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

Abstract

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 were 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-hydroxypropyl mercapturic acid (acrolein metabolite), and carboxyhemoglobin (carbon monoxide measure) were 46% to 86% lower in AEVP compared with AS (p ≤ .0001) as was nicotine equivalents (nicotine and its five metabolites; 36%, p < .01). The levels of some BOPH were significantly lower in AEVP compared with AS for 11-dehydrothromboxane-B2 (29%, p = .04; platelet activation), 8-epi-prostaglandin F2α (23%, p = .02; oxidative stress) and soluble intercellular adhesion molecule-1 (16%, p = .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 with cigarettes is not well established. This study provides data specific to BOE 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 with smoking cigarettes.

Comparison of Nicotine Dependence and Biomarker Levels among Traditional Cigarette, Heat-Not-Burn Cigarette, and Liquid E-Cigarette Users: Results from the Think Study

“…In the case of EC-only users, all biomarker levels were lower. The findings of our study are in accordance with a cross-sectional observational study conducted in the U.S. finding lower concentrations of total NNAL, CEMA, and other biomarkers among EC users [38].…”

Improving on estimates of the potential relative harm to health from using modern ENDS (vaping) compared to tobacco smoking

“…In terms of study quality, two of the five studies were funded by commercial interests in ENDS use/tobacco. 33 32 Nevertheless, a particular advantage of one of these was that it kept users in a controlled environment (albeit only five days), 32 which may have reduced the risks of contamination via undeclared dual use of ENDS use and tobacco products, as well as exposure to secondhand smoke/ENDS aerosol from others. Other study design limitations of the included studies included involving narrow demographic groups (e.g., those aged 12 to 21 years; 35 ) and allowing participants to select products themselves, 34 as opposed to being randomised.…”

Differences in Levels of Biomarkers of Potential Harm Among Users of a Heat-Not-Burn Tobacco Product, Cigarette Smokers, and Never-Smokers in Japan: A Post-Marketing Observational Study

“…Similar to our data, a major difference in NNAL levels (−86.2%) was found in exclusive EVP users under actual use conditions. 10 Therefore, the present data may represent the actual use conditions of an exclusive user of HNBP. The 2010 Surgeon General’s report states that oxidative stress and chronic inflammation are a common thread among the three major smoking-related diseases.…”

“… 13 , 14 The Food and Drug Administration authorized a manufacturer to market specific snus products with a claim which indicates lower risks of certain diseases by using the products instead of cigarettes. 15 There is a growing body of evidence from clinical studies that HNBP 3–6 and EVP 7 , 8 , 10 have the potential to reduce risks from smoking-related diseases by reducing harmful and potentially harmful constituents (HPHCs) 16 and that favorable changes in biomarkers of potential harm (BoPH) occur after conventional cigarette (CC) smokers quit. 4 , 17–21 However, as HNBP and EVP are relatively new to the world, there is scant information on their influence on actual health risks in users.…”

“…Regarding EVP, a report on findings obtained by cross-sectional evaluation has shown risk-reducing potential. 10 A novel tobacco vapor product (NTV: Ploom TECH), one of the HNBP developed by Japan Tobacco Inc., became available in the Japanese market in March 2016. The NTV consisted of a battery, a cartridge with a heater and nicotine-free liquid, and a capsule filled with tobacco blend.…”