0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review Article |

Risk of Tuberculosis From Exposure to Tobacco Smoke:  A Systematic Review and Meta-analysis FREE

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

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.


Arch Intern Med. 2007;167(4):335-342. doi:10.1001/archinte.167.4.335.
Text Size: A A A
Published online

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.

Figures in this Article

Tobacco smoking and tuberculosis (TB) are 2 of the world's greatest public health problems, although TB is largely confined to developing countries. Tobacco-attributable deaths are projected to increase from 3 million in 1990 to 8.4 million in 2020.1 After human immunodeficiency virus and AidS, TB is the leading infectious cause of death and disease worldwide, responsible for about 1.7 million deaths each year.2 One third of the world's population is infected with Mycobacterium tuberculosis, although the organism is contained by the immune system in most of these persons. Globally, an estimated 8.8 million individuals in 2003 developed active TB, and the incidence was increasing at 1% annually.3

It has long been suggested that tobacco smoking may affect rates of TB morbidity and mortality.4 This could be a result of increasing the risk of infection with TB mycobacteria, increasing the rate of active TB disease, or increasing the TB mortality rate; plausible mechanisms exist.5 However, statistical relationships found in investigations may have been a result of confounding (eg, by alcohol use or by socioeconomic factors).6 Establishing whether smoking interacts with events leading to TB morbidity and mortality would provide useful information for prevention policies for TB and smoking. This study systematically reviews the published literature on the relationship between smoking and TB infection, disease, and mortality and presents meta-analyses of the relationships. From a clinician's perspective, understanding the association between smoking and TB will facilitate educational and counseling interventions.

SEARCH

Eight major 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 published studies that included investigation of the relationship between smoking and TB infection, active pulmonary TB, or death due to TB. Variants of key words such as “tuberculosis,” “smoking,” and “tobacco smoke” were used. These yielded 3145 potentially relevant published articles between 1953 and 2005. Reference lists of articles identified were searched for additional relevant publications. We considered only articles in English, Chinese, Spanish, Portuguese, Italian, and German.

CRITERIA FOR SELECTION

Two independent reviewers (L.C. and F.L.) first screened titles and abstracts of publications using broad eligibility criteria, yielding 220 potentially eligible publications. These were reduced to 24 eligible publications by application of the following final study inclusion criteria: (1) use of an epidemiologic study design to conduct a primary or secondary data analysis, (2) inclusion of at least 1 comparison group without TB and a group of nonsmokers or never smokers, (3) provision of a relative risk (RR) estimate for the association between TB (infection, disease, or mortality) and active tobacco smoking (ie, not passive smoking exposure) stratified by (or adjusted for) at least age and sex and a corresponding 95% confidence interval (CI) (or sufficient data to calculate this), and (4) confirmation of TB status (infection, pulmonary disease, or death) in 1 of the following ways: (a) for TB infection, a tuberculin skin test, (b) for TB disease, bacteriologic confirmation (positive sputum smears or culture) or notification, and (c) for TB mortality, death certificates or verbal autopsies.

Publications were excluded if they (1) described case series or case reports or were abstracts, editorials, or literature reviews, (2) reported only extrapulmonary TB or did not distinguish pulmonary from extrapulmonary TB disease, (3) reported studies that were conducted in special populations prone to high levels of smoking or high rates of TB (eliminating studies on patients with lung cancer, stone crushers or miners, persons with silicosis, and subjects with human immunodeficiency virus or AidS [although no otherwise eligible studies in the latter category were found]), or (4) reported case-control studies in which the control population was not representative of the population generating the cases. When appropriate, authors were contacted to supply details missing from their publications.

DATA ANALYSIS

All analyses were performed using commercially available meta-analysis add-on programs (STATA version 8.0; StataCorp LP, College Station, Tex).7 Forest plots were created for each outcome (TB infection, TB disease, and TB death), and summary effect estimates were calculated using the DerSimonian-Laird random-effects model,8 usually regarded as more appropriate for meta-analysis of observational studies.9 Heterogeneity across studies was assessed using the χ2 test for homogeneity.

Subgroup analyses were used to explore sources of heterogeneity. Potential for publication bias was assessed using the Egger test and funnel plots.10

SELECTION OF ELIGIBLE PUBLICATIONS

The selected articles are listed in Table 1. Except for 1 article in Chinese,21 all were in English. Six publications dealt with TB infection, 13 with TB disease, and 5 with TB mortality.

Table Graphic Jump LocationTable 1. Studies Included in the Meta-analysis
META-ANALYSIS
TB Infection

Figure 1 shows a forest plot for studies that examined TB infection. Four of 6 CIs excluded the null value. One study15 from among 6 eligible studies1114,16 was not included in this meta-analysis (which includes 2 independent results from 1 study11), because the RR estimates presented were for different numbers of cigarettes smoked per day. The smoking measure (ex-smoker, current smoker, or ever smoker) is shown in parentheses following the first author name and publication year in Figure 1. The summary estimate of the RR was 1.58 (95% CI, 1.23-2.02). However, there is evidence of heterogeneity (P = .005), particularly because of the precise RR estimate obtained by the large study by Adib et al13 among prisoners in Lebanon. The Lebanon study used a minimum tuberculin skin test induration diameter of 8 mm for diagnosing TB infection, while all other investigations used 10 mm as the criterion. The smaller induration diameter may have led to misclassification of persons without TB infection as being infected. This, as well as the fact that the comparison group of nonsmokers likely to have included some ex-smokers, could account for the low RR estimate from this study. After excluding the Lebanon study, we obtained a summary RR estimate of 1.73 (95% CI, 1.46-2.04) with no evidence of heterogeneity (P = .71) among the remaining studies.

Place holder to copy figure label and caption
Figure 1.

Forest plot of results of 5 studies1114,16 that examined smoking and tuberculosis infection. The smoking type (current smokers [Current], ex-smokers [Ex], and ever smokers [Ever]) of the study population is shown on the y-axis.

Graphic Jump Location

Figure 2 shows a funnel plot of the RR estimates for the studies1114,16 against their standard errors. The P = .02 that was derived using the Egger test and the asymmetry of the distribution suggest potential for publication bias. When the Lebanon study13 was excluded, the Egger test provided no evidence of heterogeneity (P = .82). However, tests of publication bias are not necessarily sensitive for small numbers of studies.

Place holder to copy figure label and caption
Figure 2.

Begg funnel plot with pseudo 95% confidence limits of results of 5 studies1114,16 that examined smoking and tuberculosis infection.

Graphic Jump Location
TB Disease

A meta-analysis combining the TB disease RR estimates for men and women across all studies produced a summary RR estimate of 2.27 (95% CI, 1.90-2.71) with appreciable evidence of heterogeneity (P = .002). However, in many of the countries represented in the analysis, womenare less likely to be smokers than men.34 Therefore, we excluded the RR estimates for women only, leaving estimates for men only and for men and women combined. The resulting forest plot is shown in Figure 3. Thirteen of 16 CIs excluded the null. The summary RR estimate was 2.33 (95% CI,1.97-2.75) with less evidence of heterogeneity (P = .04).

Place holder to copy figure label and caption
Figure 3.

Forest plot of results for men only and for men and women combined in studies4,17,1928 that examined smoking and tuberculosis disease. The smoking type (ex-smokers [Ex], current smokers [Current], and ever smokers [Ever]) of the study population is shown on the y-axis.

Graphic Jump Location

Because cross-sectional studies can include selection bias, as would be caused by the death of persons with TB, we performed the meta-analysis without the single cross-sectional study.17 The summary RR estimate decreased slightly to 2.29 (95% CI, 1.93-2.71) (P = .04 for heterogeneity).

Data shown in Figure 3 suggest that, on average, the RRs may be lower for ex-smokers, which would be consistent with findings that many smoking-related RRs decline soon after smoking cessation.35 For current smokers alone (men only or men and women combined), the summary RR estimate was 2.66 (95% CI, 2.15-3.28) (P = .48 for heterogeneity), a little higher than when ex-smokers and ever smokers were included.

All the study results selected for this meta-analysis were adjusted for age and sex. Some investigations adjusted their results for additional potential confounders. After excluding results for women only, the summary RR estimate for the 5 results that were not adjusted for other potential confounding factors was 2.35 (95% CI, 1.95-2.84) (P = .80 for heterogeneity). The corresponding summary estimate for the 12 results that adjusted for other confounding factors (in addition to age and sex) was 2.33 (95% CI, 1.81-3.01), although there was more evidence of heterogeneity (P = .01).

Figure 4 shows a funnel plot that examines the likelihood of publication bias. It includes results for men only and for men and women combined, and seems symmetric. This and the Egger test value of P = .13 suggest that publication bias is not likely to be a problem in this analysis.

Place holder to copy figure label and caption
Figure 4.

Begg funnel plot with pseudo 95% confidence limits of results of studies4,17,1928 that examined smoking and tuberculosis disease.

Graphic Jump Location
TB Mortality

Figure 5 shows a forest plot of the RR estimates from the 5 eligible studies.2933 There is a great deal of heterogeneity (<.001), so the summary random-effects RR estimate of 2.15 (95% CI, 1.38-3.35) cannot be regarded as valid. Except for 2 investigations in India that used verbal autopsies to determine cause of death,31 all studies relied on official death certificates. When the studies using verbal autopsies were excluded from the analysis, the RR estimate was reduced to 1.60 (95% CI, 1.31-1.95) still with strong evidence of heterogeneity (<.001).

Place holder to copy figure label and caption
Figure 5.

Forest plot of studies2933 that examined smoking and tuberculosis mortality. The sex and age of the study population are shown on the y-axis.

Graphic Jump Location

When the 2 studies29,30 from China were considered separately, the combined RR estimate was 1.26 (95% CI, 1.14-1.40) with no evidence of heterogeneity (P = .26). When the Indian studies31,33 were combined, the RR estimate was 3.81 (95% CI, 2.98-4.87); this was dominated by the results from the studies31 that used verbal autopsies, and much heterogeneity remained (P = .001).

No useful summary RR estimates were obtained from the mortality investigations. Therefore, no assessment of publication bias was carried out for these studies.

Dose-Response Relationships

Dose-response data were available for 4 studies12,1416 of TB infection and for 3 studies18,19,27 of TB disease. One study12 included measures of smoking quantity and duration. The results are summarized in Table 2. Several smoking exposure metrics were used, making it impractical to combine results across studies. Six of 8 exposure-response analyses found a positive trend with increasing level or duration of smoking.

Table Graphic Jump LocationTable 2. Exposure-Response Relationships Between Tobacco Smoking and Tuberculosis (TB) Infection and TB Disease*

Well-known risk factors for TB infection or disease include crowding, poor nutrition, alcoholism, race/ethnicity, socioeconomic status, diabetes mellitus, and human immunodeficiency virus infection. Tobacco smoking is not widely considered a risk factor. A recent review36 of environmental risk factors for TB did not mention tobacco smoking. However, a subsequent review article37 identified smoking as a possible risk factor, although data were not combined across studies. Potentially, smoking is one of the most modifiable of exposures. In developing countries, where life expectancy is short, highlighting smoking as a risk factor for TB may have greater resonance than advertising its risks for cancer and cardiovascular disease.

Results of this meta-analysis suggest that smoking is associated with an RR of approximately 1.7 for TB infection and an RR of 2.3 to 2.7 for TB disease. The corresponding association with TB mortality is less clear because of heterogeneity in results across studies.

The RR estimates for TB infection, disease, and mortality are not independent. If smoking increases the risk of infection, this will increase the proportion of smokers who are infected and are at risk of TB disease. In turn, if smoking increases the risk of TB disease in those already infected, this will increase the proportion of smokers at risk of TB mortality. Therefore, the independent RR for TB disease can be estimated by dividing the study-derived RR for TB disease (2.3-2.7) by the RR for TB infection (1.7). This gives an estimated RR for development of TB disease in an infected population of 1.4 to 1.6. The most accurate estimate of this risk would come from a study of new TB disease occurrence in an infected population. To our knowledge, such a study has not been published.

The RR estimates for TB mortality were heterogeneous. However, for the investigations that based their cause-of-death assignments on death certificates, the summary RR was 1.60 (95% CI, 1.31-1.95). Because this is less than the estimated RR range for TB disease and smoking (2.3-2.7), it suggests that there is no additional contribution to TB mortality risk from smoking in a population with TB respiratory disease. However, 2 investigations that used verbal autopsies obtained RRs of 4.5 (95% CI, 4.0-5.0) and 4.2 (95% CI, 3.7-4.8) among urban and rural male Indian populations, respectively.31 These results suggest that the true mortality RR for smoking among patients with TB pulmonary disease is 1.6 to 2.0. This is not unreasonable because causes of death on death certificates are often unreliable, and verbal autopsies have been shown in some populations to give more complete data on cause of death.38,39 However, further studies in more countries are needed for a definitive conclusion about the relationship between TB mortality and smoking. A study examining mortality among a population with TB disease, smokers and nonsmokers, would provide the most valid results.

It is biologically plausible that smoking could increase risks for TB infection and TB disease. Suggested mechanisms include decreased immune response, CD4 lymphopenia, defects in macrophage immune responses, and mechanical disruption of cilia function in the airways.5 However, before drawing any firm conclusions, it is important to consider whether selection bias, information bias, or confounding could have accounted for our results.

The most likely form of selection bias in the eligible studies is from control selection in the case-control studies. We excluded studies in which the populations generating the cases and controls were obviously different. However, we cannot be certain that no control selection problems arose. Some investigations of TB disease used hospital and clinic control subjects, although they excluded patients with smoking-related disease. Nevertheless, it is possible that there was still some tendency for the controls to more likely be smokers than their base populations. If so, the direction of the bias would be toward the null and could not account for our results.

Misclassification of smoking behavior is a potential problem.40 As reflected in the studies we considered, there are many ways to consider smoking, ranging from a simple classification of current or ever smoking status to more sophisticated measures of lifetime smoking by amount and duration. Overall, the misclassification is likely to be nondifferential and would probably bias the RR estimates toward the null.

Except for mortality, outcome misclassification is less likely in our review than exposure misclassification because outcome was based on the results of objective tests. However, some misclassification may have occurred in the results for infection status, particularly if positive results of tuberculin skin tests were caused by nontuberculous bacteria or by prior BCG vaccine. False-negative results can occur with recent TB infections in which tuberculin skin tests may have been performed before tuberculin conversion. It is unlikely that these factors would have substantially affected our results, and not consistently across countries and studies. Any resulting bias would be toward the null. The greatest opportunity for outcome misclassification may have occurred with the use of death certificates to record cause of death. There is a high rate of inaccuracy in recording of causes of death41 and much variability in methods for identifying the principal cause of death from death certificates.42 Again, the bias is likely to be toward the null.

Most difficult to quantify is the possibility of unadjusted confounding in the analyses. For example, alcohol consumption may have confounded the RR estimates for smoking and TB, as alcohol is more likely to be consumed by smokers, and findings from studies43,44 suggest that alcohol use is a risk factor for TB disease. Other investigators have suggested more generally that socioeconomic factors may be responsible for confounding.5 The studies selected for this review had wide variation in the degree of possible confounding that was taken into account, although eligibility for this review required that age and sex were treated as confounders. The extent of further adjustment ranged from no additional confounders to extensive multivariate adjustment. Our comparison of results in which adjustment was only by age and sex with results that included additional adjustment factors produced similar summary RR estimates, suggesting that residual confounding is unlikely to account for the elevated risks found.

In conclusion, our results suggest that tobacco smoking interacts with M tuberculosis complex to the extent of promoting infection and disease. Data for TB mortality are too limited and heterogeneous for inferences to be confidently drawn.

The traditional approach to global TB control has focused on the diagnosis and treatment of smear-positive TB cases under the DOTS strategy recommended by the World Health Organization in an attempt to interrupt transmission.45 The DOTS program has achieved a modest decline in TB rates, but its success appears to have plateaued.46 It is apparent that treating active disease is insufficient for population-based TB control and that there is an urgent need to address prevention.46 Although the new Stop TB Strategy47 goes beyond the traditional paradigm by addressing issues in addition to DOTS expansion, it does not address population-based preventive interventions. Potentially modifiable risk factors that lead to TB infection and disease, such as tobacco smoking, should be targeted using appropriate interventions. Clinicians and health care workers can use the information to better educate their patients about risks of smoking, especially in countries where TB and smoking rates are high. Moreover, if cigarette smoking is a risk factor for TB, it adds credibility to the hypothesis that high smoke exposures from biomass cooking fires may also be a risk factor.20,4850

Finally, because smoking has not previously been considered a TB risk factor, acceptance that it is a risk factor will have implications for the assessment of global mortality from tobacco consumption. For illustrative purposes, we offer a simplified (but reasonable) estimate based on assumptions that the RR for TB disease associated with smoking is 2.5, that there is no additional mortality risk from smoking in those who already have TB disease, and that 30% of the at-risk population are smokers. Simple attributable proportion calculations suggest that 31% of TB cases and TB deaths are attributable to smoking. Because worldwide there are approximately 9 million new TB cases and 1.7 million TB deaths each year, this proportion equates to an annual global burden of 2.79 million new TB cases and 527 000 deaths. If smoking increases the mortality rate in those with TB, then the number of deaths would be even higher. Further studies comparing mortality rates in smoking and nonsmoking patients with TB disease could resolve this issue. Irrespective of this, it is clear that smoking prevention and cessation efforts should be a priority in any TB prevention program.

Correspondence: Kirk R. Smith, PhD, School of Public Health, University of California, Berkeley, 140 Warren Hall, Berkeley, CA 94720-7360 (krksmith@berkeley.edu).

Accepted for Publication: October 27, 2006.

Author Contributions: Dr Bates had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Bates and Khalakdina contributed equally to this work. The authors were responsible for the content of the manuscript and the decision to submit it for publication. Study concept and design: Khalakdina, Pai, and Smith. Acquisition of data: Bates, Khalakdina, Chang, and Lessa. Analysis and interpretation of data: Bates, Khalakdina, Pai, and Smith. Drafting of the manuscript: Bates, Khalakdina, and Smith. Critical revision of the manuscript for important intellectual content: Bates, Khalakdina, Pai, Chang, Lessa, and Smith. Statistical analysis: Bates, Khalakdina, and Pai. Obtained funding: Khalakdina and Smith. Administrative, technical, and material support: Khalakdina, Lessa, and Smith. Study supervision: Khalakdina and Smith.

Financial Disclosure: None reported.

Funding/Support: The study was supported by Fogarty International Training and Research Program award D43-TW000815, by grant R01-TW05938 from Fogarty International Center Global Tobacco Control Research and Training Program, and by the Center for Occupational and Environmental Health, University of California (Berkeley, Davis, and San Francisco).

Role of the Sponsor: None of the funders had any role in the design or conduct of the study or in the preparation of the manuscript.

Acknowledgment: We thank Teh-Wei Hu, PhD, director of Fogarty grant R01-TW05938, for initiating this study.

Murray  CJLopez  AD Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997;3491498- 1504
PubMed Link to Article
Dye  C Global epidemiology of tuberculosis. Lancet 2006;367938- 940
PubMed Link to Article
 World Health Organization. Global Tuberculosis Control: Surveillance, Planning, and Financing  Geneva, Switzerland World Health Organization2005;Publication WHO/HTM/TB2005.349
Lowe  CR An association between smoking and respiratory tuberculosis. BMJ 1956;21081- 1086
PubMed Link to Article
Arcavi  LBenowitz  NL Cigarette smoking and infection. Arch Intern Med 2004;1642206- 2216
PubMed Link to Article
Bothamley  GH Smoking and tuberculosis: a chance or causal association [editorial]? Thorax 2005;60527- 528
PubMed Link to Article
 Release 8.0. STATA Statistical Software College Station, Tex StataCorp LP2003;
DerSimonian  RLaird  N Meta-analysis in clinical trials. Control Clin Trials 1986;7177- 188
PubMed Link to Article
Mosteller  FColditz  GA Understanding research synthesis (meta-analysis). Annu Rev Public Health 1996;171- 23
Link to Article
Petitti  DB Meta-Analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine.  New York, NY Oxford University Press Inc2000;
McCurdy  SAArretz  DSBates  RO Tuberculin reactivity among California Hispanic migrant farm workers. Am J Ind Med 1997;32600- 605
PubMed Link to Article
Anderson  RHSy  FSThompson  SAddy  C Cigarette smoking and tuberculin skin test conversion among incarcerated adults. Am J Prev Med 1997;13175- 181
PubMed
Adib  SMAl-Takash  HAl-Hajj  C Tuberculosis in Lebanese jails: prevalence and risk factors. Eur J Epidemiol 1999;15253- 260
Link to Article
Plant  AJWatkins  REGushulak  B  et al.  Predictors of tuberculin reactivity among prospective Vietnamese migrants: the effect of smoking. Epidemiol Infect 2002;12837- 45
PubMed Link to Article
Hussain  HAkhtar  SNanan  D Prevalence of and risk factors associated with Mycobacterium tuberculosis infection in prisoners, North West Frontier Province, Pakistan. Int J Epidemiol 2003;32794- 799
PubMed Link to Article
den Boon  Svan Lill  SWBorgdorff  MW  et al.  Association between smoking and tuberculosis infection: a population survey in a high tuberculosis incidence area. Thorax 2005;60555- 557
PubMed Link to Article
Adelstein  AMRimington  J Smoking and pulmonary tuberculosis: an analysis based on a study of volunteers for mass miniature radiography. Tubercle 1967;48219- 226
Link to Article
Yu  GPHsieh  CCPeng  J Risk factors associated with the prevalence of pulmonary tuberculosis among sanitary workers in Shanghai. Tubercle 1988;69105- 112
PubMed Link to Article
Gupta  DAggarwal  ANKumar  SJindal  SK Smoking increases risk of pulmonary tuberculosis. J Environ Med 2001;365- 69
Pérez-Padilla  RPérez-Guzmán  CBáez-Saldaña  RTorres-Cruz  A Cooking with biomass stoves and tuberculosis: a case-control study. Int J Tuberc Lung Dis 2001;5441- 447
PubMed
Dong  BGe  NZhou  Y Smoking and alcohol consumption as risk factors of pulmonary tuberculosis in Chengdu: a matched case-control study [in Chinese]. Hua Xi Yi Ke Da Xue Xue Bao 2001;32104- 106
Tekkel  MRahu  MLoit  HMBaburin  A Risk factors for pulmonary tuberculosis in Estonia. Int J Tuberc Lung Dis 2002;6887- 894
PubMed
Kolappan  CGopi  PG Tobacco smoking and pulmonary tuberculosis. Thorax 2002;57964- 966
PubMed Link to Article
Leung  CCYew  WWChan  CK  et al.  Smoking and tuberculosis in Hong Kong. Int J Tuberc Lung Dis 2003;7980- 986
PubMed
Leung  CCLi  TLam  TH  et al.  Smoking and tuberculosis among the elderly in Hong Kong. Am J Respir Crit Care Med 2004;1701027- 1033
PubMed Link to Article
Ariyothai  NPodhipak  AAkarasewi  PTornee  SSmithtikarn  SThongprathum  P Cigarette smoking and its relation to pulmonary tuberculosis in adults. Southeast Asian J Trop Med Public Health 2004;35219- 227
PubMed
Crampin  ACGlynn  JRFloyd  S  et al.  Tuberculosis and gender: exploring the patterns in a case control study in Malawi. Int J Tuberc Lung Dis 2004;8194- 203
PubMed
Lienhardt  CFielding  KSilah  JS  et al.  Investigation of the risk factors for tuberculosis: a case-control study in three countries in West Africa. Int J Epidemiol 2005;34914- 923
PubMed Link to Article
Liu  BQPeto  RChen  ZM  et al.  Emerging tobacco hazards in China, 1: retrospective proportional mortality study of one million deaths. BMJ 1998;3171411- 1422
PubMed Link to Article
Lam  THHo  SYHedley  AJMak  KHPeto  R Mortality and smoking in Hong Kong: case-control study of all adult deaths in 1998. BMJ 2001;323e36.1http://www.bmj.com/cgi/reprint/323/7309/361. Accessed January 2004
Link to Article
Gajalakshmi  VPeto  RKanaka  TSJha  P Smoking and mortality from tuberculosis and other diseases in India: retrospective study of 43000 adult male deaths and 35000 controls. Lancet 2003;362507- 515
PubMed Link to Article
Sitas  FUrban  MBradshaw  DKielkowski  DBah  SPeto  R Tobacco attributable deaths in South Africa. Tob Control 2004;13396- 399
PubMed Link to Article
Gupta  PCPednekar  MSParkin  DMSankaranarayanan  R Tobacco associated mortality in Mumbai (Bombay) India: results of the Bombay Cohort Study. Int J Epidemiol 2005;341395- 1402
PubMed Link to Article
Mackay  JAmos  A Women and tobacco. Respirology 2003;8123- 130
PubMed Link to Article
 Centers for Disease Control and Prevention. The Health Benefits of Smoking Cessation: A Report of the Surgeon General.  Rockville, Md US Dept of Health and Human Services, Public Health Service1990;Publication (CDC)90-8416
Lienhardt  C From exposure to disease: the role of environmental factors in susceptibility to and development of tuberculosis. Epidemiol Rev 2001;23288- 301
Link to Article
Maurya  VVijayan  VKShah  A Smoking and tuberculosis: an association overlooked. Int J Tuberc Lung Dis 2002;6942- 951
PubMed
Gajalakshmi  VPeto  R Verbal autopsy of 80,000 adult deaths in Tamilnadu, South India. BMC Public Health 2004;4e47
Link to Article
Soleman  NChandramohan  DShibuya  K Verbal autopsy: current practices and challenges. Bull World Health Organ 2006;84239- 245
PubMed Link to Article
Thurston  SWLiu  GMiller  DPChristiani  DC Modeling lung cancer risk in case-control studies using a new dose metric of smoking. Cancer Epidemiol Biomarkers Prev 2005;142296- 2302
PubMed Link to Article
Maudsley  GWilliams  EM “Inaccuracy” in death certification: where are we now? J Public Health Med 1996;1859- 66
Link to Article
Johansson  LAWesterling  RRosenberg  HM Methodology of studies evaluating death certificate accuracy were flawed. J Clin Epidemiol 2006;59125- 131
PubMed Link to Article
Brown  KECampbell  AH Tobacco, alcohol and tuberculosis. Br J Dis Chest 1961;55150- 158
Link to Article
Lewis  JGChamberlain  DA Alcohol consumption and smoking habits in male patients with pulmonary tuberculosis. Br J Prev Soc Med 1963;17149- 152
PubMed
 An Expanded DOTS: Framework for Effective Tuberculosis Control.  Geneva, Switzerland World Health Organization2002;
Brewer  TFHeymann  SJ To control and beyond: moving towards eliminating the global tuberculosis threat. J Epidemiol Community Health 2004;58822- 825
Link to Article
Raviglione  MCUplekar  MW WHO's new Stop TB Strategy. Lancet 2006;367952- 955
PubMed Link to Article
Baris  EEzzati  M Should interventions to reduce respirable pollutants be linked to tuberculosis control programmes? BMJ 2004;3291090- 1093
PubMed Link to Article
Smith  KR National burden of disease in India from indoor air pollution. Proc Natl Acad Sci U S A 2000;9713286- 13293
PubMed Link to Article
Mishra  VKRetherford  RDSmith  KR Biomass cooking fuels and prevalence of tuberculosis in India. Int J Infect Dis 1999;3119- 129
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Forest plot of results of 5 studies1114,16 that examined smoking and tuberculosis infection. The smoking type (current smokers [Current], ex-smokers [Ex], and ever smokers [Ever]) of the study population is shown on the y-axis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Begg funnel plot with pseudo 95% confidence limits of results of 5 studies1114,16 that examined smoking and tuberculosis infection.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Forest plot of results for men only and for men and women combined in studies4,17,1928 that examined smoking and tuberculosis disease. The smoking type (ex-smokers [Ex], current smokers [Current], and ever smokers [Ever]) of the study population is shown on the y-axis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Begg funnel plot with pseudo 95% confidence limits of results of studies4,17,1928 that examined smoking and tuberculosis disease.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 5.

Forest plot of studies2933 that examined smoking and tuberculosis mortality. The sex and age of the study population are shown on the y-axis.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Studies Included in the Meta-analysis
Table Graphic Jump LocationTable 2. Exposure-Response Relationships Between Tobacco Smoking and Tuberculosis (TB) Infection and TB Disease*

References

Murray  CJLopez  AD Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997;3491498- 1504
PubMed Link to Article
Dye  C Global epidemiology of tuberculosis. Lancet 2006;367938- 940
PubMed Link to Article
 World Health Organization. Global Tuberculosis Control: Surveillance, Planning, and Financing  Geneva, Switzerland World Health Organization2005;Publication WHO/HTM/TB2005.349
Lowe  CR An association between smoking and respiratory tuberculosis. BMJ 1956;21081- 1086
PubMed Link to Article
Arcavi  LBenowitz  NL Cigarette smoking and infection. Arch Intern Med 2004;1642206- 2216
PubMed Link to Article
Bothamley  GH Smoking and tuberculosis: a chance or causal association [editorial]? Thorax 2005;60527- 528
PubMed Link to Article
 Release 8.0. STATA Statistical Software College Station, Tex StataCorp LP2003;
DerSimonian  RLaird  N Meta-analysis in clinical trials. Control Clin Trials 1986;7177- 188
PubMed Link to Article
Mosteller  FColditz  GA Understanding research synthesis (meta-analysis). Annu Rev Public Health 1996;171- 23
Link to Article
Petitti  DB Meta-Analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine.  New York, NY Oxford University Press Inc2000;
McCurdy  SAArretz  DSBates  RO Tuberculin reactivity among California Hispanic migrant farm workers. Am J Ind Med 1997;32600- 605
PubMed Link to Article
Anderson  RHSy  FSThompson  SAddy  C Cigarette smoking and tuberculin skin test conversion among incarcerated adults. Am J Prev Med 1997;13175- 181
PubMed
Adib  SMAl-Takash  HAl-Hajj  C Tuberculosis in Lebanese jails: prevalence and risk factors. Eur J Epidemiol 1999;15253- 260
Link to Article
Plant  AJWatkins  REGushulak  B  et al.  Predictors of tuberculin reactivity among prospective Vietnamese migrants: the effect of smoking. Epidemiol Infect 2002;12837- 45
PubMed Link to Article
Hussain  HAkhtar  SNanan  D Prevalence of and risk factors associated with Mycobacterium tuberculosis infection in prisoners, North West Frontier Province, Pakistan. Int J Epidemiol 2003;32794- 799
PubMed Link to Article
den Boon  Svan Lill  SWBorgdorff  MW  et al.  Association between smoking and tuberculosis infection: a population survey in a high tuberculosis incidence area. Thorax 2005;60555- 557
PubMed Link to Article
Adelstein  AMRimington  J Smoking and pulmonary tuberculosis: an analysis based on a study of volunteers for mass miniature radiography. Tubercle 1967;48219- 226
Link to Article
Yu  GPHsieh  CCPeng  J Risk factors associated with the prevalence of pulmonary tuberculosis among sanitary workers in Shanghai. Tubercle 1988;69105- 112
PubMed Link to Article
Gupta  DAggarwal  ANKumar  SJindal  SK Smoking increases risk of pulmonary tuberculosis. J Environ Med 2001;365- 69
Pérez-Padilla  RPérez-Guzmán  CBáez-Saldaña  RTorres-Cruz  A Cooking with biomass stoves and tuberculosis: a case-control study. Int J Tuberc Lung Dis 2001;5441- 447
PubMed
Dong  BGe  NZhou  Y Smoking and alcohol consumption as risk factors of pulmonary tuberculosis in Chengdu: a matched case-control study [in Chinese]. Hua Xi Yi Ke Da Xue Xue Bao 2001;32104- 106
Tekkel  MRahu  MLoit  HMBaburin  A Risk factors for pulmonary tuberculosis in Estonia. Int J Tuberc Lung Dis 2002;6887- 894
PubMed
Kolappan  CGopi  PG Tobacco smoking and pulmonary tuberculosis. Thorax 2002;57964- 966
PubMed Link to Article
Leung  CCYew  WWChan  CK  et al.  Smoking and tuberculosis in Hong Kong. Int J Tuberc Lung Dis 2003;7980- 986
PubMed
Leung  CCLi  TLam  TH  et al.  Smoking and tuberculosis among the elderly in Hong Kong. Am J Respir Crit Care Med 2004;1701027- 1033
PubMed Link to Article
Ariyothai  NPodhipak  AAkarasewi  PTornee  SSmithtikarn  SThongprathum  P Cigarette smoking and its relation to pulmonary tuberculosis in adults. Southeast Asian J Trop Med Public Health 2004;35219- 227
PubMed
Crampin  ACGlynn  JRFloyd  S  et al.  Tuberculosis and gender: exploring the patterns in a case control study in Malawi. Int J Tuberc Lung Dis 2004;8194- 203
PubMed
Lienhardt  CFielding  KSilah  JS  et al.  Investigation of the risk factors for tuberculosis: a case-control study in three countries in West Africa. Int J Epidemiol 2005;34914- 923
PubMed Link to Article
Liu  BQPeto  RChen  ZM  et al.  Emerging tobacco hazards in China, 1: retrospective proportional mortality study of one million deaths. BMJ 1998;3171411- 1422
PubMed Link to Article
Lam  THHo  SYHedley  AJMak  KHPeto  R Mortality and smoking in Hong Kong: case-control study of all adult deaths in 1998. BMJ 2001;323e36.1http://www.bmj.com/cgi/reprint/323/7309/361. Accessed January 2004
Link to Article
Gajalakshmi  VPeto  RKanaka  TSJha  P Smoking and mortality from tuberculosis and other diseases in India: retrospective study of 43000 adult male deaths and 35000 controls. Lancet 2003;362507- 515
PubMed Link to Article
Sitas  FUrban  MBradshaw  DKielkowski  DBah  SPeto  R Tobacco attributable deaths in South Africa. Tob Control 2004;13396- 399
PubMed Link to Article
Gupta  PCPednekar  MSParkin  DMSankaranarayanan  R Tobacco associated mortality in Mumbai (Bombay) India: results of the Bombay Cohort Study. Int J Epidemiol 2005;341395- 1402
PubMed Link to Article
Mackay  JAmos  A Women and tobacco. Respirology 2003;8123- 130
PubMed Link to Article
 Centers for Disease Control and Prevention. The Health Benefits of Smoking Cessation: A Report of the Surgeon General.  Rockville, Md US Dept of Health and Human Services, Public Health Service1990;Publication (CDC)90-8416
Lienhardt  C From exposure to disease: the role of environmental factors in susceptibility to and development of tuberculosis. Epidemiol Rev 2001;23288- 301
Link to Article
Maurya  VVijayan  VKShah  A Smoking and tuberculosis: an association overlooked. Int J Tuberc Lung Dis 2002;6942- 951
PubMed
Gajalakshmi  VPeto  R Verbal autopsy of 80,000 adult deaths in Tamilnadu, South India. BMC Public Health 2004;4e47
Link to Article
Soleman  NChandramohan  DShibuya  K Verbal autopsy: current practices and challenges. Bull World Health Organ 2006;84239- 245
PubMed Link to Article
Thurston  SWLiu  GMiller  DPChristiani  DC Modeling lung cancer risk in case-control studies using a new dose metric of smoking. Cancer Epidemiol Biomarkers Prev 2005;142296- 2302
PubMed Link to Article
Maudsley  GWilliams  EM “Inaccuracy” in death certification: where are we now? J Public Health Med 1996;1859- 66
Link to Article
Johansson  LAWesterling  RRosenberg  HM Methodology of studies evaluating death certificate accuracy were flawed. J Clin Epidemiol 2006;59125- 131
PubMed Link to Article
Brown  KECampbell  AH Tobacco, alcohol and tuberculosis. Br J Dis Chest 1961;55150- 158
Link to Article
Lewis  JGChamberlain  DA Alcohol consumption and smoking habits in male patients with pulmonary tuberculosis. Br J Prev Soc Med 1963;17149- 152
PubMed
 An Expanded DOTS: Framework for Effective Tuberculosis Control.  Geneva, Switzerland World Health Organization2002;
Brewer  TFHeymann  SJ To control and beyond: moving towards eliminating the global tuberculosis threat. J Epidemiol Community Health 2004;58822- 825
Link to Article
Raviglione  MCUplekar  MW WHO's new Stop TB Strategy. Lancet 2006;367952- 955
PubMed Link to Article
Baris  EEzzati  M Should interventions to reduce respirable pollutants be linked to tuberculosis control programmes? BMJ 2004;3291090- 1093
PubMed Link to Article
Smith  KR National burden of disease in India from indoor air pollution. Proc Natl Acad Sci U S A 2000;9713286- 13293
PubMed Link to Article
Mishra  VKRetherford  RDSmith  KR Biomass cooking fuels and prevalence of tuberculosis in India. Int J Infect Dis 1999;3119- 129
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 141

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles