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

INTRODUCTION: Cigarette smoking is associated with the risk of certain diseases, but non-combustible products may lower these risks. The potential long-term health effects of the next-generation non-combustible products (heat-not-burn tobacco products (HNBP) or electronic vapor products) have not been thoroughly studied. The present study aimed to investigate the impact of biomarkers of potential harm (BoPH) of one of HNBP (a novel vapor product: NTV (novel tobacco vapor)), under the conditions of actual use. AIMS AND METHODS: This study was an observational, cross-sectional, three-group, multi-center study. Exclusive NTV users (NTV, n = 259), conventional cigarette smokers (CC, n = 100) and never-smokers (NS, n = 100) were enrolled. Biomarkers of tobacco smoke exposure (cotinine and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)) and BoPH including parameters of physical pulmonary functions relevant to smoking-related diseases were examined, and subjects answered a questionnaire on cough-related symptoms (J-LCQ) and health-related quality of life (SF-36v2®). RESULTS: Levels of cotinine, total NNAL and BoPH (high-density lipoprotein (HDL)-cholesterol, triglyceride, sICAM-1, WBC count, 11-DHTXB2, 2,3-d-TXB2, 8-epi-PGF2α, forced expiratory volume in 1 second (FEV1), % predicted value of FEV1 (%FEV1) and maximum midexpiratory flow (FEF(25-75))) were significantly different in the NTV group as compared to levels in CC group (p < .05). Significantly higher levels of cotinine, total NNAL, and 2,3-d-TXB2, and lower levels of FEV1 and %FEV1, were observed among NTV users compared to the NS group. CONCLUSION: In a post-marketing study under actual use conditions, BoPH associated with smoking-related disease examined in exclusive NTV users were found to be favorably different from those of CC smokers, a finding attributable to a reduction in exposure to harmful substances of tobacco smoke. IMPLICATIONS: Cigarette smoking is associated with an increased risk of pulmonary diseases like COPD, cardiovascular diseases, and certain cancers. There is a growing body of evidence that HNBP reduces the exposure associated with smoking and that there is a favorable change in BoPH. However, long-term effects regarding the relative health risks to HNBP users compared to CC smokers have not been examined. This study provides post-marketing data under actual use conditions of the effects on biomarkers of potential harm in NTV, one of HNBP, exclusive users compared to CC smokers and never-smokers. The evidence suggests that exclusive NTV users have favorable levels of BoPH compared to CC smokers, and that is result from a sustained reduction in exposure to harmful substances of tobacco smoke.