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Transcriptomic Evidence That Switching from Tobacco to Electronic Cigarettes Does Not Reverse Damage to the Respiratory Epithelium.

ABSTRACT: The health benefits of switching from tobacco to electronic cigarettes (ECs) are neither confirmed nor well characterized. To address this problem, we used RNA-seq analysis to compare the nasal epithelium transcriptome from the following groups (n = 3 for each group): (1) former smokers who completely switched to second generation ECs for at least 6 months, (2) current tobacco cigarette smokers (CS), and (3) non-smokers (NS). Group three included one former cigarette smoker. The nasal epithelial biopsies from the EC users vs. NS had a higher number of differentially expressed genes (DEGs) than biopsies from the CS vs. NS and CS vs. EC sets (1817 DEGs total for the EC vs. NS, 407 DEGs for the CS vs. NS, and 116 DEGs for the CS vs. EC comparison). In the EC vs. NS comparison, enriched gene ontology terms for the downregulated DEGs included cilium assembly and organization, whereas gene ontologies for upregulated DEGs included immune response, keratinization, and NADPH oxidase. Similarly, ontologies for cilium movement were enriched in the downregulated DEGs for the CS vs. NS group. Reactome pathway analysis gave similar results and also identified keratinization and cornified envelope in the upregulated DEGs in the EC vs. NS comparison. In the CS vs. NS comparison, the enriched Reactome pathways for upregulated DEGs included biological oxidations and several metabolic processes. Regulator effects identified for the EC vs. NS comparison were inflammatory response, cell movement of phagocytes and degranulation of phagocytes. Disease Ontology Sematic Enrichment analysis identified lung disease, mouth disease, periodontal disease and pulmonary fibrosis in the EC vs. NS comparison. Squamous metaplasia associated markers, keratin 10, keratin 13 and involucrin, were increased in the EC vs. NS comparison. Our transcriptomic analysis showed that gene expression profiles associated with EC use are not equivalent to those from non-smokers. EC use may interfere with airway epithelium recovery by promoting increased oxidative stress, inhibition of ciliogenesis, and maintaining an inflammatory response. These transcriptomic alterations may contribute to the progression of diseases with chronic EC use.

SUBMITTER: Pozuelos GL

PROVIDER: S-EPMC9321508 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:E-cigarette (EC) use is increasing exponentially worldwide. The early cardiovascular effects of switching from tobacco cigarettes (TC) to EC in chronic smokers is unknown. Meta-analysis of flow-mediated dilation (FMD) studies indicate 13% lower pooled, adjusted relative risks of cardiovascular events with every 1% improvement in FMD. OBJECTIVES:This study sought to determine the early vascular impact of switching from TC to EC in chronic smokers. METHODS:The authors conducted a prospective, randomized control trial with a parallel nonrandomized preference cohort and blinded endpoint of smokers ?18 years of age who had smoked ?15 cigarettes/day for ?2 years and were free from established cardiovascular disease. Participants were randomized to EC with nicotine or EC without nicotine for 1 month. Those unwilling to quit continued with TC in a parallel preference arm. A propensity score analysis was done to adjust for differences between the randomized and preference arms. Vascular function was assessed by FMD and pulse wave velocity. Compliance with EC was measured by carbon monoxide levels. RESULTS:Within 1 month of switching from TC to EC, there was a significant improvement in endothelial function (linear trend ? = 0.73%; 95% confidence interval [CI]: 0.41 to 1.05; p < 0.0001; TC vs. EC combined: 1.49%; 95% CI: 0.93 to 2.04; p < 0.0001) and vascular stiffness (-0.529 m/s; 95% CI: -0.946 to -0.112; p = 0.014). Females benefited from switching more than males did in every between-group comparison. Those who complied best with EC switch demonstrated the largest improvement. There was no difference in vascular effects between EC with and without nicotine within the study timeframe. CONCLUSIONS:TC smokers, particularly females, demonstrate significant improvement in vascular health within 1 month of switching from TC to EC. Switching from TC to EC may be considered a harms reduction measure. (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use [VESUVIUS]; NCT02878421; ISRCTN59133298).

Project description:Tobacco cigarette (TC) smoking has never been lower in the United States, but electronic cigarette (EC) vaping has reached epidemic proportions among our youth. Endothelial dysfunction, as measured by flow-mediated vasodilation (FMD) is a predictor of future atherosclerosis and adverse cardiovascular events and is impaired in young TC smokers, but whether FMD is also reduced in young EC vapers is uncertain. The aim of this study in otherwise healthy young people was to compare the effects of acute and chronic tobacco cigarette (TC) smoking and electronic cigarette (EC) vaping on FMD. FMD was compared in 47 nonsmokers (NS), 49 chronic EC vapers, and 40 chronic TC smokers at baseline and then after EC vapers (n = 31) and nonsmokers (n = 47) acutely used an EC with nicotine (ECN), EC without nicotine (EC0), and nicotine inhaler (NI) at ~4-wk intervals and after TC smokers (n = 33) acutely smoked a TC, compared with sham control. Mean age (NS, 26.3 ± 5.2 vs. EC, 27.4 ± 5.45 vs. TC, 27.1 ± 5.51 yr, P = 0.53) was similar among the groups, but there were more female nonsmokers. Baseline FMD was not different among the groups (NS, 7.7 ± 4.5 vs. EC:6.6 ± 3.6 vs. TC, 7.9 ± 3.7%∆, P = 0.35), even when compared by group and sex. Acute TC smoking versus control impaired FMD (FMD pre-/postsmoking, -2.52 ± 0.92 vs. 0.65 ± 0.93%∆, P = 0.02). Although the increase in plasma nicotine was similar after EC vapers used the ECN versus TC smokers smoked the TC (5.75 ± 0.74 vs. 5.88 ± 0.69 ng/mL, P = 0.47), acute EC vaping did not impair FMD. In otherwise healthy young people who regularly smoke TCs or ECs, impaired FMD compared with that in nonsmokers was not present at baseline. However, FMD was significantly impaired after smoking one TC, but not after vaping an equivalent "dose" (estimated by change in plasma nicotine) of an EC, consistent with the notion that non-nicotine constituents in TC smoke mediate the impairment. Although it is reassuring that acute EC vaping did not acutely impair FMD, it would be dangerous and premature to conclude that ECs do not lead to atherosclerosis.NEW & NOTEWORTHY In our study of otherwise healthy young people, baseline flow-mediated dilation (FMD), a predictor of atherosclerosis and increased cardiovascular risk, was not different among tobacco cigarette (TC) smokers or electronic cigarette (EC) vapers who had refrained from smoking, compared with nonsmokers. However, acutely smoking one TC impaired FMD in smokers, whereas vaping a similar EC "dose" (as estimated by change in plasma nicotine levels) did not. Finally, although it is reassuring that acute EC vaping did not acutely impair FMD, it would be premature and dangerous to conclude that ECs do not lead to atherosclerosis or increase cardiovascular risk.

Project description:BackgroundCigarette smoking is associated with an increase in cardiovascular disease risk, attributable in part to reactive volatile organic chemicals (VOCs). However, little is known about the extent of VOC exposure due to the use of other tobacco products.MethodsWe recruited 48 healthy, tobacco users in four groups: cigarette, smokeless tobacco, occasional users of first generation e-cigarette and e-cigarette menthol and 12 healthy nontobacco users. After abstaining for 48 h, tobacco users used an assigned product. Urine was collected at baseline followed by five collections over a 3-h period to measure urinary metabolites of VOCs, nicotine, and tobacco alkaloids.ResultsUrinary levels of nicotine were ≃2-fold lower in occasional e-cigarette and smokeless tobacco users than in the cigarette smokers; cotinine and 3-hydroxycotinine levels were similar in all groups. Compared with nontobacco users, e-cigarette users had higher levels of urinary metabolites of xylene, cyanide, styrene, ethylbenzene, and benzene at baseline and elevated urinary levels of metabolites of xylene, N,N-dimethylformamide, and acrylonitrile after e-cigarette use. Metabolites of acrolein, crotonaldehyde, and 1,3-butadiene were significantly higher in smokers than in users of other products or nontobacco users. VOC metabolite levels in smokeless tobacco group were comparable to those found in nonusers with the exception of xylene metabolite-2-methylhippuric acid (2MHA), which was almost three fold higher than in nontobacco users.ConclusionsSmoking results in exposure to a range of VOCs at concentrations higher than those observed with other products, and first generation e-cigarette use is associated with elevated levels of N,N-dimethylformamide and xylene metabolites.ImplicationsThis study shows that occasional users of first generation e-cigarettes have lower levels of nicotine exposure than the users of combustible cigarettes. Compared with combustible cigarettes, e-cigarettes, and smokeless tobacco products deliver lower levels of most VOCs, with the exception of xylene, N,N-dimethylformamide, and acrylonitrile, whose metabolite levels were higher in the urine of e-cigarette users than nontobacco users. Absence of anatabine in the urine of e-cigarette users suggests that measuring urinary levels of this alkaloid may be useful in distinguishing between users of e-cigarettes and combustible cigarettes. However, these results have to be validated in a larger cohortcomprised of users of e-cigarettes of multiple brands.

Project description:BackgroundThere is considerable debate about the benefits and risks of electronic cigarettes (ECs). To better understand the risk-benefit ratio of ECs, more information is needed about net nicotine consumption and toxicant exposure of cigarette smokers switching to ECs.MethodsForty cigarette smokers (?1 year of smoking) interested in switching to ECs but not necessarily quitting smoking were enrolled in a 4-week observational study and provided an e-Go C non-variable battery and refillable atomizers and choice of eight flavors in 12 or 24 mg nicotine dosage. Measurement of urinary cotinine (metabolite of nicotine), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a pulmonary carcinogen), and eight volatile organic compounds (VOCs) that are toxic tobacco smoke constituents was conducted at baseline and week 4.ResultsAll participants with follow-up data (92.5%) reported using the study EC. Of the 40 smokers, 16 reported no cigarettes at week 2 (40%) and six continued to report no cigarettes at week 4 (15%). Change in nicotine intake over the 4 weeks was non-significant (p = .90). Carbon monoxide (p < .001), NNAL (p < .01) and metabolites of benzene (p < .01) and acrylonitrile (p = .001) were significantly decreased in the study sample. Smokers switching exclusively to ECs for at least half of the study period demonstrated significant reductions in metabolites of ethylene oxide (p = .03) and acrylamide (p < .01).ConclusionSmokers using ECs over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, NNAL, and two out of eight measured VOC metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.ImplicationsThis study extends current literature by measuring change in smoking dependence and disease-associated biomarkers, NNAL and a panel of eight common VOCs that are toxic tobacco smoke constituents in smokers who switch to ECs. The findings support the idea of harm reduction, however some levels of toxicant exposure are still of clinical concern, particularly for dual users. Extrapolation of these results must be careful to separate the different toxic exposure results for exclusive switchers versus dual cigarette + EC users, and not to equate harm reduction with the idea that using ECs is harmless.

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Transcriptomic Evidence That Switching from Tobacco to Electronic Cigarettes Does Not Reverse Damage to the Respiratory Epithelium.

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