Real-World Evidence of Differences in Biomarkers of Exposure to Select Harmful and Potentially Harmful Constituents and Biomarkers of Potential Harm between Adult E-Vapor Users and Adult Cigarette Smokers

INTRODUCTION: Real-world evidence regarding likely long-term health effects of e-vapor products (EVP) under actual use conditions relative to cigarette smoking is not well studied. METHODS: In this cross-sectional, observational study, biomarkers of exposure (BOE) to select harmful and potentially harmful constituents and biomarkers of potential harm (BOPH) relevant to smoking-related diseases were measured in exclusive adult EVP users (AEVP, n=144) and exclusive adult cigarette smokers (AS, n=73). AEVP used their own brand of EVP for 6+ months following 10+ years of cigarette smoking and AS smoked own brand of cigarettes for 10+ years. Subject recruitment and informed consent was obtained online and urine/blood samples were collected at local clinical laboratories, representing a new paradigm for collecting real-world evidence. RESULTS: The levels of total NNAL (NNK metabolite), 3-hydroxypropylmercapturic acid (acrolein metabolite), and carboxyhemoglobin (carbon monoxide measure) were 46% to 86% lower in AEVP compared to AS (p≤0.0001) as was nicotine equivalents (nicotine and its 5 metabolites; 36%, p<0.01). The levels of some BOPH were significantly lower in AEVP compared to AS for 11-dehydrothromboxane-B2 (29%, p=0.04; platelet activation), 8-epi-prostaglandin F2α (23%, p=0.02; oxidative stress) and soluble intercellular adhesion molecule-1 (16%, p=0.02; endothelial function). CONCLUSIONS: This study demonstrates the feasibility of a new approach for collecting real-world evidence. Substantially lower levels of BOEs (NNK, nicotine, acrolein, carbon monoxide) and favorable differences in BOPHs (platelet activation, oxidative stress, endothelial function) suggest EVP users may have lower health risks than cigarette smokers. IMPLICATIONS: Cigarette smoking causes serious diseases. Switching from a combustible tobacco product to a noncombustible product is a potential harm reduction pathway for adult smokers unable or unwilling to quit. Real-world evidence regarding the relative risk of EVP use compared to cigarettes is not well established. This study provides data specific to biomarkers of exposure to tobacco smoke constituents and biomarkers of potential harm collected under actual use conditions in a real-world setting. The totality of evidence suggests that exclusive EVP use may present lower health risk compared to smoking cigarettes.