Tobacco Smoke, Indoor Air Pollution and Tuberculosis

In January 2007, Harvard epidemiologists Lin, Ezzati and Murray published a paper "Tobacco Smoke, Indoor Air Pollution and Tuberculosis: A Systematic Review and Meta-Analysis" looking at associations between tobacco smoking, passive smoking, indoor air pollution (IAP) and tuberculosis. (Available at: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040020)

They concluded that there is substantial evidence for a positive association between TB and tobacco smoking; less substantial evidence but a positive association between passive smoking and IAP as risks for TB infection. They found a significant increased risk of clinical TB among smokers regardless of outcome definition, adjustment for alcohol intake or socioeconomic status, type of study or choice of controls.

Select passive smoking findings:
1. The risk of TB among children exposed to passive smoking was significantly higher than it was among adults.
2. A dose response was found in the two studies that stratified on exposure intensity.

Select discussion points:
1. 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.
2. 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 TB than those who are not exposed.
3. "Although our evidence suggests that tobacco smoking is only a moderate risk factor in TB, the implication for global health is critical. Because tobacco smoking has increased in developing countries where TB is prevalent, a considerable portion of global burden of TB may be attributed to tobacco smoking."

Evidence supporting causation link between :
1. Risk of TB and combustion smoke: risk of TB increases with both daily dose of cigarettes and duration of smoking.
2. Proposed mechanism of action:
a. chronic exposure to tobacco/certain environmental pollutants impairs the normal clearance of secretions on the tracheobronchial mucosal surface and may allow the mycobacterium to escape the first level of host defenses which prevent bacilli from reaching the alveoli.
b. smoke impairs pulmonary alveolar macrophage function, and they function as an early defense mechanism and are a target of Mycobacterium tuberculosis. (Impairment takes the form of reduced phagocytic ability, and smokers also have a lower level of proinflammatory cytokines released.)
c. nicotine may work directly on the nicotinic ACh receptors on macrophages leading to decreased intracellular tumor necrosis factor alpha (TNF-alpha) production and thus impair intracellular killing of M. tb.
d. pulmonary alveolar macrophages from smokers have a markedly elevated iron content and macrophage iron overload impairs defense mechanisms due to decreased TNF-alpha and nitric oxide production.

Limitations: see article - e.g., alcohol use lessened the association of TB and tobacco smoking in a multivariable model but smoking effect was reduced, not eliminated.

Policy/advocacy implications: Smoking cessation is an important component to stemming TB infection given the current biological paradigm. Smoking is increasing in low- and middle-income countries where TB prevalence is greatest; therefore, smoking cessation campaigns should be part of anti-TB campaigns.