MOLECULAR IMPACT OF ELECTRONIC CIGARETTE AEROSOL EXPOSURE ON HUMAN BRONCHIAL EPITHELIUM

Electronic cigarettes (ECIGs) simulate cigarette smoking and deliver nicotine and flavoring through an aerosol which is inhaled similarly to tobacco cigarettes (TCIG). There are few studies evaluating the health impact of ECIG use. Our objective was to determine the cellular and molecular impact of ECIG aerosol on human bronchial epithelial cells in vitro and in vivo. For the in vitro arm, human bronchial epithelial cells (HBECs) differentiated at an Air Liquid Interface (ALI) were directly exposed to ECIG aerosol (Blu) or TCIG smoke (KR 3R4F). In vitro ECIG exposures varied by dose, flavorings, and nicotine content. For the in vivo arm of this study, we profiled bronchial epithelial cells from the mainstem bronchus of former TCIG smokers (n=21), former smokers who had transitioned to an ECIG product for at least 1 month (n=17), and current TCIG smokers (n=9). Gene expression in both in vivo and in vitrosamples was measured using Affymetrix HuGene ST 1.0 microarrays. We identified a number of gene expression alterations that were induced by both ECIG and TCIG exposure as well as a novel set of changes uniquely induced by ECIG exposure. ECIG exposure induced the expression of genes involved in oxidative and xenobiotic stress pathways and increased the production of reactive oxygen species, similar to, but generally lower in magnitude than, the effects of TCIGs. Furthermore, TCIG and ECIG exposure both decreased the expression of genes involved in cilia assembly and movement, suggesting that the integrity of the bronchial epithelium is concordantly impaired by both exposures. We additionally identified a number of ECIG-specific cell cycle and cell division pathway changes. ECIG-induced changes were dependent on both flavor and nicotine content. Finally, we demonstrated that ECIG associated gene expression changes in vitro are similarly induced in vivo in ECIG users, suggesting that this system has physiological relevance. Modest, but significant gene expression changes associated with ECIG exposure suggest the potential for ECIGs to impact airway physiology and raise questions about the potential long-term effects of ECIG usage. Our data further suggest that an in vitro system in which differentiated airway epithelium is directly exposed to vapor from ECIG products will have utility for understanding how ECIGs and their constituents lead to these physiological alterations.