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Background/objectives: Smoking increases the risk for multiple lifestyle-related diseases. In Japan, consumption of heated tobacco products (HTPs), a novel cigarette type, is rising. However, no studies have yet compared dietary habits among HTP smokers. This study assessed food and nutrient intake and alcohol consumption by smoking status (non-smokers, cigarette smokers, HTP smokers). Methods: This cross-sectional study included 237 HTP smokers, 242 cigarette smokers, and 178 non-smokers (50% each male and female). The Brief Self-Administered Diet History Questionnaire was administered as a nutritional survey, and smokers were asked about their smoking status, including smoking history and the number of puffs smoked per day. Results: A significantly higher intake of meat was seen in HTP smokers than in cigarette smokers (p = 0.038), and HTP smokers showed the lowest intake of vitamin D in all groups. HTP and cigarette smokers had a lower intake of certain vitamins, minerals, and dietary fiber compared with non-smokers. The rate of habitual drinkers (at least one drink a month) and their alcohol consumption (g/day) were significantly lower in non-smokers (58%, 1.3 g) than in HTP smokers (67%, 4.8 g) and cigarette smokers (70%, 7.1 g) (p = 0.031). Additionally, after adjusting for sex and smoking status in a multiple regression analysis, the number of puffs was a significant contributor to alcohol intake in HTP smokers (β = 0.296, p < 0.001). Conclusions: This study identified significant dietary, nutritional, and alcohol consumption differences based on smoking status, underscoring the need to consider both diet and smoking type in nutritional counseling and smoking cessation guidance. [ABSTRACT FROM AUTHOR]

Background: With the use of heated tobacco products (HTPs) becoming more widespread in Japan, interest in the health effects of HTP has grown. Since the majority of HTP users are former smokers, information about the user's smoking history and health status before HTP use is needed when assessing the health effects of HTP use. The limited epidemiological studies available did not consistently consider this information adequately, therefore we conducted a cross-sectional study investigating the association between HTP use and respiratory chronic diseases and symptoms. Methods: The questionnaires were sent to a research panel members in Japan via the Internet, and individuals who met the study criteria and were either current exclusive HTP users, current exclusive cigarette users or those had never used tobacco products were selected. Information about the participants' smoking history and health status before they used HTPs was obtained. The effects of participant smoking history before HTP use and the impacts on outcomes upon switching to HTP were assessed using a logistic regression model. The odds ratio (OR) for current exclusive HTP users relative to never tobacco users was calculated. The OR was calculated under two scenarios, one in which the smoking history was ignored or one in which the smoking history was considered. Results: Of the participants from whom responses to the questionnaires were obtained, 17,406 participants were included in the analysis. Almost all participating current exclusive HTP users had a history of long-term smoking (mean: 30.8 years), and the occurrence of outcomes both before and after the start using HTP was reported. The ORs, without adjustment and with adjustment for smoking history before HTP use were, 3.23 (95% CI: 1.37–7.61) and 1.85 (95% CI: 0.70–4.89) respectively in COPD, same as other outcomes. Conclusions: These results suggest that smoking history before HTP using affects the occurrence of outcomes, and underscore the importance of considering smoking history when assessing the health effect of HTP use. Since the duration of HTP use is considerably shorter than that of cigarette use at present, further research, such as follow-up surveys assessing the long-term respiratory effects of HTP use, will be necessary. [ABSTRACT FROM AUTHOR]

In recent years, the tobacco- and/or nicotine-containing product (TNP) portfolio has expanded to include products such as e-vapor products, heated tobacco products, and nicotine pouches. Although scientific papers and regulatory requirements/recommendations related to the assessment of product use behavior and exposure to product use have been published for these novel TNPs, there is great diversity in the terminology used to characterize and assess these types of products. The aim of this paper is to define the terms and methods used for assessing product use behavior and exposure, with the objective to suggest a uniform application of terms used by scientists working in this field of research. This publication is the work product of a cross-industry work item commissioned by the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) Product Use Behaviour and Biomarkers Subgroups.

Abstract Background With the use of heated tobacco products (HTPs) becoming more widespread in Japan, interest in the health effects of HTP has grown. Since the majority of HTP users are former smokers, information about the user’s smoking history and health status before HTP use is needed when assessing the health effects of HTP use. The limited epidemiological studies available did not consistently consider this information adequately, therefore we conducted a cross-sectional study investigating the association between HTP use and respiratory chronic diseases and symptoms. Methods The questionnaires were sent to a research panel members in Japan via the Internet, and individuals who met the study criteria and were either current exclusive HTP users, current exclusive cigarette users or those had never used tobacco products were selected. Information about the participants’ smoking history and health status before they used HTPs was obtained. The effects of participant smoking history before HTP use and the impacts on outcomes upon switching to HTP were assessed using a logistic regression model. The odds ratio (OR) for current exclusive HTP users relative to never tobacco users was calculated. The OR was calculated under two scenarios, one in which the smoking history was ignored or one in which the smoking history was considered. Results Of the participants from whom responses to the questionnaires were obtained, 17,406 participants were included in the analysis. Almost all participating current exclusive HTP users had a history of long-term smoking (mean: 30.8 years), and the occurrence of outcomes both before and after the start using HTP was reported. The ORs, without adjustment and with adjustment for smoking history before HTP use were, 3.23 (95% CI: 1.37–7.61) and 1.85 (95% CI: 0.70–4.89) respectively in COPD, same as other outcomes. Conclusions These results suggest that smoking history before HTP using affects the occurrence of outcomes, and underscore the importance of considering smoking history when assessing the health effect of HTP use. Since the duration of HTP use is considerably shorter than that of cigarette use at present, further research, such as follow-up surveys assessing the long-term respiratory effects of HTP use, will be necessary.

Abstract Background Tobacco smoking is the leading cause of preventable death and disease worldwide, with over 8 million annual deaths attributed to cigarette smoking. This study investigates the impact of cigarette smoke and heated tobacco products (HTPs) on microglial function, focusing on toxicological profiles, inflammatory responses, and oxidative stress using ISO standard and clinically relevant conditions of exposure. Methods We assessed cell viability, reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial function, unfolded protein response, and inflammation in human microglial cells (HMC3) exposed to cigarette smoke, HTP aerosol or nicotine. Results Our findings show that cigarette smoke significantly reduces microglial viability, increases ROS formation, induces lipid peroxidation, and reduces intracellular glutathione levels. Cigarette smoke also alters the expression of genes involved in mitochondrial dynamics and biogenesis, leading to mitochondrial dysfunction. Additionally, cigarette smoke impairs the unfolded protein response, activates the NF-κB pathway, and induces a pro-inflammatory state characterized by increased TNF and IL-18 expression. Furthermore, cigarette smoke causes DNA damage and decreases the expression of the aging marker Klotho β. In contrast, HTP, exhibited a lesser degree of microglial toxicity, with reduced ROS production, lipid peroxidation, and mitochondrial dysfunction compared to conventional cigarettes. Conclusion These results highlight the differential toxicological profile of cigarette smoke and HTP on microglial cells, suggesting a potential harm reduction strategy for neurodegenerative disease for smokers unwilling or unable to quit.

Background: In Japan, heated tobacco products (HTPs) are promoted by the tobacco industry as reduced-risk tobacco products despite the lack of evidence for this claim. This study determined the distribution of HTP-harmfulness perception and identified the explanatory factors associated with the perception of HTP as less harmful than conventional cigarettes. Methods: A nationwide cross-sectional survey was conducted with Japanese people aged 20 years or older (INFORM Study 2020) using a self-administered questionnaire. We performed descriptive analysis and weighted logistic regression analysis to examine the relationship between explanatory factors (eg, individual characteristics, socioeconomic status, and trusted sources of cancer information) and the perception of HTPs as less harmful. Results: Among 3,420 participants, the proportions of those who perceived HTPs as less harmful were 40.3% and 18.3% for users and non-users of tobacco, respectively. For participants aged 20–39 years, the proportions were 49.9% and 30.4%, respectively. Among 1,160 tobacco non-users who were familiar with HTPs, male, aged under 39 years, and having lower education were associated with the perception of HTPs as less harmful. Trusted sources of cancer information were not associated with the perception of HTPs as less harmful. Conclusion: This study showed that, among tobacco non-users, being male, aged under 39 years, and having lower education were associated with a perception of HTPs as less harmful. Public health stakeholders should provide the latest evidence about HTP harmfulness in their daily practice and strengthen the regulations on HTP marketing directed at both tobacco- and tobacco non-users.

Introduction The prevalence of smoking, including heated tobacco products (HTPs), among Japanese dentists was reported to be 16.5%, significantly higher than that among Japanese physicians and United States dentists. However, large-scale studies on smoking cessation implementation based on dentists' smoking status and perceptions since the introduction of HTPs are lacking. Therefore, we aimed to investigate and assess dentists' attitudes toward smoking, including HTP use and smoking cessation, according to smoking status. Methods A self-administered questionnaire comprising six major items was mailed to 3883 dentists who were members of the Aichi Dental Association in August 2019. The primary outcome was smoking cessation status. The secondary outcome was the impact of smoking on intervention for smoking cessation. This study was reported using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Results Among the 1317 (42%) dentists analyzed, men were more positive toward smoking than women. Current and former smokers were more positive about smoking than never smokers/users, regardless of the tobacco product type. Additionally, the current smoker group using conventional cigarettes was less likely to ask for their patients' smoking status than the never smoker group. Furthermore, the current smoker (OR=2.0; 95% CI: 1.3–3.1 vs never smoker) and HTP user (OR=1.9; 95% CI: 1.2–3.1 vs never user) groups were less likely to engage in smoking cessation than the never smoker/user groups, regardless of the tobacco product type. Conclusions Since the smoking status of dentists affects the implementation of smoking cessation interventions, it is crucial to encourage them to quit using all tobacco products to promote smoking cessation interventions in dental practice. Additionally, providing proper smoking prevention education to dentists is an important task.

Background: Tobacco smoking is the leading cause of preventable death and disease worldwide, with over 8 million annual deaths attributed to cigarette smoking. This study investigates the impact of cigarette smoke and heated tobacco products (HTPs) on microglial function, focusing on toxicological profiles, inflammatory responses, and oxidative stress using ISO standard and clinically relevant conditions of exposure. Methods: We assessed cell viability, reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial function, unfolded protein response, and inflammation in human microglial cells (HMC3) exposed to cigarette smoke, HTP aerosol or nicotine. Results: Our findings show that cigarette smoke significantly reduces microglial viability, increases ROS formation, induces lipid peroxidation, and reduces intracellular glutathione levels. Cigarette smoke also alters the expression of genes involved in mitochondrial dynamics and biogenesis, leading to mitochondrial dysfunction. Additionally, cigarette smoke impairs the unfolded protein response, activates the NF-κB pathway, and induces a pro-inflammatory state characterized by increased TNF and IL-18 expression. Furthermore, cigarette smoke causes DNA damage and decreases the expression of the aging marker Klotho β. In contrast, HTP, exhibited a lesser degree of microglial toxicity, with reduced ROS production, lipid peroxidation, and mitochondrial dysfunction compared to conventional cigarettes. Conclusion: These results highlight the differential toxicological profile of cigarette smoke and HTP on microglial cells, suggesting a potential harm reduction strategy for neurodegenerative disease for smokers unwilling or unable to quit. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of smoking, including heated tobacco products (HTPs), among Japanese dentists was reported to be 16.5%, significantly higher than that among Japanese physicians and United States dentists. However, large-scale studies on smoking cessation implementation based on dentists' smoking status and perceptions since the introduction of HTPs are lacking. Therefore, we aimed to investigate and assess dentists' attitudes toward smoking, including HTP use and smoking cessation, according to smoking status. Methods: A self-administered questionnaire comprising six major items was mailed to 3883 dentists who were members of the Aichi Dental Association in August 2019. The primary outcome was smoking cessation status. The secondary outcome was the impact of smoking on intervention for smoking cessation. This study was reported using the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Results: Among the 1317 (42%) dentists analyzed, men were more positive toward smoking than women. Current and former smokers were more positive about smoking than never smokers/users, regardless of the tobacco product type. Additionally, the current smoker group using conventional cigarettes was less likely to ask for their patients' smoking status than the never smoker group. Furthermore, the current smoker (OR=2.0; 95% CI: 1.3–3.1 vs never smoker) and HTP user (OR=1.9; 95% CI: 1.2–3.1 vs never user) groups were less likely to engage in smoking cessation than the never smoker/user groups, regardless of the tobacco product type. Conclusions: Since the smoking status of dentists affects the implementation of smoking cessation interventions, it is crucial to encourage them to quit using all tobacco products to promote smoking cessation interventions in dental practice. Additionally, providing proper smoking prevention education to dentists is an important task. [ABSTRACT FROM AUTHOR]

Compared to cigarette smoke, heated tobacco product (HTP) aerosol contains significantly fewer and lower levels of harmful and potentially harmful constituents (HPHCs). However, the impact on environmental air is relatively unexplored. Therefore, this study compared levels of secondhand aerosol (SHA) constituents in air following glo HTP use with secondhand smoke (SHS) constituents following cigarette smoking in an environmental test chamber (ETC). Extracted ETC air samples following product use sessions were analyzed for 27 SHS/SHA constituents, including HPHCs. The use of glo HTPs resulted in significantly lower SHA HPHC levels in the ETC air relative to SHS HPHC levels from cigarette smoking. Some aerosol constituents (benzene, CO, formaldehyde, nicotine, respirable suspended particles, toluene, ethylbenzene, fine particulate matter, m- and p-cresol, o-cresol, pyridine, styrene, and ultraviolet particulate matter) were either below the limit of detection in ETC air or at significantly low levels following glo HTP use relative to cigarette smoking. Mean concentrations of the assessed constituents were at least 90 % lower following use of glo HTPs compared to smoking combustible cigarettes. These results suggest that glo HTP use would not contribute significantly to indoor air contamination and would reduce non-user exposure to HPHCs and other harmful constituents relative to combustible cigarettes. Such reductions in non-user exposure should be considered when assessing the tobacco harm reduction potential of glo HTPs.

Cigarette smoking is a risk factor for several diseases such as cancer, cardiovascular disease (CVD), and chronic obstructive pulmonary diseases (COPD), however, the underlying mechanisms are not fully understood. Alternative nicotine products with reduced risk potential (RRPs) including tobacco heating products (THPs), and e-cigarettes have recently emerged as viable alternatives to cigarettes that may contribute to the overall strategy of tobacco harm reduction due to the significantly lower levels of toxicants in these products’ emissions as compared to cigarette smoke. Assessing the effects of RRPs on biological responses is important to demonstrate the potential value of RRPs towards tobacco harm reduction. Here, we evaluated the inflammatory and signaling responses of human lung epithelial cells to aqueous aerosol extracts (AqE) generated from the 1R6F reference cigarette, the glo™ THP, and the Vype ePen 3.0 e-cigarette using multiplex analysis of 37 inflammatory and phosphoprotein markers. Cellular exposure to the different RRPs and 1R6F AqEs resulted in distinct response profiles with 1R6F being the most biologically active followed by glo™ and ePen 3.0. 1R6F activated stress-related and pro-survival markers c-JUN, CREB1, p38 MAPK and MEK1 and led to the release of IL-1α. glo™ activated MEK1 and decreased IL-1β levels, whilst ePen 3.0 affected IL-1β levels but had no effect on the signaling activity compared to untreated cells. Our results demonstrated the reduced biological effect of RRPs and suggest that targeted analysis of inflammatory and cell signaling mediators is a valuable tool for the routine assessment of RRPs.

Introduction Although conventional cigarette smoking has been linked to an increased risk of hearing loss, the association between heated tobacco products (HTPs) and hearing loss is unknown. The objective of this study was to investigate the association between cigarette and HTP use and hearing loss. Methods This cross-sectional study examined the data of 7769 employees from five companies (Study I) and 34404 employees from a large company (Study II), all participants in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into five groups based on their selfreported tobacco use: never smokers, former smokers, exclusive cigarette smokers, exclusive users of HTPs, and those who used both cigarettes and HTPs. Hearing levels were measured using pure-tone audiometry at 1 and 4 kHz frequencies. Separate analyses were carried out for each study, and the results were then combined using fixed-effect models to pool the estimates. Results The analysis included 42173 participants, with a prevalence of 12.9% for exclusive cigarette smoking, 9.8% for exclusive HTP use, and 5.5% for dual use. The pooled adjusted odds ratios with 95% confidence intervals for unilateral hearing loss at 4 kHz were 1.21 (95% CI: 1.10–1.33) for former smokers, 1.83 (95% CI: 1.64–2.05) for exclusive cigarette smokers,1.46 (95% CI: 1.28–1.67) for exclusive HTP users, and 1.66 (95% CI: 1.41–1.96) for dual users, compared to never smokers. Additionally, the adjusted odds ratios for hearing loss at 4 kHz among exclusive cigarette smokers, exclusive HTP users, and dual users increased with the intensity of cigarette/HTP consumption (all p for trend

Introduction: Little is known about media exposures to heated tobacco products (HTPs). In this study, we examined sources of HTP exposure, including from paid and unpaid media and social connections, in relation to HTP use and use intentions. Methods: In the fall of 2021, we conducted a cross-sectional survey among adult online panelists (aged 18–45 years) in the US and Israel, oversampling tobacco users. The current study analyzed data from participants who responded to the question about HTP awareness or use (n=2061). Multivariable linear and logistic regression analyses examined the relationship between sources of HTP exposure, HTP use, and use intentions. Results: Among those aware of HTPs, both Israelis and Americans reported past-month HTP media exposure via advertisements (58.2% vs 48.0%), nonadvertisement sources (49.7% vs 30.7%), and social connections (51.5% vs 33.6%), respectively. Factors associated with HTP awareness (n=677/2061; 32.9%) included media use frequency (AOR=1.13; 95% CI: 1.01–1.28) and social connections using HTPs (AOR=2.45; 95% CI: 1.92–3.15). Among those aware of HTPs, past-month HTP exposure via digital media advertisements (AOR=2.06; 95% CI: 1.09–3.91) and non-advertising promotion via radio, podcast, movie, television or theatre (AOR=2.30; 95% CI: 1.19–4.44) and websites (AOR=2.36; 95% CI: 1.32–4.21) were associated with current HTP use. Exposure to digital media advertisements (β=0.35; 95% CI: 0.07–0.62) and non-advertising promotion via social media (β=0.62; 95% CI: 0.34–0.91) were correlated with higher use intentions. Having social connections using HTPs was correlated with higher use (AOR=2.21; 95% CI: 1.19–4.11) and intentions (β=0.66; 95% CI: 0.42–0.91). No significant differences were found across countries. Conclusions: Digital media (e.g. online, social media) were particularly salient correlates of HTP intentions and use. Future studies are needed that further examine media exposures to these products, as well as that examine possible regulations to limit HTP promotion via these channels. [ABSTRACT FROM AUTHOR]

Introduction Certain foods and beverages are associated with smoking craving. However, only few studies have explored the relationship between food or beverage-related and taste-associated smoking craving. In this study, we aimed to identify the types of foods related to smoking craving in Japanese individuals who smoke cigarettes or heated tobacco products (HTPs). Methods A total of 657 individuals (HTP and cigarette smokers and never smokers) participated in this cross-sectional study. Participants were asked what foods/ beverages, tastes, seasonings, cooking methods, and cuisine categories, made them want to smoke and what foods they consumed. Results Alcoholic beverages such as beer, coffee, and fat-rich foods were associated with a higher likelihood of smoking craving. Fruits, dairy products such as milk, and sweet and sour tastes, were associated with a lower likelihood of smoking craving. The daily intake of fruit and dairy products was significantly lower in cigarette and HTP smokers than in non-smokers (median fruit intake: nonsmokers, 46.4 g/1000 kcal/day; cigarette smokers, 22.2 g/1000 kcal/day; HTP smokers, 31.4 g/1000 kcal/day; p

Smoking-related diseases remain a significant public health concern, and heated tobacco products (HTPs) have emerged as a potential alternative to cigarettes. While several studies have confirmed that HTP aerosols contain lower levels of harmful and potentially harmful constituents (HPHCs) than cigarette smoke, less is known about constituents that are intrinsically higher in HTP aerosols. This study provides a comprehensive comparative assessment of an HTP aerosol produced with Tobacco Heating System 2.2 (THS) and comparator cigarette (CC) smoke aiming at identifying all unique or increased compounds in THS aerosol by applying a broad set of LC–MS and GC × GC–MS methods. To focus on differences due to heating versus burning tobacco, confounding factors were minimized by using the same tobacco in both test items and not adding flavorants. Of all analytical features, only 3.5%—corresponding to 31 distinctive compounds—were significantly more abundant in THS aerosol than in CC smoke. A notable subset of these compounds was identified as reaction products of glycerol. The only compound unique to THS aerosol was traced back to its presence in a non-tobacco material in the test item and not a direct product of heating tobacco. Our results demonstrate that heating a glycerol-containing tobacco substrate to the temperatures applied in THS does not introduce new compounds in the resulting aerosol compared to CC smoke which are detectable with the method portfolio applied in this study. Overall, this study contributes to a better understanding of the chemical composition of HTP aerosols and their potential impact on human health. [ABSTRACT FROM AUTHOR]

Introduction: Heated tobacco products (HTPs) are novel tobacco products that may appeal to youth. This study explored whether HTP retailer proximity and density to secondary schools were associated with youth use of HTPs in four Canadian provinces. Methods: An online search between November 2020 and March 2021 identified retailers selling IQOS devices and HEETS (tobacco sticks used in IQOS) within 500 m, 1000 m and 1500 m radius circular buffer zones around high schools (N = 120) participating in the COMPASS study in 2020-2021. Retailer proximity/density data were linked to crosssectional student-level data (N = 40 636 students), and multilevel regression models examined the association between HTP retailer proximity and density and current HTP use, controlling for relevant covariates. Results: While only 10.0% of schools had at least one retailer selling IQOS devices within 1000 m of the school, 65.0% of schools had at least one retailer selling HEETS. The school a student attended accounted for 23.7% of the variability in the likelihood of currently using an HTP. However, HTP retailer proximity to and density around schools were not significantly associated with the likelihood of students currently using HTPs. Conclusion: While the school a student attended accounted for a significant amount of variability in HTP use, these findings suggest that students may be obtaining HTPs through other, non-retail sources. Continued monitoring is warranted as HTP use among youth may change. [ABSTRACT FROM AUTHOR]

Heated tobacco products (HTPs) are a recent category of tobacco products, with their relative safety compared to cigarette smoking and potential to help smokers to quit being two reasons why regulators may consider their market approval. Designed to heat tobacco rather than to burn in order to produce aerosol, different heating techniques are applied to commercial HTPs, which may result in differing aerosol formation. Therefore, each product requires separate assessment. This work focuses on a closed-end HTP (coded as HTP-A), which is electrically heated and designed to allow puffing air flow to bypass its tobacco section, resulting in reduced oxygen concentration within the tobacco section during heating and aerosol forming. To provide a preliminary aerosol chemistry and in vitro toxicological screening, this study assessed HTP-A against a commercial electrically heated HTP (IQOSTM, coded as HTP-B) and a 3R4F reference cigarette. Under Health Canada Intense (HCI) smoking regime, the levels of 9 regulatory priority toxicants in the aerosol of HTP-A were either reduced or comparable to those in HTP-B on a per-stick basis. Additionally, both HTPs showed significant reduction (greater than 90%) in comparison to those measured in mainstream smoke of 3R4F cigarette for these toxicants. Using a set of standard in vitro toxicological assays (Ames, Micronucleus and Neutral Red Uptake), the two HTPs showed no observable responses while significant toxicity responses were recorded for 3R4F’s total particulate matter. Based on these preliminary results, the novel closed-end HTP-A design may provide similar toxicological profiles to the comparator HTP-B. Further toxicological and clinical assessments are warranted to evaluate HTP-A’s potential for exposure or disease risk reduction. [Contrib. Tob. Nicotine Res. 32 (2023) 146–156]

The heated tobacco product (HTP) heats rather than burns tobacco to release an aerosol with significantly fewer toxicants than conventional cigarette smoke and has received global attention in recent years. To investigate whether changes in biomarkers of exposure could be detected after switching from conventional cigarettes (CCs) to HTPs, 224 subjects from four cities in China participated in this study. Nine biomarkers containing tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and the biomarkers for acrolein and crotonaldehyde were determined by UPLC-MS/MS. The levels of the sum of nine biomarkers in CCs were 5.4 and 5.2 times higher than in an Original-HTP and Menthol-HTP, respectively. Among the nine biomarkers, 3HPMA and 3HMPMA accounted for the highest proportions. Switching from CCs to HTPs is good for both men and women because the changes in each biomarker in urine samples were the same in men and women. Among all the subjects, subjects aged 20–39 years had the greatest reduction in biomarker residues in urine. The findings of the present study provided useful information for the health risk research of HTPs in China. [ABSTRACT FROM AUTHOR]

Background: To enhance tobacco control in Japan, the government set a future smoking rate target (smoking prevalence = 12% by 2022) arguing that the “smoking rate target is expected if only smokers who want to quit smoking now, actually quit”. However, ideally both those wanting to quit now and those who wanted to in the past will succeed in the future. We aimed to re-define smokers who intend to quit and estimate their number. We also examined determinants of intention to quit, including daily tobacco consumption and tobacco use categories (exclusive combustible cigarette users, exclusive heated tobacco product (HTP) users, and dual (combustible cigarette and HTP)) users. Methods: Using data from the 2021 Japan ‘Society and New Tobacco’ Internet Survey, we analyzed 5,072 current smokers (had used combustible cigarettes or HTPs in the past 30 days) aged 20–80 years. Smokers who intend to quit were defined as total smokers who want to quit now, have previously attempted or previously wanted to quit. Log-Poisson regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (95%CI) for intention to quit (current or current/past), adjusting for potential covariates such as tobacco use categories. Results: Among current smokers, 40.6% want to quit now, 27.0% have previously attempted and 9.0% have previously wanted to quit. Smokers of over 20 tobacco sticks/day are less likely to want to quit now than 1–10 /day (aOR = 0.79, 95%CI = 0.71–0.87) and less likely to intend to quit (both current and past) (aOR = 0.93, 95%CI = 0.88–0.98). Exclusive HTP and dual users were more likely to intend to quit (both current and past) than exclusive combustible cigarette users (aOR = 1.09, 95%CI = 1.04–1.14) and (aOR = 1.07, 95%CI = 1.03–1.12). Conclusions: In total, 76.6% of current smokers, were defined as having intention to quit (both current and past). Applying this percentage to the target calculation, Japan’s smoking rate target would be 3.9%, considerably lower than the current target of 12%. The Japanese government may have to revise the smoking rate target. Additionally, we found that the usage of HTPs reduces intention to quit smoking. These insights have implications for setting of smoking rate targets and regulating HTPs in different countries.

Abstract Introduction Dental staining is a common concern for tobacco users. However, little is known about which components of tobacco are responsible for the staining and whether nicotine may be implicated. This is of increasing relevance with the popularity of novel products such as heated‐tobacco products and electronic cigarettes (E‐cigarettes). Objectives This systematic review aimed to establish the evidence base for the effect if any, of the various tobacco and nicotine products in causing staining of dental hard tissues and materials. Material and Methods This systematic review was performed in accordance with the preferred reporting items for systematic reviews and meta‐analyses guidelines. There were four structured population intervention comparison outcomesquestions. A search was conducted up to December 2021 in three databases: MEDLINE, EMBASE, and Web of Science, and manual searching of relevant sources was also completed. Two researchers individually reviewed the titles then abstracts and finally full articles. A reporting quality appraisal was conducted appropriately to the study methodology. Results Of the 815 records titles identified, 56 full‐text articles were assessed for eligibility, of which 27 were included for analysis. The included studies were mainly laboratory studies of varying reporting quality. There was evidence from 18 studies that tobacco exposure caused staining of dental hard tissues (pooled results from three studies‐ enamel/dentine; mean difference [MD]: 16.22; 95% confidence interval[12.11, 20.32; I2: 96%)and materials (pooled result from four studies—resin composite; MD: 11.90; 95% CI: 11.47, 12.34; I2: 100%). There was limited evidence that E‐cigarettes 99%) and heated tobacco products (HTPs; pooled results from three studies–−1.07, 6.54; I2: 99%) cause staining, but this was lower than with traditional tobacco/found 11 compounds, of which 8 were terpenoids, from tobacco products implicated in causing staining. Finally, there was some evidence that resin composites stained more than other materials. Conclusions Tobacco smoking causes dental staining. There was limited evidence that E‐cigarettes and HTPs did cause dental staining that was less intense than that caused by traditional tobacco products.

It has previously been found that, compared with cigarette smoke, the aerosols generated by heated tobacco products contain fewer and lower harmful and potentially harmful constituents (HPHCs) and elicit lower biological activity in in vitro models and lower smoking-related exposure biomarker levels in clinical studies. It is important to accumulate such scientific evidences for heated tobacco products with a novel heating system, because different heating system may affect the quantitative aspect of the amount of HPHCs and the qualitative aspect of the biological activity of the aerosol generated. Here, the chemical properties of, and toxicological responses to aerosols emitted by DT3.0a, a new heated tobacco product with a novel heating system, and cigarette smoke (CS) were compared, using chemical analyses, in vitro battery (standardized genotoxicity and cytotoxicity) assays, and mechanistic (ToxTracker and two-dimensional cell culture) assays. Regular- and menthol-flavored DT3.0a and standard 1R6F reference cigarettes were tested. Selected HPHC yields were lower in DT3.0a aerosol than 1R6F CS. The genotoxicity-related assays indicated that DT3.0a aerosol was not genotoxic, regardless of metabolic activation. The other biological assays indicated that less cytotoxicity induction and oxidative stress response were elicited by DT3.0a aerosol compared with 1R6F CS. Similar results were found for both regular and menthol DT3.0a. Like previous reports for heated tobacco products with other heating systems, the results of this study indicated that DT3.0a aerosols have chemical and biological properties less likely to be harmful than 1R6F CS.

In addition to the market launch of heated tobacco products (HTPs) and the JUUL as well as the EVALI, they caused a widespread discussion on the risk reduction compared to a combustible cigarette. Furthermore, first data showed harmful effects on the cardiovascular system. We, therefore, conducted investigations including a control group with a nicotine-free liquid. Forty active smokers were studied in two different approaches during and after consuming an HTP, a cigarette, a JUUL, or a typical electronic cigarette with or without nicotine in a partly double-blinded randomised, cross-over trial. Inflammation, endothelial dysfunction, and blood samples (full blood count, ELISA, multiplex immunoassay) were analysed, and arterial stiffness was measured. In addition to the cigarette, an increase in the white blood cell count but also in proinflammatory cytokines was shown for the various nicotine delivery systems. These correlated with the parameters of arterial vascular stiffness as a clinical parameter of endothelial dysfunction. It can be shown that even a single consumption of the different nicotine delivery system or cigarette leads to a significant inflammatory reaction followed by endothelial dysfunction and increased arterial stiffness causing cardiovascular disease. Inflammation, endothelial dysfunction, and arterial stiffness should be addressed in long-term observational studies. [ABSTRACT FROM AUTHOR]

Many different nicotine delivery products, such as e-cigarettes (e-cigs) or heated tobacco products (HTPs), are available on the market. To better understand these products, it is crucial to learn how consumers use them and how much nicotine they deliver. Therefore, a pod e-cig, an HTP, and a conventional cigarette (CC) were each used by 15 experienced users of the respective product category for 90 min without special use instructions ("ad libitum"). Sessions were video recorded to analyze usage patterns and puff topography. At defined time points, blood was sampled to determine nicotine concentrations, and subjective effects were inquired about using questionnaires. During the study period, the CC and HTP groups averaged the same number of consumption units (both 4.2 units). In the pod e-cig group, the highest number of puffs was taken (pod e-cig 71.9; HTP: 52.2; CC: 42.3 puffs) with the most extended mean puff duration (pod e-cig: 2.8 s; HTP: 1.9 s; CC: 1.8 s). Pod e-cigs were predominantly used with single puffs or in short clusters of 2–5 puffs. The maximum plasma nicotine concentration was highest for CCs, followed by HTPs, and then pod e-cigs with 24.0, 17.7, and 8.0 ng/mL, respectively. Craving was reduced by all products. The results suggest that the high nicotine delivery known for tobacco-containing products (CCs and HTPs) may not be needed for non-tobacco-containing products (pod e-cigs) to satisfy cravings in experienced users. [ABSTRACT FROM AUTHOR]

Background It is not currently clear what impact alternative nicotine-delivery products (electronic cigarettes, heated tobacco products and snus) have on smoking rates and cigarette sales. Objective To assess whether access to these products promotes smoking in the population. Design and data sources We examined associations of alternative nicotine product use and sales with smoking rates and cigarette sales overall, and in different age and socioeconomic groups, and compared smoking prevalence over time in countries with contrasting regulations of these products. For electronic cigarettes, we examined data from countries with historically similar smoking trajectories but differing current electronic cigarette regulations (United Kingdom and United States of America vs. Australia, where sales of nicotine-containing electronic cigarettes are banned); for heated tobacco, we used data from countries with state tobacco monopolies, where cigarette and heated tobacco sales data are available (Japan, South Korea), and for snus we used data from Sweden. Analysis methods We pre-specified dynamic time series analyses to explore associations between use and sales of alternative nicotine-delivery products and smoking prevalence and cigarette sales, and time series analyses to compare trends of smoking prevalence in countries with different nicotine product policies. Results Because of data and analysis limitations (see below), results are only tentative and need to be interpreted with caution. Only a few findings reached statistical significance and for most results the Bayes factor indicated inconclusive evidence. We did not find an association between rates of smoking and rates of the use of alternative nicotine products. The increase in heated tobacco product sales in Japan was accompanied by a decrease in cigarette sales. The decline in smoking prevalence seems to have been slower in Australia than in the United Kingdom overall, and slower than in both the United Kingdom and the United States of America among young people and also in lower socioeconomic groups. The decline in cigarette sales has also accelerated faster in the United Kingdom than in Australia. Limitations Most of the available data had insufficient data points for robust time series analyses. The assumption of our statistical approach that causal interactions are more likely to be detected when longer-term changes are screened out may not apply for short time series and in product interaction scenarios, where short-term fluctuations can be caused by, for example, fluctuations in prosperity or product supplies. In addition, due to dual use, prevalence figures for smoking and alternative product use overlap. The ecological study design limits the causal inferences that can be made. Longer time periods are needed for any effects of exclusive use of the new products on smoking prevalence to emerge. Conclusions We detected some indications that alternative nicotine products are competing with cigarettes rather than promoting smoking and that regulations that allow their sales are associated with a reduction rather than an increase of smoking, but the findings are inconclusive because of insufficient data points and issues with the assumptions of the pre-specified statistical analyses. Future work As further prevalence and sales data emerge the analyses will become more informative. Accessing sales figures in particular is the current research priority. Study registration The project is registered on Open Science Framework https://osf.io/bd3ah. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR129968) and will be published in full in Public Health Research; Vol. 11, No. 7. See the NIHR Journals Library website for further project information. Plain language summary Alternative nicotine-delivery products are now available which are much less hazardous than cigarettes. These include electronic cigarettes (which contain no tobacco), Swedish snus (oral tobacco with low levels of cancer-causing chemicals) and heated tobacco products. There is concern that these products attract young people to smoking and discourage smokers from quitting (i.e. increase smoking), but it is also possible that they help smokers quit and steer young people who find nicotine attractive away from smoking, or that they have no effect on smoking. To clarify which of these end results is likely, we looked at data on smoking and on the use of these alternative products over time, and also compared data on smoking from countries that have similar tobacco control history, but that either allow (i.e. United Kingdom and United States of America) or ban the sale of electronic cigarettes (i.e. Australia). As the sale of heated tobacco products increased in Japan, sales of cigarettes seem to have gone down, suggesting that this product is competing with cigarettes rather than encouraging their use. We also found that the drop in smoking may have been slower in Australia than in the United Kingdom. For young people and those on low income specifically, the reduction in smoking was slower in Australia than in both the United Kingdom and United States of America. Allowing alternative nicotine products to be sold seems to have been linked with lowered rather than increased rates of smoking. Our findings, however, are uncertain because only limited data were available. Clearer conclusions will become possible as more data on the use and especially on the sales of alternative nicotine products are collected. Scientific summary Background The key controversy surrounding reduced-risk alternative nicotine-delivery products (ANDs), comprising electronic cigarettes (ECs), snus and heated tobacco products (HTPs), concerns their effects on smoking prevalence. They may promote smoking by enticing adolescents to cigarette use and by reducing quitting in smokers (e.g. by allowing them to circumvent smoke-free regulation), but it is also possible that ANDs redirect young nicotine seekers away from smoking and help smokers quit, or they may have no clear impact on smoking. Alternative nicotine-delivery systems have been used for a number of years, and some information may already exist in data on smoking prevalence and on AND and cigarette sales that can contribute to answering this question. If, in countries with substantial AND use, the trends in the historical decline in smoking rates and cigarette sales have slowed down or reversed, and this is not happening in countries that restrict or ban ANDs, this would be consistent with the ‘gateway into smoking’ hypothesis, while the opposite finding would suggest that these products are replacing rather than promoting smoking. A finding that ANDs have no net effect on smoking prevalence and cigarette sales, or that currently available data do not provide a clear answer, would also have implications both for policies (which will need to take account of the uncertainty) and for future research (which can aim to fill the gaps). Objectives We aimed to answer the following research questions (RQs): Is there an association between the prevalence of smoking and prevalence of AND use (in the population in general, in young adults and in different socioeconomic groups), in different countries and for different AND products? Is there an association between sales of different AND products and cigarette sales? Are there any differences in time trends of smoking prevalence (overall, in young adults and in different socioeconomic groups) and cigarette sales following the introduction of ANDs between countries that had similar tobacco control measures prior to ANDs emerging locally, but that have allowed EC sales [United Kingdom (UK) and United States of America (USA)] or banned them (Australia)? Methods We examined data from the countries and data sets described below that allow examinations of links between AND use and smoking rates, and between cigarette and AND sales. We also compared trajectories of smoking prevalence over time in countries with contrasting legislative and policy frameworks concerning ANDs. Countries selected Regarding prevalence data (RQ1), we explored links between the prevalence of EC use and cigarette smoking in the UK and USA (where data on EC use and cigarette use are available), Sweden (the only EU country where snus use is allowed and where data on snus and cigarette use are available) and Japan (where in addition to smoking prevalence data, at least some data on HTP use are available). We also looked at links between prevalence of smoking and sales of ANDs in Japan and South Korea, where data on HTP sales were available. Regarding sales data (RQ2), we explored links between sales of cigarettes and snus in Sweden, and between sales of cigarettes and sales of HTPs in Japan and South Korea. No comprehensive data on EC sales are available for the UK and USA, because ECs are produced by a large number of manufacturers, but we looked at ‘hybrid’ links between the prevalence of EC use and sales of cigarettes in the UK and USA. We also explored whether time trends in cigarette use and sales in the UK and USA, where ECs are allowed, differ from those in Australia, where sales of nicotine-containing ECs are banned (RQ3). The three countries have a broadly similar history and formats of tobacco control otherwise. Data sources Where more than one survey was available per country, we selected the survey to use based on: quality of smoking and AND use measures years covered representativeness of samples and weighting number of time points (monthly/quarterly breakdown) sample size quality of socioeconomic status (SES) information. For the UK, we used the Health Survey for England (HSE) for prevalence and HM Revenue and Customs National Statistics Tobacco Bulletin for cigarette sales data. For the USA, we used the National Health Interview Survey (NHIS) and the National Youth Tobacco Survey (NYTS) for prevalence of smoking. NielsenIQ data on cigarette sales were purchased from Chicago Booth. For Australia, we used the National Drug Strategy Household Survey (NDSHS) for prevalence of smoking and Euromonitor International reports for cigarette sales data. For Japan, we used the National Health and Nutrition Survey for prevalence, Tobacco Institute of Japan data for cigarettes sales and Philip Morris International reports for HTP sales data. For South Korea, we used the Korea National Health and Nutrition Examination Survey (KHANES) for prevalence, and Korea Tobacco and Ginseng Corporation (KT&G) reports for sales data. For Sweden, we used the Swedish Council for Information on Alcohol and Other Drugs (CAN): Monitor Studies for prevalence and Swedish Match AB provided data for cigarette and snus sales directly by e-mail. See Chapter 2 – Methods, Survey data chosen for details of where these surveys were available. For analyses looking at the interplay between cigarettes and EC/HTP use (RQ1), we included data on smoking from 2005 until the most recent available year up to 2019, before the COVID-19 epidemic started. The same timeframe was used, where available, for analyses exploring the interplay of cigarettes and EC/HTP sales (RQ2). This allowed for modelling of smoking and cigarette sales for at least 5 years prior to the emergence of these newer products. For snus, we analysed the data from 2007 to 2019. For analyses looking at trends in cigarette smoking in the UK, USA and Australia we used data from 2004 onwards as the NDSHS is triennial and we wanted to include 2004 as a proxy for 2005. Similarly, for the NYTS, which used to be biannual, we included 2004 as a proxy for 2005. For analyses looking at trends in cigarette sales for the UK, USA and Australia we looked at data from 2010 as sales data for Australia were only available from that year. Statistical methods We pre-specified in our statistical analysis plan that we would use dynamic time series applying generalised least squares (GLS) models to explore the association between prevalence of smoking and product use, as well as cigarette and product sales. Regression models were used to compare trends in smoking prevalence between countries where EC use is allowed or banned. The analyses were adjusted for two policy variables which are believed to have the strongest effect on smoking prevalence and cigarette sales and that have been implemented at different time points in most countries: the introduction of bans on smoking in public spaces where they occurred during the study period; and increases in cigarette prices exceeding normal trends (25% increase in 2010 in Australia, 37% in October 2010 in Japan, 80% increase in 2015 in South Korea, 14% increase in 2009 in the USA and 11% increase in 2015 in the UK). Each policy was modelled as a step level change, coded as one after the introduction of the policy and zero before. Unfortunately, the available data had insufficient data points for robust time series analyses. We carried out the planned analyses to adhere to the original plan, but the results need to be considered as only tentative and interpreted cautiously. Due to the short time series, it is possible that underlying trends were not correctly identified and removed, resulting in confounding. For example, in the majority of analyses, trends were identified as linear and first-order differencing was used. However, studies suggest that the decline in smoking prevalence follows a more monotonic curvilinear decline over time, which was not identified in the short series and would have required higher differencing. Conversely, with short-term non-granular time series, there is a risk of removing trends which in fact reflect short-term changes and perhaps a casual association between series. In addition, because of the short series, more sophisticated time series models, such as autoregressive integrated moving average with explanatory variable (ARIMAX), could not be used for the majority of analyses because these require more time-points. ARIMAX models have several benefits over GLS, including the use of transfer functions to model lags between multiple time series and inclusion of seasonal autocorrelation. Finally, short time series are highly influenced by outliers, and these can dominate the output from models. Longer time series are not influenced in the same way. These factors can all result in spurious associations. We used Bayes factors (BF) to help us to determine whether non-significant results provided evidence of no effect or were due to data being insensitive, with BF between 1/3 and 1 suggesting no or weak evidence for the null hypothesis, BF between 1/3 and 1/10 suggesting moderate evidence, and 1/10 or lower as strong evidence for the null hypothesis. Results Only a few associations were detected. Regarding RQ1, we did not find an association between rates of smoking and rates of alternative nicotine product use, potentially due to the analyses being under-powered. Regarding RQ2, the increase in sales of HTPs in Japan was accompanied by a decrease in sales of cigarettes (b = −1.09, p

Background: Heated tobacco product (HTP) use continues in Japan as the second most common product after cigarettes. While the health effects of HTPs and their secondhand emissions are not well-studied, the tobacco industry has actively marketed HTPs as a smokeless, health-conscious alternative to cigarettes to encourage home consumption. We investigated the prevalence of current tobacco product use and usage at home. Methods: The present study conducted a cross-sectional analysis of data from the 2023 wave of a nationwide, Internet-based, self-reported survey. 29,354 individuals aged 16–74 were included in the analysis. We assessed the prevalence of current (past-30-day) use for HTPs, cigarettes, non-cigarette combustible tobacco, and dual (combustible plus HTP) use. The frequency of use (daily or more than monthly) in the home was calculated for both HTPs and combustible tobacco. Multivariable Poisson regression models were employed to identify factors associated with home usage. Adjusted prevalence ratios (APRs) and 95% confidence intervals (CIs) were computed. All analyses were weighted to address the Internet-based sample's selectivity and yield nationally representative estimates. Results: In 2023, the prevalence of current use was 12.4% (HTPs), 18.9% (cigarettes), 3.6% (non-cigarette combustible tobacco), and 7.4% (dual use). Among current users of any tobacco (N = 5,818), 49.8% reported daily tobacco usage within their homes, and 67.1% reported monthly or more frequent home usage. Compared to exclusive combustible tobacco smokers, exclusive HTP users exhibited higher prevalence of daily home usage (APR = 1.54; 95% CI = 1.43–1.67), as did dual users (APR = 1.10; 95% CI = 1.01–1.20). Daily home usage prevalence was notably higher for those without complete tobacco-free rules at home or workplaces, older individuals, and those with lower education levels. Those living with adult or child household member and current drinkers showed significantly lower daily home usage prevalence. Conclusion: Home usage was more common among HTP users than among combustible tobacco smokers. Ongoing efforts to assess and address the impact of indoor tobacco product use, including HTPs, on health are warranted. Regulatory and educational strategies should be considered to discourage tobacco consumption in both public and private spaces.

This study compared the cytotoxicity of IQOS aerosols to smoke from Marlboro Red (MR) and 3R4F reference cigarettes. Aerosol/smoke solutions were tested as the gas vapor phase (GVP), particulate phase (total particulate matter or TPM), or whole aerosol/smoke (WA), the latter being what smokers actually inhale. Cytotoxicities were evaluated using the LDH, MTT and neutral red uptake (NRU) assays in conjunction with eight different cell types, mainly from the respiratory system. Most test solutions did not compromise the plasma membranes of cells (LDH). However, mitochondrial activity (MTT) and dye uptake/lysosomal activity (NRU) were equally depressed by IOQS aerosols and cigarette smoke solutions at the high concentrations. Our NRU data with mouse NIH/3T3 transformed fibroblasts were similar to those previously reported by the IQOS manufacturer and showed little cytotoxicity in the NRU assay. In both studies with NIH/3T3 cells, the results were significantly different from 3RF4 cigarette smoke, suggesting reduced toxicity with IQOS. However, by expanding evaluations to a broader spectrum of cells that included respiratory system cells and by including higher concentrations of GVP, as well as WA, cytotoxicity equivalent to that of Marlboro Red and 3R4F cigarettes was frequently observed with IQOS aerosols in the MTT and NRU assays.

Introduction: Dental staining is a common concern for tobacco users. However, little is known about which components of tobacco are responsible for the staining and whether nicotine may be implicated. This is of increasing relevance with the popularity of novel products such as heated-tobacco products and electronic cigarettes (E-cigarettes). Objectives: This systematic review aimed to establish the evidence base for the effect if any, of the various tobacco and nicotine products in causing staining of dental hard tissues and materials. Material and Methods: This systematic review was performed in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. There were four structured population intervention comparison outcomesquestions. A search was conducted up to December 2021 in three databases: MEDLINE, EMBASE, and Web of Science, and manual searching of relevant sources was also completed. Two researchers individually reviewed the titles then abstracts and finally full articles. A reporting quality appraisal was conducted appropriately to the study methodology. Results: Of the 815 records titles identified, 56 full-text articles were assessed for eligibility, of which 27 were included for analysis. The included studies were mainly laboratory studies of varying reporting quality. There was evidence from 18 studies that tobacco exposure caused staining of dental hard tissues (pooled results from three studies- enamel/dentine; mean difference [MD]: 16.22; 95% confidence interval[12.11, 20.32; I2: 96%)and materials (pooled result from four studies--resin composite; MD: 11.90; 95% CI: 11.47, 12.34; I2: 100%). There was limited evidence that E-cigarettes 99%) and heated tobacco products (HTPs; pooled results from three studies--1.07, 6.54; I2: 99%) cause staining, but this was lower than with traditional tobacco/found 11 compounds, of which 8 were terpenoids, from tobacco products implicated in causing staining. Finally, there was some evidence that resin composites stained more than other materials. Conclusions: Tobacco smoking causes dental staining. There was limited evidence that E-cigarettes and HTPs did cause dental staining that was less intense than that caused by traditional tobacco products. [ABSTRACT FROM AUTHOR]

Background: Heated tobacco products (HTPs) are widespread in Japan, and smoking cessation of such products has become an important issue owing to the spread of harmful effects from HTPs. The efficacy of online digital therapy has been reported in smoking cessation treatment; however, we have limited evidence of online smoking cessation programs for HTP users. Objective: In this study, we evaluate the usefulness of the Ascure program for HTP users (defined as exclusive HTP use or dual use of HTP and cigarettes) compared with exclusive cigarette users. Methods: This was a retrospective study. We recruited adult smokers participating in the Ascure online smoking cessation program in Japan from June 2019 to February 2021. The Ascure smartphone app provided four elements: (1) educational video tutorials to enhance the understanding of nicotine dependence, (2) a personalized to-do list for behavior change, (3) a digital diary for record keeping, and (4) interactive chat sessions for relief from cravings or withdrawal symptoms. The primary outcome was the continuous abstinence rate (CAR) at weeks 21 to 24, biochemically validated using salivary cotinine testing. We considered those who dropped out of the program as smoking cessation failures. We analyzed the primary outcome using inverse probability weighting against tobacco product type estimated by multinomial propensity scores. We also assessed CAR at weeks 9 to 12 and program adherence. Results: We analyzed data from 2952 participants, including 52% (1524/3478) in the cigarette group, 35% (1038/3478) in the HTP group, and 13% (390/3478) in the dual-use group, who had a mean age of 43.4 (SD 10.8) years and included 17% (513/2952) women. CAR at weeks 21 to 24 showed that exclusive HTP users were more likely to stop tobacco use than exclusive cigarette smokers (CAR 52.6% for cigarette users vs CAR 64.8% for HTP users; odds ratio [OR] 1.17, 95% CI 1.12-1.22; P <.001). There was no significant difference between the exclusive cigarette users and the dual users (CAR 52.6% for cigarette users vs CAR 48.7% for dual users; OR 0.99, 95% CI 0.93-1.05; P =.77). CAR at weeks 9 to 12 was 56.7% (95% CI 54.2%-59.2%) for the exclusive cigarette users, 68.3% (95% CI 65.5%-71.1%) for the exclusive HTP users, and 58.2% (95% CI 53.3%-63.1%) for the dual users. The program adherence rate at week 24 was 70.7% overall (68.4% for cigarette users, 75% for HTP users, and 67.9% for dual users). Conclusions: Exclusive HTP users had higher CARs and adherence compared with exclusive cigarette users, indicating a higher affinity for the Ascure online smoking cessation program. This program might be a useful smoking cessation option for HTP users, as well as for cigarette smokers. [ABSTRACT FROM AUTHOR]

The exposure and health implications of exhaled aerosol particles from tobacco products remain a critical area of concern in public health. This research aimed to characterize the cytotoxicity of exhaled aerosol particles from conventional cigarettes (CC) and heated tobacco products (HTP) using a novel "Cells-on-Particles" integrated aerosol sampling and cytotoxicity in vitro testing platform. The research uniquely captures the physical and chemical characteristics of aerosols by depositing them onto fibrous matrixes, enabling a more accurate representation of exposure conditions. New insights were provided into the differences between CC and HTP in terms of particle size distributions, cell viability, metabolic activity, and the expression of genes related to xenobiotic metabolism and oxidative stress. This approach marks a significant advancement in the field by offering a more direct and representative method to evaluate the potential health hazards of tobacco aerosol particles. [Display omitted] • Novel "Cells on Particles" in vitro model applied for tobacco aerosol cytotoxicity. • HTP & CC show distinct cell viability & cytotoxicity patterns. • Optimal aerosol doses: 50–70 μg/cm2 for HTP, <30 μg/cm2 for CC. • CC aerosols lead to dose-dependent cell death; HTP shows varied effects. • HTP upregulates anti-oxidative genes; CC increases inflammation markers. [ABSTRACT FROM AUTHOR]

In the present study, we evaluated the acute response of mice exposed to IQOS aerosol, a brand-name heated tobacco product (HTP), in the lung tissue. First, the thiobarbituric acid-reactive substances (TBA-RS) value was measured as an index to assess oxidative stress, and a significant increase was observed after exposure, followed by a significant increase in the total lung GSH concentration. The stress responses induced by IQOS aerosols was then analyzed by focusing on the changes in Nrf2 and ATF4, which are transcription factors that induce the expression of genes involved in GSH biosynthesis or metabolism. Although Nrf2 activation was not observed, significant accumulation of ATF4 in the nuclear fraction was noted three hours after exposure to IQOS aerosols. Upon an examination of changes in factors in the GSH biosynthetic system, a significant increase in cystine concentration in the lung tissue was measured, and an increase in xCT expression level was observed in the cell membrane fraction three–six hours after IQOS exposure. Furthermore, characteristic changes in HO-1, a stress-response protein regulated by ATF4, was discovered six hours after IQOS exposure. Moreover, analysis of the upstream ATF4 regulatory system revealed that phosphorylation of eIF2α was enhanced in the lung cytoplasmic fraction three hours after exposure to IQOS aerosols. These findings suggest that ER stress might be induced as an early response to IQOS aerosol exposure, accompanied by the activation of the eIF2α-ATF4 axis. These intracellular changes have also been reported after exposure to combustible cigarette smoke. Thus, the acute response found in the lungs of mice in the present study demonstrate that the inhalation of aerosols from IQOS elicits a biological response similar to that of combustible cigarette smoke. In conclusion, our results provide evidence that the biological effects of HTPs, such as IQOS, cannot be ignored in the lungs. [ABSTRACT FROM AUTHOR]

The awareness of healthcare practitioners concerning heated tobacco product (HTP) use risks has been evaluated; however, few studies have investigated general dental practitioners' awareness regarding HTP-use risks. In this cross-sectional study, we investigated dentists' awareness of the risks of smoking, particularly HTP use. A self-administered questionnaire, including eight questions on conventional cigarette and HTP smoking/using status and both knowledge and awareness of HTP-use risks, was posted to 3883 dentists belonging to the Aichi Dental Association, Japan, in August 2019. Statistical analysis was performed using the Statistical Package for Social Sciences; statistical significance was set at p < 0.05. We analyzed the data of 1317 dentists (participation rate, 41.6%). The study group included cigarette smokers (11.5%) and HTP users (8.5%), among whom 41.1% were dual users. HTP users were more likely than never smokers/users to correctly perceive HTP-use risks (p < 0.05). This study indicates that in Japan, the proportion of HTP users is higher than that of the general population. It is important to educate not only smokers/users but also never smokers/users on the risks of smoking and using HTPs. Smoking cessation, including ceasing HTP use, and aiming to quit smoking and HTP use among dentists would contribute to appropriate smoking cessation among patients. [ABSTRACT FROM AUTHOR]

Monitoring tobacco use has become more complex with the proliferation of novel tobacco products, including heated tobacco products (HTPs). We assessed the latest prevalence and denial of tobacco product use in Japan, a major market for HTPs. 28,124 individuals aged 16–74 responded to a nationwide, internet-based, self-reported survey. Current (past-30-day) tobacco use was assessed for HTPs, cigarettes, non-cigarette combustible tobacco, and dual (combustible plus HTP) use. Denial of current tobacco use was determined when respondents reported past-30-day use of a specific tobacco product (“On how many days did you use [the respective products]?”) but denied having used any tobacco (“Do you currently use tobacco?”) in the past 30 days. Descriptive and multivariable analyses were weighted to account for the selectivity of the internet-based sample. In 2022, current tobacco use was 11.8 % (HTPs), 19.4 % (cigarettes), 3.6 % (non-cigarette combustible tobacco), and 6.8 % (dual use). Among past-30-day users of specific tobacco products (N = 6,343), 19.5 % denied current tobacco use including single-product users of HTPs (10.0 %), cigarettes (21.7 %), and non-cigarette combustible tobacco (53.3 %), and dual users (20.2 %). The likelihood of denying current tobacco use was lower among exclusive HTP users and dual users compared to exclusive cigarette smokers; the likelihood was higher among females, never/non-current drinkers, less-frequent tobacco users, and those not reporting tobacco dependence. HTP use remained high in Japan. One-fifth of past-30-day tobacco users denied having used any tobacco products in the past 30 days. Increasing the sensitivity of questions to assess tobacco use can mitigate nondisclosure of tobacco use status.

Although some private companies have implemented “time-based” workplace smoking bans covering all working hours including lunchtime, little is known about their impact on tobacco use. We examined associations between workplace smoking bans during working hours (including and excluding lunchtime) versus no ban and workers’ combustible cigarette and heated tobacco product (HTP) use.We used data from the Japan “Society and New Tobacco” Internet Survey 2020 and in total 4,222 workers aged 20–74 were included in the analyses. Using inverse probability weighting, prevalence ratios (PRs) and 95% confidence interval (CI) for tobacco use were calculated according to “time-based” smoke-free policies: workplace smoking bans for working hours including lunchtime (lunchtime ban), workplace smoking ban for working hours excluding lunchtime (lunchtime allowed), and no ban for working hours (no ban).The PRs of “lunchtime ban” for workers’ use of combustible cigarettes and HTPs were lower than “no ban”: 0.43 (CI: 0.29, 0.63) for combustible cigarette use and 0.61 (CI: 0.41, 0.90) for HTPs use. Meanwhile, the PRs for “lunchtime allowed” was not significant: 0.84 (CI: 0.70, 1.01) for combustible cigarettes use and 1.15 (CI: 0.94, 1.40) for HTPs use.Workplace bans on smoking during working hours which include lunchtime may successfully reduce workers’ combustible cigarette and HTP use, but allowing their use during lunchtime may reduce the effectiveness of the ban. Not only conventional “place-based” smoke-free policies, but also “time-based” smoke-free policies are useful for tobacco control in the workplace.

The heated tobacco product (HTP) heats rather than burns tobacco to release an aerosol with significantly fewer toxicants than conventional cigarette smoke and has received global attention in recent years. To investigate whether changes in biomarkers of exposure could be detected after switching from conventional cigarettes (CCs) to HTPs, 224 subjects from four cities in China participated in this study. Nine biomarkers containing tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and the biomarkers for acrolein and crotonaldehyde were determined by UPLC-MS/MS. The levels of the sum of nine biomarkers in CCs were 5.4 and 5.2 times higher than in an Original-HTP and Menthol-HTP, respectively. Among the nine biomarkers, 3HPMA and 3HMPMA accounted for the highest proportions. Switching from CCs to HTPs is good for both men and women because the changes in each biomarker in urine samples were the same in men and women. Among all the subjects, subjects aged 20–39 years had the greatest reduction in biomarker residues in urine. The findings of the present study provided useful information for the health risk research of HTPs in China.

Introduction The consumption of heated tobacco products (HTPs) is increasing among adolescents worldwide. Although suicide and HTP use are linked, the association between suicide-related behavior, HTP use, and indirect smoking exposure are not yet properly studied. This study examined the association of HTP use and exposure to secondhand smoke (SHS) with suicidal ideation, suicide plans, and suicide attempts among South Korean adolescents. Methods Data from 57303 respondents (95.3% response rate) were obtained from the 2019 Korean Youth Risk Behavior Web-based Survey. Chi-squared tests and multivariable logistic regression analyses were used to examine the association of HTP use and SHS exposure with suicidal ideation, suicide plans, and suicide attempts among adolescents. Multivariable logistic regression analyses included: Model 1, which was adjusted for demographic characteristics such as sex, school type, perceived school performance, economic status, and residence type; and Model 2, which was adjusted for demographics, depression, and drug use. Results The risk of suicidal ideation was 1.37 (95% CI: 1.10–1.70) and 1.44 (95% CI: 1.18–1.75) times higher among HTP users who were exposed to SHS at home and at public places, respectively, compared to non-users. The risk of suicide attempts was 1.88 (95% CI: 1.37–2.57), 1.45 (95% CI: 1.63–2.00), and 2.21 (95% CI: 1.63–3.00) times higher among HTP users exposed to SHS at home, school, and at public places, respectively. Conclusions HTP use, and SHS exposure are likely indicators of risk behaviors. Our findings suggest possible directions for initiating, implementing, and evaluating programs and services to monitor HTP use and SHS exposure among Korean adolescents.

ObjectivesWe conducted a 6-month randomized clinical study to evaluate the impact of exposure to the aerosol of the Tobacco Heating System (THS), a smoke-free alternative to cigarettes, on changes in periodontal parameters after scaling and root planing (SRP) for periodontitis in subjects who were either continuing to smoke cigarettes or had switched to THS.Material and methodsSmokers with generalized periodontitis were randomized to continue smoking cigarettes or switch to THS use. They underwent SRP for up to 8 weeks, with dental assessments conducted at baseline and at 3 and 6 months after the first treatment.ResultsAfter SRP treatment, all groups showed improvements in the mean full-mouth probing depth (PD), full-mouth clinical attachment level (CAL), gingival inflammation score, plaque control record (PCR), and bleeding on probing (BoP). There were no statistically significant intergroup differences. However, as compared to smokers, THS users showed a trend toward more favorable outcomes in BoP, PCR, and PD improvement at sites with higher initial PD (≥7 mm).ConclusionsOur results indicate that SRP improves the course of periodontitis similarly in cigarette smokers and THS users. The beneficial effects of this treatment might mask the favorable changes that may occur upon modifying one of the several periodontitis risk factors, such as cigarette smoking.Clinical trial registrationClinicalTrials.gov, identifer: NCT03364751.

Many different nicotine delivery products, such as e-cigarettes (e-cigs) or heated tobacco products (HTPs), are available on the market. To better understand these products, it is crucial to learn how consumers use them and how much nicotine they deliver. Therefore, a pod e-cig, an HTP, and a conventional cigarette (CC) were each used by 15 experienced users of the respective product category for 90 min without special use instructions (“ad libitum”). Sessions were video recorded to analyze usage patterns and puff topography. At defined time points, blood was sampled to determine nicotine concentrations, and subjective effects were inquired about using questionnaires. During the study period, the CC and HTP groups averaged the same number of consumption units (both 4.2 units). In the pod e-cig group, the highest number of puffs was taken (pod e-cig 71.9; HTP: 52.2; CC: 42.3 puffs) with the most extended mean puff duration (pod e-cig: 2.8 s; HTP: 1.9 s; CC: 1.8 s). Pod e-cigs were predominantly used with single puffs or in short clusters of 2–5 puffs. The maximum plasma nicotine concentration was highest for CCs, followed by HTPs, and then pod e-cigs with 24.0, 17.7, and 8.0 ng/mL, respectively. Craving was reduced by all products. The results suggest that the high nicotine delivery known for tobacco-containing products (CCs and HTPs) may not be needed for non-tobacco-containing products (pod e-cigs) to satisfy cravings in experienced users.

Pulmonary emphysema is predominantly caused by chronic exposure to cigarette smoke (CS). Novel tobacco substitutes, such as heated tobacco products (HTPs), have emerged as healthier alternatives to cigarettes. IQOS, the most popular HTP in Japan, is advertised as harmless compared with conventional cigarettes. Although some studies have reported its toxicity, few in vivo studies have been conducted. Here, 12-wk-old C57BL6/J male mice were divided into three groups and exposed to air (as control), IQOS aerosol, or CS for 6 mo. After exposure, the weight gain was significantly suppressed in the IQOS and CS groups compared with the control ( –4.93 g; IQOS vs. air and –5.504 g; CS vs. air). The serum cotinine level was significantly higher in the IQOS group than in the control group. The neutrophils and lymphocyte count increased in the bronchoalveolar lavage fluid of the IQOS and CS groups compared with those in the control group. Chronic IQOS exposure induced pulmonary emphysema similar to that observed in the CS group. Furthermore, expression levels of the genes involved in the apoptosis-related pathways were significantly upregulated in the lungs of the IQOS-exposed mice. Cytochrome c, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase-1 were overexpressed in the IQOS group compared with the control. Single-stranded DNA and TdT-mediated dUTP nick-end labeling-positive alveolar septal cell count significantly increased in the IQOS group compared with the control. In conclusion, chronic exposure to IQOS aerosol induces pulmonary emphysema predominantly via apoptosis-related pathways. This suggests that HTPs are not completely safe tobacco products. [ABSTRACT FROM AUTHOR]

Background: Several smoke-free tobacco and/or nicotine-containing products (TNP) have emerged in recent years to support tobacco harm reduction strategies and reduce individual health risks and population harm relative to continued cigarette smoking. This paper describes the nationwide prevalence and patterns of TNP use in Japan following the commercialization of one such smoke-free TNP, the heated tobacco product IQOS® (Philip Morris International). Methods: We analyzed the first annual data (2016–2017) of two repeated cross-sectional surveys conducted in a representative sample of the Japanese general adult (≥20 years of age) population (N = 4,878) and a sample of adult IQOS users (N = 2,000). We assessed the prevalence of current TNP use according to type of product (cigarettes, IQOS, e-cigarettes, and other TNPs) in the general population and patterns of TNP use in the IQOS user sample. Results: The prevalence of current use across all TNP in the sampled general population was 18.5% (95% confidence interval 17.2–19.5%), with 17.5% (16.4–18.6%) for cigarette smoking and 1.8% (1.4–2.2%) for IQOS use. Regarding the distribution of patterns of use in the IQOS user survey, the majority (63.4% [61.2–65.6%]) were exclusive users of IQOS, followed by 20.6% (18.7–22.5%) of individuals who reported dual use of IQOS and cigarettes. Conclusions: In Japan, cigarette smoking remains the most prevalent way of consuming TNP; however, IQOS is being adopted by a growing number of adult Japanese smokers. These findings serve as baseline data for monitoring trends over time in the use and adoption of potential smoke-free TNP in Japan.

Background: Risk perception (RP) is central to smokers’ decision to switch to smoke-free tobacco and nicotine products (TNP). This study assessed temporal trends in the health RP of a novel heated tobacco product, IQOSTM, relative to cigarettes, among current IQOSTM users. Methods: The analyses included repeated cross-sectional data from online surveys in Germany (2018–19), Italy (2018–19), and Japan (2016–17, 2017–18, and 2018–19) among a random sample of current adult IQOSTM users from local registers of IQOSTM users. The health RPs of cigarettes and IQOSTM were assessed using the ABOUT™–Perceived Risk instrument, and their difference was described as the relative RP of IQOSTM to cigarettes (RPCig:IQOSTM). Results: After adjustment for covariates, the relative RPCig:IQOSTM was higher in 2018 than in 2019 (0.93; standard error, 0.33; P = 0.005). This was driven by an increase in the RP of IQOSTM over time in Italy (2018: 42.6 [95% CI, 41.6–43.5]; 2019: 44.4 [43.4–45.4]) and Japan (2017: 44.0 [43.1–44.9); 2018: 45.9 [45.2–46.7]; 2019: 48.6 [47.9–49.4]), while the RP of cigarettes remained stable. Conclusions: The relative RP of IQOSTM decreased over time, driven by an increase in the RP of IQOSTM, in agreement with epidemiological studies indicating a temporal reduction in the relative RP of smoke-free TNPs. Continued surveillance of the RP of novel TNPs is warranted to inform effective TNP risk communication and ensure that adults smokers who would otherwise continue to smoke understand the relative risks of novel TNPs.

Aims: There is limited knowledge on how ever and current heated tobacco product (HTP) users perceive the relative harm of various nicotine-containing products. The aim of this study was to explore relative harm perceptions of HTPs, e-cigarettes, and nicotine replacement therapy (NRT) relative to conventional cigarettes (CCs) among ever versus current HTP users, and exclusive (who use only a HTP) versus dual/poly-users (concurrent users of HTP and CCs and/or e-cigarettes). Methods: Data came from 1423 ever or current Hungarian adult HTP users who participated in a cross-sectional web-based survey in 2020. Unadjusted and adjusted logistic regression analyses were performed to explore the associations between relative harm perceptions, HTP use patterns, past tobacco use, HTP dependence, and socio-demographic variables. Results: 81.2% of the sample was current HTP users, of them 78.4% were exclusive HTP users. Compared to CCs, 86.2% of the sample perceived HTP to be less harmful, with current and exclusive HTP users endorsing more this belief, followed by NRT (79.8%), and e-cigarettes (45.2%). In general, neither socio-demographic variables nor past tobacco use, HTP use pattern, and HTP dependence were related to perceived harmfulness across the tested products. However, there was a specific pattern for each tested product with a set of explanatory variables. Conclusions: Ever/current HTP users presented misperceptions about the harms of HTPs, e-cigarettes, and NRT. They underestimated the potential health benefits of NRT and had distorted harm perceptions about HTPs and e-cigarettes. Public education about the relative harms of different nicotine and tobacco products is urgently needed.

Introduction Tobacco companies have introduced heated tobacco products (HTPs), such as IQOS, which may compete with e-cigarettes among smokers interested in switching to potentially reduced-risk products. Non-smokers may also start using IQOS if they believe this product is less harmful than other nicotine products. Smokers’ and non-smokers’ decisions may be driven by relative harm perceptions of emerging nicotine products. We aimed to examine relative harm perceptions between IQOS, e-cigarettes, and cigarettes, among nicotine product users and non-users. Material and Methods We conducted a web survey with Canadian respondents (aged ≥20 years; n=268) in September–October 2018. Perceptions about relative harm between IQOS (available for sale since 2017 and subject to the same comprehensive marketing restrictions as cigarettes in Canada), e-cigarettes, and cigarettes, were assessed among non-users (n=79), exclusive smokers (n=78), exclusive e-cigarette users (n=32), and dual users (n=79). Multiple logistic regression explored the association between relative harm perceptions and nicotine-use status, adjusting for sociodemographic variables. Results Over half of respondents perceived IQOS as equally or more harmful than e-cigarettes (53.7%), while almost a quarter either reported IQOS as less harmful than e-cigarettes or were uncertain (22.7% and 23.5%, respectively). Two-thirds of respondents (65.7%) perceived e-cigarettes as less harmful than cigarettes, yet only half (48.1%) perceived IQOS as less harmful than cigarettes. Both exclusive and dual e-cigarette users, but not exclusive smokers, had higher odds of perceiving IQOS as more harmful than e-cigarettes and less harmful than cigarettes compared to non-users. Conclusions Most nicotine users and non-users perceive differential health risk across IQOS, e-cigarettes, and cigarettes. Although e-cigarettes are generally viewed as less harmful than cigarettes, the perceived harm of IQOS was unclear.

The expression of some microRNAs (miRNA) is modulated in response to cigarette smoke (CS), which is a leading cause of major preventable diseases. However, whether miRNA expression is also modulated by the aerosol/extract from potentially reduced-risk products is not well studied. The present work is a meta-analysis of 12 in vitro studies in human organotypic epithelial cultures of the aerodigestive tract (buccal, gingival, bronchial, nasal, and small airway epithelia). These studies compared the effects of exposure to aerosols from electronic vapor (e-vapor) products and heated tobacco products, and to extracts from Swedish snus products (in the present work, will be referred to as reduced-risk products [RRPs]) on miRNA expression with the effects of exposure to CS or its total particulate matter fraction. This meta-analysis evaluated 12 datasets of a total of 736 detected miRNAs and 2775 exposed culture inserts. The t-distributed stochastic neighbor embedding method was used to find similarities across the diversity of miRNA responses characterized by tissue type, exposure type, and product concentration. The CS-induced changes in miRNA expression in gingival cultures were close to those in buccal cultures; similarly, the alterations in miRNA expression in small airway, bronchial, and nasal tissues resembled each other. A supervised clustering was performed to identify miRNAs exhibiting particular response patterns. The analysis identified a set of miRNAs whose expression was altered in specific tissues upon exposure to CS (e.g., miR-125b-5p, miR-132-3p, miR-99a-5p, and 146a-5p). Finally, we investigated the impact of RRPs on miRNA expression in relation to that of CS by calculating the response ratio r between the RRP- and CS-induced alterations at an individual miRNA level, showing reduced alterations in miRNA expression following RRP exposure relative to CS exposure (94 % relative reduction). No specific miRNA response pattern indicating exposure to aerosols from heated tobacco products and e-vapor products, or extracts from Swedish snus was identifiable.

Novel tobacco products that heat rather than burn tobacco (heated tobacco products or HTPs) have been shown to produce lower levels of harmful and potentially harmful constituents than conventional combusted cigarettes. The present study uses a quantitative risk assessment approach to compare non-cancer and cancer risk estimates for emissions generated by an HTP with smoke from a reference cigarette (3R4F). Fifty-four analytes were evaluated from the HTP aerosol and the 3R4F cigarette smoke. Emissions were generated using the ISO and the Health Canada Intense smoking regimes. The measured values were extrapolated to define a conservative exposure assumption for per day use and lifetime use based on an estimated maximum usage level of 400 puffs per day i.e., approximately 8 HTP tobacco capsules or 40 combustible cigarettes. Non-cancer and cancer risk estimates were calculated using these exposure assumptions for individual and per health outcome domains based on toxicological reference values derived by regulatory and/or public health agencies. The results of this assessment showed a reduction of non-cancer and cancer risk estimates by more than 90 % for the HTP versus the 3R4F cigarette, regardless of the smoking regime.

Background: Several smoke-free tobacco and/or nicotine-containing products (TNP) have emerged in recent years to support tobacco harm reduction strategies and reduce individual health risks and population harm relative to continued cigarette smoking. This paper describes the nationwide prevalence and patterns of TNP use in Japan following the commercialization of one such smoke-free TNP, the heated tobacco product IQOS® (Philip Morris International). Methods: We analyzed the first annual data (2016–2017) of two repeated cross-sectional surveys conducted in a representative sample of the Japanese general adult (≥20 years of age) population (N = 4,878) and a sample of adult IQOS users (N = 2,000). We assessed the prevalence of current TNP use according to type of product (cigarettes, IQOS, e-cigarettes, and other TNPs) in the general population and patterns of TNP use in the IQOS user sample. Results: The prevalence of current use across all TNP in the sampled general population was 18.5% (95% confidence interval 17.2–19.5%), with 17.5% (16.4–18.6%) for cigarette smoking and 1.8% (1.4–2.2%) for IQOS use. Regarding the distribution of patterns of use in the IQOS user survey, the majority (63.4% [61.2–65.6%]) were exclusive users of IQOS, followed by 20.6% (18.7–22.5%) of individuals who reported dual use of IQOS and cigarettes. Conclusions: In Japan, cigarette smoking remains the most prevalent way of consuming TNP; however, IQOS is being adopted by a growing number of adult Japanese smokers. These findings serve as baseline data for monitoring trends over time in the use and adoption of potential smoke-free TNP in Japan.

Background: Heated tobacco product (HTP) use has increased substantially between 2016 and 2017 in Japan. This study aims to clarify how HTP use (IQOS, Ploom, and glo) spread across the different combustible cigarette smoking statuses during 2015–16 and 2017–18 in Japan. Methods: We compared the two periods of (i) 2015 to 2016 (N = 5,366) and (ii) 2017 to 2018 (N = 3,422) from a longitudinal study randomly sampling members from the Japan “Society and New Tobacco” Internet Survey (JASTIS). Multivariable logistic regression models for current HTP use in the previous 30 days by combustible cigarette smoking status in the previous year were used adjusting for socio-demographic factors. Results: HTP use increased by 10 times in the 2017–18 cohort compared with the 2015–16 cohort according to the adjusted odds ratio (95% confidence interval) for current HTP use as 10.2 (7.03–14.8). According to smoking status, significantly higher adjusted ORs (95% CIs) of current HTP use for the after period were observed: 2.60 (1.37–4.94) for never smokers, 7.82 (3.64–16.8) for former smokers, 21.1 (5.73–77.9) for current smokers with intention to quit, and 17.0 (9.58–30.3) for current smokers without intention to quit. Conclusion: During 2015 to 2018 in Japan, HTP use dramatically increased in all subgroups except for never smokers.

Background: In Japan, heated tobacco products (HTPs) are promoted by the tobacco industry as reduced-risk tobacco products despite the lack of evidence for this claim. This study determined the distribution of HTP-harmfulness perception and identified the explanatory factors associated with the perception of HTP as less harmful than conventional cigarettes., Methods: A nationwide cross-sectional survey was conducted with Japanese people aged 20 years or older (INFORM Study 2020) using a self-administered questionnaire. We performed descriptive analysis and weighted logistic regression analysis to examine the relationship between explanatory factors (eg, individual characteristics, socioeconomic status, and trusted sources of cancer information) and the perception of HTPs as less harmful., Results: Among 3,420 participants, the proportions of those who perceived HTPs as less harmful were 40.3% and 18.3% for users and non-users of tobacco, respectively. For participants aged 20-39 years, the proportions were 49.9% and 30.4%, respectively. Among 1,160 tobacco non-users who were familiar with HTPs, male, aged under 39 years, and having lower education were associated with the perception of HTPs as less harmful. Trusted sources of cancer information were not associated with the perception of HTPs as less harmful., Conclusion: This study showed that, among tobacco non-users, being male, aged under 39 years, and having lower education were associated with a perception of HTPs as less harmful. Public health stakeholders should provide the latest evidence about HTP harmfulness in their daily practice and strengthen the regulations on HTP marketing directed at both tobacco- and tobacco non-users.

Halitosis is a health condition which counts cigarette smoking (CS) among its major risk factors. Cigarette smoke can cause an imbalance in the oral bacterial community, leading to several oral diseases and conditions, including intraoral halitosis. Although the best approach to decrease smoking-related health risks is quitting smoking, this is not feasible for many smokers. Switching to potentially reduced-risk products, like electronic vapor products (EVP) or heated tobacco products (HTP), may help improve the conditions associated with CS. To date, there have been few systematic studies on the effects of CS on halitosis and none have assessed the effects of EVP and HTP use. Self-assessment studies have shown large limitations owing to the lack of reliability in the participants' judgment. This has compelled the scientific community to develop a strategy for meaningful assessment of these new products in comparison with cigarettes. Here, we compiled a review of the existing literature on CS and halitosis and propose a 3-layer approach that combines the use of the most advanced breath analysis techniques and multi-omics analysis to define the interactions between oral bacterial species and their role in halitosis both in vitro and in vivo. Such an approach will allow us to compare the effects of different nicotine-delivery products on oral bacteria and quantify their impact on halitosis. Defining the impact of alternative nicotine-delivery products on intraoral halitosis and its associated bacteria will help the scientific community advance a step further toward understanding the safety of these products and their potentiall risks for consumers.

In the present study, we evaluated the acute response of mice exposed to IQOS aerosol, a brand-name heated tobacco product (HTP), in the lung tissue. First, the thiobarbituric acid-reactive substances (TBA-RS) value was measured as an index to assess oxidative stress, and a significant increase was observed after exposure, followed by a significant increase in the total lung GSH concentration. The stress responses induced by IQOS aerosols was then analyzed by focusing on the changes in Nrf2 and ATF4, which are transcription factors that induce the expression of genes involved in GSH biosynthesis or metabolism. Although Nrf2 activation was not observed, significant accumulation of ATF4 in the nuclear fraction was noted three hours after exposure to IQOS aerosols. Upon an examination of changes in factors in the GSH biosynthetic system, a significant increase in cystine concentration in the lung tissue was measured, and an increase in xCT expression level was observed in the cell membrane fraction three–six hours after IQOS exposure. Furthermore, characteristic changes in HO-1, a stress-response protein regulated by ATF4, was discovered six hours after IQOS exposure. Moreover, analysis of the upstream ATF4 regulatory system revealed that phosphorylation of eIF2α was enhanced in the lung cytoplasmic fraction three hours after exposure to IQOS aerosols. These findings suggest that ER stress might be induced as an early response to IQOS aerosol exposure, accompanied by the activation of the eIF2α-ATF4 axis. These intracellular changes have also been reported after exposure to combustible cigarette smoke. Thus, the acute response found in the lungs of mice in the present study demonstrate that the inhalation of aerosols from IQOS elicits a biological response similar to that of combustible cigarette smoke. In conclusion, our results provide evidence that the biological effects of HTPs, such as IQOS, cannot be ignored in the lungs.