MRI and Biological Markers of Acute E-Cigarette Exposure in Smokers and Vapers

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PROJECT SUMMARY Electronic cigarette (e-cig) use has grown at an alarming rate during recent years with sales projected to exceed those of their tobacco counterparts within a decade. This trend has been spurred by the notion that e-cigs are a safer alternative to tobacco-based cigarettes even though neither short nor long-term health implications of e- cig are currently understood. It has falsely been assumed that e-cigs, because no combustion is involved, are free of the constituents found in tobacco smoke such as free radicals. There is, however, emerging evidence from the investigators’ lab and elsewhere that a single vaping episode elicits an adverse reaction quantifiable in terms of a number of physiologic measures. Specifically, our recent work in healthy nonsmokers, using newly developed quantitative MRI methods, indicates impaired vasodilatory capacity of the systemic circulation and reduced hyperemia, following induced ischemia in the lower extremity, evident after a single episode of vaping a commercial brand of non-nicotinized e-cig. We have further shown in preliminary work leading up to the present proposal that the observed effects are paralleled by inflammation and oxidative stress, as evidenced in serum from healthy non-smokers taken before and after a vaping episode during the same integrated protocol. Here we propose to extend the above work to active tobacco cigarette (t-cig) smokers and e-cig vapers to examine the acute response from a single episode of each type of exposure (t-cig, e-cig ± nicotine), by means of an extended battery of quantitative MRI tests. The examination involves measurements of vascular reactivity, compliance and oxygen metabolism, along with biological markers of inflammation and oxidative stress. We hypothesize that all three paradigms will cause a transient response that will be greatest for t-cigs and nicotinized e-cigs. The projected outcome of the proposed research will provide new insight into the acute effects of e-cig aerosol inhalation in the presence and absence of nicotine in terms of markers of endothelial dysfunction and oxidative stress, both at the holistic and cellular level, and thereby aid regulators in assessing the risk of e- cigarette use, in conformance with the objectives of RFA-OD-19-028: Tobacco Regulatory Science. Specifically, our aims address the following scientific interest and priority areas explicitly stated therein: “biomarkers to assess exposure, as well as biomarkers to assess harm or toxicity of non-cigarette tobacco products, including ENDS; toxicological impact of nicotine; biomarkers to assess short- and long-term effects of non-cigarette tobacco products; clinical evaluations to distinguish changes in cell/tissue function/physiology specific to tobacco exposure (e.g., ENDS aerosol exposure) known to indicate longer term disease development and progression (health effects)”.