Heterogeneity of the association between lower respiratory illness in infancy and subsequent asthma

Viral lower respiratory tract illnesses occurring during the first years of life are associated with increased risk of subsequent asthma, but the mechanisms involved have not been completely elucidated. The available evidence suggests that the factors that explain this connection are heterogeneous. Children who start life with lower levels of airway function appear to be more prone to transient forms of wheezing in the first years of life. "Intrinsic" bronchial hyperresponsiveness, that is, that measured shortly after birth and unrelated to markers of atopy, has been reported to predict both early life wheezing and wheezing occurring during the early school years, independent of atopy. It has also been suggested that both decreased interferon-gamma responses measured before any viral lower respiratory illness and increased interferon-gamma responses measured at the time of the illness may predispose to such illnesses. Children in whom the former mechanism is involved should be expected to be more atopic later in life, whereas those with the latter mechanism should be less likely to be atopic. This may explain why early viral respiratory illnesses have been found to be both protective against and a risk factor for subsequent atopy in different studies. Current evidence thus suggests that different and often apparently contradictory mechanisms related to airway function, structure, and immune responsiveness may explain the association between viral lower airway illness in early life and subsequent asthma. Future preventive and therapeutic strategies will need to address the specific mechanisms that explain this association in different groups of subjects.