Effects of Switching to the Menthol Tobacco Heating System 2.2, Smoking Abstinence, or Continued Cigarette Smoking on Clinically Relevant Risk Markers: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 2)

Abstract

IntroductionModified-risk tobacco products are expected to reduce exposure to harmful and potentially harmful constituents of cigarette smoke, and ultimately reduce the health burden of smoking-related diseases. Clinically relevant risk markers of smoking-related diseases inform about the risk profile of new tobacco products in the absence of in-market epidemiological data. The menthol Tobacco Heating System 2.2 (mTHS) is a modified-risk tobacco product in development as an alternative to cigarettes (conventional cigarettes [CCs]).MethodsIn this parallel-group study, Japanese adult smokers (23–65 years; ≥10 mCCs/day) were randomized to mTHS, menthol CCs (mCC), or smoking abstinence (SA) for 5 days in confinement and 85 days in ambulatory settings. Endpoints included biomarkers of exposure to harmful and potentially harmful constituents and clinically relevant risk markers of smoking-related diseases.ResultsOne-hundred and sixty participants were randomized to the mTHS (n = 78), mCC (n = 42), and SA (n = 40) groups. Switching to the mTHS was associated with reductions in biomarkers of exposure compared with continuing mCCs. Reductions in 8-epi-prostaglandin F2α (biomarker of oxidative stress), 11-dehydro-thromboxane B2 (biomarker of platelet activation), soluble intracellular adhesion molecule-1 (biomarker of endothelial function), and an increase in high-density lipoprotein cholesterol (biomarker of lipid metabolism) and forced expiratory volume in 1 second (biomarker of lung function) occurred in the mTHS group compared with the mCC group. The changes in the mTHS group approached those in the SA group.ConclusionsSwitching from mCCs to mTHS was associated with improvements in clinically relevant risk markers linked to mechanistic pathways involved in smoking-related diseases.ImplicationsIn this three-way randomized study, switching from menthol cigarettes to mTHS for 5 days in confinement and 85 days in ambulatory settings was associated with reductions in biomarkers of exposure to cigarette smoke, and changes were observed in clinically relevant biomarkers of oxidative stress (8-epi-prostaglandin F2α), platelet activity (11-dehydro-thromboxane B2), endothelial function (soluble intracellular adhesion molecule-1), lipid metabolism (high-density lipoprotein cholesterol) and lung function (forced expiratory volume in 1 second), similar to the SA group. The results suggest that switching to the mTHS has the potential to reduce the adverse health effects of conventional cigarettes.

New ideas, old problems? Heated tobacco products – a systematic review

“…Brossard et al showed that the nicotine pharmacokinetic profile of IQOS was close to that of conventional cigarettes with similar urge-tosmoke levels [36]. The use of IQOS or glo reduced the exposure to smoke toxicants in a manner comparable to quitting tobacco use [74,75]. After switching from conventional cigarettes to HTPs (IQOS or glo), a significant reduction in the levels of biomarkers of exposure to harmful and potentially harmful constituents was observed [76][77][78].…”

“…The results of in vitro and in vivo studies indicate that HTP aerosols have lower toxicity and no new hazards compared to conventional cigarette smoke [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. The results of humanbased studies also suggest that switching from conventional cigarettes to IQOS or glo leads to reductions in exposure to smoke toxicants in a manner comparable to quitting tobacco use [74][75][76][77][78]. However, there have been no independent studies regarding short-term and longterm health consequences of HTP use.…”

Effects of reduced exposure to cigarette smoking on changes in biomarkers of potential harm in adult smokers: results of combined analysis of two clinical studies

“…The level of HDL-C was not significantly different between the NCIT group and the CC1 group (p ¼ 0.4293). Although, three previous-reported clinical studies showed that there was a statistically significant increase of HDL-C in the NVP (Electrically Heated Cigarette Smoking System (EHCSS/ EHCSS-K6/electric cigarette) group compared with the CC group (Roethig et al 2008, Cravo et al 2016, Ludicke et al 2018, other studies did not show this (Ogden et al 2015, Walele et al 2018. Therefore, the changes in HDL-C levels after switching to NVPs were not consistent.…”

“…In order to assess health outcomes, studies to identify biomarkers of potential harm (BoPH) associated with oxidative stress, inflammation, lipid metabolism, glucose metabolism and pulmonary functions have been conducted using smokers (SM) and nonsmokers (NS) (Burchfiel et al 1995, Prieme et al 1998, Eliasson et al 2001, Minami et al 2002, Polidori et al 2003, Flores et al 2004, Wannamethee et al 2005, Halvorsen et al 2007, Ludicke et al 2015, Ogden et al 2015. Although, there are many clinical studies on BoE using NVPs, there are few studies on BoPH associated with smoking using NVPs (Roethig et al 2008, Ogden et al 2015, Ludicke et al 2018. In addition, although, some studies have found that exposure to cigarette smoke toxicants (CSTs) with NVPs were significantly reduced compared to conventional cigarettes (CC), the changes in BoPH varied among the studies.…”

Tabakerhitzer als neues Produkt der Tabakindustrie: Gesundheitliche Risiken

“…Der Hersteller führte 4 klinische Studien durch, um zu untersuchen, ob sich eine geringere Exposition positiv auf entsprechende Biomarker und gegebenenfalls auf die Entstehung tabakassoziierter Krankheiten auswirkt [6][7][8][9]. Zwei der Studien, die in Polen und Japan durchgeführt wurden, waren stationär durchgeführte 5-tägige Studien [6,7].…”