Projects and Grants per year
Grants and Contracts Details
Description
ABSTRACT
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.
Status | Finished |
---|---|
Effective start/end date | 5/1/17 → 3/31/21 |
Funding
- National Institute of Environmental Health Sciences
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Projects
- 1 Finished
-
Center for Appalachian Research in Environmental Sciences: Administrative Core
Hahn, E., D'Orazio, J., Fondufe-Mittendorf, Y., Fowlkes, J., Giannone, P., Haynes, E., Morris, P., Pearson, K., Swanson, H. & Smyth, S.
National Institute of Environmental Health Sciences
5/1/17 → 3/31/21
Project: Research project