Systemic and Salivary Cytokine Levels among Adult E-Cigarette Users: A Systematic Review and Meta Analysis

This systematic review and meta-analysis aimed to evaluate the effects of e-cigarette use on systemic and salivary cytokine levels among adults.

This systematic review and meta-analysis, registered under PROSPERO (Prospective Register of Systematic Reviews, CRD42024571203), was conducted in compliance with Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Studies assessing systemic and salivary cytokines (e.g., IL-6 [Interleukin-6], TNF-α [Tumor Necrosis Factor-alpha], IL-10 [Interleukin-10]) among adult e-cigarette users, traditional smokers, mixed smokers, and non-smokers were included based on Population-Intervention-Comparators-Outcomes (PICO) criteria. Data were extracted, risk of bias was assessed using the Joanna Briggs Institute tool, and the quality of evidence was graded with GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Meta-analysis was performed using SPSS (Statistical Package for the Social Sciences) and R software, reporting standardized mean differences (SMD) with 95% confidence intervals (CI); p ≤ 0.05 was considered significant.

A total of 286 studies were screened, with 10 meeting the inclusion criteria. The studies, conducted in the U.S., Saudi Arabia, Kuwait, Latvia, and India, included 48 to 3,614 participants. Cytokines such as, TNF-α (SMD 0.88, 95% CI 0.23-1.13; p = 0.003) and IL-1RA (SMD 0.31, 95% CI 0.10-0.52; p = 0.004), were significantly elevated in e-cigarette users compared to conventional smokers and non-smokers. INF-γ and CRP levels did not significantly differ between groups (p = 0.81 and 0.29, respectively). Meta-analyses showed elevated levels of pro-inflammatory cytokines in e-cigarette users, with substantial heterogeneity across studies. Sensitivity analyses and publication bias tests were also conducted.

Systemic and salivary cytokine levels were significantly elevated among e-cigarette users compared to non-smokers and conventional smokers, indicating a heightened inflammatory response associated with e-cigarette use.