Differences in biomarkers of potential harm after 2+ years of tobacco heating system use compared to cigarette smoking
Cigarette smoking is a major contributor to morbidity and mortality. While the best way to reduce the risks of smoking-related diseases is to quit, switching to alternative products that do not combust tobacco could decrease harms of smoking-related diseases. The Tobacco Heating System (THS) emits substantially lower levels of many of the harmful and potentially harmful constituents in cigarette smoke. Randomized clinical trials have demonstrated favorable improvements in biomarkers of potential harm (BoPH) related to smoking-related disease at 3, 6, and 12 months after switching. The present observational study examined the longer-term impact of complete switching on BoPH related to toxicant exposure, inflammation, and oxidative stress compared to continued smoking or quitting.
This cross-sectional study enrolled healthy participants with comparable smoking histories who (i) currently smoke cigarettes (at least 10 years, exclusively), (ii) switched to THS use (at least 2 years of self-reported exclusive use [≤1 cigarette per day]), or (iii) formerly smoked (quit at least 2 years ago). The primary objective was to demonstrate that subjects who had completely switched from cigarettes to THS use had lower levels of four co-primary endpoints compared to current smokers: carboxyhemoglobin (COHb), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), white blood cells (WBC, inflammation marker), and 8-epi-prostaglandin-F2α (8-epi PGF2α, oxidative stress marker). The key secondary objectives were to assess effects on other pathways linked to smoking-related disease development by measuring five endpoints: BoPH linked to lipid metabolism (high-density lipoprotein cholesterol), endothelial dysfunction (soluble intercellular adhesion molecule-1 [sICAM-1]), and platelet adhesion (11-dehydrothromboxane B2 [11-DTX-B2]), as well as markers of cardiovascular and respiratory function (arterial stiffness and forced expiratory volume in 1 s [% predicted post-bronchodilator spirometry], respectively). In total, 982 participants were enrolled, and 888 were matched as triplets of current smokers, THS users, and former smokers (n=296 in each group). Significant differences were demonstrated for all primary and key secondary objectives in THS users compared to current smokers (p≤0.002, adjusted for multiplicity), which was consistent with the results observed in former smokers. COHb, NNAL, and 8-epi PGF2α were reduced by -50.5%, -81.1%, and -23.6%, respectively, and a -0.694×109/L difference in WBC was measured in THS users compared to current smokers. All changes were in the same direction observed in former smokers. These findings build on our previously published work because three BoPH that had not reached significance in a 6-month exposure response study (i.e., sICAM-1, 11-DTX-B2, and 8-epi-PGF2α ) were significantly lower in THS users compared to current smokers. Collectively, the results suggest that completely switching to THS instead of continuing to smoke could favorably affect key pathophysiological pathways involved in the development of smoking-related diseases.