Tobacco Smoking and Second-Hand Smoke Exposure Impact on Tuberculosis in Children

Abstract

Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays' (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9-12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79-11.94)] and active TB [aOR (95% CI): 3.40 (1.45-7.98)]. Moreover, IGRAs' sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response.

Keywords: Mycobacterium tuberculosis; child; cigarette smoking; immunology; passive smoking.

Figure 1

Flow-chart with the final diagnosis of the 616 children included in the study. Briefly, children coming from contact-tracing studies were stratified according to their age (<5 years old and 5–14 years old) and classified as uninfected, LTBI, and active TB. A Window Period Prophylaxis (WPP, primary prophylaxis) was indicated in the first screening in those children with negative TST and/or IGRAs. Then, after 8–12 weeks, a second screening was performed. In this second phase, TST and/or IGRAs were repeated. WPP was not prescribed in some cases due to non-acceptance.

Figure 2

IGRA positive or negative results stratification according to the smoking habit. T-SPOT.TB and QFN-G-IT results in the 616 children recruited in the study, and stratification regarding their tobacco exposure (unexposed, SHS, or smokers).

Figure 3

Specific cytokine responses against M. tuberculosis regarding the smoking habit. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokine levels (pg/mL) were analysed in a subgroup of uninfected controls (unexposed n = 10 and SHS n = 7) and LTBI individuals (unexposed n = 5 and SHS n = 9). Values obtained from the negative control tube were subtracted from the antigen-specific tube. Bars depict medians with interquartile ranges. Differences between conditions were calculated using the two-tailed Mann–Whitney U-test. Only significant differences between comparisons are indicated in the graphs. * p < 0.05; and ** p < 0.01.