Does BCG vaccination protect against the development of childhood asthma? A systematic review and meta-analysis of epidemiological studies.

BACKGROUND Results have been conflicting as to whether Bacillus Calmette-Guérin (BCG) vaccine, a non-specific stimulator of the immune function, protects, predisposes or is unrelated to the development of childhood asthma. In this systematic review and meta-analysis, we qualitatively and quantitatively appraised the epidemiological evidence. METHODS Eligible studies were identified using a search strategy that included a computerized literature search and a manual search of each article's reference list, up to June 2008. A total of 23 studies were included (10 cohort, 5 case-control and 8 cross-sectional). Each study was summarized and rated for methodological quality. Pooled odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated using fixed-effects (FE) or random-effects (RE) models; if heterogeneity was present, the latter was used. Three indicators of BCG exposure were considered including BCG vaccination, tuberculin response and scar diameter. RESULTS The pooled estimate of association for 23 studies reporting on any of the three indicators suggested a protective effect of BCG exposure on childhood asthma occurrence. The studies were heterogeneous, especially when tuberculin response was considered. Restriction to a subgroup of 16 studies that considered BCG vaccination indicated a protective effect with no evidence of heterogeneity. The overall pooled OR using an FE model was 0.86 (95% CI 0.79-0.93). Exclusion of three studies with the lowest quality scores showed a similar association. CONCLUSION These results strengthen the epidemiological evidence in support of the hypothesis that exposure to the BCG vaccine in early life prevents asthma, possibly through a modulation of the immune maturation process.