INT J TUBERC LUNG DIS 11(3):258–262 © 2007 The Union
EDUCATIONAL SERIES: TOBACCO AND TUBERCULOSIS
SERIALISED GUIDE Tobacco cessation interventions for tuberculosis patients NUMBER 1 IN THE SERIES
Associations between tobacco and tuberculosis C-Y. Chiang, K. Slama, D. A. Enarson International Union Against Tuberculosis and Lung Disease, Paris, France SUMMARY
The association between smoking and tuberculosis (TB) has been investigated since 1918. Both passive and active exposure to tobacco smoke have been shown to be associated with tuberculous infection and with the transition from being infected to developing TB disease. The association between smoking and developing TB disease (without separating the risk of transition from being exposed to being infected and that from being infected to developing TB disease) has been reported substantially. Smoking affects the clinical manifestations of TB. It has been shown that ever smokers are more likely to have cough, dyspnoea,
chest radiograph appearances of upper zone involvement, cavity and miliary appearance, and positive sputum culture, but are less likely to have isolated extra-pulmonary involvement than non-smokers. Smoking has been found to be associated with both relapse of TB and TB mortality. There appears to be enough evidence to conclude that smoking is causally associated with TB disease. Patients with TB need and should receive counselling and assistance in stopping smoking. K E Y W O R D S : passive smoking; smoking; tobacco; tuberculosis
STUDIES THAT INVESTIGATE the association between smoking and tuberculosis (TB) have been published since 1918.1 Two years after the preliminary publication of the ground-breaking study by Doll and Hill on the mortality of doctors in relation to their smoking habits,2 Lowe published an article examining the sex differentials in TB mortality rates in England and Wales.3 He noted that, in the period 1871–1880, mortality from pulmonary TB (PTB) was similarly high in early adult life for both males and females, whereas in 1941–1950, the TB mortality rate of males in middle and late life was much higher than that of females. Using a case-control study design, Lowe demonstrated that TB patients were more likely to be heavy smokers than control patients, but he did not control for possible confounding variables. The same hypothesis has been suggested more recently,4 because the question is still unresolved. Brown and Campbell in 19615 and Lewis and Chamberlain in 1963,6 investigated both smoking and alcohol use, and found that alcohol drinking was the major factor associated with TB. These two studies greatly influenced many people working in TB control into thinking that smoking was in fact not associated with TB, but was an artefact for poverty and/or alcohol abuse. Nevertheless, the associations between both active and passive exposure to tobacco
smoke and TB disease, tuberculous infection, TB mortality and other TB-related issues have been investigated by several researchers, especially in the last decade.
DOES EXPOSURE TO TOBACCO SMOKE INCREASE THE RISK OF TUBERCULOUS INFECTION? Both passive and active exposures to tobacco smoke have been shown to be associated with tuberculous infection. This was first shown by Kuemmerer and Comstock in 1967.7 Sociological factors of tuberculin sensitivity were investigated among 7787 junior and senior high-school students. Students with large reactions (11 mm) to 5 tuberculin units (TU) of standard purified protein derivative (PPD-S) were more likely to live in poorer and more crowded conditions, to have had household exposure to TB and to have come from broken homes. For students whose parents both smoked, the frequency of large reactions was more than twice as high as for those with at least one nonsmoking parent. The association between passive exposure to tobacco smoke and tuberculous infection was also observed in India.8 Singh et al. investigated prevalence and risk factors for tuberculous infection among children in household contact with adults with
Correspondence to: Karen Slama, International Union Against Tuberculosis and Lung Disease, 68 boulevard Saint Michel, 75006 Paris, France. Tel: (33) 1 44 32 03 60. Fax: (33) 1 43 29 90 87. e-mail:
[email protected]
Associations between tobacco and tuberculosis
PTB and found that passive exposure to tobacco smoke was significantly associated with tuberculous infection (adjusted odds ratio [aOR] 2.7, 95% confidence interval [CI] 1.5–4.7). The association between active exposure to tobacco smoke and tuberculin reactivity was shown by tuberculin skin test (TST) in residential homes for the elderly in Liverpool.9 Nisar et al. showed that Heaf test positivity grade was directly related to pack-years of smoking. The study population consisted of elderly residents who had probably been infected in the remote past. The effect of social class on the relation between smoking and tuberculin reactivity was not investigated. The association between pack-years and a significant TST reaction was also observed in a cross-sectional population survey in a high TB incidence area in South Africa.10 Of 2401 investigated adults, 1309 (55%) were current or ex-smokers and 1832 (76%) had a significant TST reaction (induration 10 mm); 82% (n 1070) of the 1309 current or ex-smokers had a significant TST reaction compared with 70% (n 762) of the 1092 never smokers (aOR 1.77, 95%CI 1.41–2.21). The aOR (1.90, 95%CI 1.28–2.81) of smoking more than 15 pack-years was slightly higher than that for less than 5 pack-years (aOR 1.77, 95%CI 1.33–2.35) and 5–15 pack-years (aOR 1.77, 95%CI 1.33–2.35), as compared with non-smokers. The association between duration of smoking and TST conversion was observed in a small case-control study conducted among incarcerated adults.11 Neither the number of cigarettes smoked per day prior to incarceration nor the number of cigarettes smoked since incarceration was significantly associated with TST conversion. However, the duration of smoking (smoking for 15 years) was significantly associated with TST conversion. The proportion of smokers who regularly drank alcohol was significantly higher than among nonsmokers. However, regular consumption of alcohol was not significantly associated with TST conversion. The limitation of this study was the small sample size.11 A significant association between the number of cigarettes smoked and tuberculous infection was also observed in a cross-sectional study among inmates in Pakistan.12 The association between duration of smoking and tuberculous infection was also observed in a crosssectional study by Plant et al.13 They studied predictors of tuberculin reactivity among 1395 Vietnamese migrants aged 15 years: 8.9% of these migrants were current smokers, 5.2% ex-smokers and 85.9% lifetime non-smokers; 44% had an induration of 10 mm and 18.6% had an induration of 15 mm. Both duration of smoking and the number of cigarettes were significantly associated with a significant reaction (induration of 10 mm and 15 mm). Furthermore, those having quit for more than 10 years were significantly less likely to have an induration of 10 mm, implying that cessation of smoking reduced susceptibility to infection.
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No cohort studies and only one case-control study have investigated the association between exposure to tobacco smoke and tuberculin reactivity. The possibility that exposure to tobacco smoke is associated with an increased exposure to the source of infection of TB cannot be excluded with certainty. Thus, in a recent systematic review, the evidence of the association between exposure to tobacco smoke and tuberculous infection was judged to be limited (article submitted).
DOES EXPOSURE TO TOBACCO SMOKE INCREASE THE RISK OF DEVELOPING TUBERCULOSIS DISEASE? Developing TB disease involves two distinct transitions, with their corresponding risk factors: the transition from being exposed to being infected and the transition from being infected to developing disease. The association between passive exposure to tobacco smoke and the transition from being infected to developing TB disease has been investigated using a case-control study design. Altet et al. investigated passive smoking and risk of PTB in children immediately following infection.14 Cases were 93 household contacts who became active TB cases, and controls were 95 household contacts who were tuberculin-positive without evidence of active disease. Passive exposure to tobacco smoke in children was a risk factor for the development of active PTB immediately following infection (aOR 5.4, 95%CI 2.4–11.9). Furthermore, there was a dose-response relationship between the number of cigarettes that family members smoked daily and the risk of developing TB in children. Alcaide et al. investigated active cigarette smoking as a risk factor for TB in young adults.15 Cases were patients with active PTB and controls were persons with positive tuberculin reactions. In multivariate analysis, active smoking was associated with TB (aOR 3.8, 95%CI 1.5–9.8) but not passive smoking. There was a dose-response relationship between the number of cigarettes smoked and the risk of TB. The association between exposure to tobacco smoke and developing TB disease (without separating the risk of transition from being exposed to being infected and that from being infected to developing TB disease) has been substantially reported.16–22 Leung et al. followed a cohort of 42 655 elderly persons in Hong Kong and found that current smokers had an excess risk of PTB (adjusted hazard ratio [aHR] 2.87, 95%CI 2.0– 4.1) but not extra-pulmonary TB (aHR 1.04, 95%CI 0.3–3.3), as compared with never-smokers.17 Among the current smokers, the number of cigarettes per day was significantly associated with developing TB (2 test for trend, P 0.01). As the cohort involved elderly persons in the community, and the majority of TB cases in Hong Kong were thought to arise from reactivation, the authors reasoned that the relationship between smoking and TB is likely to be causal. The dose-response relationship of the number of cigarettes
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smoked and TB was also demonstrated by a nested casecontrol study in Tamil Nadu, India (1–10 per day, 11– 20 per day, 20 per day, 2 test for trend, P 0.001).18 The association between passive exposure to tobacco smoke and TB was investigated by Tipayamongkholgul et al. in BCG-vaccinated children using a case-control study design.19 Cases were 130 children with TB and controls were 130 age- and sex-matched children who attended the orthopaedics department. Passive exposure to tobacco smoke was significantly associated with TB (OR 9.31, 95%CI 3.14–27.58) among children with history of TB contact. The association between passive exposure to tobacco and TB was also shown by a case-control study in Estonia.23 The association between years of smoking and TB was demonstrated by case-control studies in Tamil Nadu, India (10 years, 11–20 years, 20 years, 2 test for trend, P 0.001),18 Washington, DC, USA (persons who had smoked for 20 years were 2.6 times more likely to have TB than were non-smokers)24 and in Liverpool, North-West England (TB cases were 2.3 times more likely to have smoked for at least 30 years).25 The association between active smoking and TB was also shown by case-control studies in three countries in Africa,20 in Estonia,23 and in Mexico.26
a DOTS-based programme in Tiruvallur District, South India, revealed that smoking was significantly associated with default as compared with success in univariate analysis but not in multivariate analysis. Among patients without multidrug-resistant TB (MDR-TB), a significantly higher likelihood of failure, as compared with success, was associated with smoking in univariate analysis. Smoking was not associated with death.30 Smoking was also not associated with death among TB patients in a study in Catalunya, Spain.27 However, the cohort study by Leung et al. found that TB patients who smoked were more likely to die from any cause during follow-up than ex-smokers and never smokers (P 0.001), although only nine (24.3%) of the 37 deaths could be attributed directly to TB.17
DOES EXPOSURE TO TOBACCO SMOKE INCREASE THE RISK OF RELAPSE?
Leung et al. investigated 851 TB patients notified in 1996 in Hong Kong and found that ever smokers were more likely to have cough, dyspnoea, chest radiograph appearances of upper zone involvement, cavity and miliary appearance and positive sputum culture, but were less likely to have isolated extra-pulmonary involvement, as compared with non-smokers.16 A crosssectional study by Altet-Gomez et al. revealed that among TB patients, those who were smokers were more likely to have developed PTB, had more cavitary lesions and were more likely to be smear-positive.27
Thomas et al. investigated predictors of relapse among PTB patients treated in a DOTS-based programme in South India.31 A total of 503 cured TB patients were followed for 18 months after treatment completion. Relapse was defined as a cured patient who had two sputum smears positive for acid-fast bacilli by direct smear, one smear and one culture positive from separate samples, or two positive cultures. Of the 487 patients for whom drug susceptibility results were available at the start of treatment, 455 (93%) had susceptible organisms, 30 (6%) had isoniazid resistance and two had isolates resistant to both isoniazid and rifampicin (MDR-TB). Of the 503 patients, 62 (12%) relapsed during the 18-month period. Logistic regression analysis showed that a higher relapse rate was independently associated with irregular treatment (aOR 2.5, 95%CI 1.4–4.7), drug resistance (aOR 4.8, 95%CI 2.0–11.6), and smoking (OR 3.1, 95%CI 1.6–6.0). The relapse rate among non-smoking patients with drug-sensitive organisms and who were adherent to treatment was 4.8%.
DOES EXPOSURE TO TOBACCO SMOKE AFFECT BACTERIOLOGICAL CONVERSION?
IS EXPOSURE TO TOBACCO SMOKE ASSOCIATED WITH TUBERCULOSIS MORTALITY?
Smoking was not found to be associated with sputum smear16,28 or culture16 conversion after 2 months of anti-tuberculosis treatment. However, a clinical trial on immunotherapy with M. vaccae in the treatment of PTB analysed time to sputum conversion using multivariate Cox’s proportional hazards regression and showed that time to conversion was longer among smokers than among non-smokers.29
A cohort study by Doll et al. investigated mortality in relation to smoking among male British doctors. The relative risk of dying from PTB among smokers was 2.8 as compared with lifetime non-smokers.32 Gajalakshmi et al. investigated the smoking habits of men who had died in the state of Tamil Nadu using a case-control study design, and found that the death rates from medical causes of ever smokers were twice as high as those of never smokers. Of the excess mortality among smokers, a third involved respiratory disease, mainly TB.33 That smokers have a higher risk of TB mortality was also shown by studies in China,34 Hong Kong35 and South Africa.36 The possibility of misclassification of the cause of death in these studies is a serious limitation.
DOES EXPOSURE TO TOBACCO SMOKE AFFECT CLINICAL MANIFESTATIONS OF TUBERCULOSIS?
DOES EXPOSURE TO TOBACCO SMOKE AFFECT OUTCOME OF TREATMENT? A study investigating risk factors associated with default, failure and death among TB patients treated in
Associations between tobacco and tuberculosis
IS EXPOSURE TO TOBACCO SMOKE ASSOCIATED WITH DELAY IN THE DIAGNOSIS AND TREATMENT OF TUBERCULOSIS? Smoking was not associated with delay in the diagnosis and treatment of TB in Catalunya, Spain,27 southern Taiwan,37 but having given up smoking was shown to be associated with a total delay of more than 60 days in Recife, Brazil.38
IS EXPOSURE TO TOBACCO SMOKE ASSOCIATED WITH ANTI-TUBERCULOSIS DRUG RESISTANCE? Barroso et al. conducted a case-control study to investigate risk factors for acquired MDR-TB.39 Cases were patients with acquired MDR-TB and controls were patients with susceptible TB who had undergone a first course of treatment during a period similar to that of the first episode of TB treatment of an MDR-TB case. Both smoking and ‘alcoholism smoking’ were associated with acquired MDR-TB in univariate analysis. ‘Alcoholism smoking’ was associated with acquired MDR-TB in multivariate analysis. Smoking alone was not included in multivariate analysis. Ruddy et al. conducted a cross-sectional study to investigate both prevalence and risk factors of drug resistance.40 Smoking was found to be associated with isoniazid resistance. The authors concluded that more evidence is needed to explain this association.
CONCLUSIONS There appears to be enough evidence to conclude that smoking is causally associated with active TB. Patients with TB need and should receive counselling and assistance in stopping tobacco use. Health professionals working in TB care can set up cessation counselling without elaborate or costly training; they can do this systematically within a DOTS-based programme, and it should become as much part of the routine as any of the other standard practices of treatment. The following articles in this series present some of the steps that can be taken to help people to stop smoking in the context of TB treatment. References 1 Webb G B. The effect of the inhalation of cigarette smoke on the lungs. A clinical study. Am Rev Tuberc 1918; March: 25–27. 2 Doll R, Hill A B. The mortality of doctors in relation to their smoking habits. BMJ 1954, reprinted in BMJ 2002; 328: 1529–1533. 3 Lowe C R. An association between smoking and respiratory tuberculosis. BMJ 1956; Nov. 10: 1081–1086. Same data further analysed in Edwards J H. Contribution of cigarette smoking to respiratory disease. Br J Prev Soc Med 1957; 11: 10–21. 4 Watkins R E, Plant A J. Does smoking explain sex differences in the global tuberculosis epidemic? Epidemiol Infect 2006; 134: 333–339.
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5 Brown K E, Campbell A H. Tobacco, alcohol and tuberculosis. Brit J Dis Chest 1961; 55: 150–158. 6 Lewis J G, Chamberlain D A. Alcohol consumption and smoking habits in male patients with pulmonary tuberculosis. Brit J Prev Soc Med 1963; 17: 149–152. 7 Kuemmerer J M, Comstock G W. Sociologic concomitants of tuberculin sensitivity. Am Rev Respir Dis 1967; 96: 885–892. 8 Singh M, Mynak M L, Kumar L, Mathew J L, Jindal S K. Prevalence and risk factors for transmission of infection among children in household contact with adults having pulmonary tuberculosis. Arch Dis Child 2005; 90: 624–628. 9 Nisar M, Williams C S, Ashby D, Davies G. Tuberculin testing in residential homes for the elderly. Thorax 1993; 48: 1257– 1260. 10 den Boon S, van Lill S W P, Borgdorff M W, et al. The association between smoking and tuberculosis infection: a population survey in a high tuberculosis incidence area. Thorax 2005; 60: 555–557. 11 Anderson R H, Sy F S, Thompson S, Addy C. Cigarette smoking and tuberculin skin test conversion among incarcerated adults. Am J Prev Med 1997; 13: 175–181. 12 Hussain H, Akhtar S, Nanan D. Prevalence of and risk factors associated with Mycobacterium tuberculosis infection in prisoners, North-West Frontier Province, Pakistan. Int J Epidemiol 2003; 32: 794–799. 13 Plant A J, Watkins R E, Gushulak B, et al. Predictors of tuberculin reactivity among prospective Vietnamese migrants: the effect of smoking. Epidemiol Infect 2002; 128: 37–45. 14 Altet M N, Alcaide J, Plans P, et al. Passive smoking and risk of pulmonary tuberculosis in children immediately following infection. A case-control study. Tubercle Lung Dis 1996; 77: 537–544. 15 Alcaide J, Altet M N, Plans P, et al. Cigarette smoking as a risk factor for tuberculosis in young adults: a case-control study. Tubercle Lung Dis 1996; 77: 112–116. 16 Leung C C, Yew W W, Chan C K, et al. Smoking and tuberculosis in Hong Kong. Int J Tuberc Lung Dis 2003; 7: 980–986. 17 Leung C C, Li T, Lam T H, et al. Smoking and tuberculosis among the elderly in Hong Kong. Am J Respir Crit Care Med 2004; 170: 1027–1033. 18 Kolappan C, Gopi P G. Tobacco smoking and pulmonary tuberculosis. Thorax 2002; 57: 964–966. 19 Tipayamongkholgul M, Podhipak A, Chearskul S, Sunakorn P. Factors associated with the development of tuberculosis in BCG immunized children. Southeast Asian J Trop Med Public Health 2005; 36: 145–150. 20 Lienhardt C, Fielding K, Sillah J S, et al. Investigation of the risk factors for tuberculosis: a case-control study in three countries in West Africa. Int J Epidemiol 2005; 34: 914–923. 21 Chang K C, Leung C C, Tam C M. Tuberculosis risk factors in a silicotic cohort in Hong Kong. Int J Tuberc Lung Dis 2001; 5: 177–184. 22 Hnizdo E, Murray J. Risk of pulmonary tuberculosis relative to silicosis and exposure to silica dust in South African gold miners. Occup Environ Med 1998; 55: 496–502. 23 Tekkel M, Rahu M, Loit H-M, Baburin A. Risk factors for pulmonary tuberculosis in Estonia. Int J Tuberc Lung Dis 2002; 6: 887–894. 24 Buskin S E, Gale J L, Weiss N S, Nolan C. Tuberculosis risk factors in adults in King County, Washington, 1988–1990. Am J Public Health 1994; 84: 1750–1756. 25 Tocque K, Bellis M A, Beeching J N, Syed Q, Remmington T, Davies P D O. A case-control study of lifestyle risk factors associated with tuberculosis in Liverpool, North-West England. Eur Respir J 2001; 18: 959–964. 26 Perez-Padilla R, Perez-Guzman C, Baez-Saldana R, TorresCruz A. Cooking with biomass stoves and tuberculosis: a casecontrol study. Int J Tuberc Lung Dis 2001; 5: 441–447. 27 Altet-Gomez M N, Alcaide J, Godoy P, Romero M A, Hernandez del Rey I. Clinical and epidemiological aspects of smoking
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and tuberculosis: a study of 13 038 cases. Int J Tuberc Lung Dis 2005; 9: 430–436. Abal A T, Jayakrishnana B, Parwer S, El Shamy A, Abahussain E, Sharma P N. Effect of cigarette smoking on sputum smear conversion in adults with active pulmonary tuberculosis. Respir Med 2005; 99: 415–420. Durban Immunotherapy Trial Group. Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial. Lancet 1999; 354: 116–119. Santha T, Garg R, Frieden T R, et al. Risk factors associated with default, failure and death among tuberculosis patients treated in a DOTS programme in Tiruvallur district, South India, 2000. Int J Tuberc Lung Dis 2002; 6: 780–788. Thomas A, Gopi P G, Santha T, et al. Predictors of relapse among pulmonary tuberculosis patients treated in a DOTS programme in South India. Int J Tuberc Lung Dis 2005; 9: 556–561. Doll R, Peto R, Wheatley K, Gray R, Sutherland I. Mortality in relation to smoking: 40 years’ observations on male British doctors. BMJ 1994; 309: 901–911. Gajalakshmi V, Peto R, Kanaka T S, Jha R. Smoking and mortality from tuberculosis and other diseases in India: retrospective study of 43 000 adult male deaths and 35 000 controls. Lancet 2003; 362: 507–515.
34 Liu B-Q, Peto R, Chen Z-M, et al. Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths. BMJ 1998; 317: 1411–1422. 35 Lam T H, Ho S Y, Hedley A J, Mak K H, Peto R. Mortality and smoking in Hong Kong: case control study of all adult deaths in 1998. BMJ 2001; 323: 1–6. 36 Sitas F, Urban M, Bradshaw D, Kielkowski D, Bah S, Peto R. Tobacco attributable deaths in South Africa. Tobacco Control 2004; 13: 396–399. 37 Chiang C Y, Chang C T, Chang R E, Li C T, Huang R M. Patient and health system delays in the diagnosis and treatment of tuberculosis in Southern Taiwan. Int J Tuberc Lung Dis 2005; 9: 1006–1012. 38 Dos Santos M A P S, Albuquerque M F P M, Ximenes R A A, et al. Risk factors for treatment delay in pulmonary tuberculosis in Recife, Brazil. BMC Public Health 2005; 18: 25. 39 Barroso E C, Mota R M S, Santos R O, Sousa A L O, Barroso J B, Rodrigues J L N. Risk factors for acquired multidrugresistant tuberculosis. J Pneumol 2003; 29: 89–97. 40 Ruddy M, Balabanova Y, Graham C, et al. Rates of drug resistance and risk factor analysis in civilian and prison patients with tuberculosis in Samara Region, Russia. Thorax 2005; 60: 130–135.
RÉSUMÉ
L’association entre le tabagisme et la tuberculose (TB) a fait l’objet d’investigations depuis 1918. On a démontré que l’exposition tant passive qu’active à la fumée de tabac était associée avec l’infection tuberculeuse et avec le passage de l’infection vers le développement de la maladie tuberculeuse. L’association entre le tabagisme et le développement de la maladie tuberculeuse (sans séparer le risque de passage d’exposition à infection et celui du passage d’infection à développement de la maladie tuberculeuse) a fait l’objet de publications substantielles. Le tabagisme affecte les manifestations cliniques de la TB. Il a été démontré que les fumeurs et ex-fumeurs sont plus susceptibles de se plaindre de toux, de dyspnée et
d’être porteurs de signes radiologiques d’atteinte des champs pulmonaires supérieurs, de creusement et de formes miliaires, et d’avoir des cultures d’expectoration positives et sont moins susceptibles d’avoir des atteintes extrapulmonaires isolées par comparaison avec les nonfumeurs. On a démontré que le tabagisme est en association tant avec la rechute de TB qu’avec la mortalité tuberculeuse. Il semble qu’il y ait suffisamment de preuves pour conclure qu’il existe une relation de causalité entre tabagisme et maladie tuberculeuse. Les patients atteints de TB ont besoin et doivent recevoir des accompagnements et de l’assistance pour l’arrêt du tabagisme.
RESUMEN
Desde 1918 se ha estudiado la asociación entre el tabaquismo y la tuberculosis (TB). La exposición activa y pasiva al humo del tabaco se ha asociado con la infección tuberculosa y con la transición del estado de infección al de enfermedad tuberculosa. La asociación entre el hábito tabáquico y la aparición de enfermedad tuberculosa (sin separar el riesgo de transición entre exposición e infección y entre infección y enfermedad) se ha comunicado abundantemente en las publicaciones. El tabaquismo modifica las manifestaciones clínicas de la TB. Se ha demostrado que quienes han sido fumadores en algún momento tienen mayor probabilidad de presentar tos,
disnea, cultivos positivos de esputo y lesiones radiográficas del parénquima superior, cavernas y apariencia miliar que quienes nunca han fumado, y al mismo tiempo exhiben menor frecuencia de localizaciones extrapulmonares aisladas. Se ha observado que el tabaquismo se asocia con la recaída y con la mortalidad por TB. Parecieran existir pruebas suficientes para inferir la existencia de una relación causal entre el hábito tabáquico y la enfermedad tuberculosa. Los pacientes con TB precisan y deberían recibir orientación y ayuda con el objeto de abandonar del tabaquismo.
