Evidence for a causal relationship between respiratory syncytial virus infection and asthma

Abstract

Respiratory syncytial virus (RSV) infects all children early in life, is the most common cause of infant lower respiratory tract infections, and causes disease exacerbations in children with asthma. Episodes of lower respiratory tract infection in early life are associated with asthma development. Whether RSV infection early in life directly causes asthma or simply identifies infants who are genetically predisposed to develop subsequent wheezing is debatable. Recent studies suggest that these two explanations are not mutually exclusive, and are likely both important in asthma development. An open-label study of RSV immunoprophylaxis administered to preterm infants reduced recurrent wheezing by 50%. Clinical trials of infant RSV prevention, delay or severity reduction on the outcome of childhood asthma would confirm the causal relationship between RSV infection and asthma, and offer a primary prevention strategy.

Figures

Figure 1. Noncausal and causal explanation of the relationship between winter viral infection and early childhood asthma

In the noncausal model, a common genetic predisposition to asthma is associated with both winter viral infection and asthma, and is a confounder of the association between winter viral infection and asthma. Thus, timing of infant birth in relationship to winter virus peak has a seasonal effect on bronchiolitis (A), but not on asthma (B). In the causal model, while familial predisposition to asthma relates to both winter viral infection and asthma, winter viral infection is in the causal pathway of development of asthma. Timing of infant birth in relationship to winter virus season relates to both bronchiolitis (C) and asthma risk (D) in an identical way. The solid and dashed lines in (A), (C) and (D) are predicted probability and corresponding 95% CI of developing infant bronchiolitis and childhood asthma by infant age in months at the winter virus peak from multivariable logistic regression models. The solid line in (B) represents childhood asthma prevalence in the population. Reprinted with permission from the American Thoracic Society from [45]. © American Thoracic Society.

Figure 2. Candidate genes associated with severe RSV infection and asthma

Genes colored in red are those associated with RSV infection with at least one significant association that overlaps with asthma studies, where the evidence of an association with asthma is strongly supported; genes colored in blue indicate the genes that are associated with RSV infection but not with asthma; genes colored in green are genes associated with RSV infection but with an unconfirmed association with asthma. RSV: Respiratory syncytial virus. Updated and reprinted with permission from the American Thoracic Society from [53]. © American Thoracic Society.