Saliva and Lung Microbiome Associations with Electronic Cigarette Use and Smoking.

The microbiome has increasingly been linked to cancer. Little is known about the lung and oral cavity microbiomes in smokers, and even less for electronic cigarette (EC) users, compared with never-smokers. In a cross-sectional study (n = 28) of smokers, EC users, and never-smokers, bronchoalveolar lavage and saliva samples underwent metatranscriptome profiling to examine associations with lung and oral microbiomes. Pairwise comparisons assessed differentially abundant bacteria species. Total bacterial load was similar between groups, with no differences in bacterial diversity across lung microbiomes. In lungs, 44 bacteria species differed significantly (FDR < 0.1) between smokers/never-smokers, with most decreased in smokers. Twelve species differed between smokers/EC users, all decreased in smokers of which Neisseria sp. KEM232 and Curvibacter sp. AEP1-3 were observed. Among the top five decreased species in both comparisons, Neisseria elongata, Neisseria sicca, and Haemophilus parainfluenzae were observed. In the oral microbiome, 152 species were differentially abundant for smokers/never-smokers, and 17 between smokers/electronic cigarette users, but only 21 species were differentially abundant in both the lung and oral cavity. EC use is not associated with changes in the lung microbiome compared with never-smokers, indicating EC toxicity does not affect microbiota. Statistically different bacteria in smokers compared with EC users and never-smokers were almost all decreased, potentially due to toxic effects of cigarette smoke. The low numbers of overlapping oral and lung microbes suggest that the oral microbiome is not a surrogate for analyzing smoking-related effects in the lung. PREVENTION RELEVANCE: The microbiome affects cancer and other disease risk. The effects of e-cig usage on the lung microbiome are essentially unknown. Given the importance of lung microbiome dysbiosis populated by oral species which have been observed to drive lung cancer progression, it is important to study effects of e-cig use on microbiome.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. IMPACT: 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.

Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.

Electronic cigarette (e-cig) use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a 4-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine or to a no-use control group. Compliance to the e-cig intervention was assessed by participants sending daily puff counts and by urinary PG. Inflammatory cell counts and cytokines were determined in bronchoalveolar lavage (BAL) fluids. Genome-wide expression, miRNA, and mRNA were determined from bronchial epithelial cells. There were no significant differences in changes of BAL inflammatory cell counts or cytokines between baseline and follow-up, comparing the control and e-cig groups. However, in the intervention but not the control group, change in urinary PG as a marker of e-cig use and inhalation was significantly correlated with change in cell counts (cell concentrations, macrophages, and lymphocytes) and cytokines (IL8, IL13, and TNFα), although the absolute magnitude of changes was small. There were no significant changes in mRNA or miRNA gene expression. Although limited by study size and duration, this is the first experimental demonstration of an impact of e-cig use on inflammation in the human lung among never-smokers.