Abstract:
It has been noted by the World Health Organisation that cases of tuberculosis in 2022
globally numbered 10.6 million, resulting in 1.3 million deaths, such that TB is one of the infectious
diseases causing the greatest morbidity and mortality worldwide. Since as early as 1918, there
has been an ongoing debate as to the relationship between cigarette smoking and TB. However,
numerous epidemiological studies, as well as meta-analyses, have indicated that both active and
passive smoking are independent risk factors for TB infection, development of reactivation TB,
progression of primary TB, increased severity of cavitary disease, and death from TB, among several
other considerations. With this considerable body of evidence confirming the association between
smoking and TB, it is not surprising that TB control programmes represent a key potential preventative
intervention. In addition to coverage of the epidemiology of TB and its compelling causative link with
smoking, the current review is also focused on evidence derived from clinical- and laboratory-based
studies of disease pathogenesis, most prominently the protective anti-mycobacterial mechanisms
of the alveolar macrophage, the primary intracellular refuge of M. tuberculosis. This section of the
review is followed by an overview of the major strategies utilised by the pathogen to subvert these
antimicrobial mechanisms in the airway, which are intensified by the suppressive effects of smoke
inhalation on alveolar macrophage function. Finally, consideration is given to a somewhat underexplored, pro-infective activity of cigarette smoking, namely augmentation of antibiotic resistance
due to direct effects of smoke per se on the pathogen. These include biofilm formation, induction of
cellular efflux pumps, which eliminate both smoke-derived toxicants and antibiotics, as well as gene
modifications that underpin antibiotic resistance.
