Inflammatory and Carcinogenic Biomarker Signatures in E-Cigarette Users: A Comprehensive Meta-Analysis of ∼24,000 Adults.

Objectives: This meta-analysis examined the association between electronic cigarette (e-cig) use and biomarkers related to lung inflammation and carcinogenesis. Methods: A systematic review of PubMed, Scopus, Web of Science, EMBASE, and Cochrane Library (2014-April 2024) identified 16 studies including 24,079 adults. Biomarkers from urine, saliva, and plasma-cotinine, NNAL, NAT, and interleukins-were analyzed using one-way ANOVA and Tukey's post-hoc tests. The GRADE framework assessed evidence certainty and risk of bias. Results: Among participants, 27.2% were smokers, 2.7% e-cig users, 66.0% non-smokers, and 4.1% dual users. E-cig users showed higher salivary cotinine than non-smokers (p = 0.033) but not smokers (p = 0.99). NNAL was significantly elevated in smokers (p = 0.035). E-cig users had increased inflammatory markers (IL-6, TNF-α) compared with non-smokers but lower than smokers. Carcinogenic biomarkers were present in e-cig users at reduced concentrations versus smokers. GRADE indicated low to high certainty with no or moderate bias. Conclusion: E-cigarette use is associated with biomarker alterations indicating inflammation and potential carcinogenesis, paralleling some effects of traditional smoking. Standardized longitudinal studies are needed to establish causality and long-term risks.