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.