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.

TB and Substance Abuse in the U.S., 1997-2006

"The TB control community has been slow to recognize that TB is difficult to control in isolation and to develop effective interventions for those who abuse substances..." -Oeltmann et al.-

A very informative investigation has been just released by researchers at the Division of Tuberculosis Elimination at the Centers for Disease Control and Prevention in Atlanta.

Oeltmann et al. conclude: "Substance abuse is the most commonly reported behavioral risk factor among patients with TB in the United States. Patients who abuse substances are more contagious (e.g., smear positive) and remain contagious longer because treatment failure presumably extends periods of infectiousness. Increased transmission is consistent with our finding that patiens who abuse substances were more likely to be in a localized genotype cluster, which can represent recent transmission." Arch Intern Med. 2009;169(2):189-197.
http://archinte.ama-assn.org/cgi/content/short/169/2/189

Around the world, more studies, such as this one, are needed that lead to better interventions for substance users, particularly among patients who drink excessive amounts of alcohol. If you are a health professional with experience in TB treatment, please comment on this post with any experience or anecdotal or evidence-based experience with TB patients who are substance abusers. Any success stories or strategies for anti-TB therapy adherence and/or substance abuse cessation?