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A Systematic Review and Meta-analysis

Michael N. Bates, PhD; Asheena Khalakdina, PhD; Madhukar Pai, MD, PhD; Lisa Chang, MPH; Fernanda Lessa, MD, MPH; Kirk R. Smith, PhD

Arch Intern Med. 2007;167(4):335-342.

Background  There is no consensus whether tobacco smoking increases risk of tuberculosis (TB) infection, disease, or mortality. Whether this is so has substantial implications for tobacco and TB control policies.

Objective  To quantify the relationship between active tobacco smoking and TB infection, pulmonary disease, and mortality using meta-analytic methods.

Methods  Eight databases (PubMed, Current Contents, BIOSIS, EMBASE, Web of Science, Centers for Disease Control and Prevention Tobacco Information and Prevention Source [TIPS], Smoking and Health Database [Institute for Science and Health], and National Library of Medicine Gateway) and the Cochrane Tobacco Addiction Group Trials Register were searched for relevant articles published between 1953 and 2005.

Study Selection  Included were epidemiologic studies that provided a relative risk (RR) estimate for the association between TB (infection, pulmonary disease, or mortality) and active tobacco smoking stratified by (or adjusted for) at least age and sex and a corresponding 95% confidence interval (CI) (or data for calculation). Excluded were reports of extrapulmonary TB, studies conducted in populations prone to high levels of smoking or high rates of TB, and case-control studies in which controls were not representative of the population that generated the cases, as well as case series, case reports, abstracts, editorials, and literature reviews.

Data Extraction  Twenty-four studies were included in the meta-analysis. Extracted data included study design, population and diagnostic details, smoking type, and TB outcomes.

Data Synthesis  A random-effects model was used to pool data across studies. Separate analyses were performed for TB infection (6 studies), TB disease (13 studies), and TB mortality (5 studies). For TB infection, the summary RR estimate was 1.73 (95% CI, 1.46-2.04); for TB disease, estimates ranged from 2.33 (95% CI, 1.97-2.75) to 2.66 (95% CI, 2.15-3.28). This suggests an RR of 1.4 to 1.6 for development of disease in an infected population. The TB mortality RRs were mostly below the TB disease RRs, suggesting no additional mortality risk from smoking in those with active TB.

Conclusions  The meta-analysis produced evidence that smoking is a risk factor for TB infection and TB disease. However, it is not clear that smoking causes additional mortality risk in persons who already have active TB. Tuberculosis control policies should in the future incorporate tobacco control as a preventive intervention.

Author Affiliations: School of Public Health, University of California, Berkeley. Dr Khalakdina is now with the Program for Appropriate Technologies in Health, Bangkok, Thailand; Dr Pai is now with the Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec; and Ms Chang is now with the Division of Research, Kaiser Permanente, Oakland, Calif.

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