Molecular Impact of Electronic Cigarette Aerosol Exposure in Human Bronchial Epithelium

Abstract

Little evidence is available regarding the physiological effects of exposure to electronic cigarette (ECIG) aerosol. We sought to determine the molecular impact of ECIG aerosol exposure in human bronchial epithelial cells (HBECs). Gene-expression profiling was conducted in primary grown at air liquid interface and exposed to 1 of 4 different ECIG aerosols, traditional tobacco cigarette (TCIG) smoke, or clean air. Findings were validated experimentally with quantitative polymerase chain reaction and a reactive oxygen species immunoassay. Using gene set enrichment analysis, signatures of in vitro ECIG exposure were compared with those generated from bronchial epithelial brushings of current TCIG smokers and former TCIG smokers currently using ECIGs. We found 546 genes differentially expressed across the ECIG, TCIG, and air-exposed groups of HBECs (ANOVA; FDR q < .05; fold change > 1.5). A subset of these changes were shared between TCIG- and ECIG-exposed HBECs. ECIG exposure induced genes involved in oxidative and xenobiotic stress pathways and increased a marker of reactive oxygen species production in a dose-dependent manner. ECIG exposure decreased expression of genes involved in cilia assembly and movement. Furthermore, gene-expression differences observed in vitro were concordant with differences observed in airway epithelium collected from ECIG users (q < .01). In summary, our data suggest that ECIG aerosol can induce gene-expression changes in bronchial airway epithelium in vitro, some of which are shared with TCIG smoke. These changes were generally less pronounced than the effects of TCIG exposure and were more pronounced in ECIG products containing nicotine than those without nicotine. Our data further suggest that the gene-expression alterations seen with the in vitro exposure system reflects the physiological effects experienced in vivo by ECIG users.

Electronic cigarettes: a task force report from the European Respiratory Society

“…Cytotoxicity to various cell lines, causing cell death, decreased cell proliferation and increased oxidative stress have been reported [49][50][51]. Studies using a variety of cell types showed that effects of ECIGs on cell death and changes in gene expression were markedly lower than TCIGs [52][53][54][55][56][57][58]. However, it has been documented that ECIGs do cause a variety of adverse cellular effects on a range of cell types.…”

“…An overview of the effects of ECIGs on such human primary airway epithelial cells is provided in table 1. The design of such studies differed markedly, and only two used exposure of cells differentiated at the air-liquid interface (ALI) to ECIG vapour [54,60]. Therefore, these studies are discussed in detail.…”

Immunological and pathological effects of electronic cigarettes

“…34 Another study also investigated the exposure of primary HBECs to ECV and CS at an air-liquid interface, using geneexpression profiling as the read-out. 35 Genes up-regulated by both CS and ECV were related to apoptosis, xenobiotic stress and oxidative stress. In addition, CS and ECV down-regulated the expression of genes associated with the assembly and movement of cilia, which might cause a reduction of ciliated cells in airway epithelium and compromise mucociliary clearance function-this could contribute to chronic inflammation in the airways.…”

“…Another study also investigated the exposure of primary HBECs to ECV and CS at an air‐liquid interface, using gene‐expression profiling as the read‐out . Genes up‐regulated by both CS and ECV were related to apoptosis, xenobiotic stress and oxidative stress.…”

Electronic cigarettes—A review of the physiological health effects

“…DNA breaks could be caused by the known carcinogens that exist in EC vapours, like formaldehyde, as discussed previously. EC vapours can also induce gene expression changes in vivo in nasal epithelium or in vitro in bronchial airway epithelium (Moses et al 2017), or in acetylcholine receptors associated with tumour progression (Schaal and Chellappan 2016). It should be noted that many of the above results were not related to the nicotine that is sometimes present in the vapours but to the humectants like propylene glycol, glycerol, and any flavouring compounds that may exist in the solution (though nicotine sometimes enhanced the damaging effects).…”