Smoking is Not Beneficial for Tuberculosis

Although the recent editorial (1) accompanying the report by Blanchet and coworkers (2) states that smoking may be protective or inhibit the development of granulomatous lung disease by virtue of its anti–tumor necrosis factor(TNF) effect, it did not mention the detrimental effects of smoking on the most common granulomatous lung disease: tuberculosis. Studies from the United Kingdom, China, and, most recently, two large studies from India and Hong Kong (3, 4) have highlighted the significantly increased risk of developing active tuberculosis in smokers. Moreover, the prevalence of tuberculosis correlated with the degree and duration of tobacco use (3). The underlying mechanisms for the increased prevalence of tuberculosis in smokers have recently been elucidated. Clues about the immunosuppressive effects of tobacco smoke first came from a report showing that the parasympathetic nervous system, signaling via the vagus nerve, mediates a major, previously unnoticed, antiinflammatory pathway (5). Acetylcholinergic efferents in the vagus nerve signal to peripheral tissues via nicotinic acetylcholine receptors on macrophages, and this signal turns off production of proinflammatory cytokines such as TNF(5). Subsequently, the same group showed that acetylcholine released from the vagal efferent nerve terminals abrogates macrophagederived TNFproduction by binding to a specific type of nicotinic acetylcholine receptor ( 7), which is expressed at high levels on macrophages (6). TNFis quintessential for protective host immunity in tuberculosis, and treatment of patients with rheumatoid arthritis with monoclonal TNFinhibitors may reactivate latent tuberculosis (7). Thus, clues from the effects of smoking on inflammatory lung disorders converge on the hypothesis that smoking might oppose release or function of TNFin the lungs. Compared with other granulomatous lung diseases like sarcoidosis and hypersensitivity pneumonitis, where TNFis important in the pathogenesis, pulmonary tuberculosis causes far greater mortality (two million deaths annually) and morbidity, with consequent chronic respiratory disability due to lung remodeling (fibrosis, posttuberculous bronchiectasis, and residual cavitation). It would be more appropriate to state that the relationship of smoking to granulomatous lung disease is a doubleedged sword; the anti–TNFproperties of nicotine may be beneficial in some cases, but are clearly deleterious in others.