Pulmonary Injury Biomarkers, Oxidative Stress and Systemic Inflammation in Conventional Cigarette, Waterpipe and Electronic Cigarette Users: A Cross-Sectional Comparative Study

Abstract

Background: Tobacco smoke injures the airway epithelium, imposes an oxidant load and activates innate immunity, but the biological footprint of waterpipe smoking and electronic cigarette (e-cigarette) use is less well characterised, particularly in Middle Eastern populations where all three modalities coexist.

Objective: To compare a panel of pulmonary injury biomarkers (CC16, KL-6, YKL-40, galectin-3, TREM-1), oxidative stress indices (malondialdehyde [MDA], superoxide dismutase-1 [SOD-1] protein) and the systemic inflammatory cytokine interleukin-6 (IL-6) among conventional cigarette smokers, waterpipe smokers, exclusive e-cigarette users and non-smokers. Methods: In this cross-sectional study, 120 apparently healthy men aged 18–45 years were classified by smoking status into four equal groups (n = 30 each): non-smokers, cigarette smokers, waterpipe smokers and exclusive e-cigarette users. All eight analytes were quantified in serum by enzyme-linked immunosorbent assay. Group differences were tested by one-way ANOVA with Tukey HSD post-hoc comparisons, and associations by Pearson correlation.

Results: Serum CC16 was significantly lower, and KL-6, YKL-40, IL-6 and MDA significantly higher, in every smoking group than in non-smokers (all p < 0.001; η² = 0.64–0.74). The largest deviations occurred in the two combustible groups, which did not differ significantly from each other, whereas e-cigarette users showed an intermediate profile lying between non-smokers and combustible smokers. Galectin-3, TREM-1 and SOD-1 protein did not differ among groups (p > 0.20). CC16 correlated inversely with the injury, oxidation and inflammation markers (r = −0.63 to −0.71), which were positively inter-correlated (r = 0.69–0.73; all p < 0.001).

Conclusion: A coherent signature of airway epithelial injury, lipid peroxidation and IL-6-mediated inflammation separates smokers from non-smokers. The signature is most pronounced with combustible products, including the waterpipe, and is attenuated but clearly present in e-cigarette users. CC16, KL-6, YKL-40, IL-6 and MDA were the most discriminating circulating markers in this population.

Keywords: club cell protein 16; Krebs von den Lungen-6; YKL-40; lipid peroxidation; interleukin-6; waterpipe; electronic cigarettes; tobacco harm reduction