The role of childhood respiratory tract infections on the development of asthma and atopic disease

Background: The increasing rates of asthma and atopic disease in the last decades is unlikely to be explained by genetically determined factors but rather by changing environment and lifestyle factors, like childhood microbial exposure, socioeconomic status and dietary habits. In this thesis we explored the role of childhood respiratory tract infections (RTI) on the development of asthma and atopy. The evidence in favour of the concept that childhood infections protect against atopic development, the so-called 'hygiene hypothesis'4, is merely based on studies using indirect markers of overall microbial exposure, like attending day care or family size. There is no strong evidence that early and symptomatic childhood RTI themselves protect from atopic development. There is a general lack of longitudinal studies with extended follow-up into the association between childhood RTI and the development of atopic disease later in life. Objectives and methods: We therefore studied a large birth cohort of 1328 children, prospectively followed from age 2 to 21 years of which data on childhood respiratory tract infections (RTI) had been collected. Associations between RTI and atopic disease, both based on questionnaire assessment as well as objective measurement of lung function, IgE and exhaled bronchial Nitric Oxide (FeNO), were investigated. Furthermore we studied prognostic factors in childhood for asthma later in life to identify subjects at risk to develop asthma. Another study was performed, using factor analysis, to assess the associations between subjective domains of questionnaire-derived items of asthma and atopy and objective domains, composed of measurements of lung function, FeNO and IgE values. Results: Upper respiratory tract infections (URTI) were not associated with asthma, hay fever and eczema. This was true, both for questionnaire-based diagnosis and for objective measures of asthma and atopy. Adeno- and tonsillectomy, which is often performed in children with recurrent URTI was not associated with atopic disease at age 21 years either. Lower respiratory tract illness (LRTI) in childhood was associated with asthma at young adult age. In children, aged 2 to 4 years, independent predictors of asthma in young adulthood were female gender, smoking mother, LRTI, and parental atopic disease. However, the performance of the prognostic model including these parameters in terms of the occurrence of asthma in young adulthood was poor. Using factor analysis both questionnaire-based items and objective measures of asthma and atopy could be associated into more or less independent factors. Subjective factors comprised: 'asthma symptoms', 'doctor's diagnosed asthma', 'allergic rhinitis' and 'parental history of atopic disease'. Objective factors were: 'lung function' and 'IgE, specific IgE and FeNO'. The study showed that questionnaire-based items and objective measures of asthma and atopy appeared to be separate and largely independent dimensions. This underlines the heterogeneity of the disease and importantly, shows the limited relations between the different entities of asthma and atopy. Conclusion: The results seem to confirm that childhood RTI do not increase the risk to develop atopic disease. Furthermore, our study contributes to the main concept that asthma and atopic disease comprise different independent dimensions of only partially overlapping features.