Bronchiolitis to asthma: A review and call for studies of gene-virus interactions in asthma causation

Viral infections are important causes of asthma exacerbations in children, and lower respiratory tract infections (LRTIs), caused by viruses such as respiratory syncytial virus (RSV) and rhinovirus (RV), are a leading cause of bronchiolitis in infants. Infants hospitalized with bronchiolitis are at significantly increased risk for both recurrent wheezing and childhood asthma. To date, studies addressing the incidence of asthma after bronchiolitis severe enough to warrant hospitalization have focused almost exclusively on RSV, but a number of recent studies suggest that other respiratory pathogens, including RV, may contribute as well. It is not known whether viral bronchiolitis directly contributes to asthma causation or simply identifies infants at risk for subsequent wheezing, as from an atopic predisposition or preexisting abnormal lung function. Alternatively, the properties of the infecting virus may be important. Thus, many possible determinants exist that may contribute to the severity of bronchiolitis and the subsequent development of asthma. One such determinant is the potential involvement of genetic susceptibility loci to asthma after viral bronchiolitis, a critical area that is just beginning to be evaluated. By clarifying the roles of both host-(genetic) and virus- (environment) specific factors that contribute to the frequency and severity of viral LRTI, it may be possible to determine if severe LRTIs cause asthma, or if asthma susceptibility predisposes patients to severe LRTI in response to viral infection. Characterizing these relationships offers the potential of identifying at-risk hosts in whom preventing or delaying infection could alter the phenotypic expression of asthma.