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

Abstract

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. © Published by Oxford University Press on behalf of the International Epidemiological Association. The Author 2009; all rights reserved.