Exposure to Second-Hand Smoke and the Risk of Tuberculosis in Children and Adults: A Systematic Review and Meta-Analysis of 18 Observational Studies

BACKGROUND: According to WHO Global Health Estimates, tuberculosis (TB) is among the top ten causes of global mortality and ranks second after cardiovascular disease in most high-burden regions. In this systematic review and meta-analysis, we investigated the role of second-hand smoke (SHS) exposure as a risk factor for TB among children and adults. METHODS AND FINDINGS: We performed a systematic literature search of PubMed, Embase, Scopus, Web of Science, and Google Scholar up to August 31, 2014. Our a priori inclusion criteria encompassed only original studies where latent TB infection (LTBI) and active TB disease were diagnosed microbiologically, clinically, histologically, or radiologically. Effect estimates were pooled using fixed- and random-effects models. We identified 18 eligible studies, with 30,757 children and 44,432 adult non-smokers, containing SHS exposure and TB outcome data for inclusion in the meta-analysis. Twelve studies assessed children and eight studies assessed adult non-smokers; two studies assessed both populations. Summary relative risk (RR) of LTBI associated with SHS exposure in children was similar to the overall effect size, with high heterogeneity (pooled RR 1.64, 95% CI 1.00–2.83). Children showed a more than 3-fold increased risk of SHS-associated active TB (pooled RR 3.41, 95% CI 1.81–6.45), which was higher than the risk in adults exposed to SHS (summary RR 1.32, 95% CI 1.04–1.68). Positive and significant exposure–response relationships were observed among children under 5 y (RR 5.88, 95% CI 2.09–16.54), children exposed to SHS through any parent (RR 4.20, 95% CI 1.92–9.20), and children living under the most crowded household conditions (RR 5.53, 95% CI 2.36–12.98). Associations for LTBI and active TB disease remained significant after adjustment for age, biomass fuel (BMF) use, and presence of a TB patient in the household, although the meta-analysis was limited to a subset of studies that adjusted for these variables. There was a loss of association with increased risk of LTBI (but not active TB) after adjustment for socioeconomic status (SES) and study quality. The major limitation of this analysis is the high heterogeneity in outcomes among studies of pediatric cases of LTBI and TB disease. CONCLUSIONS: We found that SHS exposure is associated with an increase in the relative risk of LTBI and active TB after controlling for age, BMF use, and contact with a TB patient, and there was no significant association of SHS exposure with LTBI after adjustment for SES and study quality. Given the high heterogeneity among the primary studies, our analysis may not show sufficient evidence to confirm an association. In addition, considering that the TB burden is highest in countries with increasing SHS exposure, it is important to confirm these results with higher quality studies. Research in this area may have important implications for TB and tobacco control programs, especially for children in settings with high SHS exposure and TB burden.