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. In a systematic review and meta-analysis, Jayadeep Patra and colleagues explore associations between second-hand smoke exposure, demographics, lifestyle factors, and tuberculosis.Background: Tuberculosis (TB)—a bacterial disease that usually affects the lungs—is a global public health problem. Every year, 8.6 million people develop active TB and at least 1.3 million people die from the disease, mainly in resource-limited countries. Mycobacterium tuberculosis, the organism that causes tuberculosis, is spread in airborne droplets when people with active TB cough or sneeze. If another person inhales these droplets, he or she may become infected. However, only about 10% of people who become infected develop active TB, the symptoms of which include cough, weight loss, and fever. Most infected individuals contain and control the infection. Indeed, it is thought that about one-third of the world’s population has latent TB infection (LTBI). Individuals with LTBI have no symptoms and are not infectious, but they may develop active disease later in life. Both LTBI and active TB can be cured by taking antibiotics daily for several months. LTBI needs to be treated to prevent the infection progressing to active disease; active TB needs to be treated to prevent death and the spread of tuberculosis. Why Was This Study Done?: Very young and very old people, and people who are immunocompromised because of, for example, infection with HIV, are at high risk of developing active TB. Other risk factors for contracting TB include living in crowded, unsanitary conditions and poor nutrition. Another possible risk factor for TB is smoking tobacco products. Tobacco smoke is thought to damage both the fine hairs lining the lungs that normally provide a defense against bacterial infections and the lungs’ immune system. But is exposure to second-hand smoke (SHS; passive smoking) also a risk factor for TB? It is particularly important to know whether there is an association between exposure to SHS and TB among children because in some countries with a high TB burden a large proportion of children are exposed to SHS. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic) and meta-analysis (a statistical approach for combining the results of several studies), the researchers investigate whether SHS exposure is a risk factor for TB among children and adults. What Did the Researchers Do and Find?: The researchers identified 18 observational studies that recorded diagnoses of LTBI or active TB, exposure to SHS, and exposure to some other risk factors for TB among 30,757 children and 44,432 adult non-smokers. Compared to children not exposed to SHS, exposed children had a pooled relative risk (RR) of LTBI of 1.64. That is, exposure to SHS among children was associated with a 1.64-fold increased risk of LTBI. SHS exposure was also associated with a 3.41-fold increased risk of active TB among children and with a 1.32-fold increased risk of active TB among adults. Other analyses indicated that although there was an association between exposure to SHS and active TB in every age group, the highest relative risk was among children aged 0–5 years, and that children exposed to SHS living in crowded households had a higher relative risk of developing active TB than SHS-exposed children living in less crowded households. Importantly, the associations between SHS exposure and LTBI and active TB remained significant (unlikely to have occurred by chance) after adjustment for exposure to other known TB risk factors such as the presence of an individual with TB in the household. What Do These Findings Mean?: These findings suggest that exposure to SHS is associated with LTBI and active TB among children and adults after adjustment for a limited number of other risk factors for TB. Because the studies included in this meta-analysis were observational studies, individuals exposed to SHS might have also been exposed to other unknown factors (confounding factors) that were actually responsible for their increased risk of TB. Thus, these findings do not prove a causal link between exposure to SHS and TB. Moreover, because of high heterogeneity (variability) among the studies included in this meta-analysis (particularly those that included children), these findings need to be confirmed in additional studies. Such studies are essential because a causal link between SHS exposure and TB, if proved, will have important implications for the health of children living in countries with high SHS exposure and a high TB burden, and for the design of future TB and tobacco control programs. Additional Information: Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001835.The World Health Organization (WHO) provides information (in several languages) on tuberculosis; the Global Tuberculosis Report 2014 provides information about tuberculosis around the world; WHO also provides information about the health risks associated with tobacco use (in several languages)The Stop TB Partnership is working towards tuberculosis elimination and provides personal stories about tuberculosis (in English and Spanish); the Tuberculosis Vaccine Initiative (a not-for-profit organization) also provides personal stories about tuberculosisThe US Centers for Disease Control and Prevention provides information about tuberculosis (in English and Spanish), about smoking and tobacco use, and about the health effects of second-hand smokeThe US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosisThe US Environmental Protection Agency provides information about the health effects of exposure to second-hand smoke in childrenMedlinePlus has links to further information about tuberculosis, about smoking, and about the effects of second-hand smoke (in English and Spanish)