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.
Both logistic regression and Cox proportional hazards models are used widely in longitudinal epidemiologic studies for analysing the relationship between several risk factors and a time-related dichotomous event. The two models yield similar estimates of regression coefficients in studies with short follow-up and low incidence of event occurrence. Further, with just one dichotomous covariate and identical censoring times for all subjects, the asymptotic relative efficiency of the two models is very close to 1 unless the duration of follow-up is extended. We generalize this result to several qualitative or quantitative covariates. This was motivated by the analysis of mortality data from a study where all subjects are followed up during the same fixed period without loss except by death. Logistic and Cox models were applied to these data. Similar results were obtained for the two models in shorter periods of follow-up of five years or less, but not in longer periods of ten years or more, where the survival rate was lower.
The relationship between smoking and percentages and counts of T-cell subsets, in particular CD45R0+ (memory) and CD45RA+ (naive) CD4+ lymphocytes, have been assessed in a sample of 311 middle-aged men working in the Paris area. Percentages of lymphocytes with the phenotypes CD4+, CD8+, CD4+CD45R0+, and CD4+CD45RA+ were determined using double immunofluorescence labeling. All cell counts, including CD4+CD45R0+, and CD4+CD45RA+ lymphocytes increased significantly with tobacco consumption, as did the percentages of lymphocytes with the CD4+CD45R0+ and CD4+ phenotypes. The increase in the percentage of lymphocytes with the CD4+CD45RA+ phenotype, although not significant, was similar to that observed in the percentage of CD4+CD45R0+ lymphocytes. When the proportions of CD4+ cells with the CD45R0+ or the CD45RA+ phenotype were considered, no specific modification of any of these two sub-populations was observed: the effect of smoking on memory and naive Cd4+ lymphocytes seemed to be equivalent.
In preparation for a mass vaccination programme, the immune status with regard to measles was determined in over 8300 unvaccinated children aged 0-13 years, residing in eight Italian cities with different socioeconomic situations and geographical locations. The age corresponding to the 50% prevalence of immunes appeared to be intermediate (2.9-5.5 years) between that reported for industrialized (6-7 years) and developing countries (1-2 years). The 50% prevalence of natural immunity was reached at an earlier age in southern cities in which poorer socioeconomic and hygienic conditions prevailed; the earlier occurrence of measles in these areas was confirmed by a more detailed serological study of children in the first 24 months of life. For children aged 2-13 years, serological results showed that the history of measles reported by parents on questionnaires gave high positive predictive values (over 85%). Our seroepidemiological study shows that, on the basis of the ages of 25 and 75% prevalence of immunes, the target population for a mass immunization programme in Italy can be assumed to be aged from 12 months to 7 years. However, special attention should be given to the poorest areas, especially in southern Italy, where measles occurs earlier and can be particularly severe.
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