Oral Epithelium Response of Healthy Electronic Cigarette Smokers to Electronic Cigarette Smoking

Abstract

Rationale: Smoking electronic cigarettes (e-cigarettes) is increasing in popularity, but there is little information available as to the biologic consequences to the cell populations impacted by the e-cigarette smoke. Based on the knowledge that the oral epithelium is the initial site exposed to e-cigarette smoke, we assessed the hypothesis that e-cigarette smoking modifies the biology of oral epithelium of healthy e-cigarette smokers. Methods: Oral biopsies of n=23 healthy nonsmoker controls and n=24 healthy e-cigarette smokers (e-cigarette smokers for an average of 2.0 ± 1.0 years) matched for age, gender and ethnicity, were compared based on pathology and RNA transcriptome (mRNA and miRNA) using Illumina Hi-Seq 2000 sequencing. The mRNA data were assessed in e-cigarette smokers compared to nonsmokers genome-wide (n=19,724);genes previously identified as significantly dysregulated in the oral epithelium of e-cigarette smokers vs nonsmokers (n=758);genes previously identified as significantly dysregulated in the small airway epithelium of nonsmokers following an acute exposure to e-cigarettes (n=71);and genes related to the initial steps of COVID-19 infection, including ACE2, the COVID-19 receptor (n=9). The miRNA of e-cigarette smokers and nonsmokers was compared on a genome-wide basis (n=1,100 mature and human miRNAs). All comparisons were performed using ANOVA, Benajmini-Hochberg corrected p value <0.05 was considered significant. Results: The morphology of the epithelium and lamina propria in e-cigarette smokers was normal, with no thickening of the epithelium, dysplasia, basilar hyperplasia, dyskeratosis, and no abnormal vascularity, or inflammatory infiltration. The basilar layer in ecigarette smokers appeared normal, with normal mitotic activity and no nuclear pleomorphism. Assessment of the transcriptome, both on mRNA and miRNA levels, based on all gene lists did not identify any genes significantly modified in the oral epithelium of e-cigarette smokers compared to nonsmokers. Conclusions: The oral epithelium pathology and transcriptome of e-cigarette smokers are not modified in response to e-cigarette smoking.