Assessment of the influence of direct tobacco smoke on infection and active TB management

PLoS One. 2017 Aug 24;12(8):e0182998. doi: 10.1371/journal.pone.0182998. eCollection 2017.

Abstract

Background: Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs).

Objective: In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs.

Methods: A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer's instructions.

Results: In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs' false-negative results (aOR: 3.35; 95%CI:1.47-7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02-3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97-22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related.

Conclusions: Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke.

MeSH terms

  • Adult
  • Contact Tracing
  • Cross-Sectional Studies
  • Female
  • Humans
  • Interferon-gamma Release Tests / methods
  • Likelihood Functions
  • Male
  • Middle Aged
  • Prospective Studies
  • Smoke / adverse effects*
  • Smoking*
  • Spain
  • Tobacco Products
  • Tuberculosis / complications
  • Tuberculosis / diagnostic imaging
  • Tuberculosis / drug therapy*

Substances

  • Smoke

Grants and funding

JD is funded by the Miguel Servet program of the Instituto de Salud Carlos III (Spain). ML was supported by a joint ERS/SEPAR fellowship (LTRF 2015). The research was partially supported by a grant from the Instituto de Salud Carlos III (PI 13/01546 and PI 16/01912), integrated in the Plan Nacional de I+D+I and cofunded by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); and a grant from the Sociedad Española de Neumología y Cirugía Torácica (SEPAR; Barcelona, Spain) (Smoking Integrated Research Programme Call) to NA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.