Comparative effects of e-cigarette and conventional cigarette smoke on in vitro bronchial epithelial cell responses.

Because of cigarette smoking, chronic lung diseases are the third leading cause of death in the United States. Electronic cigarettes (e-cig) were originally marketed as harm reduction devices for cigarette smokers due to low success rates with traditional smoking cessation methods. While several studies show that cigarette smoke causes damage to the lungs, comparative research assessing the injury profile of e-cig to traditional cigarettes is still limited. Comparative lung injury studies are crucial in determining the validity of e-cig as a harm reduction device for chronic smokers and can be used to assess the quality of alternate nicotine delivery options to reduce the morbidity and mortality caused by cigarettes. We hypothesize that exposure to JUUL to e-cig vapor produces decreased in vitro markers of lung injury in comparison to cigarette smoke extract at equivalent and higher nicotine concentrations to that from CSE. We compared the extent of injury to airway epithelial tissue from cigarettes and e-cig using various assays of cellular function, including ciliary beat frequency (CBF), wound closure, barrier function, cytokine release, and kinase activity. Cells were treated with various concentrations of Virginia Tobacco-flavored JUUL™ vapor extract (JVE) and cigarette smoke extract (CSE) either normalized for nicotine concentration or equivalent % dilutions from a 100 % stock extract. CSE stimulated cilia in the short term, but slowed cilia after several hours of exposure, whereas cells treated with JVE showed no significant changes in CBF. CSE slowed wound repair, but nicotine-equivalent doses of JVE did not significantly slow wound repair. CSE increased epithelial cell monolayer permeability and interleukin release in a concentration-dependent manner, but these were not observed with JVE treatment. Kinase activity assays revealed activation translocation of protein kinase C (PKC) activity in cells treated with CSE, but no such change in PKC activity was observed in JVE groups. The results of these in vitro assays suggest that at nicotine-equivalent doses, JVE from Virginia Tobacco-flavored JUUL does not impact the airway epithelium in the same manner as CSE. The lack of evidence for in vitro tissue injury in this study caused by JUUL™ vapor extract is not a justification for the harm posed by nicotine addiction, particularly at the high levels of nicotine contained in these products which are several times the legal limit of many countries.