A Longitudinal Study of Exposure to Tobacco-Related Toxicants and Subsequent Respiratory Symptoms Among US Adults with Varying E-cigarette Use Status

Background: The link between e-cigarette use and subsequent development of respiratory diseases remains an open question. Aims and Methods: A subset of a probability sample of U.S. adults from the Population Assessment of Tobacco and Health Study Waves 1 and 2 were selected for biospecimen analysis (n = 4614). Subjects were divided into three mutually exclusive groups at baseline: nonusers (n = 2849), exclusive e-cigarette users (n= 222), and poly e-cigarette/tobacco users (n= 1,543). Geometric mean concentrations of baseline biomarkers from five classes of harmful and potentially harmful constituents were reported. Multivariable linear regressions were conducted to examine the relationship between baseline biomarkers and subsequent respiratory symptoms among user groups. Results: Baseline exclusive e-cigarette users (33.6%[confidence interval, CI: 26.7% to 41.4%]) and poly e-cigarette/tobacco users (50.8%[CI: 47.4% to 54.2%]) had higher prevalence of subsequent respiratory symptoms than nonusers (21.7%[19.2% to 24.4%]). As compared with nonusers, poly e-cigarette/tobacco users had higher concentrations in clinically relevant biomarkers at baseline than exclusive e-cigarette users. Among poly e-cigarette/tobacco users, baseline nicotine metabolites (TNE2, cotinine), tobacco-specific nitrosamine (NNAL), PAH (1-NAP, 3-FLU), and volatile organic compound (N-Acetyl-S-(2-carboxyethyl)-L-cysteine, N-acetyl-S-(2-cyanoethyl)-L-cysteine) were significantly higher among those reporting subsequent respiratory symptoms than those who did not. Among exclusive e-cigarette users, baseline NNAL was significantly higher among those reporting subsequent respiratory symptoms than those who did not. Within subjects with subsequent respiratory symptoms, NNAL was 2.5 times higher in exclusive e-cigarette users (10.7[6.5 to 17.5]) and 63.4 times higher in poly e-cigarette/tobacco users (199.6[176.7 to 225.4]) than nonusers (3.1[2.4 to 3.9]). Conclusions: E-cigarette use is associated with higher concentrations of known tobacco-related toxicants and risks of subsequent respiratory symptoms than nonusers. Poly e-cigarette/tobacco users exhibit higher risk than exclusive e-cigarette users. Conclusions: E-cigarette use is associated with higher concentrations of known tobacco-related toxicants and risks of subsequent respiratory symptoms than nonusers. Poly e-cigarette/tobacco users exhibit higher risk than exclusive e-cigarette users.