Association Between Respiratory Syncytial Virus Hospitalizations in Infants and Respiratory Sequelae Systematic Review and Meta-analysis

Background: The association between hospitalization for respiratory syncytial virus (RSV) infection in infancy and asthma/wheezing in later life has long been studied. However, no published studies have combined systematic review and meta-analysis of existing evidence. Purpose: To quantify the link between RSV hospitalization in early life and subsequent diagnosis of asthma. Method: A systematic search was conducted using MEDLINE and EMBASE databases. Studies were selected for meta-analysis if they assessed the association between RSV-confirmed hospitalization for up to 3 years of age and asthma/wheezing later in life. Potential sources of heterogeneity were identified by stratified analysis. Results: Twenty articles representing 15 unique studies of 82,008 unique individuals (including 1533 with RSV-confirmed hospitalization) were selected for meta-analysis. Children who had RSV disease in early life had a higher incidence of asthma/wheezing in later life (odds ratio: 3.84; 95% confidence interval: 3.23-4.58). There was moderate heterogeneity between studies (I-2 = 45%). The association was found to decrease with age at follow-up, consistent with the findings of longitudinal studies. When age at follow-up was considered, heterogeneity was low (residual I-2 = 17%). Limitations: Study quality was generally poor because randomization to hospitalization for RSV infection was not possible, appropriate blinding was rare and adjustment for confounding variables was not always appropriate. Conclusions: The meta-analysis suggests an association between infant RSV hospitalization and respiratory morbidity that decreases with age. If the association is causal, the development of an effective vaccine against RSV could decrease the burden of asthma.