Asmanet ENFUMOSA : C. Pison Severe asthma in adult and children : an approach with the Epidemiological study of the Genetics and Environment of Asthma (EGEA).

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màj 28/07/99

ENFUMOSA
(courriel: Chanez (at) montp.inserm.fr )
The European Network For Understanding
Mechanisms of Severe Asthma
BIOMED 2 Program - European Commission

4th quaterly meeting, with the support of INSERM and
Merck Sharp & Dhome Laboratory
February 13-14th 1998 in Montpellier- France
(see programm, abstracts and experts comments )

Severe asthma in adult and children : an approach with
the Epidemiological study of the Genetics and
Environment of Asthma (EGEA).
Ch. Pison, I. Pin, I. Annesi, C. Cans, F. Gormand,
M. Gousset, E. Paty, F. Kauffmann .
CHU Grenoble, Lyon, Necker, Unit INSERM U169, France

Vendredi 13 Février 1988		Présentateurs/Speakers		Modérateurs	Experts
10h30-11h30	Epidémiologie - Génétique	F. Demenais (Paris) C. Pison (Grenoble) Discussion (see abstract/résumé)	15' 15' 30'	D. Charpin (Marseille) Ph Godard (Montpellier)	J. Anton (Barcelone, E) G. Koppelman (Groningen, NL)

Asthma is a common disease affecting 4.5% of the adult european population (1) and more than 10% of the children (2). The prevalence and severity of asthma appears to be increasing (2). The socioeconomic consequences of severe asthma are significant and place a large burden on both affected individuals and society even if this phenotype is rare. For example, in Canada it is estimated that 10 % of asthmatics who are severe accounted for roughly 51% of all direct medical care expenditures and 54 % of total asthma costs (3). Since the changes in prevalence and severity are too rapid to be explained readily by changes in the gene pool, the operation of important environmental factors is suggested. In order to better understand the relative role of environment and genetics in asthma, bronchial hyperresponsiveness and atopy, the French cooperative Epidemiologic study of the Genetics and Environment of Asthma or EGEA study was designed as a combination of a case-control and a family study (4). Patients with asthma ascertained from chest clinics of 5 cities (Paris, Lyon, Marseille, Montpellier and Grenoble) and their first-degree relatives and spouses were examined with a standard protocol based on international standardized tools. Control subjects matched for age, month of exam, and city were evaluated with the same protocol. All probands and their two parents were born in France. Family structure (either proband with a spouse and at least one child, or proband with at least one sibling and 2 parents) and a positive answer to 4 questions (i-Have you ever had attack of breathessness at rest with wheezing ? ii-Have you ever had asthma attacks ? and if yes, iii-Was this diagnosis confirmed by a physician ? iv-Have you had an asthma attack in the last 12 months ?) were needed to include probands. Cases (213 adults, 135 children), relatives, spouses, and control subjects (416) totaled 1,854. Data collected included a detailed questionnaire on upper and lower airway symptoms, allergic symptoms, childhood events including infections, medical history, and environmental factors. Environmental data included active smoking, passive smoking, presence of domestic animals during childhood and at present, pollen exposure, area and month of survey, indoor moisture, home characteristics related to dust-mite exposures, type of heating and cooking fuel, occupational exposure known to be related to respiratory diseases, and occupation and industry in the last two jobs. A methacholine challenge was performed if FEV1 > 80% predicted. Skin prick tests to 11 allergens, total IgE levels, multiRAST Phadiatop test, leukocyte differential count were performed.

The first challenge in describing the epidemiology of severe asthma is to define severity. According to Stein, asthma severity could be defined through 4 dimensions : biological severity, physiological severity, functional severity, and burden of illness (5). In order to look later for the genetic and environmental factors of severity in adult asthmatics, we built a severity classification with an a-priori decisionnal tree based on recommended clinical guidelines including symptoms and physiological items (6). Treatments used by the asthmatics were not included in this severity classification which is quite different from the GINA perspective where the patients are classified before anti-asthmatic treatment (6).

For the present analysis all asthmatic adults from the EGEA study were studied (probands, relatives, spouses and controls) who answered yes to either : Have you ever had attack of breathessness at rest with wheezing ? or Have you ever had asthma attacks ? There were 410 adult asthmatics (213 probands, 154 relatives, 5 spouses, 38 controls. They were 38±13 year old, 52% were male. If we consider the frequency of attacks, 44% of adults and 18% of children reported an attack frequency of at least one per week. 36% of adults and 38% of the children had been previously hospitalized for asthma, 15% and 7% respectively, during the last 12 months. 11% of adult asthmatics had a FEV1 ² 60% predicted whereas only 17% of children with asthma had a FEV1 ² 80% predicted. Inhaled steroids treatment in the last 12 months were used by 77% of the adults and 57% by the children. We found strong relationships between asthma severity items such as hospitalization or FEV1 to treatment intensity (oral corticosteroids in the past year and inhaled corticosteroids). Asthmatics were classified as severe if they experienced more than 1 asthma attack per week and breathlessness with activity limitation between attacks or severe dyspnea on exercise, or FEV1 < 60% predicted, or hospitalization in the past year for asthma, or at least once in the ICU. On the opposite, they were considered as mild asthmatics if they had less than 1 attack per week and no persisting symptoms between attacks, and no dyspnea on exercise, and FEV1 ³ 80% predicted. The remaining asthmatics were classified as intermediate. Severe asthma were 24,6% and mild 19% in the EGEA study underlining the recruitment of the asthmatic cases in the out-patient clinics of university hospitals. When comparing mild to severe asthmatics, severe asthmatics had a higher risk for nighttime symptoms (OR 8.8 for the item attack of breathlessness at night), a higher intensity in treatment (OR 23.1 for the item inhaled corticosteroids over the pasrt year). They were older but there was no difference in the sex ratio. Severity classification for asthmatic children is in progress. A different procedure is needed as the usual guidelines seem to be inadequate since there was no with a FEV1 ² 60% for example.

Various environmental and genetic factors likely determine both the incidence and severity of asthma. The present classification of asthma severity will be used to analyse the environmental factors and genetic factors using the data collected in the EGEA study, both by the case control and familial approaches.

Ref (1): European Community Respiratory Health Survey.Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma medication in the European Community Respiratory Health Survey (ECRHS). Eur Respir J, 1996, 9, 687-95. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Source : Eur Respir J, 9(4):687-95 1996 Apr
Abstract : Asthma is a common chronic disorder which may be increasing in prevalence. However, little is known of its distribution and determinants. The European Community Respiratory Health Survey (ECRHS) is a multicentre survey of the prevalence, determinants and management of asthma. This paper presents a descriptive account of the variation in self-reported attacks of asthma and asthma symptoms across Europe, and in part fulfils the first aim of the study. A screening questionnaire, including seven questions relating to the 12 month prevalence of symptoms of asthma, was distributed to representative samples of 20-44 year old men and women in 48 centers, predominantly in Western Europe. The median response rate to the questionnaire was 75% but, after removing from the denominator those who were the wrong age, were known to have moved out of the area, or had died, it was 78% (range 54-100). The prevalence of all symptoms varied widely. Although these were generally lower in northern, central and southern Europe and higher in the British Isles, New Zealand, Australia and the United States, there were wide variations even within some countries....

Ref (2): Sears MR. Epidemiological trends in bronchial asthma. In MA Kaliner, PJ Barnes, and CGA Person, editors. Asthma. Its pathology and treatment. Marcel Dekker, New York, 1991, 1-49. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Ref (3): Moore BD, Weiss KB, Sullivan SD. Epidemiology and socioeconomic impact of severe asthma. In SJ Szefler, and DYM Leung editors. Severe asthma : pathogenesis and management. Marcel Dekker, New York, 1996, 1-34. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Ref (4): Kauffmann F, Dizier M-H, Pin I, Paty E, Gormand F, Vervloet D, Bousquet J, Neukirch F, Annesi I, Oryszczyn M-P, Lathrop M, Demenais F, Lockhart A, Feingold J. Epidemiological study ot he genetics and environment of asthma, bronchial hyperrespnsiveness, and atopy. Phenotypes issues. Am J Respir Crit Care Med, 1997, 156, S123-9. (partial abstract from http://www.healthy.net/library/search/medline.htm )

Author : Stein RE; Gortmaker SL; Perrin EC; Perrin JM; Pless IB; Walker DK; Weitzman M
Address : Preventive Intervention Research Center for Child Health, Albert Einstein College of Medicine, Bronx, NY 10461.
Source : Lancet, 2(8574):1506-9 1987 Dec 26

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Date de création: 5 Décembre 1997-Dernière mise à jour: 28/07/99Le secret des correspondances transmises sur le réseau Internet n'est pas garanti. Toute personne citée dispose d'un droit d'accès, de modification, de rectification et de suppression des données le concernant (art. 34 de laloi "Informatique et Libertés"n° 78-17 du 6 janvier 1978). Pour l'éxercer adressez-vous àMichel Godard (at)