Epidemiological study of the genetics and environment of asthma, bronchial hyperresponsiveness, and atopy: phenotype issues.

The Epidemiological Study of the Genetics and Environment of Asthma (EGEA) combined a case-control study and a family study. The total sample of 1,854 consisted of 348 patients with asthma selected through chest clinics and 416 control subjects and nuclear families ascertained through the cases. The protocol included standardized questionnaires, bronchial responsiveness, allergen skin-prick tests according to international protocols, total serum immunoglobulin E (IgE) level measurements, and blood eosinophilia. Criteria used to select subjects with asthma and determine asthma status of relatives for affected sibling pair linkage analysis are described. Based on figures from the 348 asthma cases of the EGEA study, issues relative to the definition of severe asthma and intermediate phenotypes such as bronchial responsiveness and allergic markers are discussed. Given the phenotypic heterogeneity involved, relevant phenotypes that may lead to the detection of genetic factors will depend on the hypothesis tested. Standardization of primary data and subphenotypes is a prerequisite for pooling data, which will be needed in the future to better understand the genetics and environmental factors of asthma.