Pilot: Center for Appalachian Research in Environmental Sciences: Exposure to E-cigarette Vapor Alters Gene Expression and Induces Inflammatory Responses

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Use of e-cigarettes (or electronic nicotine delivery systems, ENDS), is rising rapidly primarily due to the popular misconception that they pose little to no hazard to human health. Among adolescents, increasing ENDS use is particularly alarming and, as reported in 2015, accounts for as much as 16% of the high school and 5.3% of the middle school population in some states. The appeal of ENDS products to youth can be partly attributed to the various flavorings added to the ENDS fluids. In Appalachian Kentucky, use of tobacco products (including recent increases in adoption of ENDS) generally occurs earlier and at higher rates per capita than elsewhere in Kentucky and the U.S. These high rates of tobacco product use and secondhand exposure contribute to substantial health issues in this region, including increased respiratory disease and the highest incidence of lung cancer in the U.S. In regards to the increasing use of ENDS, recent incidents demonstrate that vaping can cause acute inflammation and lung damage in certain circumstances. Moreover, the long-term health effects associated with vaping or being exposed passively to ENDS vapor have not been studied in any depth. Our initial studies have addressed these gaps of knowledge by examining the toxicity of condensates collected from ENDS vapors on oral and lung epithelial cell models. Our results thus far show that, at physiologically relevant concentrations, ENDS vapor condensates reduced cell viability and upregulated molecular biomarkers in the aryl hydrocarbon receptor (AHR) and NFκB signaling pathways involved in generating oxidative stress and inflammatory responses. In agreement with increased oxidative stress, we also observed increased DNA damage that could contribute to injury and carcinogenesis. Notably, increases in AHR-mediated gene expression with ENDS vapor condensates were comparable to those mediated by condensates prepared from conventional cigarette smoke. These effects were generally not observed without vaporization of ENDS liquids, suggesting that heating and chemical conversion of ENDS liquid constituents contribute to these toxicological effects. Our primary hypothesis for this project is that heating during vaporization of ENDS liquids produces compounds that alter AHR- and NFκB–mediated gene expression in lung and oral tissue that can elicit harmful effects, most notably increased oxidative stress and inflammation. Our specific aims are designed to test this hypothesis by 1) screening vapor condensates from ENDS liquids for their ability to activate AHR/NFκB and increase expression of pro-inflammatory markers, oxidative stress and DNA damage, 2) specifying the impacts of heating and vaporization of ENDS fluids on their chemical composition and their harmful effects and 3) determining the in vivo effects of exposure to ENDS vapor, with an emphasis on AHR- and NFκB-mediated gene expression and inflammation in lung tissue. A strong investigative team has been assembled to carry out this project, with expertise in the toxicology of tobacco products, DNA damage and carcinogenesis, gene expression and metabolic changes in response to xenobiotics, inflammatory pathways and responses, and biological and toxicological effects of inhalation exposures. Based on our preliminary data, these studies are expected to conclusively establish that specific agents or constituents in vapors from ENDS liquids exert pro-inflammatory and other harmful effects in vitro and in vivo. We anticipate our findings will also show that components of the NFκB and AHR signaling pathways may be valuable biomarkers to assess risks associated with ENDS use. Overall, this project will provide additional preliminary data and increase competitiveness for external grant support from the NIEHS and FDA that support environmental pollution and tobacco regulatory science, respectively. This research will also be of interest to other funding sponsors focused on pulmonary health.
Effective start/end date5/1/173/31/22


  • National Institute of Environmental Health Sciences


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