Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)

doi:10.1067/mai.2002.121317

Journal of Allergy and Clinical Immunology

Volume 109, Issue 2, February 2002, Pages 251-256

https://doi.org/10.1067/mai.2002.121317 Get rights and content

Abstract

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. (J Allergy Clin Immunol 2002;109:251-6.)

Section snippets

Patients

A total of 208 children aged 6 to 14 years from European 6 pediatric centers were included in the study; of these, 205 were randomized after a baseline season (season 0; Table I).

. Patient demographic data at inclusion

Empty Cell	All included	No asthma	Asthma*
No. of patients	208 (205)†	163	42
Age (y): mean (range)	10.7 (6-15)	10.7 (6-15)	10.6 (6-14)
Sex: male/female	138/70 (137/68)†	108/55	29/13
Years with hay fever: mean (range)	4.7 (1-15)‡	4.6 (1-15)‡	4.9 (1-9)‡
	N = 171	N = 137	N = 34
Methacholine PC₂₀: mean (range)	10.8

Results

Forty-three patients were allergic to birch, 124 were allergic to grass, and 41 were allergic to both birch and grass. Before SIT, despite negative histories of asthma with need of daily medication at screening, 40 children (20%) were identified as having mild asthma. These mild seasonal asthmatic symptoms would probably not even now have been identified if the patients had not been enrolled in the study. According to the skin prick test results, the average number of sensitivities other than

Discussion

This study shows that SIT in children with rhinoconjunctivitis without asthma reduced the risk for later development of asthma. Because SIT for hay fever can prevent allergic asthma, it appears that allergic rhinoconjunctivitis and allergic asthma are different manifestations of the same disease. Children with hay fever but without asthma with need of daily medication were selected for the study. When they were initially challenged with methacholine during seasonal exposure, we found a very

Acknowledgements

Special thanks to Jannik Godt, MSc, for excellent and very qualified statistical support and to ALK-Abelló for sponsoring this study.

References (34)

FE. Simons
Allergic rhinobronchitis: the asthma-allergic rhinitis link
J Allergy Clin Immunol
(1999)
RG Townley et al.
Bronchial sensitivity to methacholine in current and former asthmatic and allergic rhinitis patients and control subjects
J Allergy Clin Immunol
(1975)
RG Townley et al.
Comparative action of acetylbeta-methylcholine, histamine, and pollen antigens in subjects with hay fever and patients with bronchial asthma
Allergy Proc
(1965)
E Madonini et al.
Seasonal increase of bronchial reactivity in allergic rhinitis
J Allergy Clin Immunol
(1987)
SS Braman et al.
Airway hyperresponsiveness in allergic rhinitis. A risk factor for asthma
Chest
(1987)
S Rak et al.
The effect of immunotherapy on bronchial hyperresponsiveness and eosinophil cationic protein in pollen-allergic patients
J Allergy Clin Immunol
(1988)
AA Gerblich et al.
Seasonal variation of airway function in allergic rhinitis
J Allergy Clin Immunol
(1986)
A Des Roches et al.
Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children
J Allergy Clin Immunol
(1997)
A. Togias
Mechanisms of nose-lung interaction
Allergy
(1999)
PA Pedersen et al.
Asthma and allergic rhinitis in the same patients
Allergy
(1983)

FM Rackemann et al.

Asthma in Children. A Follow-up Study of 688 Patients After An Interval of Twenty Years

N Engl J Med

(1952)

O Linna et al.

A 10-year prognosis for childhood allergic rhinitis

Acta Paediatr

(1992)

EH Ramsdale et al.

Asymptomatic bronchial hyperresponsiveness in rhinitis

J Allergy Clin Immunol

(1985)

HA Ferdousi et al.

Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis. ECP and EPX levels are not related to bronchial hyperreactivity

Clin Exp Allergy

(1997)

PA Pedersen et al.

Asthma and allergic rhinitis in the same patients

Allergy

(1983)

RJ Settipane et al.

Long-term risk factors for developing asthma and allergic rhinitis: a 23-year follow-up study of college students

Allergy Proc

(1994)

BN Petersen et al.

Immunotherapy with partially purified and standardized tree pollen extracts. I. Clinical results from a 3-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel

Allergy

(1988)

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^☆: Reprint requests: Christian Möller, MD, PhD, Department of Paediatrics, S-901 85 Umeå, Sweden.

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Asthma, Rhinitis, Other Respiratory DiseasesPollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)☆

Abstract

Section snippets

Patients

Results

Discussion

Acknowledgements

J Allergy Clin Immunol

J Allergy Clin Immunol

Allergy Proc

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Mechanisms of nose-lung interaction

Allergy

Asthma and allergic rhinitis in the same patients

Allergy

Asthma in Children. A Follow-up Study of 688 Patients After An Interval of Twenty Years

N Engl J Med

A 10-year prognosis for childhood allergic rhinitis

Acta Paediatr

Asymptomatic bronchial hyperresponsiveness in rhinitis

J Allergy Clin Immunol

Asthma, bronchial hyperreactivity and mediator release in children with birch pollinosis. ECP and EPX levels are not related to bronchial hyperreactivity

Clin Exp Allergy

Asthma and allergic rhinitis in the same patients

Allergy

Long-term risk factors for developing asthma and allergic rhinitis: a 23-year follow-up study of college students

Allergy Proc

Immunotherapy with partially purified and standardized tree pollen extracts. I. Clinical results from a 3-year double-blind study of patients treated with pollen extracts either of birch or combinations of alder, birch and hazel

Allergy

Asthma, Rhinitis, Other Respiratory Diseases
Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)☆