E-cigarette use and emphysema development: The VapeScan Study - PROJECT SUMMARY E-cigarette (e-cig) use is common, particularly in adolescents and young adults. While the respiratory risks of e-cig use remain controversial, cellular and animal studies have suggested potential lung toxicity, and epidemiologic studies have associated e-cigs with greater odds of respiratory symptoms and self-reported asthma and, in older adults, COPD. This application will compare early lung toxicity associated with e-cig vs cigarette (cig) use to inform ongoing debates on whether e-cigs are a “safer” alternative to cigs. Preliminary results from the VapeScan Study (R01HL155576, Oelsner; R01ES029967, Navas Acien), a highly characterized prospective cohort of 372 e-cig users and non-users aged 18-50 (mean, 28) years, suggest that e-cig use is associated with lower diffusing capacity of the lung for carbon monoxide (DLCO) and greater low attenuation areas on lung computed tomography—findings suggesting pulmonary emphysema. Yet, the lack of an exclusive cig user group in the original cohort limits inferences from dual e-cig/cig users, and additional structural, functional, and mechanistic investigation is warranted. This application aims to add innovative deep phenotyping to our unique cohort of young adult e-cig users, plus a new cig-only comparison group, to elucidate the role of e-cig vs cig use in the development of emphysema in young adults, and to examine potential mechanisms. This study will re-examine 200 young adults (50 e-cig users, 50 cig users, 50 dual e-cig/cig users, and 50 dual non-users [controls]) and perform 129Xe MRI and gene expression profiling of whole blood, hair, and nasal samples, while performing metals assessment in blood, urine, and personal e-cig aerosols, spirometry, DLCO, urinary cotinine and tetrahydrocannabinol (THC), and questionnaires on use of e-cigs, cigarettes, and other potentially relevant (e.g., occupational, environmental) exposures. Aim 1 is to determine the association of e-cig use and e-cig related metal exposures with early emphysematous changes on 129Xenon MRI. We hypothesize that compared to cig users and controls, e-cig users demonstrate dilated airspaces and impaired regional gas exchange, particularly for membrane gas transfer, and that metal exposures, particularly to Copper, Cadmium, Lead, and Zinc, will associate with the same changes. Aim 2 is to identify gene expression profiles associated with e-cig use and e-cig related metal exposures. We hypothesize that e-cig users and those with higher metal exposures show differential gene expression for pathways linked to protease activity, extracellular matrix production, and endothelial integrity. Throughout, we will leverage data in dual users to explore synergistic effects of cig and e-cig use and we will explore associations with intensity/duration of e-cig or cig use as well as nicotine and THC exposures. Accomplishment of the aims would inform e-cig regulation and address knowledge gaps on the mechanisms of emphysema development in young adults.
