Should tobacco control intervention be implemented into tuberculosis control program?

KEYWORDS:

• Tuberculosis
• smoking
• passive exposure to tobacco smoke
• latent TB infection
• smoking cessation
• smoke free environment

1. Smoking and tuberculosis (TB)

Smoking is associated with an increased risk of active TB [1]. Leung et al. conducted a cohort study that enrolled 42,655 elderly persons in Hong Kong and found that current smokers had an excess risk of pulmonary TB (adjusted hazard ratio 2.9, 95% confidence interval (CI) 2.0–4.1) as compared with never-smokers [2]. Lin et al. followed a cohort of 17,699 participants in Taiwan and reported that current smoking was significantly associated with an increased risk of active TB (adjusted odds ratio [aOR] 1.9, 95% CI 1.0–3.7) [3]. A study in South Africa reported that smoking is associated with increased risk of TB among HIV-infected people (aOR 3.2; 95% CI: 1.3–7.9) as compared to never smoking [4].

Smoking is associated with increased risk of TB infection [1]. De Boon et al. conducted a cross-sectional population survey and reported that smokers were more likely to have a positive tuberculin skin test than never-smokers [5]. Feng et al. reported that the proportion of patients with a positive test of QuantiFERON-TB Gold In-Tube was 42.4% among smoker, 39.5% ex-smoker, and 25% among non-smokers, indicating that adult smokers are at elevated risk for latent TB infection (LTBI) [6].

2. Passive exposure to tobacco smoke and TB

Passive exposure to tobacco smoke has been reported to be associated with both active TB and LTBI. Leung et al. followed up a cohort of 15,486 female never-smokers and reported that passive exposure to second-hand tobacco smoke in the household was independently associated with culture-confirmed TB (HR, 1.70; 95% CI, 1.04–2.80) [7].

du Preez et al. assessed the association between passive exposure to tobacco smoke and LTBI in children in South Africa and reported that exposure to tobacco smoke is significantly associated with LTBI with a dose–response relationship between the degree of exposure and risk of infection [8]. TB patients who smoke are more likely to transmit infection to their contacts [9,10].

Patra et al. conducted systematic review and meta-analysis on exposure to second-hand smoke and the risk of TB [11]. The identified 12 studies that assessed children and 8 studies assessed adult non-smokers; 2 studies assessed both populations. Passive exposure to tobacco smoke was associated with increased risk of LTBI (pooled relative risk [RR] 1.64, 95% CI 1.00–2.83) and active TB (pooled RR 3.41, 95% CI 1.81–6.45) in children, and with active TB in adults (summary RR 1.32, 95% CI 1.04–1.68). Positive and significant exposure–response relationships were observed among children under 5 years (RR 5.9, 95% CI 2.1–16.5) and children exposed to second-hand smoke through any parent (RR 4.2, 95% CI 1.9–9.2).

3. Smoking and clinical manifestations of TB

Smoking has been reported to be significantly associated with positive smear and cavitary pulmonary TB [12], thus may promote transmission of TB [9,10]. Bai et al. assessed the manifestations in relation to smoking in both diabetic and non-diabetic TB patients [13]. They reported that the adjusted relative risk of a pretreatment positive smear for a smoker compared with a non-smoker was 2.19 (95% CI 1.38–3.47) in non-diabetic patients and 2.23 (95% CI 1.29–3.87) in diabetic culture-positive pulmonary TB patients. Smoking was associated with an increased frequency of bilateral lung parenchyma involvement (aOR 1.84, 95% CI 1.16–2.93), far-advanced pulmonary TB (aOR 1.91, 95% CI 1.04–3.50), and cavitary lesions (aOR 2.03, 95% CI 1.29–3.20) in non-diabetic patients. Leung et al. assess 16,345 active TB patients in Hong Kong and reported that smoking was associated with more extensive lung disease, lung cavitation and positive sputum smear, and culture at the baseline [14].

4. Smoking and treatment outcomes of TB

Studies have reported that smoking is associated with delayed sputum conversion and unfavorable treatment outcomes [13,14]. Gegia et al. reported that current smokers had an increased risk of poor treatment outcome (aRR 1.7; 95% CI: 1.0–2.9) compared with those who had never smoked in Georgia [15]. Balian et al. investigated treatment outcomes of 992 TB patients in Armenia and reported that individuals who smoked during TB treatment had 1.6 higher odds of having unsuccessful TB treatment outcome [16]. Masjedi et al. reported that among smear-positive pulmonary TB patients the cure rate at the end of 6 months was 83.4% among non-smokers and 80.8% among quitters at 2 months, significantly higher than 67.7% among persisting smokers in Iran [17].

Tachfouti et al. reported that smoking was significantly associated with TB treatment failure (aOR 2.25, 95% CI 1.06–4.76) in Morocco [18]. Leung et al. reported that both current smokers and ex-smokers were significantly less likely to achieve cure or treatment completion within 2 years. Overall, 16.7% of unsuccessful treatment outcomes were attributable to smoking, with the key contributor being default in current smokers and death in ex-smokers [14]. Smoking is also associated with poor treatment outcomes of TB among HIV-infected people [19]. Vanden Driessche et al. reported that those who reported recent or current smoking were nearly three times as likely to experience adverse TB treatment outcomes (death or lost to follow-up) compared with those who had never smoked [19].

5. Smoking and recurrent TB

Smoking is associated with increased risk of recurrent TB [14]. Thomas et al. assessed recurrent TB among patients treated in a DOTS-based program in South India [20]. In total, 12% of successfully treated patients had recurrent TB during a 18-month follow-up period and smoking (aOR 3.1; 95% CI 1.6–6.0) was significantly associated with recurrent TB [20]. Batista et al. reported that 5% (37/711) of successfully treated patients had recurrent TB and that smoking (OR 2.53, 95% CI 1.23–5.21) was independent predictor of recurrent TB in Brazil [21]. Yen et al. followed 5567 adults after successful anti-TB treatment in Taiwan [22]. They reported that 84 (1.5%) had a recurrence of TB and that the risk of TB recurrence among subjects who smoked >10 cigarettes a day was double that of never/former smokers.

6. Smoking and delay in TB diagnosis and treatment

Delay (from the onset of symptom till the initiation of anti-TB treatment) in TB diagnosis and treatment is a serious public health concern. Longer delays might promote the spread of TB in the community and increase health care costs. Published studies reported that longer delay was significantly associated with current smokers in Nepal (aOR 2.03, 95% CI: 1.24–3.31) [23], Georgia (aOR: 3.03; 95% CI: 1.24–7.40)[24], and Iran [25].

7. Smoking cessation is essential

Clearly, smoking has a significant impact on TB and tobacco control is beneficial for TB care and prevention. Mathematical modeling has estimated that smoking would produce an excess of 18 million TB cases and 40 million TB deaths between 2010 and 2050, if smoking trends continued along current trajectories [26].

Smoking cessation intervention may reduce the risk of unfavorable treatment outcomes of TB, the risk of recurrent TB, and the risk of chronic obstructive pulmonary disease and other co-morbidities, and must be implemented during TB treatment. Wen et al. assess smokers’ risks on TB mortality and the change in such risks after smokers quit smoking [27]. They reported that smoking increased TB mortality by nine-fold (HR = 8.6), but when they quit smoking, the risk was reduced by more than half (65%), to a level not different from those who had never smoked.

8. Smoking cessation intervention is feasible and effective

Smoking cessation intervention in TB treatment has been implemented in several settings and was found to be feasible, resulting in abstinence in a substantial proportion of smokers [28]. El Sony et al. reported that in Sudan treatment success was 83% among TB patients who were enrolled in brief tobacco cessation advise, higher than 59% among those who were not enrolled. Among tobacco users undergoing the cessation intervention, 66% reported abstinence at the end of their TB treatment [28].

In Bangladesh, Siddiquea et al. implemented The Union’s smoking cessation guide recommending the ABC approach (A = ask, B = brief advice, C = cessation support)[29]. They reported that 82% of smokers had quitted smoking at the completion of TB treatment [30]. In China, Lin et al. assessed the integration of a smoking cessation intervention into routine TB services [31]. They reported that of the 244 current smokers, 156 (66.7%) reported abstinence at month 6 [31].

Bam et al. assessed the implementation and effectiveness of an intervention that promoted smoking cessation and smoke-free environments for TB patients [32]. The ABC intervention was offered within DOTS services at each visit. Smoking status and smoke-free environments at home were assessed at the first visit, each monthly follow-up and at month 6. They reported that 66.8% current smokers had quit smoking at month 6 and 86.1% had created a smoke-free home at 6-month follow-up compared with 18.5 % at baseline. All 80 health facilities were 100% tobacco-free at the end of year 2 of the project compared with 65% at baseline [32].

Campbell et al. provided brief advice to TB patients in Nepal [33]. They reported that 39% of the 195 in the intervention group claimed at least 6 months of abstinence, verified by carbon monoxide (CO) measurement in expired air.

Aryanpur et al. conducted a randomized controlled trial of smoking cessation methods in patients newly diagnosed with pulmonary TB [34]. They reported that abstinence rate at the end of 6 months were 71.7% for combined intervention group (counseling plus slow release bupropion), 33.9% for brief advice group, and 9.8% for the control group (p < 0.001) [34].

There may be obstacles in providing smoking cessation in TB patients. It has been reported that patients’ attempts to quit smoking may have been inhibited by exposure to smoking at the TB facility and that physicians had low levels of knowledge regarding the effect of smoking on TB [35]. To strengthen early diagnosis of TB and enhance effective TB treatment, tobacco cessation and smoking awareness program for TB patients should be integrated into TB control, smoke-free health facilities must be established and health care workers must be engaged and trained in providing tobacco control services.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.