Cardiopulmonary outcomes of dual cigarette and e-cigarette use in animal models of chronic exposure

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PROJECT SUMMARY New generation pod-style nicotine salt e-cigarettes (e-cigspod) are popular because of their sleek design and ability to deliver nicotine levels similar to those of conventional tobacco cigarettes (cigs). Nicotine salts are easier to inhale than the free-base form of nicotine found in previous generation e-cigs. While the long-term health impact of cig smoke is well known, the consequences of chronic e-cig use remain in question, and data is needed to justify immediate FDA regulations. A substantial portion of smokers are unsuccessful in using e-cigs to support their cessation efforts and instead become dual users. The chemical profile of cig smoke and e-cigpod aerosols is different, which suggests that the health effects of chronic smoking and vaping may not fully overlap. Building upon this, we hypothesize that cig smoking and e-cigpod vaping, are independent risk factors for cardiopulmonary disease, whose superposition exacerbates the maladaptive remodeling of the lungs, heart, and vasculature compared to either practice alone. To test this hypothesis, we will expose hypercholesterolemic and wildtype mice to nebulized nicotine, aerosolized solvent carrier, e-cigpod aerosols, and cig smoke (naïve mice), or a combination of the two (both naïve and previously cig smoke-exposed mice) and we will compare the structural and functional remodeling of the cardiovascular and respiratory systems. We will generate e-cigpod aerosols from pods in Tobacco flavor at 5% nicotine strength. Motivated by the idea that smokers who use e-cigs as cessation aids may vape until they satisfy their nicotine cravings, we will perform experiments to achieve equal cotinine bioavailability in the mouse blood, while maintaining the same daily duration of exposure. We will measure the mechanical properties of the of aorta (tissue stiffness, distensibility, and elastic storage), heart (fractional shortening and ejection fractions), and lungs (resistance and elastance). We will characterize tissue microstructure (air space sizes, collagen content, and elastic fiber integrity) to highlight the factors that most contribute to the observed functional changes. Knowledge gained from this project will provide scientific evidence in support of data-driven e-cig regulation under The Family Smoking Prevention and Tobacco Control Act (FSPTCA), specifically concerning the health risks of dual combustible and electronic cigarette use.