 excluding the study conducted in India where TB may have been differentially overdetected among smokers [2,61], heterogeneity was markedly reduced (I2 = 38.6%). Other sensitivity analyses are demonstrated in Table 4.
Quality Assessment and Subgroup Analysis: Tobacco Smoking and TB Mortality
Passive Smoking and TB
We identified five studies on passive smoking and TB, of which four were case-control studies assessing the risk of clinical TB [50,53–55,62,63] and one a cross-sectional study on the risk of latent infection . Two studies did not exclude active smokers while assessing passive smoking and were, therefore, not included in the analysis of passive smoking and TB [50,53]. Figure 7 shows the individual effect measures for the studies on active disease; each found a positive association between passive smoking and TB. The heterogeneity among the studies was largely explained by the age of the participants; the risk of TB among children exposed to passive smoking was significantly higher than it was among adults (p = 0.002), and there was no remaining heterogeneity within the subgroups stratified by age. The single study examining the risk of latent TB infection among those exposed to passive smoking reported an OR of 2.68 (95% CI, 1.52–4.71) . Sensitivity analyses for these estimates are given in Table 5.
Quality Assessment and Subgroup Analysis: Passive Smoking and TB Disease
A dose response was found in both of the two studies that stratified on exposure intensity; one found that TB risk increased with the number of cigarettes smoked by the family per day , and the other found that close and very close contact with smoking household members was strongly associated with TB (adjusted OR 9.31 [95% CI, 3.14–27.58]), while distant contact was not (adjusted OR 0.54 [95% CI, 0.25–1.16]) .
IAP and Clinical TB Disease
Only five studies of IAP and TB were identified (Figure 8) [36,42,48,65,66]. Of these, only two studies adjusted for tobacco smoking [42,66] while three others did not [36,48,65]. In each of the studies, IAP was assessed by questionnaire on cooking and heating with biomass fuels (wood or dung). Although three of the five studies reported a positive association between biomass use and TB disease, there was significant heterogeneity among the studies (I2 = 74.1% in case-control studies) (Figure 8). We noted that in one study, houses were reportedly well ventilated and therefore the impact of IAP might have been attenuated . The sensitivity analyses are presented in Table 6.
Quality Assessment and Subgroup Analysis: Indoor Air Pollution and TB Disease
When we plotted the natural logarithms of the effect estimates against their standard errors using the methods described by Begg (Figure 9A) , we detected some slight asymmetry of effect estimates among small studies. We also noted that several large studies fell outside the projected lines of the funnel plot, indicating substantial variability among studies with small standard errors. When we repeated this analysis excluding the five mortality studies, we found that the studies with small standard errors clustered within the funnel plot (Figure 9B). We found no evidence for substantial publication bias by either the Begg's test (p = 0.256) or the Egger's test (p = 0.977).
This analysis shows that exposure to tobacco smoke is consistently associated with TB, regardless of the specific types of exposures and specific TB outcomes. Compared with people who do not smoke, smokers have an increased risk of a positive TST, of having active TB, and of dying from TB. Although there were fewer studies for passive smoking and IAP from biomass fuels, those exposed to these sources were found to have higher risks of active TB than those who are not exposed. An important finding of this study is the suggestion that the risk of TB among those exposed to passive smoking is especially high in children who are not normally at high risk for active disease. These findings support the hypothesis that exposure to respirable pollutants from combustion of tobacco and biomass fuels increase