Epidemiology of asthma and recurrent wheeze in childhood.

To summarize, wheeze is common throughout childhood, although it decreases as children age. However, the characteristics of wheeze, its relations with asthma, and its risk factors all change with age. Longitudinal studies have shown that "transient early wheezing" predominates during the first years of life. The principal risks for this type of wheezing are largely mechanical, relating to small airways, and infectious, relating to the risk of becoming infected with respiratory viruses. Associated with passive exposure to cigarette smoke, exposure to other children, and not being breastfed, this form of wheezing was unrelated to increased airway liability or atopy in the child. For the majority of children, particularly those with low lung function at birth, wheezing with early LRIs is a benign condition, not associated with subsequent wheeze or risk for asthma. During the middle part of the first decade of life, wheezing appears to reflect a mix of infectious and allergic wheezing. By 6 yr of age, some children have already wheezed persistently. This group is more likely to have high total IgE levels, to be skin-test positive, and to be given a diagnosis of asthma. Further, their immunologic response to their early LRIs was consistent with a Th2 bias: persistent wheezers produced high levels of IgE, and did not demonstrate the normal pattern of decreased eosinophils. Nevertheless, the children who wheeze in middle childhood are a mixed group, with some being less allergic. Thus, although markers of allergy become increasingly important predictors of wheezing for the group as a whole, wheezing in middle childhood is not associated with later methacholine hyperresponsiveness (42). Finally, persistent allergic wheezing, usually associated with a diagnosis of asthma, predominates by the end of the first decade of life. Wheezing at this age is associated with methacholine responsiveness, peak-flow variability, and markers of atopy, such as total IgE and allergy skin-test response. Although children who wheezed early in life are more likely to wheeze later, early wheeze does not increase the risk of atopy, suggesting that early LRIs are markers of increased risk rather than causes. The gender differences in wheeze disappear, with boys becoming less likely to wheeze and to have asthma, whereas both conditions appear to increase in girls. Finally, some of the risk factors for early LRIs, such as exposure to other children in infancy, appear to be associated with protection from later allergic wheezing. Clearly, asthma and wheeze during childhood are complex entities, presenting with different characteristics at different ages, and implicating varied and changing causes. Genetic factors are important determinants of the intermediate phenotypes. However, environmental factors operating at different developmental stages also appear to influence the development of asthma. Additional research regarding these relationships is essential, both to elucidate possible causal mechanisms and to provide insight into the primary prevention of asthma.