The Association of Early Life Viral Respiratory Illness and Atopy on Asthma in Children: Systematic Review and Meta-Analysis.

BACKGROUND: The interaction between early life viral respiratory illness and atopy in the genesis of asthma has been widely discussed in the literature as the "two-hit hypothesis." OBJECTIVE: To synthesize evidence regarding the association of childhood viral respiratory illness and atopy in the development of persistent wheezing and asthma. METHODS: A systematic review was performed, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Human studies investigating early life associations between atopy and viral respiratory illness with outcomes of asthma and wheezing were included. Meta-analysis was performed to investigate the association of viral illness across atopic and nonatopic groups. Subgroup analysis was undertaken to investigate potential effect modification of age at outcome. RESULTS: Nine cohort studies were included, with data available for meta-analysis in 4 birth cohort studies. There was a stronger association of viral respiratory illness with persistent asthma/wheeze in atopic (odds ratio [OR], 4.02; 95% CI, 1.46-11.06) compared with nonatopic (OR, 2.32; 95% CI, 1.22-4.40) individuals; however, the evidence for this was limited. In 3 studies amenable to subanalysis based on outcome age, a stronger effect was observed up to 7 years for those with atopy (OR, 7.27; 95% CI 4.65-11.36) compared with those without atopy (OR, 3.19; 95% CI, 2.09-4.87). CONCLUSIONS: There was a stronger association between viral respiratory illness and asthma/wheeze outcomes in individuals with atopy as compared with those without atopy. When outcomes were considered at younger ages, a greater differential effect was observed. Within the limitations of the few available studies however, definite conclusions cannot be made. There was also insufficient evidence for differential effects of early versus late atopy. Further research, in particular regarding virus type, timing of atopy, and atopic phenotype, would contribute to untangling this complex association.