Pulmonary Effects of Exposure to Tobacco Smoke and New Tobacco Products

 

ABSTRACT

Since reaching the US marketplace in 2007, e-cigs have rapidly gained popularity, particularly among young adults, yet little is known regarding their health effects. Although the FDA has classified many flavorings commonly used in e-liquids as “Generally Recognized as Safe” (GRAS) for oral consumption, most flavoring additives have not been evaluated for inhalational toxicity. We have previously demonstrated that cigarette smoking significantly impairs innate and antiviral host defense responses of the respiratory mucosa, yet whether and how vaping flavored e-cigs modifies respiratory immune responses is completely unknown. Using non-invasive sampling of the nasal mucosa, ex vivo analyses, as well as in vitro experiments our studies are designed to determine whether and how vaping e-cigs affects respiratory host defense responses and compare these effects to those induced by exposure to cigarette smoke. Specifically, tissue samples obtained by superficially scraping the epithelial layer covering the inferior turbinates from non-smokers, cigarette smokers, and e-cig users are analyzed for changes in the expression of almost 600 immune genes. In addition, we obtained nasal lavage fluid samples, urine, and peripheral blood samples from these subjects to assess changes in markers of tobacco and nicotine exposure as well as other markers of inflammation or immune responses. Our data confirm that smoking cigarettes causes suppression of several key immune genes in the nasal mucosa. E-cig users showed the same changes in immune genes as cigarette smokers. However, e-cig users also demonstrated suppression of several additional immune genes, suggesting even broader suppressive effects on respiratory mucosal immune responses as compared to cigarette smokers. In separate in vitro experiments, we are examining the effects of flavored e-cigs on respiratory mucosal immune responses, specifically focusing on cinnamon-flavored e-cigarettes containing the flavoring agent cinnamaldehyde. Our data indicate that cinnamaldehyde-containing e-liquids have a significant negative effect on epithelial cell physiology and barrier function. In addition, cinnamaldehyde-containing e-liquids compromise the immune function of key respiratory immune cells, such as macrophages, Natural Killer Cells, and neutrophils. Using translational human in vitro and in vivo approaches, our studies will ascertain whether exposure to e-cigs, with a specific focus on cinnamon-flavored e-liquids/e-cigs, have immune suppressive effects on the respiratory mucosa.