Biomarkers of Exposure and Biomarkers of Potential Harm in Adult Smokers Who Switch to e-Vapor Products Relative to Cigarette Smoking in a 24-week, Randomized, Clinical Trial

Abstract

Introduction Long-term health effects of e-vapor products (EVPs) are not well-established. We compared biomarkers of exposure (BoE) to select harmful and potentially harmful constituents (HPHCs) and biomarkers of potential harm (BoPH) in adult smokers (AS) who switched to EVPs vs continued smoking for 24 weeks. Methods AS (n=450, >10 cigarettes per day [CPD] for ≥10 years), were randomly assigned to continue smoking (Control) or switch to one of two cartridge-based EVPs (Test 1 - classic; Test 2 - menthol, 4% nicotine). BoE and BoPH were measured at baseline and 12 Weeks. A subset of 150 Control and EVP subjects (switchers with eCO ≤8 ppm and <10% baseline CPD) were followed to 24 weeks, the focus of this manuscript. Results Total NNAL and carboxyhemoglobin (COHb) were significantly reduced (p<0.0001) in Test 1 and Test 2 at 24 weeks. Urinary nicotine equivalents (NE) were not statistically significantly different between the Control and EVP groups. At Week 24, statistically significant reductions (p<0.05) were observed for white blood cell counts, 11-dehydrothromboxane β2, and sICAM in both test groups, and there were several significant changes in measures of pulmonary function. High-density lipoprotein-cholesterol (HDL-C) and 8-epi-prostaglandin-F2α were directionally favorable in both EVP groups vs Control. Conclusions We demonstrate that significant reductions of selected HPHCs in EVP aerosol results in significant reductions in BoEs and favorable changes in BoPHs after switching to EVPs for 24 weeks. These changes approached those reported for smoking cessation, suggesting that switching to exclusive use of the EVPs may be less harmful than continuing smoking. Implications Cigarette smoking causes serious diseases. Switching from cigarettes to a noncombustible product is a potential harm reduction pathway for AS unable or unwilling to quit. Long-term health effects of EVPs compared to continued smoking have not been extensively studied. We present BoE evidence on select HPHCs and BoPHs related to inflammation and oxidative stress in AS completely switching to two EVPs. This study demonstrates significant reductions in BoEs (except for nicotine) accompanied with favorable changes in various BoPHs, including pulmonary function. The totality of evidence suggests that exclusive EVP use may present lower health risks compared to smoking cigarettes.

Exposure to Tobacco-Specific Nitrosamines Among People Who Vape, Smoke, or do Neither: A Systematic Review and Meta-Analysis

“…All included studies reported urinary TSNA levels, with one also reporting on salivary levels. 34 Longitudinal studies included eight RCTs 35–42 two non-randomized intervention studies 43 , 44 and two observational studies. 45 , 46 Ten cross-sectional studies 34 , 47–55 were also included.…”

“…In eight RCTs where people who smoked at baseline switched to vaping, NNAL was reduced significantly, in four short-term studies 37 , 39 , 40 , 42 by 55% to 68%, and in four medium-term studies by 53% to 95% 35 , 36 , 38 , 41 ( Table 1 ). Short-term use studies, which ranged from five to seven days, were all conducted in research facility where access to tobacco cigarettes or e-cigarettes were controlled by the research team.…”

“…One 14-day medium-term study, Morris et al, 36 was also conducted in a research facility. The three other medium-term studies ranged from 6 to 24 weeks and all utilized carbon monoxide monitoring to ensure people who were randomized to vaping were not also smoking 35 , 38 , 41 ( Table 1 and Supplementary Table S7 ).…”

Applications of biomarkers of exposure and biological effects in users of new generation tobacco and nicotine products: Tentative proposals

“…NGP-related biomarkers, both BOE and BOBE, can be beneficially applied in a number of ways and in a range of fields. As mentioned above, they have been used to assess the tobacco harm reduction potential of NGPs, particularly BOE but also BOBE, 23,[27][28][29][30][31][32] Biomarker data are now forming useful contributions among many lines of evidence indicating appropriateness for the protection of public health in NGP regulatory submissions. In the United States, such studies have been instrumental in the marketing authorizations being granted to selected HTPs, a few ECs, but as yet no NPs.…”

“…NGP‐related biomarkers, both BOE and BOBE, can be beneficially applied in a number of ways and in a range of fields. As mentioned above, they have been used to assess the tobacco harm reduction potential of NGPs, particularly BOE but also BOBE, 23,27–32 in cross‐sectional, longitudinal, and switching studies.…”