METHODS: Fifty-six patients with allergic
rhinitis were used. All the acoustic rhinometry readings were performed in
blinded fashion according to the protocol; later, the clinical information was
paired with the interpretation of the graph. RESULTS: The mean percentile
differences of baseline and decongestion values in patients with allergic
rhinitis were in the mild to moderate range difference according to our reading
system. The range of nasal congestion in patients with allergic rhinitis patients
was increased with additional pathological conditions such as sleep apnea.
CONCLUSION: The percentile difference between the baseline values and values for 
maximally decongested state reflect mucosal congestion as a "congestion factor," 
which can be graded as mild, moderate, severe, or markedly severe, for objective 
evaluation of nasal congestion.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12150630 [PubMed - indexed for MEDLINE]

1213: Am J Rhinol. 2002 May-Jun;16(3):175-7.

Heated humidification during nasal continuous positive airway pressure for
obstructive sleep apnea syndrome: objective evaluation of efficacy with nasal
peak inspiratory flow measurements.

Winck JC, Delgado JL, Almeida JM, Marques JA.

Department of Pneumology, Faculty of Medicine, Hospital de S João, Porto,
Portugal.

BACKGROUND: Nasal obstruction is one of the most frequent and sometimes
troublesome side effects of nasal continuous positive airway pressure (nCPAP)
therapy for obstructive sleep apnea syndrome (OSAS). METHODS: We describe a
60-year-old man with allergic seasonal rhinitis and OSAS, with worsening nasal
symptoms 1 week after beginning home nCPAP, making nCPAP use difficult (nasal
peak inspiratory flow [nPIF], 80 L/minute [57% of his best]). RESULTS: No
significant improvement was obtained with topical steroids or cold
humidification. Heated humidification was then considered, achieving an
improvement in mean nPIF and symptom scores. An acceptable compliance with CPAP
could be obtained during the heated humidification period (3.9 hours of mean
daily use). CONCLUSION: In this patient with moderately severe OSAS and allergic 
rhinitis, monitoring nasal symptoms and nasal PIF objectively showed the benefit 
of heated humidification to overcome nasal intolerance and increase compliance to
nCPAP treatment.

Publication Types: 
    Case Reports

PMID: 12141777 [PubMed - indexed for MEDLINE]

1214: Ann Allergy Asthma Immunol. 2002 Jul;89(1):56-62.

Comparative efficacy, safety, and effect on quality of life of triamcinolone
acetonide and fluticasone propionate aqueous nasal sprays in patients with fall
seasonal allergic rhinitis.

Gross G, Jacobs RL, Woodworth TH, Georges GC, Lim JC.

Dallas Allergy & Asthma Center, Texas, USA.

BACKGROUND: The topical potency of fluticasone propionate (FP) is known to be
four times greater than that of triamcinolone acetonide (TAA). However, the
significance of this difference has not been proven in the clinical treatment of 
seasonal allergic rhinitis (SAR). OBJECTIVE: To compare the efficacy, safety, and
effect on health-related quality of life (HRQL) of FP and TAA aqueous nasal
sprays in patients with SAR. METHODS: Single-blind, parallel-group,
active-controlled design. Patients were randomized to 3-week treatment with TAA
220 microg (n = 172) or FP 200 microg (n = 180) as two sprays/nostril once daily 
AM. Twelve-hour reflective symptom evaluations (nasal discharge, stuffiness,
itching; sneezing; ocular itching/tearing/redness) were performed AM/PM,
beginning at pretreatment baseline period. Incidences of specific
treatment-related side effects were collected in daily questionnaires. HRQL was
evaluated at baseline and end-of-treatment with a validated disease-specific,
quality-of-life instrument. RESULTS: TAA and FP produced similar improvement in
daily total nasal symptom scores overall (49.4% and 52.7%, respectively; P =
0.332) and at every weekly time point (P > 0.05). There were no significant
differences between TAA and FP in any individual symptom score at any time point 
except week 2 (FP provided greater reduction in sneezing, P = 0.046). No
significant difference was found between groups in overall occurrence of specific
treatment-related side effects. Overall Rhinoconjunctivitis Quality of Life
Questionnaire scores were similar for TAA and FP at end-of-treatment.
CONCLUSIONS: Despite differing molecular potencies, FP and TAA demonstrated
comparable efficacy in the treatment of SAR, and produced similar occurrences of 
specific treatment-related side effects and similar improvements in overall
patient HRQL.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12141721 [PubMed - indexed for MEDLINE]

1215: Ann Allergy Asthma Immunol. 2002 Jul;89(1):38-45.

Onset of action, efficacy, and safety of fexofenadine 60 mg/pseudoephedrine 120
mg versus placebo in the Atlanta allergen exposure unit.

Berkowitz RB, Woodworth GG, Lutz C, Weiler K, Weiler J, Moss M, Meeves S.

RxResearch, Woodstock, Georgia 30188, USA.

BACKGROUND: Second-generation antihistamine-decongestant combinations are often
used to treat seasonal allergies. However, onset of action and efficacy data for 
these agents in a controlled setting are limited. OBJECTIVE: Determine onset of
action of fexofenadine-pseudoephedrine (Allegra-D, Aventis, Bridgewater, NJ) for 
treating moderate-to-severe seasonal allergies in an allergen exposure unit.
METHODS: This single-dose, double-blind, placebo-controlled study was conducted
during the fall ragweed allergy season. Qualifying subjects attended one to two
priming visits; those with sufficient symptom scores returned for treatment and
were initially exposed to ragweed pollen for 90 minutes. Symptomatic subjects
received fexofenadine-pseudoephedrine or placebo and recorded symptoms for 6
hours postdose. Efficacy variables were major symptom complex (MSC; sneezes,
itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, stuffy nose),
total symptom complex (nose blows, sniffles, postnasal drip, cough, plus all MSC 
symptoms), and all individual symptoms as well as headache. Onset of action for
each efficacy variable was calculated as the earliest time at which a consistent,
significant decrease was seen for fexofenadine-pseudoephedrine versus placebo.
RESULTS: Of 571 screened subjects, 298 were randomized. Onset of relief for
fexofenadine-pseudoephedrine (n = 148) was 45 minutes postdose (MSC, P = 0.0127; 
total symptom complex, P = 0.0380). All individual symptoms were reduced to a
greater extent with fexofenadine-pseudoephedrine than with placebo (P < 0.05, not
adjusted for multiple comparisons). Decrease in headache with
fexofenadine-pseudoephedrine versus placebo began 45 minutes postdose (P =
0.0425). Incidence of treatment-related adverse events was 1.4% for
fexofenadine-pseudoephedrine and 3.3% for placebo. CONCLUSIONS:
Fexofenadine-pseudoephedrine was safe and effective in treating a broad range of 
allergy symptoms, with a rapid onset of action at 45 minutes.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12141718 [PubMed - indexed for MEDLINE]

1216: Psychosom Med. 2002 Jul-Aug;64(4):684-91.

Effects of seasonal allergic rhinitis on fatigue levels and mood.

Marshall PS, O'Hara C, Steinberg P.

Department of Psychiatry, Hennepin County Medical Center, Minneapolis, MN 55415, 
USA. paul.marshall@co.hennepin.mn.us

OBJECTIVE: Many allergy patients complain of fatigue, moodiness, and dysphoria
during their allergy seasons. This study evaluated the effect of symptomatic
allergic rhinitis on both fatigue level and mood. METHOD: Symptomatic ragweed
allergic rhinitis patients on no medications and healthy control subjects
completed the Multi-Dimensional Fatigue Inventory and the Positive
Affect-Negative Affect mood rating scales in an in-out-in ragweed season research
design. RESULTS: During ragweed seasons, allergic patients reported higher levels
of general fatigue and mental fatigue, but not physical fatigue, as well as
reduced motivation. Patients described experiencing feelings of greater sadness
and reduced pleasurable engagement. Increased anxiety or emotional distress was
not reported. CONCLUSIONS: These findings suggest that having allergic reactions 
to ragweed pollen causes significant fatigue and mood changes in at least a
subgroup of patients. Psychoneuroimmunology and medical genetics research
suggests that allergic reactions engender biochemical changes that directly
affect the central nervous system.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12140359 [PubMed - indexed for MEDLINE]

1217: Allergy Asthma Proc. 2002 May-Jun;23(3):185-90.

Cytokines in nasal lavage fluids from acute sinusitis, allergic rhinitis, and
chronic fatigue syndrome subjects.

Repka-Ramirez S, Naranch K, Park YJ, Clauw D, Baraniuk JN.

Division of Rheumatology, Immunology, and Allergy, Center for Chronic Pain and
Fatigue Research, Georgetown University, 3800 Reservoir Road, N.W., Washington,
D.C. 20007-2197, USA.

The aim of this study was to compare the degree of inflammation present in acute 
sinusitis, allergic rhinitis, chronic Fatigue Syndrome (CFS), and non-CFS control
subjects by measuring cytokine concentrations in nasal lavage fluids. The
concentrations of total protein (TP; Lowry assay), nerve growth factor (NGF),
tumor necrosis factor (TNF) alpha, and interleukin (IL)-8 were measured by ELISA 
in nasal lavage fluids from acute sinusitis (n = 13), active allergic rhinitis (n
= 16), CFS (n = 95), and non-CFS (n = 89) subjects. CFS and non-CFS groups were
subdivided further using allergy skin test and rhinitis score results. Acute
sinusitis subjects had significantly higher TP (p = 0.011, ANOVA), TNF-alpha (p =
0.00071), and IL-8 (p = 0.0000027) concentrations and IL-8/TP ratios (p = 0.0030)
than the other three patient groups. There were no differences based on skin test
or rhinitis score severity within either the CFS or non-CFS groups. The
mucopurulent discharge of acute sinusitis contained significantly higher
TNF-alpha and IL-8. Neutrophils were a likely source for these cytokines. There
were no differences between CFS and non-CFS subjects, making it unlikely that the
rhinitis of CFS has an inflammatory component.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 12125506 [PubMed - indexed for MEDLINE]

1218: Allergy. 2002 Aug;57(8):718-22.

Hemin, a heme oxygenase substrate analog, inhibits the cell surface expression of
CD11b and CD66b on human neutrophils.

Andersson JA, Egesten A, Cardell LO.

Department of Otorhinolaryngology, Malmö University Hospital, Sweden.

BACKGROUND: Neutrophils are signaled to sites of infection and inflammation by
different chemotactic stimuli. In order to reach the airways they have to adhere 
to, and then migrate through, the endothelium of pulmonary vessels. Carbon
monoxide (CO) is a gaseous mediator, endogenously produced in the human airways. 
Increased CO production has been demonstrated during airway inflammation and CO
as well as hemin, a substrate for CO producing enzymes, has been shown to affect 
neutrophil migration. Our objective was to investigate if the neutrophil cell
surface expression of CD11b, CD66b and CD63 was changed during intermittent
allergic rhinitis and to establish whether CO could affect the expression of
these markers of cellular activation. METHODS: Blood from 10 healthy volunteers
was drawn and incubated with different concentrations of hemin. Blood from 12
other healthy volunteers and from 12 patients with intermittent allergic rhinitis
was also drawn during grass pollen season. Neutrophils were then isolated from
all these three sets, and their expression of CD antigens measured using flow
cytometry. RESULTS: Patients with symptomatic intermittent allergic rhinitis
exhibited lower levels of CD11b and CD66b on the neutrophil cell surface.
Incubation with hemin decreased the expression of CD11b and CD66b. CD63 was
generally weakly expressed and not significantly affected by hemin incubation.
CONCLUSION: Our results demonstrate that expressions of neutrophil cell surface
glycoproteins are changed during the season in patents with intermittent allergic
rhinitis and that hemin, a substrate for CO production, may act as an inhibitor
of neutrophil activation. This indicates a possible role for CO in the immune
defense system.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12121191 [PubMed - indexed for MEDLINE]

1219: Clin Ther. 2002 Jun;24(6):942-52.

Efficacy and patient satisfaction with cromolyn sodium nasal solution in the
treatment of seasonal allergic rhinitis: a placebo-controlled study.

Meltzer EO; NasalCrom Study Group.

Allergy and Asthma Medical Group and Research Center, San Diego, California
92123, USA.

BACKGROUND: Because the symptoms of seasonal allergic rhinitis are readily
recognizable, many individuals self-medicate with nonprescription agents. The
mast-cell stabilizer cromolyn sodium is available for over-the-counter (OTC) use 
in the prevention and treatment of allergic rhinitis. OBJECTIVE: The goal of the 
study was to evaluate the efficacy of cromolyn sodium 4% nasal solution for the
treatment of allergic rhinitis in self-selected patients in a nonprescription
setting. A secondary objective was to determine whether the instructions and
warnings in the OTC labeling provide adequate information for safe and proper OTC
use. METHODS: This 2-week, multicenter study had a randomized, double-blind,
placebo-controlled, parallel-group design. Advertisements were used to identify
allergy sufferers who used OTC products but had not used OTC allergy medications 
within 48 hours of study entry and did not require prescription medications to
control allergy symptoms. Enrolled patients were randomized to receive either
cromolyn sodium 4% nasal solution in a metered-spray bottle containing 200 doses 
or an identical-appearing placebo. They were instructed to follow the directions 
for use on the label: that is, to administer 1 spray in each nostril every 4 to 6
hours, no more than 6 times per day, for the prevention or relief of symptoms.
Daily use of study drug and concomitant medications was recorded in patient
diaries. Patients also rated symptom severity, symptom relief, medication
efficacy, and helpfulness of the label instructions. Relief of overall and
individual rhinitis symptoms was assessed at the end of weeks 1 and 2. RESULTS:
The intent-to-treat population consisted of 1150 patients (580 cromolyn sodium,
570 placebo). Cromolyn sodium provided greater relief than placebo on all
efficacy measures and was statistically significantly more effective than placebo
in controlling allergy symptoms (P = 0.02), providing overall symptom relief (P =
0.02), and relieving sneezing (P = 0.01) and nasal congestion (P = 0.03). The
instructions for use were rated helpful to extremely helpful by >92% of patients,
although only approximately 48% of patients used the drug according to the label 
instructions. The most common adverse events in both groups were headache and
rhinitis, and there was no significant difference in the rates of such events
between groups. CONCLUSION: In this study, cromolyn sodium 4% nasal solution was 
well tolerated and effective, suggesting that it is suitable for OTC use in the
treatment of seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12117084 [PubMed - indexed for MEDLINE]

1220: Eur J Immunol. 2002 Jul;32(7):1933-8.

CCR4 in human allergen-induced late responses in the skin and lung.

Nouri-Aria KT, Wilson D, Francis JN, Jopling LA, Jacobson MR, Hodge MR, Andrew
DP, Till SJ, Varga EM, Williams TJ, Pease JE, Lloyd CM, Sabroe I, Durham SR.

Upper Respiratory Medicine, National Heart and Lung Institute, Faculty of
Medicine, Imperial College of Science, Technology and Medicine, London, GB.

We studied the regulation of CCR4 expression in peripheral blood and in human
models of cutaneous and pulmonary allergen challenge. CCR4 expression was
detectable on freshly isolated CD4+ lymphocytes and in CD4+ and CD8+ T cell lines
derived from blood of atopic donors. Numbers of CCR4+ cells were up-regulated in 
T cell lines expanded in the presence of IL-4. CCR4 mRNA was absent at baseline
in normal subjects in lung and skin, but present at baseline in the lung of some 
atopics. Baseline expression of CCR4 mRNA and protein was higher in lung vs.
skin, but allergen-induced increases in CCR4 mRNA+ cells were observed in both
organs. CCR4 protein+ cells were present at higher levels after allergen
challenge in atopics compared to normal subjects. CCR4 may be important in the
recruitment of T lymphocytes at sites of allergic inflammation, in a
non-organ-specific manner.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12115613 [PubMed - indexed for MEDLINE]

1221: Clin Allergy Immunol. 2002;17:319-36.

Cost-effectiveness of H1-antihistamines.

Blaiss MS.

University of Tennessee Center for the Health Sciences, College of Medicine,
Memphis, Tennessee, USA.

In the health care arena, assessment of a medication's clinical efficacy is no
longer enough. It is important to confirm the medication's cost-effectiveness and
the improvement in quality of life it provides in relationship to other options
in therapy. H1-antagonists are widely used in the treatment of many atopic
disorders, especially allergic rhinitis. This review has pointed out
cost-effectiveness and quality-of-life studies comparing the different
H1-antagonists among themselves, and with other treatments used in allergic
rhinitis, such as intranasal corticosteroids and allergen immunotherapy.
Cost-effective analyses among H1-antagonists in other allergic diseases, such as 
atopic dermatitis, urticaria and angioedema, and asthma, are lacking at this
time.

Publication Types: 
    Review

PMID: 12113222 [PubMed - indexed for MEDLINE]

1222: Clin Allergy Immunol. 2002;17:179-220.

Antihistamines in rhinoconjunctivitis.

Howarth P.

University of Southampton, Southampton, England.

In allergic rhinoconjunctivitis, histamine is known to contribute predominantly
to nasal itch, sneeze, rhinorrhea, conjunctival itch, and lacrimation and these
symptoms benefit most from H1-antihistamine therapy. The discovery in the early
1980s of nonsedating H1-receptor antagonists contributed dramatically to the more
widespread acceptance of this mode of therapy. This also led to the undertaking
of well-designed clinical trials that have added significantly to our
understanding of allergic rhinitis. Oral treatment modifies both nasal and ocular
symptoms and provides effective control throughout a 24-h period with once- or
twice-daily medication. The advent of topical H1-receptor antagonists offers a
wider choice of treatments and provides equal or greater efficacy with lower
systemic bioavailability. While having a major impact on rhinoconjunctivitis
symptoms, H1-antihistamines do not fully modify disease since histamine is not
the only contributor to symptom generation in allergic rhinoconjunctivitis. While
the search for oral H1-antihistamines with more widespread "antiallergic"
activity continues, the currently available medications modify predominantly
histamine-regulated events despite in vitro evidence of greater potential. The
development of these new medications may be the next significant advance in this 
mode of treatment.

Publication Types: 
    Review

PMID: 12113217 [PubMed - indexed for MEDLINE]

1223: Pediatr Pulmonol. 2002 Aug;34(2):112-21.

Impact of respiratory illness on expiratory flow rates in normal, asthmatic, and 
allergic children.

Rappaport EB, Gilliland FD, Linn WS, Gauderman WJ.

Department of Preventive Medicine, University of Southern California, Los Angeles
90089, USA. erappap@usc.edu

We examined the effects of current respiratory illness (RI) on pulmonary function
(PF) in 1,103 subjects who underwent spirometry at schools twice within a 4-month
period. Before spirometry, subjects were asked if they had a "cold or other chest
illness" during the previous month, and if so, whether they had fully recovered. 
Those who had not recovered were considered to have an RI.We found that children 
without RI at their first PF test who reported RI on retest had significantly
lower forced expiratory volume in 1 sec (FEV(1)) (-0.8%), peak expiratory flow
rate (PEFR) (-2.2%), forced expiratory flow between 25-75% of vital capacity
(FEF(25-75)) (-3.5%), and forced expiratory flow at 75% of vital capacity
(FEF(75)) (-5.1%) than those without RI on both test and retest. Restriction of
subjects to those without a history of doctor-diagnosed asthma did not
appreciably change these findings. Children with hay fever had significantly
larger RI-associated decreases for FEV(1), FEF(25-75), and FEF(75), but not PEFR,
than those without hay fever. Among asthmatic subjects, those with active asthma 
had larger RI-associated decreases in FEF(25-75) and FEF(75), but not PEFR, than 
those without asthma. There was limited evidence that small airway losses were
greater in children less than 12.5 years old.We conclude that RI in children who 
are well enough to attend school may reduce expiratory flow rates. These effects 
are greater for children with active asthma or hay fever than in those without,
and may be inversely related to age. Copyright 2002 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 12112777 [PubMed - indexed for MEDLINE]

1224: J Allergy Clin Immunol. 2002 Jul;110(1):68-71.

The effect of omalizumab on nasal allergic inflammation.

Plewako H, Arvidsson M, Petruson K, Oancea I, Holmberg K, Adelroth E, Gustafsson 
H, Sandström T, Rak S.

Asthma and Allergy Research Group, Department of Respiratory Medicine and
Allergology, Sahlgrenska University Hospital, Göteborg, Sweden.

BACKGROUND: In sensitized patients, coupling between IgE and FcepsilonRI
receptors on mast cells leads to release of proinflammatory mediators and a
subsequent influx of inflammatory cells to the affected organ. Omalizumab
(Xolair; formerly rhuMAb-E25) binds to circulating IgE, thus preventing induction
of the allergic process. OBJECTIVE: We investigated the effect of treatment with 
omalizumab on seasonal allergic rhinitis and related changes in inflammatory cell
numbers in nasal biopsy specimens. METHODS: Patients were randomized to treatment
with omalizumab or placebo before the pollen season; the treatment was started
and continued during season. Symptoms and use of medication were recorded, and
blood samples and nasal biopsy specimens were obtained before and during season. 
Immunocytochemistry was performed on biopsy sections through use of the following
antibodies: anti-CD4, CD8 (T lymphocytes), EG2, and anti-eosinophil peroxidase
(eosinophils), anti-tryptase (mast cells), human neutrophil lipocalin
(neutrophils), and antibodies against IgE and FcepsilonRI. RESULTS: During the
season, blood eosinophils increased in placebo-treated patients but not in
omalizumab-treated patients (P =.01); the difference between the treatment groups
was significant (P =.04). Free IgE in serum decreased significantly (P =.0002) in
omalizumab-treated patients but not in placebo-treated patients; the difference
between the groups was significant (P =.0001). In nasal biopsy specimens, the
number of eosinophil peroxidase-positive staining cells increased in the
placebo-treated patients (P =.003) but not in the actively treated patients
during the season; the difference between the groups was significant (P =.0001). 
The number of IgE(+) staining cells decreased significantly in the omalizumab
group during the season in comparison with the placebo group (P =.04).
CONCLUSION: The clinical benefit of treatment with omalizumab is associated with 
an anti-inflammatory effect on cellular markers in blood and nasal tissue.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12110823 [PubMed - indexed for MEDLINE]

1225: Eur Respir J. 2002 Jun;19(6):1040-6.

Trends in prevalence of atopic diseases and allergic sensitization in children in
Eastern Germany.

Heinrich J, Hoelscher B, Frye C, Meyer I, Wjst M, Wichmann HE.

GSF-National Research Centre for Environment and Health Institute of
Epidemiology, Neuherberg, Germany. joachim.heinrich@gsf.de

Trends in prevalence of atopic diseases and allergic sensitization in children
from Eastern Germany during the 1990s were analysed. The study consisted of three
regional cross-sectional surveys of a total of 7,632 children (aged 5-14 yrs) in 
1992-1993, 1995-1996, and 1998-1999. Information was gathered on atopic diseases 
and potential predictors by a parental questionnaire. Allergic sensitization for 
birch, grass, mite, cat, and cladosporium were assessed by radioallergosorbent
test (RAST). After adjustment for age, sex and the study area of the
participants, prevalence increased between the first and third survey for hay
fever, for asthma and for atopic eczema. The adjusted prevalence of allergic
sensitization (RAST > 0.35 kU x L(-1)) showed a decrease, whereas the prevalence 
of strong sensitization (RAST > or = 17.5 kU x L(-1)) increased significantly,
specifically in cohorts born after 1989. Further adjustment for possible
determinants of these atopic diseases did not change the trend estimates. A clear
increase in the prevalence of atopic diseases, with the exception of hay fever,
was observed as well as a shift towards a stronger allergic sensitization, which 
might affect the onset of clinical manifestations of atopic diseases. Differences
in the epidemiology of respiratory symptoms, illnesses and allergies between
populations living in the former East Germany and those living in the former West
Germany have been reported. Among East German children, lower prevalence rates of
asthma, and positive skin-prick tests were observed compared to West German
children in the early 1990s. Similarly, among East German adults, lower specific 
immunoglobulin (Ig) E levels and lower prevalence rates of asthma, wheezing,
positive methacholine-challenge tests, allergic rhinitis, and positive skin-prick
tests have been reported compared to those of West German adults.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12108854 [PubMed - indexed for MEDLINE]

1226: Am J Otolaryngol. 2002 Jul-Aug;23(4):191-5.

Variations of nasal nitric oxide in a subject with allergic rhinitis: a
longitudinal study.

Vural C, Gungor A.

Sisli Etfal Training and Research Hospital, Istanbul, Turkey.

PURPOSE: Nitric oxide (NO) in the exhaled air is mainly produced by the upper
respiratory airway mucosa, and the output of NO has been found to differ from
normal in sinonasal disease. In allergic rhinitis (AR) nasal NO output (V(NO))
has been reported to increase compared with healthy individuals. The purpose of
this study was to observe daily variations in V(NO) in a subject with AR and to
investigate the effect of environmental factors on V(NO). MATERIAL AND METHODS:
We measured V(NO) daily in an individual with AR over a period of 5-1/2 months to
determine the variability of V(NO) from day to day. We used a 41-year-old,
nonsmoking volunteer with AR as our subject to investigate the relationship
between V(NO) and some environmental factors likely to affect V(NO). The
correlation between V(NO) and nasal symptom scores was also investigated. Daily
ambient NO concentrations, humidity, atmospheric pressure, and atmospheric grass 
pollen concentrations were recorded along with morning nasal NO measurements. At 
each measurement session, online NO measurements were done from both nostrils at 
5 L/min constant transnasal flow. During the study the subject had a short period
of a cold and a short period of purulent rhinitis and started using a nasal
steroid spray at the end of the study. RESULTS: V(NO) levels for our subject were
higher than previously published values for normal and allergic adults. There was
an increase in V(NO) (the highest value throughout the study) in the prodromal
period of the cold and a significant decrease (the lowest values throughout the
study) during the cold. Change during the purulent rhinitis was less remarkable
than change during the cold. CONCLUSION: No correlations between environmental
conditions (humidity, atmospheric pressure, pollen count) and V(NO) were found.
V(NO) changes were also independent of specific and cumulative nasal symptom
scores. Copyright 2002, Elsevier Science (USA). All rights reserved.)

PMID: 12105782 [PubMed - indexed for MEDLINE]

1227: Allergy. 2002 Jul;57(7):586-91.

Effects of budesonide and fluticasone propionate in a placebo-controlled study on
symptoms and quality of life in seasonal allergic rhinitis.

Ciprandi G, Canonica WG, Grosclaude M, Ostinelli J, Brazzola GG, Bousquet J.

Università digli Studi di Genova, Italy.

BACKGROUND: Intranasal glucocorticosteroids are effective in seasonal allergic
rhinitis. This study compared the efficacy of budesonide (Rhinocort Turbuhaler)
and fluticasone propionate (Flixonase) in this respect. METHODS: Patients (n =
280) were randomized to receive budesonide, 140 microg (delivered dose) once
daily, fluticasone, 200 microg once daily, or matching placebos for 5 weeks. The 
primary efficacy variable was the change in combined nasal symptom (nasal
blockage, runny nose, sneezing) scores. Quality of life was measured in 121
patients by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
and the Short-form Health Survey (SF-36). RESULTS: Both steroids significantly
reduced combined nasal symptoms, compared with placebo. There was no significant 
difference between the two treatments. Substantial or total symptom control was
achieved in 89.9% of the budesonide-treated patients, compared with 88.7% with
fluticasone and 42.7% with placebo. Four of the five domains of the RQLQ were
significantly improved with budesonide, whereas with fluticasone only two domains
were improved. Budesonide significantly improved scores in five out of eight
domains of the SF-36, whereas no domains were improved with fluticasone.
CONCLUSION: There was no significant difference in efficacy between budesonide
and fluticasone in this study. However, greater improvements in quality of life
were seen with budesonide than with fluticasone.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12100298 [PubMed - indexed for MEDLINE]

1228: Clin Exp Allergy. 2002 Jul;32(7):1029-32.

Negative association of Enterobius infestation with asthma and rhinitis in
primary school children in Taipei.

Huang SL, Tsai PF, Yeh YF.

Institute of Environmental Health Sciences, National Yang Ming University,
Taipei, Taiwan. slhuang@ym.edu.tw

BACKGROUND: The relationship between allergy and parasites has been
controversial, especially in non-tropical countries. Enterobius vermicularis
(human pinworm) is the most prevalent intestinal parasite in industrialized
countries. OBJECTIVE: To examine the association between pinworm infestation and 
allergy in primary school children. METHOD: Peri-anal tape test for pinworm is
routinely performed in Taipei primary schools. We collected data from school
records and questionnaires distributed to all children in four primary schools
grades 1 through 6 (n = 3107). RESULTS: The prevalence of physician-diagnosed
asthma (9.3% vs. 14.1%, P = 0.007) and allergic rhinitis (27.4% vs. 38.3%, P =
0.001) was lower in pinworm-positive compared to uninfested children. Pinworm was
not correlated with atopic dermatitis or parent allergy. With logistic regression
controlling for sex, parent allergy and lower respiratory infection, current
asthma (OR = 0.25, 95% CI 0.10-0.63) and rhinitis (OR = 0.61, 95% CI 0.45-0.84)
were negatively associated with pinworm. Among children in grades 3-6 who had no 
asthma or rhinitis before age 7, those with early infestation (pinworm diagnosis 
at or before grade 1) had a lower risk of having diagnosis of rhinitis during
school years, compared to the uninfected group (5.4% vs. 12.3%, P = 0.03;
adjusted OR = 0.47, 95% CI 0.21-1.02). CONCLUSIONS: We identified a negative
association between pinworm infestation and allergic airway diseases, which could
in part be attributed to protective effect of pinworm infestation on development 
of allergic symptoms. Other mechanisms of association could not be ruled out.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12100049 [PubMed - indexed for MEDLINE]

1229: Clin Exp Allergy. 2002 Jul;32(7):1020-8.

Montelukast for treating seasonal allergic rhinitis: a randomized, double-blind, 
placebo-controlled trial performed in the spring.

Philip G, Malmstrom K, Hampel FC, Weinstein SF, LaForce CF, Ratner PH, Malice MP,
Reiss TF; Montelukast Spring Rhinitis Study Group.

Merck & Co., Inc., Rahway, New Jersey, USA.

BACKGROUND: Cysteinyl leukotrienes are important proinflammatory mediators
believed to have a role in allergic rhinitis. OBJECTIVE: This multicentre,
randomized, double-blind, placebo- and active-controlled trial evaluated the
effectiveness and tolerability of montelukast, a cysteinyl leukotriene receptor
antagonist, for treating patients with seasonal allergic rhinitis. METHODS: After
a 3- to 5-day, single-blind placebo run-in period, 1302 male and female patients 
(aged 15-81 years) with active allergic rhinitis symptoms were randomly assigned 
to receive montelukast 10 mg (n = 348), loratadine 10 mg (n = 602), or placebo (n
= 352) administered once daily at bedtime for 2 weeks during the spring allergy
season. RESULTS: Mean patient characteristics and symptom scores at baseline were
similar for the three treatment groups. The primary end-point, daytime nasal
symptoms score (mean of nasal congestion, rhinorrhea, nasal pruritus, and
sneezing scores; 0-3 scale), improved from baseline during treatment by (least
squares mean, 95% confidence interval) - 0.37 (- 0.43, - 0.31), - 0.47 (- 0.52, -
0.43), and - 0.24 (- 0.29, - 0.18) in the montelukast, loratadine, and placebo
groups, respectively (P < or = 0.001 comparing each active treatment with
placebo). Mean changes from baseline in all other diary-based scores, including
night-time and eye symptom scores, were significantly greater for each active
treatment than for placebo. The rhinoconjunctivitis quality of life overall score
improved significantly with montelukast and with loratadine as compared with
placebo. Montelukast and loratadine showed a safety profile comparable to that of
placebo. CONCLUSION: Montelukast is well tolerated and provides improvements in
daytime and night-time symptoms, as well as quality of life parameters, for
patients with seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12100048 [PubMed - indexed for MEDLINE]

1230: Rhinology. 2002 Jun;40(2):66-8.

Short-term repeatability and correlates of laboratory measures of nasal function 
in patients with seasonal allergic rhinitis.

Sims EJ, Wilson AM, White PS, Gardiner Q, Lipworth BJ.

Asthma & Allergy Research Group, Department of Clinical Pharmacology &
Therapeutics, University of Dundee, Dundee, Scotland, UK.

The purpose of this study was to determine the variability of laboratory nasal
function tests in 26 patients (18 female) with seasonal allergic rhinitis (SAR)
(mean age 38.1 years). Their usual medication for SAR was withheld for 2 separate
one week washout periods, separated by at least 2 weeks, in order to produce
clinically significant nasal airflow obstruction. Measurements were made on both 
occasions for nasal nitric oxide (NO), nasal peak inspiratory flow (nPIF), oral
PIF (oPIF), nasal forced inspiratory flow rate in 1 second (nFIV1), oral FIV1
(oFIV1). The respective nasal-oral ratios for FIV1 and PIF were also determined. 
The intra-individual coefficient of variation was: NO = 14%, nFIV1 = 4%,
nFIV1/oFIV1 ratio = 10%, nPIF = 8% and nPIF/oPIF ratio = 12%. Linear regression
analysis showed significant (p < 0.05) correlations between nPIF and nFIV1 (R2 = 
0.45) and between nPIF/oPIF and nFIV1/oFIV1 (R2 = 0.20). In conclusion, there was
a good correlation between the two methods of nasal inspiratory flow, although
FIV1 had a lesser degree of variability.

PMID: 12091995 [PubMed - indexed for MEDLINE]

1231: Cytokine. 2002 Apr 7;18(1):20-5.

DNA microarray analysis of transforming growth factor-beta and related
transcripts in nasal biopsies from patients with allergic rhinitis.

Benson M, Carlsson B, Carlsson LM, Mostad P, Svensson PA, Cardell LO.

Allergy Laboratory, Department of Oto-Rhino-Laryngology, Malmö University
Hospital, Malmö, Sweden. Mikael.benson@pediat.gu.se

Decreased activity of anti-inflammatory cytokines like transforming growth factor
(TGF)-beta may contribute to allergic inflammation. In vivo effects of
TGF-beta-effects are difficult to infer from local concentrations, since
TGF-beta-effects depend on a complex system of regulatory proteins and receptors.
Instead the effects of TGF-beta might be inferred by examining TGF-beta-inducible
transcripts. In this study DNA microarrays were used to examine local expression 
of TGF-beta, TGF-beta-regulatory and -inducible transcripts in nasal biopsies
from patients with symptomatic allergic rhinitis and healthy controls. In
addition, nasal fluids were analysed with cytological and immunological methods. 
Nasal fluid eosinophils, albumin, eosinophil granulae proteins and IgE, but not
TGF-beta, were higher in patients than in controls. DNA microarray analysis of
nasal mucosa showed expression of transcripts encoding TGF-beta,
TGF-beta-regulatory proteins and -receptors at variable levels in patients and
controls. By comparison, analysis of 28 TGF-beta-inducible transcripts indicated 
that 23 of these had lower measurement values in patients than in controls, while
one was higher, and the remaining four were absent in both patients and controls.
In summary, TGF-beta and a complex system of regulatory genes and receptors are
expressed in the nasal mucosa. Low expression of TGF-beta-inducible transcripts
may indicate decreased TGF-beta activity in allergic rhinitis. DNA microarray
analysis may be a way to study cytokine effects in vivo. Copyright 2002 Elsevier 
Science Ltd. All rights reserved.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12090756 [PubMed - indexed for MEDLINE]

1232: J Am Osteopath Assoc. 2002 Jun;102(6 Suppl 2):S7-14.

Improved strategies and new treatment options for allergic rhinitis.

Willsie SK.

University of Health Sciences-College of Osteopathic Medicine in Kansas City, MO,
USA. swillsie@uhs.edu

Primary principles relevant to the clinical management of allergic rhinitis
include (1) avoidance of allergens and triggering factors, (2) use of appropriate
pharmacotherapy, (3) evaluation regarding need for and appropriate use of
immunotherapy, and (4) patient education and follow-up. Currently available
pharmacotherapeutic options include oral and topical (intranasal) decongestants
and corticosteroids, mast cell stabilizers, intranasal anticholinergics, and
antihistamines. Future therapeutic options include leukotriene modifiers and
anti-IgE antibodies.

Publication Types: 
    Review

PMID: 12090644 [PubMed - indexed for MEDLINE]

1233: J Am Osteopath Assoc. 2002 Jun;102(6 Suppl 2):S2-6.

Scope and impact of allergic rhinitis.

D'Alonzo GE Jr.

Division of Pulmonary and Critical Care Medicine, Temple University Hospital in
Philadelphia, PA 19140, USA. gdalonzo@nimbus.temple.edu

Allergic rhinitis is estimated to affect as many as 40 million people in the
United States on a regular basis, and even more individuals who have occasional
symptoms. The disease is associated with a considerable burden on the healthcare 
system, accounting for a total of $7.9 billion in direct and indirect costs in
1997, and with significant adverse effects on patients' quality of life,
including disturbed sleep and impaired function at work and school. The
pathophysiology of allergic rhinitis is complex, involving inflammatory mediators
and immune cells that produce allergy symptoms via multiple mechanisms. The first
principle of clinical management of patients with allergic rhinitis is avoidance 
of exposure to allergens, but this measure can be very difficult, and most
patients require pharmacotherapy. Allergy vaccine therapy may be an appropriate
and necessary option in selected patients with allergies refractory to other
treatment modalities.

Publication Types: 
    Review

PMID: 12090643 [PubMed - indexed for MEDLINE]

1234: Ann Allergy Asthma Immunol. 2002 Jun;88(6):592-600.

Efficacy and tolerability of montelukast alone or in combination with loratadine 
in seasonal allergic rhinitis: a multicenter, randomized, double-blind,
placebo-controlled trial performed in the fall.

Nayak AS, Philip G, Lu S, Malice MP, Reiss TF; Montelukast Fall Rhinitis
Investigator Group.

University of Illinois, College of Medicine at Peoria, USA.

BACKGROUND: Histamine and cysteinyl leukotrienes seem to be important mediators
of allergic rhinitis. OBJECTIVE: This multicenter, randomized, double-blind,
parallel-group, placebo-controlled trial evaluated the effectiveness and
tolerability of montelukast, loratadine, and combination therapy with montelukast
and loratadine for treating patients with fall seasonal allergic rhinitis.
METHODS: After a 1-week, single-blind, placebo run-in period, 907 male and female
patients aged 15 to 82 years were randomized to 1 of 4 treatments: montelukast 10
mg (n = 155), loratadine 10 mg (n = 301), combination montelukast 10 mg and
loratadine 10 mg (n = 302), or placebo (n = 149), administered once daily at
bedtime for 2 weeks. The primary endpoint was the daytime nasal symptoms score
(mean of congestion, rhinorrhea, pruritus, and sneezing). RESULTS: Mean symptom
scores at baseline were similar for the four treatment groups. For each of the
three active treatments, the difference was significant for the mean change from 
baseline compared with placebo (P < or = 0.001). However, the effect of
montelukast/loratadine compared with loratadine alone, the primary comparison,
was not significantly different. Differences for each therapy alone compared with
placebo were also significant for most secondary endpoints, including nighttime
symptom scores, eye symptoms scores, and rhinitis-specific quality of life.
Differences for montelukast/loratadine compared with each therapy alone generally
showed numerical superiority, and a few endpoints showed differences that were
statistically significant. All active treatments showed a safety profile
generally similar to placebo. CONCLUSIONS: Montelukast alone or in combination
with loratadine is well tolerated and provides clinical and quality-of-life
benefits for patients with seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12086367 [PubMed - indexed for MEDLINE]

1235: Ann Allergy Asthma Immunol. 2002 Jun;88(6):556-9.

Comment in:
    Ann Allergy Asthma Immunol. 2002 Jun;88(6):539-40.    Ann Allergy Asthma Immunol. 2003 Mar;90(3):361; author reply 361-2.

Self-reported hay fever and panic attacks in the community.

Goodwin RD.

Division of Epidemiology, The Mailman School of Public Health, Columbia
University, New York, New York, USA. rdg66@columbia.edu

OBJECTIVE: The objective of this study was to determine the relationship between 
self-reported hay fever and common mental disorders among adults in the general
population. METHODS: Data were drawn from the Midlife Development in the United
States Survey, a representative household survey of the adult US population (25
to 74 years old; n = 3,032). Multivariate logistic regression analyses were used 
to determine the relationship between self-reported hay fever and current major
depression, panic attacks, generalized anxiety disorder, and alcohol/substance
use disorders. RESULTS: Self-reported hay fever was associated with a
significantly increased odds of panic attack (odds ratio = 1.8 [1.2, 2.6]), which
persisted after adjusting for differences in sociodemographic characteristics and
comorbid mental disorders. Self-reported hay fever was not associated with a
significantly increased likelihood of major depression, generalized anxiety
disorder, or alcohol/substance use disorders. CONCLUSIONS: Consistent with
previous findings, these data show a relationship between self-reported hay fever
and increased likelihood of panic attacks among adults in the general population.
The mechanism of the observed association remains unknown. Future work that
examines the relationship between hay fever and panic attacks, as well as other
mental disorders using both self-report and objective measurement of allergic
response in prospective, longitudinal, epidemiologic data may be useful in
improving our understanding of this observed link.

PMID: 12086361 [PubMed - indexed for MEDLINE]

1236: Otolaryngol Head Neck Surg. 2002 May;126(5):475-80.

Acoustic rhinometry findings in patients with mild sleep apnea.

Houser SM, Mamikoglu B, Aquino BF, Moinuddin R, Corey JP.

Section of Otolaryngology-Head and Neck Surgery, Department of Surgery,
University of Chicago, IL 60637, USA.

BACKGROUND: Nasal obstruction may contribute to the development of obstructive
sleep apnea (OSA). Acoustic rhinometry (AR) measures nasal patency and
congestion, which are useful parameters in objectively evaluating nasal
obstruction. The nasal obstruction produced by allergic rhinitis may contribute
to the development of OSA and can be easily assessed with AR. OBJECTIVE: This
study was undertaken to assess the degree of nasal obstruction seen in allergic
patients with and without OSA. STUDY DESIGN AND SETTING: This study was a
retrospective data analysis from a tertiary referral center. The AR data from 10 
patients with and 40 patients without mild OSA were compared. RESULTS: The mean
congestion factors at the first cross-sectional area (CSA1) on the AR graph were 
found to be significantly higher in the OSA group than in the non-OSA group (P = 
0.03). The classification of change in congestion factors demonstrated
significant differences at CSA1, CSA2, and CSA3 and in volume (t distributions
<0.001, 0.0312, <0.001, and <0.001, respectively). The non-OSA patients noted a
significant subjective improvement in nasal congestion after topical nasal
decongestion, whereas the OSA patients did not (P <or= 0.0001 and 0.064,
respectively). CONCLUSION: Although the role of nasal obstruction in OSA is
controversial, our study lends evidence to the thought that the nasal obstruction
associated with allergic rhinitis is associated with the presence of mild OSA.
SIGNIFICANCE: Whether allergic rhinitis is a direct cause of OSA is debatable,
but we have shown that greater nasal congestion is related to the presence of OSA
in a population of patients with allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12075220 [PubMed - indexed for MEDLINE]

1237: Am J Chin Med. 2002;30(1):1-11.

Effect of acupuncture in the treatment of seasonal allergic rhinitis: a
randomized controlled clinical trial.

Xue CC, English R, Zhang JJ, Da Costa C, Li CG.

The Chinese Medicine Unit, RMIT University, Bundoora, Victoria, Australia.
charlie.xue@rmit.edu.au

The clinical efficacy and safety of acupuncture in the treatment of Seasonal
Allergic Rhinitis (SAR) was evaluated by employing a two-phase crossover
single-blind clinical trial. Thirty subjects were randomly assigned to two groups
with 17 and 13 subjects respectively and treated with real or sham acupuncture
(three times per week) for four consecutive weeks and then a crossover for
treatments for a further four weeks without a washout period. The administration 
of real acupuncture treatment was guided by a syndrome differentiation according 
to Chinese Medicine Theory. Subjects were assessed by various criteria before,
during and after the treatments. Outcome measures included subjective symptom
scores using a five-point scale (FPS), relief medication scores (RMS) and adverse
effect records. Twenty-six (26) subjects completed the study. There was a
significant improvement in FPS (nasal and non-nasal symptoms) between the two
types of acupuncture treatments. No significant differences were shown in RMS
between the real acupuncture treatment group and the sham acupuncture treatment
group. No side effects were observed for both groups. The results indicate that
acupuncture is an effective and safe alternative treatment for the management of 
SAR.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12067084 [PubMed - indexed for MEDLINE]

1238: Eur Rev Med Pharmacol Sci. 2001 Jul-Aug;5(4):139-42.

Antihistamines and the torsade de point in children with allergic rhinitis.

Cantani A, Mocini V.

Department of Pediatrics, Roma University La Sapienza.

Allergic rhinitis (AR) is a very common disease, occurring in approximately 10%
of children and up to 20% of adolescents. It is often underdiagnosed and its
importance as a cause of morbidity is also underestimated, especially in
asthmatic children. It has been estimated that 75% of asthmatic children suffer
from AR, and its prevalence has increased during the last years, due to changes
in environmental factors. AR may be a cause of serious discomfort for the child
as well as for the family. AR may cause several complication, including serous
otitis media, abnormal facial development with orthodontic problems, eustachian
tube dysfunction and sinusitis. The frequent association of paranasal sinusitis
in children with asthma has been observed and sinusitis has been considered a
contributing factor in bronchial asthma Second-generation antihistamines are the 
golden therapy for AR. However, reports of potentially life-threatening
dysrhythmias, specifically torsades de pointes, were described. In conclusion, we
comment the in vitro inhibition of several ion channels, in particular
predisposing the heart to dysrhythmias by terfenadine and astemizole. In this
paper we examine recent reports on safety of both cetirizine and loratadine.

Publication Types: 
    Review

PMID: 12067082 [PubMed - indexed for MEDLINE]

1239: Int Arch Allergy Immunol. 2002 Jun;128(2):165-7.

Prevalence of Japanese cedar pollinosis among schoolchildren in Japan.

Ozasa K, Dejima K, Takenaka H.

Department of Social Medicine and Cultural Sciences, Research Institute for
Neurological Diseases and Geriatrics, Kyoto, Japan. kozasa@basic.kpu-m.ac.jp

BACKGROUND: Japanese cedar pollinosis is an important allergic
rhinoconjunctivitis in Japan in spring. We investigated the relationship between 
the amount of pollen in the air and the prevalence of the disease and
sensitization to Japanese cedar pollen in this ecological study. METHODS: The IgE
antibody to Japanese cedar pollen (JCP-IgE) was determined in human serum and
rhinoconjunctival symptoms were surveyed in 407-510 children in May or June every
year from 1995 to 2001. Japanese cedar pollinosis was defined as being JCP-IgE
>or=1.5 IU/ml and having any rhinoconjunctival symptom lasting 3 weeks or longer 
in March or April. RESULTS: Prevalence rates of Japanese cedar pollinosis were
13.8-22.9%. Prevalence rates of being JCP-IgE >or=1.5 IU/ml were 39.0-50.1%, and 
those of being JCP-IgE >or=15.01 IU/ml were 11.4-23.2%. All prevalence rates were
significantly related to the amount of pollen in the air. The proportion of
subjects with rhinoconjunctival symptoms was relatively constant in each stratum 
of low JCP-IgE levels (<0.35, 1.50-2.99, 3.0-14.9 IU/ml). CONCLUSION: High
exposure to Japanese cedar pollen was associated with higher levels of JCP-IgE
antibody and a high prevalence of Japanese cedar pollinosis. The relationship
between the level of JCP-IgE and the proportion of subjects with symptoms was
relatively constant. Copyright 2002 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12065917 [PubMed - indexed for MEDLINE]

1240: Chest. 2002 Jun;121(6):1853-9.

Exhaled nitric oxide and bronchial responsiveness to adenosine 5'-monophosphate
in subjects with allergic rhinitis.

Prieto L, Gutiérrez V, Uixera S.

Sección de Alergología (The NAOMI Project), Universidad de Valencia, Valencia,
Spain.

STUDY OBJECTIVES: To determine differences in exhaled nitric oxide (ENO) between 
subjects with allergic rhinitis with and without increased responsiveness to
direct and indirect bronchoconstrictor agents. STUDY DESIGN: Cross-sectional
study with the order of challenge tests randomized. SETTING: Specialist allergy
unit in a university hospital. PATIENTS: Thirty-eight subjects without asthma
with allergic rhinitis and 10 healthy nonatopic control subjects. MEASUREMENTS
AND RESULTS: Participants were challenged with increasing concentrations of
adenosine 5'monophosphate (AMP) and methacholine. ENO was measured with the
single-exhalation method. A positive response to both bronchoconstrictor agents
was detected in nine subjects with allergic rhinitis, whereas four subjects
showed increased responsiveness to AMP but not to methacholine. The geometric
mean (range) ENO values were significantly higher in subjects with allergic
rhinitis with increased responsiveness to either methacholine or AMP than in
subjects with normal responsiveness to both agonists: 51.3 parts per billion
(ppb) [22.0 to 108.5 ppb] vs 25.1 ppb (5.7 to 102.9 ppb, respectively; p = 0.007)
and healthy control subjects (11.2 ppb [5.0 to 31.9 ppb], p < 0.001). Subjects
with allergic rhinitis with normal responsiveness to both agonists also had
higher concentrations of ENO than healthy control subjects (p = 0.007). No
correlation was found between ENO and either of the provocative concentrations of
methacholine or AMP causing a 20% fall in FEV(1). CONCLUSIONS: In subjects
without asthma but with allergic rhinitis, the presence of bronchoconstriction in
response to methacholine or AMP is associated with increased ENO concentrations. 
However, elevated concentrations of ENO are detected even in subjects with
allergic rhinitis without airway hyperresponsiveness. These results suggest that 
the presence of airway hyperresponsiveness is not the only factor that determines
the increased NO levels detected in subjects with allergic rhinitis.

Publication Types: 
    Comparative Study

PMID: 12065349 [PubMed - indexed for MEDLINE]

1241: J Allergy Clin Immunol. 2002 Jun;109(6):956-61.

Comment in:
    J Allergy Clin Immunol. 2003 Mar;111(3):653; author reply 653-4.

Effect of desloratadine versus placebo on nasal airflow and subjective measures
of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in
an allergen-exposure unit.

Horak F, Stübner UP, Zieglmayer R, Harris AG.

ENT-University Clinic AKH Vienna, University of Vienna, Vienna, Austria.

BACKGROUND: Unlike many antihistamines, desloratadine can reduce nasal congestion
in patients with seasonal allergic rhinitis (SAR). OBJECTIVE: We compared the
effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms,
including nasal congestion, in response to grass pollen in an allergen-exposure
unit. METHODS: In a randomized, double-blind, placebo-controlled, crossover
trial, 47 subjects with histories of SAR received desloratadine or placebo every 
morning for 7 days and, after a 10-day washout period, were crossed over to the
other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on 
day 7 of each treatment period. Nasal airflow and nasal secretion weights were
measured before and every 30 minutes during allergen exposure; SAR symptoms
(including nasal congestion) were scored before exposure and every 15 minutes
thereafter. RESULTS: Nasal obstruction, as measured by nasal airflow, was less
severe with desloratadine than with placebo (P <.02). Individual and combined SAR
symptom severity scores, including nasal congestion and sneezing, were
significantly lower with desloratadine than with placebo (all P < or =.003).
Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P 
<.02), less nasal secretions (P <.001), and less severe symptoms, including nasal
congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine
compared with placebo, and this continued throughout (0-6 hours) allergen
exposure. Desloratadine was well tolerated, with an adverse event profile similar
to that of placebo. CONCLUSION: In subjects with allergen-induced SAR symptoms,
desloratadine significantly reduced the severity of nasal obstruction and
accompanying complaints of nasal congestion and other SAR symptoms compared with 
the effects of placebo.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12063524 [PubMed - indexed for MEDLINE]

1242: J Allergy Clin Immunol. 2002 Jun;109(6):949-55.

Comment in:
    J Allergy Clin Immunol. 2002 Dec;110(6):939; author reply 940.

Comparison of a nasal glucocorticoid, antileukotriene, and a combination of
antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis.

Pullerits T, Praks L, Ristioja V, Lötvall J.

Lung Pharmacology Group, Department of Respiratory Medicine and Allergology,
Institute of Internal Medicine, Göteborg University, Gothenburg, Sweden.

BACKGROUND: Allergic rhinitis requires active intervention for symptom relief. A 
combination of antileukotriene and antihistamine drugs has been suggested to
provide additive treatment benefits for patients with allergic rhinitis.
OBJECTIVE: We evaluated how such a combination treatment would affect symptoms
and local mucosal eosinophilia in comparison with a nasal glucocorticoid.
METHODS: In a double-blind, randomized study 62 patients with grass
pollen-induced allergic rhinitis received a nasal glucocorticoid (fluticasone
propionate aqueous nasal spray [FPANS], 200 microg/d), an antileukotriene
(montelukast, 10 mg/d), a combination of montelukast with an antihistamine
(loratadine, 10 mg/d), or placebo throughout the season. Cromoglycate eyedrops
and a limited amount of loratadine were allowed as rescue medication for severe
symptoms. Patients recorded their symptoms for nasal blockage, itching,
rhinorrhea, and sneezing. Before and during the season, nasal biopsy specimens
were obtained from patients for evaluation of local eosinophilic inflammation.
RESULTS: During the peak season, both FPANS and combined montelukast-loratadine
were significantly more effective than placebo and montelukast alone for daytime 
symptom prevention. For nighttime symptoms, FPANS was significantly more
effective compared with all other treatments, whereas combined
montelukast-loratadine and montelukast alone did not provide significant symptom 
prevention compared with placebo. The pollen-induced increase in the numbers of
epithelial eosinophils was significantly lower for FPANS-treated patients
compared with that seen in all other treatment groups. CONCLUSION: In patients
with seasonal allergic rhinitis, intranasal glucocorticoids are more effective
than an antileukotriene drug or combined antileukotriene-antihistamine for the
reduction of pollen-induced nasal eosinophilic inflammation and for control of
nasal symptoms.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12063523 [PubMed - indexed for MEDLINE]

1243: Inflamm Res. 2002 Apr;51(4):206-12.

Effect of oral antigen administration on nasal blockage in experimental allergic 
rhinitis in guinea pigs.

Terada T, Nabe T, Mizutani N, Takenaka H, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
tetsu@yc4.so-net.ne.jp

OBJECTIVE AND DESIGN: We evaluated the effectiveness of oral treatment with
Japanese cedar pollen on experimental allergic rhinitis in guinea pigs. SUBJECTS:
Male Hartley guinea pigs. TREATMENT: From 16 days before the first sensitisation,
1 and 100 mg/time/animal pollen suspension was orally administered twice weekly. 
Animals were then sensitised and repeatedly challenged with the pollen. METHOD:
Guinea pigs were sensitised by intranasal instillation of cedar pollen extracts
adsorbed onto Al(OH)3 at a dose of 0.3 microg pollen protein/0.3 mg Al(OH)3/3
microl/nostril twice a day for 7 days. Then the animal was challenged by
inhalation with cedar pollen (1.8 mg/nostril) once every week. We evaluated the
effects of the oral treatment with antigen on: 1) sneezing frequency, 2) nasal
blockage after antigen challenge, 3) nasal hyperresponsiveness to histamine and
leukotriene D4, and 4) titres of anaphylactic antibodies. RESULTS: During the
course of the high dose administration, several animals died from a possible
cytotoxicity, whereas the low dose caused no discernible change. The oral
administration of the pollen at both the doses significantly inhibited nasal
blockage, and the hyperresponsiveness to the stimuli was also strongly suppressed
by the oral treatment. Inhibitory effectiveness did not differ substantially
between the 1 and 100 mg/animal-treated groups. In contrast, neither sneezing
frequency nor the increasing level of anaphylactic antibodies was influenced by
the oral administration. CONCLUSIONS: In this study, we found that the
pollen-induced nasal blockage and hyperresponsiveness were suppressed by the oral
administration of the pollen in the sensitised guinea pig.

PMID: 12058959 [PubMed - indexed for MEDLINE]

1244: ORL J Otorhinolaryngol Relat Spec. 2002 May-Jun;64(3):191-9.

Nasal and bronchial histamine responsiveness in pollen-exposed patients with
seasonal rhinitis.

Ehnhage A, Kölbeck KG, Mossberg B, Juto JE.

Department of ENT Surgery, Karolinska Institutet at Huddinge University Hospital,
Huddinge, Sweden. anders.ehnhage@ent.hs.sll.se

In a previous study, we found an increased nasal responsiveness as measured by
rhinostereometry and histamine challenge out of season in a sample of 12 patients
suffering mainly from hay fever. The aim of the present study was to investigate 
whether airway responsiveness in these patients was further increased after
direct pollen exposure, after a single nasal pollen provocation as well as by
repeated exposure during the pollen season. In spite of increased allergic
symptoms, the basal degree of nasal mucosal swelling was unchanged before
histamine challenge under these circumstances. After histamine challenge, nasal
mucosal swelling was increased in the same way over the seasons. Also bronchial
responsiveness was unchanged during the pollen season. It correlated to frequent 
sneezing following nasal histamine challenge during the season (p = 0.0071, r =
-0.74). We interpret the results as an indication of a continuos airway
inflammation regardless of season in these patients with pollen allergy, with
acute symptoms added on direct exposure to the allergen. Copyright 2002 S. Karger
AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12037386 [PubMed - indexed for MEDLINE]

1245: ORL J Otorhinolaryngol Relat Spec. 2002 May-Jun;64(3):180-5.

Neuronal nitric oxide synthase immunoreactivity in the nasal mucosa of patients
with idiopathic and allergic rhinitis.

Olthoff A, Rohrbach S, Faber M, Götz W, Laskawi R.

Department of Otorhinolaryngology, Georg August University Göttingen, Germany.
olthoff@uni.de

The localization of neuronal nitric oxide synthase (nNOS) in the mucosa of the
inferior and middle turbinates of 30 patients with and without allergic rhinitis 
was examined by immunohistochemical methods. Staining of paraffin sections from
allergic and nonallergic patients revealed nNOS immunoreactivity (nNOS-IR) in the
muscular layer of vessels, in the basal portion of submucosal glands and in the
periost and the osteocytes of the turbinate bones. In contrast to earlier
investigations, nNOS-IR was also seen in the nasal respiratory epithelium of
allergic and nonallergic patients. The immunostaining of sections of submucosal
glands from allergic patients was stronger than that of sections from patients
with idiopathic rhinitis or patients with no nasal obstruction. The present
result - nNOS-IR around glands is elevated in patients with allergic rhinitis -
could indicate that this enzyme is involved in the pathogenesis and
symptomatology of allergic rhinitis. Copyright 2002 S. Karger AG, Basel

PMID: 12037384 [PubMed - indexed for MEDLINE]

1246: Allergy. 2002 Jun;57(6):488-92.

Natural history of hay fever and pollen sensitization, and doctors' diagnosis of 
hay fever and pollen asthma in German schoolchildren.

Riedinger F, Kuehr J, Strauch E, Schulz H, Ihorst G, Forster J; Ozone Working
Group.

University Children's Hospital Freiburg, Germany.

BACKGROUND: In order to prevent pollen asthma by immunotherapy it is mandatory to
know the best time to initiate it. Children with hay fever complaints are at
considerable risk of developing pollen asthma. Population-based data on their
natural history is urgently needed. METHODS: A longitudinal cohort study was
conducted over four years in six rural towns in Baden-Württemberg, Germany. A
questionnaire with questions taken from the International Study of Asthma and
Allergies in childhood (ISAAC) was filled in every spring and autumn. Hay fever
complaints, asthma defining symptoms and new doctors' diagnosis of hay fever and 
asthma were recorded. Additionally a skin prick test with pollen allergens was
performed every autumn. RESULTS: In 1996, 19.7% of 1101 elementary school
children (age: 8.1-9.9 years (5-95%)) were found to be sensitized to pollen and
8.7% had already been diagnosed as having hay fever. In a pooled analysis of 2478
children-summers, children with positive pollen sensitization had a significantly
higher risk of developing hay fever symptoms (2.63; 2.17-3.10 odds ratio (OR);
95% confidence interval (CI)) and of being diagnosed as suffering from hay fever 
(7.88; 4.70-13.20). Furthermore, although their OR for the development of asthma 
symptoms during the pollen season was 3.88 (2.48-6.07 CI), it was only 0.69
(0.24-2.01 CI) for doctors' diagnosis of pollen asthma. CONCLUSION: Children of
elementary school age with pollen sensitization and a history of hay fever are at
considerable risk of getting pollen asthma, but they are not quickly diagnosed as
such. Specific immunotherapy might be a means of preventing asthma completely in 
such a situation. Our data helps to estimate the sample size for intervention
studies of this kind.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12028113 [PubMed - indexed for MEDLINE]

1247: J Altern Complement Med. 2002 Apr;8(2):167-73.

Comment in:
    J Altern Complement Med. 2002 Jun;8(3):229.

A multicentered, open-label trial on the safety and efficacy of
methylsulfonylmethane in the treatment of seasonal allergic rhinitis.

Barrager E, Veltmann JR Jr, Schauss AG, Schiller RN.

GENESIS Center for Integrative Medicine, Graham, WA, USA.

BACKGROUND: Seasonal allergic rhinitis (SAR) affects more than 23 million
Americans annually, and current epidemiologic studies indicate that its
prevalence within the United States is increasing. Numerous clinical observations
and case studies have led researchers to hypothesize that methylsulfonylmethane
(MSM) may help ameliorate the symptoms associated with SAR. OBJECTIVE: The
primary goal of this study was to evaluate the efficacy of MSM in the reduction
of SAR-associated symptoms. This study also examined possible adverse reactions
associated with methylsulfonylmethane supplementation. Finally, this study
attempted to elucidate the method of action by which MSM elicits its effect on
allergy symptoms. DESIGN: Fifty-five (55) subjects were recruited for the study. 
All met the criteria for participation in the study. 50 subjects completed the
study. Those subjects completing the study consumed 2,600 mg of MSM orally per
day for 30 days. Clinical respiratory symptoms and energy levels were evaluated
by a Seasonal Allergy Symptom Questionnaire (SASQ) at baseline and on days 7, 14,
21, and 30. Immune and inflammatory reactions were measured by plasma
immunoglobulin E (IgE) and C-reactive protein at baseline and on day 30. An
additional inflammatory biomarker, plasma histamine, was measured in a subset of 
subjects (n = 5). RESULTS: Day 7 upper and total respiratory symptoms were
reduced significantly from baseline (p < 0.01 and p < 0.005, respectively). Lower
respiratory symptoms were significantly improved from baseline by week 3 (p <
0.001). All respiratory improvements were maintained through the 30-day visit.
Energy levels increased significantly by day 14 (p < 0.0001); this increase
continued through day 30. No significant changes were observed in plasma IgE or
histamine levels. The results of this study are promising. It would be worthwhile
to conduct a larger, randomized, double-blind, placebo-controlled study to
establish further if MSM would be a useful agent in the treatment of symptoms
associated with SAR. CONCLUSION: The results of this study suggest that MSM
supplementation of 2,600 mg/day for 30 days may be efficacious in the reduction
of symptoms associated with SAR. Furthermore, few side effects are associated
with the use of this compound. Recent acute and subacute chronic toxicologic data
on the same source of MSM as used in this study, further validate the safety of
this product.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12006124 [PubMed - indexed for MEDLINE]

1248: Clin Exp Allergy. 2002 Jan;32(1):126-32.

Comment in:
    Clin Exp Allergy. 2002 Jan;32(1):4-7.

A comparison of once daily fexofenadine versus the combination of montelukast
plus loratadine on domiciliary nasal peak flow and symptoms in seasonal allergic 
rhinitis.

Wilson AM, Orr LC, Coutie WJ, Sims EJ, Lipworth BJ.

Asthma & Allergy Research Group, Department of Clinical Pharmacology &
Therapeutics, Ninewells Hospital & Medical School, University of Dundee,
Scotland, UK.

BACKGROUND: The combination of montelukast (ML) and loratadine (LT) has
previously been shown to be superior to either drug alone in managing seasonal
allergic rhinitis (SAR), whilst fexofenadine (FEX) has been shown to be better
than LT as monotherapy. OBJECTIVES: We wished to compare ML + LT vs. FEX alone
for effects on daily measurements (am/pm) of peak inspiratory flow (PIF) and
symptoms. METHODS: Thirty-seven patients with SAR (skin prick positive to grass
pollen) were randomised into a single-blind, double-dummy placebo (PL)-controlled
cross-over study during the grass pollen season, comparing 2 weeks of once daily 
treatment with (a) 120mg FEX or (b) 10mg ML + 10mg LT. There was a 7-10 day
placebo run-in and washout prior to each randomised treatment. The average of
am/pm PIF (the primary outcome variable) was analysed. Patients recorded their
symptom scores (from 0 to 3) twice daily, for nasal blockage, discharge, itching 
and sneezing with; total eye symptoms, ocular cromoglycate use, and daily
activity. The total nasal symptom score was calculated as a composite (out of
24). RESULTS: There were no significant differences between baselines after the
run-in and washout placebos for any variables. There were significant (P < 0.05, 
Bonferroni) improvements in all symptoms and PIF compared to pooled placebo with 
both treatments for all end-points, but no differences between the two treatment 
regimes (as means and within-treatment 95% confidence intervals): PIF: PL 102
(98-107), FEX 111 (107-116), ML+LT 113 (109-118); total nasal symptoms: PL 7.4
(6.7-2.0), FEX 5.0 (4.3-5.7), ML + LT 4.0 (3.3-4.7). CONCLUSIONS: Once daily FEX 
as monotherapy was equally effective as the combination of once daily ML + LT in 
improving nasal peak flow and controlling symptoms in SAR. Further studies are
indicated to assess whether ML confers additional benefits to FEX in SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12002729 [PubMed - indexed for MEDLINE]

1249: Ann Allergy Asthma Immunol. 2002 Apr;88(4 Suppl 1):23-9.

Clinical evidence for antileukotriene therapy in the management of allergic
rhinitis.

Meltzer EO.

Allergy & Asthma Medical Group & Research Center, San Diego, California 92123,
USA. eomeltzer@aol.com

OBJECTIVE: This article presents information summarizing the findings of several 
clinical trials that evaluated the efficacy and safety of leukotriene receptor
antagonists in the treatment of allergic rhinitis. After reading this article,
readers will have a greater understanding of these clinical findings and their
implications for the management of allergic rhinitis. DATA SOURCES: Relevant and 
appropriately controlled clinical trials were used. Only literature in the
English language was reviewed. STUDY SELECTION: Material was taken from
academic/scholarly publications, published abstracts, and papers presented at a
major congress. RESULTS: Similar to their contribution to the pathogenesis of
asthma, cysteinyl leukotrienes have been found to exert potent inflammatory
effects in the upper airways and to play a role in the pathogenesis of allergic
rhinitis. The guidelines for the diagnosis and treatment of allergic rhinitis
emphasize the importance of treating the pathophysiologic pathways of the
disease. Thus, the use of antileukotriene therapy is a rational therapeutic
option for patients with allergic rhinitis. Findings from several randomized,
placebo-controlled clinical trials confirm the efficacy of leukotriene receptor
antagonists in reducing the symptoms of allergic rhinitis and improving quality
of life. Clinical experience with these medications has also demonstrated their
tolerability and safety. CONCLUSIONS: Results from recently completed and ongoing
clinical trials have expanded the body of evidence for the safety and efficacy of
antileukotrienes in the treatment of allergic rhinitis.

Publication Types: 
    Review

PMID: 11991547 [PubMed - indexed for MEDLINE]

1250: Immunol Invest. 2002 Feb;31(1):29-40.

Differences in the sensitisation to ragweed pollen and occurrence of late summer 
allergic symptoms between native and immigrant workers of the nuclear power plant
of Hungary.

Dervaderics M, Fust G, Otos M, Barok J, Pataky G.

3rd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, 
Budapest, Hungary.

Regular medical screening including allergic symptoms of workers of the Nuclear
Power Plant in Paks, Hungary, offered a unique opportunity to study the influence
of the environmental factors on the development of allergy. The city Paks has
been one the areas of the country most heavily exposed to ragweed pollen
allergens. The occurrence and extent of sensitisation assessed by skin prick test
to common allergens and prevalence of seasonal and perennial allergic symptoms
were compared among 880 workers (695 immigrants, 185 natives) with self-reported 
allergic symptoms. The percentage of sensitised people against common allergens
(ragweed, grass, D. pteronyssinus) was almost the same in the natives and
immigrants. When, however, the strength of sensitivity to ragweed was determined 
by quantitative skin prick test and specific IgE determination, significantly
(P<0.0001) more immigrants (69%) than native workers (20%) exhibited high
sensitivity to ragweed and the titres of specific IgE antibodies was also
significantly (p < 0.0001) higher in the former group. Similar differences were
found in the occurrence and type of allergic symptoms. Seasonal symptoms alone
occurred in 69% and 38% of the immigrant and native workers (p < 0.0001). This
difference was mostly due to those with late summer symptoms characteristic to
ragweed allergy. These symptoms occurred in 57% of the immigrant workers, much
more frequently (p < 0.0001) than in the natives (18%). Our findings indicate
that the length of exposure to an inhalant allergen does affect the extent of
sensitisation to ragweed allergen and markedly influences the clinical symptoms
that develop in the ragweed allergic patients upon allergen exposure. It can be
assumed that the natives who have been living with ragweed pollen for a long time
(that is were exposed to natural immunotherapy), developed a natural tolerance to
it.

Publication Types: 
    Comparative Study

PMID: 11990461 [PubMed - indexed for MEDLINE]

1251: Int Arch Allergy Immunol. 2002 Mar;127(3):234-44.

Oligoclonal analysis of the atopic T cell response to the group 1 allergen of
Cynodon dactylon (bermuda grass) pollen: pre- and post-allergen-specific
immunotherapy.

Eusebius NP, Papalia L, Suphioglu C, McLellan SC, Varney M, Rolland JM, O'Hehir
RE.

Department of Allergy, Asthma and Clinical Immunology, Monash University Medical 
School, Alfred Hospital, Prahran, Vic. Australia.

BACKGROUND: Bermuda grass pollen (BGP) is an increasingly important seasonal
aeroallergen in Australia and other subtropical and temperate regions. BGP shares
minimal allergenic cross-reactivity with pollens of rye grass or other Pooideae
grasses often used for desensitization regimens in grass pollen allergy. Current 
allergen immunotherapy is seldom used in asthmatic patients due to IgE-mediated
side effects. Since clinically effective immunotherapy is linked with altered
allergen-specific T cell response, characterisation of human T cell reactivity to
Cyn d 1, the major B cell allergen of BGP, should permit the design of effective 
and safe immunotherapy for BGP allergy. METHODS: Short-term BGP-specific CD4+ T
cell lines were established from peripheral blood of 14 BGP-sensitive patients
before and after conventional 50% BGP and 50% 7-grass mix subcutaneous specific
allergen immunotherapy (SIT). T cell diversity of antigen specificity and
function was assessed by proliferation and cytokine production to BGP, Cyn d 1
and Cyn d 1 peptides. RESULTS: Three highly immunogenic regions of Cyn d 1 were
identified in 13/14 patients pre-SIT: Cyn d 1 (109-128), (181-209) and (217-241).
The SIT regimen was clinically efficacious. Following SIT, decreased
proliferation to BGP, Cyn d 1 and Cyn d 1 peptides was observed with a marked
decrease in the IL-5:IFN-gamma ratio. CONCLUSIONS: Cyn d 1 is a major T cell
allergen of BGP. Decreased Cyn d 1-specific IL-5 dominant T cell responses were
observed in association with clinically effective treatment with the 50% BGP and 
50% 7-grass mix. Identified dominant T cell regions of Cyn d 1 should facilitate 
safer vaccine development for BGP-induced asthma in addition to rhinitis.
Copyright 2002 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11979049 [PubMed - indexed for MEDLINE]

1252: Clin Exp Allergy. 2002 Apr;32(4):590-4.

Assessment of cross-reactivity between Japanese cedar (Cryptomeria japonica)
pollen and tomato fruit extracts by RAST inhibition and immunoblot inhibition.

Kondo Y, Tokuda R, Urisu A, Matsuda T.

Department of Pediatrics, School of Medicine, Fujita Health University, Toyoake, 
Japan. ykondo@fujita-hu.ac.jp

BACKGROUND: An association between pollinosis and sensitivity to fruits and
vegetables has been reported. Although Japanese cedar (Cryptomeria japonica)
pollinosis is one of the most widespread diseases in Japan, there have been no
reports demonstrating cross-reactivity between Japanese cedar pollen and other
plant food. OBJECTIVE: The aim of this study was to demonstrate cross-reactivity 
between Japanese cedar pollen and tomato fruit (Lycopersicon esculentum) using
RAST inhibition and immunoblot inhibition. METHODS: The RAST and immunoblot
inhibition were performed using sera from patients with oral allergy syndrome
(OAS) after ingesting fresh tomatoes. We identified some proteins that took part 
in cross-reactive IgE by the determination of N-terminal amino acid sequences and
a homology search through the SWISS-PROT database. RESULTS: In the RAST
inhibition, the bindings of IgE from the sera from four out of five (4/5)
subjects to Japanese cedar pollen discs were inhibited by more than 50% by
preincubation of the serum with tomato fruit extracts. Likewise, the IgE bindings
to tomato fruit discs were inhibited more than 50% by Japanese cedar pollen
extracts in 3/5 sera. In immunoblot inhibition, IgE binding activities of some
protein bands on both membranes were decreased by heterologous inhibitors.
However, the combinations of these protein bands involved in cross-reactivity
were different between patients. CONCLUSION: We have demonstrated
cross-reactivity between Japanese cedar pollen and tomato fruit using RAST
inhibition and immunoblot inhibition.

PMID: 11972607 [PubMed - indexed for MEDLINE]

1253: Clin Exp Allergy. 2002 Apr;32(4):507-14.

Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a
randomized controlled trial.

Lima MT, Wilson D, Pitkin L, Roberts A, Nouri-Aria K, Jacobson M, Walker S,
Durham S.

Upper Respiratory Medicine, Faculty of Medicine, Imperial College of Science,
Technology and Medicine at the National Heart & Lung Institute, and Royal
Brompton and Harefield Hospital NHS Trust, London, UK.

BACKGROUND: Previous studies suggest that sublingual immunotherapy (SLIT)
represents a safer alternative to injection immunotherapy but equivalent efficacy
is yet to be confirmed. OBJECTIVE: To evaluate the efficacy and safety of SLIT in
grass pollen-induced seasonal rhinoconjunctivitis. METHODS: A randomized,
placebo-controlled trial in 56 adults over 18 months. Outcome measures included
diary scores of seasonal symptoms and medication use, overall assessments,
conjunctival and intradermal provocation tests and serum antibody measurements.
To investigate possible mechanisms, sublingual biopsies were taken for
measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression.
RESULTS: There were no significant differences between the immunotherapy (IT) and
placebo groups for diary symptom scores (P = 0.48) or rescue medication (P =
0.19). The patients' overall assessment of hayfever severity compared with
previous years showed a highly significant improvement in favour of the IT group 
(P < 0.02). After treatment the late skin response was smaller (P = 0.003) and
the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT
group. Both of these variables correlated with the clinical response to SLIT.
There were no differences between groups in either the sublingual epithelium or
lamina propria for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P 
= 0.2), CD1a+ cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL-12 
mRNA+ cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no
serious treatment-related adverse events. CONCLUSION: Grass pollen sublingual
immunotherapy was well tolerated. Although there was no significant change in
diary scores, the improvement in overall assessments, which correlated with
inhibition of the late skin response and increases in serum IgG4 : IgE ratio,
indicates the need for larger, dose-ranging studies.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11972594 [PubMed - indexed for MEDLINE]

1254: Curr Opin Allergy Clin Immunol. 2001 Feb;1(1):105-8.

Comment in:
    Curr Opin Allergy Clin Immunol. 2001 Feb;1(1):47-50.

Anti-immunoglobulin E for the treatment of allergic disease.

Busse W, Neaville W.

Department of Medicine, Allergy and Clinical Immunology Section, University of
Wisconsin, Madison, Wisconsin 53792, USA. wwb@medicine.wisc.edu

IgE plays a central role in allergic disease and participates in the associated
inflammatory process. A mainstay of treatment of allergic disease, including
asthma, is allergen avoidance and treatment of symptoms. Presently, the most
effective treatments for allergic diseases are directed towards a regulation of
the inflammatory process with corticosteroids. An exciting new approach is
anti-IgE (rhuMAb-E25), which would regulate the allergic process at the level of 
IgE. The following information will review recent experiences with anti-IgE and
discuss the conditions in which this approach may be effective.

PMID: 11964677 [PubMed - indexed for MEDLINE]

1255: Curr Opin Allergy Clin Immunol. 2001 Feb;1(1):43-6.

Allergen-specific immunotherapy in allergic rhinitis.

Malling HJ.

Allergy Unit, National University Hospital, Copenhagen, Denmark.
hans_joergen_rh00450_malling@rh.dk

The scope of this review is to highlight important and interesting articles in
the field of allergen-specific immunotherapy in allergic rhinitis published
within the past year. The review is not intended to give a full overview of
published literature but rather to focus on some subjects that I find significant
in relation to the understanding of the specific treatment of allergies and to
the selection of different treatment modalities. The most important aspects are
how to define the most suitable candidates for the specific treatment, the
mechanisms of action of immunotherapy and how to optimize treatment, and finally 
I include some reflections on the optimal presentation of the allergen to the
immune system.

Publication Types: 
    Review

PMID: 11964668 [PubMed - indexed for MEDLINE]

1256: Curr Opin Allergy Clin Immunol. 2001 Feb;1(1):7-13.

The nose-lung interaction in allergic rhinitis and asthma: united airways
disease.

Passalacqua G, Ciprandi G, Canonica GW.

Allergy and Respiratory Diseases, Department of Internal Medicine, Genoa
University, Italy. gpass@smartino.ge.it

The link between upper and lower respiratory tracts has been repeatedly observed 
in the past 50 years but only carefully investigated during the past decade.
Several clinical and experimental observations suggested the hypothesis of the
unity of upper and lower airways (allergic rhinobronchitis or united airways
disease). The relationships between rhinitis (and sinusitis) and asthma also
include non-epidemiological aspects such as viral infections and bronchial
hyperreactivity. The hypotheses have been confirmed by means of epidemiological
observations, functional and immunological evidence and, indirectly, by observing
the effects of drugs used mainly for rhinitis on asthma symptoms. In this
article, therefore, we collected and reviewed the most relevant experimental
results available to support the hypothesis for united airways disease and the
studies conducted on the possible mechanisms of nose-lung interaction.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11964663 [PubMed - indexed for MEDLINE]

1257: Chest. 2002 Apr;121(4):1308-16.

The increase in allergic respiratory diseases: survival of the fittest?

Varner AE.

Allergy Diagnostic, Beachwood, OH 44122, USA. Wiscart@aol.com

The prevalence of allergic respiratory diseases, asthma and allergic
rhinoconjunctivitis, has increased since the advent of industrialization. The
inverse relationship between the number of infections early in life and atopy has
been interpreted as the "hygiene hypothesis." That is, many infections early in
life promote the development of T helper type 1 cytokines, while fewer infections
early in life favor the development of T helper type 2 (Th2) cytokines and atopy.
An alternate interpretation of the same data, that atopy is protective against
infections early in life, is rarely considered. With epidemiologic, historical,
and immunologic data, I suggest that human evolution has favored individuals with
an atopic predisposition. Th2 immune responses promote parity, and ensure
successful pregnancy and term birth; provide the infant protection against
infections and the inflammation induced by common pathogens in the first years of
life until the immune system matures; and protect young adults exposed to viral
respiratory pathogens. These traits are of particular value with the advent of
industrialization, especially so in the era prior to the development of
antibiotics. This theory contradicts the assumption that there is no biological
or evolutionary advantage for allergic disease to exist in humans and has
significant implications for our current and future treatments of allergic
diseases.

Publication Types: 
    Review

PMID: 11948067 [PubMed - indexed for MEDLINE]

1258: Mayo Clin Proc. 2002 Apr;77(4):350-4.

Use of intranasal cromolyn sodium for allergic rhinitis.

Ratner PH, Ehrlich PM, Fineman SM, Meltzer EO, Skoner DP.

Sylvana Research Associates and Department of Pediatrics, University of Texas
Health Science Center, San Antonio, USA. ratnermd@swbell.net

Allergic rhinitis affects 10% to 20% of Americans. It frequently coexists with
other conditions, such as allergic conjunctivitis, sinusitis, and asthma, and is 
associated with impaired occupational function and performance in school,
decreased quality of life, and increased health care costs. An efficacious agent 
with minimal adverse effects and a lack of drug interactions is needed to help
simplify treatment of allergic rhinitis, especially in patients with
comorbidities. Controlled studies of intranasal cromolyn sodium therapy for
patients with seasonal and perennial allergic rhinitis are reviewed, and
appropriate candidates for treatment with this agent are discussed. Cromolyn
inhibits the degranulation of sensitized mast cells, thereby blocking the release
of inflammatory and allergic mediators. It reduces symptoms of allergic rhinitis,
and, when used prophylactically, cromolyn can prevent symptoms from occurring.
Controlled studies comparing cromolyn with placebo, intranasal corticosteroids,
and antihistamines have shown the efficacy of cromolyn in relieving rhinitis
symptoms. In addition, because cromolyn is poorly absorbed systemically, it is
well tolerated and not associated with drug interactions. Intranasal cromolyn has
an excellent safety record, is available as an over-the-counter medication, and
has been proved to be efficacious in patients with allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11936930 [PubMed - indexed for MEDLINE]

1259: Acta Otolaryngol. 2002 Mar;122(2):202-5.

Epithelial cells in nasal fluids from patients with allergic rhinitis: how do
they relate to epidermal growth factor, eosinophils and eosinophil cationic
protein?

Benson M, Uddman R, Cardell LO.

Allergy Laboratory, Department of Oto-Rhino-Laryngology, Malmö University
Hospital, Sweden.

The nasal epithelium protects the underlying tissue from damage. Epithelial cell 
growth is controlled by epidermal growth factor (EGF) and is possibly affected by
toxic proteins, e.g. eosinophil cationic protein (ECP). The aims of this study
were to examine nasal fluid epithelial cell counts and their relations to EGF,
eosinophils and ECP in 23 patients with seasonal allergic rhinitis and 20 healthy
controls. Nasal fluid epithelial cell counts were lower in patients than in
controls. EGF levels did not differ between patients and controls, and correlated
with epithelial cell counts in controls but not in patients. Eosinophils and ECP 
were higher in patients than in controls, but did not correlate with epithelial
cell counts. The role of growth factors, such as EGF, in regulating epithelial
cells merits further study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11936914 [PubMed - indexed for MEDLINE]

1260: Environ Health Perspect. 2002 Apr;110 Suppl 2:211-6.

Different slopes for different folks: socioeconomic and racial/ethnic disparities
in asthma and hay fever among 173,859 U.S. men and women.

Chen JT, Krieger N, Van Den Eeden SK, Quesenberry CP.

Department of Health and Social Behavior, Harvard School of Public Health,
Boston, Massachusetts 02122, USA. jarvis@hsph.harvard.edu

Although allergic diseases such as asthma and hay fever are a major cause of
morbidity in industrialized countries, most studies have focused on patterns of
prevalence among children and adolescents, with relatively few studies on
variations in prevalence by race/ethnicity and socioeconomic position among
adults. Our study examined racial/ethnic and socioeconomic patterns in the
prevalence of asthma overall, asthma with hay fever, asthma without hay fever,
and hay fever overall, in a population of 173,859 women and men in a large
prepaid health plan in northern California. Using education as a measure of
socioeconomic position, we found evidence of a positive gradient for asthma with 
hay fever with increasing level of education but an inverse gradient for asthma
without hay fever. Hay fever was also strongly associated with education.
Compared with their White counterparts, Black women and men were more likely to
report asthma without hay fever, and Black women were less likely to have asthma 
with hay fever. Asian men were also more likely to report asthma with hay fever, 
and Asian women and men were much more likely to have hay fever. Racial/ethnic
disparities in prevalence of allergic diseases were largely independent of
education. We discuss implications for understanding these social inequalities in
allergic disease risk in relation to possible differences in exposure to
allergens and determinants of immunologic susceptibility and suggest directions
for future research.

PMID: 11929730 [PubMed - indexed for MEDLINE]

1261: Clin Exp Allergy. 2002 Feb;32(2):224-7.

Comment in:
    Clin Exp Allergy. 2002 Feb;32(2):172-4.

Increased carbon monoxide levels in the nasal airways of subjects with a history 
of seasonal allergic rhinitis and in patients with upper respiratory tract
infection.

Andersson JA, Uddman R, Cardell LO.

Department of Otorhinolaryngology, Malmö University Hospital, Malmö 205 02,
Sweden.

BACKGROUND: Carbon monoxide (CO) has emerged as an endogenously produced gaseous 
mediator known to be involved in bronchial smooth muscle regulation. Increased
amounts of CO have been found in exhaled air during asthma and lower airway
inflammation. Recently CO has been shown to be produced in the nasal airways, but
there are no reports of altered CO levels in nasal airways during inflammation.
OBJECTIVE: This study was designed to investigate if CO levels increase in the
human nasal airways during inflammatory conditions, such as allergy and upper
airway respiratory tract infection (URTI). METHODS: CO was sampled separately
from the upper and lower airways of 13 healthy control subjects, six patients
with a history of allergic rhinitis and six patients with URTI. RESULTS: Nasal CO
levels were increased in subjects with allergic rhinitis, compared to healthy
controls (2.07 +/- 0.15 ppm, n = 6 and 1.62 +/- 0.08 ppm, n = 13, respectively, P
< 0.01). CO levels were also increased in patients with URTI, compared to the
same controls (1.92 +/- 0.09 ppm, n = 6, P < 0.05). Normal levels of CO were
found in air from the lower airways among subjects with allergic rhinitis,
whereas corresponding levels in the URTI patients were increased. CONCLUSION: The
present data demonstrates that upper airway CO levels increase in parallel with
different inflammatory stimuli, such as allergy and infection, suggesting a role 
for CO as marker or mediator of nasal inflammation.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11929486 [PubMed - indexed for MEDLINE]

1262: Allergy. 2002 Feb;57(2):107-14.

The score for allergic rhinitis (SFAR): a simple and valid assessment method in
population studies.

Annesi-Maesano I, Didier A, Klossek M, Chanal I, Moreau D, Bousquet J.

INSERM U472, Villejuif CEDEX, France.

BACKGROUND: No validated assessment of allergic rhinitis (AR) is presently
available that can be used in population studies in the absence of medical
diagnosis and of objective measurements of allergy. To compensate for this lack, 
a quantitative Score For Allergic Rhinitis (SFAR) ranging between 0 and 16 has
been developed by experts. METHODS: The SFAR, encompassing eight features of AR, 
was validated in three different ways: 1) among 269 outpatients taking the
specialist's diagnosis of AR and skin prick tests (SPT) positivity as a gold
standard (diagnosis validation); 2) using psychometric methods (internal
validation); and 3) in a random population-based sample of 3001 individuals by
telephone interview (population acceptability). RESULTS: A SFAR value > or = 7
allowed satisfactory discrimination between the outpatients with AR from those
without (sensitivity = 74% [95% confidence interval CI: 0.69,0.79], specificity =
83% [0.79, 0.87], positive predictive value = 84% [0.80, 0.88], negative
predictive value = 74% [0.69, 0.79] and Youden's index = 0.57, respectively).
Internal consistency of the score was also high (among others, Cronbach's alpha
coefficient = 0.79). On average, it took only 3 min for the individuals
interviewed on the phone to complete the questionnaire, the questions of which
were well understood. Among these subjects, the prevalence of AR was 21% [95% CI:
19.5%, 22.5%], which is comparable to other determinations in France.
CONCLUSIONS: The newly a priori proposed Score For Allergic Rhinitis (SFAR) is
easy to use and can be useful to estimate prevalence and to study causation of AR
in population settings.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 11929412 [PubMed - indexed for MEDLINE]

1263: Allergy. 2002 Feb;57(2):92-7.

Privet pollen (Ligustrum sp.) as potential cause of pollinosis in the city of
Cordoba, south-west Spain.

Cariñanos P, Alcázar P, Galán C, Domínguez E.

Department of Botany, University of Córdoba, Campus Universitario de Rabanales,
Colonia San José, Córdoba, Spain.

BACKGROUND: Privet pollen rarely accounts for more than 1% of the annual total of
daily pollen concentrations measured in a city; however in areas where these
trees are widely used as ornamentals the amounts collected may be high enough to 
cause allergy symptoms. METHODS: Air samples taken with volumetric particle
samplers Lanzoni VPPS 1000 (Lanzoni s.r.l., Bologna, Italy) show that there are
differences in privet pollen concentrations measured in neighbourhoods with a
high incidence of privet trees and in those taken at some distance from the
source of emission. RESULTS: The results suggest that differences are due to the 
short dispersal range of the pollen grains once released from the plant,
resulting from both the entomophilous nature of the plant and the large size of
the pollen grains. Urban design, moreover, may play an important role in impeding
pollen grain dispersion if the air cannot flow freely through long, narrow
avenues. Another important consideration is that the last stages of the flowering
period of privet overlaps with the flowering period of olive trees, the main
allergen in the area. The fact that the two pollen types share common allergens
means that there may be a cross-reaction between olive tree pollen and privet
pollen. CONCLUSIONS: Privet pollen should be considered as a potential causative 
agent of local allergy problems in areas where its presence is extensive and is
in combination with other allergens.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11929410 [PubMed - indexed for MEDLINE]

1264: Ann Allergy Asthma Immunol. 2002 Mar;88(3):279-82.

Comment in:
    Ann Allergy Asthma Immunol. 2002 Mar;88(3):251-2.

Production of allergenic pollen by ragweed (Ambrosia artemisiifolia L.) is
increased in CO2-enriched atmospheres.

Wayne P, Foster S, Connolly J, Bazzaz F, Epstein P.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge,
Massachusetts, USA. pwayne@nesa.edu

BACKGROUND: The potential effects of global climate change on allergenic pollen
production are still poorly understood. OBJECTIVE: To study the direct impact of 
rising atmospheric CO2 concentrations on ragweed (Ambrosia artemisiifolia L.)
pollen production and growth. METHODS: In environmentally controlled greenhouses,
stands of ragweed plants were grown from seed through flowering stages at both
ambient and twice-ambient CO2 levels (350 vs 700 microL L(-1)). Outcome measures 
included stand-level total pollen production and end-of-season measures of plant 
mass, height, and seed production. RESULTS: A doubling of the atmospheric CO2
concentration stimulated ragweed-pollen production by 61% (P = 0.005).
CONCLUSIONS: These results suggest that there may be significant increases in
exposure to allergenic pollen under the present scenarios of global warming.
Further studies may enable public health groups to more accurately evaluate the
future risks of hay fever and respiratory diseases (eg, asthma) exacerbated by
allergenic pollen, and to develop strategies to mitigate them.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 11926621 [PubMed - indexed for MEDLINE]

1265: Ann Allergy Asthma Immunol. 2002 Mar;88(3):272-8.

Comment in:
    Ann Allergy Asthma Immunol. 2002 Mar;88(3):249-50.

Evaluation of the clinical efficacy and safety of grapeseed extract in the
treatment of fall seasonal allergic rhinitis: a pilot study.

Bernstein DI, Bernstein CK, Deng C, Murphy KJ, Bernstein IL, Bernstein JA, Shukla
R.

Division of Immunology, University of Cincinnati College of Medicine, Ohio 45267,
USA.

BACKGROUND: Herbal products are widely used by consumers as alternatives to
prescription drugs in treating symptoms of allergic rhinitis. However, there have
been few placebo-controlled clinical trials that have examined the efficacy or
safety of these products. Although grapeseed extract (GSE) is an herbal that is
marketed for treating allergic rhinitis, its efficacy is unproven. OBJECTIVE: The
aim of this study was to compare the efficacy and safety of GSE with placebo in
the treatment of seasonal allergic rhinitis (SAR). METHODS: This was a
randomized, double-blind, placebo-controlled study of GSE 100 mg, twice daily,
versus placebo. Patients with SAR and skin prick test sensitivity to ragweed were
randomized to 8 weeks of active treatment or placebo which was begun before the
ragweed pollen season. Outcomes included: daily symptom diary scores recorded by 
patients, rhinitis quality of life scores at baseline and after 4 and 8 weeks of 
treatment; and requirements for rescue chlorpheniramine. Safety was monitored
with routine laboratory studies. RESULTS: Over 8 weeks of treatment, no
significant differences were observed between active and placebo groups in
rhinitis quality of life assessments, symptom diary scores, or requirements for
rescue antihistamine. No significant laboratory abnormalities were detected.
CONCLUSIONS: This study did not show trends supporting the efficacy of GSE in the
treatment of SAR.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11926620 [PubMed - indexed for MEDLINE]

1266: Curr Allergy Asthma Rep. 2002 May;2(3):239-44.

The role of leukotriene inhibitors in allergic rhinitis and paranasal sinusitis.

Parnes SM.

Department of Surgery, Division of Otolaryngology, Albany Medical College, 47 New
Scotland Avenue, MC-41, NY 12208, USA. Sparnes@pol.net

Leukotrienes are inflammatory mediators that are known as the slow-reacting
substance of anaphylaxis produced by a number of cell types, including mast
cells, eosinophils, basophils, macrophages, and monocytes. Synthesis of these
meditators in the text result from the cleavage of arachidonic acid in cell
membranes, and exert their biologic effects by binding and activating specific
adaptors. This occurs in a serious of events that lead to contraction of the
human airway smooth muscle, chemotaxis, and increased vascular permeability.
These effects have lead to their important role in the diseases of asthma,
allergic rhinitis, and possible paranasal sinusitis with the formation of nasal
polyps. Since these agents lead to the production of symptoms in patients who are
asthmatic, the use of leukotriene enzyme inhibitors, particularly montelukast,
zafirlukasts seem appropriate.

Publication Types: 
    Review

PMID: 11918866 [PubMed - indexed for MEDLINE]

1267: Curr Allergy Asthma Rep. 2002 May;2(3):231-8.

Local IgE synthesis in allergic rhinitis and asthma.

Smurthwaite L, Durham SR.

The Randall Centre for Molecular Mechanisms of Cell Function, King's College
London, Guy's Campus, St. Thomas Street, SE1 9RT, UK. lyn.smurthwaite@kcl.ac.uk

Local IgE production has been a contentious concept for over 40 years. Although a
host of clinical observations suggested a local source of IgE, co-localization of
IgE to B cells in the nasal mucosa could not be demonstrated. In contrast,
igE-producing B cells were observed in local lymphoid tissue. Definitive proof of
local IgE synthesis in the nasal mucosa has now become available. Here, we review
the recent developments in local IgE research in allergic rhinitis and asthma
within their historical context, and speculate on the implications of both local 
IgE synthesis and ongoing research into local immunoglobulin isotype switching
for patient therapy.

Publication Types: 
    Review

PMID: 11918865 [PubMed - indexed for MEDLINE]

1268: Curr Allergy Asthma Rep. 2002 May;2(3):223-30.

The cost of treating allergic rhinitis.

Stempel DA, Woolf R.

Virginia Mason Clinic, Virginia Mason Medical Center, 1100 Ninth Avenue, Seattle,
WA 98004, USA. immdas@vmmc.org

Allergic rhinitis is a high-cost, high-prevalence disease. In the year 2000, over
$6 billion was spent on prescription medications to treat this illness. Although 
it is not associated with severe morbidity and mortality, allergic rhinitis has a
major effect on the quality of life of the more than 50 million Americans with
this illness. Intranasal corticosteroids (INCS) and nonsedating antihistamines
(NSAH) are the most common prescription medications for this disease. INCS are
recognized as the most effective treatment regimen for chronic symptoms. NSAH are
perceived as important in the treatment of patients with mild disease, or as
add-on therapy to INCS. When the literature is reviewed, the INCS produce the
greatest decrease in total nasal symptom scores, the largest effect size, when
compared with NSAH. Both classes of medications produce similar effects on
concurrent allergic conjunctivitis. Further recent studies indicate that the INCS
are also superior when used on an as-needed basis, and that there is little
clinical benefit from the addition of loratadine to intranasal fluticasone. INCS 
have lower average wholesale prices as a class than the NSAH. Since the INCS are 
the dominant medication in efficacy studies and cost less, cost-effectiveness
studies always favor intranasal corticosteroids.

Publication Types: 
    Review

PMID: 11918864 [PubMed - indexed for MEDLINE]

1269: Curr Allergy Asthma Rep. 2002 May;2(3):210-5.

Neurology of allergic inflammation and rhinitis.

Canning BJ.

Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, 
MD 21224, USA. bjc@jhmi.edu

Afferent nerves, derived from the trigeminal ganglion, and postganglionic
autonomic nerves, derived from sympathetic and parasympathetic ganglia expressing
many different neurotransmitters, innervate the nose. Reflexes that serve to
optimize the air-conditioning function of the nose by altering sinus blood flow, 
or serve to protect the nasal mucosal surface by mucus secretion, vasodilatation,
and sneezing, can be initiated by a variety of stimuli, including allergen, cold 
air, and chemical irritation. Activation of nasal afferent nerves can also have
profound effects on respiration, heart rate, blood pressure, and airway caliber
(the diving response). Dysregulation of the nerves in the nose plays an integral 
role in the pathogenesis of allergic rhinitis. Axon reflexes can precipitate
inflammatory responses in the nose, resulting in plasma extravasation and
inflammatory cell recruitment, while allergic inflammation can produce neuronal
hyper-responsiveness. Targeting the neuronal dysregulation in the nose may be
beneficial in treating upper airway disease.

Publication Types: 
    Review

PMID: 11918862 [PubMed - indexed for MEDLINE]

1270: Curr Allergy Asthma Rep. 2002 May;2(3):194-202.

Human nasal allergen provocation for determination of true allergic rhinitis:
methods for clinicians.

Litvyakova LI, Baraniuk JN.

Division of Rheumatology, Immunology, and Allergy, Georgetown University, Lower
Level Gorman Building, 3800 Reservoir Road NW, Washington, DC, 20007-2197, USA.

The nasal provocation test (NPT) could be more extensively used in the diagnosis 
of allergic rhinitis by practicing physicians. However, the procedure has not
been standardized, and has mainly been utilized for scientific purposes in the
US. This review illustrates a wide variety of techniques and approaches to dosing
and concentration of allergen extracts, and delivery systems. It also outlines
the lack of a unified outcomes-evaluation system, including clinical symptom
scores and nasal patency measurements, in different countries. NPT is a safe,
simple, and useful method when conducted with the consideration of indications
and contraindications. Standardized NPT has the potential to become a more
frequently used additional clinical test in the diagnosis of allergic rhinitis.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11918860 [PubMed - indexed for MEDLINE]

1271: Complement Ther Nurs Midwifery. 2002 Feb;8(1):17-20.

Erratum in:
    Complement Ther Nurs Midwifery 2002 Aug;8(3):175.

Establishment of a nurse-run acupuncture treatment for hayfever. By Mary Anne
Cochrane [corrected].

Cochrane MA.

This interview describes how the need to set up an acupuncture clinic for the
treatment of hayfever, was identified in a large teaching practice in south-east 
London. It then details the preliminary consultations for establishing the
service, while taking into consideration the UKCC (1992a,b, 2000) guidelines,
especially in relation to nurses' accountability and recognition of boundaries.
It examines the issues of training and consultation time, as well as costs to the
practice, and evaluates the benefits and costs of treatment to the patient. It
also identifies some of the potential problems that may be encountered in
providing acupuncture.The summary includes some guidance to others considering
implementation of a similar service.

PMID: 11898906 [PubMed - indexed for MEDLINE]

1272: Curr Allergy Asthma Rep. 2001 Nov;1(6):515-22.

Allergic rhinitis and asthma in children: disease management and outcomes.

Baena-Cagnani CE.

Division of Immunology and Respiratory Medicine, Infantile Hospital, Santa Rosa
381, (5000), Córdoba, Argentina. baena@powernet.net.ar

Antihistamines and inhaled glucocorticoids, which can be targeted toward multiple
points in the "allergic cascade" underlying allergic rhinitis and asthma, extend 
the promise of enhanced outcomes in children with allergic rhinitis, asthma, or
both. Antihistamine therapy confers significant relief of subjective ratings of
seasonal and perennial allergic symptoms (e.g., rhinorrhea, congestion, sneezing,
pruritus), whereas topical steroids alleviate such discomfort while also
improving objective anatomic and functional indices of nasal patency (e.g., nasal
peak inspiratory flow). Youngsters with asthma also experience substantial
clinical benefits from inhaled steroids, which improve objective measures of
pulmonary function and reduce rescue beta 2-agonists for symptom management and
quality-of-life enhancement. This paper reviews recent clinical findings on the
role of antihistamines and topical corticosteroids in pediatric allergy and
asthma management, as well as the favorable effects of these medications on both 
objective and subjective health outcomes.

Publication Types: 
    Review

PMID: 11892081 [PubMed - indexed for MEDLINE]

1273: Curr Allergy Asthma Rep. 2001 Nov;1(6):498-505.

Allergic rhinitis in children.

Berger WE.

Allergy and Asthma Associates, 27800 Medical Center Road, Suite 244, Mission
Viejo, CA 92691, USA. weberger@uci.edu

Epidemiologic and pathophysiologic evidence indicates that allergic rhinitis,
whether seasonal or perennial, is one piece of a larger atopic clinical picture
that often occurs concomitantly with asthma. Allergic rhinitis usually develops
during childhood and has a prevalence of up to 40% in the pediatric population.
Careful attention to food allergies and the presence of household allergens
during infancy and early childhood may limit potential sensitizations. Many
antihistamines and topical corticosteroids now are available for the treatment of
allergic rhinitis in children, which is all the more important because optimal
management may improve quality of life and curtail the development of serious
sequelae.

Publication Types: 
    Review

PMID: 11892079 [PubMed - indexed for MEDLINE]

1274: Acta Otolaryngol. 2002 Jan;122(1):54-60.

The effect of Japanese cedar-specific immunotherapy on cytokine production in
peripheral blood mononuclear cells.

Nakano A, Nakano K, Okawa T, Yamakoshi T, Terada N, Numata T, Konno A.

Department of Otolaryngology, Chiba Cardiovascular Center, Ichihara City, Japan. 
atsuko.nakano@hosp.pref.chiba.jp

The most common cause of seasonal allergic rhinitis in Japan is the Japanese
cedar (JC). Recently, a pullulan-conjugated antigen (CS-560) has been developed
to reduce adverse effects and to enhance the effect of JC-specific immunotherapy 
(IT). If the mechanism of IT can be fully elucidated and the treatment can be
used safely and with specificity, IT should be reconsidered as a superior
treatment for JC pollinosis. Thirteen patients with JC pollinosis who received IT
were compared to 10 patients who did not receive IT. All patients were followed
through two pollen seasons by means of allergy diaries. Peripheral blood
mononuclear cells (PBMC) were collected before IT and just before each pollen
season, and these were stimulated with pollen extract. The concentrations of
IL-4, IL-5, IL-13 and IFN-gamma in the culture supernatants were determined using
an ELISA. Furthermore, messenger (m)RNA expressions of IL-4 and IL-5 from
cultured PBMC were also studied. As a result of the allergy diaries, we confirmed
the clinical efficacy of CS-560. The symptom-medication scores were significantly
decreased by IT. The levels of IL-4, IL-5 and IL-13 declined only in the IT
group. However, the level of IFN-gamma did not change in either group. IL-4 and
IL-5 mRNA expressions were inhibited in the IT group compared to that in the
non-IT group. In conclusion, specific IT for JC pollinosis using CS-560 clearly
modified cytokine expression by PBMC.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 11876600 [PubMed - indexed for MEDLINE]

1275: Twin Res. 2001 Oct;4(5):392-9.

Perinatal risk factors for hay fever--a study among 2550 Finnish twin families.

Räsänen M, Kaprio J, Laitinen T, Winter T, Koskenvuo M, Laitinen LA.

Helsinki University Central Hospital, Department of Medicine, Helsinki, Finland. 
Maija.Rasanen@vshp.fi

Previous studies have suggested that perinatal factors influence the risk for
asthma but population studies on perinatal factors and risk for hay fever are
few. We studied the effect of perinatal factors on the risk for hay fever among
adolescent twins by a questionnaire study involving five consecutive nation-wide 
birth cohorts of 16-year-old twins and their parents. The risk for
parent-reported, doctor-diagnosed hay fever in the adolescents associated with
several perinatal characteristics was assessed with logistic regression analysis 
among individuals and by a discordant pair analysis. In the univariate analysis
of the birth factors, the risk for hay fever increased with increasing birth
weight (p for trend = 0.048, OR for those > or = 3000 g 1.35, 95% CI 0.91-2.02
compared to those < 2000 g) and gestational age (p for trend = 0.04, OR for those
born after 40 weeks of gestation 2.24, 95% CI 1.03-4.86, compared to those born
before 33 weeks of gestation) and was lower in those subjects hospitalised in the
neonatal period (OR 0.74, 95% CI 0.58-0.93). Because of significant interactions 
between parental hay fever status and birth factors (ponderal index, p = 0.03 and
maternal age p = 0.04), stratified analysis were performed. The positive
association between birth weight and hay fever was most obvious among adolescents
with no parental history of hay fever (p for trend = 0.03). Similar, though not
significant, trends were found with other birth factors among these families,
whereas no such trend was found among adolescents with parental hay fever,
suggesting that gestational maturity increases the risk for hay fever in the
absence of genetic predisposition. However, of the perinatal factors only
neonatal hospitalisation (OR 0.75, 95% CI 0.59-0.96) remained a significant risk 
factor for the development of hay fever, when adjusted for non-perinatal factors.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Twin Study

PMID: 11869494 [PubMed - indexed for MEDLINE]

1276: Ann Allergy Asthma Immunol. 2002 Feb;88(2):183-9.

Prevalence of food allergies in young adults and their relationship to asthma,
nasal allergies, and eczema.

Woods RK, Thien F, Raven J, Walters EH, Abramson M.

Department of Epidemiology and Preventive Medicine, Central and Eastern Clinical 
School, Monash University and The Alfred Hospital, Prahran, Victoria, Australia. 
Rosalie.Woods@med.monash.edu.au

BACKGROUND: The true prevalence of food allergy in adults is generally thought to
be uncommon. It is unknown whether there are any relationships between food
allergy and atopic diseases. OBJECTIVE: To determine the prevalence of probable
immunoglobulin (Ig)E-mediated food allergy to peanut, shrimp, cow's milk, wheat, 
and egg as defined by a positive skin prick test result and relevant clinical
history to the same food, and to explore the relationship with atopic diseases.
METHODS: Cross-sectional epidemiologic study. One thousand one hundred forty-one 
randomly selected young adults (aged 20 to 45 years) underwent skin prick testing
to five common food allergens (cow's milk, peanut, egg white, shrimp, and wheat),
completed a detailed questionnaire, including validated items on respiratory
symptoms, history of asthma and other allergic conditions, as well as undergoing 
lung function testing. RESULTS: Just over one percent (1.3%, n = 15) had probable
IgE-mediated food allergy. The prevalence of probable IgE food allergy was:
<0.27% for wheat, 0.09% (95% confidence interval = 0.0 to 0.49%) each for cow's
milk and egg, 0.53% (0.21 to 1.09%) for shrimp, and 0.61% (0.25 to 1.26%) for
peanut. Those with probable IgE peanut and shrimp allergy were significantly more
likely to have current asthma and doctor-diagnosed asthma. Wheeze and history of 
eczema were also associated with peanut allergy, whereas nasal allergies were
associated with shrimp allergy. CONCLUSIONS: The prevalence of probable
IgE-mediated food reactions is rare in young adults. Some positive associations
between probable IgE-mediated food allergy and allergic diseases were found, but 
larger study numbers are required to confirm these results.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11868923 [PubMed - indexed for MEDLINE]

1277: Acta Otorhinolaryngol Belg. 2001;55(4):305-12.

Efficacy and safety of levocetirizine in seasonal allergic rhinitis.

Leynadier F, Mees K, Arendt C, Pinelli ME.

Hôpital Tenon, Paris, France. francisque.leynadier@tnn.ap-hop-paris.fr

OBJECTIVE: Pharmacodynamic studies have demonstrated that levocetirizine is the
active enantiomer of cetirizine. This first therapeutic trial of levocetirizine
aimed at determining the dosage with the best benefit/risk ratio in patients with
seasonal allergic rhinitis (SAR). METHODS: Patients with seasonal allergic
rhinitis were randomised in a placebo-controlled, double-blind, parallel-group
multicentre study 2.5, 5, 10 mg levocetirizine or placebo once daily during 2
weeks. Patients filled in a diary evaluation card every evening before taking
study medication using the classical (0-3) scale for assessment of severity of
sneezing, rhinorrhea, nasal congestion, nasal pruritus and ocular pruritus over
the preceding 24 hours. The Total Four-Symptom Score (T4SS) was calculated by
adding the individual symptom scores, excluding nasal congestion. RESULTS: 470
patients were included and constituted the intent-to-treat population. All 3
doses of levocetirizine were significantly superior to placebo in reducing the
mean T4SS over the 2 weeks (all P (0.001). Additionally, individual symptom
severity scores for sneezing, rhinorrhea, itchy nose, and itchy eyes were also
significantly decreased for all doses of levocetirizine. Levocetirizine was
significantly superior to placebo in reducing symptom severity with an important 
global treatment effect (P = 0.0001), except for nasal congestion. Furthermore,
there was simple linear relationship between levocetirizine dosages and reduction
of T4SS (P = 0.001). All doses were well tolerated, somnolence was higher with 10
mg (10.2%) than 5 mg (1.7%) and other adverse events were more frequent with the 
highest dose. CONCLUSION: Levocetirizine 5 mg once daily has an optimal
benefit/risk ratio in the treatment of SAR.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11859651 [PubMed - indexed for MEDLINE]

1278: Genes Immun. 2002 Feb;3(1):9-13.

A genome-wide linkage analysis of orchard grass-sensitive childhood seasonal
allergic rhinitis in Japanese families.

Yokouchi Y, Shibasaki M, Noguchi E, Nakayama J, Ohtsuki T, Kamioka M,
Yamakawa-Kobayashi K, Ito S, Takeda K, Ichikawa K, Nukaga Y, Matsui A, Hamaguchi 
H, Arinami T.

Department of Medical Genetics, Institute of Basic Medical Sciences, University
of Tsukuba, Tsukuba, Japan.

Seasonal allergic rhinitis (SAR) is an inflammatory disease of the nose and eyes 
that follows sensitization to air-born pollens. We conducted a genome-wide
linkage screening of 48 Japanese families (188 members) with orchard grass
(OG)-sensitive SAR children (67 affected sib-pairs) in a farming community in
central Japan where OG was planted for apple farming and OG pollen is a major
cause of SAR. We used the GENEHUNTER program to performed nonparametric
multipoint linkage analysis for OG-sensitive SAR as a qualitative trait and for
log total serum IgE levels and OG-RAST IgE levels as quantitative traits.
Genotyping data of 400 microsatellite markers suggested linkage of SAR to
chromosomes 1p36.2, 4q13.3, and 9q34.3 (P < 0.001), linkage of serum total IgE
levels to 3p24.1, 5q33.1, 12p13.1, and 12q24.2 (P < 0.001), and linkage of
OG-RAST IgE levels to 4p16.1, 11q14.3, and 16p12.3 (P < 0.001). Weak evidence for
linkage of SAR to 5q33.1 was also observed (P = 0.01). All these regions, with
the exception of 9q34.3, have been previously reported to be linked to asthma
and/or atopy. These data suggest that, although loci linked to SAR are likely to 
be common to asthma, a strong contribution by specific gene(s) to OG-sensitive
SAR is unlikely.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11857054 [PubMed - indexed for MEDLINE]

1279: Immunology. 2002 Jan;105(1):56-62.

Grass pollen immunotherapy for hayfever is associated with increases in local
nasal but not peripheral Th1:Th2 cytokine ratios.

Wachholz PA, Nouri-Aria KT, Wilson DR, Walker SM, Verhoef A, Till SJ, Durham SR.

Upper Respiratory Medicine, National Heart and Lung Institute, Imperial College
School of Medicine, London, UK.

Grass pollen immunotherapy is the only treatment for hayfever that is both
effective and confers long-term benefit. Immunotherapy may act by altering the
local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either
by down-regulation and/or immune deviation of T-lymphocyte responses. There is
controversy as to whether these changes are detectable in peripheral blood. We
therefore examined both local nasal and peripheral T-cell responses to allergen
exposure in the same subjects before and after immunotherapy. In a double-blind
trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and
during the peak pollen season following 2 years of immunotherapy. Placebo-treated
patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in
interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma
(IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the
immunotherapy-treated group, there were no changes in the number of CD3(+) T
cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the 
number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement
in the immunotherapy-treated group was accompanied by a seasonal increase in the 
ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In
contrast, there were no significant changes in peripheral T-cell proliferative
responses or cytokine production for IFN-gamma or IL-5 in response to grass
pollen either within or between the two treatment groups. We conclude that
successful grass pollen immunotherapy was associated with an increase in the
ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these
changes were not reflected by alterations in peripheral blood T-cell
proliferative responses or cytokine production before/after treatment.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11849315 [PubMed - indexed for MEDLINE]

1280: J Allergy Clin Immunol. 2002 Feb;109(2):274-80.

Efficacy of combination treatment with anti-IgE plus specific immunotherapy in
polysensitized children and adolescents with seasonal allergic rhinitis.

Kuehr J, Brauburger J, Zielen S, Schauer U, Kamin W, Von Berg A, Leupold W,
Bergmann KC, Rolinck-Werninghaus C, Gräve M, Hultsch T, Wahn U.

University Children's Hospital, Freiburg, Germany.

BACKGROUND: Specific immunotherapy (SIT) and treatment with monoclonal anti-IgE
antibody have complementary modes of action. OBJECTIVE: The purpose of this study
was to determine whether combined therapy could provide better efficacy than
either treatment alone. METHODS: We conducted a randomized, double-blinded trial 
to assess the efficacy and safety of subcutaneously administered anti-IgE
(omalizumab) or placebo in children and adolescents with seasonal allergic
rhinitis in both a birch pollen season and a grass pollen season (sequential
seasons together lasting an average of 84 days). There were 4 treatment arms.
Each subject was started on SIT-birch or SIT-grass, and anti-IgE or placebo was
started before and maintained during the anticipated pollen seasons (a total of
24 weeks). The primary efficacy variable was symptom load, the sum of daily
symptom severity score plus rescue medication use. RESULTS: A total of 221
subjects (intent-to-treat population) aged 6 to 17 years were analyzed for
efficacy. Combination therapy reduced symptom load over the 2 pollen seasons by
48% (P <.001) over SIT alone. When analyzed separately by season, the 2 groups
receiving unrelated SIT were considered placebo controls. In the grass season,
symptom loads were as follows: unrelated (birch) SIT + placebo, 0.89 (reference
value); unrelated (birch) SIT + anti-IgE, 0.49 (-45%); SIT-grass + placebo, 0.61 
(-32%); SIT-grass + anti-IgE, 0.26 (-71%). CONCLUSION: Anti-IgE therapy conferred
a protective effect independent of the type of allergen. Additional clinical
benefit was demonstrated in both pollen seasons, whether there was coverage by
SIT or not. This combination might prove useful for the treatment of allergic
rhinitis, particularly for polysensitized patients.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11842297 [PubMed - indexed for MEDLINE]

1281: J Allergy Clin Immunol. 2002 Feb;109(2):251-6.

Comment in:
    J Allergy Clin Immunol. 2002 Oct;110(4):671; author reply, 671-2.    J Allergy Clin Immunol. 2002 Oct;110(4):672-3; author reply 273.

Pollen immunotherapy reduces the development of asthma in children with seasonal 
rhinoconjunctivitis (the PAT-study).

Möller C, Dreborg S, Ferdousi HA, Halken S, Høst A, Jacobsen L, Koivikko A,
Koller DY, Niggemann B, Norberg LA, Urbanek R, Valovirta E, Wahn U.

Department of Paediatrics, Umeå University, Sweden.

BACKGROUND: Children with allergic rhinitis are likely to develop asthma.
OBJECTIVE: The purpose of this investigation was to determine whether specific
immunotherapy can prevent the development of asthma and reduce bronchial
hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis.
METHODS: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean 
age, 10.7 years) with grass and/or birch pollen allergy but without any other
clinically important allergy were randomized either to receive specific
immunotherapy for 3 years or to an open control group. All subjects had moderate 
to severe hay fever symptoms, but at inclusion none reported asthma with need of 
daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, 
sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by
peak flow. Methacholine bronchial provocation tests were carried out during the
season(s) and during the winter. RESULTS: Before the start of immunotherapy, 20% 
of the children had mild asthma symptoms during the pollen season(s). Among those
without asthma, the actively treated children had significantly fewer asthma
symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P
<.05). Methacholine bronchial provocation test results improved significant in
the active group (P <.05). CONCLUSION: Immunotherapy can reduce the development
of asthma in children with seasonal rhinoconjunctivitis.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11842293 [PubMed - indexed for MEDLINE]

1282: Eur J Hum Genet. 2001 Dec;9(12):945-52.

Allergic rhinitis--a total genome-scan for susceptibility genes suggests a locus 
on chromosome 4q24-q27.

Haagerup A, Bjerke T, Schøitz PO, Binderup HG, Dahl R, Kruse TA.

Institute of Human Genetics, Aarhus University, Aarhus, Denmark. AH@humgen.au.dk

Allergic rhinitis is a common disease of complex inheritance and is characterised
by mucosal inflammation caused by allergen exposure. The genetics of closely
related phenotypes such as asthma, atopy and to some extend atopic dermatitis has
attracted attention in recent years. Genetic reports of allergic rhinitis on the 
contrary have as yet been most sparse. To identify candidate regions holding
genes for allergic rhinitis we performed a total genome-scan on affected sib-pair
families. From 100 Danish sib-pair families selected for allergy, families
containing sib-pairs matching a phenotype definition of both clinical allergic
rhinitis and confirmed specific allergy were chosen. Thirty-three affected
sib-pair families qualified for the scan that was undertaken using 446
microsatellite markers. Non-parametric linkage results were obtained from
MAPMAKER/SIBS computer program. The study revealed one major candidate region on 
chromosome 4q24-q27 (LOD=2.83) and eight minor candidate regions 2q12-q33, 3q13, 
4p15-q12, 5q13-q15, 6p24-p23, 12p13, 22q13, and Xp21 (LOD=1.04-1.63) likely to
contain susceptibility genes for allergic rhinitis. Our findings did not support 
a previous report of linkage of allergic rhinitis to chromosome 12q14-q24 but
they added positive evidence to the asthma and atopy candidate regions 2q33 and
6p23. Further identification of the specific genes involved in allergic rhinitis 
will give opportunities for improved diagnosis and treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11840197 [PubMed - indexed for MEDLINE]

1283: Allergol Immunopathol (Madr). 2001 Nov-Dec;29(6):245-54.

Standardisation of glutaraldehyde-modified tyrosine-adsorbed tree pollen vaccines
containing the Th1-inducing adjuvant, monophosphoryl lipid A (MPL).

Hopkins M, Lees BG, Richardson DG, Woroniecki SR, Wheeler AW.

Allergy Therapeutics Ltd, West Sussex, UK.

BACKGROUND: a new range of allergy vaccines has been developed by the
introduction of a relatively new Th1-inducing adjuvant known as 3-deacylated
monophosphoryl lipid A (MPL). MPL adjuvant is of natural origin, derived from the
lipopolysaccharide of Salmonella minnesota R595. This adjuvant is incorporated in
a glutaraldehyde-modified pollen extract adsorbed to L-tyrosine (Pollinex
Quattro). A major potential benefit provided by MPL adjuvant is the promotion of 
a Th1 response which enhances the efficacy of allergy vaccination and can
consequently allow a reduction in the number of injections required for
treatment. The standardisation of Pollinex Quattro tree pollen allergy vaccine is
described and we include details of some innovative analytical procedures.
METHODS AND RESULTS: an essential feature of the analytical strategy is the assay
of the MPL adjuvant using a recently developed HPLC technique. The adjuvant has a
complex chemical structure and the analysis is illustrated in detail. We give a
full picture of the vaccine standardisation by describing biochemical and
immunological characterisation of the allergen extract, together with some brief 
manufacturing details. CONCLUSIONS: a high overall level of standardisation is
illustrated by a number of different tests applied to all stages of vaccine
manufacture. Tree pollen allergen potency is measured following the pollen
extraction, chemical modification and formulation as a tyrosine adsorbate. Good
batch-to-batch reproducibility is shown. The HPLC assay for MPL adjuvant showed
high quality resolution which did not vary when measuring raw material or when
incorporated in the vaccine and the technically complex assay is shown to be
reliable.

Publication Types: 
    Comparative Study

PMID: 11834183 [PubMed - indexed for MEDLINE]

1284: Allergol Immunopathol (Madr). 2001 Nov-Dec;29(6):238-44.

Efficacy of sublingual specific immunotherapy in Cupressaceae allergy using an
extract of Cupressus arizonica. A double blind study.

Ariano R, Spadolini I, Panzani RC.

Modulo di Allergologia ed Immunologia Clinica, A.S.L. Imperiese-Ospedale S.
Charles di Bordighera, Italy.

BACKGROUND: non-injective routes of immunotherapy in respiratory allergy have
being proposed as an alternative to conventional immunotherapy. We carried out a 
study to evaluate the clinical efficacy and effects sublingual immunotherapy
(SLIT) in patient with Cupressaceae pollen respiratory allergy. METHODS: twenty
patients with Cupressaceae pollen (C. sempervirens) rhinoconjunctivitis, mild
asthma or both were randomly chosen for sublingual immunotherapy (10 patients) or
placebo treatment (10 patients) using a double blind placebo controlled
technique. We have used an extract of Cupressus arizonica because of its better
stability in solution and its crossreactivity with Cupressus sempervirens. The
patients underwent treatment for 12 months (from april 1999 to april 2000).
Symptoms and drug scores as well as nasal provocation tests were recorded. The
pollen counts were carried out, during all the same period. RESULTS: we found
significantly lower symptom scores (p < 0.05) and drug consumption scores (p <
0.05) in the immunotherapy group than in the placebo group, during the pollen
season, after the first year of therapy. Besides threshold of allergen reactivity
in nasal provocation tests was increased in the active group (p < 0.01). No
untoward reactions have been observed. CONCLUSIONS: SLIT with Cupressus arizonica
(pollen extracts) produced, after one year treatment, a significant improvement
of allergic symptoms and a decrease of drug consumption scores and
allergen-specific nasal reactivity. SLIT with Cupressus arizonica appeared to be 
effective and safe in the treatment of Cupressaceae pollen respiratory allergy.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11834182 [PubMed - indexed for MEDLINE]

1285: J Investig Allergol Clin Immunol. 2001;11(3):149-56.

Safety and efficacy of specific immunotherapy with standardized allergenic
extracts adsorbed on aluminium hydroxide.

Wüthrich B, Gumowski PL, Fäh J, Hürlimann A, Deluze C, André C, Fadel R, Carat F.

Department of Dermatology, University Hospital, Zurich, Switzerland.
wuethric@derm.unizh.ch

Specific immunotherapy (SIT) with standardized allergenic extracts is the only
specific treatment of allergic patients. In order to evaluate the safety, side
effects, and efficacy of SIT with standardized extracts adsorbed to aluminium
hydroxide manufactured by Stallergènes S.A., a prospective multicenter open study
was performed in Switzerland. Fifteen patients suffering from seasonal or
perennial rhinoconjunctivitis with or without asthma were included in the trial
and received a total of 442 injections with standardized mix of grass pollens (n 
= 8) or house dust mites (n = 7) over one year. Low incidence of local reactions 
was noted (7%). Subcutaneous nodules (granuloma) following injections were not
recorded. Only a few systemic reactions (one mild rhinitis, one mild asthma
attack, one worsening of eczema) were recorded. No anaphylactic reactions
requiring adrenaline were recorded. No admission to the hospital was required.
Global appreciation of the physicians and the patients after the first year of
treatment showed a good efficacy of SIT: Only two patients (13%) did not improve.
A worsening of the symptoms was not observed. In order to assess the efficacy,
skin reactivity and conjunctival reactivity to allergen challenge were compared
before and after one year of treatment as well as immunologic parameters (such as
specific IgE, specific IgG4) in blood samples. A significant decrease in skin
reactivity (p = .001) and in conjunctival reactivity (p = .01) was observed.
Specific IgE level decreased for both types of allergens but to a significantly
greater extent for grass pollen allergen (p = .03). Specific IgG4 level increased
significantly for grass (p = 0.01) and for mites (p = 0.04). Specific
immunotherapy appears to be a valuable tool in the efficient management of the
allergic respiratory diseases.

Publication Types: 
    Multicenter Study

PMID: 11831445 [PubMed - indexed for MEDLINE]

1286: Laryngoscope. 2002 Jan;112(1):47-52.

Effects of intranasal azelastine on the response to nasal allergen challenge.

Saengpanich S, Assanasen P, deTineo M, Haney L, Naclerio RM, Baroody FM.

Section of Otolaryngology-Head and Neck Surgery, The Pritzker School of Medicine,
The University of Chicago, 5841 South Maryland Avenue, MC 1035, Chicago, IL
60637, U.S.A.

OBJECTIVES/HYPOTHESIS: Azelastine, a second-generation H1-receptor antagonist, is
available for topical administration. The aim of the study was to evaluate the
effects of topical intranasal azelastine on the early-phase and the late-phase
allergic responses and on nasal hyper-responsiveness to methacholine. STUDY
DESIGN: Double-blind, placebo-controlled, two-way crossover study in 20 subjects 
with seasonal allergic rhinitis, out of their allergy season. METHODS: Subjects
were randomly assigned to receive either placebo or two puffs of azelastine twice
a day (548 microg/d) for 2 weeks followed by nasal challenge with allergen.
Twenty-four hours later, while still receiving treatment, subjects underwent a
nasal lavage and a nasal challenge with methacholine. End points included symptom
scores, levels of mediators and number of eosinophils in nasal lavages, and the
weight of secretions after methacholine challenge. RESULTS: Compared with
placebo, treatment with intranasal azelastine resulted in significant reductions 
in allergen-induced sneezing, rhinorrhea, itching, nasal congestion, and levels
of albumin during the early-phase response (P <.05). Azelastine had no effect on 
levels of histamine or tryptase during the early-phase response. There was a
significant eosinophil influx 24 hours after challenge, which was not inhibited
by azelastine. Treatment with azelastine had no effect on the levels of albumin, 
interleukin-4, interleukin-5, intercellular adhesion molecule-1, tumor necrosis
factor-alpha, and eosinophil cationic protein during the late-phase response.
However, azelastine did show a significant inhibitory effect on the methacholine 
response 24 hours after nasal allergen challenge (P <.05). CONCLUSIONS: The
effects of intranasal azelastine are similar to those of oral second-generation
antihistamines.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11802037 [PubMed - indexed for MEDLINE]

1287: J Allergy Clin Immunol. 2002 Jan;109(1):57-62.

Treating allergic rhinitis in patients with comorbid asthma: the risk of
asthma-related hospitalizations and emergency department visits.

Crystal-Peters J, Neslusan C, Crown WH, Torres A.

MEDSTAT Group, Washington, DC, USA.

BACKGROUND: Although asthma and allergic rhinitis commonly occur together, the
nature of the association has yet to be determined. Treatments for one condition 
could potentially alleviate the coexisting condition. OBJECTIVE: Patients with
both allergic rhinitis and asthma were studied to test the hypothesis that
treating allergic rhinitis reduces health care utilization for co-morbid asthma. 
METHODS: A retrospective cohort study was carried out with 1994-1995 MarketScan
claims data. The cohort was limited to patients with both allergic rhinitis and
asthma, aged 12 to 60 years, who were continuously enrolled and had no evidence
of chronic obstructive pulmonary disease. Allergic rhinitis treatment and
asthma-related events (hospitalizations and emergency department visits) were
identified. An incidence density ratio (IDR) associated with exposure to allergic
rhinitis treatment was calculated. A multivariate Poisson regression was
estimated, and the parameter estimates were transformed into IDRs for each
explanatory variable. An allergic rhinitis treatment indicator was included in
all regressions. RESULTS: The study sample population consisted of 4944 patients 
with allergic asthma, approximately 73% of whom were treated for their allergic
rhinitis. Asthma-related events occurred more often for the untreated group
compared with the treated group, 6.6% compared with 1.3%. An IDR of 0.49 for the 
treatment group (P =.001) indicates that the risk of an asthma-related event for 
the treated group was about half that for the untreated group. CONCLUSION: In
summary, those who were treated for allergic rhinitis have a significantly lower 
risk of subsequent asthma-related events (emergency department visits or
hospitalizations) than those who were not treated.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11799366 [PubMed - indexed for MEDLINE]

1288: BMJ. 2002 Jan 19;324(7330):144-6.

Comment in:
    BMJ. 2002 May 25;324(7348):1277; author reply 1277.    BMJ. 2002 May 25;324(7348):1277; author reply 1277.

Randomised controlled trial of butterbur and cetirizine for treating seasonal
allergic rhinitis.

Schapowal A; Petasites Study Group.

Allergy Clinic, Hochwangstrasse 3, CH-7302 Landquart, Switzerland.
andreas.schapowal@freesurf.ch

OBJECTIVES: To compare the efficacy and tolerability of butterbur (Petasites
hybridus) with cetirizine in patients with seasonal allergic rhinitis (hay
fever). DESIGN: Randomised, double blind, parallel group comparison. SETTING:
Four outpatient general medicine and allergy clinics in Switzerland and Germany. 
PARTICIPANTS: 131 patients were screened for seasonal allergic rhinitis and 125
patients were randomised (butterbur 61; cetirizine 64). INTERVENTIONS: Butterbur 
(carbon dioxide extract tablets, ZE 339) one tablet, four times daily, or
cetirizine, one tablet in the evening, both given for two consecutive weeks. MAIN
OUTCOME MEASURES: Scores on SF-36 questionnaire and clinical global impression
scale. RESULTS: Improvement in SF-36 score was similar in the two treatment
groups for all items tested hierarchically. Butterbur and cetirizine were also
similarly effective with regard to global improvement scores on the clinical
global impression scale (median score 3 in both groups). Both treatments were
well tolerated. In the cetirizine group, two thirds (8/12) of reported adverse
events were associated with sedative effects (drowsiness and fatigue) despite the
drug being considered a non-sedating antihistamine. CONCLUSIONS: The effects of
butterbur are similar to those of cetirizine in patients with seasonal allergic
rhinitis when evaluated blindly by patients and doctors. Butterbur should be
considered for treating seasonal allergic rhinitis when the sedative effects of
antihistamines need to be avoided.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11799030 [PubMed - indexed for MEDLINE]

1289: J Voice. 2001 Dec;15(4):558-60.

Response of asthma-related voice dysfunction to allergen immunotherapy: a case
report of confirmation by methacholine challenge.

Cohn JR, Sataloff RT, Branton C.

Jefferson Medical College, Thomas Jefferson University, Philadelphia,
Pennsylvania 19107, USA. john.cohn@mail.tju.edu

Professional singers and other serious voice users are particularly susceptible
to alterations in their vocal apparatus. As the support for vocalization, lung
function is an essential element of the production of speech and song. Patients
have been described who presented with voice complaints along with minimal or no 
abnormalities on spirometry, but responded to conventional bronchodilator and
other asthma therapy. It was proposed that this represented an exercise-induced
asthmalike condition, brought on by the hyperventilation associated with
performing. The objective of this study was to establish whether improvement in
vocalization while performing correlated with a decrease in non-specific
bronchial reactivity. We concluded that resolution of vocal complaints in
conjunction with a decrease in methacholine reactivity supports the hypothesis
that these patients do have an exercise-induced asthmalike condition brought on
by airway drying. As with other patients with asthma, it appears to respond to
allergy-directed therapy.

Publication Types: 
    Case Reports

PMID: 11792032 [PubMed - indexed for MEDLINE]

1290: Am J Rhinol. 2001 Nov-Dec;15(6):387-90.

Allergic rhinitis as a risk factor for orbital complication of acute
rhinosinusitis in children.

Holzmann D, Willi U, Nadal D.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital
Zürich and University Children's Hospital, Switzerland.

The purpose of this article is to determine allergic rhinitis and age as
potential risk factors for the development of orbital complications of acute
rhinosinusitis in children. One hundred two children presenting with orbital
swelling were investigated by computed tomography (CT) of the paranasal sinuses
and the orbit as well as for underlying allergic rhinitis. Sixty (58.8%) patients
had orbital complications of clinical and radiological acute rhinosinusitis. They
were grouped accordingly: preseptal cellulitis (n = 24), periostitis (n = 10),
and subperiosteal abscess (n = 26). No abscess within the orbit or cavernous
sinus thrombosis was found. Thirty-four (56.7%) of the 60 patients underwent
allergy investigation. Allergic rhinitis was found in 9 (64.3%) of 14 children
with preseptal cellulitis, in 1 (25%) out of 4 children with periostitis, and in 
13 (76.5%) out of 17 children with subperiosteal abscess. The prevalence of
allergic rhinitis was significantly higher in patients presenting in pollen
season from February to August (17:4) than in patients presenting in the period
between September and January (6:7). Thus, allergic rhinitis may be a cofactor in
the pathogenesis of orbital complications of acute rhinosinusitis. According to
our study population, age only influences the type of orbital complication of
acute rhinosinusitis in the sense that older children are more likely to develop 
subperiosteal abscess, whereas younger children develop preseptal cellulitis.

Publication Types: 
    Comparative Study

PMID: 11777246 [PubMed - indexed for MEDLINE]

1291: Allergy Asthma Proc. 2001 Nov-Dec;22(6 Suppl 1):S17-22.

Physician prescribing practices: the role of patient preference in the selection 
of nasal steroids.

Kaliner MA.

Institute for Asthma and Allergy, 11160 Veirs Mill Road, Suite 114, Wheaton, MD
20902, USA.

A telephone survey of 100 primary care physicians was performed to assess the
awareness of the influence patient preference, patient satisfaction, and other
factors have on the selection of nasal steroids for the treatment of allergic
rhinitis. Results indicated that physicians believe drug efficacy is the primary 
reason why one product is chosen over another, while sensory attributes are the
next most important criteria for distinguishing among products. Physicians agree 
that patients would prefer a preparation that has no odor or aftertaste and that 
patients are willing to switch products if their physicians recommend that they
do so.

Publication Types: 
    Comparative Study

PMID: 11775400 [PubMed - indexed for MEDLINE]

1292: Allergy Asthma Proc. 2001 Nov-Dec;22(6 Suppl 1):S11-5.

Patient preferences and satisfaction with prescribed nasal steroids for allergic 
rhinitis.

Kaliner MA.

Institute for Asthma and Allergy, 1160 Veirs Mill Road, Suite 414, Wheaton, MD
20902, USA.

A telephone survey of 503 patients with seasonal and perennial allergic rhinitis 
was performed to assess satisfaction with their nasal steroid therapy and their
reasons for preferences for particular products. Product attributes such as
efficacy and various sensory features (e.g., nasal irritation, odor, and taste)
were evaluated. Although patients generally are satisfied with their nasal
steroid preparations, they do show clear preferences for the sensory attributes
of different products. Patients are willing to switch on their physicians'
recommendations and clearly prefer products with no odor and no taste.

PMID: 11775399 [PubMed - indexed for MEDLINE]

1293: Drugs. 2001;61(15):2231-40; discussion 2241-2.

Cetirizine/pseudoephedrine.

Wellington K, Jarvis B.

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Cetirizine is the carboxylated metabolite of hydroxyzine, and has high specific
affinity for histamine H(1) receptors. Pseudoephedrine is a sympathomimetic drug 
that acts directly on alpha-adrenergic receptors. black triangle
Cetirizine/pseudoephedrine 5/120 mg twice daily was significantly more effective 
than intranasal budesonide 100 microg or placebo at improving nasal obstruction, 
nasal patency and reducing the volume of nasal secretion, and was significantly
more effective than intranasal xylometazoline 0.1% with respect to nasal
secretion, during house dust mite faeces challenge in three randomised, cross-
over studies among volunteers with seasonal or perennial rhinitis. The onset of
action of cetirizine/pseudoephedrine was reported to be approximately 30 minutes.
black triangle The bioavailability of cetirizine and pseudoephedrine is similar
after administration of cetirizine/pseudoephedrine 5/120 mg bilayer tablets or
coadministration of cetirizine 5 mg tablets plus pseudoephedrine
sustained-release (SR) 120 mg caplets. black triangle Cetirizine 5mg plus
pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was significantly more
effective than each drug given alone at reducing mean total symptom scores for
seasonal or perennial allergic rhinitis in two randomised, double-blind,
multicentre trials. In both studies, the mean proportion of days during which the
five measured symptoms (nasal obstruction, sneezing, rhinorrhoea, nasal pruritus 
and ocular pruritus) were absent or mild was significantly greater in recipients 
of the cetirizine plus pseudoephedrine SR. black triangle In one study,
cetirizine 5 mg plus pseudoephedrine SR 120 mg was significantly more effective
at reducing nasal obstruction than either drug alone. black triangle Cetirizine
5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was well
tolerated in patients with seasonal or perennial allergic rhinitis. The most
common adverse events were dry mouth, insomnia, headache, somnolence, asthenia
and nervousness.

Publication Types: 
    Review

PMID: 11772135 [PubMed - indexed for MEDLINE]

1294: Ann Allergy Asthma Immunol. 2001 Dec;87(6):474-81.

Comparative onset of action and symptom relief with cetirizine, loratadine, or
placebo in an environmental exposure unit in subjects with seasonal allergic
rhinitis: confirmation of a test system.

Day JH, Briscoe M, Rafeiro E, Chapman D, Kramer B.

Division of Allergy and Immunology, Kingston General Hospital, Ontario, Canada.
dayj@KGH.KARI.NET

BACKGROUND: The environmental exposure unit (EEU) is an instrument designed to
determine onset of action of antiallergic treatment. Confirmation of test results
would be useful in defining its role. OBJECTIVE: This study was intended to
confirm a previous study comparing cetirizine, loratadine, and placebo in the EEU
using an identical protocol design (randomized, double-blind, parallel-group
comparison having the same symptom scoring system, endpoints, and statistical
analyses), thus demonstrating reproducibility of studies conducted in the EEU.
METHODS: Onset of action and symptom relief with once-daily cetirizine 10 mg,
loratadine 10 mg, and placebo (n = 120 each group) were evaluated replicating a
previous study design. Subjects meeting inclusion and exclusion criteria and
qualifying symptom scores were randomized to 2 days' exposure (6 to 7 hours
daily) with treatment. Changes in total and major symptom complex (TSC, MSC)
scores based on 14 symptoms evaluated at 30-minute intervals served as primary
efficacy variables. RESULTS: Onset of action again was earlier with cetirizine
(at 1 hour, P < or = 0.001) versus loratadine (at 3 hours, P < or = 0.01).
Cetirizine produced a 25.4% least-square mean reduction in TSC scores overall
versus an 11.2% decrease with loratadine (P = 0.006) and a 4.8% increase with
placebo (P < 0.001); loratadine and placebo were also significantly different (P 
= 0.002). Similar changes were also noted in MSC scores. Cetirizine consistently 
reduced TSC and MSC scores after the first dose versus placebo (P < or = 0.001)
and at most time points versus loratadine (P < or = 0.05). Adverse events were
reported in 1.7% of patients in each active-treatment group and in 2.5% on
placebo. CONCLUSIONS: Cetirizine acted earlier and was more effective than
loratadine or placebo in reducing symptoms of seasonal allergic rhinitis in
subjects undergoing a controlled pollen challenge, replicating results from an
earlier, identically designed study, demonstrating reproducibility of these
assessments by the EEU.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11770694 [PubMed - indexed for MEDLINE]

1295: Allerg Immunol (Paris). 2001 Oct;33(8):323-6.

Immunotherapy in allergic rhinitis.

Palma-Carlos AG, Spinola-Santos A, Ferreira MB, Santos MC, Palma-Carlos ML.

1st Medical Clinic, University Faculty of Medicine, Immuno-Allergology Unit and
Hematology, Immunology Center (CHIUL), Lisbon.

Allergen specific immunotherapy (IT) represents a cornerstone of allergic
rhinitis treatment and his efficacy has been confirmed, through open and double
blind trials and meta-analysis. In the last few years non invasive routs for IT
(oromucosal, nasal) were developed gained general acceptation mainly in children 
and were validated by WHO. The efficacy of IT could be markers, the pattern of
specific antibody response or by the effect on sequential nasal challenges. We
have evaluated the effect of IT in allergic rhinitis by different methods. Nasal 
IT decreased mean symptoms and pharmacological scores as well as in seasonal as
in perennial rhinitis. The same decrease has been observed after oromucosal IT.
The effect of IT in allergic inflammation has been confirmed by a decrease in the
level of soluble adhesion molecule sVCAM-1 which is related to eosinophilic
inflammation but not statistically for sICAM-1. We have also evaluated the
immunoblotting pattern or specific IgE after oromucosal IT for house dust mites. 
For D. pteronyssinus in 4 patients the bands intensity decreased and in 3
patients the bands decreased and in 10 disappeared. IT decreases tryptase and ECP
in nasal lavage after sequential nasal challenges. Therefore IT decreases
clinical scores, inflammation markers, specific IgE immunoblotting bands and
response to allergen challenge. These different results confirm his efficacy and 
usefulness in allergic rhinitis.

Publication Types: 
    Review

PMID: 11763723 [PubMed - indexed for MEDLINE]

1296: JAMA. 2001 Dec 19;286(23):2956-67.

Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized
controlled trial.

Casale TB, Condemi J, LaForce C, Nayak A, Rowe M, Watrous M, McAlary M,
Fowler-Taylor A, Racine A, Gupta N, Fick R, Della Cioppa G; Omalizumab Seasonal
Allergic Rhinitis Trail Group.

Department of Medicine, Creighton University, Omaha, NE, USA.
tbcasale@creighton.edu

CONTEXT: Seasonal allergic rhinitis is a common IgE-mediated disorder that
produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE
antibody (omalizumab) forms complexes with free IgE, blocking its interaction
with mast cells and basophils and lowering free IgE levels in the circulation.
OBJECTIVE: To assess the efficacy and safety of omalizumab for prophylaxis of
symptoms in patients with seasonal allergic rhinitis. DESIGN: Randomized,
double-blind, dose-ranging, placebo-controlled trial conducted from July 25
through November 21, 1997. SETTING: Twenty-five outpatient centers throughout the
United States. PATIENTS: Five hundred thirty-six patients aged 12 to 75 years
with at least a 2-year history of moderate to severe ragweed-induced seasonal
allergic rhinitis and a baseline IgE level between 30 and 700 IU/mL.
INTERVENTIONS: Patients were randomly assigned to receive omalizumab, 50 mg (n = 
137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously 
just prior to ragweed season and repeated during the pollen season every 3 weeks 
in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and
every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total
treatments). MAIN OUTCOME MEASURES: Self-assessed daily nasal symptom severity
scores (range, 0-3), rescue antihistamine use, and rhinitis-specific quality of
life during the 12 weeks from the start of treatment. RESULTS: Nasal symptom
severity scores were significantly lower in patients who received 300 mg of
omalizumab than in those who received placebo (least squares means, 0.75 vs 0.98,
respectively; P =.002). A significant association was observed between IgE
reduction and nasal symptoms and rescue antihistamine use. Rhinitis-specific
quality of life scores were consistently better in patients who received 300 mg
of omalizumab than in those who received lower dosages or placebo and did not
decline during peak season. The frequency of adverse events was not significantly
different among the omalizumab and placebo groups. CONCLUSION: Omalizumab
decreased serum free IgE levels and provided clinical benefit in a dose-dependent
fashion in patients with seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11743836 [PubMed - indexed for MEDLINE]

1297: Arch Intern Med. 2001 Nov 26;161(21):2581-7.

Superiority of an intranasal corticosteroid compared with an oral antihistamine
in the as-needed treatment of seasonal allergic rhinitis.

Kaszuba SM, Baroody FM, deTineo M, Haney L, Blair C, Naclerio RM.

Section of Otolaryngology-Head and Neck Surgery, University of Chicago, 5841 S
Maryland Ave, Mail Code 1035, Chicago, IL 60637, USA.

BACKGROUND: The daily use of either intranasal corticosteroids or histamine(1)
(H(1)) receptor antagonists has proved to be efficacious in the treatment of
seasonal allergic rhinitis. Most patients, however, use these medications as
needed. Our objective was to compare the effectiveness of as-needed use of H(1)
receptor antagonists with that of intranasal corticosteroids in the treatment of 
seasonal allergic rhinitis. METHODS: We performed a randomized, open-label,
parallel-group study comparing the as-needed use of an H(1) receptor antagonist
(loratadine) with that of an intranasal corticosteroid (fluticasone propionate)
in the management of fall seasonal allergic rhinitis in the fall of 1999.
Subjects kept a diary of their daily symptoms and were examined at enrollment
into the study and biweekly for 4 weeks during treatment. Outcome measures were
the Rhinoconjunctivitis Quality of Life Questionnaire score, daily symptom diary 
scores, and the number of eosinophils and the levels of eosinophilic cationic
protein in nasal lavage samples. RESULTS: Patients in the fluticasone-treated
group reported significantly better scores in the activity, sleep, practical,
nasal, and overall domains (P<.05) of the Rhinoconjunctivitis Quality of Life
Questionnaire. The median total symptom score in the fluticasone-treated group
was significantly lower than that in the loratadine-treated group (4.0 vs 7.0;
P<.01). After treatment, the number of eosinophils was significantly smaller in
the fluticasone-treated group compared with the loratadine-treated group (P
=.001). Eosinophilic cationic protein levels followed the same pattern, with a
significant correlation between the levels of eosinophilic cationic protein and
the number of eosinophils (r(s) = 0.70, P<.01). CONCLUSION: As-needed intranasal 
corticosteroids reduce allergic inflammation and are more effective than
as-needed H(1) receptor antagonists in the treatment of seasonal allergic
rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11718589 [PubMed - indexed for MEDLINE]

1298: Eur J Immunol. 2001 Dec;31(12):3422-31.

Persistent IgE synthesis in the nasal mucosa of hay fever patients.

Smurthwaite L, Walker SN, Wilson DR, Birch DS, Merrett TG, Durham SR, Gould HJ.

The Randall Centre, King's College London, London, UK.

The location of IgE synthesis has been a longstanding controversy, with previous 
evidence favoring either the mucosa or lymphoid tissue in the region of allergen 
entry. The evidence for IgE synthesis in mucosal tissues has always been
circumstantial. We have developed a novel explant culture system, using ELISA and
radioactive amino acid incorporation, to measure de novo IgE protein synthesis in
the nasal mucosa of hay fever patients. Surprisingly, IgE synthesis continues
between seasons in the explants from grass pollen-sensitive patients and a higher
proportion of this IgE compared to serum IgE is allergen specific. Persistent IgE
synthesis may ensure the expression of immediate hypersensitivity in the mucosa
and promote rapid amplification of the allergic response in the local lymphoid
tissue on allergen provocation. Our work demonstrates definitively for the first 
time that the local mucosa is a site of ongoing IgE synthesis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11745361 [PubMed - indexed for MEDLINE]

1299: Pharmacol Res. 2001 Dec;44(6):461-6.

Second generation antihistamines in the treatment of seasonal allergic rhinitis
due to Parietaria and cypress pollen.

Macchia L, Caiaffa MF, Di Paola R, De Michele G, Bariletto G, Iudice A, Tursi A.

Department of Allergology and Clinical Immunology, University of Bari, 70124
Bari, Italy. g.macchia@area.ba.cnr.it

Second generation antihistamines have been employed in the treatment of seasonal 
allergic rhinitis for many years. However, their effects on two distinctive
Mediterranean allergic conditions, viz. Parietaria pollinosis and cypress
pollinosis, have been scarcely investigated, so far. A comparative efficacy and
side effect trial of astemizole and terfenadine in the treatment of seasonal
allergic rhinitis due to either Parietaria or cypress pollen was carried out in
27 adult patients, according to a double-blind, double-dummy parallel-group
design. Airborne pollen monitoring allowed comparison of symptom scores with
pollen counts. Seven patients (26%) withdrew, due to poor symptom control. In
contrast, in a subset of 15 patients who completed the trial, treatment led to a 
substantial and statistically significant decline in symptom severity in both the
astemizole and the terfenadine study group. However, no statistically significant
inter-group differences could be detected. Copyright 2001 Academic Press.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11735351 [PubMed - indexed for MEDLINE]

1300: Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1829-34.

Does living on a farm during childhood protect against asthma, allergic rhinitis,
and atopy in adulthood?

Leynaert B, Neukirch C, Jarvis D, Chinn S, Burney P, Neukirch F; European
Community Respiratory Health Survey.

INSERM Unité 408, Paris, France. leynaernt@bichat.inserm.fr

Recent studies of children suggest that factors encountered in a farm environment
might protect against the development of allergy. However, it remains uncertain
whether living on a farm in childhood is associated with a decreased risk of
atopic diseases in adulthood. We analyzed data from 6,251 randomly selected
adults 20 to 44 yr of age participating in the European Community Respiratory
Health Survey (ECRHS). Subjects answered a detailed questionnaire and underwent
specific IgE measurements to five allergens. After adjustment for potential
confounders, including pet exposure in childhood, number of siblings, severe
respiratory infection in childhood, and parental history of allergy, living on a 
farm in childhood was associated with a reduced risk of atopic sensitization in
adulthood (OR = 0.76, CI 95% = 0.60-0.97). Compared with other adults, those who 
had lived on a farm as a child were less frequently sensitized to cat (OR = 0.63,
CI 95% = 0.41-0.96) and to Timothy grass (OR = 0.68, CI 95% = 0.50-0.94), and
were at lower risk of having nasal symptoms in the presence of pollen (OR = 0.80,
CI 95% = 0.64-1.02). The protective effect of farming environment in childhood
observed in this population-based sample of young adults provides evidence in
favor of the hypothesis that environmental factors encountered in childhood may
have a lifelong protective effect against the development of allergy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11734431 [PubMed - indexed for MEDLINE]

1301: Am J Respir Crit Care Med. 2001 Oct 15;164(8 Pt 2):S18-21.

Anti-immunoglobulin E (omalizumab) therapy in seasonal allergic rhinitis.

Casale TB.

Department of Medicine, Creighton University School of Medicine, Omaha, Nebraska 
68131, USA. tbcasale@creighton.edu

Anti-immunoglobulin E (anti-IgE) (omalizumab), a humanized monoclonal anti-IgE
antibody that binds to circulating IgE, has been studied in several large
double-blind, randomized, placebo-controlled clinical trials to determine its
pharmacokinetic characteristics, efficacy, and safety in ragweed- or birch
pollen-induced seasonal allergic rhinitis (SAR). The consequences of
readministering omalizulab after a lapse of time have also been studied. These
studies have confirmed that serum-free IgE declines in a dose-related manner with
such treatment and that omalizumab-induced declines in IgE correlate with symptom
improvement. Whether omalizumab is administered intravenously or subcutaneously, 
its pharmacokinetics do not differ. A Phase II dose-ranging study demonstrated
that the optimum efficacious dose of omalizumab for the treatment of seasonal
allergic rhinitis is 300 mg administered subcutaneously. The dosing frequency, in
terms of whether the antibody is administered every 3 or 4 wk, is based on the
patient's baseline IgE level. With adequate dosing, nasal and ocular symptoms are
significantly reduced, and quality of life is significantly improved. Omalizumab 
is safe and well tolerated and can be safely readministered in subsequent pollen 
seasons.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11704613 [PubMed - indexed for MEDLINE]

1302: Allergy. 2001 Nov;56(11):1077-80.

Desloratadine reduces nasal congestion in patients with intermittent allergic
rhinitis.

Nayak AS, Schenkel E.

School of Medicine, University of Illinois, Peoria, IL, USA.

Nasal congestion is among the most bothersome of the symptoms of intermittent
allergic rhinitis (IAR). Decongestants such as pseudoephedrine are often
accompanied by adverse effects and should be avoided by patients with
hypertension, arrhythmia, and other medical conditions. Most of the currently
available antihistamines are ineffective for nasal congestion. Oral
desloratadine, a new, potent H1-receptor antagonist, was examined for its ability
to relieve nasal congestion/stuffiness in 346 patients (172 in the desloratadine 
group and 174 in the placebo group) with IAR. Desloratadine, administered once
daily at a dose of 5 mg, demonstrated significant improvement in nasal
congestion/stuffiness at all time points assessed in the study. This benefit was 
observed as early as the first patient evaluation on day 2 and continued
throughout the 2 weeks of the study. Desloratadine is a new treatment option for 
patients with IAR and nasal congestion.

Publication Types: 
    Clinical Trial
    Comparative Study
    Evaluation Studies
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11703222 [PubMed - indexed for MEDLINE]

1303: Hum Genet. 2001 Sep;109(3):262-6.

Association between nasal allergy and a coding variant of the Fc epsilon RI beta 
gene Glu237Gly in a Japanese population.

Nagata H, Mutoh H, Kumahara K, Arimoto Y, Tomemori T, Sakurai D, Arase K, Ohno K,
Yamakoshi T, Nakano K, Okawa T, Numata T, Konno A.

Department of Otorhinolaryngology, Chiba University School of Medicine, 1-8-1
Inohana, Chuoh-ku, Chiba 260-8670, Japan. nagatah@ho.chiba-u.ac.jp

The gene for the beta-chain of the high-affinity receptor for IgE (Fc epsilon RI 
beta) has been proposed as a candidate gene for atopy. A coding variant Glu237Gly
has been studied in various populations with asthma and atopy, and the results
were controversial for association of the variant with atopy/asthma. Because
nasal allergy is a more common atopic disease and shows less remission than
asthma, we analyzed whether the Glu237Gly variant is correlated with nasal
allergy. The study enrolled 233 patients with nasal allergy and 100 control
subjects. Further, three subgroups were selected: patients with perennial nasal
allergy (n=149), Japanese cedar pollinosis (n=189), and allergy to multiple
allergens (n=45). The allele frequency of Gly237 in the controls and patients was
0.14 and 0.20, and the frequency of Gly237-positive subjects was 0.23 and 0.356, 
respectively. There was a significant association between Gly237-positivity and
nasal allergy, perennial nasal allergy, Japanese cedar pollinosis, and allergy to
multiple allergens. Among all 333 subjects we observed a significant relationship
between Gly237 and elevated levels of serum total IgE (>250 IU/ml) and very high 
IgE (>1000 IU/ml). Among patients positive for a specific IgE, Gly237 was
significantly associated with high IgE for house dust, mite, and Japanese cedar
pollen. These results suggest that the Glu237Gly variant of the Fc epsilon RI
beta gene is involved in the development of nasal allergy through the process for
the production of both specific and nonspecific IgE antibodies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11702205 [PubMed - indexed for MEDLINE]

1304: J Allergy Clin Immunol. 2001 Nov;108(5):703-8.

Intranasal heparin reduces eosinophil recruitment after nasal allergen challenge 
in patients with allergic rhinitis.

Vancheri C, Mastruzzo C, Armato F, Tomaselli V, Magrì S, Pistorio MP, LaMicela M,
D'amico L, Crimi N.

Institute of Respiratory Diseases, University of Catania, Italy.

BACKGROUND: Recently, several studies have shown that heparin possesses various
anti-inflammatory and antiallergic properties. It has been proposed that heparin 
might play an important role in limiting the inflammatory events associated with 
asthma and allergic rhinitis by neutralizing inflammatory mediators, such as
eosinophil cationic protein and major basic protein, and by limiting eosinophil
recruitment. OBJECTIVE: To test the hypothesis that heparin can limit the extent 
and magnitude of eosinophilic inflammation, we examined the effect of inhaled
intranasal heparin on nasal response to allergen challenge in 10 patients with
allergic rhinitis. METHODS: The capacity of heparin to reduce nasal response was 
studied by evaluating symptom score, eosinophil cationic protein concentration,
and eosinophil counts in nasal lavage fluids 10, 60, and 360 minutes after
allergen challenge. RESULTS: Pretreatment with intranasal heparin produced a
significant reduction in symptom score 10 minutes after allergen challenge and
reduced the eosinophil influx at each time point after antigen challenge,
statistical significance being reached 60 and 360 minutes after allergen
challenge. Similarly, the amount of eosinophil cationic protein in the nasal wash
was reduced at each time point; this reached statistical significance 360 minutes
after allergic challenge. CONCLUSION: Heparin was shown to provide protection
with respect to nasal allergen challenge. The mechanism by which heparin produces
its protective activity seems to be related to the neutralization of eosinophil
cationic protein as well as to the reduction of eosinophil recruitment.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11692092 [PubMed - indexed for MEDLINE]

1305: Ann Allergy Asthma Immunol. 2001 Oct;87(4):350-5.

The risk of adenoid hypertrophy in children with allergic rhinitis.

Huang SW, Giannoni C.

Department of Pediatrics, University of Florida, Gainesville, USA.
huangsw@peds.ufl.edu

BACKGROUND: Adenoid hypertrophy (AH) may cause significant morbidity in children 
but its relationship to allergic rhinitis (AR) has not been studied. OBJECTIVE:
To determine the risk factor of AH in patients with AR. METHODS: We studied 315
children (ages 1 to 18 years) who had AH and AR. We compared them with 315
age-matched controls who had AR alone. To identify risk factors, they were
divided into four groups according to age and clinical parameters, including the 
prevalence of otitis media, sinusitis, lower respiratory infection, exposure to
smoking, sleep disorders, use of antihistamine/decongestants, and results of
allergy skin testing. RESULTS: The prevalence of upper or lower respiratory
infections was higher in the group with AR and AH, but not in all age groups. A
high prevalence of exposure to smoking and skin test reactivity against house
dust mites were found in both groups. However, the prevalence of positive
reactivity to molds was significantly higher in the group with AH and AR (P
ranged from 0.013 to <0.0001 and the relative risk ranged from 1.609 to 2.375).
Further, the risk of AH was positively correlated with number of skin test
reactivity to mold spores (P ranged from 0.0035 to 0.0001). Positive skin test
reactivity to animal danders or seasonal allergens failed to predict the risk of 
AH. CONCLUSIONS: Sensitivity to mold allergens is an important risk factor for AH
in children with AR; therefore, early prevention of exposure to molds may help
reduce occurrence of AH.

PMID: 11686429 [PubMed - indexed for MEDLINE]

1306: Ann Allergy Asthma Immunol. 2001 Oct;87(4):344-9.

Effects of topical corticosteroid and combined mediator blockade on domiciliary
and laboratory measurements of nasal function in seasonal allergic rhinitis.

Wilson AM, Sims EJ, Orr LC, Coutie WJ, White PS, Gardiner Q, Lipworth BJ.

Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital &
Medical School, University of Dundee, Scotland, UK.

BACKGROUND: Both domiciliary and laboratory measures of nasal function have been 
used to evaluate treatment response in allergic airways disease; however, these
measures have not been compared. OBJECTIVE: To determine the relationship of
domiciliary measures (daily symptoms, peak inspiratory nasal flow, and nasal oral
index) and laboratory measures (rhinomanometry, acoustic rhinometry) in assessing
treatment response with topical steroids and specific inflammatory mediator
blockage. METHODS: Twenty-one patients with seasonal allergic rhinitis and asthma
were enrolled into a single-blind, placebo-controlled, crossover study comparing 
2 weeks of 1) 400 microg inhaled plus 200 microg intranasal budesonide once daily
and 2) 10 mg montelukast plus 10 mg cetirizine once daily. Before each treatment,
patients received 7 to 10 days of placebo period. Laboratory measurements were
made of nasal resistance by posterior rhinomanometry, and nasal volume between 0 
and 5 cm by acoustic rhinometry after both placebo and active treatment periods. 
Daily domiciliary recordings were made of allergic rhinitis nasal symptoms scores
and peak nasal and oral inspiratory flow rate (enabling the calculation of a
nasal/oral index) throughout the study. RESULTS: There were significant (P <
0.05) improvements for all allergic rhinitis symptoms with both therapies, after 
factoring for pollen count. Spearman's rank correlation for comparison among
nasal symptoms and the objective responses were: nasal inspiratory flow rate (R =
-0.50, P = 0.02); nasal/oral index (R = -0.55 P = 0.01); rhinomanometry (R =
0.24, P = 0.30); and acoustic rhinometry (R = -0.21, P = 0.36). CONCLUSIONS: Both
treatments were effective in managing allergic rhinitis symptoms, and patients'
symptoms were more closely associated with domiciliary measurements of nasal flow
than laboratory measurements of nasal function.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11686428 [PubMed - indexed for MEDLINE]

1307: Ann Allergy Asthma Immunol. 2001 Oct;87(4):311-8.

Air pollutants enhance rhinoconjunctivitis symptoms in pollen-allergic
individuals.

Riediker M, Monn C, Koller T, Stahel WA, Wüthrich B.

Institute for Hygiene and Applied Physiology, Environmental Hygiene Section,
Swiss Federal Institute of Technology, Zurich. michael.riediker@alumni.ethz.ch

BACKGROUND: Little is know about the relation of airborne pollen allergens to
nasal and ocular symptoms in combination with air pollutants. OBJECTIVE: The
hypothesis was that air pollutants exacerbate allergic symptoms of the nose and
eyes during the pollen season. In addition, the use of allergen measurements
instead of pollen counts should be tested. METHODS: Fifteen pollen-allergic,
nonsmoking subjects with weak reactivity of the airways recorded
rhinoconjunctival symptoms and medication every morning and evening throughout
the pollen season. Symptoms were compared with air pollutants (nitrogen oxide
[NOx], particulate matter smaller than 10 microm, and ozone) and birch and grass 
pollen counts or, alternatively, to airborne birch and grass allergens determined
using ELISA-techniques. A multiple linear regression model was used which
controlled for autocorrelation of the residuals of the time series
(Cochrane-Orcutt approach). This model was applied to each subject individually, 
followed by calculations of summary scores for the group. RESULTS: Air pollution 
levels were moderate, often meeting air quality standards. Effect estimates
(increase of score with 10-fold increase of concentration) were NOx = 1.06, P <
0.01; ozone = 1.59, P < 0.01; and pollen = 0.48, P < 0.001. Using allergen
concentrations instead of pollen counts resulted in similar effect estimates.
Using particulate matter smaller than 10 microm instead of NOx gave comparable
but less consistent results. CONCLUSIONS: Symptoms were related to moderate
levels of pollutants, suggesting that rhinoconjunctival tissue is very sensitive 
to irritant stimuli during an ongoing allergic inflammation, and that
susceptibility toward allergens might be increased in areas with increased levels
of air pollutants. Allergen measurements seem equally usable as pollen counts to 
investigate rhinoconjunctivitis.

Publication Types: 
    Comparative Study

PMID: 11686424 [PubMed - indexed for MEDLINE]

1308: Int Arch Allergy Immunol. 2001 Sep;126(1):91-6.

Melatonin and beta-endorphin changes in children sensitized to olive and grass
pollen after treatment with specific immunotherapy.

Girón-Caro F, Muñoz-Hoyos A, Ruiz-Cosano C, Bonillo-Perales A, Molina-Carballo A,
Escames G, Macías M, Acuña-Castroviejo D.

Departamento de Pediatría, Hospital Universitario San Cecilio, Almería, España.

BACKGROUND: Specific immunotherapy for respiratory allergy, a seasonal disease,
significantly reduces the inflammatory process, attenuating the clinical
symptoms. The mechanism for the clinical beneficial effect of immunotherapy has
not yet been clarified. Melatonin shows a circadian and seasonal variation and
together with the endogenous opioid system plays an immunomodulatory role acting 
on both specific and nonspecific immunity responses. Thus, the possibility that
immunotherapy involved changes in the melatonin-opioid system was investigated.
METHODS: Thirty-five children aged 3-15 years with rhinitis and asthma due to
olive + grass pollen sensitization were studied. The patients were treated with
depot extracts containing the identified allergens with increasing doses from 1
to 1,000 IU/ml during 3 months. Melatonin, beta-endorphin, total and specific IgE
and IgG4 were determined before and after treatment. RESULTS: All children showed
a significant improvement of their symptoms at the end of the treatment,
coinciding with a significant drop of both melatonin and beta-endorphin levels.
Total IgE decreased in most of the cases although the mean values did not show
significant changes. Specific IgE and IgG4 were also unchanged. A significant
correlation between melatonin and beta-endorphin and between beta-endorphin and
IgG4 was found before immunotherapy, and these correlations disappeared when the 
treatment was finished. CONCLUSIONS: The decrease in the levels of melatonin and 
beta-endorphin suggests the disappearance of their stimulating influence on the
immune system. Thus, hyposensitization after immunotherapy may involve, at least 
in part, the inhibition of the immunoenhancing properties of the melatonin-opioid
system. Copyright 2001 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11641610 [PubMed - indexed for MEDLINE]

1309: Inflamm Res. 2001 Sep;50(9):474-82.

Pharmacological characterization of the leukocyte kinetics after intranasal
antigen challenge in a guinea pig model of allergic rhinitis.

Yamasaki ML, Sasaki K, Mizutani N, Nabe T, Sakura Y, Matsumoto T, Ashida Y, Kohno
S.

Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Osaka, Japan. 
Yamasaki_Masashi@takeda.co.jp

OBJECTIVE AND DESIGN: We characterized the leukocyte kinetics after antigen
challenge, and investigated the effects of the thromboxane (TX) A2 antagonist
seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the
antihistaminic drug terfenadine and the glucocorticoid dexamethasone on this
leukocyte response in a guinea pig model of allergic rhinitis. SUBJECTS: Male
Hartley guinea pigs were used. TREATMENT: Intranasally sensitized guinea pigs
were challenged once every week for 15 weeks by inhalation of Japanese cedar
pollen as the antigen. Dexamethasone and other agents were administered orally 3 
and 1 h, respectively, before the 15th challenge. METHODS: The time-related
changes in the numbers of differential leukocytes in nasal cavity lavage fluid
(NCLF) and in peripheral blood after pollen inhalation challenge were
investigated. The effects of the drugs on the antigen-induced changes in the
leukocyte counts were evaluated. In addition, histopathological examination of
the nasal mucosa was also performed 5 h after the challenge. RESULTS: There was a
marked increase in the number of leukocytes in NCLF, especially of eosinophils,
which peaked at 5 h, after antigen challenge in this model. This response was
also accompanied by the peripheral blood eosinophilia and neutrophilia.
Seratrodast (30 mg/kg), pranlukast (30 mg/kg) and dexamethasone (10 mg/kg)
inhibited the eosinophilia in all of the blood, the nasal mucosa and NCLF seen 5 
h after the antigen challenge. Terfenadine (10 mg/kg) had no apparent effect on
the blood and the mucosal eosinophilia, although it tended to suppress the
eosinophil accumulation in NCLF. CONCLUSIONS: These results suggest that the
present model is useful for analyzing the mechanisms of antigen-induced
eosinophilic inflammation in allergic rhinitis and that both TXA2 and p-LTs, but 
not histamine, contribute to the antigen-induced eosinophilia in this model of
allergic rhinitis.

PMID: 11603853 [PubMed - indexed for MEDLINE]

1310: Inflamm Res. 2001 Sep;50(9):466-73.

Involvement of thromboxane A2 and peptide leukotrienes in early and late phase
nasal blockage in a guinea pig model of allergic rhinitis.

Yamasaki M, Mizutani N, Sasaki K, Nabe T, Matsumoto T, Ashida Y, Kohno S.

Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Osaka, Japan. 
Yamasaki_Masashi@takeda.co.jp

OBJECTIVE AND DESIGN: We investigated the effects of the thromboxane (TX) A2
antagonist seratrodast, the peptide leukotriene (p-LT) antagonist pranlukast, the
antihistaminic drug terfenadine and the glucocorticoid dexamethasone on
antigen-induced sneezing, biphasic nasal blockage and nasal hyperresponsiveness
to histamine using a guinea pig model of allergic rhinitis. SUBJECTS: Male
Hartley guinea pigs were used. TREATMENT: Intranasally sensitized guinea pigs
were challenged once every week for 13 weeks by inhalation of Japanese cedar
pollen as the antigen. Dexamethasone and other agents were administered orally 3 
and 1 h, respectively, before the 4th, 6th and 13th challenge. METHODS: Sneezing 
frequency and the change in specific airway resistance (sRaw) were measured at
these challenges. Two days after the 13th challenge, nasal responsiveness to
histamine was evaluated by measuring sRaw after intranasal instillation of
increasing doses of histamine. Moreover, the levels of TXB2, p-LTs and histamine 
were estimated in nasal cavity lavage fluid (NCLF) collected at the 13th
challenge. RESULTS: Only terfenadine (10 mg/kg) significantly inhibited sneezing 
at any challenge time. Seratrodast (3 and 10 mg/ kg), pranlukast (30 mg/kg) and
dexamethasone (10 mg/kg), but not terfenadine, suppressed both the early and late
phase elevation of sRaw (biphasic nasal blockage), although the degree of
inhibition on the early phase response varied with the challenge time. In
contrast, the development of nasal hyperresponsiveness to histamine was inhibited
by only dexamethasone. Furthermore, biphasic increases in TXB2, p-LTs and
histamine in NCLF were observed after the challenge in sensitized animals.
CONCLUSIONS: These results suggest that TXA2 and p-LTs, but not histamine, play
important roles in both the early and the late phase nasal blockage in this model
of allergic rhinitis.

PMID: 11603852 [PubMed - indexed for MEDLINE]

1311: Acta Otolaryngol. 2000 Mar;120(2):323-6.

Assessment of smell and taste in patients with allergic rhinitis.

Rydzewski B, Pruszewicz A, Sulkowski WJ.

ENT Department Raszejo Municipal Hospital, Poznań, Poland.

We examined the senses of smell and taste in 240 patients with verified
hypersensitivity reactions of the respiratory tract. Olfactometry was performed
according to Elsberg and Levy's method and followed by electrogustometry. The
examinations revealed that the incidence of smell and taste disorders in patients
with allergic rhinitis is 21.4% and 31.2%, respectively. No significant
relationships between smell and taste dysfunction were found. We evaluated
statistically positive correlations between the olfactory and gustatory
thresholds compared with 78 qualitative and quantitative factors assessed in the 
study. There was a statistically significant relationship between the olfactory
thresholds and levels of eosinophils in blood and in nasal discharge. acid
reaction of the nasal mucosa, coexisting nasal polyps and X-ray changes in the
ethmoid sinuses. There was a positive influence of pharmacotherapy as well as
specific desensitization and surgery on the impairment of the sense of smell in
allergic rhinitis.

PMID: 11603799 [PubMed - indexed for MEDLINE]

1312: J Allergy Clin Immunol. 2001 Oct;108(4):530-6.

The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of
allergic rhinitis.

Schmidt BM, Kusma M, Feuring M, Timmer WE, Neuhäuser M, Bethke T, Stuck BA,
Hörmann K, Wehling M.

Institute of Clinical Pharmacology, Mannheim University Hospital,
Ruprecht-Karls-University Heidelberg, Mannheim, Germany.

BACKGROUND: The beneficial effects of phosphodiesterase 4 (PDE4) inhibitors in
allergic asthma have been shown in previous preclinical and clinical studies.
Because allergic rhinitis and asthma share several epidemiologic and
pathophysiologic factors, PDE4 inhibitors might also be effective in allergic
rhinitis. OBJECTIVE: The main objective of this study was to investigate the
efficacy of oral roflumilast (500 microg/day) in allergic rhinitis. METHODS: In a
randomized, placebo-controlled, double-blinded, crossover study, 25 subjects (16 
male, 9 female; median age, 28 years) with histories of allergic rhinitis but
asymptomatic at screening received roflumilast (500 microg once daily) and
placebo for 9 days each with a washout period of at least 14 days in between
treatment periods. In each of the treatment periods, controlled intranasal
allergen provocation with pollen extracts was performed daily beginning the third
day of treatment, each time approximately 2 hours after study drug
administration. Five and 30 minutes after each allergen provocation, rhinal
airflow was measured by means of anterior rhinomanometry and the subjective
symptoms obstruction, itching, and rhinorrhea were assessed by means of a
standardized visual analog scale. RESULTS: Rhinal airflow improved almost
consistently during the 9 days of roflumilast treatment, and it was significantly
higher at study day 9 on roflumilast in comparison with placebo, a result also
found for itching and rhinorrhea. With respect to the subjective obstruction
score, a significant difference in comparison with placebo could be demonstrated 
within 4 days. CONCLUSION: This study shows that a PDE4 inhibitor, roflumilast,
effectively controls symptoms of allergic rhinitis. Thus PDE4 inhibitors might be
a future treatment option not only in allergic asthma but also in allergic
rhinitis or the combination of the 2 diseases.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11590377 [PubMed - indexed for MEDLINE]

1313: Drugs. 2001;61(11):1563-79.

Intranasal corticosteroids for allergic rhinitis: superior relief?

Nielsen LP, Mygind N, Dahl R.

Department of Clinical Pharmacology, University of Aarhus, Denmark.
lpn@dadlnet.dk

Whether first-line pharmacological treatment of allergic rhinitis should be
antihistamines or intranasal corticosteroids has been discussed for several
years. First-generation antihistamines are rarely used in the treatment of
allergic rhinitis, mainly because of sedative and anticholinergic adverse
effects. On the basis of clinical evidence of efficacy, no second-generation
antihistamine seems preferable to another. Similarly, comparisons of topical and 
oral antihistamines have been unable to demonstrate superior efficacy for one
method of administration over the other. Current data documents no striking
differences in efficacy and safety parameters between intranasal corticosteroids.
When the efficacy of antihistamines and intranasal corticosteroids are compared
in patients with allergic rhinitis, present data favours intranasal
corticosteroids. Interestingly, data do not show antihistamines as superior for
the treatment of conjunctivitis. Safety data from comparative studies in patients
with allergic rhinitis do not indicate differences between antihistamines and
intranasal corticosteroids. Combining antihistamines and intranasal
corticosteroids in the treatment of allergic rhinitis does not provide any
additional effect to intranasal corticosteroids alone. On the basis of current
data, intranasal corticosteroids seem to offer superior relief in allergic
rhinitis than antihistamines.

Publication Types: 
    Comparative Study
    Review

PMID: 11577794 [PubMed - indexed for MEDLINE]

1314: Allergy. 2001 Oct;56(10):957-63.

Generic or disease-specific quality of life scales to characterize health status 
in allergic rhinitis?

Kremer B, Klimek L, Bullinger M, Mösges R.

Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty of the 
University of Maastricht, The Netherlands.

BACKGROUND: In patients with allergic rhinitis (AR), various instruments have
been validated for the measurement of quality of life (QOL), which may be greatly
reduced. However, it is not clear which QOL instruments should be used for the
different types of AR and whether they are sensitive to treatment. METHODS: The
QOL of patients suffering from symptomatic seasonal AR (sSAR) (before and during 
treatment with a topical or systemic antihistamine), symptomatic perennial AR
(sPAR), and asymptomatic seasonal AR (aSAR) was determined with the
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) as disease specific and 
with the Munich Life Dimension List (MLDL) and the Visual Analogue Scale for
Quality of Life (VAS-QOL) as generic QOL instruments. RESULTS: The different
forms of AR were associated with typical QOL patterns. In sSAR, we found severe
limitation of the global QOL, reduced global life satisfaction, high ranking of
practical problems, high limitation of activity, and a high degree of disturbance
in all subscales of the RQLQ. In sPAR, there were moderate limitation of the
global QOL, normal global life satisfaction, high ranking of practical problems, 
moderate limitation of activity, and a high degree of disturbance by common
symptoms. Under antihistamine treatment, both systemic and nasal, a significant
improvement of QOL parameters was found, reaching the levels of patients with
aSAR after 2 weeks. CONCLUSION: QOL instruments can distinguish the impairment
resulting from sSAR from that of sPAR and are sensitive to treatment with topical
and systemic antihistamines. However, as the RQLQ was not designed to measure the
short-term variations of disease status that appear in SAR, it may not
demonstrate the rapid improvement of QOL under antihistamine treatment.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 11576074 [PubMed - indexed for MEDLINE]

1315: Allergy Asthma Proc. 2001 Jul-Aug;22(4):239-47.

Variations of pollen and mold concentrations in 1998 during the strong El Niño
event of 1997-1998 and their impact on clinical exacerbations of allergic
rhinitis, asthma, and sinusitis.

Freye HB, King J, Litwin CM.

Department of Pediatrics, Brown University Medical School, Rhode Island, USA.

Previous studies of pollen and mold dispersal have not correlated meteorological 
phenomena with clinical exacerbations of asthma, allergic rhinitis, and
sinusitis. We utilized the resources of 11 New England Society of Allergy (NESA) 
pollen collectors, a certified palynologist, over a dozen weather stations for
meteorological data, and 10 emergency rooms to explore the effects of the strong 
"El Niño" of 1997-1998 on our region during the 1998 pollen season. There was a
marked increase in the number of clinical exacerbations of asthma, allergic
rhinitis, and sinusitis in April, May, and June of 1998. Several emergency rooms 
reported a greater increase in visits for sinusitis as compared to asthma. In
addition, maximum mold counts occurred two to three months earlier than in 1997. 
Maximum pollen counts were also higher than in 1997, and occurred two to four
weeks earlier for most tree pollen types.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11552675 [PubMed - indexed for MEDLINE]

1316: Allergy. 2001 Sep;56(9):871-7.

Effect of seasonal allergen exposure on mucosal IL-16 and CD4+ cells in patients 
with allergic rhinitis.

Pullerits T, Lindén A, Malmhäll C, Lötvall J.

Lung Pharmacology Group, Institute of Heart and Lung Diseases, Department of
Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden.

BACKGROUND: CD4+ T cells constitute a major source of cytokines in allergic
diseases such as allergic rhinitis. Interleukin (IL)-16 selectively recruits CD4+
cells. METHODS: We evaluated the effect of natural allergen exposure during a
grass-pollen season on IL-16 expression and number of CD4+ cells in nasal mucosa.
Patients with allergic rhinitis (n=16) were treated with either a nasal
glucocorticoid beclomethasone (BDP; 400 microg/day) or placebo, and gave nasal
biopsies prior to and during the grass-pollen season. The evaluated markers in
allergic rhinitis patients were also compared to those in healthy control
subjects (n=5). RESULTS: Prior to the pollen season, the expression of IL-16, but
not the number of CD4+ cells, was significantly higher in patients with allergic 
rhinitis than in healthy control subjects. The grass-pollen season further
increased IL-16 expression and also increased the number of CD4+ cells in
placebo-treated, but not in BDP-treated, allergic rhinitis patients. The
pollen-season-induced change in IL-16 expression and in CD4+ cells was
significantly more pronounced in placebo- than in BDP-treated patients. There was
a significant correlation between the change in IL-16 expression and the number
of CD4+ cells. CONCLUSIONS: These data suggest that local upregulation of IL-16
expression contributes to the inflammation observed in seasonal allergic
rhinitis. Hypothetically, inhibition of IL-16 expression can be one of several
mechanisms by which nasal glucocorticoids achieve their anti-inflammatory effect 
in allergic rhinitis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11551252 [PubMed - indexed for MEDLINE]

1317: Clin Exp Allergy. 2001 Aug;31(8):1321-7.

Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical
glucocorticosteroid treatment.

Greiff L, Petersen H, Mattsson E, Andersson M, Erjefält JS, Linden M, Svensson C,
Persson CG.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital,
Lund, Sweden. lennart.greiff@onh.lu.se

BACKGROUND: Eotaxin is a chemokine that attracts and activates eosinophils. The
present study examines the occurrence of eotaxin in nasal mucosal surface liquids
in patients with seasonal allergic rhinitis without allergen exposure and during 
repeat allergen challenge with and without topical glucocorticosteroid treatment.
The number of subepithelial eosinophils and mucosal outputs of bulk plasma
(alpha2-macroglobulin) and eosinophil cationic protein (ECP) are also examined.
METHODS: Twelve patients underwent daily allergen challenges for 6 days.
Separately, 14 patients, who were receiving budesonide and placebo in a parallel 
group design, also underwent allergen challenge for 6 days. Nasal biopsies were
obtained before and 24 h after the allergen challenge series, and lavages were
carried out before and 15 min after selected allergen challenges. RESULTS: At
baseline nasal lavage fluid levels of eotaxin correlated to levels of
alpha2-macroglobulin and ECP. After the first allergen challenge there was a
correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen
exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as
well as eosinophil numbers (P <0.01), but no correlation was found between
increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels
during repeat allergen challenge (P <0.05). CONCLUSIONS: Repeat allergen exposure
in allergic rhinitis is associated with increased mucosal output of eotaxin.
Topical budesonide attenuates this effect, suggesting the possibility that
inhibitory effects on mucosal eotaxin may contribute to anti-eosinophilic actions
of topical glucocorticosteroids.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11529904 [PubMed - indexed for MEDLINE]

1318: Am J Respir Crit Care Med. 2001 Aug 15;164(4):575-9.

The kinetics of allergen-induced eotaxin level in nasal lavage fluid: its key
role in eosinophil recruitment in nasal mucosa.

Terada N, Hamano N, Kim WJ, Hirai K, Nakajima T, Yamada H, Kawasaki H, Yamashita 
T, Kishi H, Nomura T, Numata T, Yoshie O, Konno A.

Department of Otorhinolaryngology, Chiba University School of Medicine, Chiba,
Japan. terada@med.m.chiba-u.ac.jp

Eotaxin (CCL11) is a potent eosinophil chemoattractant belonging to the C-C
chemokine. To evaluate the role of eotaxin in eosinophilic inflammation in nasal 
mucosa, we investigated the levels of eosinophil chemoattractants in nasal lavage
fluids obtained after antigen challenge, compared with eosinophil counts and
eosinophil protein X (EPX) levels. In subjects with allergic rhinitis, allergen
challenge led to parallel increases in eosinophil counts, levels of EPX, and
eotaxin concentrations in nasal lavage fluid. The levels of eotaxin in lavage
samples showed strong correlation with lavage levels of eosinophil counts and
EPX. Normal subjects had few, if any, eosinophils and EPX as well as the measured
parameters in their nasal lavage fluids before and after antigen challenge. In
our experiments of eosinophil endothelial transmigration (TEM) assay using the
nasal microvascular endothelial cells, eotaxin showed the most potent effect
among various eosinophil chemoattractants. In addition, treatment of eosinophils 
with anti-CCR-3 mAb significantly blocked eosinophil TEM induced by homogenate of
nasal mucosa. These results indicate that eotaxin has an important role in
eosinophil-dependent inflammation in nasal mucosa and suggest that blocking
eotaxin or CCR-3 might be useful for new therapeutic tools of allergic rhinitis.

PMID: 11520718 [PubMed - indexed for MEDLINE]

1319: BioDrugs. 2001;15(7):453-63.

Clinical prescribing of allergic rhinitis medication in the preschool and young
school-age child: what are the options?

Galant SP, Wilkinson R.

Department of Paediatric Allergy/Immunology, University of California, Irvine,
California, USA.

Allergic rhinitis (AR) is the most common chronic condition in children and is
estimated to affect up to 40% of all children. It is usually diagnosed by the age
of 6 years. The major impact in children is due to co-morbidity of sinusitis,
otitis media with effusion, and bronchial asthma. AR also has profound effects on
school absenteeism, performance and quality of life. Pharmacotherapy for AR
should be based on the severity and duration of signs and symptoms. For mild,
intermittent symptoms lasting a few hours to a few days, an oral
second-generation antihistamine should be used on an as-needed basis. This is
preferable to a less expensive first-generation antihistamine because of the
effect of the latter on sedation and cognition. Four second-generation
antihistamines are currently available for children under 12 years of age:
cetirizine, loratadine, fexofenadine and azelastine nasal spray; each has been
found to be well tolerated and effective. There are no clearcut advantages to
distinguish these antihistamines, although for children under 5 years of age,
only cetirizine and loratadine are approved. Other agents include
pseudoephedrine, an oral vasoconstrictor, for nasal congestion, and the
anticholinergic nasal spray ipratropium bromide for rhinorrhoea. Sodium
cromoglycate, a mast cell stabiliser nasal spray, may also be useful in this
population. For patients with more persistent, severe symptoms, intranasal
corticosteroids are indicated, although one might consider azelastine nasal
spray, which has anti- inflammatory activity in addition to its antihistamine
effect. With the exception of fluticasone propionate for children aged 4 years
and older, and mometasone furoate for those aged 3 years and older, the other
intranasal corticosteroids including beclomethasone dipropionate, triamcinolone, 
flunisolide and budesonide are approved for children aged 6 years and older. All 
are effective, so a major consideration would be cost and safety. For short term 
therapy of 1 to 2 months, the first-generation intranasal corticosteroids
(beclomethasone dipropionate, triamcinolone, budesonide and flunisolide) could be
used, and mometasone furoate and fluticasone propionate could be considered for
longer-term treatment. Although somewhat more costly, these second-generation
drugs have lower bioavailability and thus would have a better safety profile. In 
patients not responding to the above programme or who require continuous
medication, identification of specific triggers by an allergist can allow for
specific avoidance measures and/or immunotherapy to decrease the allergic
component and increase the effectiveness of the pharmacological regimen.

Publication Types: 
    Review

PMID: 11520256 [PubMed - indexed for MEDLINE]

1320: J Allergy Clin Immunol. 2001 Aug;108(2 Suppl):S84-8.

Experience with monoclonal antibodies in allergic mediated disease: seasonal
allergic rhinitis.

Casale TB.

Creighton University, Omaha, Nebraska 68231, USA.

Current therapies for the treatment of seasonal allergic rhinitis include
allergen avoidance; pharmacologic interventions such as sympathomimetics, topical
and systemic cortico-steroids, and chromones; and immunotherapy. In an attempt to
create a novel therapy, therapeutic agents have been designed to inhibit IgE
responses that are intimately involved in the induction of the allergic response.
Omalizumab, a humanized monoclonal antibody against IgE, represents a novel
therapeutic intervention for seasonal allergic rhinitis. Complex formation of
omalizumab with serum-free IgE reduces the amount of IgE available for binding to
effector cells and thus has the potential to reduce IgE-mediated allergic
symptoms. Clinical trial results confirmed that omalizumab reduces free IgE to a 
level that is associated with suppressed allergic symptoms, reduces concomitant
rescue medication use, and improves rhinitis-specific quality of life. Patients
treated with omalizumab during one pollen season can be re-treated during the
subsequent season with minimal risk of adverse events. Omalizumab is
non-allergen-specific and does not induce acute anaphylaxis because of the lack
of IgE crosslinking with basophil- or mast-cell-bound IgE. Furthermore,
subcutaneous or intravenous administration of omalizumab does not invoke the
generation of anti-omalizumab antibodies. Thus, omalizumab represents a novel
agent that should assist in the treatment of allergic rhinitis.

Publication Types: 
    Review

PMID: 11498678 [PubMed - indexed for MEDLINE]

1321: Ann Allergy Asthma Immunol. 2001 Jul;87(1):22-6.

Safety of fexofenadine in children treated for seasonal allergic rhinitis.

Graft DF, Bernstein DI, Goldsobel A, Meltzer EO, Portnoy J, Long J.

Park Nicollet Clinic, Minneapolis, MN 55416, USA. graftd@parknicollet.com

BACKGROUND: The incidence of allergic rhinitis in children is increasing.
OBJECTIVE: To evaluate the safety of fexofenadine HCI in children ages 6 through 
11 years for treatment of seasonal allergic rhinitis. METHODS: Two large,
double-blind, randomized, placebo-controlled, parallel studies with identical
protocols included patients with a positive skin test to fall allergen(s) and
allergic rhinitis symptoms. Patients were randomized to receive fexofenadine 15, 
30, or 60 mg or placebo twice daily for 2 weeks after a 1-week placebo lead-in.
Safety was evaluated through adverse event reporting, electrocardiograms, and
pre- and posttreatment laboratory panels and physical examinations. RESULTS: A
total of 875 patients from both studies were eligible for safety analyses. Ten
patients (5 on placebo, 5 on fexofenadine) discontinued because of an adverse
event; no event that resulted in discontinuation was judged to be caused by study
medication. Incidence of adverse events was similar in active and placebo groups,
and did not increase with increasing fexofenadine dose: 36.2% (83 of 229) in the 
placebo group versus 35.3% (79 of 224), 36.8% (77 of 209), and 34.7% (74 of 213) 
in the 15, 30, and 60 mg twice-daily fexofenadine groups, respectively. Headache 
was the most commonly reported adverse event (6.6%, 8.0%, 7.2%, and 9.4% in the
placebo, 15, 30, 60 mg twice-daily fexofenadine groups, respectively). Clinical, 
vital sign, electrocardiogram, and laboratory measures were similar in active and
placebo groups. There was no statistically significant mean change from baseline 
in any electrocardiogram parameter after fexofenadine treatment. CONCLUSIONS:
Fexofenadine, 15, 30, and 60 mg twice daily, was safe and well tolerated in this 
large pediatric patient population.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11476456 [PubMed - indexed for MEDLINE]

1322: Med J Aust. 2001 Jul 2;175(1):10-3.

Comment in:
    Med J Aust. 2001 Jul 2;175(1):4-5.

Asthma and hayfever in Aboriginal and non-Aboriginal children living in
non-remote rural towns.

Downs SH, Marks GB, Belosouva EG, Peat JK.

Institute of Respiratory Medicine, NSW, University of Sydney, Camperdown.

OBJECTIVE: To compare the prevalence and risk factors for wheeze, asthma
diagnosis and hayfever in Aboriginal and non-Aboriginal children living in rural 
towns in Australia. DESIGN AND SETTING: Cross-sectional study in two towns in
rural NSW, Australia, 1997. PARTICIPANTS: Primary school children (aged 7-12
years) classified by their parents as being of Aboriginal (n = 158) or of
non-Aboriginal (n = 1,282) origin. Main outcome measures: Atopy measured by
skinprick tests and respiratory symptoms measured by parent-completed
questionnaire. RESULTS: Aboriginal children were less likely to be atopic (36.2% 
v 45.6%; 95% CI for the difference, -17.6 to -1.3) and to have hayfever (23.3% v 
35.2%; 95% CI for the difference, -19.1 to -4.6) than non-Aboriginal children,
but were equally likely to have had wheeze (31.0% v 27.3%) and asthma (39.4% v
39.3%). Among Aboriginal children, having had bronchitis before age two was a
strong risk factor for wheeze (adjusted odds ratio (aOR), 9.3; 95% CI, 2.8-30.2) 
and asthma (aOR, 19.3; 95% CI, 4.7-79.3) and having a parent with hayfever was a 
strong risk factor for hayfever (aOR, 17.9; 95% CI, 3.5-90.8), but these risk
factors were weaker among non-Aboriginal children. CONCLUSIONS: Asthma and wheeze
are equally prevalent in Aboriginal and non-Aboriginal children living in the
same towns, but appear to have a different aetiology.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11476195 [PubMed - indexed for MEDLINE]

1323: Stat Med. 2001 Aug 15;20(15):2261-85.

Cumulative logit models for ordinal data: a case study involving allergic
rhinitis severity scores.

Lunn DJ, Wakefield J, Racine-Poon A.

Department of Epidemiology and Public Health, Imperial College School of
Medicine, Norfolk Place, London W2 1PG, U.K. d.lunn@ic.ac.uk

Ordered categorical data arise in numerous settings, a common example being pain 
scores in analgesic trials. The modelling of such data is intrinsically more
difficult than the modelling of continuous data due to the constraints on the
underlying probabilities and the reduced amount of information that discrete
outcomes contain. In this paper we discuss the class of cumulative logit models, 
which provide a natural framework for ordinal data analysis. We show how viewing 
the categorical outcome as the discretization of an underlying continuous
response allows a natural interpretation of model parameters. We also show how
covariates are incorporated into the model and how various types of correlation
among repeated measures on the same individual may be accounted for. The models
are illustrated using longitudinal allergy data consisting of sneezing scores
measured on a four-point scale. Our approach throughout is Bayesian and we
present a range of simple diagnostics to aid model building. Copyright 2001 John 
Wiley & Sons, Ltd.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11468763 [PubMed - indexed for MEDLINE]

1324: Dermatology. 2001;202(4):330-2.

Asthma, rhinitis and dermatitis triggered by fungal infection: therapeutic
effects of terbinafine.

Hürlimann A, Fäh J.

Dermatological Practice, Wetzikon, Switzerland. haut@bluewin.ch

We report 2 atopic patients suffering from tinea unguium caused by Trichophyton
rubrum. In addition, both patients had symptoms of allergies: one had perennial
rhinoconjunctivitis and bronchial asthma, the other had chronic dermatitis of the
face and neck. In both cases, their allergy symptoms improved dramatically during
oral therapy with the antifungal agent terbinafine (250 mg/day) and relapsed
after its discontinuation. Copyright 2001 S. Karger AG, Basel

Publication Types: 
    Case Reports

PMID: 11455147 [PubMed - indexed for MEDLINE]

1325: Respir Med. 2001 Jul;95(7):606-11.

The role of outdoor air pollution and climatic changes on the rising trends in
respiratory allergy.

D'Amato G, Liccardi G, D'Amato M, Cazzola M.

Division of Pneumology and Allergology, Azienda Ospedaliera ad Alta Specialità
A.Cardarelli, Napoli, Italy. gdamato@qubisoft.it

Evidence suggests that allergic respiratory diseases such as hay fever and
bronchial asthma have become more common world-wide in the last two decades, and 
the reasons for this increase are still largely unknown. A major responsible
factor could be outdoor air pollution, derived from cars and other vehicles.
Studies have demonstrated that urbanization and high levels of vehicle emissions 
and westernized lifestyle is correlated with the increasing frequency of
pollen-induced respiratory allergy. People who live in urban areas tend to be
more affected by pollen-induced respiratory allergy than those from of rural
areas. Pollen allergy has been one of the most frequent models used to study the 
interrelationship between air pollution and respiratory allergic diseases. Pollen
grains or plant-derived paucimicronic components carry allergens that can produce
allergic symptoms. They may also interact with air pollution (particulate matter,
ozone) in producing these effects. There is evidence that air pollutants may
promote airway sensitization by modulating the allergenicity of airborne
allergens. Furthermore, airway mucosal damage and impaired mucociliary clearance 
induced by air pollution may facilitate the access of inhaled allergens to the
cells of the immune system. In addition, vegetation reacts with air pollution and
environmental conditions and influence the plant allergenicity. Several factors
influence this interaction, including type of air pollutants, plant species,
nutrient balance, climatic factors, degree of airway sensitization and
hyperresponsiveness of exposed subjects.

Publication Types: 
    Review

PMID: 11453319 [PubMed - indexed for MEDLINE]

1326: Allergol Immunopathol (Madr). 2001 Jan-Feb;29(1):9-15.

Specific immune response to Phleum pratense plant profilin in atopic patients and
control subjects.

Benítez D, García-Ortega P, Picado C, Milà J, Vives J, Martínez J, Vilella R.

Servei Immunologia, IDIBAPS, Hospital Clínic Barcelona.

BACKGROUND: Phleum pratense (Phl p) pollen is a known cause of allergic disease
worldwide. Profilins have been identified as functional plant pan-allergens. The 
role of Phl p profilin in the specific immune response in sensitized Phl p
patients is unknown. METHODS: Skin prick test and specific serum IgE levels were 
performed in 26 patients allergic to Phl p and in 18 nonallergic control donors. 
Peripheral blood mononuclear cells were isolated from both groups and stimulated 
with crude extract or highly purified Phl p profilin, and the production of type 
I and type II cytokines was determined in patients and controls stimulated with
specific and polyclonal stimulus. T-cell lines specific to Phl p profilin were
established from PBMCs and cross-reactivity with another highly purified profilin
from Parietaria judaica (Pj) was evaluated. RESULTS: Patients allergic to Phl p
profilin showed increased T-cell-proliferative responses to this profilin
compared with control subjects. The production of IL-4 and IFN-gamma in response 
to the specific stimulus was undetectable. However, the production of IL-4 and
IFN-gamma in response to a polyclonal stimulus (PHA) was measurable and different
for atopic patients and control subjects: IL-4 was higher (p < 0.001) in allergic
patients and IFN-gamma lower (although not significant) in controls. Neither the 
T-cell responses nor the production of IL-4 in response to a polyclonal stimulus 
(PHA) correlated with the individual degree of cutaneous response to Phl p
profilin or to the levels of specific Phl p IgE. The T-cell lines tested did not 
show any cross-reactivity with Pj profilin. CONCLUSIONS: Phl p profilin is in
part responsible for the T-cell mediated immunological response in patients
allergic to Phl p. The response is very specific since Phl p profilin specific
T-cell lines did not show cross-reactivity with a highly homologous profilin from
Parietaria judaica (Pj). The lack of correlation between the proliferative T-cell
response and polyclonal IL-4 production with allergen-specific serum IgE and SPT 
probably indicates that some of the responding T-cells may be involved in immune 
reactions other than the support of IgE production.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11449535 [PubMed - indexed for MEDLINE]

1327: J Allergy Clin Immunol. 2001 Jul;108(1 Suppl):S59-64.

Corticosteroids in the treatment of pediatric allergic rhinitis.

Scadding GK.

Royal National Throat, Nose and Ear Hospital, London, United Kingdom.

The goal of treatment in pediatric allergic rhinitis is to provide effective
prevention of or relief from allergic rhinitis symptoms as safely and effectively
as possible. Removing or avoiding allergens is always advised; however,
pharmacotherapy is often necessity. Pharmacologic options include systemic
decongestants, which are associated with irritability and insomnia, particularly 
in children. Antihistamines are widely used; however, first-generation
antihistamines are known to cause dry mouth and sedation. Oral corticosteroids
are very effective but can have unwanted systemic effects. Over the past decade, 
intranasal corticosteroids have been shown to be the most effective form of
pharmacologic treatment for allergic rhinitis. Data support the use of intranasal
corticosteroids as first-line therapy over oral antihistamines; nonetheless, some
clinicians have been reluctant to prescribe these agents, particularly for
children, because of concerns for systemic effects. Overall, the newer
corticosteroids, including mometasone furoate (MF), beclomethasone dipropionate, 
and budesonide have an improved risk-benefit ratio compared with older
cortico-steroids and are now considered the drug of choice for pediatric allergic
rhinitis. A good deal of evidence exists that confirms the lack of systemic
effects from intranasal cortico-steroids. However, reports of decreased bone
growth in children receiving intranasal budesonide short-term and beclomethasone 
dipropionate long-term have heightened concerns that some of these drugs may have
systemic effects. A new intranasal corticosteroid, MF nasal spray, has been
studied in children 3 to 12 years of age and has been shown to be effective.
Intranasal MF is available with once-daily dosing, which has the potential to
decrease systemic side effects.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11449208 [PubMed - indexed for MEDLINE]

1328: J Allergy Clin Immunol. 2001 Jul;108(1 Suppl):S54-8.

Safety and efficacy of mometasone furoate aqueous nasal spray in children with
allergic rhinitis: results of recent clinical trials.

Dibildox J.

Centro Médico del Postosí, San Luis Potosí, Mexico.

Intranasal mometasone furoate (MF) has been extensively studied in adults and has
been found to be safe and effective therapy for the treatment of allergic
rhinitis. Several studies have now been conducted on pediatric patients. In all, 
990 pediatric patients given mometasone furoate nasal spray (MFNS) have been
studied in phase I, II, and III clinical trials. In a dose-ranging study, 5 doses
of nasal spray (25, 100, and 200 microg MFNS daily and 168 microg beclomethasone 
dipropionate daily) were compared with placebo. The 100- and 200-microg daily
doses of MFNS were found to be more effective than 168 microg beclomethasone
dipropionate or 25 microg MFNS given daily. MFNS (100 microg once daily) was
chosen as the appropriate dose. In clinical efficacy and safety trials, MFNS was 
given to 381 patients 3 to 11 years of age for 4 weeks (357 patients received 100
microg MFNS daily for 6 months) and was found to decrease symptom scores from
baseline significantly better than placebo. The long-term safety of MFNS was also
studied in 166 patients treated for one year; no significant changes in
intraocular pressure were detected. Cosyntropin stimulation showed no decreases
in cortisol. In adults, nasal mucosa showed improvement in appearance of
epithelium and reduction of inflammatory infiltrates, and there were no signs of 
nasal atrophy.

Publication Types: 
    Meta-Analysis

PMID: 11449207 [PubMed - indexed for MEDLINE]

1329: J Allergy Clin Immunol. 2001 Jul;108(1 Suppl):S45-53.

Quality of life in adults and children with allergic rhinitis.

Meltzer EO.

Allergy and Asthma Medical Group and Research Center, San Diego, CA 92123, USA.

Quality of life, when referring to an individual's health, is called
health-related quality of life (HRQL). HRQL focuses on patients' perceptions of
their disease and measures impairments that have significant impact on the
patient. Similar symptoms may vary in their effect on different individuals; the 
goal of therapy should be to reduce impairments that patients consider important.
HRQL can be measured with generic or specific questionnaires. Specific
questionnaires may be more sensitive and are much more likely to detect
clinically important changes in patients' impairments. Specific questionnaires
used to assess HRQL in rhinitis are the Rhinoconjunctivitis Quality of Life
Questionnaire, the Adolescent Rhinoconjunctivitis Quality of Life Questionnaire, 
and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire. HRQL issues 
in adult rhinitis patients include fatigue, decrease in energy, general health
perception, and social function; impairment of HQRL generally increases with
increasing degree of symptoms and severity of disease. In children, HRQL issues
include learning impairment, inability to integrate with peers, anxiety, and
family dysfunction. Comorbid disorders often associated with rhinitis, including 
sinusitis, otitis media, and frequent respiratory infections, can further
compromise HRQL. Pharmacologic treatments can have both positive and negative
effects on HRQL. Agents that have troublesome adverse effects such as sedation
can have a negative impact, whereas nonsedating antihistamines and intranasal
cortico-steroids can significantly improve HRQL in patients of all ages with
rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11449206 [PubMed - indexed for MEDLINE]

1330: J Allergy Clin Immunol. 2001 Jul;108(1 Suppl):S32-9.

Effects of intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis 
in children.

Boner AL.

Department of Pediatrics, University of Verona, Italy.

In adults, morning plasma cortisol levels are twice that of late afternoon and
evening values. In children, a delay in the time of onset in peak cortisol levels
has been observed in those treated with inhaled corticosteroids. Consequently,
the single morning cortisol level has a low sensitivity for detecting adrenal
insufficiency in children. It is not clear which test is best for detection of
clinically relevant hypothalamic-pituitary-adrenal (HPA) axis suppression in
children; 24-hour plasma cortisol is a good test because it measures biologically
active, free cortisol levels for the entire day and is noninvasive. For research 
purposes, the 24-hour integrated concentration plasma cortisol test is preferred.
Studies that have looked at HPA axis suppression with intranasal corticosteroids 
indicate that overall, intranasal corticosteroids have minimal effect on the HPA 
axis. A review of the literature reveals one study in which there was a decreased
output of urinary cortisol during treatment with either budesonide or fluticasone
propionate in adults. Other studies of fluticasone propionate or budesonide have 
shown no effect on the HPA axis in children. Beclomethasone dipropionate was
shown to affect urinary cortisol output in one study of healthy volunteers.
However, in a long-term study in children, no effect on the HPA axis was found.
Mometasone furoate has been extensively studied in more than 20 trials of adults 
and children. No effects on the HPA axis were detected in either children or
adults. It is unlikely that children are more sensitive to corticosteroids than
are adults. There seems to be little point in performing routine monitoring of
adrenal function in children who are treated with intranasal corticosteroid
treatment.

Publication Types: 
    Review

PMID: 11449204 [PubMed - indexed for MEDLINE]

1331: J Allergy Clin Immunol. 2001 Jul;108(1 Suppl):S16-25.

Mode of action of intranasal corticosteroids.

Mygind N, Nielsen LP, Hoffmann HJ, Shukla A, Blumberga G, Dahl R, Jacobi H.

Department of Respiratory Diseases, Aarhus University Hospital, Denmark.

The mode of action of intranasal corticosteroids (INCS) is complex. It is not
known whether INCS penetrate the nasal mucosa or act on target cells; however,
their low systemic activity supports the concept of local action on nasal mucosa.
This local effect can nonetheless influence a variety of inflammatory cells and
their mediators such as epithelial cells, lymphocytes, basophils, mast cells, and
Langerhans cells. Corticosteroid-induced inhibition of immunoglobulin E-dependent
release of histamine is a possible but unproven mode of action. Epithelial cells 
are an important target for corticosteroids, and INCS concentration is high at
the epithelial surface. INCS may combine with the corticosteroid receptors in
epithelial cells, which are then expelled into the airway lumen together with the
dead epithelial cells or migrating inflammatory cells. A reduced influx of
mediator cells may explain some of the effects of INCS on rhinitis symptoms, but 
it cannot explain all of the effects because INCS also reduce the early-phase
sneezing and rhinorrhea after an allergen challenge outside the pollen season. In
this situation, the number of surface mast cells/basophils is very low, as it is 
in the absence of allergic rhinitis. The mechanism by which INCS treatment of
allergic rhinitis reduces itching, sneezing, and rhinorrhea, the characteristic
symptoms of an early-phase response involving mast cell release of histamine,
remains to be determined. Studies should be conducted to characterize the broad
range of mechanisms by which INCS produce their therapeutic effects in allergic
rhinitis.

Publication Types: 
    Review

PMID: 11449202 [PubMed - indexed for MEDLINE]

1332: J Allergy Clin Immunol. 2001 Jul;108(1 Suppl):S9-15.

Pediatric allergic rhinitis and comorbid disorders.

Lack G.

Department of Pediatric Allergy and Immunology, St Mary's Hospital, London, UK.

Allergic rhinitis (AR) is rarely found in isolation and needs to be considered in
the context of systemic allergic disease associated with numerous comorbid
disorders, including asthma, chronic middle ear effusions, sinusitis, lymphoid
hypertrophy with obstructive sleep apnea, disordered sleep, and consequent
behavioral and educational effects. The coexistence of AR and asthma is complex. 
First, the diagnosis of asthma may be confounded by symptoms of cough caused by
rhinitis and postnasal drip. This may lead to either inaccurate diagnosis of
asthma or inappropriate assessment of asthma severity with over treatment of the 
patient. The term "cough variant rhinitis" is therefore proposed to describe
rhinitis that manifests itself primarily as cough that results from postnasal
drip. AR, however, also has a causal role in asthma; it appears both to be
responsible for exacerbating asthma and to have a role in its pathogenesis.
Postnasal drip with nasopharyngeal inflammation leads to a number of other
conditions. Thus sinusitis is a frequent extension of rhinitis and is one of the 
most frequently missed diagnoses in children. Allergen exposure in the
nasopharynx with release of histamine and other mediators can cause Eustachian
tube obstruction possibly leading to middle ear effusions. Chronic allergic
inflammation of the upper airway causes lymphoid hypertrophy with prominence of
adenoidal and tonsillar tissue. This may be associated with poor appetite, poor
growth, and obstructive sleep apnea. AR is therefore part of a spectrum of
allergic disorders that can profoundly affect the well being and quality of life 
of a child. Prospective cohort studies are required to assess the disease burden 
caused by AR in childhood and to further assess the potential educational
impairment that may result. Because AR is part of a systemic disease process, its
management requires a coordinated approach rather than a fragmented, organ-based 
approach.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11449201 [PubMed - indexed for MEDLINE]

1333: J Allergy Clin Immunol. 2001 Jul;108(1 Suppl):S2-8.

Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and
diagnosis.

Skoner DP.

Department of Pediatrics and Otolaryngology, University of Pittsburgh School of
Medicine, and Children's Hospital of Pittsburgh, PA 15231, USA.

Allergic rhinitis (AR) is a heterogeneous disorder that despite its high
prevalence is often undiagnosed. It is characterized by one or more symptoms
including sneezing, itching, nasal congestion, and rhinorrhea. Many causative
agents have been linked to AR including pollens, molds, dust mites, and animal
dander. Seasonal allergic rhinitis (SAR) is fairly easy to identify because of
the rapid and reproducible onset and offset of symptoms in association with
pollen exposure. Perennial AR is often more difficult to detect than SAR because 
of the overlap with sinusitis, respiratory infections, and vasomotor rhinitis.
SAR can result in hyperresponsiveness to allergens such as cigarette smoke, once 
pollen season is over. Perennial AR is defined as occurring during approximately 
9 months of the year. AR affects an estimated 20 to 40 million people in the
United States alone, and the incidence is increasing; an estimated 20% of cases
are SAR; 40% of cases are perennial rhinitis; and 40% of cases are mixed. The
pathophysiology of SAR is complex. There is a strong genetic component to the
allergic response, which is driven through mucosal infiltration and action on
plasma cells, mast cells, and eosinophils. The allergic response occurs in two
phases, which are considered the "early" and "late" phase responses. Early phase 
response occurs within minutes of exposure to the allergen and tends to produce
sneezing, itching, and clear rhinorrhea; late phase response occurs 4 to 8 hours 
after allergen exposure and is characterized by congestion, fatigue, malaise,
irritability, and possibly neurocognitive deficits. The key to diagnosis of AR is
awareness of signs and symptoms. IgE antibody tests to detect specific allergens 
are the standard method used today; however, in addition, diagnosis must be
confirmed with a positive history and demonstration that the symptoms are the
result of IgE-mediated inflammation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11449200 [PubMed - indexed for MEDLINE]

1334: J Allergy Clin Immunol. 2001 Jul;108(1):125-7.

Rhinoconjunctivitis and occupational asthma caused by Diplotaxis erucoides (wall 
rocket).

Brito FF, Mur P, Bartolomé B, Galindo PA, Gómez E, Borja J, Martínez A.

Section of Allergy, Hospital Complex, Ronda del Carmen, Ciudad Real, Spain.

Wall rocket (Diplotaxis erucoides) is a common Crucifera plant that grows in
European and American vineyards and olive groves. We present the cases of 2
farmers with rhinoconjunctivitis and asthma related to wine-growing tasks during 
D erucoides pollination (March-April). The aim of this work was to demonstrate
that occupational symptoms were caused by D erucoides pollen sensitization.
Cutaneous tests, specific IgE measurements, conjunctival and bronchial
provocation tests, and peak-flow measurements during working days were performed.

Publication Types: 
    Case Reports

PMID: 11447393 [PubMed - indexed for MEDLINE]

1335: J Allergy Clin Immunol. 2001 Jul;108(1):101-8.

Roles of carbohydrates on Cry j 1, the major allergen of Japanese cedar pollen,
in specific T-cell responses.

Okano M, Kino K, Takishita T, Hattori H, Ogawa T, Yoshino T, Yokoyama M,
Nishizaki K.

Departments of Otolaryngology and Pathology, Okayama University Medical School,
Okayama, Japan.

BACKGROUND: Carbohydrates expressed on allergens are known to be important for
allergenicity. However, little is known about whether the carbohydrates drive the
T(H)2 response. OBJECTIVE: We sought to determine a role for carbohydrates
expressed on Cry j 1, which is the major allergen of Cryptomeria japonica pollen 
and causes the most prevalent pollinosis in Japan, in in vitro cellular
responses. METHODS: Carbohydrates on Cry j 1 were destroyed by
periodate-oxidation under mild conditions. Proliferative responses and cytokine
productions against native, periodate-treated, and mock-treated Cry j 1 were
compared in peripheral blood mononuclear cells, Cry j 1-specific T-cell lines,
and clones from patients with Japanese cedar pollinosis. RESULTS: We found that
peripheral blood mononuclear cells from patients with Japanese cedar pollinosis
displayed a significant decrease in proliferation and IL-5 production in response
to periodate-treated Cry j 1 in comparison with native and mock-treated Cry j 1. 
Decreased proliferative responses against periodate-treated Cry j 1 were also
seen in polyclonal T-cell lines, and the responses showed a heterogeneity. In
addition, Cry j 1-specific CD4+ T-cell clones also displayed a significant
decrease in proliferation and IL-4 and IL-5 production-but not IFN-gamma
production-in comparison with the control antigens. However, most of the clones
showed decreased but positive proliferative responses against periodate-treated
Cry j 1. Blockade of the mannose receptor had no effect on cellular responses.
CONCLUSION: The results suggest that carbohydrates on Cry j 1 play a major role
in promoting Cry j 1-specific T(H)2 response in vitro, though they are not major 
targets as T-cell epitopes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11447389 [PubMed - indexed for MEDLINE]

1336: J Allergy Clin Immunol. 2001 Jul;108(1):94-100.

Preclinical evaluation of an immunotherapeutic peptide comprising 7 T-cell
determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens.

Hirahara K, Tatsuta T, Takatori T, Ohtsuki M, Kirinaka H, Kawaguchi J, Serizawa
N, Taniguchi Y, Saito S, Sakaguchi M, Inouye S, Shiraishi A.

Sankyo Co, Ltd, Tokyo; Hayashibara Biochemical Laboratories, Inc, Okayama, Japan.

BACKGROUND: Peptide immunotherapy is a new approach to treating allergic
diseases, but a therapeutic peptide for Japanese cedar pollinosis has not yet
been developed. OBJECTIVE: The aim of this study is to prepare and preclinically 
evaluate a hybrid peptide comprising 7 T-cell determinants of Cry j 1 and Cry j
2, the major Japanese cedar pollen allergens. METHODS: The recombinant hybrid
peptide was prepared after immunodominance of 7 T-cell determinants was confirmed
by means of PBMC proliferation assay in 113 volunteers with pollinosis. The
hybrid peptide was compared with a mixture of the 7 T-cell determinants in a
dose-dependent PBMC proliferation assay in 6 volunteers with pollinosis. PBMC
proliferation and binding activity of serum IgE antibody against the hybrid
peptide, Cry j 1, and Cry j 2 were investigated in 48 volunteers with pollinosis.
RESULTS: The hybrid peptide induced T-cell proliferation with an average 100-fold
lower concentration than a mixture of the 7 peptides. PBMCs from 44 (92%) of 48
volunteers proliferated against the hybrid peptide, with significant correlation 
(r = 0.87) in T-cell proliferation against Cry j 1 and Cry j 2. No serum IgE
antibodies specific to Cry j 1 or Cry j 2 bound to the hybrid peptide.
CONCLUSION: A hybrid peptide comprising 7 T-cell determinants has the potential
for inducing T-cell proliferative responses that is superior to the potential of 
a mixture of the T-cell determinants and comparable with that of Cry j 1 and Cry 
j 2. The hybrid peptide will be of use in specific immunotherapy against Japanese
cedar pollinosis.

PMID: 11447388 [PubMed - indexed for MEDLINE]

1337: Eur J Pharmacol. 2001 Jun 29;423(1):63-70.

Involvement of nitric oxide in pollen-induced biphasic nasal blockage in
sensitised guinea pigs.

Imai A, Nabe T, Mizutani N, Sakurai H, Takenaka H, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi,
Misasagi, Yamashina, Kyoto 607-8414, Japan.

We have developed a reproducible allergic rhinitis model showing biphasic nasal
blockage on repetitive inhalation challenge with Japanese cedar pollen in
sensitised guinea pigs. The role of nitric oxide (NO) in inducing nasal blockage 
was evaluated with this model. N(omega)-nitro-L-arginine methyl ester (L-NAME), a
non-selective NO synthase (NOS) inhibitor, intravenously administered before the 
challenge, significantly inhibited both early and late nasal blockage by
approximately 80% and 50%, respectively. When L-NAME treatment was performed
after the challenge, the late response was inhibited by approximately 70%. This
inhibition was completely reversed by co-administration of L-arginine. However,
aminoguanidine and L-N(6)-(1-iminoethyl)lysine, selective inhibitors of inducible
NOS, negligibly influenced the degree of nasal blockage. Meanwhile, the
alpha-adrenergic agonist, naphazoline, strongly suppressed both early and late
nasal blockage. These results indicate that NO, likely produced by constitutive
rather than inducible NOS, plays a major role in the occurrence of biphasic nasal
blockage, primarily by inducing vasodilatation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11438308 [PubMed - indexed for MEDLINE]

1338: J Investig Allergol Clin Immunol. 2001;11(1):46-8.

Serum soluble tumor necrosis factor receptor levels in patients with seasonal
allergic rhinitis.

Kokuludağ A, Terzioğlu E, Kírmaz C, Sin A, Sebik F.

Division of Immunology, Ege University Medical Faculty, Bornova, Izmir, Turkey.
akokulu@med.ege.edu.tr

It is known that several inflammatory cells and cytokines play a role in allergic
inflammation. Furthermore, there are seasonal changes in several mediators
responsible for allergic inflammation. The aim of this study was to determine
seasonal changes in serum concentrations of soluble tumor necrosis factor
receptors (sTNFRs) and the relationship with disease activity and other
inflammation markers such as eosinophil cationic protein (ECP) in patients with
seasonal allergic rhinitis. Serum levels of sTNFRI and sTNFRII were measured
before and during the pollen season in 18 patients with seasonal allergic
rhinitis and in 17 healthy controls by using commercially available enzyme-linked
immunosorbent assay (ELISA) kits. The serum levels of sTNFRI, sTNFRII, IgE, and
ECP were significantly higher in patients than those in controls before and
during season. sTNFRI, sTNFRII, and IgE levels were higher before season, whereas
ECP levels were higher during season. We suggest that sTNFRs might play
regulatory roles even in early stages of allergic rhinitis when patients do not
have clinical symptoms yet.

Publication Types: 
    Comparative Study

PMID: 11436971 [PubMed - indexed for MEDLINE]

1339: J Investig Allergol Clin Immunol. 2001;11(1):34-40.

Treatment of severe seasonal rhinoconjunctivitis by a combination of azelastine
nasal spray and eye drops: a double-blind, double-placebo study.

Duarte C, Baëhre M, Gharakhanian S, Leynadier F; French Azelastine Study Group.

Allergology Center, Tenon Hospital, University of Paris VI, France.

BACKGROUND: Evaluation of combined azelastine nasal spray and eye drops treatment
in patients with severe rhinoconjunctivitis. METHODS: Phase III, multicenter,
randomized, double-blind study of patients with a history of grass pollen
allergy, confirmed by skin testing/specific IgE, total symptom scores > or =6
(ocular) or > or =8 (nasal). Intent-to-treat analysis. RESULTS: 99 patients
(azelastine = 53, placebo = 46) enrolled homogeneously from May to September 1997
in 7 venues in France. The efficacy of azelastine was significantly higher
compared to placebo (49% vs. 28%, p = 0.04), considering response as a decrease
of the total sum of ocular and nasal scores by at least 50% and no use of
cetirizine by day 7. The decrease of total ocular and nasal scores by at least
50% at day 7, with cetirizine rescue <3 tablets was higher, but not
significantly, in azelastine patients (43% vs. 30%). Cetirizine rescue was more
frequent, from day 0 to 7, in the placebo patients (4.9 +/- 5.0 vs. 2.7 +/- 4.1, 
p = 0.02). Global efficacy was rated higher for azelastine by investigators (26% 
vs. 10%, p = 0.05) and patients (28% vs. 7%, p = 0.01). Adverse events were
burning sensation, "red eyes," nasal irritation, bitter taste. No serious adverse
events were reported. Tolerance of azelastine was "very good/good"/"satisfactory"
in the majority (62%/82% assessed by investigators, or 55%/79% by patients,
respectively). CONCLUSIONS: Combining azelastine eye drops and nasal spray is a
safe and effective treatment of severe seasonal rhinoconjunctivitis.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 11436969 [PubMed - indexed for MEDLINE]

1340: Int J Pediatr Otorhinolaryngol. 2001 Jul 30;60(1):21-7.

Doppler echocardiographic evaluation of pulmonary arterial pressure in children
with allergic rhinitis.

Yüksel H, Coşkun S, Onağ A.

Department of Pediatrics, Medical Faculty, Celal Bayar University, Manisa,
Turkey. hyukselefe@hotmail.com

In children, persistent upper airway obstruction may lead to increased pulmonary 
arterial pressure (PAP). Allergic rhinitis (AR) is one of the frequent cause of
persisting upper airway obstruction by nasal blockage in childhood. Regular use
of nasal topical corticosteroids are effective in reducing nasal blockage and
obstruction. However, whether symptomatic children with AR have increased PAP and
curative effect of topical steroids are not known. The aims of this study were to
clarify whether children having active symptoms of AR have increased PAP and to
investigate the curative effect of reducing nasal obstruction by topical
corticosteroids. Twenty-three children, aged between 5 and 16, diagnosed as AR,
consisted of 17 seasonal AR (SAR) and seven perennial AR (PAR), were included in 
the study. Nineteen age and sex matched healthy children were received as
controls. PAP was measured by using Doppler echocardiography in all subjects and 
symptom scores of AR were recorded in rhinitis group. After first evaluation,
nasal steroid, budesonid, was given to rhinitis group for three months. Mean
systolic PAP was 33.4+/-3.1 for children with AR mmHg and 23.6+/-4.3 mmHg for the
control group. The difference was statistically significant (P<0.05). Mean
systolic PAP of children with PAR was significantly higher than children with SAR
(P<0.05). In rhinitis group, mean PAP decreased significantly after relief of
upper airway obstruction by nasal corticosteroid therapy to normal level of
24.9+/-3.6 mmHg (P<0.05). Our results showed that children with AR may have
significantly higher PAP than healthy subjects and decreased to normal levels
after relieving nasal blockage by nasal corticosteroids. Nevertheless, Doppler
echocardiography is a safe, non-invasive and practical tool for cardiac
investigation of children with AR. Therefore, in symptomatic period, evaluation
of PAP of children with AR by using Doppler echocardiography may be useful in the
planning and following of their therapy.

PMID: 11434950 [PubMed - indexed for MEDLINE]

1341: J La State Med Soc. 2001 May;153(5):241-5.

The inflammatory nature of allergic rhinitis.

Ben Gaudin L 2nd.

The importance of the role of mucosal inflammation in the pathophysiology of
allergic rhinitis is becoming clearer. Only by addressing the underlying
inflammation can adequate control of allergic rhinitis be achieved. Appropriate
management of allergic rhinitis is necessary to help control the significant
morbidity of this disease, which includes reduced school and work productivity
due to absences and cognitive impairment as well as diminished quality of life
due to rhinitis symptoms. A review of allergic rhinitis is presented emphasizing 
the concept of nasal mucosal inflammation in regard to management choices.

Publication Types: 
    Review

PMID: 11433932 [PubMed - indexed for MEDLINE]

1342: Allergy Asthma Proc. 2001 May-Jun;22(3):167-72.

Clinical and basic science research on allergic rhinitis and asthma from Nassau
University Medical Center.

Frieri M.

Department of Medicine, Pediatrics, Pathology, Nassau University Medical Center, 
State University of New York at Stony Brook, Stony Brook, New York, USA.

Allergic inflammatory disorders involved with the upper and lower airway are
related to allergic rhinitis and asthma. The role of nasal provocation and airway
epithelium as models to evaluate allergic rhinitis and asthma are illustrated in 
studies from our research center. New concepts related to the anti-inflammatory
effect of nasal steroids, antihistamines, isomers of beta 2 agonists, cromolyn
sodium, and enoxaparin sodium related to airway remodeling are addressed in this 
article.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11424878 [PubMed - indexed for MEDLINE]

1343: Allergy Asthma Proc. 2001 May-Jun;22(3):127-32.

Nasal IL-16 and MIP-1 alpha in late-phase allergic response.

Kramer MF, Ostertag P, Pfrogner E, Rasp G.

Department of Oto-Rhino-Laryngology/Head and Neck Surgery,
Ludwig-Maximilians-University, Munich, Germany.

Late-phase response in allergic rhinitis is characterized by tissue eosinophilia 
and influx of CD4+ T-cells. IL-16 and MIP-1 alpha are highly chemotactic on
T-cells and on eosinophils. Both IL-16 and MIP-1 alpha have been demonstrated to 
be up-regulated after challenge in the late-phase response in various atopic
conditions other than allergic rhinitis. The aim of our study was to determine
the expression of IL-16 and MIP-1 alpha in nasal secretions following allergen
challenge in allergic rhinitis, and to compare these with characteristic
late-phase mediators such as IL-5 and ECP. Nasal secretions of 14 allergic
volunteers challenged intranasally by their specific allergen were studied from
20 minutes to 8 hours after allergen challenge. Nasal secretions were analyzed by
routine ELISA for IL-16, MIP-1 alpha, IL-5, and ECP. IL-16 and MIP-1 alpha
increased significantly in nasal secretions of challenged allergic patients in
the late-phase response. IL-16 revealed highest amounts 5 hours after challenge, 
whereas MIP-1 alpha peaked at 7 hours. Both correlated significantly (r = 0.917, 
p < 0.05) at 6 hours. IL-5 and ECP peaked between 6 and 8 hours and correlated
significantly (r = 0.951, p < 0.01) at 6 hours as well. Our data demonstrate that
IL-16 and MIP-1 alpha are expressed in the late-phase response in allergic
rhinitis in a more or less similar kinetic like IL-5 and ECP. They are suggested 
to be responsible for the observed influx of eosinophils (IL-5, IL-16, and MIP-1 
alpha) and CD4+ T-cells (IL-16 and MIP-1 alpha) into the challenged allergic
mucosa.

Publication Types: 
    Comparative Study

PMID: 11424872 [PubMed - indexed for MEDLINE]

1344: Allergy. 2001 Jul;56(7):653-9.

Mizolastine in the treatment of seasonal allergic rhinoconjunctivitis: a European
clinical experience with 5408 patients managed in daily practice (PANEOS SAR
Study).

Bachert C, Vovolis V, Margari P, Murrieta-Aguttes M, Santoni JP.

ENT Department, University Hospital Ghent, Ghent, Belgium, Sotiria Chest
Hospital, Athens, Greece.

BACKGROUND: Mizolastine, a potent H1 antihistamine with additional antiallergic
properties, is marketed for the treatment of allergic rhinoconjunctivitis and
urticaria. The objective was to investigate the safety and effectiveness of
mizolastine under conditions of daily practice in patients with seasonal allergic
rhinoconjunctivitis (SAR). METHODS: In an open multicenter study, mizolastine 10 
mg daily was administered for 14 days during the pollen season. Nasal and ocular 
symptoms, time to onset of symptom relief, and effect of the drug on diurnal
alertness were evaluated. Safety was evaluated on the basis of self-reported
adverse events (AE). RESULTS: A total of 5408 patients (36+/-14 years of age,
females=57%) with a history of SAR for 8+/-9 years were treated for a mean of
17.1+/-5.0 days. SAR symptoms improved in 93% and decreased by at least 50% in
86% of patients; 78% reported improvement after the first drug intake and 51%
from the first hour. Sixty-nine percent considered mizolastine more effective
than other antihistamines taken previously. The incidence of AE was low (3.8%).
CONCLUSION: The high responder rate, the rapid onset of action, and the low
incidence of AE observed in this large multicenter study confirm the previously
reported beneficial efficacy and safety of mizolastine in the management of SAR.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 11421924 [PubMed - indexed for MEDLINE]

1345: Respir Med. 2001 Jun;95(6):457-63.

Relationship between airway sensitivity to adenosine 5' monophosphate and the
shape of the concentration-response curve to methacholine in subjects with
allergic rhinitis.

Prieto L, Gutiérrez V, Marín J.

Sección de Alergología (The NAOMI Project), Valencia, Spain.

The objective of this study was to determine differences in airway sensitivity to
adenosine 5'-monophosphate (AMP) between allergic rhinitis subjects with plateau 
and those without evidence of plateau on the concentration response curves to
methacholine. A total of 51 adults (38 subjects with allergic rhinitis and 13
healthy controls) were challenged with increasing concentrations of methacholine 
and AMP. The methacholine challenge was terminated when there was a 40% or more
decrease in forced expiratory volume in 1 sec (FEV1), whereas the AMP challenge
was stopped when FEV1 had fallen by more than 20%. A plateau for methacholine was
detected in all 13 healthy controls and in 27 patients with allergic rhinitis
(AR-plateau group), whereas 11 subjects with allergic rhinitis did not exhibit a 
plateau (AR-non-plateau group). The median (range) PC20 AMP (provocative
concentration required to produce a 20% fall in FEV1) value for the
AR-non-plateau group was 44.0 mg ml(-1) (3.3-400.0), compared with 400.0 mgml(-1)
(12.1-400.0) in the AR-plateau group (P=0.03) and 400.0 mgml(-1) in the healthy
control group (P=0.007). The proportion of subjects who showed
bronchoconstriction in response to AMP was higher in the AR-non-plateau group
(73%) than in the AR-plateau group (30%) (P=0.03). However, three subjects with
allergic rhinitis who had normal sensitivity to methacholine and plateau showed
bronchoconstriction in response to AMP. We conclude that, in subjects with
allergic rhinitis, the absence of plateau on the concentration response curves to
methacholine is associated with a higher prevalence and degree of
bronchoconstriction in response to AMP. However, the two bronchoconstrictor
stimuli were not identifying the same abnormalities of the airways.

Publication Types: 
    Comparative Study

PMID: 11421502 [PubMed - indexed for MEDLINE]

1346: Arzneimittelforschung. 2001;51(5):387-93.

Comparative efficacy and safety of azelastine and levocabastine nasal sprays in
patients with seasonal allergic rhinitis.

Falser N, Wober W, Rahlfs VW, Baehre M.

Institute for Medical Research, Munich, Germany.

The aim of the present investigation was to compare the efficacy and tolerability
of azelastine (CAS 58581-89-8) (1.12 mg/day) and levocabastine (CAS 79547-78-7)
(0.4 mg/day) nasal spray administered twice daily to patients with seasonal
allergic rhinitis. A total of 180 patients participated in a 4-week,
double-blind, parallel group (n = 90 each) study. Symptom severity of nasal,
ocular and other symptoms were recorded, out of which a total symptom score (TSS)
was calculated. Physicians assessed symptoms at baseline and at days 7, 14, and
28, patients and physicians evaluated the efficacy and tolerability. After 4
weeks of treatment with azelastine the mean overall TSS was reduced from a
baseline score of 18.7 to 4.2, after levocabastine from 17.8 to 5.9. Patients
morning scores for treatment days 1 to 28 gave a mean total score of 212.4 for
the azelastine group and 230.6 for the levocabastine group; the equivalent
evening scores yielded a mean total score of 115.5 and 175.6 respectively. Global
efficacy was judged by physicians as either 'very good' or 'good' for 90% of
azelastine patients and for 74% of the levocabastine group; 92% of azelastine
patients and 76% of levocabastine patients judged treatment to be either 'very
good' or 'good'. No serious adverse events were reported, all adverse events were
related to nasal symptoms. Both azelastine and levocabastine administered twice
daily as a nasal spray provide effective and well tolerated symptomatic treatment
of seasonal allergic rhinitis. Azelastine, however, was statistically superior in
efficacy as well as in safety (PWei-Lachin < 0.0001, combined results).

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 11413739 [PubMed - indexed for MEDLINE]

1347: J Immunol Methods. 2001 Aug 1;254(1-2):109-18.

Simultaneous measurement of six cytokines in a single sample of human tears using
microparticle-based flow cytometry: allergics vs. non-allergics.

Cook EB, Stahl JL, Lowe L, Chen R, Morgan E, Wilson J, Varro R, Chan A, Graziano 
FM, Barney NP.

Department of Medicine, University of Wisconsin-Hospital and Clinics, H6/368 CSC,
600 Highland Ave., Madison, WI 53792-3244, USA.

Tears play an essential role in maintaining corneal and conjunctival integrity by
providing a tightly regulated, optimal extracellular environment critical to its 
numerous functions, which include anti-microbial defense, wound healing and
inflammatory responses such as allergies. Elevated levels of inflammatory
cytokines have been reported in tears from various ocular disease states.
Characterization of tear cytokines has been limited by the small volume
(microliter amounts) attainable. This limitation was addressed with the newly
developed Becton Dickinson Cytometric Bead Array (CBA), which combines the
principles of the "sandwich" immunoassay with the capability of flow cytometry
for simultaneous measurement of the characteristics of multiple particles. This
technique allows determination of six human cytokine (IFNgamma, TNFalpha, IL-2,
IL-4, IL-5, IL-10) concentrations simultaneously in a single tear sample. Tears
were collected from the inferior fornix of non-allergic (n=7) and allergic (n=9) 
donors. Each tear sample or cytokine standard was incubated with a mixture of
capture Ab-bead reagent and detector Ab-phycoerythrin (PE) reagent, and analyzed 
using flow cytometry. All six cytokines were detectable in both non-allergic and 
allergic tears. Tears from allergic donors contained significantly less IL-10
(p=0.035), and had significant increases in the ratios of TNFalpha/IFNgamma,
IL-5/IFNgamma and IL-5/IL-10 (p=0.0008, 0.0124 and 0.011, respectively). The
small volume required (5-10 microl/test) by the Cytometric Bead Array allows
measurement of all six cytokines from a single collection of tears. This
decreases collection time, minimizing the confounding effect of stimulation on
cytokine concentration in tears, as well as allowing calculation of cytokine
ratios.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11406157 [PubMed - indexed for MEDLINE]

1348: Eur Respir J. 2001 Apr;17(4):596-603.

Comment in:
    Eur Respir J. 2002 Jan;19(1):202-3.

Prevalence of nasal symptoms and their relation to self-reported asthma and
chronic bronchitis/emphysema.

Montnémery P, Svensson C, Adelroth E, Löfdahl CG, Andersson M, Greiff L, Persson 
CG.

Dept of Community Health Sciences, Umeå University, Sweden.

Little information is available on associations between rhinitis and chronic
bronchitis/emphysema (CBE). Self-reported upper airway symptoms, asthma, and CBE 
were examined in 12,079 adults living in southern Sweden. The response rate was
70% (n=8,469), of whom 33% reported significant nasal symptoms: a blocked nose
was reported by 21%; sneezing by 18%; nasal discharge by 17%; and thick yellow
nasal discharge by 5.7%. Nasal symptoms and combined nasal and self-reported
bronchial disease were generally more common among smokers than nonsmokers. There
was little overlap between asthma and CBE, but 46% of those with asthma and 40%
of those with CBE had significant nasal symptoms. Best predicting factors (odds
ratios >3) for asthma and CBE were nasal symptoms due to exposure to animals and 
damp/cold air, respectively. One-third of an adult, southern Swedish population, 
had significant allergic and/or nonallergic nasal symptoms. Nasal symptoms were
frequently found to coexist with both asthma and chronic bronchitis/emphysema,
suggesting that pan-airway engagement is common in both diseases. Differing
associations between types of nasal symptoms and allergic and irritant triggers
of nasal symptoms, with regard to asthma and chronic bronchitis/emphysema,
emphasize the different natures of these bronchial diseases.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11401051 [PubMed - indexed for MEDLINE]

1349: J Allergy Clin Immunol. 2001 Jun;107(6):971-6.

Grass pollen immunotherapy: symptomatic improvement correlates with reductions in
eosinophils and IL-5 mRNA expression in the nasal mucosa during the pollen
season.

Wilson DR, Nouri-Aria KT, Walker SM, Pajno GB, O'Brien F, Jacobson MR, Mackay IS,
Durham SR.

Department of Upper Respiratory Medicine, Imperial College School of Medicine at 
The National Heart and Lung Institute, Dovehouse St., London, SW3 6LY, UK.

BACKGROUND: Tissue eosinophilia and infiltration by T(H)2-type T cells are
characteristic features of allergic rhinitis both after allergen challenge and
during natural allergen exposure. Specific immunotherapy inhibits
allergen-induced nasal eosinophilia. OBJECTIVES: We sought to assess, in the
context of a randomized trial, the relationships between symptomatic improvement 
after immunotherapy and eosinophil numbers and IL-5 expression in the nasal
mucosa during the pollen season. METHODS: Nasal biopsy specimens were taken from 
37 adults with severe summer hay fever at baseline (out of season) and at peak
season after 2 years of treatment with a depot grass pollen extract or placebo.
Biopsy specimens were processed for immunohistochemistry by using mAbs against
eosinophils (EG2), T cells (CD3), and IL-2 receptor-positive cells (CD25), as
well as for in situ hybridization by using a sulfur 35-labeled antisense
riboprobe directed against IL-5. RESULTS: Immunotherapy significantly reduced
symptoms (49%, P =.01) and medication requirements (80%, P =.007) compared with
placebo. There was a 400% increase (P =.004) in eosinophils during the pollen
season in placebo-treated patients, which was inhibited in the immunotherapy
group (20% increase, P =.04 between groups). Seasonal increases were also
observed for CD25(+) cells (P =.002), CD3(+) cells (P =.02), and IL-5
mRNA-expressing cells (P =.03) in the placebo group but not in the immunotherapy 
group. A significant correlation was observed between eosinophils and IL-5
expression (r = 0.5, P <.05). Both eosinophils (r = 0.6, P <.02) and IL-5 (r =
0.6, P <.02) correlated with symptoms after immunotherapy. CONCLUSION:
Improvement in symptoms after grass pollen immunotherapy may result, at least in 
part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen
season.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11398073 [PubMed - indexed for MEDLINE]

1350: Jpn J Pharmacol. 2001 Apr;85(4):409-15.

Comparison of cedar pollen-induced allergic rhinitis in passively and actively
sensitized guinea pigs.

Nabe T, Mizutani N, Osaki S, Sugahara S, Takenaka H, Kohno S.

Department of Pharmacology, Kyoto Pharmaceutical University, Yamashina, Japan.

We have developed an allergic rhinitis model in guinea pigs using Japanese cedar 
pollen as antigen. In the present study, we examined whether provocation by
pollen induces similar magnitudes of rhinitis symptoms in passively and actively 
sensitized guinea pigs. One group of animals was actively sensitized by
intranasal application of pollen extract, and another was passively sensitized by
intraperitoneal injection with anti-pollen serum. Actively and passively
sensitized groups were then challenged by repeated and a single pollen
inhalation, respectively. In both groups, sneeze was induced immediately after
the challenge. The actively sensitized animals developed not only early but also 
late nasal blockage, whereas the passively sensitized animals showed only early
nasal blockage. In both groups, an H1 antagonist, mepyramine, inhibited the
occurrence of sneezing but did not inhibit nasal blockage. Nasal
hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only
in the actively sensitized animals. We thus conclude that although early nasal
blockage is induced by a single antigen-antibody reaction, repetitive
anaphylactic reaction is required for occurrence of late nasal blockage and
hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in
induction of sneezing but not in nasal blockage, irrespective of whether animals 
are actively or passively sensitized.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11388645 [PubMed - indexed for MEDLINE]

1351: Int Arch Allergy Immunol. 2001 May;125(1):73-9.

Controlled comparison of the efficacy and safety of cetirizine 10 mg o.d. and
fexofenadine 120 mg o.d. in reducing symptoms of seasonal allergic rhinitis.

Horak F, Stübner P, Zieglmayer R, Kavina A, De Vos C, Burtin B, Donnelly F.

ENT Clinic, University of Vienna, Austria.

BACKGROUND: The efficacy, onset and duration of action and safety of cetirizine
10 mg o.d., fexofenadine 120 mg o.d., and placebo were compared in this
investigator-blinded, crossover study involving the use of the Vienna Challenge
Chamber. METHODS: 40 volunteers with seasonal allergic rhinitis were exposed to a
controlled grass pollen concentration for 6 h on 2 consecutive days. Subjective
symptoms and objective measurements were recorded during the allergen exposure
periods. RESULTS: Both active medications were significantly more effective than 
placebo and had a comparable onset of action in alleviating the symptoms of
seasonal allergic rhinitis. The efficacy of both active drugs was comparable for 
the first 4 h after administration of the drugs on day 1 and day 2. However from 
22 to 24 h after the first dose cetirizine was significantly superior to
fexofenadine for the major symptom complex score and for sneezing. Concerning the
total symptom complex score at day 2 fexofenadine could not reach superiority to 
placebo. No serious adverse events were reported. CONCLUSIONS: Cetirizine and
fexofenadine were significantly better than placebo, also in reducing the symptom
of nasal congestion. However cetirizine appears to have a longer duration of
action than fexofenadine. Copyright 2001 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11385291 [PubMed - indexed for MEDLINE]

1352: J Assoc Physicians India. 2001 May;49:518-22.

Efficacy of nimesulide alone and in combination with cetirizine in acute allergic
rhinitis.

Kotwani A, Puri R, Gupta U.

Department of Pharmacology, Maulana Azad Medical College and Associated LN
Hospital, New Delhi.

OBJECTIVE: To study the effect of cetirizine and nimesulide given alone and in
combination in allergic rhinitis. METHOD: A double blind, double dummy,
randomised, parallel controlled clinical study in three groups consisting of 18
patients each suffering from allergic rhinitis was conducted. Group A was given
nimesulide alone (100 mg BD), Group B received combination (nimesulide 100 mg +
cetirizine 10 mg) and Group C was given cetirizine alone (10 mg) for one week.
The efficacy of each treatment in reducing nasal stuffiness, nasal discharge,
itching nose and watery eyes was assessed at base line (day 0), on days four and 
eight of treatment. Patients used diary cards twice daily to rate symptom
severity on a four point scale. RESULTS: Nimesulide and cetirizine alone could
decrease nasal discharge, nasal stuffiness and sneezing significantly in allergic
rhinitis patients by day four. Cetirizine was more effective in relieving nasal
discharge and sneezing compared to nimesulide. By combining cetirizine and
nimesulide four symptoms of allergic rhinitis, i.e., nasal discharge, nasal
stuffiness, sneezing and watery eyes decreased significantly. CONCLUSION: Present
study has shown that nimesulide alone could decrease three symptoms of allergic
rhinitis like certirizine and combination of cetirizine (anti-histaminic) and
nimesulide (anti-inflammatory) exerts synergistic action in reducing symptoms in 
patients of allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11361264 [PubMed - indexed for MEDLINE]

1353: Clin Exp Allergy. 2001 Apr;31(4):616-24.

A comparison of topical budesonide and oral montelukast in seasonal allergic
rhinitis and asthma.

Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ.

Department of Clinical Pharmacology & Therapeutics, Ninewells Hospital & Medical 
School, University of Dundee, Dundee, UK.

BACKGROUND: Allergic rhinitis and asthma commonly coexist and are both mediated
by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an
alternative to corticosteroid therapy. OBJECTIVE: To compare oral montelukast
with inhaled plus intranasal budesonide in patients with seasonal allergic
rhinitis and asthma. PATIENTS AND METHODS: A single-blind double-dummy
placebo-controlled crossover study was performed comparing once daily 10 mg oral 
montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12
patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7),
forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was 
for 2 weeks with a 1-week placebo run-in and washout. Measurements were made
after each active treatment and placebo for: adenosine monophosphate bronchial
challenge, exhaled and nasal nitric oxide. Patients also recorded their
domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and
seasonal allergic rhinitis symptoms. RESULTS: There were no significant
differences between the placebos for any measurement. For adenosine monophosphate
PC20, geometric mean fold differences (95% confidence interval (CI) for
difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for
placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For
exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with
both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For
nasal nitric oxide and nasal peak flow there were only significant differences
with budesonide compared with placebo. Both treatments reduced total seasonal
allergic rhinitis symptoms but only budesonide had a significant effect on nasal 
symptoms. CONCLUSION: Once-daily inhaled plus intranasal budesonide and once
daily montelukast showed comparable efficacy on lower airway, but only the
budesonide had significant efficacy on upper airway inflammatory markers. Both
treatments significantly reduced allergic rhinitis symptoms.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11359431 [PubMed - indexed for MEDLINE]

1354: Clin Exp Allergy. 2001 Apr;31(4):555-64.

Comment in:
    Clin Exp Allergy. 2001 Apr;31(4):513-7.

IL-5 priming of the PMA-induced oxidative metabolism of human eosinophils from
allergic and normal subjects during a pollen season.

Woschnagg C, Garcia R, Rak S, Venge P.

Asthma Research Centre, University of Uppsala, Uppsala, Sweden.

AIM: To study the effect of IL-5 priming on the PMA-induced oxidative metabolism 
of blood eosinophils from allergic patients and healthy controls, during pollen
exposure. METHODS: Twenty birch pollen allergic patients with seasonal symptoms
of rhinitis or rhinitis plus asthma were studied during the birch pollen season
of Sweden. Eosinophils were purified to > 95% by Percoll gradients followed by
the MACS system. Oxidative metabolism was measured by a lucigenin enhanced
chemiluminescence (CL) assay. Eosinophils were primed with IL-5 and subsequently 
stimulated with PMA. The signal transduction mechanisms of IL-5 priming were
studied using the MEK inhibitor PD 98059, the PkC inhibitors Staurosporine, Ro
318220, Gö 6983 and the PI3kinase inhibitor Wortmannin. RESULTS: During the
season, the eosinophils from the allergic patients showed a reduced t(1/2)rise
compared to the non-allergic controls (P = 0.019) after stimulation. IL-5 reduced
the total PMA CL response both in control and patients' cells (P = 0.012 and
0.0054 resp.), whereas it primed it in terms of the t(1/2)rise of the curves, in 
both groups (P = 0.012 and 0.0015 resp.). The PMA-induced CL reactions were
inhibited by PD 98059, all PkC-inhibitors and Wortmannin. IL-5 priming
counteracted only the MEK inhibition significantly. CONCLUSIONS: Blood
eosinophils from allergic patients are primed in vivo, as compared to eosinophils
from non-allergic controls, during a pollen season. Interleukin-5 primes equally 
the PMA-induced oxidative metabolism of human eosinophils from healthy or
allergic subjects. The mechanism of IL-5 priming after PMA stimulation of oxygen 
radical production is MEK independent.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11359422 [PubMed - indexed for MEDLINE]

1355: N Z Med J. 2001 Mar 23;114(1128):114-20.

The burden of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema 
in children and adolescents in six New Zealand centres: ISAAC Phase One.

Asher MI, Barry D, Clayton T, Crane J, D'Souza W, Ellwood P, Ford RP, Mackay R,
Mitchell EA, Moyes C, Pattemore P, Pearce N, Stewart AW; International Study of
Asthma and Allergies in Childhood (ISAAC) Phase One.

Division of Paediatrics, Faculty of Medical and Health Sciences, University of
Auckland.

AIM: To describe the burden of symptoms of asthma, allergic rhinoconjunctivitis
and atopic eczema in children in six New Zealand centres. METHODS: The
International Study of Asthma and Allergies in Childhood (ISAAC) Phase One was
undertaken in Auckland, Bay of Plenty, Hawke's Bay, Wellington, Nelson and
Christchurch during 1992-1993. In each centre, approximately 3,000 six to seven
year old children and 3,000 thirteen to fourteen year old adolescents were
studied, a total of 37,592 participants. Both age groups answered written
questionnaires and the adolescents a video questionnaire about asthma symptoms.
RESULTS: The prevalences of symptoms were high, for asthma 25% and 30%, allergic 
rhinoconjunctivitis 10% and 19%, and atopic eczema 15% and 13% in each age group 
respectively. More than 40% of participants had symptoms in the last year of at
least one condition, most commonly asthma. There were no significant differences 
among regions, except for six to seven year olds in Nelson who had significantly 
lower prevalences of some symptoms of asthma and allergic rhinoconjunctivitis.
CONCLUSIONS: Asthma and allergies are common in New Zealand, with resultant
morbidity and cost. However, there is little regional variation with the
exception of lower rates in Nelson children. Explanations for these findings will
be the subject of further studies.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 11346157 [PubMed - indexed for MEDLINE]

1356: Ann Allergy Asthma Immunol. 2001 Apr;86(4):444-8.

Clinical and immunologic changes after allergen immunotherapy with Hop Japanese
pollen.

Park HS, Nahm DH, Kim HY, Suh YJ, Cho JW, Kim SS, Lee SK, Jung KS.

Department of Allergy and Clinical Immunology, Ajou University School of
Medicine, Suwon, Korea. hspark@madang.ajou.ac.kr

BACKGROUND AND OBJECTIVE: Hop Japanese (Hop J) pollen has been reported as one of
the major causative pollen allergens in the autumn season. There have been no
published data regarding the clinical and immunologic effects of Hop J pollen
immunotherapy in sensitized patients. In this study, we evaluated clinical and
immunologic effects of Hop J immunotherapy. PATIENTS AND METHODS: Pollens were
collected in our area, and "Depo-Hop J" was prepared in the laboratory of
Allergopharma (Reinbek, Germany). Fifteen asthmatic patients who had Hop J
immunotherapy for > 1 year were enrolled. Their clinical parameters, such as
asthma symptom scores, were monitored. Skin reactivity to Hop J and degree of
airway hyperresponsiveness to methacholine were measured before and 1 year after 
the immunotherapy. Sera were collected before the immunotherapy, at the end of
initial therapy, and 1 year after the therapy. Serum total IgE levels were
compared by radioimmunoassay. Serum-specific IgE, IgG1, and IgG4 levels to Hop J 
were compared by ELISA. To evaluate the changes of cellular mechanisms, soluble
CD30 (sCD30), soluble interleukin (IL)-2 receptor (sIL-2R), soluble CD23 (sCD23),
and IL-10 levels were measured by ELISA. RESULTS: Specific IgG1 and IgG4 levels
began to increase at the end of the initial therapy (P < 0.05) with significant
decreases in symptom scores (P < 0.05), whereas total and specific IgE levels
showed variable responses during the immunotherapy with no statistical
significance (P > 0.05). Serum sIL-2R and sCD30 levels decreased significantly (P
< 0.05) 1 year after immunotherapy. No significant changes were noted in sCD23,
IL-10, skin reactivity to Hop J, or airway responsiveness to methacholine (P >
0.05). CONCLUSIONS: We are certain that Hop J allergen immunotherapy, if carried 
out properly according to suitable indications, can favorably influence asthma.
Thus, an increase in specific IgG4 and IgG1 antibodies and reduction of a
possible Th2 lymphocyte marker (sCD30) may be associated with symptomatic
improvements.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11345290 [PubMed - indexed for MEDLINE]

1357: Ann Allergy Asthma Immunol. 2001 Apr;86(4):433-8.

Intranasal mometasone furoate reduces late-phase inflammation after allergen
challenge.

Ciprandi G, Tosca MA, Passalacqua G, Canonica GW.

Allergy & Respiratory Diseases, Department of Internal Medicine, University of
Genoa, Italy. giocip@unige.it

BACKGROUND: Allergen specific nasal challenge (ASNC) is an optimal model to study
the pathophysiologic mechanisms sustaining allergic inflammation, particularly
the adhesion molecules promoting cellular infiltration of nasal mucosa. Topical
corticosteroids have been accepted as a highly effective anti-inflammatory
therapy for allergic rhinitis. OBJECTIVE: The aim of this double-blind,
randomized, placebo-controlled study was the evaluation of inflammatory events,
during the late-phase, after a 2-week treatment with nasal mometasone furoate
(MF), 200 microg daily, or placebo, using the model of ASNC. METHODS: A total of 
42 patients with allergic rhinitis underwent nasal challenge before and after
treatment. The following parameters were evaluated at baseline, and 6 hours
(late-phase) after ASNC: 1) nasal symptoms (rhinorrhea, itching, sneezing,
obstruction); 2) inflammatory cells (eosinophils and neutrophils); 3) eosinophil 
cationic protein (ECP) and tumor necrosis factor-alpha (TNF-alpha) in nasal
lavage; and 4) intercellular adhesion molecule-1 expression on nasal epithelial
cells. RESULTS: MF nasal spray was associated with late-phase reductions of: 1)
clinical symptoms (P < 0.03); 2) eosinophil (P < 0.004) and neutrophil (P <
0.003) infiltration; 3) ECP (P < 0.001) and TNF-alpha (P < 0.05); and 4)
intercellular adhesion molecule-1 expression on nasal epithelial cells (P <
0.001). CONCLUSIONS: The present results demonstrate that MF has a significant
effect on late-phase events, reducing the cellular influx and activation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11345288 [PubMed - indexed for MEDLINE]

1358: Ann Allergy Asthma Immunol. 2001 Apr;86(4):393-6.

Quality of life indices may be predictive of placebo and medication response to
treatment for allergic rhinitis.

Ellis AK, Rafeiro E, Day JH.

Internal Medicine, Queen's University, Kingston, Ontario, Canada.

BACKGROUND: Quality of life (QOL) is known to be an important clinical endpoint
in determining medication efficacy; however, the predictive value of QOL indices 
for response to medication or placebo has not been tested. OBJECTIVE: To
determine whether a correlation between measures of QOL and response to
medication/placebo exists in an evaluation of budesonide for allergic rhinitis.
METHODS: Two hundred nine participants completed the 36-item short-form health
QOL survey at screening for entry into a study examining the onset of action of
budesonide in an allergen challenge system. During the treatment phase, symptom
assessments were recorded hourly after dosing of double-blind medication.
Participants were determined to be responders or nonresponders to study
medication. A responder was defined as a participant who rated medication
effectiveness as fair to excellent with regard to symptom relief, for three
consecutive hourly assessments during the study day or one whose total symptom
score decreased by > or =25% for three consecutive hourly assessments. Baseline
QOL scores were compared between responders and nonresponders. RESULTS:
Differences were noted among responders and nonresponders on the basis of whether
budesonide or placebo was received. Ratings of general health perception, pain,
physical function, and role limitation due to physical health were significantly 
lower among participants who responded to placebo, compared with placebo
nonresponders. In addition, the overall physical health and 36-item short-form
health survey averages were significantly lower. Differences between responders
and nonresponders to budesonide did not reach statistical significance.
CONCLUSIONS: Lower baseline QOL scores were associated with a clinically
significant response to placebo in a trial of treatment for allergic rhinitis.
QOL may be a factor in participant response to medication in clinical studies
and, hence, a predictor of outcome.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11345281 [PubMed - indexed for MEDLINE]

1359: Ann Allergy Asthma Immunol. 2001 Apr;86(4):382-6.

Is it important to perform pollen skin prick tests in the season?

Sin BA, Inceoglu O, Mungan D, Celik G, Kaplan A, Misirligil Z.

University of Ankara, Faculty of Medicine, Department of Allergic Diseases,
Turkey. betulayse83@hotmail.com

BACKGROUND: Seasonal exposure to pollens causes the characteristic symptoms of
respiratory allergy as well as an increase in specific IgE levels and
inflammatory mediator release. However, little is known about the effect of
natural allergen exposure on the skin test reactivity of patients with seasonal
allergy. OBJECTIVE: The aim of this study was to investigate the monthly
variation in skin test reactions with pollen allergens during pollen season and
its relation to pollen counts. METHODS: Fifteen subjects with seasonal allergic
rhinitis and/or asthma (4 male, 11 female) between the ages of 13 and 52 (mean
33.9 +/- 2.9) who lived in Ankara, Turkey were selected for this study. Patients 
were monitored from the beginning of March to the end of September 1997, and skin
prick tests were performed using 5 grass, 12 tree, and 5 weed pollen allergen
extracts every month. Atmospheric pollen grains were counted in the Ankara area
between January and December, 1997. RESULTS: There were small but statistically
significant increases in tree pollen-induced wheal sizes in May when compared
with other months (P < 0.05). Skin test reactivity was correlated with tree
pollen counts (r = 0.978, P < 0.05). There was not a significant difference in
skin test reactivity to grass and weed pollens between months. CONCLUSIONS:
Although skin test reactivity may be slightly greater to tree pollen during the
tree pollen season, the timing of skin testing is not a critical determinant in
patients with pollen allergy.

PMID: 11345279 [PubMed - indexed for MEDLINE]

1360: J Allergy Clin Immunol. 2001 May;107(5):878-86.

Perforin hyperreleasability and depletion in cytotoxic T cells from patients with
exacerbated atopic dermatitis and asymptomatic rhinoconjunctivitis allergica.

Ambach A, Bonnekoh B, Gollnick H.

Department of Dermatology and Venereology, Otto-von-Guericke-University,
Magdeburg, Germany.

BACKGROUND: As a plasma membrane pore-forming protein, perforin is essential for 
T-cell cytotoxicity mediated by lytic granules. Recent studies on the immune
system of perforin knockout mice demonstrated striking similarities to the
immunopathology of atopic diseases. OBJECTIVE: We sought to investigate the
perforin system of atopic patients. METHODS: Monoclonal antibodies were used to
characterize perforin-positive PBMCs of patients with exacerbated atopic
dermatitis (AD) and asymptomatic rhinoconjunctivitis allergica (RCA) by means of 
immunoflow cytometry. In addition, a perforin release assay was developed to
quantify the velocity of ionomycin and phorbol 12-myristate 13-acetate-induced
secretion of lytic granules. RESULTS: In atopic patients significantly fewer
lymphocytes contained perforin-positive lytic granules compared with those of
healthy control subjects (patients with AD: 14% +/- 5%, n = 13, P <.0001;
patients with RCA: 24% +/- 5%, n = 9, P <.01; healthy control subjects: 33% +/-
11%, n = 13). Of all CD8(hi+) cytotoxic T lymphocytes (CTLs), only 18% +/- 9% and
17% +/- 12% were perforin-positive in patients with AD and RCA, respectively,
compared with 44% +/- 13% in control subjects (P <.0001). In addition,
perforin-positive CD8(hi+) CTLs of atopic patients released their perforin twice 
as fast and more completely than control CTLs. This means that 50% of initially
perforin-positive CD8(hi+) CTLs from patients with AD and RCA released their
perforin completely within 32 +/- 16 and 36 +/- 19 minutes, respectively, and an 
over 85% release was reached within 113 +/- 41 and 118 +/- 60 minutes,
respectively. In CTLs of healthy control subjects, however, it took 64 +/- 40
minutes to achieve a 50% release of lytic granules, and an 85% depletion was not 
reached in 60% of healthy control subjects, even after 180 minutes. CONCLUSION:
The perforin hyperreleasability explains, at least in part, the decreased
percentage of perforin-positive CD8(hi+) CTLs in atopic patients. These
distortions in the system of lytic granules of atopic patients may contribute to 
the functional defects observed in T-cell cytotoxicity in vivo and in vitro in
patients with AD and RCA.

Publication Types: 
    Comparative Study

PMID: 11344356 [PubMed - indexed for MEDLINE]

1361: Br Homeopath J. 2001 Apr;90(2):73-8.

Prophylactic and acute treatment with the homeopathic medicine, Betula 30c for
birch pollen allergy: a double-blind, randomized, placebo-controlled study of
consistency of VAS responses.

Aabel S.

Institute of General Practice and Community Medicine, Department of General
Practice, University of Oslo, Norway. siri.aabel@samfunnsmed.uio.no

A study of the consistency of responses by allergic patients in repeated studies 
of the homeopathic remedy Betula 30c or placebo against birch pollen allergy, was
made. A randomized, double-blind, placebo-controlled trial was performed
including participants with a known allergy to birch pollen. Allergy symptoms
were assessed on a visual analogue scale (VAS) by patients or parents each day
during a 20-day period during two different pollen seasons. The work was carried 
out in Oslo, Norway during May 1995, 1996 and 1997. There were 51 patients
ranging in age from 7 to 50y. The homeopathic remedy Betula 30c or placebo was
given as tablets, both as a prophylactic agent, once a week for 4 weeks before
the pollen season started, and as an acute remedy during the pollen season. The
mean value of the symptom scores on the visual analogue scale, for all
registration days from each patient was the main outcome. The patient groups that
received either placebo or Betula 30c for two successive years showed a
consistent response (r=0.75, P=0.01 and r=0.70, P=0.003, respectively). No such
correlation was found in the two groups that changed remedy from one year to
another (either from placebo to Betula or vice versa). Subjective assessment of
allergic symptoms to birch pollen differed more from one year to another when
different regimens (placebo or homeopathic) had been administered these two
seasons, than when the same treatment had been given.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11341460 [PubMed - indexed for MEDLINE]

1362: Pediatr Allergy Immunol. 2001 Apr;12(2):95-101.

International Study of Asthma and Allergies in Childhood: validation of the
rhinitis symptom questionnaire and prevalence of rhinitis in schoolchildren in
São Paulo, Brazil.

Vanna AT, Yamada E, Arruda LK, Naspitz CK, Solé D.

Division of Allergy, Clinical Immunology and Rheumatology, Department of
Pediatrics, Universidade Federal de São Paulo, Escola Paulista de Medicina
(UNIFESP-EPM), São Paulo, SP, Brazil.

Written questionnaires (WQ) have been widely used in epidemiologic studies. In
order to yield comparable results, they must be validated after translation to
another language. The International Study of Asthma and Allergies in Childhood
(ISAAC) WQ has been previously validated by a comprehensive study, but its
validation in Brazil has not been performed. Our objectives were to validate the 
rhinitis component of the ISAAC's self-applicable WQ following its translation to
Portuguese, and to determine the prevalence of rhinitis and related symptoms
among Brazilian children living in the city of São Paulo. A group of 10
pediatricians and 10 pediatric allergists graded the questions from 0 to 2 and
established a maximum score for each question. The WQ was answered by parents or 
guardians of children 6-7 years of age with rhinitis (R) (n = 27) and of control 
children of the same age without rhinitis (C) (n = 27). The WQ was also completed
by adolescents 13-14 years of age with rhinitis (R) (n = 32) and without rhinitis
(C) (n = 32). Half of these individuals answered the same WQ after 2-4 weeks, to 
ensure reproducibility. Cut-off scores of 4 and 3 were identified for the 6-7-
and 13-14-year-old groups, respectively, as scores predictive of rhinitis. The
prevalence of rhinitis was 28.8% in the group of 3005 children 6-7 years of age
and 31.7% in the group of 3008 children 13-14 years of age, respectively. Using
the global cut-off score, these prevalences were even higher, in the order of
34.7% and 40.7%, respectively. In conclusion, the rhinitis component of the ISAAC
WQ was proven to be reproducible, adequate and able to discriminate children and 
adolescents with and without rhinitis, and revealed that the prevalence of
rhinitis among Brazilian children living in the city of São Paulo was as high as 
the prevalence of rhinitis in other areas of the world.

Publication Types: 
    Comparative Study

PMID: 11338293 [PubMed - indexed for MEDLINE]

1363: Am J Respir Crit Care Med. 2001 Apr;163(5):1108-12.

Erratum in:
    Am J Respir Crit Care Med. 2002 Sep 1;166(5):774-5.

Asthma, rhinitis, and skin test reactivity to aeroallergens in families of
asthmatic subjects in Anqing, China.

Celedón JC, Palmer LJ, Weiss ST, Wang B, Fang Z, Xu X.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital,
Boston, Massachusetts 02115, USA. juan.celedon@channing.harvard.edu

In industrialized countries with a Western lifestyle, sensitization to perennial 
aeroallergens is strongly associated with asthma, whereas sensitization to
seasonal aeroallergens is closely related to allergic rhinitis. Little is known, 
however, about the relation between skin test reactivity to aeroallergens and
either asthma or rhinitis in mainland China. We studied 10,009 members of 2,544
families in Anqing (China) that were selected on the basis of physician-diagnosed
asthma in at least two siblings. Generalized estimating equations were employed
to study the association between skin test reactivity to aeroallergens and either
asthma or rhinitis. After adjustment for age, sex, intensity of smoking, skin
test reactivity to other aeroallergens, and household correlations, sensitization
to dust mite was an independent predictor of both asthma (OR = 1.3, 95% CI = 1.1 
to 1.5, p = 0.008) and rhinitis (OR = 1.3, 95% CI = 1.0 to 1.8, p = 0.04).
Sensitization to mold was significantly associated with asthma (OR = 1.6, 95% CI 
= 1.1 to 2.3, p = 0.008), and sensitization to silk was an independent predictor 
of rhinitis (OR = 1.5, 95% CI = 1.1 to 2.2, p = 0.02). Although 46.9% of the
study participants were sensitized to at least one allergen, only 3.5% of study
subjects reported nasal symptoms consistent with rhinitis. Among asthmatic
subjects, 6.2% reported nasal symptoms. Whereas sensitization to perennial
aeroallergens was associated with asthma among families of asthmatic subjects in 
rural China, sensitization to silk was the strongest predictor of rhinitis in
this population. Our findings also suggest that allergic rhinitis is far less
common among asthmatic subjects in rural China than in asthmatic subjects in
industrialized countries with a Western lifestyle.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11316644 [PubMed - indexed for MEDLINE]

1364: Asian Pac J Allergy Immunol. 2000 Dec;18(4):187-94.

Survey of the prevalence of asthma, allergic rhinitis and eczema in
schoolchildren from Khon Kaen, Northeast Thailand. an ISAAC study. International 
Study of Asthma and Allergies in Childhood.

Teeratakulpisarn J, Pairojkul S, Heng S.

Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Thailand.

This survey of schoolchildren from Khon Kaen, Northeast Thailand used the
standardized ISAAC questionnaires to estimate the prevalence of asthma and other 
allergic diseases and to compare the results with two previous studies. A total
of 6,068 questionnaires were analyzed (2,658, 45.6% males from the 6 to 7 years
old group and 3,410, 49.5% male from the 13 to 14 years old group). The three
predominant cumulative and 12-month conditions discerned from the written
questionnaires among the 6 to 7 vs 13 to 14 years old were: wheezing, at 18.6%
and 10.2% vs 20.5% and 11.0%; rhinitis at 38.4% and 33.5% vs 59.4% and 42.5%; and
eczema at 18.0% and 15.2% vs 9.9% and 7.4%, respectively. The observed
prevalences in our study were similar to those found in Bangkok and slightly
higher than those in Chiang Mai, except for 'exercise wheezing' in older children
which was two times higher in our study than in the two previous studies. Our
study showed seasonal variation of the 'nose' symptoms. The peak prevalence was
in the relatively cool and dry season (between November and January), which was
the same pattern as Chiang Mai but different from Bangkok (which had a perennial 
pattern and less climatic variation). Our results concurred with the two previous
Thai ISAAC studies. There is a high prevalence of asthma and other allergic
diseases among Thai children and there has been a four-fold increase in symptoms 
since the last decade. If the trend persists asthma and allergic disease may
become a pressing health concern of the country.

PMID: 11316038 [PubMed - indexed for MEDLINE]

1365: Eur Respir J. 2001 Jan;17(1):64-70.

Bronchoconstriction induced by inhaled adenosine 5'-monophosphate in subjects
with allergic rhinitis.

Prieto L, Gutiérrez V, Liñana J, Marín J.

Sección de Alergología and Universidad de Valencia, Spain.

Adenosine and its related nucleotide, adenosine 5'-monophosphate (AMP) induce
bronchoconstriction in asthmatics, probably caused by histamine release from
airway mast cells. The objective of this study was to determine the effect of
inhaled AMP on lung function in subjects with allergic rhinitis. A total of 52
adults (28 subjects with allergic rhinitis, 14 asthmatics and 10 healthy
subjects) were challenged with increasing concentrations of AMP and methacholine.
Airflow was assessed after each concentration and the response to each
bronchoconstrictor agent was measured by the provocative concentration required
to produce a 20% fall (PC20) in forced expired volume in one second (FEV1). All
14 asthmatics, 10 subjects with allergic rhinitis and none of the healthy
controls were hyperresponsive to AMP. Subjects with allergic rhinitis had higher 
prevalence of hyperresponsiveness to AMP than healthy controls (p=0.038).
Although the prevalence of hyperresponsiveness for methacholine and for AMP in
subjects with allergic rhinitis was similar (39% and 36%, respectively), four
subjects had hyperresponsiveness to methacholine but not to AMP, whereas three
subjects had hyperresponsiveness to AMP but not to methacholine. To conclude,
inhaled adenosine 5'-monophosphate causes airway narrowing in a significantly
higher proportion of subjects with allergic rhinitis than healthy volunteers.
Furthermore, methacholine and adenosine 5'-monophosphate hyperresponsiveness are 
not detected in the same individuals with allergic rhinitis, thus suggesting that
responsiveness to the two bronchoconstrictor stimuli is not reflecting the same
abnormalities of the airways.

PMID: 11307758 [PubMed - indexed for MEDLINE]

1366: Arzneimittelforschung. 2001;51(3):232-7.

Efficacy and safety of intranasally applied dimetindene maleate solution.
Multicenter study in children under 14 years suffering from seasonal allergic
rhinitis.

Bauer CP, Unkauf M.

Kinderfachklinik, Gaissach, Germany.

The aim of this study was to investigate the efficacy and tolerability of
intranasally applied dimetindene (CAS 3614-69-5) 0.1% spray in children suffering
from seasonal allergic rhinitis. A total of 100 children under 14 years with
acute seasonal allergic rhinitis participated in this randomised, single-blind,
reference-controlled, multi-center, parallel group study with two treatment
groups. The study took place between 2nd April and 16th September 1996 during the
pollen season. Patients were examined at enrollment (day 1), day 8 and day 15.
Patients kept diary throughout the 2-week treatment phase. Patients were
randomised to receive either dimetindene 0.1% (Fenistil Nasal Spray) or a
levocabastine (CAS 79516-68-0) 0.05% solution as reference medication. Both
medications were supplied in similar outer packages. A single-blind approach was 
chosen, because the reference medication levocabastine requires two spray puffs
per nostril as a single dose, whereas for dimetindene maleate solution a single
spray puff per nostril is sufficient. Dimetindene 0.1% was applied with 1 spray
puff (= 0.14 mg dimetindene) in each nostril and levocabastine with 2 spray puff 
(= 0.10 mg levocabastine) in each nostril every day in the morning before leaving
the house and in the evening before going to bed. Additional administration of
the spray was allowed up to 4 times a day if needed. Efficacy was assessed as
change in severity of characteristic symptoms associated with pollen rhinitis:
nasal rhinorrhea, nasal itching, nasal sneezing and nasal congestion. In
addition, changes in ocular symptoms, lacrimation, ocular itching and red eyes,
global physician's assessment of efficacy at the end of treatment were assessed. 
The primary criterion change of total nasal symptom severity score between day 1 
and day 3 resulted in a statistically equivalent and therapeutically relevant
symptom reduction for the two treatments. All secondary criteria showed a similar
reduction in symptoms, thus underlining the consistency of the findings. Both
nasal sprays were well tolerated. It is concluded from these results that
dimetindene 0.1% nasal spray solution is a safe and efficient treatment option
for children under 14 years suffering from seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11304939 [PubMed - indexed for MEDLINE]

1367: J Allergy Clin Immunol. 2001 Apr;107(4):627-33.

Fluticasone propionate aqueous nasal spray reduces inflammatory cells in
unchallenged allergic nasal mucosa: effects of single allergen challenge.

Holm A, Dijkstra M, Kleinjan A, Severijnen LA, Boks S, Mulder P, Fokkens W.

Departments of Otorhinolaryngology and Biostatistics, Erasmus University Medical 
Center Rotterdam, The Netherlands.

BACKGROUND: Topical corticosteroid therapy reduces symptoms and nasal mucosal
inflammatory cells in patients with allergic rhinitis. Usually patients are
advised to start their medication (1 week) before the beginning of the pollen
season. The effect of pretreatment with a topical corticosteroid on unchallenged 
nasal mucosa is not well documented. OBJECTIVES: The purpose of this study was to
investigate, in a double-blind, placebo-controlled study, the effect of 6 weeks' 
pretreatment with 200 microg twice daily fluticasone propionate on nasal symptoms
and inflammatory cell numbers after nasal allergen provocation in patients with
seasonal allergic rhinitis. METHODS: Nineteen patients with grass pollen-induced 
allergic rhinitis were treated for a 6-week period out of the grass pollen
season. After completing the treatment period, patients were challenged with
grass pollen. Nasal mucosal biopsy specimens were taken 5 times in every patient.
In nasal mucosa changes in numbers of T cells, B cells, mast cells, eosinophils, 
macrophages, and Langerhans' cells were investigated. RESULTS: After 4 weeks of
treatment but before allergen provocation, significantly fewer epithelial
Langerhans' cells, macrophages, mast cells, T cells, and eosinophils were found
in the fluticasone propionate group compared with those found in the placebo
group. In the lamina propria significantly fewer Langerhans' cells and
eosinophils were found in the fluticasone propionate group. Cell influx in nasal 
mucosa after allergen provocation was significantly inhibited in the fluticasone 
propionate group compared with that in the placebo group for epithelial
Langerhans' cells, mast cells, macrophages, and T cells and for lamina propria
eosinophils, mast cells, Langerhans' cells, macrophages, and T cells.
CONCLUSIONS: Fluticasone propionate is effective in reducing early- and
late-phase nasal symptoms. Topical corticosteroid treatment reduces inflammatory 
cells in unchallenged nasal mucosa.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11295650 [PubMed - indexed for MEDLINE]

1368: Yonsei Med J. 2001 Feb;42(1):106-13.

The effect of immunotherapy on nonspecific bronchial hyperresponsiveness in
bronchial asthma and allergic rhinitis.

Chang J, Hong CS.

Department of Internal Medicine and Institute of Allergy, Yonsei University
College of Medicine, Seoul, Korea.

Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness,
but results at the moment are less than convincing. The present study was
conducted to evaluate the effect of immunotherapy on the degree of nonspecific
bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA)
and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test,
allergic skin test, serum IgE and peripheral blood eosinophil counts were
performed before and after 12 months or more of immunotherapy. The improved
group, as determined by a shift of at least two doubling concentrations of
methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR
(n=13). The geometric mean of the methacholine provocational concentration (PC20)
changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA
(not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In
conclusion, nonspecific bronchial hyperresponsiveness was improved by
immunotherapy in three quarters of the allergic rhinitis cases and in about a
half of the allergic bronchial asthma patients, which suggests that immunotherapy
might be helpful at preventing the development of bronchial hyperresponsiveness
in allergic rhinitis patients, and that it does not improve bronchial
hyperresponsiveness in about a half of allergic bronchial asthma patients.

PMID: 11293488 [PubMed - indexed for MEDLINE]

1369: Allergy. 2000;55 Suppl 64:7-16.

Allergic rhinitis: not purely a histamine-related disease.

Howarth PH, Salagean M, Dokic D.

Department of Medical Specialities, University of Southampton, UK.

Allergic rhinitis is an inflammatory disorder of the nasal mucosa typified by the
symptoms of nasal itch, sneeze, anterior nasal secretions, and nasal blockage.
These symptoms arise from the interaction between mediators and neural, vascular,
and glandular structures within the nose. Nasal itch, sneezes, and rhinorrhoea
are predominantly neural in origin, while nasal obstruction is predominantly
vascular. Nasal biopsy studies show accumulation of eosinophils within the lamina
propria and epithelium and an increase in tissue and cell surface basophils in
both seasonal and perennial allergic rhinitis. These cells are in an activated
state. Within the epithelium, increased numbers of mast cells, T cells and
Langerhans' cells, which induce T-cell activation, are found. The accumulation of
these cells can be linked to chemokine and cytokine generation by the epithelial 
cells themselves. Thus, the tissue cell recruitment is orchestrated by activated 
mast cells, T cells, and epithelial cells, with the recruited tissue eosinophils 
also contributing to their persistence at this site through autocrine mechanisms.
Mast cells generate an array of mediators including histamine, tryptase,
leukotrienes, and prostaglandins. Histamine is also generated by basophils.
Eosinophils and basophils contribute to the leukotriene synthesis within the
tissue. Histamine nasal insufflation induces nasal itch, sneeze, and rhinorrhoea 
as well as nasal blockage, thereby reproducing all the symptoms of allergic
rhinitis. These effects are primarily mediated by H1-receptors, and H1-receptor
antagonists are a prominent treatment. Antagonism of histamine at these receptors
reduces symptoms by about 40-50%, with the greatest effect on the neurally
mediated responses. Thus, histamine is a major mediator of allergic rhinitis, but
not the sole contributor. Nasal insufflation with leukotrienes, prostaglandins,
or kinins is associated with the development of nasal blockage. These mediators
act primarily on the nasal vasculature and, in this respect, leukotrienes are
potent mediators. Leukotrienes also induce plasma protein exudation, which
contributes to the anterior nasal secretions. Studies with combination products
have suggested that modifying the effects of both leukotrienes and histamine has 
complementary effects in relieving nasal symptoms, indicating that both these
mediators are relevant to disease expression.

Publication Types: 
    Review

PMID: 11291780 [PubMed - indexed for MEDLINE]

1370: Ann Allergy Asthma Immunol. 2001 Mar;86(3):337-42.

Pollen-specific rush immunotherapy: clinical efficacy and effects on antibody
concentrations.

Movérare R, Vesterinen E, Metso T, Sorva R, Elfman L, Haahtela T.

Pharmacia Diagnostics AB, Uppsala, Sweden. robertmoverare@hotmail.com

BACKGROUND: Studies of rush immunotherapy (RIT) with standardized extracts for
the treatment of seasonal pollen allergy are few, especially for birch-pollen
RIT. OBJECTIVE: The study was performed to investigate the efficacy of RIT with
standardized birch- or timothy-pollen extracts. Further, the serum antibody
levels were evaluated for correlation with clinical efficacy. METHODS: This open,
longitudinal study included 30 allergic patients treated with RIT and 16 allergic
patients serving as a control group. The therapy was continued for 3 years and
blood samples were collected at regular intervals for antibody measurements using
the Pharmacia CAP System. RESULTS: The RIT was generally well tolerated. An
increase in the total and specific IgE concentrations during the early months of 
RIT was observed, followed by decreased levels. Specific IgG and IgG4 increased
continuously for 2 years. The symptom and medication scores were significantly
decreased, compared with preRIT, at both the first and third pollen seasons after
the start of RIT treatment (P < .0001 and P < .001, respectively). The clinical
improvement during RIT was significantly greater compared with the control group 
(P < .05). The decreased medication and the symptom improvement during the third 
year of RIT correlated with the relative decrease in specific IgE (rs = .52, P < 
.05) and with the specific IgG4 level before the start of RIT (rs= -.68, P <
.01), respectively. CONCLUSIONS: Our study indicates that RIT with standardized
birch- or timothypollen extracts is clinically effective and safe. Measurements
of specific antibody levels during treatment may be helpful in monitoring RIT.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11289336 [PubMed - indexed for MEDLINE]

1371: Allergy. 2001 Apr;56(4):313-7.

Health-related quality of life assessment in young adults with seasonal allergic 
rhinitis.

Majani G, Baiardini I, Giardini A, Senna GE, Minale P, D'Ulisse S, Ciprandi G,
Canonica GW.

Servizio di Psicologia, Fondazione S Maugeri, Clinica del Lavoro e della
Riabilitazione, IRCCS, Istituto Scientifico di Montescano, Italy.

BACKGROUND: In health-related quality of life (HRQL) studies on allergic
rhinitis, both disease-specific and generic questionnaires have been extensively 
used. Seasonal allergic rhinitis (SAR) has been studied mainly by focusing on
symptomatology. The present study aimed to evaluate the SAR-HRQL by means of two 
questionnaires, the Medical Outcome Study Short Form Health Survey (SF-36) and a 
new instrument examining satisfaction in 32 aspects of daily life: the
Satisfaction Profile (SAT-P). METHODS: Thirty-three patients with SAR (aged
33.5+/-8.5 years; 12 men, 21 women) were evaluated during and 2 months after the 
pollen season. Data were compared with reference samples by t-test, and baseline 
and follow-up HRQL scores were compared by a matched-pair test. RESULTS:
Patients' HRQL scores collected during the pollen season were significantly lower
than reference sample data in many SF-36 scores and in one SAT-P item. No
differences emerged between SF-36 and SAT-P scores collected outside the pollen
season and reference sample scores. Compared to baseline, outside the pollen
season, patients reported significantly higher scores in the following SF-36
scales: physical functioning (P=0.002), physical role (P=0.00001), bodily pain
(P=0.01), and vitality (P=0.008); and significantly higher scores in only two
SAT-P items (physical well-being [P=0.009] and resistance to stress [P=0.01]).
CONCLUSIONS: Our data confirm the utility of using symptomatologic and
health-status questionnaires in evaluating the HRQL of SAR patients. More general
quality of life questionnaires may prevent the symptomatologic and functional
problems from being adequately recognized and managed. SAT-P can be a fruitful
additional tool in HRQL evaluation.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11284798 [PubMed - indexed for MEDLINE]

1372: Am J Epidemiol. 2001 Apr 1;153(7):704-14.

Association between air pollution and daily consultations with general
practitioners for allergic rhinitis in London, United Kingdom.

Hajat S, Haines A, Atkinson RW, Bremner SA, Anderson HR, Emberlin J.

Department of Primary Care and Population Sciences, Royal Free and University
College Medical School, London, United Kingdom. Shakoor.Hajat@lshtm.ac.uk

Few published studies have looked at the health effects of air pollution in the
primary care setting, and most have concentrated on lower rather than upper
respiratory diseases. The authors investigated the association of daily
consultations with general practitioners for allergic rhinitis with air pollution
in London, United Kingdom. Generalized additive models were used to regress time 
series of daily numbers of patients consulting for allergic rhinitis against
1992--1994 measures of air pollution, after control for possible confounders and 
adjustment for overdispersion and serial correlation. In children, a 10th--90th
percentile increase in sulfur dioxide (SO(2)) levels 4 days prior to consultation
(13-31 microg/m(3)) was associated with a 24.5% increase in consultations (95%
confidence interval: 14.6, 35.2; p < 0.00001); a 10th--90th percentile increase
in averaged ozone (O(3)) concentrations on the day of consultation and the
preceding 3 days (6--29 parts per billion) was associated with a 37.6% rise (95% 
confidence interval: 23.3, 53.5; p < 0.00001). For adults, smaller effect sizes
were observed for SO(2) and O(3). The association with SO(2) remained highly
significant in the presence of other pollutants. This study suggests that air
pollution worsens allergic rhinitis symptoms, leading to substantial increases in
consultations. SO(2) and O(3) seem particularly responsible, and both seem to
contribute independently.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11282799 [PubMed - indexed for MEDLINE]

1373: Ann N Y Acad Sci. 2000;917:853-9.

Conditioning rhinitis in allergic humans.

Barrett JE, King MG, Pang G.

Department of Psychology, University of Newcastle, NSW, 2308, Australia.
judy.barrett@dsto.defence.gov.au

A classical Pavlovian paradigm pairing an olfactory cue with allergen challenge
for a single training trial was used to produce conditioned histamine release and
conditioned nasal airflow decrease in seasonal allergic rhinitis sufferers. There
was no conditioned increase in subjective symptoms. Histamine release and airflow
decrease showed evidence of extinction by a second test trial. A second study
comparing the effects of the number of training trials showed that three training
trials produced greater histamine release and airflow decrease than a single
training trial, suggesting stronger effects with additional training.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11268416 [PubMed - indexed for MEDLINE]

1374: Clin Exp Allergy. 2001 Mar;31(3):409-16.

Exhaled nitric oxide in seasonal allergic rhinitis: influence of pollen season
and therapy.

Gratziou C, Rovina N, Lignos M, Vogiatzis I, Roussos C.

Asthma and Allergy Center, Pulmonary and Critical Care Department, University of 
Athens Medical School, Evgenidio Hospital, 20 Papadiamantopoulou, 115 28 Ilisia, 
Athens, Greece. chgratziou@hotmail.com

Exhaled nitric oxide (eNO) has been proposed as a potential indirect marker of
lower airway inflammation in asthma. To investigate the existence of lower
airways inflammation in allergic rhinitis eNO measurements were performed in 32
patients with symptomatic and asymptomatic seasonal allergic rhinitis early in
and out of pollen seasons and in 80 healthy volunteers. To further define how
exhaled NO is modified by therapy, NO levels were detected following 1-month
treatment with either inhaled steroids or non-steroids therapy with nedocromil.
Exhaled NO (mean +/- SE) was significantly elevated in patients with seasonal
allergic rhinitis with and without symptoms (24.2 + 2.5 and 13.9 + 2.9 ppb,
respectively) as compared to healthy volunteers (4.5 + 0.3 ppb) both in and out
of pollen season (21.2 + 2.1 and 9.0 + 1.4 p.p.b., respectively) with a higher
increase during the allergen exposure in season. Higher levels of exhaled NO were
detected in patients with symptoms, either from the upper or lower airways, and
with bronchial hyperreactivity. The increased exhaled NO in symptomatic patients 
was reduced only by inhaled steroids and not by nedocromil. These findings
possibly suggest the existence of lower airway inflammation in both symptomatic
and asymptomatic patients with seasonal allergic rhinitis in and out of pollen
season. Thus, exhaled NO may be used as a non-invasive index for early detection 
of lower airway inflammation and for monitoring the optional treatment in
patients with seasonal allergic rhinitis.

PMID: 11260152 [PubMed - indexed for MEDLINE]

1375: Ann Allergy Asthma Immunol. 2001 Feb;86(2):222-5.

Validation of the rhinitis outcomes questionnaire (ROQ).

Santilli J, Nathan R, Glassheim J, Rockwell W, Gold K.

Bridgeport, Connecticut 06606, USA. john@santilli.org

BACKGROUND: Currently, there is no easy-to-use and comprehensive questionnaire
that measures the effectiveness of treatment of rhinitis-related symptoms in a
private practice setting. OBJECTIVE: To validate a brief, effective,
self-administered rhinitis symptoms questionnaire that can easily be used in a
private practice setting for tracking treatment outcomes. METHODS: One hundred
seventy-five patients were randomly chosen from three private practices
nationwide and were surveyed regarding systemic problems, nasal, eye, and chest
symptoms, as well as medical treatment obtained. This survey was administered
twice in one sitting with the first administration a recall of symptoms before
immunotherapy, and the second administration an evaluation of current symptoms.
Appropriate statistical methods were used to evaluate the validity, reliability, 
and responsiveness of the questionnaire presented. The validation of this
instrument included content, statistical, construct, and predictive validity.
RESULTS: Both the content and statistical validity were very good in that the
questionnaire was easily understood and covered required domains. Construct
validity revealed that the items were sensibly related to the domains that
contained them and had less association with items from different domains. The
reliability of the scales was very good (Cronbach's alpha = 0.80) to outstanding 
(Cronbach's alpha = 0.92). CONCLUSIONS: Functionality was established for the
rhinitis outcomes questionnaire (ROQ) for use in a private practice setting. This
allows private practice allergists to collect reliable data with the ROQ.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 11258694 [PubMed - indexed for MEDLINE]

1376: Allergy. 2001 Mar;56(3):243-6.

Receiver operating characteristics curve analysis of cutaneous skin test
reactions to predict hay fever and asthma symptoms in the Normative Aging Study.

Weintraub JM, Sparrow D, Weiss ST.

Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA, USA.

BACKGROUND: We used receiver operating characteristic (ROC) curves to determine
optimal cutoff values and to evaluate the ability of ragweed, mixed grasses,
mixed trees, and house-dust antigens to predict symptoms of hay fever and asthma.
METHODS: Between 1984 and 1993, 1386 members of the Normative Aging Study cohort 
had at least one examination that included evaluation of cutaneous
hypersensitivity to common aeroallergens by skin prick testing. Standard
questionnaires based on the American Thoracic Society DLD-78 questionnaire
obtained information on respiratory symptoms, illness, and smoking habits.
RESULTS: Ragweed was the best univariate predictor for both hay fever and asthma 
symptoms: the area under the ROC curve for hay fever was 0.71 (95%) CI
0.67-0.74); for asthma, it was 0.65 (95% CI 0.55-0.75). For hay fever,
dichotomizing the average reaction to four antigens at 2 mm gave a sensitivity of
56% and a specificity of 83%; at 3 mm, the sensitivity was 38% and specificity
92%. For asthma, dichotomizing the skin test reaction at 2 mm gave a sensitivity 
ranging from 30% for reaction to mixed grasses to 56% for the ragweed antigen
reaction. CONCLUSIONS: Although in this older population skin test reactivities
did not predict current asthma symptoms with high sensitivity, our results
support the use of cutoff values of 2 or 3 mm as commonly used in studies of hay 
fever symptoms.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 11251405 [PubMed - indexed for MEDLINE]

1377: Allergy. 2001 Mar;56(3):231-6.

Eosinophil cationic protein and specific IgE in serum and nasal mucosa of
patients with grass-pollen-allergic rhinitis and asthma.

Marcucci F, Sensi LG, Migali E, Coniglio G.

Institute of Pediatrics, University of Perugia, Italy.

BACKGROUND: After allergen exposure, IgE-bearing mast cells surface in
respiratory mucosa. Eosinophils are also recruited locally by chemotactic
mediators; they are the main cell directly involved in the late phase of allergic
inflammation. IgE antibody and eosinophil cationic protein (ECP) are routinely
determined mainly in serum although they exert their pathogenetic role more
directly on mucosal surfaces. METHODS: We performed a comparative study of IgE
antibody to grass and ECP on nasal mucosa and blood samples in order to evaluate 
the relevance of monitoring allergic inflammation in the target organ. Thirty-one
patients and 10 nonatopic controls were enrolled in the protocol. Twenty-six
subjects allergic to grass, 11 with rhinitis (group 1) and 15 with asthma and
rhinitis (group 2), completed the study. Five patients dropped out. Specific IgE 
to grass and ECP was determined in nasal mucosa by our method based on in situ
incubation. RESULTS: Serum IgE to grass did not increase during the pollen peak, 
as did nasal IgE, in group 1 from before the pollen peak, from 2.3 to 3.2 kU/l
(P=0.02), and in group 2 at the pollen peak, from 4.8 to 12.2 kU/l (P=0.01).
Serum ECP did not show any significant variation in group 1, but it increased at 
pollen peak from 6 to 11.2 microg/l (P=0.01) in group 2. Nasal ECP increased
significantly in both groups even before the pollen peak. In group 1, ECP values 
rose from 15 to 39.9 microg/l (P=0.01). In group 2, ECP increase was much higher 
than in group 1, from 9 to 213 microg/l (P=0.001). Serum eosinophils, like nasal 
ECP, showed a significant increase of values from before the pollen peak in both 
groups, without correlation with serum ECP in rhinitic patients. CONCLUSIONS:
Both specific IgE and ECP in the nasal mucosa showed a better correlation with
allergen exposure than serum evaluations. With an appropriate method, allergic
inflammation may be best monitored in the nasal mucosa.

PMID: 11251403 [PubMed - indexed for MEDLINE]

1378: Curr Opin Investig Drugs. 2000 Oct;1(2):219-26.

Norastemizole Sepracor.

Bachmann KA.

University of Toledo, College of Pharmacy, 2801 W Bancroft Street, Toledo, OH
43606, USA. kbachma@utnet.utoledo.edu

Sepracor and Janssen are developing the histamine H1 antagonist, norastemizole
(an active metabolite of Johnson & Johnson's Hismanal), for the potential,
non-sedating treatment of allergy. Sepracor expects to file an NDA with the FDA
by the fourth quarter of 2000 [337315,358429]. As of September 1999, Sepracor was
conducting two large-scale phase III seasonal allergic rhinitis studies [340260].
Sepracor expects norastemizole to be the most potent non-sedating histamine, with
equal or more rapid onset of action than other therapies [229516]. Norastemizole 
is 13- to 16-fold more potent as an H1 antagonist than astemizole and 20- to
40-fold more potent in inhibiting histamine-induced bronchoconstriction.
Following a single dose of norastemizole (25 mg p.o.), there is significant
attenuation of histamine-induced wheal and flare responses within 30 min. The
drug's major advantage is its lack of cardiotoxicity or interactions with other
drugs that increase the risk of developing serious arrhythmias [301469]. In July 
2000, Morgan Stanley Dean Witter predicted filing for FDA approval for allergic
rhinitis during the first half of 2001, and a partnership announcement around the
time of this NDA filing. The analysts also forecast European sales of $8.3
million in 2002, rising to $16.7 m by 2005 [384868].

PMID: 11249577 [PubMed - indexed for MEDLINE]

1379: Expert Opin Pharmacother. 2000 Dec;1(7):1289-306.

Paediatric issues relating to the pharmacotherapy of allergic rhinitis.

Schenkel EJ.

Valley Clinical Research Center, 3729 Easton-Nazareth Highway, Ste 202, Easton,
Pennsylvania 18045, USA.

The prevalence of allergic rhinitis in children has risen significantly over the 
last two decades. Important comorbidities like asthma have grown in parallel due 
to a complex mix of environmental and genetic factors. These conditions have
similar allergic inflammatory mechanisms, which raises the possibility of
treating both conditions by targeting shared inflammatory mediators
pharmacologically. The first line treatment for paediatric allergic rhinitis is a
topical nasal corticosteroid or a non-sedating antihistamine. Available
intranasal corticosteroids show superior symptom control to second-generation
antihistamines. However, most topical steroids and non-sedating antihistamines
have equivalent clinical efficacy within their respective classes, so the choice 
of agent depends on safety and tolerability. Ideally, topical nasal steroids
should exhibit high local receptor binding affinity and low systemic
bioavailability, allied with a lack of long-term growth suppression in children
and adolescents. Regular use of topical steroids is advisable, but intermittent
and prophylactic use is also effective. Second-generation antihistamines are
effective and some have no adverse cardiac or sedative effects. Non-sedating
antihistamine treatment can ameliorate rhinitis-induced decrements in learning.
alpha-Adrenergic nasal decongestants provide short-term benefit, but topical
agents can cause rebound symptoms. Prophylactic treatment with chromones is safe 
and effective, but multiple daily dosing is needed. Ipratroprium bromide nasal
spray is useful as an intermittent therapy for mild disease or as add-on
treatment, but its effect is limited to the control of rhinorrhoea. Children with
allergic rhinitis should receive pharmacotherapy if allergen avoidance measures
are ineffective, ideally with a topical intranasal steroid or a second-generation
antihistamine.

Publication Types: 
    Review

PMID: 11249466 [PubMed - indexed for MEDLINE]

1380: ORL J Otorhinolaryngol Relat Spec. 2001 Mar-Apr;63(2):92-5.

Evaluation of a new method for assessing symptoms.

Hallén H, Djupesland P, Kramer J, Toll K, Graf P.

ENT Department, Soder Hospital/Huddinge University Hospital, Stockholm, Sweden.

BACKGROUND: Many studies in rhinology are based on results from symptom scoring. 
Numerous methods are used to estimate symptoms. With some of them the patients
choose between various alternatives for estimating the severity of their
symptoms, but the commonest method is the visual analogue scale (VAS), which is
regarded as reliable. METHODS: In this study, we evaluate a new method for
assessing symptoms, with which the patient uses the telephone to call a computer.
We compare the results using the new method with those using symptoms estimation 
with VAS. RESULTS: The results are based on 487 observations in patients with
birch pollen allergic rhinitis in the pollen season. A high correlation was found
between the results using the new method and those using the VAS. In a
questionnaire, the patients answered questions concerning the two methods. Most
patients preferred the new telephone method. They found it easier to estimate
their symptoms properly and easier to perform. CONCLUSION: We conclude that
telephone scoring of symptoms is a reliable and adequate method when symptom
scoring is used as hard data in a study. Copyright 2001 S. Karger AG, Basel

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 11244368 [PubMed - indexed for MEDLINE]

1381: Allergy. 2001;56 Suppl 65:21-7.

Desloratadine activity in concurrent seasonal allergic rhinitis and asthma.

Baena-Cagnani CE.

Division of Immunology and Respiratory Medicine, Infantile Hospital, Córdoba,
Argentina.

Seasonal allergic rhinitis (SAR) and asthma, which are frequently comorbid, share
some common allergic pathogenic bases. Clinical manifestations of these disorders
might therefore be viewed as local manifestations of a systemic inflammatory
state. Not only do the onsets of allergic-rhinitis (AR) and asthma symptoms often
coincide (within 1 year), but also nasal challenges with SAR allergens can induce
airways hyperreactivity (AHR). Eosinophils, which are key effector cells in both 
SAR and asthma, cause AHR, tissue damage, and neuronal effects through secretion 
of toxic granule proteins, enzymes, and other mediators. The novel, nonsedating, 
histamine H1-receptor antagonist, desloratadine, which exerts various favorable
effects on the allergic cascade, significantly decreased SAR symptoms (e.g.,
nasal congestion) and diminished daily beta2-agonist use and improved asthma
symptoms, while maintaining pulmonary function, in patients with SAR-asthma who
were treated with once-daily desloratadine regimens.

Publication Types: 
    Review

PMID: 11243501 [PubMed - indexed for MEDLINE]

1382: Allergy. 2001;56 Suppl 65:14-20.

Decongestant efficacy of desloratadine in patients with seasonal allergic
rhinitis.

Bachert C.

ENT Department, University Hospital Ghent, Belgium.

Recent advances in experimental immunologic approaches to seasonal allergic
rhinitis (SAR) have led to a shift in the concepts of its pathogenesis. The
conventional view of SAR as a local response to inhaled allergens has largely
given way to a new view of this disorder as a systemic condition with local
tissue manifestations. This concept, together with an increasing recognition of
specific mediators' distinct roles in driving the early- and late-phase allergic 
responses, has opened multiple lines of therapeutic attack within the allergic
cascade. Potent inhibition of inflammatory mediator release at distinct points in
this cascade is conferred by desloratadine. In addition to the familiar range of 
SAR symptoms amenable to antihistamine therapy, desloratadine uniquely attenuates
patient ratings of nasal congestion. This novel, nonsedating histamine
H1-receptor antagonist is the only once-daily antiallergic product with a
consistent decongestant effect that begins within hours of the first morning dose
and is sustained for the entire treatment period.

Publication Types: 
    Review

PMID: 11243500 [PubMed - indexed for MEDLINE]

1383: J Vet Med Sci. 2001 Jan;63(1):79-81.

Seasonal rhinitis in a cat sensitized to Japanese cedar (Cryptomeria japonica)
pollen.

Masuda K, Kurata K, Sakaguchi M, Yamashita K, Hasegawa A, Ohno K, Tsujimoto H.

Department of Veterinary Internal Medicine, Graduate School of Agricultural and
Life Sciences, The Universitly of Tokyo, Japan.

A cat showing seasonal allergic symptoms of rhinitis was examined for
reactivities to Japanese cedar (Cryptomeria japonica, CJ) pollen allergen by
intradermal skin test (IDST), Prausnitz-Kustner (P-K) test, and lymphocyte
blastogenic response. In IDST for 26 common allergens. the cat showed a positive 
reaction to CJ pollen allergen. P-K test using CJ pollen allergen also showed a
positive reaction, indicating the presence of serum IgE specific to CJ pollen. In
the lymphocyte blastogenic response, the stimulation index in the presence of CJ 
pollen allergen was 2.4. These data suggested that the seasonal rhinitis observed
in the cat was caused by the sensitization to CJ pollen allergen.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11217069 [PubMed - indexed for MEDLINE]

1384: Laryngoscope. 2001 Feb;111(2):236-9.

Changes in serum interferon-gamma, interleukin-4, and interleukin-12 cytokine
levels in anti-histamine type 2-treated allergic rhinitis patients.

Testa B, Mesolella C, Mosti MR, Mesolella M, Testa D, Motta G.

Institute of Otolaryngology, School of Medicine, Second University of Naples,
Italy.

OBJECTIVES/HYPOTHESIS: Markedly elevated immunoglobulin E (IgE) synthesis
characterizes allergic diseases. Interferon-gamma (IFN-gamma) and interleukin-4
(IL-4) regulate IgE synthesis. It has been shown that immunotherapy and histamine
type 2 (H2) receptor antagonists induce a clinical improvement, decrease IgE
antibodies, and increase T-cell subsets, which express a suppressor function. In 
addition, immunotherapy brings about a reduction in the amount of IL-4 in T-cell 
clones of allergic individuals. The purpose of this study was to investigate the 
profile of cytokines IFNgamma and IL-4 that occurs in vivo in anti-H2-treated
patients with allergic rhinitis (AR). METHODS: Enrolled were 65 AR patients with 
sensitivity to a single allergen, the Parietaria, 36 of whom were randomly
assigned to treatment with ranitidine at a dosage of 1 mg/kg per day
intravenously for 20 days, and 29 to placebo treatment. RESULTS: A comparison of 
the serum cytokine values recorded before and after anti-H2 treatment showed a
significant increase in INF-gamma serum level (P = .003) and a decrease in IL-4
(P = .016). Negligible variations were found in the placebo-treated group.
CONCLUSION: H2 antagonists probably induce their effects by enhancing the amount 
of IFN-gamma and by reducing IL-4 cytokines, which, respectively, induce a
decrease and an increase in the IgE synthesis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11210867 [PubMed - indexed for MEDLINE]

1385: J R Soc Health. 2000 Dec;120(4):236-41.

Is childhood allergy more common amongst an island population?

Jeffs D, Grainger R, Powell P.

States of Guernsey, John Henry House, St Martin's, Guernsey GY4 6UU, Channel
Islands.

A rise in the prevalence of childhood asthma has been reported in both the UK and
in several overseas countries during recent years. Wide geographical variations
have also been demonstrated in the distribution of hay fever, atopic eczema and
other allergic symptoms. It is the impression of many parents and some clinicians
that allergic symptoms may be even higher amongst children in an island
environment compared with a similar population on the mainland. To test this
hypothesis, Guernsey and Jersey in the Channel Islands, and the Isle of Man in
the Irish Sea participated as an independent arm in the International Study of
Asthma and Allergy in Childhood (ISAAC). This entailed self-completion of a
38-part pretested and validated questionnaire in a classroom setting under
standardised conditions. A total of 3,772 secondary students in school years
eight and nine living in the three islands were compared with 27,507 students of 
similar age in 93 British secondary schools enrolled in the larger UK study.
There are a number of demonstrable differences in climate, home environment and
lifestyle factors between the islands and mainland UK. Although results were
generally above the UK mean, they were comparable with the reference region of
South West England and invariably below the UK maximum. For instance, the
prevalence of 'ever wheezed?', 'wheezed in last twelve months?', 'wheezed with
exercise?' and 'diagnosis of asthma' were a mean of 50.5%, 34.5%, 31% and 19.7%
in the islands compared with a UK prevalence of 48.8%, 33.3%, 28.5% and 20.7%,
whilst the prevalence of 'runny nose ever?' and 'runny nose in last twelve
months?' was a mean of 46.6% and 36.7% in the islands, compared with 47.1% and
37.9% in the UK mean. These differences were not statistically significant. This 
information will be reassuring to parents of island children, and also
demonstrates that services for the management of asthma and other allergic
conditions should not be a higher public health priority in these locations than 
on the mainland of Britain.

Publication Types: 
    Comparative Study
    Multicenter Study

PMID: 11197451 [PubMed - indexed for MEDLINE]

1386: Allergy Asthma Proc. 2000 Nov-Dec;21(6):371-5.

The course of asthma parallels that of allergic rhinitis: a 23-year follow-up
study of college students.

Greisner WA 3rd, Settipane RJ, Settipane GA.

Brown University School of Medicine, Providence, Rhode Island, USA.

The purpose of this study is to examine the relationship between the course of
asthma and allergic rhinitis among former Brown University students who were
diagnosed with these diseases either before or after their freshman year of 1962 
or 1963. A total of 738 former students, who were evaluated and underwent skin
testing during their freshman year, completed a 23-year follow-up questionnaire
inquiring of their history of allergies and asthma and are the focus of this
study. The activity of asthma as related to the course of allergic rhinitis (hay 
fever and/or nonseasonal allergic rhinitis) was examined. Among 44 asthmatic
subjects with purely seasonal allergic rhinitis (hay fever and no history of
nonseasonal allergic rhinitis), asthma was active in 75% of those with worse hay 
fever, 70% of those with unchanged hay fever, 50% of those with better (but not
symptom-free) hay fever, and 10% of those with symptom-free hay fever. The
resolution of asthma symptoms correlated significantly with improvement in hay
fever (p = 0.0053). Among 70 asthmatics with any form of allergic rhinitis (hay
fever and/or nonseasonal allergic rhinitis), asthma was active in 75.0% of those 
with worse allergic rhinitis, 66.7% of those with unchanged allergic rhinitis,
53.3% of those with better (but not symptom-free) allergic rhinitis, and 20.0% of
those with symptom-free allergic rhinitis. The resolution of asthma symptoms
correlated significantly with improvement in allergic rhinitis (p = 0.0052). The 
activity of allergic rhinitis as related to the course of asthma was also
examined. Among 44 asthmatic subjects with purely seasonal allergic rhinitis (hay
fever and no history of nonseasonal allergic rhinitis), hay fever was active in
100% of those with worse asthma, 100% of those with unchanged asthma, 90.9% of
those with better (but not symptom-free) asthma, and 60.9% of those with
symptom-free asthma. The resolution of hay fever symptoms correlated
significantly with improvement in asthma (p = 0.0109). Among 71 asthmatic
subjects with any form of allergic rhinitis (hay fever and/or nonseasonal
allergic rhinitis), allergic rhinitis was active in 91.9% of those with active
asthma and 64.7% of those with symptom-free asthma. The resolution of allergic
rhinitis symptoms correlated significantly with improvement in asthma (p =
0.0078). In summary, among individuals with asthma and allergic rhinitis,
improvement of allergic rhinitis was associated with a resolution of asthma
symptoms, whereas a worsening of allergic rhinitis was associated with the
persistence of asthma symptoms. Likewise, among asthmatic subjects with allergic 
rhinitis, improvement of asthma was associated with a resolution of allergic
rhinitis symptoms, whereas a worsening of asthma was associated with the
persistence of allergic rhinitis symptoms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11191104 [PubMed - indexed for MEDLINE]

1387: Allergy Asthma Proc. 2000 Nov-Dec;21(6):367-70.

Allergic rhinitis update: Epidemiology and natural history.

Bellanti JA, Wallerstedt DB.

Departments of Pediatrics and Microbiology-Immunology and the International
Center for Interdisciplinary Studies of Immunology, Georgetown University Medical
Center, Washington, DC, USA.

Allergic rhinitis is the most common chronic condition, with an estimated
prevalence in the United States of 5-22%, which increases from infancy, peaks in 
childhood and adolescence, and decreases in the elderly. As a major cause of
morbidity, absenteeism, and restricted activity in both children and adults,
allergic rhinitis, similar to asthma, appears to be increasing with time.
Allergic rhinitis is commonly defined as seasonal or perennial, depending upon
whether symptoms are manifested at defined yearly intervals or throughout the
year, respectively. While trees, grasses, weeds, and molds are the most frequent 
causes of seasonal allergic rhinitis, dust mites and molds are the major
contributors to perennial allergic rhinitis. The pathogenesis of allergic
rhinitis is based upon interactions of allergen with membrane-bound
allergen-specific IgE on the surface of mediator cells, i.e., basophils and mast 
cells, leading to the release of allergic mediators (both performed and newly
synthesized) including histamine, leukotrienes, and eosinophil cationic protein
(ECP). These are responsible for both immediate allergic responses characteristic
of acute allergic rhinitis and the late inflammatory reactions responsible for
chronic allergic rhinitis. The evaluation of rhinitis should include a detailed
patient history, a careful physical examination, and appropriate diagnostic tests
including skin prick tests or serum assays for allergen-specific IgE. Seasonal
allergic rhinitis is readily distinguished from perennial allergic rhinitis by
history and confirmed by positive skin tests to causative aeroallergens. It is
important to differentiate seasonal rhinitis from non-allergic disorders
including infectious rhinitis, structural or anatomic problems such as nasal
polyps or septal deviation, rhinitis medicamentosa (due to the overuse of topical
vasoconstrictors), hormonal rhinopathy (e.g., pregnancy, hypothyroidism),
non-allergic vasomotor rhinopathy, non-allergic inflammatory rhinitis with
eosinophils (NARES), or rarely, a neoplasm. A knowledge of the epidemiologic and 
clinical presentation of allergic rhinitis together with these pathophysiologic
mechanisms is essential for a modern-day diagnostic and therapeutic approach to
the patient who suffers from allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11191103 [PubMed - indexed for MEDLINE]

1388: Arzneimittelforschung. 2000 Dec;50(12):1099-105.

Efficacy and tolerability of intranasally applied dimetindene maleate solution
versus placebo in the treatment of seasonal allergic rhinitis.

Horak F, Unkauf M, Beckers C, Mittermaier EM.

Universitäts-Klinik für Hals-Nasan-Ohrenheilkunde, Allgemeines Krankenhaus der
Stadt Wien, Vienna, Austria.

The aim of this study was to investigate the efficacy and tolerability of a 0.1% 
dimetindene maleate spray (Fenistil Nasal Dosierspray) compared to placebo when
applied intranasally. Dimetindene (dimetindene maleate, CAS 3614-69-5, DMM) is a 
very potent and well established H1-receptor antagonist. A total of 36
asymptomatic patients (17 female, 19 male), suffering from seasonal allergic
rhinitis from grass pollen, were randomly assigned to treatment with matching
topicalnasal sprays with either dimetindene maleate 0.1% or placebo as control in
a double-blind, randomised, cross-over-design, with 2 weeks wash-out periods
between. The trial period was chosen in a pollen-free time from 20th October to
5th November 1998 to guarantee asymptomatic patients. The patients being allergic
to grass pollen, verified by positive case history, positive skin prick test and 
positive nasal provocation test, were challenged under controlled conditions with
purified airborne grass pollen in the Vienna Challenge Chamber. The nasal spray
were applied as single doses (1 puff = 0.14 ml of the respective solution with or
without 0.14 mg dimetindene maleate) in the evening before at 7.30 p.m. and in
the morning at 7.30 a.m. to each nostril exactly 15 min before the onset of
allergen provocation. The dosage scheme relates to a daily dose of 0.56 mg DMM in
the active treatment group. Subjective nasal and ocular symptoms were measured
on-line in time intervals of 30 min during the 4 h allergen provocation. The
statistical analysis was a priori sequentially ordered to account for multiple
testing and keep the 5% level of significance. All measured primary criteria,
Total Nasal Symptom Score (p < 0.0001) calculated from the three single symptoms 
running of the nose (p = 0.0032) sneezing stimulus (p < 0.0001) and nasal itching
(p < 0.0001), as well nasal secretion (p = 0.0031), resulted consistently in a
statistically significant and clinically relevant superiority of 0.1% DMM
compared to placebo. The same superior treatment effect was observed for all the 
other criteria, despite the nasal flow, but including the ocular variables. This 
can be interpreted as a positive efficacy also in secondary allergic
conjunctivitis. No systemic or topical adverse events were reported. The results 
of the study demonstrate that 0.1% DMM as nasal spray is an efficient and safe
application form for patients suffering from seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11190775 [PubMed - indexed for MEDLINE]

1389: Arch Otolaryngol Head Neck Surg. 2001 Feb;127(2):193-9.

Absence of nasal mucosal atrophy with fluticasone aqueous nasal spray.

Baroody FM, Cheng CC, Moylan B, deTineo M, Haney L, Reed KD, Cook CK, Westlund
RE, Sengupta E, Corey JP, Togias A, Naclerio RM.

MD, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, 5841 
S Maryland Ave, MC1035, Chicago, IL 60637, USA. fbaroody@surgery.bsd.uchicago.edu

OBJECTIVE: To evaluate whether 1 year of continuous treatment with intranasal
fluticasone propionate would lead to atrophy in the nasal mucosa compared with an
active control, oral terfenadine. DESIGN: Prospective, randomized, multicenter,
open-label, parallel-group study. SETTING: Two tertiary care academic
institutions. PATIENTS: Seventy-five subjects older than 18 years with perennial 
allergic rhinitis. INTERVENTIONS: Patients received either fluticasone propionate
aqueous nasal spray, 200 microg once daily, or terfenadine, 60 mg twice daily,
for 1 year. Nasal biopsy specimens were obtained before and after 1 year of
treatment and were evaluated for evidence of atrophy. MAIN OUTCOME MEASURES:
Epithelial and collagen layer thickness of the nasal mucosa as assessed by light 
microscopy and the presence and degree of edema, and regularity of collagen
fibrils as assessed by electron microscopy. Analyses were performed without
knowledge of subject identity or treatment assignment. RESULTS: Neither
fluticasone nor terfenadine treatment led to atrophy in the nasal mucosa by
clinical or histologic observation. No significant changes from baseline were
observed for any assessment of atrophy. In contrast to what would have been
expected if atrophy were to occur, mean epithelial layer thickness in the
fluticasone group significantly increased compared with terfenadine treatment (P 
= .03). CONCLUSIONS: Treatment with intranasal fluticasone for 1 year increases
the thickness of the nasal epithelium as compared with a year's treatment with
terfenadine and does not lead to atrophy in the nasal mucosa. The increased
thickness in the fluticasone treatment may represent repair from epithelial
damage caused by chronic allergic inflammation.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11177038 [PubMed - indexed for MEDLINE]

1390: Clin Exp Allergy. 2001 Jan;31(1):61-8.

Comment in:
    Clin Exp Allergy. 2001 Jan;31(1):11-7.

Effects of monotherapy with intra-nasal corticosteroid or combined oral histamine
and leukotriene receptor antagonists in seasonal allergic rhinitis.

Wilson AM, Orr LC, Sims EJ, Lipworth BJ.

Asthma & Allergy Research Group, Department of Clinical Pharmacology &
Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Dundee, 
Scotland.

BACKGROUND: The combination of a leukotriene receptor antagonist with an
antihistamine may have beneficial effects in seasonal allergic rhinitis (SAR).
OBJECTIVE: To determine how combined oral mediator blockade compares to
monotherapy with intranasal corticosteroid in the treatment of SAR. METHODS:
Twenty-two patients with seasonal allergic rhinitis were enrolled in a placebo
controlled crossover study comparing 2 weeks therapy of either (a) 200 microg
intranasal mometasone furoate (MF) once daily or (b) 10 mg oral montelukast plus 
10 mg oral cetirizine once daily (MON/CZ), with a 7-10 day placebo period prior
to each treatment period. Domiciliary measures of symptoms and nasal flow were
recorded daily. Measurements of posterior rhinomanometry, acoustic rhinometry and
nasal nitric oxide were made after all treatment and placebo periods. RESULTS:
There were significant (P < 0.05) improvements in domiciliary peak nasal flow
(l/min) with both MF (133 (3.8)) and MON/CZ (124 (3.8)) compared to pooled
placebo (110 (4.0). Both treatments also showed significant improvement in terms 
of nasal blockage (units) (PL: 1.1(0.1), MF: 0.5 (0.1), MON/CZ 0.7 (0.1); and
total nasal symptoms (units) (PL: 3.5 (0.3), MF 1.6 (0.3), MON/CZ 1.7 (0.3)),
although there was no significant difference between the two active treatments.
There were no significant differences between placebo and treatment for
rhinomanometry, acoustic rhinometry or nitric oxide. CONCLUSIONS: Both intranasal
mometasone furoate as monotherapy and oral cetirizine plus montelukast as
cotherapy were equally effective for objective and subjective measures of
treatment response in SAR. Domiciliary measurements of symptoms and peak flow
were more sensitive than laboratory measurements of rhinomanometry, acoustic
rhinometry and nasal nitric oxide.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11167952 [PubMed - indexed for MEDLINE]

1391: Allergy. 2001 Feb;56(2):126-31.

Recruitment of CD1a+ Langerhans cells to the nasal mucosa in seasonal allergic
rhinitis and effects of topical corticosteroid therapy.

Till SJ, Jacobson MR, O'Brien F, Durham SR, KleinJan A, Fokkens WJ, Juliusson S, 
Löwhagen O.

Upper Respiratory Medicine, Imperial College School of Medicine at the National
Heart and Lung Institute of Medicine at the National Heart and Lung Institute,
London, UK.

BACKGROUND: Local antigen presentation may be necessary for both primary and
recall T-cell responses to grass pollen in hay fever patients. We examined the
effect of seasonal allergen exposure on nasal mucosal antigen-presenting cell
(APC) populations and the effects of topical corticosteroid therapy. METHODS:
Nasal biopsies were collected from 46 grass pollen-sensitive seasonal rhinitis
patients before the grass-pollen season. A second biopsy was collected during the
pollen season, when patients had received 6 weeks' treatment with either
fluticasone propionate (200 microg, twice daily) or placebo. Cell populations in 
biopsy sections were quantified by immunocytochemistry. RESULTS: Significant
increases in submucosal and epithelial CD1a+ Langerhans cells, but not CD68 +
macrophages or CD20 + B cells, were observed during the pollen season. Seasonal
increases in CD1a+ Langerhans cells were inhibited by corticosteroid therapy.
CONCLUSIONS: Recruitment of CD1a+ Langerhans cells to the nasal mucosa during
natural seasonal allergen exposure may contribute to local T cell responses.
Topical corticosteroids may act, at least in part, by inhibiting effective
allergen presentation to T cells through inhibition of recruitment of Langerhans 
cells to the nasal mucosa.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11167372 [PubMed - indexed for MEDLINE]

1392: Allergy. 2001 Feb;56(2):109-17.

Double-blind, placebo-controlled food challenge with apple.

Skamstrup Hansen K, Vestergaard H, Stahl Skov P, Søndergaard Khinchi M, Vieths S,
Poulsen LK, Bindslev-Jensen C.

Allergy Unit, National University Hospital, Copenhagen, Denmark.

The aim of the study was to develop and evaluate different methods of
double-blind, placebo-controlled food challenge (DBPCFC) with apple. Three
different DBPCFC models were evaluated: fresh apple juice, freshly grated apple, 
and freeze-dried apple powder. All challenges were performed outside the pollen
season and took place from 1997 to 1999. The freeze-dried apple material was
characterized by means of leukocyte histamine release (HR), skin prick test
(SPT), and immunoblotting experiments. The study population consisted of birch
pollen-allergic patients with a history of rhinitis in the birch-pollen season
and positive specific IgE to birch. For comparison of the DBPCFC models, 65
patients with a positive open oral challenge with apple were selected. In the
characterization of the freeze-dried apple material, 46 birch pollen-allergic
patients were included. The IgE reactivity to apple was evaluated by measurement 
of specific IgE, HR, and SPT. Golden Delicious apples were used in all
experiments. The results of this study showed that it was possible to perform
DBPCFC with apple in birch pollen-allergic individuals. The model with freshly
squeezed apple juice had a low sensitivity and displayed a high frequency of
reactions to placebo, probably due to the ingredients used for blinding. The
sensitivity of the models with freshly grated apple and freeze-dried apple powder
was 0.74/0.60. An increase in sensitivity is desirable. The freeze-dried apple
powder proved to be useful for SPT, HR, and oral challenges, but further
investigation of the stability and the allergenic profile of the material is
needed.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 11167370 [PubMed - indexed for MEDLINE]

1393: Allergy. 2001 Jan;56(1):65-8.

The role of patient training in the management of seasonal rhinitis and asthma:
clinical implications.

Gani F, Pozzi E, Crivellaro MA, Senna G, Landi M, Lombardi C, Canonica GW,
Passalacqua G.

Respiratory Diseases, Allergy Service, University of Turin, Italy.

BACKGROUND: Allergic rhinitis is an inflammatory disease often associated with
bronchial asthma. Intranasal corticosteroids and oral antihistamines are the
first-choice drugs. Patient training is relevant to asthma management, but little
is known about its impact on rhinitis. We evaluated the role of patient training 
in the treatment of allergic rhinitis and its effects on nasal and bronchial
symptoms. METHODS: One hundred and one patients (M/F = 62/39, age range 12-62
years) with pollen-induced rhinitis (32 with concomitant mild asthma) were
enrolled. They were randomized into three groups: A (n = 30) with drug therapy
alone, B (n = 35) with drug therapy plus training on the use of nasal spray, and 
C (n = 36) the same as B plus a lesson on rhinitis and asthma. All patients
received mometasone furoate nasal spray for 8 weeks as regular therapy, plus
rescue medications on demand. Symptoms and drug consumption were evaluated during
the pollen season. RESULTS: The rate of noncompliance/dropout was highest in the 
untrained patients (P = 0.001). No difference in nasal symptoms was seen among
the three groups. On the other hand, group C had significantly fewer asthma
symptoms (P = 0.02) and less albuterol use (P = 0.005) than group A. Moreover,
the trained group globally used less rescue medication than the other groups (P =
0.02). CONCLUSIONS: Detailed training of patients seems to improve compliance
with treatment, reduce concomitant asthma symptoms, and reduce the use of
symptomatic drugs.

Publication Types: 
    Clinical Trial
    Evaluation Studies
    Randomized Controlled Trial

PMID: 11167354 [PubMed - indexed for MEDLINE]

1394: Allergy. 2001 Jan;56(1):35-42.

Effect of cetirizine on bronchial hyperresponsiveness in patients with seasonal
allergic rhinitis and asthma.

Aubier M, Neukirch C, Peiffer C, Melac M.

Service de Pneumologie-Unité INSERM U 408, H pital Bichat, Paris, France.

Although H1 antihistamine compounds (H1) are highly effective in the treatment of
allergic rhinitis (AR), their role in the treatment of asthma is still
controversial. Because a strong association between AR and bronchial
hyperresponsiveness (BHR) has been reported, this study was designed to assess
the effect of a new H1 anti histamine, cetirizine (C), on nonspecific BHR in
patients with AR. Twelve patients were included in a double-blind, crossover,
placebo-controlled trial. All patients had positive skin tests for common
allergens and showed BHR to inhaled methacholine after specific nasal allergenic 
challenge. After a washout period of 1 week to ensure the stability of the BHR,
the patients received, by crossover randomization, C 10 mg daily or placebo (P)
for 2 weeks. After each treatment period, BHR and nasal blocking index (NBI) were
measured 1 and 6 h after nasal challenge. Bronchial responsiveness was expressed 
as methacholine PD20, the provocation dose of methacholine causing a 20% decrease
in FEV1. Measurements were then performed after 2 weeks of C and after 2 weeks of
P. Baseline values of PD20 (median) measured before challenge showed no
difference after cetirizine or after placebo (1.36 mg). Results 1 h after
allergen did not show significant differences between C (methacholine PD20=0.522 
mg) and placebo (methacholine PD20=0.455 mg). By contrast, 6 h after challenge,
methacholine PD20 was 0.918 mg for C and 0.483 mg for P (P=0.042). Similarly, NBI
showed no change between C and P 1 h after challenge, whereas the difference was 
significant 6 h after challenge (P=0.011 ). These data demonstrate a protective
nasal effect of C against BHR measured 6 h after nasal allergen challenge in
patients with AR. They suggest that C may be useful in patients with asthma
associated with AR.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11167350 [PubMed - indexed for MEDLINE]

1395: Allergy. 2001 Jan;56(1):29-34.

Retrospective study on fluticasone propionate aqueous nasal spray efficacy in
patients with allergic rhinitis: evaluation of clinical and laboratory
parameters.

Ventura MT, Piccinni T, Matino MG, Giuliano G, Di Corato R, Di Napoli P, Tursi A.

Department of Internal Medicine, Immunology, and Infectious Diseases, University 
of Bari Medical School, Policlinico, Italy.

BACKGROUND: In allergic rhinitis, allergenic stimulation causes the release of
various mediators that induce symptoms and the development of chronic
inflammation, which, in turn, is caused by cells involved in the late phase of
inflammation, such as eosinophils. The eosinophils also cause damage at the
mucosal level through the secretion of eosinophil cationic protein and other
preformed factors contained in their granules. The objective was to verify the
efficacy of fluticasone propionate aqueous nasal spray in patients with allergic 
rhinitis; in a retrospective study, we have evaluated mediators of inflammation, 
making correlations with the clinical symptoms score during and outside the
pollen season. METHODS: Forty patients with allergic rhinitis and 15 normal
controls were included in our study. Eosinophil cationic protein, eosinophil
chemotactic activity, and blood and nasal lavage eosinophil count were evaluated 
as laboratory parameters. RESULTS: We found a significant increase in nasal
lavage levels of eosinophil cationic protein in allergic patients, and this was
strictly correlated with the clinical symptoms score. No differences were found
in the eosinophil count of allergic patients and in the serum eosinophil cationic
protein of patients sensitized to seasonal allergens in comparison with normal
subjects. By contrast, an increase in serum eosinophil cationic protein level was
found in patients sensitized to perennial allergens. After topical administration
of fluticasone propionate aqueous nasal spray, a reduction in nasal lavage
eosinophil cationic protein secretion was obtained with a reduction of eosinophil
chemotactic activity at the local level. This reduction correlated with an
improvement of clinical symptoms. CONCLUSIONS: The clinical improvement and
reduction in nasal lavage eosinophil cationic protein and eosinophil chemotactic 
activity after administration of fluticasone propionate aqueous nasal spray
further confirms the role of this treatment in allergic rhinitis.

PMID: 11167349 [PubMed - indexed for MEDLINE]

1396: Ann Epidemiol. 2001 Jan;11(1):59-64.

Seasonal allergic rhinoconjunctivitis and fatty acid intake: a cross-sectional
study in Japan.

Wakai K, Okamoto K, Tamakoshi A, Lin Y, Nakayama T, Ohno Y.

Department of Preventive Medicine/Biostatistics and Medical Decision-Making,
Nagoya University Graduate School of Medicine, Japan.

PURPOSE: To investigate the associations of fatty acid intake with seasonal
allergic rhinoconjunctivitis. METHODS: The study subjects consisted of 1012 women
aged 22 to 57 years (mean age +/- SD: 36.5+/-7.7 years), who had graduated from
the Aichi Prefectural Junior College of Nursing, Nagoya, Japan. They completed a 
self-administered questionnaire on symptoms of the disease in August 1998.
Symptoms of seasonal allergic rhinoconjunctivitis in spring were determined by
response to the questionnaire, and fatty acid intake was estimated using a food
frequency questionnaire. Odds ratios (ORs) were computed using unconditional
logistic models to assess the strength of associations between the symptoms and
fatty acid intake. RESULTS: An increasing trend in the ORs was observed with
increasing dietary intake of n-6 polyunsaturated fatty acids. After adjustment
for potential confounders, the ORs for the second, third, and highest quartiles
of intake relative to the lowest were 1.28 [95% confidence interval (CI),
0.78-2.10], 1.55 (0.96-2.50), and 1.74 (1.09-2.77), respectively (trend p =
0.015). Consumption of saturated, monounsaturated, and n-3 polyunsaturated fatty 
acids was not significantly related to the symptoms. CONCLUSIONS: Dietary intake 
of n-6 polyunsaturated fatty acids was positively associated with seasonal
allergic rhinoconjunctivitis in spring.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11164121 [PubMed - indexed for MEDLINE]

1397: Allergy. 2000 Mar;55(3):246-50.

The IgE-binding epitopes of rPar j 2, a major allergen of Parietaria judaica
pollen, are heterogeneously recognized among allergic subjects.

Costa MA, Duro G, Izzo V, Colombo P, Mirisola MG, Locorotondo G, Cocchiara R,
Geraci D.

Istituto di Biologia dello Sviluppo, CNR, Palermo, Italy.

Pollen allergens are multivalent proteins that cross-link IgE antibodies on mast 
or basophil cells, inducing secretion of biologic mediators, and resulting in
various allergic symptoms. The IgE-binding regions of the Parietaria judaica (Pj)
pollen major allergen rPar j 2 were investigated. Twenty-nine single sera from
Pj-allergic subjects were tested by Western blot against five recombinant
peptides. At least four putative IgE-binding epitopes were identified. The
analysis of their diffusion suggested a heterogeneous IgE-binding response. In
fact, 75% of the sera reacted with peptide 1-54, 48% with peptide 48-101, 24%
with peptide 1-30, 7% with peptide 29-54, and none with peptide 48-76. These five
peptides were analyzed with the histamine-release assay. Only peptide 48-101 was 
capable of inducing degranulation and release of histamine. These results suggest
that the recombinant rPar j 2 allergen contains IgE epitopes that are
heterogeneously recognized by sensitive patients, and that therefore the
therapeutic approach based on the use of haptenic peptides needs a careful
evaluation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10753015 [PubMed - indexed for MEDLINE]

1398: Exp Clin Immunogenet. 2001;18(1):13-23.

Can HLA typing predict the outcome of grass pollen immunotherapy?

Fleva A, Daniilidis M, Sidiropoulos J, Adam K, Tourkantonis A, Daniilidis J,
Hadzipetrou L.

First Department of Internal Medicine, Hippokration General Hospital,
Thessaloniki, Greece.

OBJECTIVE: The aim of this study was to investigate the relationship between HLA 
molecules and the positive or negative response of atopic patients to specific
immunotherapy (SIT). METHODS: We studied 42 atopic multisensitive patients
undergoing grass pollen immunotherapy, 42 parents of patients (30 mothers and 12 
fathers) and 173 control individuals. HLA class I and class II antigens were
typed by a microlymphocytotoxicity test. The typing of DRB1* alleles for atopic
patients and their parents was based on the reverse hybridization principle,
while for the control group, DNA-RFLP and PCR-SSP methods were used. RESULTS: The
frequency of B14 and DRB1*1101-4 antigens/alleles, as well as the A2B5DR11
haplotype, showed a statistically significant difference in those patients who
responded to immunotherapy. On the other hand, HLA-A28, B8 and DRB1*0301
antigens/alleles, as well as the frequency of the A1B8 and A1B8DR3 haplotypes,
were found to be significantly higher in patients who responded poorly to SIT.
DISCUSSION: Our findings support the hypothesis that treatment responsiveness may
show an association to HLA molecules, which could thus play a role in the
immunological selection and monitoring of atopic patient candidacy for SIT.
Copyright 2001 S. Karger AG, Basel.

PMID: 11150849 [PubMed - indexed for MEDLINE]

1399: J Allergy Clin Immunol. 2001 Jan;107(1):105-13.

Role of kinins in seasonal allergic rhinitis: icatibant, a bradykinin B2 receptor
antagonist, abolishes the hyperresponsiveness and nasal eosinophilia induced by
antigen.

Turner P, Dear J, Scadding G, Foreman JC.

Department of Pharmacology, University College London, London, United Kingdom.

BACKGROUND: Icatibant, a bradykinin B(2) receptor antagonist, inhibits the
reduction in nasal patency after challenge with house dust mite antigen in
sensitive subjects and abolishes the nasal hyperresponsiveness induced by
platelet-activating factor in nonatopic subjects. OBJECTIVE: We sought to
investigate the effect of icatibant on the response to nasal antigen challenge in
subjects with seasonal allergic rhinitis. METHODS: Patients allergic to grass
pollen antigen (n = 9-13) were included in a double-blind, randomized-block,
placebo-controlled, crossover study outside the pollen season. Subjects first
received an intranasal spray of icatibant (200 microg per nostril) or a saline
control. Subjects were then challenged with antigen or diluent (control), and
their responses were monitored by using acoustic rhinometry. Six hours later,
nasal lavage fluid was collected and quantified for inflammatory cells and
various inflammatory mediators (kinin, eosinophil cationic protein, IL-5, and
IL-8). At 24 hours, the response of the nasal airways to 200 microg of histamine 
was assessed, and a further nasal lavage was carried out. RESULTS: Antigen
challenge caused a significant increase in nasal obstruction and albumin
extravasation, which was not affected by icatibant. Nasal hyperresponsiveness to 
histamine was present 24 hours after antigen and was abolished by pretreatment
with icatibant. Icatibant also reduced the antigen-induced increase in
eosinophils, eosinophil cationic protein, kinin, and IL-8 in nasal lavage fluid. 
CONCLUSION: Pretreatment with icatibant does not affect the acute inflammatory
response in seasonal allergic rhinitis. However, our results imply the
involvement of kinins and the bradykinin B(2) receptor in the development of
antigen-induced hyperresponsiveness and the associated eosinophilia in the human 
nasal airway.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11149999 [PubMed - indexed for MEDLINE]

1400: J Allergy Clin Immunol. 2001 Jan;107(1):87-93.

Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized,
controlled trial.

Walker SM, Pajno GB, Lima MT, Wilson DR, Durham SR.

Upper Respiratory Medicine, Imperial College School of Medicine at the National
Heart and Lung Institute, London, UK.

BACKGROUND: Grass pollen immunotherapy significantly reduces hay fever symptoms
and medication requirements. Effects on seasonal asthma are less clear, and
concerns over safety persist. OBJECTIVE: The goal of this study was to assess the
effects of grass pollen immunotherapy on symptoms, bronchial hyperresponsiveness,
and quality of life in seasonal rhinitis and asthma. METHODS: Forty-four patients
with severe summer hay fever (of whom 36 reported seasonal chest symptoms and 28 
had seasonal bronchial hyperresponsiveness) participated in a randomized,
double-blind, placebo-controlled, parallel group study. After symptom monitoring 
for one summer, participants received injections of a depot grass pollen vaccine 
(n = 22) or matched placebo injections (n = 22) in a rapid updosing cluster
regimen for 4 weeks, followed by monthly injections for 2 years. Outcome measures
included hay fever symptoms and medication use, health-related quality of life,
and measurements of nonspecific bronchial responsiveness. RESULTS: Significant
reductions were observed in the immunotherapy group compared with the placebo
group in hay fever symptoms (49%, 15%; P =.01), medication scores (80%, 18%; P
=.007), and seasonal chest symptoms (90%, 11%; P <.05). Impairment of overall
quality of life (mean score of 7 domains) during the pollen season was less in
the immunotherapy group than in the placebo group (median difference [95% CI],
0.8 [0.18-1.5]; P =.02). During the pollen season there was no change in airway
methacholine PC(20) (provocation concentration producing a 20% fall in FEV(1)) in
the immunotherapy-treated group (P =.5), compared with an almost 3 doubling-dose 
decrease in the placebo-treated group (P =.01, between-group difference). There
were no significant local or systemic side effects during the study. CONCLUSION: 
Grass pollen immunotherapy improves quality of life in seasonal allergic rhinitis
and reduces seasonal asthma symptoms and bronchial hyperresponsiveness.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11149996 [PubMed - indexed for MEDLINE]

1401: Arzneimittelforschung. 2000 Nov;50(11):1037-42.

Animal models of allergic rhinitis.

Szelenyi I, Marx D, Jahn W.

Department Pulmonary Pharmacology, Corporate Research & Development, ASTA Medica 
AG, Radebeul and Halle-Künsebeck, Germany. stefan.szelenyi@astamedica.de

Actively sensitized Brown Norway rats and guinea pig are useful species for
studying drug effects on symptoms of experimental rhinitis. Even if not all
symptoms of human rhinitis can be induced and detected in the same animal
species, the predictablity of methods generally used is well acceptable. In the
present review, advantages and disadvantages of experimental methods of rhinitis 
will be discussed.

Publication Types: 
    Review

PMID: 11148861 [PubMed - indexed for MEDLINE]

1402: Graefes Arch Clin Exp Ophthalmol. 2000 Nov;238(11):900-4.

Correlation between tear IgE levels and HLA-DR expression by conjunctival cells
in allergic and nonallergic chronic conjunctivitis.

Baudouin C, Bourcier T, Brignole F, Bertel F, Moldovan M, Goldschild M, Goguel A.

Department of Ophthalmology, Ambroise Paré Hospital, University of Paris-V, 9
avenue Charles de Gaulle, 92100 Boulogne/Seine, France.

BACKGROUND: Chronic conjunctival inflammatory diseases may depend upon various
mechanisms. Discriminating allergy from nonspecific inflammation has become of
striking importance for diagnosis and treatment. We investigated conjunctival
inflammatory response by comparing two objective biological tools, tear IgE and
HLA-DR expression by conjunctival epithelium, as indirect indicators of
activation of the Th2 and Th1 subsets, respectively. METHODS: Eighty-two patients
with chronic conjunctivitis underwent tear IgE measurement by an ELISA technique 
and quantitation of HLA-DR expression in impression cytology specimens. Forty-two
had direct or indirect clinical indications of allergic mechanisms, 26 had
chronic conjunctivitis without any sign of allergy, and 14 suffered from isolated
nonallergic dry eyes. RESULTS: Patients clinically considered as allergic only
showed positive IgE in 47 of 84 eyes (56%), whereas 21% and 25% of eyes with
nonspecific conjunctivitis and dry eyes respectively were also positive. IgE
levels were significantly higher in the allergic group than in the other two
groups. HLA-DR positivity in epithelial cells was found in 28.5%, 48% and 50% of 
eyes, respectively. HLA-DR expression by epithelial cells was negatively
correlated with tear IgE, as most specimens positive to one criterion were
negative to the other one (49 eyes DR+, IgE-; 47 eyes DR-, IgE+; only 9 eyes
positive to both criteria; chi-square: P = 0.0001). CONCLUSION: As IgE synthesis 
and HLA-DR induction may represent indirect indicators of the activation of the
Th2 and Th1 subsets, association of these two simple tests could be interesting
for the routine assessment of the mechanisms of inflammatory ocular surface
diseases.

Publication Types: 
    Comparative Study

PMID: 11148813 [PubMed - indexed for MEDLINE]

1403: J Indian Med Assoc. 2000 Jul;98(7):397-9.

The changing face of antihistamines and cardiac adverse drug reactions: a
clinical perspective.

Shaikh WA.

Hony Allergist, Bombay Hospital & Medical Research Centre, Mumbai 400020.

Recent times have witnessed a qualitative shift in the recognition and management
of adverse drug effects. Many of them occur in organs that are unconnected to the
primary target of pharmacological action. Out of these, cardiac side-effects have
drawn particular attention because of their potential to cause death. Starting
with the early observations on antibiotics such as macrolides, followed by
fluoroquinolones and others, the focus has now shifted to the antihistamine class
of drugs which are used extensively by patients all over the world, thanks to the
ever increasing levels of environmental pollution. The occurrence of prolonged
QTc interval following treatment with terfenadine leading to ventricular
tachycardia of torsades de points variety with a potentially fatal outcome has
forced many regulatory authorities of the world to clamp a ban the use of this
drug. Alerted by these developments, studies on a new member, followed by
fluoroquinolones and others, the focus has now shifted to the antihistamine class
of drugs which are used extensively by patients all over the world, thanks to the
ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc
interval following treatment with terfenadine leading to ventricular tachycardia 
of torsades de points variety with a potentially fatal outcome has forced many
regulatory authorities of the world to clamp a ban use of this drug. Alerted by
these developments, studies on a new member of non-sedating antihistamine class
viz, fexofenadine, have been reviewed especially because of the structural
similarity between terfenadine and fexofenadine. It is now clear that despite the
closeness of its chemical structure to terfenadine fexofenadine behaves in a
different manner and does not affect the electrophysiology of the heart muscle
tissue, as proved by data from extensive clinical trials as well as membrane
models in vitro. Interestingly, the solitary false alarm that was sounded on the 
drug by a group of workers in the Netherlands was later rectified by the same
group. Clinically speaking, the cardiovascular safety of fexofenadine has been
convincingly demonstrated at various dose levels and various time intervals,
alone and together with other drugs of potential toxigenicity. All things put
together, it appears reasonable to conclude that fexofenadine is free from
cardiovascular ADRs of clinical significance. It could also be concluded that
cardiac side-effects of antihistamines is not a class effect.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11143865 [PubMed - indexed for MEDLINE]

1404: Ann Otol Rhinol Laryngol. 2000 Dec;109(12 Pt 1):1120-4.

Time course of changes in absorption of macromolecule through the nasal mucosa
after antigen challenge in guinea pig model of allergic rhinitis.

Numata T, Konno A, Terada N, Hanazawa T, Nagata H, Motosugi H, Okamoto Y.

Department of Otorhinolaryngology, Chiba University, School of Medicine, Chiba
City, Japan.

The time course of changes in absorption of horseradish peroxidase (HRP) through 
the nasal mucosa after antigen challenge was evaluated in a guinea pig model of
allergic rhinitis immunized with ovalbumin. Before and at 5 minutes, 4 hours, and
24 hours after nasal antigen challenge, both nasal cavities were filled with 5%
HRP solution for 30 minutes, and blood was obtained to measure serum HRP levels
by enzyme-linked immunosorbent assay. In immunized animals, the serum HRP levels 
were 2.3 times higher than those of normal controls (p<.05) before antigen
challenge, which was performed 7 days after a series of nasal antigenic
sensitizations. At 5 to 35 minutes after antigen challenge, the HRP levels
decreased to one sixth of the prechallenge levels (p<.05), and they did not show 
a difference from the control levels. However, they increased markedly at 4 and
24 hours after antigen challenge (p<.01). The present study suggests that the
absorption of macromolecules through the allergic nasal mucosa is enhanced
markedly, depending upon the time course after antigen challenge, although it
shows no apparent difference from normal controls during the dominant exudative
process.

PMID: 11130823 [PubMed - indexed for MEDLINE]

1405: Clin Otolaryngol Allied Sci. 2000 Dec;25(6):551-7.

Patient and physician perspectives on the impact and management of perennial and 
seasonal allergic rhinitis.

Scadding GK, Richards DH, Price MJ.

Royal National Throat Nose and Ear Hospital, London and Respiratory Therapeutic
Development and Global Health Outcomes Research, GlaxoWellcome plc, Uxbridge, UK.
g.scadding@ucl.ac.uk

Patient and physician perspectives on the impact and management of perennial
(PAR) and seasonal allergic rhinitis (SAR) were studied. In all, 2139 subjects
were questioned about their medical conditions, severity and frequency of
symptoms and satisfaction with treatment. A group of general practitioners (GPs) 
were also invited to discuss their experiences in the management of rhinitis. In 
this UK survey, allergic rhinitis was more common than asthma, hypertension, skin
rashes, eczema and diabetes. The prevalence of SAR and PAR was 15% and 2%,
respectively. Sneezing and runny nose were the most common symptoms and GPs were 
the main contact for advice and treatment (54% of patients). Symptoms were
well-controlled in 32% of patients. Allergic rhinitis affected work, home and
social life in 29%, 34% and 30% of patients, respectively. The GPs considered PAR
to be more difficult to treat than SAR, and GP and patient level of satisfaction 
in the treatment of PAR was low. This suggests that education of patients and
physicians on the benefits of allergen avoidance, and the selective use of the
highly effective therapies available on prescription could improve the level of
satisfaction with therapy. Adherence to current guidelines on the management of
rhinitis could lead to an effective, structured treatment plan for patients.

PMID: 11122298 [PubMed - indexed for MEDLINE]

1406: Allergy. 2000 Dec;55(12):1142-7.

Preseasonal local allergoid immunotherapy to grass pollen in children: a
double-blind, placebo-controlled, randomized trial.

Caffarelli C, Sensi LG, Marcucci F, Cavagni G.

Pediatric Department, Parma.

BACKGROUND: We assessed the efficacy of preseasonal local allergoid immunotherapy
in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due
to grass pollen. METHODS: We randomly assigned 24 children allergic to grass
pollen to receive local allergoid immunotherapy for 3 months before the pollen
season and 24 such patients to receive identically appearing placebo. The
immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens 
held in the mouth until they dissolved and then swallowed. The study was
double-blind. Symptoms and medications were scored on diary cards during the
pollen season. Nasal eosinophil cationic protein levels were measured by the
monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at
high pollen concentration during the pollen season. RESULTS: The active-treatment
group had a statistically significant reduction of total symptoms (P<0.05),
especially bronchial symptoms (P<0.05), in comparison with the placebo group.
Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and
EG1 increased significantly during the pollen season, but there was no difference
between groups. EG2/EG1 increased significantly only in the placebo group during 
natural allergen exposure (P<0.01). CONCLUSIONS: Our results suggest that this
immunotherapy is effective for the treatment of asthma due to grass pollen in
children.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11117271 [PubMed - indexed for MEDLINE]

1407: Otolaryngol Head Neck Surg. 2000 Dec;123(6):687-91.

Chronic rhinosinusitis: allergy and sinus computed tomography relationships.

Emanuel IA, Shah SB.

University of California, San Francisco, USA.

The management of chronic or recurrent rhinosinusitis problems is multifaceted
and should include consideration of contributory and potentially correctable
medical and anatomic factors. To date, the relationship between allergy and
rhinosinusitis has not been clearly defined. The purpose of this study is to
improve understanding of the relative roles of perennial and seasonal allergens
in the cause of chronic rhinosinusitis. A retrospective review of 200 consecutive
patients was carried out on patients who had chronic rhinosinusitis refractory to
medical therapy and who subsequently underwent functional endoscopic sinus
surgery. All of these patients had allergy testing for common perennial and
seasonal inhalant allergens before surgery. Each patient had sinus CT imaging
before undergoing the surgery. The CT scans of each patient were staged according
to a validated, standardized grading system by investigators blinded to allergic 
profile. Allergy testing indicated that 84% of all patients tested positive for
allergies. Moreover, 60% of all patients had significant allergic sensitivity;
52% of all patients had multiple allergen sensitivities. Furthermore, there was a
predominance of perennial allergens, especially house dust mite over seasonal
allergens. The vast majority of our patients undergoing functional endoscopic
sinus surgery had concomitant allergy. This study highlights the potential
contribution of perennial allergies to the development of rhinosinusitis. Given
this direction, future studies may reveal that in the care of patients with
perennial allergic rhinitis, early intervention with identification of the
offending allergen(s), and subsequent treatment through avoidance,
pharmacotherapy, and/or immunotherapy may help in the prevention of recurrent and
chronic rhinosinusitis.

PMID: 11112958 [PubMed - indexed for MEDLINE]

1408: J Allergy Clin Immunol. 2000 Dec;106(6):1045-52.

Natural and induced allergic responses increase the ability of the nose to warm
and humidify air.

Assanasen P, Baroody FM, Abbott DJ, Naureckas E, Solway J, Naclerio RM.

Section of Otolaryngology-Head and Neck Surgery and the Section of Pulmonary and 
Critical Care Medicine, The Pritzker School of Medicine, The University of
Chicago, IL 60637, USA.

BACKGROUND: We have previously shown that subjects with seasonal allergic
rhinitis out of season had a reduced ability to warm and humidify air compared
with normal subjects. OBJECTIVE: We sought to investigate whether allergic
reactions induced by either seasonal exposure or nasal challenge with antigen
would decrease the capacity of the nose to condition cold, dry air. METHODS: We
performed two prospective studies comparing the effects of allergic inflammation,
induced by either seasonal exposure or nasal challenge with antigen, on nasal
conditioning capacity (NCC). The total water gradient (WG) across the nose was
used to represent the NCC. In the first study, the NCC was measured and compared 
before and during the allergy season in 10 subjects with seasonal allergic
rhinitis. In the second study, 20 subjects with seasonal allergic rhinitis were
recruited outside of the allergy season. NCC was measured and compared before and
24 hours after challenge with antigen. RESULTS: In the first study, seasonal
allergic subjects in season showed a significant increase in NCC when compared
with their preseason baseline (total WG in season: 2050 +/- 138 mg vs total WG
preseason: 1524 +/- 100 mg; P <.01). In the second study, antigen challenge led
to early-phase and late-phase responses. There was a statistically significant
increase in NCC 24 hours after antigen challenge compared with that before
antigen challenge (total WG after antigen challenge: 1938 +/- 101 mg vs total WG 
before antigen challenge: 1648 +/- 84 mg; P =.01). CONCLUSION: Allergic reactions
induced by either seasonal exposure or antigen challenge increase the ability of 
the nose to condition inspired air. We speculate that allergic inflammation
increases this ability by changing the perimeter of the nasal cavity.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 11112885 [PubMed - indexed for MEDLINE]

1409: Pediatr Allergy Immunol. 2000 Nov;11(4):256-9.

Nasal peak inspiratory flow through Turbuhaler in children with symptomatic
rhinitis and in healthy children.

van Zoest JG, van der Weij AM, Duiverman EJ, Akerlund A, Kouwenberg JM.

Juliana Children's Hospital, Department of Paediatric Pulmonology, The Hague, The
Netherlands.

Topical treatment of allergic or vasomotor rhinitis is possible by means of
pressurized metered dose inhalers, aqueous spray, or dry powder inhalers. In
children, little is known about nasal drug delivery by dry powder inhalation. The
airflow through the device is critical for the drug release and a sufficient
nasal inspiratory flow is needed for intranasal drug delivery from a dry powder
inhaler. In order to investigate from what age children with allergic or
vasomotor rhinitis can reliably use such a device, device-dependent nasal peak
inspiratory flow (DnPIF) was measured. The maximal DnPIF was measured in children
aged 4-13 years making use of a dry powder inhaler (Turbuhaler) connected to a
spirometer (Vitalograph). In the clinically relevant context, instructions from
the doctor and one week's use of a Turbuhaler at home were found to be sufficient
to obtain a good inhalation technique and were shown to improve DnPIF at least as
effectively as visual feedback training at the clinic. Children with rhinitis, as
well as healthy children from the age of 6 years, were able to generate a DnPIF
sufficient to obtain a reliable nasal delivery of a dry powder drug dose. DnPIF
values correlated with age. Consequently, a recommendation to use a nasal
Turbuhaler from the age of 6 for topical drug delivery in the treatment of
allergic or vasomotor rhinitis seems reasonable.

PMID: 11110582 [PubMed - indexed for MEDLINE]

1410: J Investig Allergol Clin Immunol. 2000 Sep-Oct;10(5):300-4.

Local nasal immunotherapy and bronchial hyperreactivity in seasonal allergic
rhinitis: an observational pilot study.

Olivieri M, Mohaddes Zadeh MR, Talamini G, Lampronti G, Lo Cascio V.

Department of Biomedical Science and Surgery, Internal Medicine D, Italy.

The clinical efficacy of local nasal immunotherapy (LNIT) in patients with
allergic rhinitis is amply documented. The aim of the study was to determine the 
effect on bronchial hyperresponsiveness (BHR) assessed at baseline and after 3
years of LNIT or pharmacological treatment alone. Forty-three randomized patients
with allergic oculorhinitis were enrolled (26 positive to Graminaceae and 17 to
Parietaria judaica pollens). All patients were asked whether they were willing to
follow a 3-year treatment course involving preseasonal LNIT with a powder extract
of Graminaceae or Parietaria pollens. Twenty-four patients (16 allergic to
Graminaceae and eight to Parietaria) selected LNIT and the other 19 opted for
symptomatic pharmacological treatment only. The latter was considered the control
group. On the basis of positive or negative bronchial hyperresponsiveness and the
LNIT, four subgroups were established and followed in open conditions, during
which a record was kept of symptom scores, drug use, spirometry and methacholine 
test findings. After 3 years, patients treated with LNIT had a significant
reduction of symptoms and drug intake. In the controls, symptoms worsened, thus
requiring more drugs to control them. Bronchial hyperresponsiveness significantly
improved in hyperreactive patients receiving LN7IT 10 of whom were no longer
hyperreactive and one at a higher threshold. Among controls, bronchial
hyperresponsiveness did not change, with the exception of three nonreactive
patients who became hyperreactive, one of them with asthma. These findings
confirm the efficacy of LNIT in allergic rhinitis suggesting that it might have
systemic activity interfering with bronchial hyperresponsiveness and hence the
onset of bronchial asthma.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11108443 [PubMed - indexed for MEDLINE]

1411: Ann Allergy Asthma Immunol. 2000 Nov;85(5):338-47; quiz 347-8.

Quality of life in patients with allergic rhinitis.

Thompson AK, Juniper E, Meltzer EO.

US Medical Affairs, Aventis Pharmaceuticals Inc, Kansas City, Missouri 64137,
USA.

LEARNING OBJECTIVES: Reading this article will familiarize the practitioner with 
ongoing efforts to measure the effects of allergic rhinitis symptoms and its
treatments on the health-related quality of life (HRQOL) of patients. The reader 
will learn about instruments used to collect HRQOL data, results of studies
showing the burden of illness and the effects of treatments on HRQOL, and efforts
to interpret the clinical relevance of changes in HRQOL status. DATA SOURCES:
Information was gleaned from articles listed in MEDLINE regarding HRQOL in
allergic rhinitis between 1966 and 2000 (English language only), and from the
personal experiences of the authors. STUDY SELECTION: Questionnaire validation
studies and representative controlled trials employing measures to assess the
effects of allergic rhinitis symptoms and its treatments on HRQOL are described. 
RESULTS FROM THIS REVIEW: Allergic rhinitis symptoms can have detrimental effects
on the physical, psychologic, and social aspects of patients' lives. Clinical
trial data suggest a variety of pharmacologic therapies can significantly improve
HRQOL in patients with allergic rhinitis. Validated questionnaires are now
available that can easily be used in clinical practice to measure the effects of 
interventions on HRQOL for individual patients. CONCLUSIONS: Evaluating the
effects of interventions on HRQOL may be particularly important in a
non-life-threatening condition such as rhinitis. Health-related quality of life
measures can be used to indicate the risk/benefit and the cost/benefit ratios of 
competing treatment options. Clinicians and policy makers are already using HRQOL
data to evaluate results of medical interventions to guide patient management and
reimbursement decisions.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11101172 [PubMed - indexed for MEDLINE]

1412: Acta Otolaryngol. 2000 Sep;120(6):757-60.

Nasal secretion in ragweed-sensitized dogs: effect of leukotriene synthesis
inhibition.

Cardell LO, Agustí C, Nadel JA.

Cardiovascular Research Institute and the Department of Medicine, University of
California at San Francisco, USA. Lars-Olaf.Cardell@oron.mas.lu.se

Allergic rhinitis is an inflammatory disease associated with local leukotriene
release during periods of symptoms. Zileuton, a leukotriene synthesis inhibitor, 
is known to inhibit the release of leukotriene B4. Because we previously showed
that leukotriene B4 is a potent mediator of neutrophil-dependent nasal secretion,
we investigated whether Zileuton inhibited allergen-induced nasal secretion.
Using a newly developed method for isolating and superfusing a nasal segment, we 
examined the effect of Zileuton on nasal secretion and neutrophil recruitment in 
ragweed-sensitized dogs. Instillation of ragweed into the nasal segment caused
time-dependent increases in the volume of airway fluid and the recruitment of
neutrophils. Zileuton prevented ragweed-induced neutrophil recruitment and nasal 
secretion. These results indicate that leukotrienes are important mediators of
allergy-induced nasal secretion in dogs. Future clinical studies in allergic
patients will determine whether there is a therapeutic role for leukotriene
synthesis inhibitors in modulating neutrophil recruitment and hypersecretion in
the nose.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11099154 [PubMed - indexed for MEDLINE]

1413: Allergy. 2000 Nov;55(11):1019-24.

Prevalence and predictors of rhinitis in Danish children and adolescents.

Ulrik CS, von Linstow ML, Backer V.

Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet,
Copenhagen, Denmark.

BACKGROUND: The prevalence of self-reported symptoms of allergic rhinitis is
increasing in many countries, but the reasons for this trend are not well
understood. Data from a 6-year follow-up study of a population sample of children
and adolescents (n=408), aged 7-17 years at enrolment in 1986, were analyzed to
investigate the prevalence and predictors of self-reported rhinitis. METHODS:
Case history was used to assess the presence or absence of rhinitis (sneezing and
running or blocked nose not associated with a cold), asthma, and eczema.
Pulmonary function, skin prick test reactivity, and airway responsiveness to
histamine were measured in all participants; a screening test for IgE antibodies 
to common allergens (Magic Lite SQ, Allergy Screen, ALK, Denmark) was performed
in 237 (58%) of the participants. RESULTS: The point prevalence of rhinitis
increased from the first to the second survey, 14% and 22%, respectively; 54
(13%) of the subjects reported rhinitis only at the second survey (new rhinitis).
Confining the analysis to participants without symptoms of rhinitis at the first 
survey showed that self-reported eczema (relative risk [RR] 2.3, 95% confidence
interval [CI] 1.2-4.7), airway hyperresponsiveness (RR 2.5, CI 1.8-3.0), atopy to
grass pollen (RR 2.6, CI 1.7-3.3), atopy to dog dander (RR 2.4, CI 1.6-3.3), and 
atopy to house-dust mite (RR 2.7, CI 1.4-5.2) at the first survey predicted an
increased risk of the presence of rhinitis at the second survey. A positive
Allergy Screen test at enrollment was associated with an increased risk of
self-reported rhinitis at follow-up (RR 2.4, CI 1.4-3.4). CONCLUSIONS: This
longitudinal population study of children and adolescents showed an age-related
increase in the point prevalence of self-reported rhinitis; furthermore,
sensitization to common aeroallergens, airway hyperresponsiveness, and the
presence of self-reported eczema were significantly associated with an increased 
risk of subsequent development of rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11097310 [PubMed - indexed for MEDLINE]

1414: J Allergy Clin Immunol. 2000 Nov;106(5 Suppl):S247-50.

Systemic immunologic and inflammatory aspects of allergic rhinitis.

Togias AG.

Division of Clinical Immunology, Johns Hopkins University, School of Medicine,
Baltimore, MD, USA.

Allergic rhinitis is a common chronic condition that is characterized by
inflammation of the nasal mucosa. Although allergic rhinitis is a condition with 
upper respiratory symptoms, there is a growing body of evidence to suggest that
allergic rhinitis may be linked to the development of systemic allergic
manifestations that include allergic asthma. The evidence reveals that
individuals with allergic rhinitis are sensitized to the eliciting allergens and 
exhibit cutaneous and respiratory hypersensitivity responses on exposure to the
allergen. On exposure to a nasal allergen, circulating immunoglobulin E levels
increased and remained elevated 2 weeks after the initial provocation. Patients
with allergic rhinitis exhibit peripheral eosinophilia and basophilia, the
magnitude of which correlates with the severity of symptoms. Additionally, there 
are several links between allergic rhinitis and asthma. First, 85% to 95% of
patients with allergic asthma report rhinitis symptoms, and the severity of the 2
conditions increases in parallel on exposure to an allergen. Second, nasal
administration of allergens can provoke impaired lower airway airflow in 25% to
30% of individuals and cause airway eosinophilia, as evidenced by increased
numbers of eosinophils in sputum and mucosal biopsy specimens. Third, the
treatment of seasonal allergic rhinitis with both systemic (eg, antihistamines)
and local agents (eg, glucocorticosteroid analogues) can alleviate the symptoms
of asthma. In summary, evidence that associates allergic rhinitis with systemic
immunologic and inflammatory processes is growing, thereby warranting further
in-depth investigation.

Publication Types: 
    Review

PMID: 11080739 [PubMed - indexed for MEDLINE]

1415: J Allergy Clin Immunol. 2000 Nov;106(5):904-10.

Cytokine expression in the lower airways of nonasthmatic subjects with allergic
rhinitis: influence of natural allergen exposure.

Chakir J, Laviolette M, Turcotte H, Boutet M, Boulet LP.

Unité de Recherche en Pneumologie, Centre de Recherche de l'H opital Laval,
Institut de Cardiologie et Pneumologie de l'Université Laval, Sainte-Foy, Quebec,
Canada.

BACKGROUND: Natural exposure to pollen provokes an increase in airway
responsiveness in nonasthmatic subjects with seasonal allergic rhinitis. This
natural exposure may induce inflammatory cell recruitment and cytokine release,
leading to lower airway inflammation. OBJECTIVE: The aim of this study was to
characterize lower airway inflammation in nonasthmatic pollen-sensitive subjects.
METHODS: We performed immunohistochemical tests on bronchial biopsy specimens
from subjects with rhinitis who had no past or current history of asthma to
evaluate cytokine expression and inflammatory cell numbers and activation both in
and out of the pollen season. RESULTS: The number of CD4(+), CD8(+), and
CD45RO(+) lymphocyte subpopulations were significantly higher during the pollen
season compared with the out-of-season period (P <.04). Furthermore, EG1(+) cells
tended to increase after natural pollen exposure (P =.06). The number of IL-5(+) 
cells increased significantly after natural exposure to pollen compared with
out-of-season numbers (P <.01). This increase in IL-5 expression was correlated
with the numbers of CD3(+), CD4(+), CD45RO(+), and EG1(+) cells. The numbers of
tryptase-positive, IFN-gamma(+), and IL-4(+) cells did not change after natural
exposure. CONCLUSION: This study showed that natural pollen exposure was
associated with an increase in lymphocyte numbers, eosinophil recruitment, and
IL-5 expression in the bronchial mucosa of nonasthmatic subjects with allergic
rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11080713 [PubMed - indexed for MEDLINE]

1416: J Allergy Clin Immunol. 2000 Nov;106(5):832-9.

Development of seasonal allergic rhinitis during the first 7 years of life.

Kulig M, Klettke U, Wahn V, Forster J, Bauer CP, Wahn U.

Institute of Social Medicine and Epidemiology, Charité Hospital, Humboldt
University at Berlin, Berlin, Germany.

BACKGROUND: Against the background of the controversial discussion about an
increase in allergic rhinitis in recent years, intraindividual longitudinal data 
is lacking for IgE-mediated seasonal allergic rhinitis (SAR). Little is known
about the development of SAR in terms of prevalence and incidence rates from
birth to school age. OBJECTIVE: In a prospective birth cohort, we investigated
the development of sensitization and symptoms of SAR. SAR should be defined with 
high specificity, and associated risk factors should be determined. METHODS:
Annual longitudinal data about seasonal allergic symptoms and sensitization was
available for 587 children from birth to their seventh birthday. The definition
of SAR was based on a combination of exposure-related symptoms and sensitization.
RESULTS: Up to 7 years of age, SAR developed in 15% of the children. Incidence
and prevalence of symptoms and sensitization were low during early childhood
(<2%) and increased steadily with age. Children in which SAR had already
developed in the second year all were born in spring or early summer, resulting
in at least two seasons of pollen exposure before manifestation of SAR. Risk
factors assessed by multiple logistic regression analysis were male sex (odds
ratio [OR] = 2.4), atopic mothers (OR = 2.6) and fathers (OR = 3.6) having
allergic rhinitis themselves, first-born child (OR = 2.0), early sensitization to
food (OR = 3.3), and atopic dermatitis (OR = 2.5), whereas early wheezing was not
associated with SAR. CONCLUSION: The development of SAR is characterized by a
marked increase in prevalence and incidence after the second year of life. Our
longitudinal data further indicate that in combination with the risk of allergic 
predisposition, at least 2 seasons of pollen allergen exposure are needed before 
allergic rhinitis becomes clinically manifest.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 11080703 [PubMed - indexed for MEDLINE]

1417: Acta Paediatr. 2000 Sep;89(9):1056-61.

Allelic association of gene markers on chromosome 11q in Italian families with
atopy.

Rigoli L, Salpietro DC, Lavalle R, Cafiero G, Zuccarello D, Barberi I.

Department of Pediatrics, University of Messina, School of Medicine, Italy.

In our study, the genetic linkage of the Fcepsilon RIbeta gene with atopy in 77
affected sibling pairs recruited from an Italian panel of 201 subjects has been
examined. Atopy was defined by the presence of a positive skin prick test to one 
or more common aeroallergens, a positive RAST test to one or more common
aeroallergens and an elevated circulating total IgE. Genotype analysis was
performed by PCR amplification of Fcepsilon RIbeta CA and CI11-319 CA
microsatellites. All the family members were also tested for the Ilepsilon 181
mutation with the ARMS method and for Leu181/Leu183 polymorphism. Seventy-two
point five percent (72.5%) of the affected sibling pairs shared their maternal
allele and 27.5% did not. Therefore, an increased maternal allele sharing was
observed: chi2 = 8.10, p < 0.01. Comparing paternal versus maternal allele
sharing, a significant difference was observed for the C1II-319 CA marker (chi2 =
4.32, p < 0.05). Atopy phenotype with positive skin prick test, RASTs, and high
total serum IgE also showed greater sharing of maternal than paternal alleles in 
affected sibling pairs. Of the 201 subjects studied, 17 (8.4%) were positive for 
Leu181. Ten of these were children and seven (70%) had inherited the variant
maternally. The seven children had maternally inherited Leu181/Leu183 and were
atopic. Within this sample the maternal inheritance of Fcepsilon RIbeta
Leu181/Leu183 was associated with an increased risk of IgE responses to common
allergens, raised eosinophil counts and increased skin prick test reactions.
Therefore, the variant identified a genetic risk factor for atopy. CONCLUSION:
The central role of Fcepsilon RIbeta in atopy and the linkage data presented here
point to the possibility that genetic variation in Fcepsilon RIbeta or its
controlling element may cause differences in the extent of IgE responses between 
atopic and non-atopic subjects. A search for such mutations or polymorphisms will
need to take into account some carriers of atopy among the normal population and 
genetic heterogeneity among atopic individuals.

PMID: 11071084 [PubMed - indexed for MEDLINE]

1418: Am J Respir Crit Care Med. 2000 Nov;162(5):1705-8.

Immediate effect of topical budesonide on allergen challenge-induced nasal
mucosal fluid levels of granulocyte-macrophage colony-stimulating factor and
interleukin-5.

Linden M, Svensson C, Andersson E, Andersson M, Greiff L, Persson CG.

Experimental Medicine, AstraZeneca R&D, Lund, Sweden.
margareta.linden@astrazeneca.com

The nasal antiinflammatory effects produced by maintenance treatment with topical
steroids include reduced production of cytokines. The present study explored
nasal mucosal effects induced during the first 9 h after a single dose of topical
budesonide. Nine subjects with allergic rhinitis due to birch or timothy pollen
were given budesonide (256 microg; Rhinocort Aqua) or placebo in a double-blind, 
randomized, crossover (4 wk washout) manner. Nasal allergen challenges were
performed 30 min after the steroid/placebo pretreatment. Before and 30 min, 1, 3,
5, 7, and 9 h after challenge, filter paper strips were placed on the nasal
septum and inferior turbinates for 10 min to sample undiluted mucosal fluids.
Strips were then extracted in 1 ml buffer for cytokine analysis (ELISA). Allergen
challenge produced acute nasal symptoms that peaked at 30 min and then tapered
off. Conversely, both GM-CSF and IL-5 were increased only at 3, 5, 7 and 9 h (p <
0.05 compared with baseline). Budesonide did not affect the nasal symptoms but
inhibited (p < 0. 05; compared with placebo treatment) the allergen
challenge-induced mucosal output of GM-CSF and IL-5. These data demonstrate that 
GM-CSF and IL-5 are induced in a nonsymptomatic, late phase response to nasal
allergen challenge, and that this cytokine response is prevented by single dose
budesonide pretreatment.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11069800 [PubMed - indexed for MEDLINE]

1419: Am J Rhinol. 2000 Sep-Oct;14(5):335-8.

Pathophysiology of nasal symptoms.

Eccles R.

Common Cold Centre, Cardiff University, Wales, UK.

Symptoms are perceived by the patient and all nasal symptoms must eventually
relate to stimulation of sensory nerves or some change in the activity of the
CNS. Although it is the symptoms that are of prime importance to the patient, the
role of sensory nerves and psychology in the generation and perception of
symptoms has been relatively neglected compared to the large amount of research
on inflammatory mediators. This paper discusses how physical and chemical changes
in the nasal epithelium result in the generation of inflammatory mediators that
are responsible for symptoms. Inflammatory mediators can cause symptoms in three 
ways. (1) By having direct action on glands and blood vessels to cause glandular 
secretion, vasodilation, increased vascular permeability, and transudation of a
plasma exudate. (2) By stimulation of sensory nerve endings to cause reflex
glandular secretion, sneezing, and sensations such as itching, irritation, pain, 
and pressure. (3) By effects on the central nervous system to cause, headache,
fever, tiredness, and mood changes.

Publication Types: 
    Review

PMID: 11068659 [PubMed - indexed for MEDLINE]

1420: Am J Rhinol. 2000 Sep-Oct;14(5):325-33.

Pathogenic mechanisms underlying the clinical symptoms of allergic rhinitis.

Wang DY, Clement P.

Department of Otolaryngology, National University of Singapore, Republic of
Singapore.

This paper reviews our previous studies on an objective evaluation of nasal
symptoms, a quantitative determination of biochemical mediators, and inflammatory
cells in nasal secretions of atopic patients after nasal allergen challenge (NAC)
and during natural allergen exposure. The use of the microsuction technique has
proved to be a useful and reliable nasal sampling method permitting quantitative 
analysis of important mediators in nasal secretions. This has provided accurate
data on the activity of some important inflammatory cells such as mast cells,
basophils, and eosinophils in allergic rhinitis. Our studies demonstrate that a
significant increase in the concentrations of histamine, tryptase, and LTC4 in
nasal secretions occurs within seconds or minutes after NAC, and this is
accompanied by itching, sneezing, rhinorrhea, and nasal obstruction. The
infiltration and activation of eosinophils are found to be the predominant
condition during the late-phase reaction (LPR), which is mainly characterized by 
unilateral and/or bilateral nasal obstruction with little sneezing and
rhinorrhea. The latter condition is found to be very much similar to the
pathophysiology of patients with ongoing allergic rhinitis. In conclusion, our
studies demonstrate that patients with ongoing allergic rhinitis seem to be in a 
continuous late phase state of eosinophilia and increased mediator release, a
condition that can explain priming and nonspecific hyperreactivity of the nasal
mucous membrane.

Publication Types: 
    Review

PMID: 11068658 [PubMed - indexed for MEDLINE]

1421: Am J Rhinol. 2000 Sep-Oct;14(5):319-23.

Nonsteroidal antiallergic treatments in allergic rhinitis.

Canonica GW, Ciprandi G, Passalacqua G.

Department of Internal Medicine, Genoa University, Genova, Italy.

Allergic rhinitis is characterized by an inflammatory reaction consequent to an
initial IgE-dependent mast cell activation. The conventional treatment is mainly 
based on antihistamine and topical corticosteroid prescriptions. In this article 
the authors consider the antiallergic-antiinflammatory activity exerted by some
nonsteroidal drugs or immunologic treatments. Clinical and experimental evidence 
demonstrates that these treatments are able to control allergic inflammation in
patients with allergic rhinitis. In conclusion, treatment of allergic rhinitis
may also be based on the prescription of nonsteroidal drugs with antiallergic
activity.

Publication Types: 
    Review

PMID: 11068657 [PubMed - indexed for MEDLINE]

1422: Immunol Lett. 2000 Nov 1;74(3):201-5.

Differences in the changes of allergen-specific IgE serum levels and the
chemiluminescence of peripheral blood phagocytes in patients with allergic
rhinoconjunctivitis during the ragweed season.

Szabó Z, Szilasi M, Brúgós L, Szántó S, Kovács I, Széles M, Lakos G,
Antal-Szalmás P, Edes I, Sipka S.

Third Department of Internal Medicine, Medical and Health Science Center,
University Medical School of Debrecen, Móricz Zs. St. 22, 4004, Debrecen,
Hungary. szaboz@iibel.dote.hu

The objective of this study was to compare the changes in the values of
allergen-specific serum IgE levels and zymosan-induced whole blood
chemiluminescence (CL) in 41 patients who had exclusively only ragweed allergy in
the season of acute symptoms of disease in July, August and September. All
patients had allergic rhinitis or rhinoconjunctivitis. Each patient was
investigated as a self-control. The ragweed-specific IgE levels were measured by 
enzyme immunoassay (EIA). The luminol amplified zymosan-induced CL of whole human
blood was detected. The allergen-specific serum IgE levels showed slight, but not
significant, gradually increasing elevations during the whole season. On the
other hand, significant increases were found in the values of the basal but
especially in the zymosan-stimulated CL of peripheral blood phagocytes during the
acute phase of allergy. Both the basal and the zymosan-induced CL reflected
significantly the activated state of the immune system. These observations
clearly show that there are well detectable signs of the systemic activation of
the immune system in allergic rhinoconjunctivitis beside the local alterations.
In addition, the measurements of the basal and zymosan-induced CL of peripheral
phagocytes could clearly reflect the clinical state of disease in vitro.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11064101 [PubMed - indexed for MEDLINE]

1423: Arch Immunol Ther Exp (Warsz). 2000;48(4):287-92.

Effect of recombinant IFN-gamma on igE-dependent leukotriene generation by
peripheral blood leukocytes in patients with pollinosis and asthma.

Krasnowska M, Medrala W, Małolepszy J, Krasnowski R.

Department of Internal Diseases and Allergology, University Medical School,
Wrocław, Poland.

Interferon gamma (IFN-gamma) is considered one of the causative and intensifying 
factors in inflammation. The reaction to allergens releases IFN-gamma, an
immunomodulatory cytokine known to inhibit IgE synthesis and Th cell
proliferation. The aim of the study was to evaluate the influence of IFN-gamma on
leukotriene (LT) release in vitro, from human leukocytes of atopic patients with 
pollinosis and asthma. Thirty-eight patients were enrolled in the study: 15 with 
pollinosis and 23 asthmatics. In the presence of IL-3, leukocytes were stimulated
with specific allergens. Other samples of leukocytes were preincubated with
different concentrations of IFN-gamma for 15 min before allergen stimulation. The
concentration of LT in supernatants was measured according to the CAST-ELISA
procedure. We stated that IFN-gamma had significantly diminished LT release in a 
dose-dependent mode from the leukocytes of pollinotics. IFN-gamma did not change 
LT release in the asthmatic group, although, in leukocytes the small and medium
basic production of LT, IFN-gamma caused a statistically significant fall in LT
generation.

PMID: 11059646 [PubMed - indexed for MEDLINE]

1424: Br Homeopath J. 2000 Oct;89(4):169-73.

Comment in:
    Br Homeopath J. 2000 Oct;89(4):159-60.

No beneficial effect of isopathic prophylactic treatment for birch pollen allergy
during a low-pollen season: a double-blind, placebo-controlled clinical trial of 
homeopathic Betula 30c.

Aabel S.

Institute of General Practice and Community Medicine, Department of General
Practice, Blindern, Oslo, Norway.

The objective of this research was to determine if the homeopathic medicine
Betula 30c is more effective than placebo at reducing symptoms of pollen allergy 
in patients sensitive to birch pollen. It was a double-blind, randomized,
placebo-controlled trial. Tablets were given both as a prophylactic agent, once a
week four weeks before the pollen season and as an acute remedy during the pollen
season. The study was done in Oslo, Norway, in May 1996 and involved 73 children,
adolescents and young adults from 7 to 25 y of age. Allergy-symptoms were
assessed on a visual analogue scale (VAS) by patients or parents. Main outcome
measure was the median (with its 95% confidence interval) of the symptom scores
for all the treated patients, each day during a 10-day period. The pollen count
was very low in 1996, only three days were high enough to provoke allergic
symptoms. Surprisingly, the verum treated patients fared worse than the placebo
group; they used more rescue medication and had higher symptom scores during
these three days. Homeopaths might attribute the findings to a putative
aggravation response, but the results certainly do not lend support to the
usefulness of the tested prophylactic approach, under conditions of low allergen 
exposure.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11055773 [PubMed - indexed for MEDLINE]

1425: Br Homeopath J. 2000 Oct;89(4):161-8.

Comment in:
    Br Homeopath J. 2000 Oct;89(4):159-60.

Is homeopathic 'immunotherapy' effective? A double-blind, placebo-controlled
trial with the isopathic remedy Betula 30c for patients with birch pollen
allergy.

Aabel S, Laerum E, Dølvik S, Djupesland P.

Institute of General Practice and Community Medicine, Department of General
Practice, Oslo, Norway.

The objective of the study was to examine the effect of the homeopathic remedy
Betula 30c vs. placebo for patients with birch pollen allergy. A double-blind,
randomized, placebo-controlled trial was carried out. Tablets were given for 4
weeks during the birch pollen season. The setting was Oslo, Norway, May 1995.
Patients were aged between 18 and 50 y; 32 patients received Betula 30c tablets
and 34 patients received placebo tablets. The main outcome measure was the total 
score of 17 different allergy symptoms. Daily total scores were calculated, as
well as differences and ratios between the run-in and the following time periods.
Point estimates of the median difference between the experimental and placebo
groups, with their 95% confidence intervals, were the main measure of effect. No 
statistically significant difference between the groups was found during the
first and last period of May. However, from 8 to 18 May, a clinically interesting
difference was revealed between the groups, those receiving Betula 30c having
fewer and less serious symptoms. For some days these differences were
statistically significant. Surprisingly, this group reported more aggravation
from the tablets than did the placebo group. With a statistical power of 70% for 
a defined clinically interesting difference (25%), the present results indicate
that treatment with Betula 30c during the pollen season deserves further
attention.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11055772 [PubMed - indexed for MEDLINE]

1426: Drug Saf. 2000 Oct;23(4):309-22.

A risk-benefit assessment of intranasal triamcinolone acetonide in allergic
rhinitis.

Gawchik SM, Saccar CL.

Asthma and Allergy Research Associates, Upland, Pennsylvania 19013, USA.
smgawchik@aol.com

The efficacy of intranasal triamcinolone acetonide in seasonal and allergic
rhinitis has been evaluated in clinical trials and has been compared with
antihistamines and other intranasal corticosteroids. Intranasal corticosteroids
are either as equally effective as or more effective than comparative drugs.
Intranasal corticosteroids are particularly useful as they decrease membrane
permeability and inhibit both early and late phase reactions to allergens. They
minimise the nasal secretory response and reduce the sensitivity of local nasal
irritant receptors. A potential benefit of topical application is the flushing
action of the nasal mucosa, which may reduce allergens and secretions. In
addition to seasonal and perennial rhinitis, intranasal corticosteroids have
additional benefits when used to reduce inflammation in the treatment of
sinusitis and may help in decreasing secondary rhinovirus infections.
Furthermore, suboptimal control of asthma can be avoided by treatment of allergic
rhinitis with intranasal corticosteroids. In clinical trials, common adverse
effects for triamcinolone acetonide include sneezing, dry, mucosa, nasal
irritation, sinus discomfort, throat discomfort, epistaxis and headache.
Posterior subcapsular cataract formation has not been seen with triamcinolone
acetonide. Recent literature evaluating systemic absorption of intranasal
corticosteroids have shown surprising results where significant absorption has
occurred with intranasal budesonide and fluticasone propionate. Growth and
hypothalamic pituitary axis (HPA) function studies have been reviewed, with some 
intranasal corticosteroids showing changes with continual use. A retrospective
study in children receiving daily triamcinolone acetonide for 12 months showed no
effect on height and bodyweight. Triamcinolone acetonide at standard dosages (110
or 220microg once or twice a day) does not appear to suppress adrenal gland
function and is effective in relieving most symptoms of allergic rhinitis. The
International Consensus Conference Proceedings on Rhinitis now currently
recommends the use of intranasal corticosteroids as first line therapy, since
they have been found to be well tolerated and effective with minimal adverse
effects and, specifically, no cognitive impairment. The recommended maximum dose 
of aqueous triamcinolone acetonide in adults and children is 220microg once a
day. The aerosol form may be recommended in children between 7 and 12 years old, 
up to 440microg once a day or in divided doses. Duration of allergy treatment is 
generally for the length of each allergy season. If symptoms are perennial, then 
a reduction of dosage is made to the lowest effective dose with monitoring every 
3 months for risk and benefit assessment. Complications to watch for include
bleeding, and possible septal perforation and nasal candidiasis, although these
are rare.

Publication Types: 
    Review

PMID: 11051218 [PubMed - indexed for MEDLINE]

1427: Pediatr Allergy Immunol. 2000;11 Suppl 13:19-22.

Allergic diseases in farmers' children.

Braun-Fahrländer C.

Department of Environment and Health, Institute of Social and Preventive
Medicine, University of Basel, Switzerland.

Several studies have reported lower rates of allergic sensitization and allergies
in children living in rural as compared to urban communities. This has been
attributed to the lower levels of air pollution in rural areas. The question
arises whether other factors in the rural environment could explain the lower
prevalence rates of allergic sensitization and hay fever. A first report from
rural South Bavaria in Germany demonstrated that children living in a home where 
coal and wood were used for heating had a significantly lower risk of suffering
from hay fever (odds ratio 0.57 (0.34-0.98)), of being sensitized to common
allergens (OR 0.67 (0.49-0.93)) and of having bronchial hyperresponsiveness (OR
0.55 (0.34-0.90)) than their peers living in homes with other heating systems.
Subsequently, the Swiss Study on Childhood Allergy and Respiratory Symptoms with 
Respect to Air Pollution (SCARPOL) tested the hypothesis that farming as parental
occupation was associated with a lower risk of hay fever and atopy. A total of
1620 (86.0%) 6-15-year-old schoolchildren living in three rural communities of
Switzerland were examined using a standardized questionnaire completed by the
parents and IgE antibodies against six common aeroallergens in serum samples of
404 (69.3.0%) of the 13-15-year-olds. Farming as parental occupation was
significantly associated with lower rates of reported hay fever symptoms and
allergic sensitization. Comparing children from farming with those from
non-farming environments, the adjusted OR was 0.34 (95% CI: 0.12-0.89) for
sneezing attacks during the pollen season, and 0.31 (95% CI: 0.13-0.73) for a
sensitization to allergens. These results have recently been confirmed in a new
and much larger survey in rural South Bavaria. Several alternative explanations
have to be considered when interpreting these findings, namely, selection bias,
the development of tolerance, increased microbial stimulation and a more
traditional lifestyle (diet and housing conditions). Based on present knowledge, 
the underlying environmental factor explaining the protective effect of the
farming environment has not yet been identified.

PMID: 11048766 [PubMed - indexed for MEDLINE]

1428: J Allergy Clin Immunol. 2000 Oct;106(4):677-86.

Basophil and eosinophil accumulation and mast cell degranulation in the nasal
mucosa of patients with hay fever after local allergen provocation.

KleinJan A, McEuen AR, Dijkstra MD, Buckley MG, Walls AF, Fokkens WJ.

Department of Otorhinolaryngology, Erasmus Medical Centre Rotterdam, Rotterdam,
The Netherlands.

BACKGROUND: Basophils and mast cells have certain similarities and are believed
to be important in upper and lower respiratory allergy. OBJECTIVE: We sought to
apply immunohistology to investigate the distribution and numbers of mast cells
and basophils in the nasal mucosa after allergen provocation. METHODS: Allergen
challenge with grass pollen was performed in 9 patients with seasonal allergic
rhinitis out of the hay fever season. Nasal biopsy specimens were taken before
and approximately 1 hour, 24 hours, and 1 week after intranasal allergen
provocation. We determined relative numbers and their phenotypic characteristics 
by using mAbs specific for tryptase, chymase, IgE, eosinophils (BMK-13), and a
new mAb against basophils (BB1) by using immunohistochemistry in frozen sections.
RESULTS: In the nasal mucosa at baseline, practically no basophils were found in 
the epithelium. A significant increase in numbers was found in the epithelium and
lamina propria of the nasal mucosa in the early phase as early as 1 hour after
allergen provocation. At 24 hours and 1 week after allergen provocation, a
significant increase in basophil numbers was found in the lamina propria only.
The proportion of mast cells staining for chymase in the lamina propria decreased
from a median of 38% (range, 0%-82%) to 14% (range, 0%-78%) within 1 hour of
allergen provocation. The proportion of mast cells staining for chymase increased
from 1% (range, 0%-86%) at baseline to 21% (range, 3%-85%) within 1 hour of
allergen provocation. One week after provocation, mast cells returned to baseline
numbers. A definite tissue eosinophilia was observed after allergen provocation. 
CONCLUSION: Basophil numbers are increased in the epithelium and lamina propria
of the nasal mucosa of subjects with rhinitis after allergen challenge, with
influx already apparent at 1 hour. Moreover, changes in mast cell percentages and
numbers were observed within 1 hour of allergen provocation.

Publication Types: 
    Comparative Study

PMID: 11031338 [PubMed - indexed for MEDLINE]

1429: Allergy. 2000 Oct;55(10):945-50.

Symptoms suggestive of atopic rhinitis in children aged 6-9 years and the indoor 
environment.

Zacharasiewicz A, Zidek T, Haidinger G, Waldhör T, Vutuc C, Zacharasiewicz A,
Goetz M, Pearce N.

Department of Epidemiology, Institute for Cancer Research, University of Vienna, 
Austria.

BACKGROUND: We aimed to investigate the influence of indoor factors on the
prevalence of symptoms suggestive of atopic rhinitis in children aged 6-9 years
in Upper Austria. METHODS: We analyzed the results from an extended ISAAC
(International Study of Asthma and Allergies in Childhood) questionnaire,
answered by the parents, about indoor environment and symptoms strongly
suggesting atopic rhinitis. This was defined as having reported a running,
obstructed, or itchy nose apart from having a cold in the last year. The overall 
response rate was 93.4%. After excluding 6,016 children (17.1%) with changed
indoor environment (due to allergies in the family), we analyzed the remaining
subsample of 18,606 questionnaires. RESULTS: The following factors were
associated with an increased risk: mother's smoking during pregnancy and/or
during time of breast-feeding (OR 1.28; CI 1.07-1.52), synthetic bedding (OR
1.21; CI 1.09-1.36), dampness/mold at home (OR 1.51; CI 1.31-1.74), central
heating with gas (OR 1.75; CI 1.06-2.87), and space heating (OR 1.66; CI
1.01-2.98). Cooking with wood (OR 0.62; CI 0.46-0.84) was negatively associated
with symptoms. CONCLUSIONS: The indoor environment plays a role in the symptoms
of atopic rhinitis in children. However, the population-attributable risks were
not particularly high; they were between -2.7% and 9% for the various exposures
considered in this study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11030375 [PubMed - indexed for MEDLINE]

1430: Allergy. 2000 Oct;55(10):923-30.

Ash (Fraxinus excelsior)-pollen allergy in central Europe: specific role of
pollen panallergens and the major allergen of ash pollen, Fra e 1.

Hemmer W, Focke M, Wantke F, Götz M, Jarisch R, Jäger S, Götz M.

Dermatologic and Pediatric Allergy Clinic, Vienna, Austria.

BACKGROUND: The role of ash (Fraxinus excelsior) pollen as a cause of spring
pollinosis in central Europe has received little attention. It is not clear
whether ash pollen is a primary cause of sensitization or whether it is
implicated through cross-sensitization to other pollens. METHODS: Over a 22-month
period, ash pollen was included in a screening series for inhalant allergies.
Pollen data were documented from 1976 through 1999. The frequency of IgE-binding 
to the ash-specific allergen Fra e 1 and pollen panallergens, respectively, was
compared by Western blot between mono- (n = 6), oligo- (n = 16), and
polysensitized (n=25) patients. RESULTS: Of 5,416 consecutive patients sensitized
to any pollen, 920 (17.6%) had a positive skin prick test to ash. Total pollen
counts varied extensively between years (229-5,351) as did peak concentrations
(23-837 grains/m3/24 h). Western blotting revealed Fra e 1 sensitization in 100% 
of monosensitized, 93% of oligosensitized, but only 44% of polysensitized
patients. IgE against profilins (Fra e 2), Ca-binding proteins (Fra e 3), and
carbohydrate epitopes in the three groups was found in 0/0/17%, 0/19/31%, and
32/72/60%, respectively. At least 50% of sera from patients with Fra e 1
sensitization did not bind with the protein in Western blots under reducing
conditions. CONCLUSIONS: Ash pollen should be considered a relevant factor and
distinct entity in spring pollinosis. In all, only 20% of positive skin tests to 
ash appear to result from cross-sensitization to pollen panallergens.

PMID: 11030372 [PubMed - indexed for MEDLINE]

1431: Allergy. 2000 Oct;55(10):916-22.

Comment in:
    Allergy. 2000 Oct;55(10):903-4.

The initial care of newborn infants and subsequent hay fever.

Montgomery SM, Wakefield AJ, Morris DL, Pounder RE, Murch SH.

Department of Medicine, Royal Free and University College Medical School, London,
UK.

BACKGROUND: Patterns of neonatal exposure to microorganisms have changed
substantially over the last 100 years, and it has been suggested that this has
influenced the risk of immune-mediated disease. Using a proxy measure, we tested 
the hypothesis that the initial handling of newborn infants, which is known to
affect the pattern of exposure to microorganisms, may alter the risk of
developing subsequent atopy, as indicated by hay fever. METHODS: Analysis was
performed on 5,519 members of the 1970 British Cohort Study, a nationally
representative birth cohort. Cohort members with hay fever were identified at
intervals up to the age of 26 years. Details of neonatal care and childhood
circumstances were recorded prospectively. Those who had spent their first night 
away from their mother in the communal infant nursery were selected as likely to 
have experienced atypical exposure compared with infants who remained with their 
mother. Adjustment was made for potential confounding factors in infancy and
childhood by multiple logistic regression analysis. RESULTS: Unadjusted relative 
odds (with 95% CI) for developing hay fever among those spending the first night 
in the communal nursery, when compared with other infants who remained with the
mother, were 1.48 (1.23-1.77), P<0.001. Comprehensive adjustment for the
potential confounding factors, including feeding practices on the first day of
life, markers of social and material circumstances, and region, did not
substantially alter this relationship, with adjusted relative odds of 1.31
(1.08-1.59), P=0.005. CONCLUSIONS: While our proxy measure is associated with an 
increased risk of hay fever, further research is required to confirm that this is
due to the pattern of infectious exposure in very early life. The results are
consistent with the hypothesis that the first challenges are particularly
important in the development of the newborn infant's immune system.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11030371 [PubMed - indexed for MEDLINE]

1432: Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1391-6.

Quality of life in allergic rhinitis and asthma. A population-based study of
young adults.

Leynaert B, Neukirch C, Liard R, Bousquet J, Neukirch F.

INSERM Unité 408, Paris, France. leynaert@bichat.inserm.fr

Quality of life has been found to be impaired both in patients with asthma and in
patients with allergic rhinitis, but the relative burden of these diseases has
not been investigated. We analyzed answers to the SF-36 questionnaire from 850
subjects recruited in two French centers participating in the European Community 
Respiratory Health Survey, a population-based study of young adults. Both asthma 
and allergic rhinitis were associated with an impairment in quality of life.
However, 78% of asthmatics also had allergic rhinitis. Subjects with allergic
rhinitis but not asthma (n = 240) were more likely than subjects with neither
asthma nor rhinitis (n = 349) to report problems with social activities,
difficulties with daily activities as a result of emotional problems, and poorer 
mental well-being. Patients with both asthma and allergic rhinitis (n = 76)
experienced more physical limitations than patients with allergic rhinitis alone,
but no difference was found between these two groups for concepts related to
social/mental health. As asthma was not found to further impair the quality of
life in subjects with allergic rhinitis for concepts related to mental disability
and well-being, and as subjects with asthma often also suffer from allergic
rhinitis, further studies on quality of life in asthma should ensure that the
impairment in quality of life attributed to asthma could not result from
concomitant allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11029350 [PubMed - indexed for MEDLINE]

1433: Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1377-82.

Attenuation of the allergen-induced late asthmatic reaction by cyclosporin A is
associated with inhibition of bronchial eosinophils, interleukin-5, granulocyte
macrophage colony-stimulating factor, and eotaxin.

Khan LN, Kon OM, Macfarlane AJ, Meng Q, Ying S, Barnes NC, Kay AB.

Allergy and Clinical Immunology, Imperial College School of Medicine, National
Heart and Lung Institute, London, United Kingdom.

The allergen-induced late asthmatic reaction (LAR) is associated with increases
in bronchial eosinophils and basophils as well as upregulation of several
eosinophil active cytokines and C-C chemokines. Cyclosporin A (CsA) was
previously shown to inhibit the LAR, but not the early asthmatic reaction (EAR), 
and this was associated with a decrease in blood eosinophils. For these reasons, 
we determined whether CsA inhibited the allergen-induced increases in bronchial
eosinophils, basophils, eotaxin, interleukin-5 (IL-5), and granulocyte macrophage
colony-stimulating factor (GM-CSF). Subjects with a demonstrable LAR underwent
bronchoscopy with biopsy and bronchoalveolar lavage (BAL) at baseline and then
were randomly allocated to receive either CsA (n = 13) or placebo (n = 11) before
challenge. A second bronchoscopy was performed 24 h later. The LAR, but not the
EAR, was significantly attenuated in the CsA group compared with placebo (p <
0.05). CsA significantly inhibited the allergen-induced increases in IL-5 (p =
0.02) and GM-CSF (p = 0. 0028) in mRNA+ cells in BAL, and in a mAB against human 
activated eosinophils (EG2+) (p = 0.0227). We conclude that inhibition of the LAR
by CsA may be related to its inhibitory effects on eosinophil-associated
cytokines and chemokines. The beneficial effect of CsA in asthma may also be the 
result of inhibition of eosinophil accumulation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11029348 [PubMed - indexed for MEDLINE]

1434: Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1297-301.

Antiasthmatic effects of mediator blockade versus topical corticosteroids in
allergic rhinitis and asthma.

Wilson AM, Orr LC, Sims EJ, Dempsey OJ, Lipworth BJ.

Asthma and Allergy Research Group, Department of Clinical Pharmacology and
Therapeutics, Ninewells Hospital and Medical School, University of Dundee,
Dundee, Scotland, United Kingdom.

To compare the antiasthmatic efficacy of inflammatory mediator blockade versus
topical corticosteroid therapy in patients with seasonal allergic rhinitis (SAR) 
and asthma, 14 patients were enrolled into a single-blind, double-dummy,
placebo-controlled crossover study comparing 2 wk therapy of (1) 400 microgram
orally inhaled budesonide plus 200 microgram intranasal budesonide (BUD) or (2)
10 mg oral montelukast plus 10 mg oral cetirizine (ML + CZ). Before each
treatment period, patients received 7 to 10 d placebo washout. All treatments
were given once daily in the morning. Throughout the study, patients recorded the
following domiciliary measures: peak expiratory flow (PEF), rescue inhaler
requirement, asthma symptoms, and daily activity score. Laboratory measurements
were made at trough of adenosine monophosphate (AMP) bronchial challenge and
exhaled nitric oxide (NO). Compared with pooled placebo (PL), there were
significant (p < 0.05) improvements in all domiciliary measures with both
treatments (mean PEF [L/min] PL: 463; BUD: 478; ML + CZ: 483). For geometric mean
AMP PC(20) (mg/ml), there was an improvement (p < 0.05), compared with PL (47),
for ML + CZ (133) but not for BUD (51); whereas for NO (ppb) there was
significant suppression with BUD (7.6) but not ML + CZ (11.5) compared with PL
(13.6). In conclusion, both combined mediator blockade and combined topical
corticosteroids are equally effective antiasthma therapy in patients with asthma 
and SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11029334 [PubMed - indexed for MEDLINE]

1435: Allergol Immunopathol (Madr). 2000 Jul-Aug;28(4):238-42.

Local nasal immunotherapy: efficacy and tolerability of two different
administration schedules in grass pollen rhinitis.

Senna GE, Andri G, Dama AR, Falagiani P, Andri L.

Allergology Service, Ospedale Maggiore, Verona, Italy.

BACKGROUND: Efficacy and safety of local nasal immunotherapy has been
demonstrated by many placebo-controlled clinical trials. The treatment schedule
consists of an induction phase at increasing dosages followed by a maintenance
phase. Aim of present study has been to evaluate a new simplified treatment
schedule at constant dosage. METHODS AND RESULTS: 26 grass-allergic rhinitic
patients have been treated according to the new constant dosage schedule, while
15 patients in a control group were treated with conventional incremental dosage 
schedule. A commercial preparation of allergens incorporated into powder
(Allerkin). The total cumulative dosage administered with conventional schedule
resulted higher than simplified constant schedule (5,025 vs 3,000 AU). To
evaluate efficacy, symptom and rescue medication scores were recorded during the 
spring pollen season, and a subjective overall evaluation was asked to the
patients at the end of the season. The analysis of scores showed that the two
treatment schedules were equivalent as regards both efficacy and safety, being
side effects light and restricted to the administration site (sneezing).
CONCLUSIONS: The use of a constant dosage schedules is suggested for the
administration of local nasal immunotherapy, having as advantage a better
simplicity. Avoidance of mistakes in dosages is considered important in a therapy
which is self-administered by patients.

Publication Types: 
    Clinical Trial

PMID: 11022271 [PubMed - indexed for MEDLINE]

1436: Allergol Immunopathol (Madr). 2000 Jul-Aug;28(4):207-12.

International Study of Asthma and Allergies in Childhood. Results on rhinitis of 
first phase in Pamplona, Spain.

Carvalho N, Fernández-Benítez M, Cascante L, Aguinaga I, Guillén F.

Department of Allergology and Clinical Immunology, University Clinic of Navarra, 
Faculty of Medicine, University of Navarra, Pamplona, Spain.

BACKGROUND: The ISAAC (International Study of Asthma and Allergies in Childhood) 
was thought in order to maximize the value of epidemiological research into
asthma and allergic diseases in childhood, establishing a standardized
methodology and facilitating collaboration and comparison between several
countries. METHODS AND RESULTS: The written questionnaires in the group of
children aged 6-7 years was answered by the parents and the group of children
aged 13-14 years self-completed the written questionnaires. RESULTS: 3,040
children aged 13-14 years answered the questionnaire and 3,002 in the group aged 
6-7 years. In the group of children aged 13-14, 49.7% referred rhinitis symptoms 
some time, and 15.6% in the 6-7 year old group. The prevalence of nasal symptoms 
in the last year was 35.5% in the 13-14 year group and 10.6% in the 6-7 year
group. The presence of nasal symptoms was more frequent in winter. The prevalence
of seasonal allergic rhinitis (hay fever) was 6.1% in the 13-14 year group and
4.8% in the group of children aged 6-7 years. CONCLUSIONS: These results can
contribute to a better control of some factors and to future studies where the
etiology and incidence of the disease could be investigated.

PMID: 11022266 [PubMed - indexed for MEDLINE]

1437: Am J Respir Cell Mol Biol. 2000 Oct;23(4):521-9.

Piecemeal degranulation of peripheral blood eosinophils: a study of allergic
subjects during and out of the pollen season.

Karawajczyk M, Sevéus L, Garcia R, Björnsson E, Peterson CG, Roomans GM, Venge P.

Department of Medical Sciences, Clinical Chemistry, University of Uppsala,
Sweden. Malgorzata.Karawajczyk@klinkem.uu.se

The variability of serum and plasma levels of eosinophil granule proteins in
different clinical conditions, interpreted as the result of different patterns of
cytokine priming, suggests a selective mobilization of granule proteins. Inasmuch
as piecemeal degranulation (PM) is the mechanism proposed for the differential
release of eosinophil granule proteins, we decided to investigate whether blood
eosinophils from allergic subjects show characteristics of PM during natural
allergen challenge. Eosinophils from three birch-sensitive subjects were studied 
before and during the pollen season. Electron microscopy analysis showed that
during the season, eosinophils presented morphologic features of PM. By
immunogold labeling, eosinophil cationic protein (ECP) was detected not only in
normal specific granules but also in the cytoplasm, in the vicinity of partially 
lucent specific granules. These results were confirmed by subcellular
fractionation, where the amount of ECP associated with compartments containing
small vesicles increased 2-fold during the pollen season. A study of the
distribution of ECP, eosinophil peroxidase, and hexosaminidase in eosinophils of 
different densities showed that the profile of each of these proteins differed
depending on cell density. All of these proteins decreased in the specific
granule of hypodense cells and increased in other cell compartments. We conclude 
that allergen exposure causes PM of the peripheral blood eosinophils of allergic 
subjects, and that the density of these cells reflects the degree of
degranulation. Our results provide novel information for the understanding of the
selective mobilization of granule proteins into the circulation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11017918 [PubMed - indexed for MEDLINE]

1438: Allergy. 2000 Sep;55(9):827-35.

Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. II.
Side-effects.

Winther L, Malling HJ, Mosbech H.

Allergy Unit, National University Hospital, Copenhagen, Denmark.

BACKGROUND: Allergen-specific immunotherapy (IT) involves the risk of
side-effects. Different side-effect profiles have been reported for different
allergens, and it would be of great benefit to be able more precisely to predict 
patient- and allergen-related risk factors. METHODS: Fifty-two patients with
rhinoconjunctivitis and allergy to birch as well as grass pollen participated in 
a 3-year IT study, with a baseline year followed by 2 years of treatment. During 
the first treatment year, the patients received double-blinded IT with either
birch (Betula verrucosa) or grass (Phleum pratense) pollen extracts adsorbed to
aluminum hydroxide. The following year, the other allergen extract was added.
Assessment of systemic reactions (SRs) was performed, and related to patient
pretreatment parameters such as seasonal symptoms and medication requirement,
skin prick test (SPT), conjunctival provocation test (CPT), nasal provocation
test (NPT), total and specific IgE, basophil histamine release (HR), eosinophil
count (EOS), eosinophil cationic protein (ECP), and eosinophil protein X (EPX).
RESULTS: In total, 44 and 47 patients started IT with birch- and grass-pollen
extracts, respectively. All SRs occurred during the dose-increase phase. No
life-threatening SRs were observed. There were a higher number of patients with
SRs during IT with grass pollen than IT with birch pollen, 21 vs five patients
(P<0.001), with SRs to 3.3% of grass-pollen injections compared to 0.7% of
birch-pollen injections (P<0.0001). The SRs of birch-pollen IT were mild,
consisting of rhinoconjunctivitis and oral-pharyngeal itching, whereas asthma and
urticaria episodes were observed in the grass-pollen IT. No difference was found 
in sensitivity to birch and grass, when measured by SPT, CPT, NPT, specific IgE, 
or HR, and no difference was found in age, duration of allergic symptoms,
prevalence of asthma, mean seasonal birch/grass symptom score, eye-drop use, or
antihistamine or prednisolone intake between the group with and without
subsequent SRs to IT. No difference was found in EOS, serum ECP, or EPX, between 
the group with and without subsequent SRs to IT. CONCLUSIONS: IT with
grass-pollen extract seems to be associated with a higher number and more severe 
SRs than birch-pollen IT. Neither demographic data nor diagnostic tests of
allergy such as specific IgE, HR, SPT, CPT, and NPT could identify the patients
with subsequent SRs.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11003446 [PubMed - indexed for MEDLINE]

1439: Allergy. 2000 Sep;55(9):818-26.

Allergen-specific immunotherapy in birch- and grass-pollen-allergic rhinitis. I. 
Efficacy estimated by a model reducing the bias of annual differences in pollen
counts.

Winther L, Malling HJ, Moseholm L, Mosbech H.

Allergy Unit, National University Hospital, Copenhagen, Denmark.

BACKGROUND: Evaluation of the efficacy of allergen-specific immunotherapy (IT)
with pollen extracts is complicated by annual variation in pollen intensity. Our 
study aimed to evaluate the efficacy of birch and grass IT, taking into
consideration these variations. METHODS: After 1 year of observation, 52 patients
with rhinoconjunctivitis and allergy to birch as well as grass pollen were
allocated to double-blinded clustered IT with aluminum-adsorbed extract produced 
from either birch (Betula verrucosa) pollen or grass (PIleum pratense) pollen.
After 1 year of treatment, the patients continued IT with their original extract 
and also received the other extract. During the three consecutive pollen seasons,
the rhinoconjunctivitis symptom score and the use of antihistamines, eye-drops,
and oral prednisolone were recorded. Longitudinal data analysis was used to
investigate the relation between different pollen counts and the magnitude of
clinical efficacy. RESULTS: An effect of IT was found on symptom score,
antihistamine intake, and eye-drop use for both birch and grass (P values <0.05).
The mean reduction in symptom score/medication by IT ranged from 24% to 95%,
depending on mean seasonal pollen counts. A minimum mean seasonal grass-pollen
count of 20-30 pollen grains m3 was required for the efficacy of grass IT to
emerge. CONCLUSIONS: A model was developed for evaluation of efficacy in
longitudinal IT studies, taking the differences in annual pollen counts into
consideration. The model showed a significant beneficial role of pollen IT in
rhinoconjunctivitis patients allergic to birch and grass pollen.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11003445 [PubMed - indexed for MEDLINE]

1440: Clin Exp Allergy. 2000 Oct;30(10):1476-85.

Preventive treatment of intranasal fluticasone propionate reduces cytokine mRNA
expressing cells before and during a single nasal allergen provocation.

Kleinjan A, Holm AF, Dijkstra MD, Boks SS, Severijnen L, Mulder PG, Fokkens WJ.

Departments of Otorhinolaryngology, Biostatistics, Erasmus University Medical
Centre Rotterdam, Rotterdam, The Netherlands.

BACKGROUND: The local production and release of a number of cytokines regulate
allergic upper airway inflammation. Medication is usually used at the
presentation of the first symptoms. There are, however, clues that it is
advisable to start taking the corticosteroid before the grass pollen season
begins. METHODS: This single allergen provocation study was conducted in autumn, 
out of the hay fever season. Nasal mucosa biopsies were taken twice before
provocation (before and after 4 weeks of preventive treatment) and three times
after allergen provocation (1 h, 24 h and 1 week). The preventive treatment used 
was fluticasone propionate aqueous nasal spray (FPANS) (n = 10) or a placebo (n =
9). Eosinophils and mRNA positive cells (in situ hybridization for IL-2, IL-3,
IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IFNgamma, RANTES and TNFalpha) were counted
in the biopsies. RESULTS: Preventive treatment with FPANS out of season resulted 
in a decrease in eosinophils and mRNA positive cells for IL-5 and IL-6. After
allergen provocation, levels of most of the measured cytokines (IL-3, IL-5, IL-6,
IL-13, IFNgamma, RANTES and TNFalpha) and eosinophils were reduced using
corticosteroids. The numbers of cells (eosinophils, IL-3, IL-6 and IL-8)
correlated with nasal symptoms. Significant correlations in the early and late
allergic phase were found between eosinophils and cytokines (IL-3, IL-10 and
IL-13). CONCLUSION: These results indicate that preventive treatment with FPANS
prior to contact with grass pollen is effective in reducing the increase of
cytokine mRNA positive cells in reaction to grass pollen contact.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10998026 [PubMed - indexed for MEDLINE]

1441: Clin Exp Allergy. 2000 Oct;30(10):1469-75.

Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during
grass pollen season: effect of a local glucocorticoid.

Pullerits T, Lindén A, Praks L, Cardell LO, Lötvall J.

Lung Pharmacology Group, Institute of Heart and Lung Diseases, Department of
Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden.

BACKGROUND: Allergic rhinitis is a common disease characterized by infiltration
of eosinophils into the nasal mucosa during the periods of symptoms. Among
chemokines, which attract cells to the site of inflammation, eotaxin is
relatively specific for eosinophils. OBJECTIVE: We examined the influence of
grass pollen season on nasal eotaxin expression in patients with seasonal
allergic rhinitis, as well as the effect of a nasal glucocorticoid on this
eotaxin expression. METHODS: Nineteen patients with allergic rhinitis received
treatment with either nasal beclomethasone (400 microgram/day) or placebo over a 
grass pollen season. In these patients, nasal biopsies were taken prior to and
during the peak of the pollen season and stained immunohistochemically for
eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave 
nasal biopsies once prior to the pollen season. RESULTS: Prior to pollen season, 
there was no significant difference in nasal eotaxin expression between patients 
with allergic rhinitis and healthy subjects. Grass pollen season induced
significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9)
but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During
peak grass pollen season, the eotaxin expression in placebo-treated patients was 
significantly higher compared with healthy subjects outside season (P = 0.03).
There was no significant correlation between the expression of eotaxin and the
number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in
rhinitis patients remained stable over the pollen season. CONCLUSION: Expression 
of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is
upregulated during pollen season and treatment with a nasal glucocorticoid
protects against this upregulation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10998025 [PubMed - indexed for MEDLINE]

1442: Clin Exp Allergy. 2000 Oct;30(10):1417-22.

Comment in:
    Clin Exp Allergy. 2000 Oct;30(10):1342-3.

Preliminary criteria for the definition of allergic rhinitis: a systematic
evaluation of clinical parameters in a disease cohort (II)

Ng ML, Warlow RS, Chrishanthan N, Ellis C, Walls RS.

Immunology Department, Concord Repatriation Hospital, Concord, Sydney, NSW 2139, 
Australia.

BACKGROUND: This study is a development of the work done in 'Preliminary criteria
for the definition of allergic rhinitis: a systematic evaluation of clinical
parameters in a disease cohort (I)'. OBJECTIVE: We sought to develop criteria
which could be routinely used to define allergic rhinitis. METHODS: A total of 47
allergic rhinitis and 23 normal subjects were evaluated with a detailed
questionnaire and history, physical examination, serum total immunoglobulin (Ig) 
E, skin prick tests and serum EAST's. RESULTS: Based on this data, we developed a
preliminary scoring system by which a reliable diagnosis of allergic rhinitis can
be made, which is based on the prevalence adjusted strength of association delta 
( partial differential) rank values described in this report. Cumulative
frequency histograms were constructed for allergic rhinitis and normal subjects
in a variety of configurations. CONCLUSION: A simple scoring system which can be 
used to diagnose allergic rhinitis on a routine basis was developed in this
study.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 10998018 [PubMed - indexed for MEDLINE]

1443: Thorax. 2000 Oct;55(10):826-32.

Influence of intranasal steroids during the grass pollen season on bronchial
responsiveness in children and young adults with asthma and hay fever.

Thio BJ, Slingerland GL, Fredriks AM, Nagelkerke AF, Scheeren RA, Neijens HJ,
Roord JJ, Dankert-Roelse JE.

Department of Pediatrics, University Hospital, Academisch Ziekenhuis van de Vrije
Universiteit, Amsterdam, The Netherlands.

BACKGROUND: It has been reported that intranasal corticosteroids can influence
bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis.
The purpose of the present study was to evaluate the effect of intranasal
fluticasone propionate and beclomethasone dipropionate on BHR and bronchial
calibre (forced expiratory volume in one second, FEV(1)) in children and young
adults with seasonal rhinitis and mild asthma during two consecutive grass pollen
seasons. METHODS: In the first pollen season 25 patients aged 8-28 years were
included in a double blind, placebo controlled study. The active treatment group 
used fluticasone aqueous spray 200 microgram once daily. In the second pollen
season 72 patients aged 8-28 years participated in a double blind, placebo
controlled study of a similar design to that of the previous year except that an 
additional treatment group of patients using beclomethasone 200 microg twice
daily was included. FEV(1) was measured before and after three and six weeks of
treatment; BHR to methacholine (PD(20)) was measured before and after six weeks
of treatment. RESULTS: In the first season the mean (SD) logPD(20) of the
patients decreased significantly both in the fluticasone group (from 2.43 (0.8)
microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42)
microgram to 1.87 (0.78) microgram) without any intergroup difference in the
change in logPD(20). In the second pollen season the mean logPD(20) in the
fluticasone, beclomethasone, and placebo groups did not change significantly.
CONCLUSIONS: Intranasal steroids did not influence BHR during two grass pollen
seasons in children and young adults with seasonal rhinitis and mild asthma.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10992533 [PubMed - indexed for MEDLINE]

1444: Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):920-4.

Onset and remission of allergic rhinitis and asthma and the relationship with
atopic sensitization and smoking.

Plaschke PP, Janson C, Norrman E, Björnsson E, Ellbjär S, Järvholm B.

Amager Hospital, Copenhagen University Hospitals, Denmark. Sciences, pp@email.dk

The aim of this study was to assess the influence of some risk factors for onset 
and remission of allergic rhinitis and asthma in Swedish adults. A random sample 
of 1,370 subjects, age 20 to 44 yr was investigated by means of postal
questionnaires in 1990 and 1993. Skin prick tests were conducted in 1991-1992.
The association between risk factors and onset or remission of allergic rhinitis 
and asthma was estimated using multivariate logistic regression analysis. Onset
of allergic rhinitis was associated with sensitization to birch (odds ratio [OR] 
= 6.5), Parietaria (OR = 7.4); and pets (OR = 3.0) and with female sex (OR =
1.9). Onset of asthma was associated with allergic rhinitis (OR = 4.9),
sensitization to pets (OR = 2.4); and with smoking (OR = 3.0). Onset of asthma
was strongly associated with allergic rhinitis among atopics (OR = 5.7), but
onset of asthma and rhinitis also tended to be related among nonatopics (OR =
3.5). A strong association between smoking and onset of asthma was found among
nonatopics (OR = 5.7). In conclusion, sensitization to pollens and pets were risk
factors for onset of allergic rhinitis, whereas allergic rhinitis, sensitization 
to pets, and smoking were risk factors for onset of asthma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10988106 [PubMed - indexed for MEDLINE]

1445: J Allergy Clin Immunol. 2000 Sep;106(3):521-9.

Mechanism of topical glucocorticoid treatment of hay fever: IL-5 and eosinophil
activation during natural allergen exposure are suppressed, but IL-4, IL-6, and
IgE antibody production are unaffected.

Kita H, Jorgensen RK, Reed CE, Dunnette SL, Swanson MC, Bartemes KR, Squillace D,
Blomgren J, Bachman K, Gleich GJ.

Departments of Immunology and Medicine, Division of Allergy, Mayo Clinic and
Foundation, Mayo Graduate School of Medicine, Rochester, MN 55905, USA.

BACKGROUND: Allergic rhinitis is traditionally defined as an IgE- and mast
cell-mediated hypersensitivity reaction. Allergen challenge models suggest that
cytokines and eosinophil mediators may also play roles. However, the causal
relationship among inflammatory cells, their products, and patients' symptoms
during natural allergen exposure has not been established. OBJECTIVE: We sought
to elucidate the mechanisms of seasonal allergic rhinitis and the beneficial
effects of topical glucocorticoids. METHODS: Thirty patients with ragweed-induced
hay fever and a strongly positive serologic test response for ragweed IgE
antibody received budesonide nasal spray or placebo in a randomized, parallel,
double-blind study. Nasal wash fluids and sera were collected before and during
the hay fever season. The levels of inflammatory mediators and allergen-specific 
immunoglobulins were measured by immunoassay. The activation markers on blood
eosinophils were quantitated by flow cytometry. RESULTS: Compared with
placebo-treated patients, budesonide-treated patients had strikingly reduced
symptoms. In the placebo group, nasal symptoms correlated with nasal lavage fluid
eosinophil-derived neurotoxin and IL-5 levels. At the season peak, the
budesonide-treated group had significantly lower nasal fluid eosinophil-derived
neurotoxin, IL-5, and soluble intracellular adhesion molecule-1 levels. In the
treated group eosinophil expression of CD11b was suppressed at the season peak.
In contrast, levels of IL-4 and IL-6 in nasal fluid and the seasonal increases in
serum ragweed-specific IgE and nasal fluid IgA antibodies did not differ between 
groups. CONCLUSION: Eosinophilic inflammation plays a critical role in seasonal
allergic rhinitis symptoms. One of the therapeutic effects of glucocorticoids is 
to suppress this inflammation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10984373 [PubMed - indexed for MEDLINE]

1446: Ann Allergy Asthma Immunol. 2000 Aug;85(2):111-4.

Comment in:
    Ann Allergy Asthma Immunol. 2000 Aug;85(2):87-8.

Subjective and objective markers of treatment response in patients with seasonal 
allergic rhinitis.

Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ.

Department of Clinical Pharmacology & Therapeutics, Ninewells Hospital & Medical 
School, University of Dundee, Scotland, UK.

BACKGROUND: Although there is a recognized association between upper and lower
allergic airways disease, it is unknown how seasonal allergic rhinitis (SAR)
therapy will effect sensitive markers of airway function in patients with no
history of asthma. OBJECTIVE: To prospectively evaluate subjective and objective 
markers of treatment response in 26 patients with SAR who have been screened to
exclude a diagnosis of asthma. METHODS: The patients' usual treatment, with
antihistamine alone (n = 13) or in combination with intranasal corticosteroid (n 
= 13), was withheld for 1 week to achieve a baseline and then resumed.
Measurements were made after baseline and after 2 and 4 weeks of treatment for
nasal peak inspiratory flow rate (nPIFR); airways resistance (Raw) and specific
conductance (sGaw); and nasal nitric oxide (NO). Patients reported their symptom 
(nasal, throat and eye) scores, daily activity scores, and ocular sodium
cromoglycate usage over the preceding 24 hours. RESULTS: Compared with baseline, 
there were significant (P < .05) improvements with nPIFR, symptom scores and
cromoglycate usage at 2 and 4 weeks of treatment. There was no significant
suppression for NO at 2 or 4 weeks. There was a significant correlation between
nPIFR and nasal symptoms (r = -0.52, P < .001). After 4 weeks of treatment there 
were significant (P < .05) improvements in sGaw (143.3% predicted) and Raw (91.6%
predicted) compared with baseline (sGaw: 111.8%, Raw: 104.2% predicted).
CONCLUSION: Treatment of SAR improves upper and lower airway parameters but not
NO. Nasal PIFR correlates significantly with nasal symptoms.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 10982217 [PubMed - indexed for MEDLINE]

1447: Ann Allergy Asthma Immunol. 2000 Aug;85(2):102-5.

Fever of unknown origin in a 10-year-old boy with allergic rhinitis and asthma.

Caliskaner AZ, Karaayvaz M, Ozanguc N.

Department of Allergy, GATA Gulhane Military Medical Academy, Ankara, Turkey.

We believe this case represents a clear example of drug fever, and it appears to 
be the first report to implicate ketotifen as the responsible agent, confirmed
with double rechallenge. The recognition of drug fever is clinically important.
Failure to recognize the etiologic relationship between the drug and fever has
unnecessary consequences, including extra testing, empiric therapy, and longer
hospital stays. We suggest that ketotifen should be considered as a possible
cause of fever in allergic patients receiving this drug.

Publication Types: 
    Case Reports
    Clinical Conference
    Research Support, Non-U.S. Gov't

PMID: 10982215 [PubMed - indexed for MEDLINE]

1448: Immunol Lett. 2000 Jul 3;73(1):51-6.

Cytokine production by peripheral blood mononuclear cells following birch-pollen 
immunotherapy.

Movérare R, Elfman L, Björnsson E, Stålenheim G.

Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala
University, Uppsala, Sweden.robert.moveare@eu.pnu.com

We studied the Th2/Th1 balance by short-term stimulation of peripheral blood
mononuclear cells (PBMC) isolated during the pollen season from seven allergic
patients treated with conventional birch-pollen immunotherapy (IT) for 18 months,
eight matched allergic control patients and 10 non-atopic individuals. The PBMC
were cultured for 7 days with birch-pollen extract (BPE) or tetanus toxoid (TT), 
and then restimulated with PHA and PMA to induce high IL-5, IL-10 and IFN-gamma
production. The serum levels of birch-pollen-specific IgG and IgG4 were
significantly elevated after IT treatment. The proliferative response to BPE was 
significantly enhanced in the allergic control group, but not in the IT-treated
group, compared to the non-atopic group (P<0.05). Birch-pollen-specific IL-5
production was significantly enhanced in both the IT-treated group and the
allergic control group (P<0.01-0. 05). Furthermore, both the IT-treated group and
the allergic control group had a cytokine profile to BPE significantly more Th2
polarized (high IL-5/IFN-gamma ratio) than to TT (P<0.05 and P<0.01,
respectively). No differences in IL-10 production between the three study groups 
were observed. The Th2/Th1 balance in vitro correlated with the serum
concentrations of birch-pollen-specific IgE (r=0.60, P<0.05), and in the
IT-treated group, also with the IgG and IgG4 levels (r=0.79, P<0.05 and r=0.86,
P<0.05, respectively). We conclude that conventional birch-pollen IT does not
lead to changes in the cytokine profile of the circulating pool of
allergen-specific T cells during birch-pollen season. However, induction of
peripheral T-cell tolerance and increased production of specific IgG and IgG4
might be part of the mechanisms of IT.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 10963811 [PubMed - indexed for MEDLINE]

1449: Am J Manag Care. 2000 Mar;6(3):373-8.

The cost of productivity losses associated with allergic rhinitis.

Crystal-Peters J, Crown WH, Goetzel RZ, Schutt DC.

Medstat Group, Washington, DC 20008, USA.

OBJECTIVE: To measure the cost of absenteeism and reduced productivity associated
with allergic rhinitis. METHODS: The National Health Interview Survey (NHIS) was 
used to obtain information on days lost from work and lost productivity due to
allergic rhinitis. Wage estimates for occupations obtained from the Bureau of
Labor Statistics (BLS) were used to calculate the costs. RESULTS: Productivity
losses associated with a diagnosis of allergic rhinitis in the 1995 NHIS were
estimated to be $601 million. When additional survey information on the use of
sedating over-the-counter (OTC) allergy medications, as well as workers'
self-assessments of their reduction in at-work productivity due to allergic
rhinitis, were considered, the estimated productivity loss increased
dramatically. At-work productivity losses were estimated to range from $2.4
billion to $4.6 billion. CONCLUSION: Despite the inherent difficulty of measuring
productivity losses, our lowest estimate is several times higher than previous
estimates of the indirect medical costs associated with allergic rhinitis
treatment. The most significant productivity losses resulted not from absenteeism
but from reduced at-work productivity associated with the use of sedating OTC
antihistamines.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10977437 [PubMed - indexed for MEDLINE]

1450: Allerg Immunol (Paris). 2000 Jun;32(6):246-9.

Preventive symptomatic immunotherapy versus placebo in seasonal rhinitis due to
grasses in children and to Parietaria in adult patients.

Troise C, Bignardi D, Modena P, Pissacroia C, Di Berardino F.

Ospedale San Martino, Servizio di Allergologia e d'Immunologia clinica, Genova,
Italia.

BACKGROUND: EPD is the only preventive symptomatic immunotherapy available on the
market and approved by competent bodies. Recent double-blind placebo controlled
(DBPC) studies have demonstrated its efficacy in seasonal and perennial rhinitis.
The aim of the study was to confirm the efficacy and safety of a single dose of
immunotherapy administered six-eight weeks before the pollen season. METHODS: Two
simultaneous DBPC trials were carried out. The first consisted of 20 children
with grass-pollen seasonal rhinitis (Bollate-Milano, Italy) and the second
included 30 adult patients with Parietaria-pollen seasonal rhinitis (Genova,
Italy). EPD was administered only to the active groups. RESULTS: A significant
difference in favour of the active treatment groups was seen in oral
antihistamine use (p < 0.05) during the peak pollen seasons. Throughout the
pollen seasons, rhinoconjunctivitis scores for the two groups in both studies
presented no significant difference, even if the values were lower in the active 
groups. CONCLUSIONS: The oral antihistamine reduction, observed in the active
groups during the seasonal period, supports the efficacy of this treatment,
although a significant improvement in the rhinoconjunctivitis symptoms was not
observed, probably due to the use of oral antihistamine in the placebo groups.
The overall profile of the EPD was good. It could be particularly suited for
short term therapy to prevent seasonal symptoms in allergic patients.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 10971859 [PubMed - indexed for MEDLINE]

1451: Clin Exp Allergy. 2000 Sep;30(9):1314-31.

Preliminary criteria for the definition of allergic rhinitis: a systematic
evaluation of clinical parameters in a disease cohort (I).

Ng ML, Warlow RS, Chrishanthan N, Ellis C, Walls R.

Immunology Department, Concord Repatriation Hospital, Concord, Australia.

BACKGROUND: The aim of this study is to formulate criteria for the definition of 
allergic rhinitis. Other studies have sought to develop scoring systems to
categorize the severity of allergic rhinitis symptoms but it was never used for
the formulation of diagnostic criteria. These other scoring systems were
arbitrarily chosen and were not derived by any statistical analysis. To date, a
study of this kind has not been performed. OBJECTIVE: The hypothesis of this
study is that it is possible to formulate criteria for the definition of allergic
rhinitis. This is the first study to systematically examine and evaluate the
relative importance of symptoms, signs and investigative tests in allergic
rhinitis. We sought to statistically rank, from the most to the least important, 
the multiplicity of symptoms, signs and test results. METHODS: Forty-seven
allergic rhinitis and 23 normal subjects were evaluated with a detailed
questionnaire and history, physical examination, serum total immunoglobulin E,
skin prick tests and serum enzyme allergosorbent tests (EAST). RESULTS:
Statistical ranking of variables indicated rhinitis symptoms (nasal, ocular and
oronasal) were the most commonly occurring, followed by a history of allergen
provocation, then serum total IgE, positive skin prick tests and positive EAST's 
to house dust mite, perennial rye and bermuda/couch grass. Throat symptoms ranked
even lower whilst EAST's to cat epithelia, plantain and cockroach were the least 
important. Not all symptoms, signs and tests evaluated proved to be statistically
significant when compared to a control group; this included symtoms and signs
which had been considered historically to be traditionally associated with
allergic rhinitis, e.g. sore throat and bleeding nose. CONCLUSION: In performing 
statistical analyses, we were able to rank from most to least important, the
multiplicity of symptoms signs and test results. The most important symptoms and 
signs were identified for the first time, even though some of these were not
included in our original selection criteria for defining the disease cohort i.e. 
sniffing, postnasal drip, oedematous nasal mucosa, impaired sense of smell, mouth
breathing, itchy nose and many of the specific provocation factors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10971479 [PubMed - indexed for MEDLINE]

1452: Int Arch Allergy Immunol. 2000 Aug;122(4):270-8.

Involvement of eosinophils in the early-phase allergic reaction in a guinea pig
rhinitis model.

Imai N, Miyahara A, Yamazaki Y, Homma R, Ino Y, Kurumi M.

Section of Allergology, Research Laboratories, Torii Pharmaceutical Co., Ltd.,
Chiba, Japan.

BACKGROUND: Eosinophils are found in the nasal lavage fluid (NLF) and nasal
biopsies of patients with allergic rhinitis after a nasal antigen challenge, and 
associated not only with a late-phase allergic reaction (LPR) but also an early
phase allergic reaction (EPR). Numerous studies have been carried out to clarify 
the participation of eosinophils in LPR or airway hyperresponsiveness. However,
there has been no published report describing in detail the role of eosinophils
during EPR. To better understand the involvement of eosinophils in EPR, we
studied the effects of repeated antigen challenges on nasal airway responsiveness
and eosinophilic inflammation in EPR using a guinea pig rhinitis model. METHODS: 
Nasal airway responsiveness was measured as the nasal airway resistance (NAR)
after nasal antigen provocation. Eosinophilic inflammation during EPR was
assessed by nasal lavage and histopathological examination using two groups of
animals: those in group 1 were subjected to a sensitization pretreatment only,
and those in group 2 were subjected to a pretreatment of sensitization followed
by repeated nasal challenges. RESULTS: Repeated antigen challenges induced nasal 
hyperresponsiveness as indicated by a decrease in the antigen provocation dose
and a significant increase in NAR. Furthermore, significant increases in
eosinophil counts, eosinophil peroxidase (EPO) activity and protein content in
NLF during EPR were observed following antigen provocation in group 2. There were
significant correlations between the levels of these parameters, and albumin was 
the most prevalent of the proteins in NLF. Histopathological examination showed
that the degree of eosinophil infiltration into the lamina propria of the nasal
mucosa of the animals in group 2 was significantly and apparently higher than in 
group 1. Particularly, epithelial disruption and mucosal edema were significantly
elevated after antigen provocation in group 2. CONCLUSIONS: These results suggest
that chronic eosinophil accumulation is induced by repeated antigen challenges in
the nasal tissue, and that once antigen provocation occurs, eosinophils in the
tissue are activated and responsible for the amplification of EPR such as
vascular permeability and mucosal edema. Copyright 2000 S. Karger AG, Basel.

PMID: 10971118 [PubMed - indexed for MEDLINE]

1453: Acta Derm Venereol. 2000 May;80(3):192-5.

No increased skin reactivity in subjects with allergic rhinitis during the active
phase of the disease.

Conti A, Seidenari S.

Department of Dermatology, University of Modena, Italy.

Data on skin reactivity in patients with respiratory atopy without atopic
dermatitis are scarce and controversial. Our purpose was to assess whether skin
reactivity in patients with seasonal allergic rhinitis varies according to the
phase of the disease and the possible release of inflammatory mediators acting on
the skin during the pollen season. The volar forearm skin of eleven patients with
seasonal allergic rhinitis without atopic dermatitis was challenged with a single
exposure to sodium lauryl sulfate. The skin response was evaluated instrumentally
over 72 h by transepidermal water loss, capacitance and echogenicity measurements
for the assessment of skin damage and the inflammatory response. Tests were
performed in winter and repeated in spring in seasonal allergic rhinitis
patients, when they showed respiratory symptoms. Fifteen subjects with atopic
dermatitis underwent the same experimental procedure in winter as a control
population. Baseline and postexposure values were similar both in winter and in
spring in seasonal allergic rhinitis patients. After sodium lauryl sulfate
challenge, atopic dermatitis patients showed a higher degree of skin barrier
damage and inflammation compared to patients with seasonal allergic rhinitis.
These findings suggest that subjects with seasonal allergic rhinitis without
atopic dermatitis have normal epidermal barrier function and normal skin
reactivity during both the inactive and the active phase of the disease.
Inflammatory mediators possibly released by mucous membranes during active
allergic rhinitis do not influence skin barrier function.

PMID: 10954210 [PubMed - indexed for MEDLINE]

1454: J Allergy Clin Immunol. 2000 Aug;106(2):307-12.

Topical steroid treatment of allergic rhinitis decreases nasal fluid TH2
cytokines, eosinophils, eosinophil cationic protein, and IgE but has no
significant effect on IFN-gamma, IL-1beta, TNF-alpha, or neutrophils.

Benson M, Strannegård IL, Strannegård O, Wennergren G.

Department of Pediatrics and Clinical Virology, Sahlgrenska University Hospital, 
Göteborg.

BACKGROUND: Topical treatment with glucocorticoids (GCs) is known to decrease
eosinophils but not neutrophils in patients with allergic rhinitis. OBJECTIVE: We
sought to examine whether the differential effects of GC treatment on eosinophils
and neutrophils are mirrored by differential effects on T(H)1/T(H)2 cytokines and
the neutrophil-associated cytokines IL-1beta and TNF-alpha. METHODS: Differential
counts of eosinophils and neutrophils in nasal fluids from 60 children with
seasonal allergic rhinitis treated with a topical GC were examined after staining
with May-Grünwald-Giemsa stain. Nasal fluid levels of IFN-gamma, IL-4, IL-6,
IL-10, IL-1beta, and TNF-alpha were examined with ELISA, and IgE and eosinophil
cationic protein (ECP) levels were examined with RIA. RESULTS: After GC
treatment, there was a statistically significant decrease of the T(H)2 cytokines 
IL-4, IL-6, and IL-10, as well as ECP and IgE. By contrast, there were no
significant changes of the levels of IFN-gamma, IL-1beta, TNF-alpha, or
neutrophils. In the GC-treated patients IL-1beta and TNF-alpha levels correlated 
with neutrophils and ECP, and IL-1beta correlated with eosinophils. Furthermore, 
ECP correlated with both eosinophils and neutrophils. Neither IL-1beta nor
TNF-alpha correlated with IgE. Patients with high neutrophil counts after GC
treatment were found to have significantly higher eosinophil counts and ECP than 
patients with low counts. CONCLUSIONS: The beneficial effects of topical
treatment with GC in patients with allergic rhinitis could be attributed to
downregulation of T(H)2 cytokines, with an ensuing decrease of eosinophils, ECP, 
and IgE. It is possible that neutrophils could counteract the beneficial effects 
of GCs by releasing the proinflammatory cytokines IL-1beta and TNF-alpha.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10932075 [PubMed - indexed for MEDLINE]

1455: J Allergy Clin Immunol. 2000 Aug;106(2):253-9.

Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal 
allergic rhinitis.

Adelroth E, Rak S, Haahtela T, Aasand G, Rosenhall L, Zetterstrom O, Byrne A,
Champain K, Thirlwell J, Cioppa GD, Sandström T.

Department of Respiratory Medicine and Allergy, University Hospital, Umea,
Sweden.

BACKGROUND: Allergic rhinitis is a common condition often requiring treatment.
OBJECTIVE: We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant
humanized construct of a murine antibody that binds to circulating IgE, could
control symptoms and reduce intake of concomitant medication in seasonal allergic
rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule
predicted to reduce serum free IgE levels below 25 ng/mL. METHODS: We randomly
assigned 251 adult subjects with a history of SAR and a positive skin test
response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3 
times during the season, depending on baseline IgE levels. The primary efficacy
variable was the subject's average daily nasal symptom severity score (sneezing, 
itching, runny, and stuffy nose) from diary data collected over the double-blind 
treatment period. Secondary efficacy variables included the average number of
rescue antihistamine tablets per day, the proportion of days with any SAR
medication use, and rhinoconjunctivitis-specific quality of life (QOL). RESULTS: 
Significant between-treatment differences in favor of rhumAb-E25 were observed in
average daily nasal symptom severity scores, the average number of tablets of
rescue antihistamines per day, the proportion of days with any SAR medication
use, and all domains of QOL. Serum-free IgE levels were markedly lower in
rhumAb-E25-treated subjects and were associated with clinical effectiveness.
Recombinant humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies
were detected. CONCLUSION: Compared with placebo, rhumAb-E25 was safe and
effective in controlling birch pollen-induced SAR symptoms, with less concomitant
medication use and improved QOL. This study shows the therapeutic potential of
anti-IgE antibody in SAR.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10932067 [PubMed - indexed for MEDLINE]

1456: Scand J Immunol. 2000 Aug;52(2):200-6.

Changes in cytokine production in vitro during the early phase of birch-pollen
immunotherapy.

Movérare R, Elfman L, Björnsson E, Stâlenheim G.

Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala
University, Uppsala, Sweden. robert.moverare@eu.pnu.com

The kinetics of the immunological mechanisms during allergen-specific
immunotherapy (IT) has not been thoroughly evaluated. In this investigation we
study the changes in T-cell responses during the early phase of IT. Ten patients 
(IT group) with birch-pollen allergy were treated with conventional IT. Blood
samples were collected at regular intervals for specific immunoglobulin (Ig)E
measurements and preparation of peripheral blood mononuclear cells (PBMC). Seven 
allergic control patients (AC group) were included during the subsequent
birch-pollen season. The PBMC were stimulated with birch-pollen extract or
tetanus toxoid (TT) and mitogens. After a short decrease, probably owing to
seasonal variation, the birch-pollen-specific proliferation and the interleukin
(IL)-4, IL-5, and IL-10 production significantly increased when reaching the
maintenance dose and during the subsequent pollen season. The increase in IL-4
correlated with a temporary increased serum level of birch-pollen-specific IgE.
Interestingly, also the TT-specific response was affected by IT, resulting in
weaker, but in time similar, changes in proliferation and cytokine production as 
in the birch-pollen-specific response. We speculate that the early phase of IT
might lead to systemic changes in the capacity of Th2-like cytokine production,
and that the early increase in allergen-specific IgE is a consequence of enhanced
IL-4 production.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    In Vitro

PMID: 10931388 [PubMed - indexed for MEDLINE]

1457: Clin Ther. 2000 Jun;22(6):760-9.

Efficacy and tolerability of loratadine versus fexofenadine in the treatment of
seasonal allergic rhinitis: a double-blind comparison with crossover treatment of
nonresponders.

Prenner BM, Capano D, Harris AG.

Allergy Associates Medical Group, Inc, San Diego, California, USA.

BACKGROUND: Nonsedating antihistamines are well-established treatment for
seasonal allergic rhinitis (SAR), but patients do not always respond to the first
antihistamine prescribed. OBJECTIVE: This double-blind, double-dummy, randomized,
2-phase, multicenter study was designed primarily to compare the therapeutic
responses to loratadine and fexofenadine in patients who failed initial therapy
with the other drug. METHODS: Male and female patients aged 12 to 60 years
received loratadine 10 mg once daily (n = 331) or fexofenadine 60 mg twice daily 
(n = 328) for 14 days (phase 1); nonresponders (ie, those who had <25% reduction 
in the sum of 5 SAR symptoms rated by the investigator on a 4-point scale)
subsequently received the alternate medication for 14 days (phase 2). The
investigator's rating of relief (complete, marked, moderate, or slight relief of 
symptoms or treatment failure) at the end of phase 2 was the primary efficacy
measure; changes in total symptom severity (TSS) assessed by the investigator
(4-point scale) and the patient (11-point visual analog scale) were secondary
measures. RESULTS: Mean decreases in TSS were significantly greater with
loratadine than with fexofenadine for the 659 patients who completed phase 1
(-12.7 vs -10.2, respectively; P = 0.019; patient assessment) and for the 389
patients who responded to initial therapy (-6.6 vs -6.1, respectively; P = 0.037;
investigator assessment). Of the 389 patients who responded to initial therapy,
61.0% had received loratadine and 57.0% had received fexofenadine. More
nonresponders to initial therapy had moderate, marked, or complete relief of
symptoms after switching to loratadine than after switching to fexofenadine
(62.4% vs 51.2%, respectively; P = 0.005) and treatment failure in 10.6% vs
21.7%, respectively (P = 0.011). CONCLUSION: Overall, ioratadine provided
significantly better therapeutic response than fexofenadine in patients who
failed to respond to initial therapy with the other drug.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10929922 [PubMed - indexed for MEDLINE]

1458: Allergy. 2000;55 Suppl 62:12-4.

A comparison of the clinical efficacy and safety of intranasal fluticasone
propionate and antihistamines in the treatment of rhinitis.

Foresi A.

Servizio di Fisiopatologia Respiratoria Modulo dii Allergologia e
d'Immunopatologia Polmonare, Milan, Italy.

Adequate management of allergic rhinitis is needed to avoid its considerable
adverse social, clinical, and economic impact. Both topical intranasal steroids
and oral or topical antihistamines are recognised as effective treatments for
this condition. In comparative studies, however, intranasal steroids and, in
particular, fluticasone propionate aqueous nasal spray (FPANS), have afforded
consistently better symptomatic relief, and have a greater beneficial effect on
quality of life. Furthermore, the addition of an antihistamine to FPANS therapy
has generally produced little further benefit. Intranasal administration is
associated with a low systemic absorption of fluticasone propionate and,
following regular use of FPANS, placebo, or an oral antihistamine, no significant
differences were seen between treatment groups in plasma or urinary cortisol.
Overall, therefore, the data indicate that FPANS is superior to second-generation
antihistamines in the management of allergic rhinitis.

Publication Types: 
    Comparative Study
    Review

PMID: 10929863 [PubMed - indexed for MEDLINE]

1459: Ann Allergy Asthma Immunol. 2000 Jul;85(1):58-63.

Prevalence of asthma, allergic rhinitis, and eczema in 13- to 14-year-old
children in Kuwait: an ISAAC study. International Study of Asthma and Allergies
in Childhood.

Behbehani NA, Abal A, Syabbalo NC, Abd Azeem A, Shareef E, Al-Momen J.

Department of Medicine, Kuwait University, Safat.

OBJECTIVES: To determine the prevalence of asthma and allergic diseases in 13 to 
14 years old children in Kuwait. DESIGN: Supervised self-administered written and
video questionnaires of the international study of asthma and allergies in
childhood (ISAAC). SUBJECTS: Students at third and fourth years from 40
intermediate level schools chosen randomly from across Kuwait. RESULTS: 3,110
students were surveyed. The prevalence rates (95% CI) in the written
questionnaire for wheeze ever, current wheeze (within the last 12 months), and
physician diagnosis of asthma are 25.9% (24.5 to 27.4), 16.1% (15.8 to 17.4), and
16.8% (15.5 to 18.1) respectively. The prevalence rates (95% CI) for symptoms of 
allergic rhinitis (AR) ever, current symptoms of allergic rhinitis (AR), and
diagnosis of AR are 43.9% (42.2 to 45.6), 30.7% (29.1 to 32.4) and 17.1% (14.8 to
18.4) respectively. The prevalence rates (95% CI) for itchy rash ever, current
itchy rash, and diagnosis of eczema are 17.5% (16.2 to 18.8), 12.6% (11.4 to
13.8), and 11.3% (10.2 to 12.4) respectively. The prevalence of wheeze ever,
wheeze during the last year, and physician diagnosis of asthma are higher in
males compared with females, P < .01. In multiple logistic regression: male
gender (OR 1.6, 95% CI, 1.3 to 2.0) and diagnosis of AR (OR 1.7, 95% CI, 1.4 to
2.2) were associated with the physician diagnosis of asthma even after
controlling for symptoms of asthma. CONCLUSION: This is the first study on the
prevalence of allergic diseases in Kuwait and it shows that children in Kuwait
have a moderate prevalence of asthma, AR, and eczema compared with other
countries where the ISAAC study is done. The prevalence of asthma is higher in
boys compared with girls.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10923606 [PubMed - indexed for MEDLINE]

1460: Arch Otolaryngol Head Neck Surg. 2000 Aug;126(8):997-1000.

Local levels of soluble tumor necrosis factor receptors in patients with allergic
rhinitis are regulated by amount of antigen.

Kato M, Kato Y, Takeuchi K, Nakashima I.

Department of Immunology, Nagoya University School of Medicine, Tsurumai-cho,
Showa-ku, Nagoya, Aichi, Japan.

OBJECTIVES: To examine the possible correlation between the amount of antigen and
the level of soluble tumor necrosis factor receptor (sTNFR), and to assess its
biologic significance in allergic reactions. DESIGN: Randomized control trial.
SUBJECTS: Twelve volunteers with Japanese cedar pollinosis and 10 healthy
volunteers. INTERVENTIONS: The levels of p55 sTNFR (sTNFR1) and p75 sTNFR
(sTNFR2) in samples of serum and nasal epithelial lining fluid (ELF) from 12
subjects with pollinosis and 10 healthy subjects were measured 4 times
(preseason, early season, midseason, and postseason) in low (total, 415/cm( 2)
per season) and high (total, 19,935/cm(2) per season) pollen-count periods, and
the results were compared among the 4 groups. RESULTS: In the low-pollen-count
period, increased levels of sTNFR1 and sTNFR2 were observed in ELF samples from
the allergic subjects during the midseason. In contrast, in the high-pollen-count
period, those levels were already elevated during the preseason and reduced
during the midseason. Especially, the levels of sTNFR2 in ELF samples from the
allergic subjects during the midseason in the high-pollen-count period were
significantly lower than those in the low-pollen-count period. Moreover, a
significant negative correlation (sTNFR1, R = -0.82; sTNFR2, R = -0. 73) was
found between the levels of sTNFR1 and sTNFR2 in ELF samples and the scores of
symptoms in the allergic subjects in the high-pollen-count period, but not in the
low-pollen-count period. CONCLUSION: In patients with pollinosis, the amounts of 
antigen regulate the local levels of sTNFRs, possibly inhibiting nasal allergic
inflammation.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 10922234 [PubMed - indexed for MEDLINE]

1461: Arch Otolaryngol Head Neck Surg. 2000 Aug;126(8):992-6.

Allergen-induced mRNA expression of IL-5, but not of IL-4 and IFN-gamma, in
peripheral blood mononuclear cells is a key feature of clinical manifestation of 
seasonal allergic rhinitis.

Nakai Y, Ohashi Y, Kakinoki Y, Tanaka A, Washio Y, Nasako Y, Masamoto T, Sakamoto
H, Ohmoto Y.

Department of Otolaryngology, Osaka City University Medical School, 1-4-3
Asahimachi, Abeno, Osaka 545-8585, Japan.

OBJECTIVES: To investigate the allergen-induced messenger RNA (mRNA) expression
of interleukin (IL) 4, IL-5 and interferon gamma (IFN-gamma) in peripheral blood 
mononuclear cells from individuals sensitized by Japanese cedar (Cryptomeria
japonica) pollens, and to elucidate the clinical role of IL-4, IL-5, and
IFN-gamma in the allergen sensitization and clinical manifestation of allergic
disorders. DESIGN: This study included 30 patients sensitized to the pollen and
14 nonatopic healthy volunteers. Peripheral blood mononuclear cells (1.0 x 10(6) 
cells/mL) of each individual were cultured at 37 degrees C for 24 hours in the
presence of 10 microg/mL of Cry j 1, a major allergen of the pollens. Total
cellular RNA was extracted from the peripheral blood mononuclear cells, and IL-4,
IL-5, and IFN-gamma mRNA expression was determined with a reverse transcriptase
polymerase chain reaction. RESULTS: From the results of a survey of symptom diary
cards and interviews regarding nasal symptoms during the pollen season in 1998,
we found that 20 patients (symptomatic group), but not 10 patients (asymptomatic 
group), had typical symptoms of seasonal allergic rhinitis. Interleukin 4 mRNA
was not expressed in the nonatopic subjects but was expressed in 9 asymptomatic
patients and in 17 symptomatic patients. Interleukin 5 mRNA was exclusively
expressed in the symptomatic patients. Interferon gamma mRNA expression did not
differ significantly among the nonatopic subjects, asymptomatic patients, and
symptomatic patients. CONCLUSIONS: This study has clearly highlighted an
interesting and new concept that IL-4 is implicated in allergen sensitization but
not in clinical manifestation, and that IL-5 may not be a feature of atopy in
itself but seems to be a hallmark of clinical manifestation of ongoing atopic
diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10922233 [PubMed - indexed for MEDLINE]

1462: J Laryngol Otol. 2000 May;114(5):354-8.

Clinico-pathological correlation between allergic rhinitis and bronchial asthma.

Varghese BT, Murthy PS, Rajan R.

Department of Ear, Nose and Throat, Kasturba Medical College and Hospital,
Manipal, Karnataka, India. rcctvm@md2.vsnl.net.in

A prospective study was carried out on 52 patients with allergic rhinitis, during
March 1993-January 1995. This was to analyse the occurrence of bronchial asthma
among them and to correlate the symptoms, signs and pathological findings of
allergic rhinitis with that of bronchial asthma in those patients with both the
disorders. The therapeutic benefits with regard to the symptoms of bronchial
asthma in these patients were assessed after treatment of their nasal allergy for
a period of at least four months. A definite aetio-clinico-pathological
correlation could be established between allergic rhinitis and bronchial asthma
and it could be concluded from the study that prompt attention to nasal symptoms 
in cases with co-existent bronchial asthma helps to a large extent in curbing the
symptoms of the latter.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10912264 [PubMed - indexed for MEDLINE]

1463: Pediatr Allergy Immunol. 2000 May;11(2):116-9.

Clinical pharmacology of the H1-receptor antagonists cetirizine and loratadine in
children.

Simons FE, Johnston L, Simons KJ.

Health Sciences Clinical Research Center, Faculty of Medicine, University of
Manitoba, Winnipeg, Canada.

H1-receptor antagonists are widely used in children but are not as well-studied
in children as they are in adults. Our objective was to determine the onset and
duration of action and the relative potency of the H1-receptor antagonists
cetirizine and loratadine in children. We performed a prospective, randomized,
placebo-controlled, double-blind, crossover, single-dose study of cetirizine and 
loratadine using suppression of the histamine-induced wheal and flare as the
primary outcome. In 15 allergic children, mean age 9 years, compared with
baseline, cetirizine (10 mg) suppressed the wheals and flares significantly from 
0.25 to 24 h, achieving nearly 100% of flare suppression from 2 to 24 h,
inclusive, and loratadine (10 mg) suppressed the wheals and flares significantly 
from 0.75 to 24 h, inclusive. Cetirizine suppressed the wheals and flares
significantly more than loratadine from 0.25 to 1 h, inclusive, and at 0.5, 1, 2,
3, 5, 6, 7, and 24 h, respectively. Placebo also suppressed the wheal and flare
significantly at some assessment times. Cetirizine and loratadine both have
excellent antihistaminic activity in children, with a rapid onset of action and a
24-h duration of action in this population.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 10893015 [PubMed - indexed for MEDLINE]

1464: BMJ. 2000 Jul 8;321(7253):88-92.

Intergenerational 20 year trends in the prevalence of asthma and hay fever in
adults: the Midspan family study surveys of parents and offspring.

Upton MN, McConnachie A, McSharry C, Hart CL, Smith GD, Gillis CR, Watt GC.

Department of General Practice, University of Glasgow, Glasgow G12 0RR.
maknupton@aol.com

OBJECTIVE: To estimate trends between 1972-6 and 1996 in the prevalences of
asthma and hay fever in adults. DESIGN: Two epidemiological surveys 20 years
apart. Identical questions were asked about asthma, hay fever, and respiratory
symptoms at each survey. SETTING: Renfrew and Paisley, two towns in the west of
Scotland. SUBJECTS: 1,477 married couples aged 45-64 participated in a general
population survey in 1972-6; and 2,338 offspring aged 30-59 participated in a
1996 survey. Prevalences were compared in 1,708 parents and 1,124 offspring aged 
45-54. Main outcome measures: Prevalences of asthma, hay fever, and respiratory
symptoms. RESULTS: In never smokers, age and sex standardised prevalences of
asthma and hay fever were 3.0% and 5.8% respectively in 1972-6, and 8.2% and 19. 
9% in 1996. In ever smokers, the corresponding values were 1.6% and 5.4% in
1972-6 and 5.3% and 15.5% in 1996. In both generations, the prevalence of asthma 
was higher in those who reported hay fever (atopic asthma). In never smokers,
reports of wheeze not labelled as asthma were about 10 times more common in
1972-6 than in 1996. With a broader definition of asthma (asthma and/or wheeze), 
to minimise diagnostic bias, the overall prevalence of asthma changed little.
However, diagnostic bias mainly affected non-atopic asthma. Atopic asthma
increased more than twofold (prevalence ratio 2.52 (95% confidence interval 1.01 
to 6.28)) whereas the prevalence of non-atopic asthma did not change (1.00 (0.53 
to 1.90)). CONCLUSION: The prevalence of asthma in adults has increased more than
twofold in 20 years, largely in association with trends in atopy, as measured
indirectly by the prevalence of hay fever. No evidence was found for an increase 
in diagnostic awareness being responsible for the trend in atopic asthma, but
increased awareness may account for trends in non-atopic asthma.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10884260 [PubMed - indexed for MEDLINE]

1465: Arch Otolaryngol Head Neck Surg. 2000 Jun;126(6):749-54.

Hot, humid air partially inhibits the nasal response to allergen provocation.

Baroody FM, Assanasen P, Chung J, Naclerio RM.

Section of Otolaryngology-Head and Neck Surgery, Pritzker School of Medicine,
University of Chicago, Ill 60637, USA. fbaroody@surgery.bsd.uchicago.edu

BACKGROUND: We have previously reported that preconditioning allergic subjects
with hot, humid air (HHA) (temperature, 37 degrees C; relative humidity >95%) in 
an environmental chamber resulted in partial inhibition of the early response to 
nasal allergen challenge. OBJECTIVE: To investigate whether this inhibitory
effect could be achieved by inhalation of HHA via a face mask. DESIGN:
Randomized, 4-way crossover study. SUBJECTS: Eighteen subjects with seasonal
allergic rhinitis participated in the study outside of their allergy season.
INTERVENTIONS: Subjects underwent preconditioning with room air (RA)
(temperature, 25 degrees C; relative humidity <20%) or HHA either in a chamber or
delivered via a face mask for 1 hour prior to and during nasal challenge with
diluent for the allergen extract followed by 2 increasing doses of allergen.
RESULTS: Net changes from diluent challenge for all parameters were compared
between HHA and RA in each delivery method. Hot, humid air delivered by mask
significantly inhibited the mean+/-SEM number of allergen-induced sneezes (HHA,
2.7+/-0.6; RA, 6.6+/-2.1; P=.03), congestion score (HHA, 2.3+/-0.5; RA,
3.4+/-0.5; P=.01), and secretion weights (HHA, 26.9+/-4.4 mg; RA, 38.6+/-5.0 mg; 
P=.048). However, HHA inhaled in a chamber significantly inhibited only the
mean+/-SEM allergen-induced congestion (HHA, 1.2+/-0.4; RA, 3.6+/-0.6; P=.002)
and pruritus (HHA, 0.7+/-0.3; RA, 2.3+/-0.5; P=.002) scores. CONCLUSIONS:
Preconditioning the nasal mucosa with HHA partially decreases the early response 
to nasal challenge with antigen irrespective of the administration technique. The
secretory response, however, is only inhibited by localized delivery of HHA to
the nose. The inhibitory effects of HHA are therefore probably related to local
changes in the nasal mucosa and are not dependent on total body exposure to HHA.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 10864113 [PubMed - indexed for MEDLINE]

1466: J Immunol. 2000 Jul 1;165(1):331-8.

Dominant epitopes and allergic cross-reactivity: complex formation between a Fab 
fragment of a monoclonal murine IgG antibody and the major allergen from birch
pollen Bet v 1.

Mirza O, Henriksen A, Ipsen H, Larsen JN, Wissenbach M, Spangfort MD, Gajhede M.

Protein Structure Group, Department of Chemistry, University of Copenhagen,
Denmark.

The symptoms characteristic of allergic hypersensitivity are caused by the
release of mediators, i.e., histamine, from effector cells such as basophils and 
mast cells. Allergens with more than one B cell epitope cross-link IgE Abs bound 
to high affinity FcepsilonRI receptors on mast cell surfaces leading to
aggregation and subsequent mediator release. Thus, allergen-Ab complexes play a
crucial role in the cascade leading to the allergic response. We here report the 
structure of a 1:1 complex between the major birch pollen allergen Bet v 1 and
the Fab fragment from a murine monoclonal IgG1 Ab, BV16, that has been solved to 
2.9 A resolution by x-ray diffraction. The mAb is shown to inhibit the binding of
allergic patients' IgE to Bet v 1, and the allergen-IgG complex may therefore
serve as a model for the study of allergen-IgE interactions relevant in allergy. 
The size of the BV16 epitope is 931 A2 as defined by the Bet v 1 Ab interaction
surface. Molecular interactions predicted to occur in the interface are likewise 
in agreement with earlier observations on Ag-Ab complexes. The epitope is formed 
by amino acids that are conserved among major allergens from related species
within the Fagales order. In combination with a surprisingly high inhibitory
capacity of BV16 with respect to allergic patients' serum IgE binding to Bet v 1,
these observations provide experimental support for the proposal of dominant IgE 
epitopes located in the conserved surface areas. This model will facilitate the
development of new and safer vaccines for allergen immunotherapy in the form of
mutated allergens.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10861069 [PubMed - indexed for MEDLINE]

1467: Cytokine. 2000 May;12(5):543-5.

Seasonal variation in interleukin 4 in patients with hayfever.

Jones KP, Morris RH, Rolf S, Davies BH.

School of Biomedical Sciences, University of Wales Institute Cardiff, UK.
KPJones@UWIC.ac.uk

This study was performed to investigate the value of interleukin 4 as a marker of
activity in mild atopic disease. We compared IL-4 levels to eosinophil cationic
protein (ECP), a suggested inflammatory marker in allergic disease, in patients
with hayfever. Patients with hayfever were assessed during January and then in
late June at the height of the grass pollen season, and their levels of serum ECP
and IL-4 compared. Serum ECP was determined by radio-immunoassay and serum IL-4
by a high-sensitivity enzyme-linked immunosorbent assay. ECP was found to
increase significantly in patients with hayfever during the grass pollen season
(P<0.01). Conversely, serum levels of IL-4 were found to decrease significantly
over the same period when compared with winter values. ECP and IL-4 were not seen
to correlate significantly with each other. The fall in serum IL-4 seen during
the grass pollen season in the hayfever patients may reflect allergen driven
upregulation of membrane IL-4 receptor expression or sequestration of cytokine
producing cells to inflammatory sites. These findings suggest that serum IL-4 is 
a poor indicator of inflammatory status in allergic disease.

PMID: 10857776 [PubMed - indexed for MEDLINE]

1468: J Allergy Clin Immunol. 2000 Jun;105(6 Pt 1):1101-7.

Comparison of once-daily ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, and
placebo in the treatment of seasonal allergic rhinitis. The Ebastine Study Group.

Ratner PH, Lim JC, Georges GC.

Sylvana Research, San Antonio, TX, USA.

BACKGROUND: Ebastine and loratadine are 2 nonsedating second-generation H(1)
antihistamines with once-daily dosing. OBJECTIVE: We compared the efficacy and
safety of ebastine 20 mg and 10 mg, loratadine 10 mg, and placebo administered
once daily for 4 weeks in controlling the symptoms of seasonal allergic rhinitis 
(SAR). METHODS: In a double-blind, placebo-controlled, randomized, parallel-group
study, 565 patients with ragweed SAR, ages 12 to 70 years, received either
ebastine 20 mg, ebastine 10 mg, loratadine 10 mg, or placebo once daily for 4
weeks. Patients recorded morning and evening reflective scores (past 12 hours) as
well as snapshot scores (at time of recording) for nasal discharge, congestion,
sneezing, itching, and total eye symptoms. Total symptom score (TSS) is the sum
of these 5 scores. RESULTS: Ebastine 20 mg produced significantly greater (P
<.05) reductions from baseline compared with loratadine 10 mg over the entire
treatment period in the mean daily reflective (42.5% vs 36.3%) and mean morning
snapshot (40.3% vs 31.3%) TSS. The overall improvement in daily reflective and
morning snapshot TSS was comparable between ebastine 10 mg and loratadine 10 mg
and significantly better than placebo (P <.05). The total percent of patients
with adverse events was similar among all 4 treatment groups (P =.78).
CONCLUSION: Ebastine 20 mg given once daily was significantly superior to
loratadine 10 mg given once daily at improving the rhinitis total symptom score
throughout the day and at awakening over a 4-week period. Ebastine 20 mg and 10
mg doses were both efficacious and well tolerated in the treatment of SAR.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10856142 [PubMed - indexed for MEDLINE]

1469: J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S616-21.

Therapeutic approaches to allergic rhinitis: treating the child.

Fireman P.

Departments of Pediatrics and Internal Medicine, University of Pittsburgh School 
of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213-2524, USA.

Allergic rhinitis is currently the most common of all chronic diseases in
children. However, children frequently lack the ability to verbalize their
symptoms, with the result that the condition may go undiagnosed and untreated.
Unfortunately, untreated allergic rhinitis not only detrimentally affects
children's physical and psychosocial well-being, quality of life, and capacity to
function and learn, but it is also associated with and may contribute to
potentially serious sequelae, including asthma, sinusitis, and otitis media.
Because children may not accurately describe their symptoms, the classic signs of
allergic rhinitis in the pediatric population, including the allergic shiner, the
allergic crease, and the allergic salute, are particularly important in enabling 
the clinician to recognize those children who may have this condition; other
significant signs include mouth breathing, snoring, chronic cough, and continual 
throat clearing. The options for treating allergic rhinitis in the child are the 
same as those for the adult, and the clinician can expect the same level of
efficacy. Environmental control for allergen avoidance is an important goal, but 
the clinician must prescribe it within the context of the family's lifestyle to
obtain compliance. Complete avoidance of inhalant allergens is not always
feasible, and medications are necessary. Oral antihistamines remain the mainstay 
of initial treatment for allergies. Given evidence of the significant deleterious
effects of the sedating antihistamines on learning, the clinician should
prescribe nonsedating second-generation agents whenever possible. Decongestants
may be needed. Intranasal corticosteroids are a most effective option, and these 
agents lack the systemic side effects associated with orally administered
steroids. In persistent disease, allergen immunotherapy injections may be
considered. In all cases, the clinician should consider issues that are likely to
influence compliance in the pediatric population.

Publication Types: 
    Review

PMID: 10856167 [PubMed - indexed for MEDLINE]

1470: J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S610-5.

Allergic rhinitis: treating the adult.

Corren J.

Department of Medicine and Pediatrics, University of California, Los Angeles, CA,
USA.

Allergic rhinitis is now recognized as a chronic medical condition that markedly 
affects patient quality of life and is a cause of substantial medical care
expenditures. Effective treatment of adults with allergic rhinitis usually
requires an integrated regimen that combines allergen avoidance measures,
pharmacotherapy, and possible specific-allergen immunotherapy. This approach can 
control bothersome symptoms with minimal adverse effects in most patients. New
medications, such as anti-immunoglobulin E therapy and cytokine antagonists, may 
provide relief to patients who are refractory to or do not tolerate currently
available treatments.

Publication Types: 
    Review

PMID: 10856166 [PubMed - indexed for MEDLINE]

1471: J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S605-9.

Complications of allergic rhinitis.

Skoner DP.

Department of Allergy and Immunology, Children's Hospital of Pittsburgh,
Pittsburgh, PA 15213, USA.

Upper and lower respiratory diseases, including asthma, sinusitis, and otitis
media with effusion, frequently complicate allergic rhinitis. The close
association of nasal allergies with these conditions has been supported by
extensive epidemiologic evidence. Similar models have been proposed to explain
the pathophysiologic links between allergic rhinitis and both sinusitis and
otitis media with effusion. In these models, inflammation caused by nasal allergy
and/or viral infection leads to obstruction, fluid accumulation, bacterial
infection, and acute disease. If these diseases are unsuccessfully treated, a
chronic state of inflammation, obstruction, and infection develops that can cause
mucosal damage and, ultimately, chronic disease. A number of studies have
investigated the roles and interactions of viruses and allergens in the
development of otitis media with effusion. Diagnosing and prophylactically
treating nasal allergies in patients with this condition may help prevent
recurrent episodes and improve the response to therapy.

Publication Types: 
    Review

PMID: 10856165 [PubMed - indexed for MEDLINE]

1472: J Allergy Clin Immunol. 2000 Jun;105(6 Pt 2):S599-604.

Unique mechanistic features of allergic rhinitis.

Togias A.

Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA.

Symptoms of allergic rhinitis are produced by inflammatory mediators that are
released upon activation of mast cells by antigen-IgE interaction. These
mediators target the end organs directly or indirectly. Stimulation of sensory
nerves by histamine, for example, leads to sneezing, pruritus, rhinorrhea, and
nasal congestion. The clinical presentation of allergic rhinitis is also
characterized by the phenomenon of hyperresponsiveness to nonallergic stimuli,
such as cold air and various irritants. This phenomenon is believed to result
from the effect of allergic inflammation on the sensory nerves that supply the
upper airway mucosa. Various nonallergic triggers have been shown to act on the
nasal mucosa through sensorineural stimulation. In allergic rhinitis,
responsiveness to these stimuli is increased compared with the healthy state. A
similar phenomenon is observed against such products of the allergic reaction as 
his-tamine and bradykinin. Also, in allergic rhinitis, stimulation of sensory
nerves per se can produce inflammatory changes, a phenomenon known as neurogenic 
inflammation. The mechanism behind the development of sensorineural
hyperresponsiveness and of increased propensity for neurogenic inflammation is
unknown. However, evidence exists that the neurotrophin nerve growth factor,
which can induce all these changes on sensory nerves, is produced in the human
nasal mucosa and found in higher quantities in nasal secretions of patients with 
perennial allergic rhinitis as compared with healthy control subjects. Also,
nerve growth factor is acutely released into nasal fluids after allergen
provocation of patients with allergic disease. In patients with asthma of atopic 
origin, allergic rhinitis is almost ubiquitous. Because the nose is the air
conditioner of the respiratory system, its dysfunction may negatively affect the 
lower airways. In addition to the conditioning of inhaled air, the association
between allergic rhinitis and asthma may involve various mechanisms. For example,
allergen provocation in the nose of a patient with asthma can lead to reductions 
in pulmonary function and to increased lower airway responsiveness after several 
hours. Also, nasal inflammation may propagate through a systemic route to affect 
the lower airways.

Publication Types: 
    Review

PMID: 10856164 [PubMed - indexed for MEDLINE]

1473: Am J Respir Crit Care Med. 2000 Jun;161(6):2051-7.

Segmental bronchial provocation induces nasal inflammation in allergic rhinitis
patients.

Braunstahl GJ, Kleinjan A, Overbeek SE, Prins JB, Hoogsteden HC, Fokkens WJ.

Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam,
Rotterdam, The Netherlands.

Allergic rhinitis and asthma often coexist and share a genetic background.
Pathophysiologic connections between the nose and lungs are still not entirely
understood. This study was undertaken to compare allergic inflammation and
clinical findings in the upper and lower airways after segmental bronchial
provocation (SBP) in nonasthmatic allergic rhinitis patients. Eight nonasthmatic,
grass pollen-sensitive patients with allergic rhinitis and eight healthy controls
were included. Bronchial biopsies and blood samples were taken before (T(0)) and 
24 h (T(24)) after SBP. Nasal biopsies were obtained at T(0), 1 h after SBP
(T(1)), and T(24). Immunohistochemical staining was performed for eosinophils
(BMK13), interleukin (IL)-5, and eotaxin. The number of eosinophils increased in 
the challenged and unchallenged bronchial mucosa (p < 0.05) and in the blood (p =
0.03) of atopic subjects at T(24). We detected an increase of BMK13-positive and 
eotaxin-positive cells in the nasal lamina propria and enhanced expression of
IL-5 in the nasal epithelium of atopic subjects only at T(24) (p < 0.05). SBP
induced nasal and bronchial symptoms as well as reductions in pulmonary and nasal
function in the allergic group. No significant changes could be observed in
healthy controls. The study shows that SBP in nonasthmatic allergic rhinitis
patients results in peripheral blood eosinophilia, and that SBP can induce
allergic inflammation in the nose.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10852787 [PubMed - indexed for MEDLINE]

1474: Laryngoscope. 2000 Jun;110(6):1056-62.

Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble
intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and
nasal polyposis.

Kramer MF, Ostertag P, Pfrogner E, Rasp G.

Department of Otorhinolaryngology--Head and Neck Surgery, Ludwig Maximilians
University, Munich, Germany.

OBJECTIVE: To compare concentrations of interleukin-5 (IL-5), immunoglobulin E
(IgE), eosinophilic cationic protein (ECP), and soluble intercellular adhesion
molecule-1 (sICAM-1) in nasal secretion and serum of patients with chronic
nonallergic sinusitis, allergic rhinitis, and nonallergic nasal polyposis to
obtain information about the pathogenesis of these diseases. METHODS: Nasal
secretion and serum were analyzed by routine enzyme-linked immunosorbent assay
techniques. Nineteen patients with chronic nonallergic sinusitis, 24 patients
with seasonal allergic rhinitis, and 18 patients with nonallergic nasal polyposis
were included in the study. Eight healthy, nonallergic probands served as control
subjects. RESULTS: Significantly elevated concentrations of IL-5 (5-fold, P <
.05) and IgE (15-fold, P < .01) were detected in nasal secretion of patients with
allergic rhinitis (IL-5, 51.8 +/- 13.2 pg/mL; IgE, 41.9 +/- 20.9 kU/L) or
nonallergic nasal polyposis (IL-5, 57.9 +/- 36.9 pg(mL; IgE, 40.5 +/- 20.2 kU/L) 
compared with controls (IL-5, 10.6 +/- 7.8 pg/mL; IgE, 2.8 +/- 0.5 kU/L) or with 
patients with chronic nonallergic sinusitis (IL-5, 16.5 +/- 13.2 pg/mL; IgE, 5.4 
+/- 3.1 kU/L). There were no significant differences between patients with
allergic rhinitis and those with nonallergic nasal polyposis. Concentrations of
ECP were significantly elevated (sixfold, P < .01) in patients with allergic
rhinitis (297.8 ng/mL +/- 173.1) compared with controls (52.4 +/- 28.0 ng/mL) or 
patients with chronic nonallergic sinusitis (44.8 +/- 40.1 ng/mL), whereas
twofold higher concentrations (not significant) of ECP were observed in patients 
with nonallergic nasal polyposis (107.1 +/- 26.6 ng/mL). Significantly elevated
concentrations of sICAM-1 in nasal secretion (threefold, P < .05) were detected
only in patients with chronic nonallergic sinusitis (79.4 +/- 45.6 ng/mL). The
elevated sICAM-1 nasal secretion values in this group correlated significantly (P
< .05) to the serum values. CONCLUSIONS: Equally elevated concentrations of IL-5 
and IgE in patients with allergic rhinitis and nonallergic nasal polyposis
implicated similar pathogenic processes in both diseases. Whereas the
pathogenesis of allergic rhinitis is IgE-specific, the pathogenesis of nasal
polyps is not as clear. IL-5 was suggested to play a pivotal role in tissue
eosinophilia, which was confirmed by data in the present study. Elevated
concentrations of ECP were suggested to result from tissue eosinophilia--a
characteristic of both diseases. Elevated concentrations of sICAM-1 in patients
with chronic nonallergic sinusitis pointed to its key role in the recruitment of 
neutrophils into the inflamed tissue, whereas an important role in eosinophil
recruitment was ruled out.

PMID: 10852530 [PubMed - indexed for MEDLINE]

1475: Clin Exp Allergy. 2000 Jun;30(6):891-9.

Comparison of the efficacy, safety and quality of life provided by fexofenadine
hydrochloride 120 mg, loratadine 10 mg and placebo administered once daily for
the treatment of seasonal allergic rhinitis.

Van Cauwenberge P, Juniper EF.

Department of Otorhinolaryngology, University Hospital, Ghent, Belgium.
paul.vancauwenberge@rug.ac.be

BACKGROUND: As there have been no previously published studies, this
multinational, double-blind, randomized, placebo-controlled, parallel group study
compared the efficacy, safety and impact on quality of life (QoL) in seasonal
allergic rhinitis patients (SAR) of fexofenadine and loratadine (with placebo),
when administered once daily. METHODS: Six hundred and eighty-eight SAR patients 
were randomized to receive fexofenadine HCl 120 mg, loratadine 10 mg or placebo, 
once daily for 2 weeks. The key parameters were the change from baseline in: mean
24-h reflective total symptom scores (TSS); sum of four individual symptom
scores, excluding nasal congestion; instantaneous TSS; individual symptom scores 
including nasal congestion; and Rhinoconjunctivitis Quality of Life Questionnaire
(RQLQ). Adverse events were recorded. RESULTS: Mean 24-h reflective and
instantaneous TSS were significantly reduced by both fexofenadine HCl (both P </=
0.0001) and loratadine (P </= 0.001 and P </= 0.005, respectively) compared with 
placebo (n = 639). Among individual symptom scores, fexofenadine HCl was
significantly better than loratadine in improving 24-h reflective itchy, watery, 
red eyes, as well as relieving nasal congestion (P </= 0.05 for both).
Fexofenadine HCl was also significantly better than loratadine (P </= 0.03) and
placebo (P </= 0.005) in improving QoL, and the differences were of a magnitude
considered to be clinically relevant. Loratadine had no statistically significant
effect on QoL compared with placebo. The incidence of adverse events was low and 
similar across all treatment groups. CONCLUSION: Fexofenadine HCl and loratadine 
administered once daily are effective and well tolerated in SAR. In this study,
fexofenadine HCl was significantly more effective than loratadine in relieving
eye symptoms and nasal congestion. Furthermore, fexofenadine was significantly
better than loratadine in improving QoL.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10848909 [PubMed - indexed for MEDLINE]

1476: Clin Exp Allergy. 2000 Jun;30(6):833-8.

Evaluation of treatment response in patients with seasonal allergic rhinitis
using domiciliary nasal peak inspiratory flow.

Wilson A, Dempsey OJ, Sims EJ, Coutie WJ, Paterson MC, Lipworth BJ.

Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and
Medical School, University of Dundee, Scotland.

BACKGROUND: Measurement of domiciliary nasal peak inspiratory flow rate (PIFR)
may have a role in the objective assessment of treatment response in seasonal
allergic rhinitis (SAR). OBJECTIVE: We wished to evaluate the relationship
between domiciliary measurement of nasal PIFR and a variety of symptoms
associated with rhinitis. METHODS: Thirty-eight nonasthmatic patients, mean age
(SEM) 30 years (1.4), with symptomatic SAR were evaluated in a
placebo-controlled, single-blind, double-dummy, three way parallel group study.
Patients received oral cetirizine 10 mg once daily and were randomized to
receive, in addition, either: (i) intranasal mometasone furoate 200 microgram (n 
= 14); (ii) oral montelukast 10 mg (n = 11); or (iii) placebo (n = 13). All
treatments were given once daily for 4 weeks and were preceded by a 1 week
placebo period. Domiciliary diary cards were used to record morning (am) and
evening (pm) domiciliary nasal PIFR and symptom (nasal, eye, throat) scores and
impact on daily activity. A total daily symptom score was then calculated from
the sum of these separate symptom scores. RESULTS: Baseline values for symptom
scores and PIFR after placebo run-in were not significantly different when
comparing the three groups. After 4 weeks of active treatment, there were
significant (P < 0.05) improvements in nasal symptoms, total daily symptoms and
PIFR with all treatments, with there being no significant confounding effect of
pollen count, when analysed as a covariate. There were significant (P < 0.01)
correlations for nasal symptom scores vs PIFRam (r = - 0.51) and PIFRpm (r = -
0.56), and similarly for daily activity vs PIFRam (r = - 0.42) and PIFRpm (r = - 
0.48). CONCLUSIONS: These results suggest that domiciliary measurements of nasal 
peak flow correlate significantly with symptoms of seasonal allergic rhinitis and
may therefore be a potentially useful objective short-term marker of treatment
response.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10848901 [PubMed - indexed for MEDLINE]

1477: Ear Nose Throat J. 2000 May;79(5):362-4, 366.

The importance of quantifying skin reactivity in treating allergic rhinitis with 
immunotherapy.

Trevino RJ, Veling MC.

Department of Otolaryngology, Louisiana State University, Shreveport, USA.

Therapeutic options for the treatment of allergic rhinitis include environmental 
modifications to decrease exposure to allergens, pharmacotherapy, and
immunotherapy for those patients who do not experience satisfactory relief of
their symptoms with medical management. Skin testing is the best established and 
most sensitive indicator of allergic disease. Several techniques are currently in
use to identify pertinent antigens in the treatment of inhalant allergies. We
describe the various skin testing techniques that are associated with such
inhalant allergies. Quantification of skin reactivity to formulate a successful
antigen vial for effective immunotherapy is necessary in the management of
allergic disease.

PMID: 10832201 [PubMed - indexed for MEDLINE]

1478: Ann Allergy Asthma Immunol. 2000 May;84(5):533-8.

Triamcinolone acetonide aqueous nasal spray versus loratadine in seasonal
allergic rhinitis: efficacy and quality of life.

Condemi J, Schulz R, Lim J.

University of South Carolina, Columbia, USA.

BACKGROUND: The new aqueous formulation of triamcinolone acetonide (TAA) was
compared with loratadine in patients with seasonal allergic rhinitis. OBJECTIVE: 
The primary objective of the study was to compare the safety and efficacy of TAA 
aqueous with loratadine in relieving the symptoms of seasonal allergic rhinitis. 
METHODS: A total of 351 patients were enrolled into this 4-week, double-blind,
double-dummy, randomized, parallel group study. Patients received either TAA
aqueous nasal spray (220 microg) or loratadine (10 mg) once daily. Efficacy
variables were rhinitis symptom changes from baseline, physician global
evaluations, and the patient dropout rate due to insufficient treatment effect.
Safety and quality of life also was evaluated. RESULTS: Both TAA aqueous-treated 
and loratadine-treated patients had improvement in symptoms as early as day 1.
Overall, TAA aqueous was significantly (P < .05) more effective than loratadine
in reducing total nasal symptoms and individual symptoms of nasal congestion,
nasal itch, and sneezing. Ocular symptoms improved from baseline in both groups. 
There was no statistically significant difference between groups based on
physician global evaluation. A similar number of patients in each group
discontinued the study due to ineffective treatment. Triamcinolone acetonide
aqueous patients maintained a significantly (P < .05) better quality of life in
three of the dimensions (activity, nasal symptoms, and practical problems) and
for overall quality of life. There were no differences between the two treatment 
groups in the incidence of adverse events, none of which were clinically
significant. CONCLUSIONS: Both TAA aqueous and loratadine were effective and
well-tolerated in the treatment of patients with seasonal allergic rhinitis.
Triamcinolone acetonide aqueous was significantly (P < .05) more effective than
loratadine in controlling nasal symptoms of seasonal allergic rhinitis and
maintaining a better quality of life for the patients.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10831008 [PubMed - indexed for MEDLINE]

1479: J Allergy Clin Immunol. 2000 May;105(5):923-32.

Comment in:
    J Allergy Clin Immunol. 2000 May;105(5):889-91.

Effects of allergic inflammation of the nasal mucosa on the severity of
rhinovirus 16 cold.

Avila PC, Abisheganaden JA, Wong H, Liu J, Yagi S, Schnurr D, Kishiyama JL,
Boushey HA.

Divisions of Pulmonary Medicine and Allergy and Immunology, Department of
Medicine, Cardiovascular Research Institute, University of California, San
Francisco 94143-0130, USA.

BACKGROUND: Despite the strong association of asthma exacerbations with
rhinovirus (RV) infection, inoculation of asthmatic subjects with RV only causes 
small changes in lower airway function, suggesting that RV infection is not
itself sufficient to provoke asthma exacerbations. OBJECTIVE: Our purpose was to 
test whether allergic inflammation increases the airway response to RV infection.
METHODS: We compared the severity of RV type 16-induced colds in 2 groups of 10
subjects with allergic rhinitis. One group received 3 nasal challenges with
allergen and the other received challenges with placebo over the week before
nasal inoculation with RV type 16 (4000 tissue culture infective dose 50% per
subject). Subjects kept symptom diaries and were assessed with spirometry,
methacholine challenge, nasal lavage, and sputum induction on days 2, 4, 7, 10,
15, and 30 after inoculation. RESULTS: The 2 groups developed equal rates of
infection (90%), similar cold symptoms (Jackson score median [interquartile
range], 11 [6-33] vs 20.5 [6-42] for allergen and placebo groups respectively, P 
=.54), and similar changes in cellular profile and in IL-6 and IL-8
concentrations in nasal lavage fluid and induced sputum after RV inoculation. The
incubation period was significantly longer in the allergen group (2.5 [1-5.5] vs 
1 [1-1] day, P =.03) and the duration of cold symptoms was shorter (5 [4-7] vs
8.5 [6-10] days, P =.008). We also found an inverse correlation between the
percent of eosinophils in nasal lavage fluid before inoculation and the severity 
of cold symptoms (r = -0.58, P =. 008). CONCLUSION: In subjects with allergic
rhinitis, augmented nasal allergic inflammation before inoculation with RV type
16 does not worsen the severity of cold symptoms but delays their onset and
shortens their duration.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10808173 [PubMed - indexed for MEDLINE]

1480: J Allergy Clin Immunol. 2000 May;105(5):917-22.

Concomitant montelukast and loratadine as treatment for seasonal allergic
rhinitis: a randomized, placebo-controlled clinical trial.

Meltzer EO, Malmstrom K, Lu S, Prenner BM, Wei LX, Weinstein SF, Wolfe JD, Reiss 
TF.

Allergy and Asthma Medical Group and Research Center, San Diego, CA, USA.

BACKGROUND: Nasal challenge studies have suggested histamine and cysteinyl
leukotrienes are important proinflammatory mediators in allergic rhinitis. This
study was designed to determine the efficacy of montelukast, a cysteinyl
leukotriene receptor antagonist, administered alone or concomitantly with
loratadine, an H(1)-receptor antagonist, in seasonal allergic rhinitis.
OBJECTIVE: The purpose of this study was to determine the effect of concomitant
use of montelukast and loratadine in the treatment of seasonal allergic rhinitis.
METHODS: In this multicenter (N = 12) double-blind, randomized, parallel-group,
placebo-controlled 2-week trial, 460 men and women, aged 15 to 75 years, with
spring seasonal allergic rhinitis were randomly allocated to receive 1 of the
following 5 treatments: montelukast 10 or 20 mg, loratadine 10 mg, montelukast 10
mg with loratadine 10 mg, or placebo, once daily in the evening. The primary end 
point was daytime nasal symptoms score (average of congestion, rhinorrhea,
itching, and sneezing). Other end points were eye symptoms, nighttime symptoms,
individual daytime nasal symptoms, global evaluations (patient's and
physician's), and rhinoconjunctivitis quality-of-life scores. RESULTS:
Concomitant montelukast with loratadine improved the primary end point
significantly (P <.001) compared with placebo and each agent alone. Compared with
placebo, montelukast with loratadine also significantly improved eye symptoms,
nighttime symptoms, individual daytime nasal symptoms, global evaluations, and
quality of life. Montelukast alone and loratadine alone caused modest
improvements in rhinitis end points. All treatments were similarly well
tolerated. CONCLUSIONS: Concomitant montelukast with loratadine provided
effective treatment for seasonal allergic rhinitis and associated eye symptoms
with a safety profile comparable with placebo.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10808172 [PubMed - indexed for MEDLINE]

1481: Am J Respir Crit Care Med. 2000 May;161(5):1631-5.

Nerve growth factor expression and release in allergic inflammatory disease of
the upper airways.

Sanico AM, Stanisz AM, Gleeson TD, Bora S, Proud D, Bienenstock J, Koliatsos VE, 
Togias A.

Department of Medicine, Division of Clinical Immunology, and Johns Hopkins Asthma
and Allergy Center, Baltimore, Maryland, USA. amsanico@welch.jhu.edu

It is well known that allergic airways disease is characterized by inflammation
and hyperresponsiveness, but the link between these two conditions has not been
elucidated. We have previously shown that in allergic rhinitis,
hyperresponsiveness is attributable to increased neural reactivity. We thus
hypothesized that nerve growth factor (NGF), which is expressed by inflammatory
cells and effects changes that lead to increased neural responsiveness, could be 
a pivotal mediator in this disease. Using reverse transcription-polymerase chain 
reaction (RT-PCR), Western immunoblotting, and ELISA to evaluate NGF expression
and release, we found that subjects with allergic rhinitis have significantly
decreased NGF mRNA in superficial nasal scrapings and significantly higher
baseline concentrations of NGF protein in nasal lavage fluids, compared with
control subjects. Nasal provocation with allergen significantly increased NGF
protein in nasal lavage fluids of subjects with allergic rhinitis, but not of
control subjects. The concentrations of NGF protein in nasal lavage fluids were
not affected by provocation with the vehicle for allergen or with histamine.
These data provide the first evidence of a steady state of dysregulation in
mucosal NGF expression and release in allergic rhinitis, and support a role of
this neurotrophin in the pathophysiology of allergic inflammatory disease of the 
human airways.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10806167 [PubMed - indexed for MEDLINE]

1482: Ann Allergy Asthma Immunol. 2000 Apr;84(4):451-9.

Onset-of-action for antihistamine and decongestant combinations during an outdoor
challenge.

Georgitis JW, Meltzer EO, Kaliner M, Weiler J, Berkowitz R.

Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157,
USA. jgeorgitis@wfubmc.edu

BACKGROUND: Medications containing a combination antihistamine-decongestant are
commonly used for allergic rhinitis yet onset-of-action comparisons for symptom
relief after a single dose have not been performed. OBJECTIVE: To determine the
onset of symptom relief and efficacy of antihistamine-decongestant medications
(acrivastine-pseudoephedrine and loratadine-pseudoephedrine) compared with
placebo in an outdoor park. METHODS: This study was conducted during the spring
of 1997 using a double-blind, placebo-controlled design. Patients completed
baseline rhinitis symptom diaries from 7:30 to 9:30 AM. Subjects with qualifying 
symptom scores received one dose of either acrivastine-pseudoephedrine,
loratadine-pseudoephedrine, or placebo at 10:00 AM. Symptom diaries were recorded
for the next 4 hours. RESULTS: Of 593 patients randomized to treatment, 592 were 
included in efficacy analysis. Acrivastine-pseudoephedrine and
loratadine-pseudoephedrine demonstrated a mean onset-of-action by 45 and 30
minutes respectively for total symptom and rhinitis symptom scores for the five
sites. Onset-of-action for nasal congestion scores was 45 minutes for both
medications. Sites having higher pollen exposure (>100 pollen grains over 6
hours) demonstrated a difference between the antihistamine combinations:
acrivastine-pseudoephedrine had an onset of action at 45 minutes for total
symptom and rhinitis symptom scores, and 15 minutes for nasal congestion scores
whereas loratadine-pseudoephedrine had onset-of-action for nasal congestion score
of 105 minutes but failed to reach significance at any timepoint for total
symptom and rhinitis symptom scores. CONCLUSIONS: Both antihistamine-decongestant
combinations demonstrate an onset-of-action within 60 minutes of administration
but under conditions of higher pollen exposure, the acrivastine combination was
more effective for total symptoms, rhinitis symptoms, and nasal congestion with
an onset-of-action within 45 minutes for rhinitis symptoms and 15 minutes for
congestion.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10795655 [PubMed - indexed for MEDLINE]

1483: Ann Allergy Asthma Immunol. 2000 Apr;84(4):411-6.

Eosinophil apoptosis in induced sputum from patients with seasonal allergic
rhinitis and with asymptomatic and symptomatic asthma.

Foresi A, Teodoro C, Leone C, Pelucchi A, D'Ippolito R, Chetta A, Olivieri D.

Servizio di Fisiopatologia Respiratoria, Modulo di Allergologia ed
Immunopatologia Polmonare, Sesto San Giovanni, Italy. foresi@betacom.it

BACKGROUND: Eosinophilic inflammation is known to play an important role in the
pathogenesis of allergic diseases. Apoptosis, a form of programmed cell death, is
characterized by morphologic cell changes and leads to recognition and ingestion 
by macrophages. Apoptosis could be an important mechanism controlling the
resolution of tissue eosinophilia. OBJECTIVE: This study was designed to
investigate the presence of apoptotic eosinophils in induced sputum of patients
with seasonal allergic rhinitis (SAR), when examined during natural pollen
exposure and of patients with perennial asthma of different degrees of severity. 
METHODS: We recruited 11 patients with SAR to grass pollens, 26 patients with
asymptomatic asthma (AA), and 18 patients with symptomatic asthma (SA). The
severity of asthma was assessed by clinical scoring. Sputum was induced following
a standard method and differential cell count was estimated. Eosinophils showing 
cell shrinkage and nuclear coalescence were classified as apoptotic. The number
of apoptotic eosinophils was expressed as the percentage of total cells in sputum
and as the proportion of apoptotic eosinophils relative to normal bilobed
eosinophils ("apoptotic ratio"). RESULTS: We found the number of eosinophils in
the SA group was significantly greater than that in the SAR and the AA groups (P 
< .001 and P < .0001 respectively). The number of apoptotic eosinophils in the AA
group was significantly lower than that in the SAR group (P < .001) and in the SA
group (P < .0001). The apoptotic ratio for eosinophils in the SAR group was
significantly greater than in the AA group (P < .05) and in the SA group (P <
.05). There was no difference in the apoptotic ratio between the AA and SA
groups. CONCLUSIONS: This study confirms that apoptotic eosinophils are
detectable in induced sputum of allergic patients. Further, the results of our
study suggest that apoptosis could be an important mechanism in the control of
acute eosinophilic inflammation in patients with SAR exposed to the sensitizing
antigens. It appears that the apoptotic mechanism could be less effective in
controlling tissue eosinophilia in asthmatic patients with chronic eosinophilic
inflammation.

PMID: 10795649 [PubMed - indexed for MEDLINE]

1484: Ann Allergy Asthma Immunol. 2000 Apr;84(4):403-10.

Comment in:
    Ann Allergy Asthma Immunol. 2000 Apr;84(4):371-3.

Effects of seasonal allergic rhinitis on selected cognitive abilities.

Marshall PS, O'Hara C, Steinberg P.

Department of Psychiatry, Hennepin County Medical Center, Minneapolis, Minnesota 
55415, USA.

BACKGROUND: Many allergy patients complain of slowed thinking, memory problems,
and difficulty sustaining attention during their allergy seasons. OBJECTIVE: This
study evaluated the effect of symptomatic allergic rhinitis on speed of cognitive
processing, ability to divide and sustain attention, working memory, and recent
verbal memory. METHODS: Symptomatic ragweed-allergic rhinitis patients and
nonatopic control subjects did cognitive testing in, out of, and in ragweed
seasons. RESULTS: Test results indicate that, during ragweed seasons, allergic
patients experience subtle slowed speed of cognitive processing but not deficits 
in attention and recent memory. Some patients also have difficulties in working
memory. CONCLUSIONS: These findings suggest that having allergic reactions to
ragweed pollen causes significant cognitive difficulties in a subgroup of
patients.

PMID: 10795648 [PubMed - indexed for MEDLINE]

1485: Otolaryngol Head Neck Surg. 2000 May;122(5):758-62.

Skin prick test reactivity to foods in adult Malaysians with rhinitis.

Gendeh BS, Murad S, Razi AM, Abdullah N, Mohamed AS, Kadir KA.

Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine,
National University of Malaysia, Kuala Lumpur.

The aim of the study was to determine the incidence of food and house dust mite
(HDM) allergy in patients with nasal congestion and rhinorrhea attending the
Otorhinolaryngology Clinic, National University of Malaysia, Kuala Lumpur. This
was a prospective matched, controlled study of patients skin prick tested with
commercial food and common aeroallergens. The participants were 148 Malaysian
adults with symptoms of nasal congestion and rhinorrhea and 113 adult Malaysian
control subjects without rhinitis symptoms. The skin prick test (SPT) was used to
evaluate 11 foods common to the Malaysian diet and 3 HDM inhalants. Forty-eight
percent of the patients with rhinitis had positive SPT results to foods, compared
with 4.4% of control subjects (P < 0.05). The most commonly implicated foods were
shrimp (48%) and rice (30%), which are common in the Malaysian diet. Seventy-two 
percent of rhinitis patients had positive SPT results to HDM, compared with 22.2%
of control subjects (P < 0.05). Patients with rhinitis also had significantly
more gastrointestinal problems than control subjects (P < 0.05). The incidences
of HDM and food allergy are significantly greater in Malaysian adults with
rhinitis symptoms than in control subjects without rhinitis. The effect of
avoidance or immunotherapy awaits further study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10793361 [PubMed - indexed for MEDLINE]

1486: Otolaryngol Head Neck Surg. 2000 May;122(5):706-11.

Nitric oxide is a mediator of the late-phase response in an animal model of nasal
allergy.

Durland WF Jr, Lane AP, Durland KW, Smith TL, Johnson KL, Prazma J, Pillsbury HC.

University of North Carolina at Chapel Hill, USA.

The presence of nitric oxide (NO) in the nose is well documented; however, the
role of this molecule in nasal physiology is still poorly understood. Our
laboratory has previously demonstrated that NO is a mediator of the immediate
secretory response to an intranasal histamine challenge in a rat model of nasal
allergy. Histamine challenge, however, does not elicit a late-phase response
(LPR). To study the role of NO in the LPR, we developed a model of nasal allergy 
in which brown Norway rats are actively sensitized to the allergen ovalbumin and 
later challenged intranasally with either phosphate-buffered saline solution
(vehicle), ovalbumin in vehicle, or ovalbumin and the NO synthase inhibitor N
-nitro-l -arginine methyl ester. In each experiment, nasal lavage samples were
collected 30, 120, 240, and 360 minutes after challenge. Lavage samples were
analyzed for albumin content by ELISA, inflammatory cell concentration with a
hemocytometer, and evidence of inflammation by light microscopy. Blocking NO
synthesis with N -nitro-l -arginine methyl ester significantly inhibited both
albumin exudation and inflammatory cell influx into the nasal cavity during the
LPR. These data suggest that NO plays a role in the LPR of nasal allergy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 10793351 [PubMed - indexed for MEDLINE]

1487: Otolaryngol Head Neck Surg. 2000 May;122(5):681-5.

Health status in allergic rhinitis.

Corey JP, Kemker BJ, Branca JT, Kuo F, Chang Y, Gliklich RE.

Department of Surgery, Section of Otolaryngology, University of Chicago, Pritzker
School of Medicine, Illinois 60637, USA.

Although valid and reliable instruments exist to measure the quality of life of
allergic rhinitis patients, a statistically sensitive and clinically meaningful
way to evaluate patients undergoing immunotherapy has not been reported. A
21-site prospective, observational study was performed in a population of
consecutive patients with allergic rhinitis. Baseline general health measures
revealed significant (P < 0.05) decrements from reported normative levels in 8
domains for patients choosing to undergo immunotherapy and 5 domains for patients
choosing not to undergo immunotherapy. The General Health Survey was less
sensitive in detecting change than the Nasal Health Survey (Chronic Sinusitis
Survey) and allergy-specific (Rhinoconjunctivitis Quality of Life Questionnaire
and Allergy Outcome Survey) surveys. Severity of symptoms was associated with
both the likelihood to choose immunotherapy and the likelihood for early
improvement. We conclude that general and condition-specific measures can be used
to observe patients after immunotherapy; however, obtaining baseline data and
controlling for seasonality are important considerations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10793346 [PubMed - indexed for MEDLINE]

1488: Ear Nose Throat J. 2000 Apr;79(4):254, 257-8, 260 passim.

Loratadine/pseudoephedrine for nasal symptoms in seasonal allergic rhinitis: a
double-blind, placebo-controlled study.

McFadden EA, Gungor A, Ng B, Mamikoglu B, Moinuddin R, Corey J.

Allergy Clinic, University of Chicago Medical Center, IL, USA.

In this double-blind, placebo-controlled, crossover, parallel study, we treated
20 adults who had seasonal allergic rhinitis with once-daily fixed-combination
loratadine/pseudoephedrine sulfate to observe its effect on relieving symptoms,
primarily nasal congestion. Acoustic rhinometry detected a trend toward
improvement in nasal patency, although the difference between pre- and
post-treatment measures was not statistically significant. Endoscopic inferior
turbinate photography documented that treatment led to statistically significant 
reductions in the amount of nasal edema and nasal secretions. The results of a
quality-of-life questionnaire suggested that treatment alleviated nasal and
ocular symptoms of rhinoconjunctivitis. An analysis of subjective visual analog
scale scores showed a trend toward improvement in most but not all nasal
symptoms. We conclude that once-a-day fixed-combination
loratadine/pseudoephedrine is effective in relieving nasal congestion in patients
with seasonal allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10786387 [PubMed - indexed for MEDLINE]

1489: Allergy. 2000 Apr;55(4):363-8.

Glucocorticosteroids rapidly inhibit allergen-induced expression of E-selectin in
vitro in a mucosal model of allergic rhinitis.

Rudack C, Bachert C.

ENT Department, University Hospital WWU Münster, Germany.

BACKGROUND: Transendothelial migration of cells to sites of inflammation is a
hallmark of the allergic reaction. The adhesion cascade involves the initial
expression of the adhesion molecule E-selectin on endothelial cells. The aim of
the study was to determine the efficacy of a 30-min preincubation of the
glucocorticosteroids (GCS) fluticasone, prednisolone, and fluocortin butyl on
allergen- and interleukin (IL)-1beta-induced E-selectin expression in allergic
rhinitis. METHODS: Freshly taken nasal inferior turbinate mucosa of 19 subjects
with allergic rhinitis was cut into small cubes and preincubated for 30 min with 
prednisolone (n = 6), fluticasone (n = 5), and fluocortin butyl (n = 3) in
different concentrations, followed by allergen exposure at a concentration of
1000 BU/ml for 1 and 2 h. Additionally, fluticasone-preincubated tissues were
exposed to recombinant human rhIL-1beta (n = 5) at a concentration of 2 pg/ml.
The expression of E-selectin was assessed by immunohistochemistry (APAAP
technique) and computerized image evaluation. RESULTS: In this model, E-selectin 
expression was significantly upregulated by allergen and rhIL- 1beta within 1 and
2 h. After 30-min preincubation with prednisolone and fluocortin butyl at drug
concentrations of 10-8 mol/1, we found a significant (> or = 50%) reduction of
the E-selectin expression after 1 and 2 h. Allergen-induced E-selectin expression
was nearly abolished at concentrations of 10-5 (prednisolone) and 10-4 mol/l
(fluocortin butyl). Fluticasone significantly inhibited E-selectin expression by 
> or = 50% at concentrations of 10-14 and 10-12 mol/l after 1 and 2 h, and
abolished E-selectin induction at concentrations of 10-12 and 10-10 mol/l,
respectively. Exposure of mucosal cubes to rhIL-lbeta (n = 5) also induced rapid 
upregulation of E-selectin expression, an effect which could be only partially
suppressed by fluticasone preincubation at concentrations of 10-l0 mol/l.
CONCLUSIONS: Allergen-induced E-selectin expression is significantly and rapidly 
inhibited by GCS preincubation, fluticasone being more potent than prednisolone
and fluocortin butyl. We suggest that this rapid effect is mainly indirect,
possibly by inhibition of allergen-induced cytokine release.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10782521 [PubMed - indexed for MEDLINE]

1490: Allergy. 2000 Apr;55(4):340-7.

Evaluation of the allergenicity of tropical pollen and airborne spores in
Singapore.

Chew FT, Lim SH, Shang HS, Dahlia MD, Goh DY, Lee BW, Tan HT, Tan TK.

Department of Paediatrics, National University of Singapore, Singapore.

BACKGROUND: Sensitization to pollen and spores of the Southeast Asian tropical
region is not well documented. This study evaluated the allergenicity of the
tropical airspora in Singapore. METHODS: On the basis of the results of an
aerobiologic survey of the airspora profile of Singapore, crude extracts of 23
main spore (fungal and fern) and pollen types were prepared. A total of 231
patients with asthma and/or allergic rhinitis and 76 healthy controls were
evaluated by skin prick test (SPT). Total and specific IgE levels were also
quantified by the fluorescence allergosorbent test (FAST). RESULTS: All 23
allergenic extracts tested elicited positive SPT responses. Among the patients
with atopic diseases, extracts of oil-palm pollen (Elaeis guineensis) were
observed to have the highest frequency of positive reactions (40%), followed by
extracts of resam-fern spores (Dicranopteris linearis) (34%) and sea-teak pollen 
(Podocarpus polystachyus) (33.8%). Fungal spores with the highest SPT responses
were Curvularia spp. (26-32%) and Drechslera-like spores (31%). Positive
responses to these extracts correlated with total serum IgE levels of the
subjects and were significantly associated with the presence of atopic disease.
CONCLUSIONS: We have documented sensitization to tropical pollen and spores in
our population. Its association with atopy suggests that it has a role in
allergic diseases in the tropics.

PMID: 10782518 [PubMed - indexed for MEDLINE]

1491: Pediatr Allergy Immunol. 2000 Feb;11(1):20-8.

Low levels of interferon-gamma in nasal fluid accompany raised levels of T-helper
2 cytokines in children with ongoing allergic rhinitis.

Benson M, Strannegård IL, Wennergren G, Strannegård O.

Department of Pediatrics, Sahlgrenska University Hospital, Göteborg, Sweden.
mikael.benson@pediat.gu.se

The T-helper 2 (Th2) cytokines interleukin-(IL-) 4, IL-5, IL-6, IL-10 and the Th1
cytokine IFN-gamma and their associations with eosinophil, eosinophil cationic
protein (ECP) and immunoglobulin (Ig) E were studied in nasal lavage fluid from
60 school children with allergic seasonal rhinitis and 36 nonatopic healthy
controls, before and during the pollen season. Eosinophil differential counts and
IgE increased significantly in the patients during the pollen season. The
eosinophil differential counts, ECP and IgE were all significantly higher during 
the season than in specimens simultaneously obtained from the nonatopic controls.
Before season, the levels of ECP and IgE, but not eosinophils, were significantly
higher in the patients than in the controls. During the season the nasal lavage
fluid levels of IFN-gamma were significantly lower and the IL-4/IFN-gamma
quotients significantly higher in the allergic than in the control children. In
the allergic children, but not in the controls, the nasal fluid levels of the Th2
cytokines IL-4, IL-5 and IL-10 increased during the season, and together with
IL-6, were correlated with the differential counts of eosinophils, and with the
levels of ECP and IgE. These findings are compatible with the hypothesis that a
deficient release of the Th1 cytokine IFN-gamma plays an important role in the
pathogenesis of allergic inflammation. Regardless of whether the defective
IFN-gamma secretion is primary or a consequence of suppression by other
cytokines, it will in the atopic subjects enhance the release of Th2 cytokines,
which in turn will facilitate the development of allergic inflammation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10768732 [PubMed - indexed for MEDLINE]

1492: Eur Respir J. 2000 Mar;15(3):491-7.

Local production and detection of (specific) IgE in nasal B-cells and plasma
cells of allergic rhinitis patients.

KleinJan A, Vinke JG, Severijnen LW, Fokkens WJ.

Department of Otorhinolaryngology, Erasmus University Medical Centre Rotterdam,
The Netherlands.

Allergic diseases are characterized by allergic complaints in the shock organ and
specific immunoglobulin (Ig)E in serum. Literature data indicate that the nasal
mucosa itself could produce at least a large part of the specific IgE in allergic
rhinitis patients. In order to investigate this hypothesis, nasal mucosal
biopsies from the inferior turbinate were taken from symptomatic grass pollen
allergic rhinitis patients, symptomatic house dust mite allergic rhinitis
patients and nonallergic healthy controls, confirmed by radioallergosorbent test 
and skin-prick test. Immunohistochemical double-staining was performed for
B-cells (CD19) with IgE, plasma cells (CD138) with IgE and plasma cells with
biotinylated allergens. Significantly more IgE-positive B-cells and IgE-positive 
plasma cells were found in the nasal mucosa of allergic patients than in that of 
nonallergic controls. Double staining with biotinylated allergens and plasma
cells showed allergen-positive plasma cells in the nasal mucosa of allergic
patients and no allergen-positive plasma cells in the nasal mucosa of nonallergic
patients. Blocking experiments using polyclonal antibodies directed against IgE
showed a significant reduction in the number of allergen-positive cells in
contrast to experiments using polyclonal antibodies directed against IgG, IgA or 
IgM. This study describes new evidence that specific immunoglobulin E is produced
locally in the nasal mucosa in patients with seasonal allergic rhinitis and
perennial allergic rhinitis, but not in nonallergic controls.

PMID: 10759442 [PubMed - indexed for MEDLINE]

1493: J Allergy Clin Immunol. 2000 Apr;105(4):803-13.

Dissociation of allergen-specific IgE and IgA responses in sera and tears of
pollen-allergic patients: a study performed with purified recombinant pollen
allergens.

Aghayan-Ugurluoglu R, Ball T, Vrtala S, Schweiger C, Kraft D, Valenta R.

Department of Pathophysiology, Clinical Institute for Medical and Chemical
Laboratory Diagnostics, University of Vienna, Vienna, Austria.

BACKGROUND: Trees and grass pollen allergens represent potent elicitors of
allergic rhinoconjunctivitis and asthma. Little is known regarding the presence
of allergen-specific IgA antibodies in sera and tears and their association with 
IgE responses in patients with allergic conjunctivitis. OBJECTIVE: The purpose of
this study was to compare the specificities of IgE and IgA antibodies in sera and
tears of pollen-allergic patients with conjunctivitis by using purified
recombinant pollen allergens. METHODS: Sera and tears collected from 23
pollen-allergic and from 23 nonatopic individuals were analyzed for IgE and IgA
reactivity to nitrocellulose-blotted birch and timothy grass pollen extracts. In 
addition, we determined the specificities of IgE, IgG(1-4), and IgA antibodies
with use of a panel of purified recombinant pollen allergens (timothy grass: rPhl
p 1, rPhl p 2, rPhl p 5; birch: rBet v 1, rBet v 2) in serum and tear samples by 
immunoblotting and ELISA. Statistical analyses of data were performed by t test
and Mann Whitney U test. RESULTS: Serum and tears of many of the pollen-allergic 
individuals with conjunctivitis exhibited specificity for the very same pollen
allergens. No allergen-specific IgE antibodies were detected in tears of
nonatopic individuals. IgA antibodies in sera and tears of patients with allergic
conjunctivitis were mainly directed against nonallergenic moieties and showed
specificities that were significantly different from those of IgE antibodies.
CONCLUSION: The dissociation of IgE and IgA responses and the lack of
allergen-specific IgA antibodies in mucosal secretions (eg, tears) may contribute
to allergic manifestations in target organs of atopy. Induction of
allergen-specific IgA antibodies may hence be considered as a promising strategy 
for the treatment of mucosal forms of atopy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10756233 [PubMed - indexed for MEDLINE]

1494: J Allergy Clin Immunol. 2000 Apr;105(4):732-8.

As-needed use of fluticasone propionate nasal spray reduces symptoms of seasonal 
allergic rhinitis.

Jen A, Baroody F, de Tineo M, Haney L, Blair C, Naclerio R.

Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, Pritzker 
School of Medicine, University of Chicago, Chicago, Illinois, USA.

BACKGROUND: The daily use of intranasal corticosteroids is approved for the
treatment of seasonal allergic rhinitis. OBJECTIVE: Our objective was to test the
effectiveness of as-needed use of intranasal corticosteroids in the treatment of 
seasonal allergic rhinitis. METHODS: A double-blind, placebo-controlled,
randomized, parallel-group study of the as-needed usage of fluticasone propionate
nasal spray in the management of seasonal allergic rhinitis was performed.
Outcome measures were symptom score, Rhinitis Quality of Life Questionnaire
(RQLQ), and the number of eosinophils and the level of eosinophilic cationic
protein (ECP) in nasal lavage. RESULTS: Twenty-six subjects in each group
completed the 4-week study. The median symptom score over the duration of the
study in the placebo group was 8.5 versus 4.5 in the active group. The active
group had significant improvement on the interim visit in the sleep,
non-nose/eye, activities, nasal, practical, and overall domains (P <.05) of the
RQLQ and on the final visit in the nasal symptom domain. The number of
eosinophils was significantly lower in the active than in the placebo group at
the final visit. Changes in ECP were not significant. CONCLUSION: As-needed
fluticasone propionate nasal spray is efficacious in the treatment of seasonal
allergic rhinitis.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10756223 [PubMed - indexed for MEDLINE]

1495: Allergy Asthma Proc. 2000 Jan-Feb;21(1):45-54.

Rhinitis and asthma connection: management of coexisting upper airway allergic
diseases and asthma.

Fireman P.

Asthma and Allergic Disease Center, University of Pittsburgh School of Medicine, 
Pennsylvania, USA.

Asthma is a chronic inflammatory disease of the lower airways. Epidemiologic
surveys and clinical reports have documented that allergic rhinitis coexists with
asthma in many patients. Provocative bronchial challenge with allergens
responsible for allergic rhinitis in susceptible asthma patients can elicit
asthma, and these responses have been linked to bronchial airway hyperreactivity.
Provocative bronchial methacholine challenge in allergic rhinitis patients will
demonstrate increased airway responsiveness to the bronchial challenge in 30% of 
those allergic rhinitis patients who had no past history of asthma. These data
suggest that subclinical asthma may be present in certain patients with allergic 
rhinitis. The focus of the National Heart, Lung, and Blood Institute (NHLBI)
guidelines for the pharmacologic treatment of asthma focuses on medications to
relieve the symptoms of asthma, i.e., bronchodilators and anti-inflammatory
agents (i.e., inhaled corticosteroids, cromolyn, and leukotriene modifiers) to
control asthma. Avoidance of allergens such as house dust mite are also
recommended. Although not emphasized in these NHLBI guidelines, recent studies
have observed that treatments, including intranasal steroid, cromolyn,
antihistamines, and decongestants, which provide relief of nasal symptoms in
patients with both allergic rhinitis and asthma, will also improve the pulmonary 
symptoms of allergic asthma. This article will review the recent literature.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 10748952 [PubMed - indexed for MEDLINE]

1496: Manag Care Interface. 2000 Jan;13(1):60-2.

The treatment of seasonal allergic rhinitis: cost implications of pharmacotherapy
for managed care.

Trotter JP.

Ovation Research Group, Highland Park, Illinois, USA.

Seasonal allergic rhinitis affects a large proportion of both the general and the
managed care populations. Whereas matching treatment to the needs of individual
patients remains somewhat of an art, decisions regarding which drugs to add to
the formulary of an MCO should incorporate an assessment of a medication's
efficacy and safety profile, as well as a review of the overall costs associated 
with its utilization. Recognizing that the overall costs of drug utilization
include more than the actual price of a prescription, a utilization analysis of
annual drug therapy was undertaken. The results of this recent study demonstrate 
that fewer prescriptions and lower costs were associated with certain products.
In this study, azelastine nasal spray was associated with an overall lower cost
of pharmacotherapy.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10747693 [PubMed - indexed for MEDLINE]

1497: Cleve Clin J Med. 2000 Mar;67(3):165-8.

Erratum in:
    Cleve Clin J Med 2000 Jun;67(6):448.

New therapies for allergic rhinitis.

Graft DF.

Department of Asthma and Allergic Diseases, Park Nicollet Clinic, Minneapolis,
Minnesota 55416-2699, USA.

New therapies for allergic rhinitis are more effective and have fewer side
effects than older medications. Antihistamines, decongestants, and cromolyn
sodium nasal sprays are often tried first. Second generation prescription
antihistamines have fewer side effects than over-the-counter ones. Steroid nasal 
sprays are extremely effective and safe for the entire range of allergy symptoms.
Immunotherapy requires a lengthy course of injections, but it can bring long-term
relief for severe allergies.

PMID: 10743304 [PubMed - indexed for MEDLINE]

1498: Eur J Immunol. 2000 Mar;30(3):964-8.

A flavonoid sulfate antigen activates human alphabeta CD8+ Th2 lymphocytes in
pollen allergy.

Sallusto F, Poupot R, Clergue M, DePalma R, Fournié JJ.

Basel Institute for Immunology, Switzerland.

Cellular immune responses are initiated when T lymphocytes expressing alphabeta
TCR recognize peptide antigens bound to MHC molecules or, less frequently,
double-stranded glycolipid antigens bound to CD1 molecules. In the allergy to
Parietaria judaica, human alphabeta CD8+ Th2 lymphocytes react to a non-peptide
pollinic antigen presented by B cells. The environmental allergen was purified
and identified as a new flavonoid pigment: 2'-O-sulfate,
6-O-betaD-glucuronopyranosyl, 2',5,6-trihydroxy-isoflavone. Its specific
recognition by alphabeta CD8+ Th2 T cells (1) depends upon an MHC- and
CD1-independent presentation mediated by B cells, (2) is determined by the
flavonoid carbohydrate and sulfate groups and (3) leads to positive skin prick
test in allergic patients. Hence, an unusual mode of aromatic sulfated antigen
recognition by alphabeta CD8+ Th2 T lymphocytes might underlie the cellular
mediation of human allergy to plant allergens.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 10741415 [PubMed - indexed for MEDLINE]

1499: Auris Nasus Larynx. 2000 Apr;27(2):141-5.

Changes in unilateral nasal airflow in patients with seasonal allergic rhinitis
measured in and out of season.

Takeuchi H, Jawad M, Eccles R.

Department of Otorhinolaryngology, Faculty of Medicine, Tottori University,
Yonago, Japan.

OBJECTIVE: Nasal congestion is a common complaint of patients suffering from
seasonal allergic rhinitis yet there are very few investigations which have
studied the objective changes in nasal airflow in and out of season. The aim of
this study was to investigate the changes in nasal airflow in and out of season. 
METHODS: In the present study unilateral nasal airflow was measured in and out of
the pollen season in 13 patients with seasonal allergic rhinitis. Unilateral
nasal airflow was measured using posterior rhinomanometry at an inspiratory
reference pressure of 75 Pa. RESULTS: There was no significant difference between
median total nasal airflow in season (325 cm3/s) and out of season (324 cm3/s) (P
= 0.15, n = 13) yet there was a significant difference between maximum unilateral
airflow in season (278 cm3/s) and out of season (234 cm3/s) (P = 0.007, n = 26). 
CONCLUSION: The results of the present study indicate that although patients with
seasonal allergic rhinitis may experience a sensation of nasal congestion at the 
start of the pollen season there is little or no change in total nasal airflow
and unilateral nasal airflow may be increased.

PMID: 10733142 [PubMed - indexed for MEDLINE]

1500: ORL J Otorhinolaryngol Relat Spec. 2000 Mar-Apr;62(2):68-75.

Epithelial changes in seasonal allergic rhinitis throughout the year: evidence of
coexistent air pollution and local secretory IgA deficiency?

Glück U, Gebbers J.

Division of Occupational Medicine, Suva, Luzern, Switzerland.

To determine possible epithelial changes in seasonal allergic rhinitis, we
examined epithelial cells in cytology swab preparations of 38 non-smoking
patients, exclusively sensitized to grass pollen, throughout the year, and
surgical material of 8 patients. Cytologically, we found a marked goblet cell
hyperplasia during the period of grass pollen exposure, while meta- and dysplasia
were found throughout the year. Immunohistochemically, a lack of secretroy IgA in
the altered epithelium was detected. These results were not obtained in the
control group of 60 healthy non-smokers. Since we have recently found the same
epithelial changes of meta- and dysplasia in smokers, these findings may point to
non-specific toxic damage of the nasal epithelium possibly caused by other air
pollutants. The altered epithelium may lead to an impairment of the local
secretory IgA defence system and thereby to an increased allergen uptake.
Copyright 2000 S. Karger AG, Basel

PMID: 10729795 [PubMed - indexed for MEDLINE]

1501: Drugs. 2000 Feb;59(2):301-21.

Erratum in:
    Drugs 2000 May;59(5):1089.

Fexofenadine: a review of its use in the management of seasonal allergic rhinitis
and chronic idiopathic urticaria.

Simpson K, Jarvis B.

Adis International Limited, Mairangi Bay, Auckland, New Zealand.
demail@adis.co.nz

Fexofenadine, the active metabolite of terfenadine, is a selective histamine H1
receptor antagonist that does not cross the blood brain barrier and appears to
display some anti-inflammatory properties. Fexofenadine is rapidly absorbed
(onset of relief < or = 2 hours) and has a long duration of action, making it
suitable for once daily administration. Clinical trials (< or = 2 weeks'
duration) have shown fexofenadine 60 mg twice daily and 120 mg once daily to be
as effective as loratadine 10 mg once daily, and fexofenadine 120 mg once daily
to be as effective as cetirizine 10 mg once daily in the overall reduction of
symptoms of seasonal allergic rhinitis. When given in combination, fexofenadine
and extended release pseudoephedrine had complementary activity. Fexofenadine was
effective in relieving the symptoms of sneezing, rhinorrhoea, itchy nose palate
or throat, and itchy, watery, red eyes in patients with seasonal allergic
rhinitis. There were often small improvements in nasal congestion that were
further improved by pseudoephedrine. Fexofenadine produced greater improvements
in quality of life than loratadine to an extent considered to be clinically
meaningful, and enhanced patients' quality of life when added to pseudoephedrine 
treatment. Although no comparative data with other H1 antagonists exist,
fexofenadine 180 mg once daily was effective in reducing the symptoms of chronic 
idiopathic urticaria for up to 6 weeks. Fexofenadine was well tolerated in
clinical trials in adults and adolescents and the adverse event profile was
similar to placebo in all studies. The most frequently reported adverse event
during fexofenadine treatment was headache, which occurred with a similar
incidence to that seen in placebo recipients. Fexofenadine does not inhibit
cardiac K+ channels and is not associated with prolongation of the corrected QT
interval. When given alone or in combination with erythromycin or ketoconazole,
it was not associated with any adverse cardiac events in clinical trials. As it
does not cross the blood brain barrier, fexofenadine is free of the sedative
effects associated with first generation antihistamines, even at dosages of up to
240 mg/day. CONCLUSIONS: fexofenadine is clinically effective in the treatment of
seasonal allergic rhinitis and chronic idiopathic urticaria for which it is a
suitable option for first-line therapy. Comparative data suggest that
fexofenadine is as effective as loratadine or cetirizine in the treatment of
seasonal allergic rhinitis. In those with excessive nasal congestion the
combination of fexofenadine plus pseudoephedrine may be useful. In clinical
trials fexofenadine is not associated with adverse cardiac or
cognitive/psychomotor effects.

PMID: 10730552 [PubMed - indexed for MEDLINE]

1502: Allergy. 2000 Feb;55(2):171-5.

Study of the Th1/Th2 balance, including IL-10 production, in cultures of
peripheral blood mononuclear cells from birch-pollen-allergic patients.

Movérare R, Elfman L, Stålenheim G, Björnsson E.

Department of Allergy/Asthma, Pharmacia & Upjohn Diagnostics AB, Uppsala, Sweden.

BACKGROUND: Excessive production of interleukin (IL)-4, IL-5, IL-10, and IL-13 is
thought to be important in the development of allergy and asthma. The objective
of this investigation was to study Th1/Th2-like cytokine profiles in vitro in
seven patients allergic to birch pollen and six nonallergic controls during the
birch-pollen season. METHODS: Peripheral blood mononuclear cells (PBMC) were
isolated and cultured with birch-pollen extract (BPE) or tetanus toxoid (TT) for 
7 days, harvested, and restimulated with the mitogens phytohemagglutinin (PHA)
and phorbol 12-myristate 13-acetate (PMA) for 24 h. Cytokine production was
determined by ELISA, and logarithmic cytokine ratios were compared between the
two groups and between the antigens. RESULTS: In the allergic group, the cultures
prestimulated with BPE had a more Th2-like cytokine response than the
TT-prestimulated cultures; i.e., lower IFN-gamma and higher IL-10 production
(P<0.05), as well as higher IL-5/IFN-gamma and IL-13/ IFN-gamma ratios (P<0.05). 
There were also significantly higher IL-4/IFN-gamma (P<0.005) and IL-5/IFN-gamma 
(P<0.05) ratios in BPE-stimulated cultures in the allergic group than in the
control group. The IL-4 and IL-13 production in vitro correlated with the
specific serum IgE levels. CONCLUSIONS: BPE stimulation induces a Th2-like
cytokine response by PBMC isolated during the pollen season from
birch-pollen-allergic patients, indicating a Th2-type immune response to birch
pollen in vivo.

PMID: 10726732 [PubMed - indexed for MEDLINE]

1503: Allergy. 2000 Feb;55(2):181-4.

Evaluation of IgE antibodies to recombinant pollen allergens (Phl p 1, Phl p 2,
and Phl p 5) in a random sample of patients with specific IgE to Phleum pratense.

Rossi RE, Monasterolo G, Operti D, Operti R, Berlen R.

Unità Territoriale di Allergologia, Ospedale S.S. Trinità, Fossano, Italy.

BACKGROUND: We measured specific IgE levels against the recombinant allergens
(RAs) rPhl p 1, rPhl p 2, and rPhl p 5 in patients allergic to grass pollen, and 
examined the existence of different patterns of IgE production to RAs. The
seasonal variations of IgE levels to rPhl p 1, rPhl p 2, and rPhl p 5 were
considered, too. METHODS: Blood was taken from 276 consecutive patients with
allergy to grass pollen diagnosed by patient history and skin prick testing.
Total and specific serum IgE was measured by the immunoenzymatic CAP FEIA System.
Eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were assessed by
radioimmunoassay according to the instructions of the manufacturers. RESULTS: We 
observed eight different patterns of IgE production to rPhl p 1, rPhl p 2, and
rPhl p 5 in patients with specific IgE to timothy grass. A significant difference
between the values of IgE levels to timothy and the sum of each level of specific
IgE to individual RAs was found (P = 0.039, Wilcoxon matched pairs test) in the
whole population (n = 276 subjects). In four subgroups of patients, the sum of
each level of specific IgE to individual RAs was equal to the levels of specific 
IgE to timothy grass extract. In one subgroup, the sum of IgE to RAs was lower
than the levels of IgE to the natural counterpart (P = 0.013). A lack of subjects
in two subgroups did not permit comparison at all. Finally, three subjects with
specific IgE to timothy did not show specific IgE to RAs. Out of 276 patients,
blood was taken from two different groups of subjects at different time points:
November-January and May-July, respectively. The median values were as follows:
total IgE = 139 kU/l, IgE to timothy = 10.2 kUA/l; IgE to rPhl p 1 = 3.6 kUA/l,
to rPhl p 2 = <0.35 kUA/l, and to rPhl p 5 = 1.1 kUA/l; ECP = 8.25 microg/l; MPO 
= 303.08 microg/l (before exposure to grass pollen); total IgE = 159 kU/l, IgE to
timothy = 57.2 kUA/l; IgE to rPhl p 1 = 22.1 kUA/l, to rPhl p 2 = 5.9 kUA/l, and 
to rPhl p 5 = 3.9 kUA/l; ECP = 16.21 microg/l; MPO = 413.09 microg/l (during the 
pollen season). There were significant variations of specific IgE levels between 
the patients exposed to pollen and the unexposed patients. Moreover, there were
statistical differences in the IgE, ECP, and MPO levels in sera before and during
the pollen season P<0.035, P<0.017, and P<0.0062, respectively. CONCLUSIONS: The 
results suggest that RAs allow establishment of the patient's IgE-reactivity
profile, encourage future research, and encourage manufacturers to produce
further RAs for precise diagnosis and substantially improved immunotherapy
injection of only those allergens against which significant amounts of specific
IgE are produced.

Publication Types: 
    In Vitro

PMID: 10726734 [PubMed - indexed for MEDLINE]

1504: Ann Allergy Asthma Immunol. 2000 Feb;84(2):176-85; quiz 185-7.

Role for cysteinyl leukotriene receptor antagonist therapy in asthma and their
potential role in allergic rhinitis based on the concept of "one linked airway
disease".

Meltzer EO.

Allergy and Asthma Medical Group and Research Center, San Diego, California
92123, USA.

OBJECTIVE: This review focuses on the shared pathophysiology of asthma and
allergic rhinitis. The similarities illustrate the "one linked airway disease"
concept, a unifying theory of these upper and lower airway inflammatory
disorders. Since leukotrienes are mediators in both conditions, studies have been
performed to assess the potential therapeutic role of cysteinyl leukotriene
antagonists. The purpose of this paper is to provide an overview of the
accumulating data concerning these agents in treating asthma and allergic
rhinitis. DATA SOURCES: Relevant publications obtained from a literature review. 
STUDY SELECTION: Relevant publications on the topics of leukotrienes, leukotriene
receptor antagonists, asthma, and allergic rhinitis were critically evaluated.
RESULTS AND CONCLUSIONS: Studies to date have documented the efficacy of
cysteinyl leukotriene receptor antagonists for asthma. The pathophysiology of
allergic rhinitis and its similarities to asthma suggest that these agents could 
play a significant therapeutic role in managing this upper airway disorder.
Because the leukotriene antagonists are oral agents, they may be valuable in
treating not only either condition but also both at the same time when they
coexist. They appear to be beneficial when prescribed as the initial medicine and
when used in conjunction with other therapies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 10719774 [PubMed - indexed for MEDLINE]

1505: Eur Respir J. 2000 Jan;15(1):30-5.

Comment in:
    Eur Respir J. 2000 Aug;16(2):374.    Eur Respir J. 2000 Oct;16(4):793.

Bronchial hyperresponsiveness and airway inflammation markers in nonasthmatics
with allergic rhinitis.

Polosa R, Ciamarra I, Mangano G, Prosperini G, Pistorio MP, Vancheri C, Crimi N.

Istituto Malattie Apparato Respiratorio, University of Catania, Italy.

Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma which
is often associated with airways inflammation. However, some patients with
allergic rhinitis and no clinical evidence of asthma also exhibit BHR. This study
therefore investigated whether inflammatory cell infiltrate is present in the
induced sputum of nonasthmatic subjects with allergic rhinitis during the pollen 
season and examined its relationship with airway hyperresponsiveness to inhaled
methacholine and adenosine 5'-monophosphate (AMP). Twenty subjects (12 allergic
rhinitis, eight nonallergic controls) underwent methacholine and AMP challenge
and sputum induction with hypertonic saline on separate days. Cell differentials 
were calculated from whole sputum samples. A significantly greater number of
eosinophils was found in the sputum of nonasthmatic subjects with allergic
rhinitis compared to that of nonallergic controls, their median (range)
percentages being 17.5 (4-47) and 1.5 (0-5) (p<0.001) respectively. Although
sputum eosinophilia failed to be significantly associated with methacholine
responsiveness (r(s)=-0.50; p=0.095), the provocative concentration of AMP
causing a 20% fall in forced expiratory volume in one second correlated strongly 
and significantly with the absolute number of eosinophils (r(s)= -0.73; p=0.007).
Eosinophil cationic protein levels in the sputum of rhinitic subjects were
significantly elevated compared to controls and correlated with eosinophil number
(r(s)=0.67; p=0.017). These findings support the view that bronchial eosinophilia
alone is insufficient to cause asthmatic symptoms. Diverse agonists for assessing
bronchial hyperresponsiveness are selectively associated with airway inflammation
in allergic rhinitis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10678617 [PubMed - indexed for MEDLINE]

1506: J Epidemiol. 2000 Jan;10(1):42-7.

Exposure to Japanese cedar pollen in early life and subsequent sensitization to
Japanese cedar pollen.

Ozasa K, Dejima K, Hama T, Watanabe Y, Takenaka H.

Department of Social Medicine and Cultural Sciences, Kyoto Prefectural University
of Medicine, Japan.

The effect of exposure to Japanese cedar pollen (JCP) in early life on subsequent
sensitization to it was evaluated. Specific IgE antibody to JCP was examined in
440-504 school children in a rural town each year during 1995-98. The amount of
dispersed pollen measured by a Durham sampler widely ranged from 165 to 5941
grains/cm2/year during this period. The amount had been measured during the
period of 1982-91 in which these children were born, and it also widely ranged
from 148 to 8566 grains/cm2/year. Children born during November to January, who
were exposed to JCP within 6 months of age, increased at the risk of
sensitization to JCP, especially severe sensitization, relative to those born in 
the other months. Age-adjusted prevalence rate ratio (RR) of having a JCP-IgE >
or = 15 U/ml (control; < 0.35 U/ml) for children born in December to February
relative to children born in the other months was 1.74 (95% confidence interval; 
1.06-2.87, examined in 1998), and for those born in November to January was 1.57 
(95% CI; 1.00-2.46, examined in 1997). The risk of sensitization to JCP was low
for those born in May to July (RR = 0.42, 95% CI; 0.19-0.93, examined in 1998).
There was also a strong correlation between the amount of the dispersed pollen
during the period of 2-6 months after birth and the prevalence of sensitization
to JCP.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10695260 [PubMed - indexed for MEDLINE]

1507: Clin Exp Allergy. 2000 Mar;30(3):383-92.

The role of costimulatory molecules (B7-1 and B7-2) on allergen-stimulated B
cells in cedar pollinosis subjects.

Morikawa H, Nagashima S.

Department of Microbiology, Dokkyo University School of Medicine, Tochigi, Japan.

BACKGROUND: B7-1 (CD80) and B7-2 (CD86), which are costimulatory molecules in
T-cell activation, play important roles in the differentiation of TH1- or
TH2-phenotypes. These molecules were also suggested to play important roles in
sensitization to a cedar pollen antigen by blocking studies using neutralizing
antibodies, but there have been very few studies concerning the effects following
induction by antigen. OBJECTIVE: In this study, we investigated the roles of B7-1
and B7-2 in the differentiation of TH1 and TH2 subsets after stimulation with the
antigen in subjects with cedar pollinosis. METHODS: Skin-prick test was performed
in nine subjects with pollinosis and in nine normal controls. Peripheral blood
mononuclear cells (PBMCs) were isolated and stimulated with Japanese cedar pollen
extract. After in vitro stimulation, the expression of CD80 and CD86 on CD19+
cells was analysed by two-colour flow cytometry. Culture supernatants were
collected for all subjects and the production of type 1 and type 2 cytokines was 
measured by ELISA. RESULTS: After in vitro stimulation, the expression of CD80
(B7-1) was upregulated in both pollinosis and control subjects, but no
significant difference was observed between the two groups. On the other hand,
CD86 (B7-2) was significantly upregulated following stimulation in pollinosis
subjects (P = 0.02). A significantly higher level of IL-5 (P = 0.04) was produced
by PBMCs of pollinosis subjects than by those of normal controls. A significantly
higher level of interferon (IFN)-gamma (P = 0.03) was produced by PBMCs of normal
controls than by those of pollinosis subjects. CONCLUSION: These results
indicated that TH2 response was predominant in pollinosis subjects, and that
CD19+ cells of pollinosis subjects expressed higher levels of B7-2 than those of 
control subjects after in vitro stimulation. In pollinosis subjects, B7-2 rather 
than B7-1 may be the costimulatory molecule involved in allergen-induced
activation of PBMCs.

PMID: 10691897 [PubMed - indexed for MEDLINE]

1508: Ann Allergy Asthma Immunol. 2000 Jan;84(1):55-62.

A cost-benefit analysis using a willingness-to-pay questionnaire of intranasal
budesonide for seasonal allergic rhinitis. Rhinocort Study Group.

Keith PK, Haddon J, Birch S.

McMaster University, Hamilton, Ontario, Canada.

BACKGROUND: The cost-benefit of intranasal steroids for the treatment of seasonal
allergic rhinitis is unknown. OBJECTIVE: To determine the cost-benefit of
intranasal budesonide for seasonal allergic rhinitis. METHODS: Subjects who were 
symptomatic for a baseline period of 7 to 10 days were randomized to receive
intranasal budesonide by Turbuhaler (400 microg) (n = 121) or aqueous spray (256 
microg) (n = 121) once daily for 4 weeks. A willingness-to-pay questionnaire that
measured benefits of treatment was administered before and at study completion.
Costs were collected and compared with benefits. RESULTS: Subjects were willing
to spend on average $15.89/wk (range $1 to $75) to alleviate the problems of
seasonal ragweed rhinitis. Eighty percent of subjects felt that, with treatment, 
rhinitis had less of an impact on their lives, compared with previous years. The 
mean willingness-to-pay for the drug used during another ragweed season was
$12.95/wk. This was 92% (95% CI, 85% to 100%) of the pre-treatment estimate.
There was no relationship between an indirect assessment of income and
willingness-to-pay estimates. The benefit was greater than the cost by a mean of 
$5.80/wk (95% CI, $3.52 to 8.08), P < .0001. There was no difference in costs,
willingness-to-pay, or cost-benefit comparing delivery modes. A sensitivity
analysis revealed the conclusions were robust. CONCLUSIONS: Intranasal budesonide
is cost-beneficial in the treatment of seasonal allergic rhinitis and a
willingness-to-pay questionnaire may provide a useful method to assess a
therapy's benefit.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 10674566 [PubMed - indexed for MEDLINE]

1509: J Allergy Clin Immunol. 2000 Feb;105(2 Pt 1):339-45.

In vitro diagnosis of cypress pollen allergy by using cytofluorimetric analysis
of basophils (Basotest).

Pâris-Köhler A, Demoly P, Persi L, Lebel B, Bousquet J, Arnoux B.

INSERM U454-IFR3, CHU Montpellier, France.

BACKGROUND: Cupressaceae pollen allergy is a worldwide pollinosis, but its in
vitro diagnosis is notoriously difficult. The Basotest is a newly available in
vitro test for the detection of allergen-specific IgE based on the level of
cellular activation of basophils by using flow cytometry. OBJECTIVES: The
Basotest was compared with the measurement of cypress pollen-specific IgE in
highly selected patients. METHODS: We analyzed 34 patients allergic to cypress
pollen selected on the basis of a suggestive clinical history and positive skin
test and nasal challenge responses to cypress pollen extract. We also analyzed 8 
patients with positive skin test responses to cypress pollen extract who did not 
present symptoms during the pollen season (intermediate group) and 33 control
subjects. Sensitivity, specificity, and efficiency of the Basotest and
serum-specific IgE levels measured by using the CAP System were determined in
patients allergic to cypress pollen. Histamine release was studied in a selected 
group of patients. RESULTS: The Basotest was more sensitive (91.2%) than the CAP 
System (76%) for the in vitro diagnosis of cypress pollen allergy. A
dose-response curve was observed in basophils obtained from patients allergic to 
cypress pollen. There were no false-positive results with either test
(specificity 100%). The results of the Basotest or those of the CAP System did
not correlate with the patients' in vivo threshold sensitivity assessed by skin
tests and nasal challenge. CONCLUSIONS: The Basotest was found to be an effective
diagnostic test in patients allergic to cypress pollen.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10669856 [PubMed - indexed for MEDLINE]

1510: J Allergy Clin Immunol. 2000 Feb;105(2 Pt 1):211-23.

Molecular pathology of allergic disease. II: Upper airway disease.

Christodoulopoulos P, Cameron L, Durham S, Hamid Q.

Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.

Allergic upper airway diseases such as allergic rhinitis and chronic sinusitis
are an increasing problem. Although the pathogenesis remains elusive, an
individual's genetic predisposition as well as exposure to the allergen are
currently considered factors in their development. Clinical symptoms of sneezing,
rhinorrhea, and congestion are primarily a consequence of granulocyte release of 
chemical mediators such as histamine, prostanoids, and leukotrienes as well as
the infiltration of inflammatory cells. Observations subsequent to allergen
provocation are comparable to natural exposure and as such much of our
understanding of allergic responses is derived from this model. A prominence of
CD4(+) T cells and eosinophils, synthesis and release of T(H)2 cytokines, and the
coordinate expression of chemokines and adhesion molecules are all characteristic
of the allergic response observed in rhinitis and sinusitis. Corticosteroids and 
immunotherapy target these inflammatory processes and have been observed to
successfully reduce and shift the predominantly T(H)2 environment toward T(H)1
cytokine expression. As our understanding of the pathophysiologic features of
allergic upper airway disease improves, as well as the relationship between their
development and that of lower airway disease, new strategies of diagnosis and
treatment will allow for more effective modulation of the allergic process and
associated morbidity.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 10669839 [PubMed - indexed for MEDLINE]

1511: ORL J Otorhinolaryngol Relat Spec. 2000 Jan-Feb;62(1):33-8.

Intranasal histamine challenge in normal subjects and allergic rhinitis before
and after intranasal budesonide studied with rhinostereometry and
micromanipulator-guided laser Doppler flowmetry.

Grudemo H, Juto JE.

Department of Otorhinolaryngology, Huddinge University Hospital, Karolinska
Institute, Stockholm, Sweden.

Ten healthy subjects and 10 patients suffering from allergic rhinitis to birch
pollen were investigated with the combination of rhinostereometry and laser
Doppler flowmetry, thus simultaneously measuring changes in mucosal swelling and 
microcirculation, following intranasal histamine challenge. Compared to normals, 
the allergies had a higher degree of congestion and a lower increase in perfusion
and velocity of flow. In the allergies there was a decrease in CMBC
(concentration of moving blood cells) that was not seen in normals. The decrease 
in CMBC seen in allergies could be attributed to an increase in vascular
permeability producing an interstitial edema, a well-known effect of histamine.
After treatment with 1 week of intranasal steroid, most of the differences in the
reaction pattern between normals and allergies had disappeared.

PMID: 10654315 [PubMed - indexed for MEDLINE]

1512: Scand J Immunol. 2000 Feb;51(2):202-8.

Allergen induced mRNA expression of interleukin-5, but not of interleukin-4 and
interferon-gamma, in peripheral blood mononuclear cells obtained before the
pollen season predicts the clinical efficacy of immunotherapy for seasonal
allergic rhinitis.

Kakinoki Y, Ohashi Y, Nakai Y, Washio Y, Nasako Y, Tanaka A, Nakai Y.

Department of Otolaryngology, Osaka City University Medical School, 1-4-3
Asahimachi, Abeno, Osaka 545-8585, Japan.

The primary aim of this study was to investigate whether the allergen-induced
synthesis of cytokines by peripheral blood mononuclear cells (PBMCs) obtained
immediately before the pollen season could predict the clinical efficacy of
immunotherapy during the following pollen season. PBMCs (1.0 x 106 cells/ml) were
obtained from 17 nonatopic subjects and from 60 patients receiving immunotherapy 
for seasonal allergic rhinitis (caused by Japanese cedar pollens) immediately
before the pollen season of 1998, and were cultured for 24 h in the presence of
10 mg/ml of Cry j 1, a major allergen of Japanese cedar pollens, at 37 degrees C 
in a fully humidified 5% CO2 atmosphere. Total cellular RNA was extracted from
the PBMCs, and the allergen-induced interleukin (IL)-4, IL-5 and interferon-gamma
(IFN-gamma) mRNA expression was determined using a reverse
transcription-polymerase chain reaction. According to the nasal symptoms during
the pollen season of 1998, the 60 patients on immunotherapy were divided into 36 
good responders (who had no nasal symptoms and no requirement for rescue
medications) and 24 poor responders who needed rescue medications to control
nasal symptoms. Neither IL-4 mRNA nor IL-5 mRNA was expressed in any of the 17
nonatopic individuals. By contrast, IL-4 mRNA was expressed in 26 good responders
and in 22 poor responders, and IL-5 mRNA was expressed in eight good responders
(22.2%) and in 23 poor responders (95.8%). IFN-gamma mRNA was expressed in four
nonatopic subjects, in nine good responders and in seven poor responders. The
expression of IFN-gamma did not differ significantly among the nonatopic
subjects, the good responders and the poor responders. The mRNA expression of
IL-5 (P < 0.0001), but not of IL-4 (P = 0.0999) and IFN-gamma (P = 0. 7713),
differed significantly between the good and poor responders. Therefore, our study
has highlighted that positive expression of IL-5 mRNA in PBMCs sampled
immediately before the pollen season could be predictive of a poor clinical
outcome of immunotherapy during the following pollen season and that the
down-regulation of IL-5 mRNA expression in PBMCs could be an important mechanism 
of pollen immunotherapy related to the clinical efficacy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10652165 [PubMed - indexed for MEDLINE]

1513: Clin Exp Allergy. 2000 Feb;30(2):242-54.

Phleum pratense-specific T cells of allergic rhinitis patients display a broader 
recognition pattern than phleum pratense-specific serum immunoglobulin E.

Van Neerven RJ, Arnved J, Ipsen H.

ALK-Abelló, Horsholm, Denmark; Current address: Tanox Pharma BV, Amsterdam, The
Netherlands.

BACKGROUND: The role of allergen-specific CD4+ T lymphocytes in the
pathophysiology of atopic disease is well established. Previous studies on
allergen-specific T-cell responses have focused on the recognition of single
major allergens to identify T-cell epitopes. OBJECTIVE: However, it is not clear 
whether immune responses to allergen extracts are exclusively targeted at major
allergens or whether additional proteins are recognized. METHODS: Here we
describe the Phleum pratense-specific immunoglobulin E (IgE) and T-cell responses
of six allergic rhinitis patients. Reactivity was measured to size-separated
fractions of a P. pratense extract as well as to the purified major allergens Phl
p 1, Phl p 2/3 and Phl p 5. RESULTS: The specificity of the patients' serum IgE, 
measured in a fluid phase assay, was restricted to one or two of the major
allergens. Even though the majority of the patients had IgE antibodies reactive
with a single major allergen, one patient reacted with both Phl p 5 and with Phl 
p 2/3. Analysis of the T-cell repertoire with P. pratense-specific T-cell lines
(TCLs) and CD4+ T-cell clones (TCCs) revealed that at least six different
proteins were recognized, including the three major allergens, most notably Phl p
5. Simultaneous production of IL-5 and interferon (IFN) -gamma was detected in
supernatants of the TCLs stimulated with P. pratense extract and the major
allergens. CONCLUSION: These results indicate that allergic rhinitis patients
have a large pool of circulating allergen-specific CD4+ T cells that recognize
many different proteins in an allergenic extract, whereas only a small number of 
these proteins are recognized by serum IgE.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10651777 [PubMed - indexed for MEDLINE]

1514: Clin Exp Allergy. 2000 Feb;30(2):194-200.

Comment in:
    Clin Exp Allergy. 2000 Feb;30(2):153-7.

Austrian children living on a farm have less hay fever, asthma and allergic
sensitization.

Riedler J, Eder W, Oberfeld G, Schreuer M.

Paediatric Pulmonology, Children's Hospital Salzburg, Austria.
j.riedler@lkasbg.gv.at

BACKGROUND AND OBJECTIVES: In some studies, the prevalence of hay fever and
asthma has been found to be lower in children from rural areas than in children
from an urban environment. We hypothesized that living on a farm might be
protective against development of allergic sensitization and allergic diseases.
METHODS: In a cross-sectional survey, parents of 2283 children aged 8-10 years
from a mostly rural area in Austria answered a standardized questionnaire on
allergic diseases and environmental factors. 1137 children performed a skin prick
test to seven local allergens. RESULTS: The prevalence of hay fever (3.1 vs
10.3%, P = 0.0002), asthma (1.1 vs 3.9%, P = 0.017) and a positive skin prick
reactivity to at least one of the common local allergens (18.8 vs 32.7%, P = 0.
001) was significantly lower in children living on a farm than in children from a
non-farming environment. In a multivariate logistic regression model, adjusting
for genetic background, parent education, living and housing conditions and
dietary factors did not change the odds ratio for the association of farming and 
allergic sensitization. Only after including 'regular contact with livestock and 
poultry' into the model did the odds ratio change significantly (cOR 0.48 95% CI 
0.30-0.75 to aOR 0.75 95% CI 0.37-1.52) indicating an association between regular
contact with farm animals and reduced risk of atopic sensitization. CONCLUSION:
Possible explanations for the lower prevalence of hay fever, asthma and allergic 
sensitization in children living on a farm might be the development of
immunotolerance or the stimulation of TH1 cells and suppression of TH2 cells by
increased exposure of farm children to microbial antigens in the stables or
farmhouses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10651771 [PubMed - indexed for MEDLINE]

1515: Clin Exp Allergy. 2000 Feb;30(2):187-93.

Comment in:
    Clin Exp Allergy. 2000 Feb;30(2):153-7.

Reduced risk of hay fever and asthma among children of farmers.

Von Ehrenstein OS, Von Mutius E, Illi S, Baumann L, Böhm O, von Kries R.

University Children's Hospital, Ludwig Maximilians University.
u7r11a1@mail.lrz-muenchen.de

BACKGROUND: The prevalence of atopic diseases is on the rise. Traditional
lifestyles may be associated with a reduced risk of atopy. OBJECTIVES: To test
the hypothesis that children living on a farm have lower prevalences of atopic
diseases. To identify differences in living conditions between farmers and other 
families which are associated with the development of atopic conditions. DESIGN: 
Cross-sectional survey among children entering school (aged 5-7 years). A written
questionnaire including the ISAAC core questions and asking for exposures on a
farm and elsewhere was administered to the parents. Setting: School health entry 
examination in two Bavarian districts with extensive farming activity. Subjects: 
10 163 children. MAIN OUTCOME MEASURES: The prevalence of doctor's diagnoses and 
symptoms of hay fever, asthma and eczema as assessed by parental report. RESULTS:
Farmers' children had lower prevalences of hay fever (adjusted odds ratio = 0.
52, 95% CI 0.28-0.99), asthma (0.65, 0.39-1.09), and wheeze (0.55, 0. 36-0.86)
than their peers not living in an agricultural environment. The reduction in risk
was stronger for children whose families were running the farm on a full-time
basis as compared with families with part-time farming activity. Among farmers'
children increasing exposure to livestock was related to a decreasing prevalence 
of atopic diseases (aOR = 0.41, 95% CI 0.23-0.74). CONCLUSIONS: Factors related
to environmental influences on a farm such as increased exposure to bacterial
compounds in stables where livestock is kept prevent the development of allergic 
disorders in children.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10651770 [PubMed - indexed for MEDLINE]

1516: J Allergy Clin Immunol. 2000 Jan;105(1 Pt 1):54-7.

Minimal persistent inflammation is also present in patients with seasonal
allergic rhinitis.

Ricca V, Landi M, Ferrero P, Bairo A, Tazzer C, Canonica GW, Ciprandi G.

Allergy Section, Koellider Hospital, Turin, Italy.

BACKGROUND: The allergic reaction is characterized by an inflammatory response,
which is correlated to the allergen exposure, and is detectable in mite allergic 
patients, even when symptoms are absent. OBJECTIVE: The study was aimed at
assessing the presence of inflammation in patients with pollen allergy during a
long observation period. METHODS: Six patients, sensitized only to Betula alba,
were enrolled. Evaluated parameters were (1) nasal symptoms, (2) inflammatory
markers (ie, neutrophil and eosinophil number and intercellular adhesion
molecule-1 expression on nasal epithelial cells), and (3) pollen count. Patients 
were examined during the pollen season every 4 days for 40 days and were observed
3 times after the pollen season. RESULTS: A significant inflammatory reaction was
evident throughout the pollen season, even during the days with a low pollen
count and low or absent symptoms. CONCLUSIONS: The results of this study indicate
that the global therapeutic strategy for allergic rhinitis should be revised and 
targeted to inflammatory phenomena rather than to symptoms alone.

PMID: 10629452 [PubMed - indexed for MEDLINE]

1517: Clin Exp Allergy. 2000 Jan;30(1):86-93.

In vivo expression of signal transducer and activator of transcription factor 6
(STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical
corticosteroids.

Ghaffar O, Christodoulopoulos P, Lamkhioued B, Wright E, Ihaku D, Nakamura Y,
Frenkiel S, Hamid Q.

Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.

BACKGROUND: The allergen-induced late nasal response is associated with a high
local expression of interleukin (IL) -4, a TH2-type cytokine implicated in
immunoglobulin (Ig) E production, tissue eosinophilia and other events considered
to be relevant to allergic inflammation. Interaction of IL-4 with its receptor
activates at least two distinct signalling pathways that culminate in the
transcription of specific target genes. One pathway involves the activation of a 
transcription factor termed signal transducer and activator of transcription
factor 6 (STAT6). OBJECTIVE: To investigate the expression of STAT6 in the
allergen-induced late nasal response and to examine the effect of local steroid
treatment on STAT6 expression. METHODS: Inferior turbinate biopsies were obtained
from subjects with allergic rhinitis out of the allergen season. Subjects were
then randomized into topical steroid- (n = 6) and placebo-treated (n = 6) groups 
in a double-blind fashion. After a 6-week treatment period, a second nasal biopsy
was performed 24 h after local challenge with allergen. STAT6 immunoreactivity
was examined in biopsy specimens by immunocytochemistry using a specific
monoclonal antibody. Numbers of inflammatory cells (CD3+ T cells and MBP+
eosinophils) and IL-4 mRNA+ cells were investigated by immunocytochemistry and in
situ hybridization, respectively. RESULTS: STAT6 immunoreactivity was detected in
all biopsies studied and localized predominantly to inflammatory tissue of the
nasal mucosa. After allergen challenge, expression of STAT6 was markedly
increased in placebo-treated patients (P < 0.01). By confocal microscopy, STAT6
was localized to the cytoplasm and the nucleus of positively-staining cells. The 
allergen-induced increase in STAT6 immunoreactive cells was not observed in the
steroid-treated patients. The change in STAT6 immunoreactivity after allergen
challenge correlated significantly with the change in numbers IL-4 mRNA+ cells (r
= 0.74, P = 0.006) and CD3+ T cells (r = 0.76, P = 0. 004), but not MBP+
eosinophils. CONCLUSION: This study provides the first evidence of increased
STAT6 expression in vivo in human allergic inflammation. The results support a
role for STAT6 and IL-4 in the pathogenesis of late nasal response and show that 
decreases in STAT6 expression parallel the reduction in IL-4 expression that
occurs with topical steroid treatment.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10606935 [PubMed - indexed for MEDLINE]
