Biomarkers of Exposure and Effect in the Lungs of Smokers, Nonsmokers, and Electronic Cigarette Users.

Abstract

Nicotine-containing electronic cigarette (e-cig) use has become widespread. However, understanding the biological impact of e-cigs compared with smoking on the lung is needed. There are major gaps in knowledge for chronic effects and for an etiology to recent acute lung toxicity leading to death among vapers. We conducted bronchoscopies in a cross-sectional study of 73 subjects (42 never-smokers, 15 e-cig users, and 16 smokers). Using bronchoalveolar lavage and brushings, we examined lung inflammation by cell counts, cytokines, genome-wide gene expression, and DNA methylation. There were statistically significant differences among never-smokers, e-cig users, and smokers for inflammatory cell counts and cytokines (FDR q < 0.1). The e-cig users had values intermediate between smokers and never-smokers, with levels for most of the biomarkers more similar to never-smokers. For differential gene expression and DNA methylation, e-cig users also more like never-smokers; many of these genes corresponded to smoking-related pathways, including those for xenobiotic metabolism, aryl hydrocarbon receptor signaling, and oxidative stress. Differentially methylated genes were correlated with changes in gene expression, providing evidence for biological effects of the methylation associations. These data indicate that e-cigs are associated with less toxicity than cigarettes for smoking-related pathways. What is unknown may be unique effects for e-cigs not measured herein, and a comparison of smokers completely switching to e-cigs compared with former smokers. Clinical trials for smokers switching to e-cigs who undergo serial bronchoscopy and larger cross-sectional studies of former smokers with and without e-cig use, and for e-cigs who relapse back to smoking, are needed. These data can be used for product regulation and for informing tobacco users considering or using e-cigs. What is unknown may be unique effects for e-cigs not measured herein, and clinical trials with serial bronchoscopy underway can demonstrate a direct relationship for changes in lung biomarkers.