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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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: New generation tobacco products (NGPs) hold promises as modified-risk alternatives to conventional cigarettes (CCs), given their comparable characteristics. This study investigated the nicotine pharmacokinetics (PK) of NGPs, encompassing closed pod systems, refillable e-cigarettes (ECs), and heated tobacco products (HTPs), in comparison to CCs through systematic review and meta-analysis., Methods: A comprehensive search was conducted on PubMed, Embase, and Web of Science for articles published between January 2013 and July 2023. Maximum nicotine concentration (Cmax), time to the peak concentration (Tmax), and total nicotine exposure (area under the concentration-time curve, AUC) were extracted to evaluate nicotine delivery PK. Random effects meta-analyses were performed to determine pooled standardized mean differences (SMD), facilitating a comparison of PK profiles between NGPs and CCs. Subgroup analyses exploring flavors and nicotine concentrations across NGPs, and CCs were also conducted., Results: The meta-analysis incorporated 30 articles with 2728 participants. Cmax and AUC were significantly lower for NGPs, while Tmax demonstrated statistical similarity compared to CCs. Among three NGPs, Cmax and AUC were lower for closed pod systems and refillable ECs. In HTPs, Cmax was statistically similar while AUC was lower compared to CCs. Tmax was statistically similar in closed pod systems and HTPs compared to that of CCs. No significant difference was observed in the comparisons of PK between each type of NGPs versus CCs., Conclusions: NGPs delivered less nicotine than CCs but reached Cmax over a similar timeframe, indicating that NGPs may serve as modified-risk alternatives with lower nicotine delivery to CCs for craving relief and smoking cessation., Implication: This study suggested that NGPs, such as the closed pod systems, the refillable ECs, and the HTPs, delivered either lower or comparable nicotine levels and achieved peak nicotine concentration at a similar rate as CCs. Our findings carry implications that NGPs can serve as modified-risk nicotine alternative to CCs in helping smokers to manage cravings and potentially quit smoking, thereby highlighting their value in the field of tobacco harm reduction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Oya-Watanabe Y. et al.)

Introduction: We evaluated the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on biomarkers and cigarette use patterns in Chinese adult smokers unwilling to quit smoking., Methods: In this pilot randomized controlled trial, 50 eligible participants were allocated to either Control group (smoking conventional cigarettes) or HTP device group (switching to using heated conventional cigarettes by the HTP device). Participants in the HTP device group went through a 2-day run-in period then used heated conventional cigarettes exclusively for 5 days, followed by flexible use for 14 days. Five biomarkers of exposure (BoEs) were measured at baseline and on Day 7. Thirteen biomarkers of biological effect (BoBEs) were measured at baseline and on Day 21. Safety, daily cigarette consumption, craving, withdrawal symptoms, and device acceptability, were assessed., Results: BoE levels decreased by 26.4 % to 71.4% from baseline in the HTP device group, while BoBE levels did not significantly change in either group. In the HTP group, 56% exclusively used heated conventional cigarettes during the flexible use period, experiencing reduced cravings and withdrawal symptoms, while dual users consumed more cigarettes. Mild to moderate device-related reactions were reported in 36% of users. Satisfaction, taste, and harm reduction belief scores averaged 7.4, 6.6, and 8.7 (out of 10), respectively., Conclusions: Switching to heated cigarettes with the HTP device may reduce short-term exposure to smoke toxicants. However, it can lead to increased tobacco use among dual users. Further investigation is needed to confirm these preliminary findings., Implications: This study is the first to evaluate the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on health-related biomarkers and cigarette use patterns among Chinese adult smokers. This novel HTP device can directly heat conventional cigarettes without the necessity for specifically designed tobacco products, avoiding potential additive risks of traditional HTPs. If the results of this study could be further verified by randomized controlled clinical trials with larger sample sizes, this novel HTP device could serve as a short-term harm reduction alternative for smokers unwilling to quit., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: The primary objective of this in vitro experiment was an assessment of proliferative capacity, metabolic activity, and potential cellular detriment of human periodontal ligament cells (hPDL) exposed to cigarette smoke (CS), electronic cigarette vapor (eCV), and heated tobacco product aerosol (HTP), or air (control)., Materials and Methods: Using a CAD/CAM-designed exposition chamber, hPDL were exposed to CS, eCV, HTP, or air (control) based on the Health Canada Intense Smoking Regime. Cell proliferation, metabolic activity, and cellular detriment were assessed at various time points., Results: Compared to the control, hPDL exposed to CS exhibited significantly decreased cell numbers at all time points. HTP exposure led to reduced cell numbers 48 h and 72 h post-exposure, while eCV-exposed cells showed no significant decrease. The metabolic activity of eCV-treated hPDL was slightly reduced at 7 h but recovered at 24 h and 48 h. In contrast, CS-treated cells exhibited significantly decreased metabolic activity at 24 h and 48 h, and HTP-exposed cells showed a significant decrease after 48 h. Flow cytometry indicated both apoptotic and necrotic cell death following CS exposure, with necrotic cell death being more pronounced., Conclusions: eCV and HTP demonstrated comparatively reduced detrimental effects on hPDL compared to CS., Clinical Relevance: The findings suggest that conventional cigarette smoke poses a substantial risk to periodontal health by significantly impairing cell proliferation and metabolic activity. However, alternatives such as eCV and HTP may offer a comparatively reduced risk., (© 2024. The Author(s).)

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 self-reported 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 <0.001). No significant associations were found between exclusive HTP use, dual use, and hearing loss at 1 kHz, apart from exclusive cigarette smoking., Conclusions: In this cross-sectional study, associations were found between exclusive cigarette smoking, exclusive HTP use, dual use, and hearing loss, particularly at 4 kHz. Further research is needed to confirm these findings., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Hu H. et al.)

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%), non-advertisement 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., Competing Interests: The authors have each completed and submitted an ICMJE form for Disclosure of Potential Conflicts of Interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. LCA declares that she receives royalties for the sale of Text2Quit. YB-Z has received fees for lectures from Pfizer, Novartis NCH, and GSK Consume Health (distributors of smoking cessation pharmacotherapy in Israel) in the past (2012–July 2019). CJB reports that she is supported by US National Institutes of Health funding, including the National Cancer Institute (R01CA215155, PI: Berg; R01CA278229, MPIs: Berg, Kegler; R01CA275066, MPIs: Yang, Berg; R21CA261884, MPIs: Berg, Arem), the Fogarty International Center (R01TW010664, MPIs: Berg, Kegler; D43TW012456, MPIs: Berg, Paichadze, Petrosyan), and the National Institute of Environmental Health Sciences/Fogarty., (© 2024 Abroms L. C. et al.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Traditional combustion cigarette (TCC) smoking is an established risk factor for several types of cancer and cardiovascular diseases. Circulating microRNAs (miRNAs) represent key molecules mediating pathogenetic mechanisms, and potential biomarkers for personalized risk assessment. TCC smoking globally changes the profile of circulating miRNAs. The use of heat-not-burn cigarettes (HNBCs) as alternative smoking devices is rising exponentially worldwide, and the circulating miRNA profile of chronic HNBC smokers is unknown. We aimed at defining the circulating miRNA profile of chronic exclusive HNBC smokers, and identifying potentially pathogenetic signatures., Methods: Serum samples were obtained from 60 healthy young subjects, stratified in chronic HNBC smokers, TCC smokers and nonsmokers (20 subjects each). Three pooled samples per group were used for small RNA sequencing, and the fourth subgroup constituted the validation set., Results: Differential expression analysis revealed 108 differentially expressed miRNAs; 72 exclusively in TCC, 10 exclusively in HNBC and 26 in both smoker groups. KEGG pathway analysis on target genes of the commonly modulated miRNAs returned cancer and cardiovascular disease associated pathways. Stringent abundance and fold-change criteria nailed down our functional bioinformatic analyses to a network where miR-25-3p and miR-221-3p are main hubs., Conclusion: Our results define for the first time the miRNA profile in the serum of exclusive chronic HNBC smokers and suggest a significant impact of HNBCs on circulating miRNAs., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

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., (© 2024. The Author(s).)

Heated tobacco products (HTPs) are marketed worldwide as less harmful alternatives to combustible cigarettes; however, their cytotoxic mechanisms in vascular smooth muscle cells are poorly understood. Ferroptosis is defined as iron-dependent cell death caused by the accumulation of lipid peroxidation products. In this study, the cytotoxic effects of nicotine- and tar-free cigarette smoke extracts (CSE) derived from three types of HTPs and the ferroptosis inducer, erastin, on vascular smooth muscle A7r5 cells were compared. Cigarette smoke from all HTPs was generated according to the following puffing regime: 55 mL, puff volume; 30 s, puff interval; 2 s, puff duration; bell-shaped, puff profile; and no blocking of the ventilation holes. Erastin and CSE decreased mitochondrial metabolic activity and increased lactate dehydrogenase leakage. The cytotoxic effects of erastin were almost completely inhibited by the radical-trapping antioxidant, UAMC-3203; iron chelator, deferoxamine mesylate (DFO); 12/15-lipoxygenase (12/15-LOX) inhibitor, baicalein; and selective 15-LOX inhibitor, ML351. In contrast, CSE-induced cell damage was partially attenuated by UAMC-3203, baicalein, and ML351 but not by DFO. These results suggest that erastin induces ferroptosis via 15-LOX-mediated iron-dependent lipid peroxidation, whereas CSE causes iron-independent cell damage via 15-LOX-mediated lipid peroxidation-dependent and -independent mechanisms., Competing Interests: Declaration of competing interest T.H. received a scholarship fund from Japan Tobacco Inc. (Japan)., (Copyright © 2023 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Heated tobacco product (HTP) considered to be a novel tobacco product which was reported safer than traditional cigarettes evidenced by lower potential harmful components released. Liver is an important detoxification organ of the body, the chemical components in aerosols are metabolized in the liver after absorbed, so it is necessary to explore the effect of HTP on the liver., Materials and Methods: The potential effect of HTP and cigarette smoke (CS) on SD rats was explored according to OECD 413 subchronic inhalation. The rats were randomly divided into Sham (air), different dosage of HTP groups (HTP&#95;10, 23 and 50 μg nicotine/L aerosol) and Cig&#95;23 (23 μg nicotine/L aerosol) group. After exposure, the clinical pathology, inflammation and oxidative stress were measured., Results: The clinical pathology results showed that both HTP&#95;50 and Cig&#95;23 led to abnormality of ALT for male rats. CS and HTP exposure reduced the expression of IL-1β, IL-6 and TNF-α and mitochondrial medicated oxidative stress. In addition, the ATP production was reduced in Cig&#95;23 group. Although inflammation and oxidative stress were displayed, no apoptosis were observed by TUNEL assay and these existed obvious pathological changes only in HTP&#95;50 group, while in CS group with equivalent nicotine, hepatocytes swelling were observed in liver., Conclusion: CS exposure induced liver damage through mitochondrial mediated oxidative stress and inflammation, which was also observed in high concentration of HTP exposure group. For the same equivalent nicotine, HTP may show lower toxic effect on liver than CS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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: non-smokers, 46.4 g/1000 kcal/day; cigarette smokers, 22.2 g/1000 kcal/day; HTP smokers, 31.4 g/1000 kcal/day; p<0.001; median dairy product intake: non-smokers, 76.3 g/day; cigarette smokers, 48.2 g/day; HTP smokers, 57.6 g/day; p<0.001) as assessed using a food frequency questionnaire (BDHQ)., Conclusions: Specific foods and beverages such as alcohol, fruits, and dairy products are related to smoking craving, and their intake differs according to smoking status., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Miyawaki T. et al.)

Heated tobacco (HT), a new tobacco product, is presented by the tobacco industry as an effective and safe alternative to cigarettes. Even if the quantities of harmful compounds emitted by HT are lower than those found in cigarette smoke, this reduction in exposure cannot be equated with a reduction in risk. No study has provided evidence that switching from cigarettes to HT reduces the risk of tobacco-related diseases. HT cannot be considered as a cigarette cessation product and was even designed as a product to initiate or return to tobacco consumption. To promote this product, the tobacco industry essentially exploits the concept of harm reduction and, as such, tries in its commercial communication to create confusion between HT and electronic cigarettes, despite these two products having nothing in common. This promotion is based, on the one hand, on the data of internal studies in contradiction with those of independent studies, and, on the other, illegally, on social networks and communication in contradiction with the statements of regulation authorities. HT is a new lure offered by the tobacco industry, intended to maintain its profits in a world that is moving away from “traditional” cigarettes. It should be strictly advised against for both non-smokers and smokers.

Introduction: Smoking increases the risk of lung cancer due to a number of components of smoke. The use of novel heated tobacco products (HTPs), alternative to conventional combustion cigarettes, has increased in recent years. However, the in vivo biological effects of HTPs are poorly understood. This study aimed to clarify the acute effects of injecting aerosol extract prepared from an HTP on regional cerebral blood flow (rCBF) in rat cortex by comparing them to the effects of injecting smoke extract prepared from conventional combustible cigarettes., Methods: In urethane anesthetized rats, rCBF was measured using laser speckle contrast imaging simultaneously with arterial pressure., Results: Both cigarette smoke extract and HTP aerosol extract, at a dose equivalent to 30 μg nicotine/kg, injected intravenously, increased cortical rCBF without changing arterial pressure. The magnitude and time course of the increased rCBF response to both extracts were similar throughout the cortical area, and the rCBF increases were all abolished by dihydro-β-erythroidine, an α4β2-preferring nicotinic acetylcholine receptor (nAChR) antagonist., Conclusion: In conclusion, our study demonstrated that the effect of injecting aerosol extract prepared from an HTP, an acute increase in cortical rCBF, is mediated via activation of α4β2-like neuronal nAChRs in the brain., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

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 was a randomized, controlled, open-label, confinement study to assess change in exposure to selected cigarette smoke constituents in healthy adult cigarette smokers who switched to using a novel heated tobacco product (direct heating tobacco system, platform 3, generation 3, version a [DT3.0a]). Sixty nonmenthol cigarette smokers were randomized into 1 of the 4 study groups in which subjects switched to a nonmenthol type of tobacco stick used with DT3.0a, switched to a nonmenthol tobacco stick used with an in-market heated tobacco product device (THS), continued to smoke nonmenthol cigarettes, or stopped smoking. Furthermore, 30 menthol cigarette smokers were randomized into 1 of the 2 study groups in which subjects switched to a menthol tobacco stick used with DT3.0a (mDT3.0a) or continued to smoke menthol cigarettes. Fifteen biomarkers of exposure to selected harmful and potentially harmful constituents (HPHCs) were measured during the 5-day exposure period, followed by assessment of nicotine pharmacokinetics with the assigned product. Results indicated that switching to DT3.0a, THS, and mDT3.0a showed significant exposure reductions in most of the selected HPHCs as compared to continuing smoking cigarettes, with reductions being similar in magnitude to reductions observed with smoking cessation. For DT3.0a and mDT3.0a, nicotine pharmacokinetic parameters were not remarkably different from those obtained for cigarettes and the THS except that a longer time to maximum concentration was obtained following use of the mDT3.0a. In conclusion, switching from smoking cigarettes to DT3.0a or THS use reduced exposure to most of the selected HPHCs, and no remarkable differences were observed for the measurements obtained from different flavors of DT3.0a stick., (© 2023 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

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.

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., Competing Interests: Scott Leatherdale is one of this journal’s associate scientific editors, but has recused himself from the review process for this article. The authors have no other conflicts of interest to declare.

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.

The epidermal growth factor receptor (EGFR) signaling pathway has essential roles in maintaining homeostasis of various tissues by regulating cell proliferation and differentiation. Deregulation of the EGFR signaling pathway is associated with various chronic diseases including chronic obstructive pulmonary disease. Cigarette smoke (CS) is known to activate EGFR, which is linked to chronic obstructive pulmonary disease. The biological sequence from CS exposure to EGFR activation is initiated by oxidative stress caused by intracellular reactive oxygen species (ROS) and the depletion of glutathione, which led to EGFR ligand secretion and EGFR activation. We hypothesized that reducing exposure to CS constituents contributes to preventing CS-inducible EGFR activation. Therefore, we examined the aerosol from heated tobacco products (HTPs) because the aerosol contains fewer chemical constituents at lower levels than CS. We exposed primary human bronchial epithelial cells from four donors to the extracts of CS from a 1R6F reference cigarette or HTP aerosol from three in-market products, including our DT3.0a. The biological sequence from ROS to EGFR activation was assessed. CS induced all the tested endpoints although inter-donor differences were observed, whereas HTPs elicited most of the biological events at higher concentrations; however, EGFR phosphorylation was not observed even at fivefold higher concentration than CS. Overall, our results indicate that HTPs are less effective than CS to elicit ROS-induced EGFR activation. The reduced-risk potential of HTPs on EGFR-related diseases should be investigated further. In addition, testing with multiple donors is warranted when considering the individual differences in responses of primary cells to stimuli., (© 2023 Japan Tobacco Inc. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

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.

Objectives: Conventional cigarette smoking increases inflammation and white blood cell (WBC) counts. However, there have been limited studies on the relationship between heated cigarette smoking and WBC counts. This study aimed to examine this relationship using nationally representative population-based health data., Study Design: This was a population-based cross-sectional study., Methods: The Korea National Health and Nutrition Examination Survey database was used to analyze this relationship. Data related to sex, age, body mass index (BMI), WBC count, and smoking history were obtained from the database. The smoking-related questionnaires included smoking status, smoking type (heated or conventional cigarettes), and smoking amount. The summary statistics of the WBC counts were calculated according to sex, smoking status, and smoking type. In addition, the exposure-response relationship between the smoking amount and WBC count was examined by smoking type, controlling for sex, age, and BMI., Results: In total, 9747 WBC measurements were used in the analyses. WBC count increased in conventional cigarette smokers, while there was no significant difference in WBC count between heated cigarette smokers and non-smokers. The WBC count showed a positive dose-response relationship with the smoking amount in both conventional and heated cigarette smokers., Conclusions: The results confirm that conventional cigarette smoking increases WBC counts. Furthermore, the results suggest that heated cigarette smoking does not lead to a significant increase in WBC counts, although it indicates a potential dose-response relationship with WBC count. Further research with larger sample sizes is needed to confirm whether these results reflect true associations., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective and Background: Heated tobacco products have recently become commercially available. These products, as well as combustible cigarettes, produce aerosols; the risk of various diseases associated with heated tobacco products may be the same or higher than that with combustible cigarettes. In this study, we examined the effect of Ploom TECH + extract on gingival epithelial cells., Methods: Tobacco leaves from Ploom TECH + tobacco capsules and water were mixed and heated; the supernatant subsequently collected was the heated tobacco product (HTP; control: HTP not added). Normal human gingival epithelial progenitors were cultured alternately with or without HTP for a total of 1 month. Subsequently, RNA, DNA, and proteins were isolated from these samples and comprehensively analyzed using RNA sequencing (RNA-seq), reduced representation bisulfite sequencing (RRBS), and western blotting, respectively., Results: RNA-seq revealed that 284 genes showed a twofold increase and 145 genes showed a twofold decrease in gene expression. A heat map showed genetic differences between the control and HTP groups. A principal component analysis plot showed a clear genetic distribution between the control and HTP. Gene Ontology (GO) analysis showed that genes related to seven GO terms, including cornification and keratinization, were induced by long-term HTP stimulation. By contrast, GO pathways with a significant decrease in component expression were not detected. RRBS revealed that CpG island methylation increased more than twofold in 158 genes and decreased to less than twofold in 171 genes. Methylation of these CpG islands was not correlated with changes in gene expression levels. HTP treatment increased S100A7 expression., Conclusion: Long-term HTP stimulation affected epithelial differentiation and keratinization of gingival epithelial cells. Thus, habitual use of Ploom TECH + may be a risk factor for tobacco-related oral mucosal diseases., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Heated tobacco products (HTPs) are expected to have the potential to reduce risks of smoking-associated cardiovascular disease (CVD). However, mechanism-based investigations of the effect of HTPs on atherosclerosis remain insufficient and further studies under human-relevant situations are desired for deeper understanding of the reduced risk potential of HTPs. In this study, we first developed an in vitro model of monocyte adhesion by considering macrophage-derived proinflammatory cytokine-mediated endothelial activation using an organ-on-a-chip (OoC), which provided great opportunities to mimic major aspects of human physiology. Then biological activities of aerosol from three different types of HTPs in terms of monocyte adhesion were compared with that of cigarette smoke (CS). Our model showed that the effective concentration ranges of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were close to the actual condition in CVD pathogenesis. The model also showed that monocyte adhesion was less induced by each HTP aerosol than CS, which may be caused by less proinflammatory cytokine secretion. In summary, our vasculature-on-a-chip model assessed the difference in biological effects between cigarettes and HTPs, and suggested a reduced risk potential of HTPs for atherosclerosis., Competing Interests: Declaration of Competing Interest This work was funded by Japan Tobacco Inc., and all authors are employees of this company., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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.

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., (©Yuko Noda, Ryuhei So, Misaki Sonoda, Takahiro Tabuchi, Akihiro Nomura. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 17.03.2023.)

Tobacco and nicotine derivatives uses are multiple in nature. These include conventional cigarettes (CCs), heated tobacco products (HTPs), and electronic cigarettes (ECs). This study aims to determine the practices, nicotine dependency profile, association with exhaled carbon monoxide (eCO) level, and pulmonary function (PF) among adult product users and non-smokers. This cross-sectional study involved smokers, nicotine users, and non-smokers from two public health facilities in Kuala Lumpur from December 2021 to April 2022. Data on socio-demography, smoking profile, nicotine dependency level, anthropometry, eCO monitor, and spirometer measurements were recorded. Out of 657 respondents, 52.1% were non-smokers, 48.3% were CC only smokers, poly-users (PUs) (27.3%), EC-only users (20.9%), and HTP-only users (3.5%). EC use was prevalent among the younger aged, tertiary educated, and females; HTP use was prevalent among those of an older age and CC users was common among lower educated males. The highest median eCO (in ppm) seen were as follows: in CC users only (13.00), PUs (7.00), EC users (2.00), HTP users (2.00), and the least was observed among non-smokers (1.00), which is significantly different across the groups ( p <0.001). Comparison of practice between the different product users showed significant differences in age of product initiation ( p <0.001, youngest in CC users in PUs), duration of product use ( p <0.001, longest in exclusive CC users), cost per month ( p <0.001, highest in exclusive HTP users) and attempt to quit product ( p <0.001, CC use in PUs had the highest attempt to quit), while there is no significant difference in Fagerström score across the groups. Among EC users, 68.2% successfully switched from smoking CCs to ECs. The findings suggest that EC and HTP users are exhaling less CO. The use of these products in a targeted approach may manage nicotine addiction. Switching practice was higher among current EC users (from using CCs), hence emphasizing the need of switching encouragement and total nicotine abstinence later on. Lower eCO levels in the PU group, (as compared to CC-only users) and high quit attempt rate among in CC use in PUs may indicate attempt of PUs in reducing CC use through alternative modalities such as ECs and HTPs.

Aims: We aimed to assess the cross-sectional association of heated tobacco product (HTP) use with prediabetes and diabetes., Methods: The present analysis included 8950 workers from 5 companies (Study I) and 31,341 workers from another large company (Study II), who participated in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were divided into five groups: never smokers, past smokers, exclusive HTP users, dual users of cigarettes and HTPs, and exclusive cigarette smokers. Diabetes and prediabetes were defined according to the fasting blood glucose and HbA1c levels and self-reported diabetes treatment, using the American Diabetes Association criteria. We analyzed the data of Study I and II separately, and then pooled these estimates using the fixed-effect models, with adjustment for a wide range of covariates., Results: In this study that included 40,291 participants (mean age, 46.6 years; men, 84.3%), about half of the current tobacco-related product users reported using HTPs. Exclusive HTP users had higher odds of prediabetes (pooled odds ratio 1.36; 95% CI 1.25-1.47) and diabetes (1.68; 95% CI 1.45-1.94) than never smokers. Similarly, dual users also had increased odds of prediabetes (pooled odds ratio, 1.26; 95% CI 1.13-1.39) and diabetes (1.93; 95% CI 1.63-2.29). The strength of these associations was comparable to that of cigarette smokers. We observed significantly higher HbA1c and fasting blood glucose levels among both exclusive HTP users and dual users compared to never smokers., Conclusion: HTP use was associated with an increased likelihood of prediabetes and diabetes. Prospective studies are warranted to confirm the cross-sectional association., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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; I 2 : 96%)and materials (pooled result from four studies-resin composite; MD: 11.90; 95% CI: 11.47, 12.34; I 2 : 100%). There was limited evidence that E-cigarettes 99%) and heated tobacco products (HTPs; pooled results from three studies--1.07, 6.54; I 2 : 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., (© 2022 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

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.

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.

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., Competing Interests: The authors declare no conflicts of interest.

Online analysis of chemical composition of cigarette smoke of a heated tobacco product (HTP) was performed by using a home-made vacuum ultraviolet (VUV) lamp-based photoionization time-of-flight (TOF) mass spectrometer. A capillary inlet and an aerodynamic lens were utilized to sample the gas- and particulate-phase of the HTP smoke, without dilution and pretreatment, which can be switched from each other within minutes. A thermal desorption unit was installed to vaporize the particulate-phase into gas and its vaporization temperature was determined, based on an equilibrium between the evaporation efficiency and the thermal decomposition of organic compounds. Then these species were softly ionized by VUV photons and their ions were measured by a reflectron TOF mass analyzer. Meanwhile, the puff-by-puff resolved size distributions of the HTP smoke were probed with a commercial scanning mobility particle sizers (SMPS). The mean diameters of particles firstly increase with the puff number, mainly located in the range of 200 - 300 nm, and then approached a steady state. This method was validated to measure the physical-chemical characteristics of the HTP cigarette smoke.•A capillary inlet and an aerodynamic lens were utilized to sample the gas- and particulate-phase of the HTP smoke.•Chemical composition of the HTP smoke was measured by using a compact VUV photoionization mass spectrometer.•The particle size distribution of the HTP smoke without dilution was measured online., (© 2022 The Author(s).)

Heated tobacco products (HTPs) are increasingly popular in Hong Kong (HK) even though they have not been formally launched and the sale of duty-not-paid tobacco sticks is illegal. We investigated how Facebook was used against regulations to sell HTPs in HK. We screened Facebook pages run by HTP businesses targeting HK users in June 2019 and included pages with over 300 "Likes" for inductive content analysis by coding their "About" descriptions and all posts including comments published since January 2017. HTPs included heating devices, accessories, and tobacco sticks. Various attributes were recorded including methods of customer inquiries (telephone, Instant Messaging [IM], address), business responses (comments or private messages, PM), and services provided (warranty/repair). Among 30 pages (50.9% of all 59 eligible pages with related information on HTPs), two-thirds provided phone numbers (66.7%), IM accounts (65.5%), and addresses (66.7%). Most pages sold heating devices (26, 86.7%) and accessories (22, 73.3%) with over 72% providing phone numbers, IM accounts, or addresses. Only 8 pages (26.7%) sold tobacco sticks with 75.0% providing telephone numbers but fewer provided IM accounts (62.5%) and addresses (50.0%). All pages responded using PMs and only 12.5% also used comments. Warranty/repair services were provided by 43.3% of the pages. We found Facebook pages were used as dedicated stores to promote and sell HTPs including heating devices, accessories, and even illicit tobacco sticks in HK, a non-official market., (© 2022 John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The actual use of heated tobacco products (HTPs) among smokers with rheumatoid arthritis (RA) is little known. The objective of this study was to clarify the prevalence and reasons for HTP use among smokers with RA. We administered a web survey to a research company panel in Japan between December 2020 and January 2021. After 170,000 panelists completed a primary questionnaire regarding smoking and disease status, 198 smokers with RA completed a secondary questionnaire regarding the reasons for HTP use and perceptions about the harmfulness of HTPs. The primary questionnaire revealed that smokers with RA were more likely to use HTPs than smokers without RA, and the adjusted odds ratio of RA for HTP use was one of the highest factors among other diseases (adjusted OR: 2.34, 95% CI: 1.92-2.85, p < 0.001). The secondary questionnaire revealed that 43.7% of HTP smokers with RA had considered using HTPs due to their RA, and 42.0% of them felt that starting HTPs relieved the symptoms of RA. These results indicated that smokers with RA tend to start using HTPs due to their RA, despite the lack of evidences that HTPs are safer alternatives.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Although the amount of chemicals in heated tobacco products (HTPs) aerosols is reduced compared to conventional combustible cigarette smoke, the association between HTPs and reduced health effects remains unclear. In this study, we hypothesized that exposure to IQOS, an HTP, would increase oxidative stress and affect the secretion of inflammatory cytokines. First, C57BL/6 mice exposed to IQOS aerosols were evaluated to determine the adverse effects of IQOS exposure. IQOS exposure significantly decreased the concentration of GSH in alveolar macrophages in a dose-dependent manner and increased the percentage of GSSG in lung tissues. These results indicate that IQOS exposure increases oxidative stress, and GSH is consumed to remove oxidative stress. In addition, foamy alveolar macrophages were observed in the bronchial alveolar lavage fluid after IQOS exposure. Although the concentration of inflammatory cytokines, IL-6, and GM-CSF, in the plasma increased significantly after IQOS exposure, there were no significant changes in other cytokines. These results indicate that short-term exposure to IQOS aerosols may increase oxidative stress and induce the secretion of inflammatory cytokines. Lastly, the longer-term effects of IQOS aerosols exposure should be evaluated in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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, IQOS TM , relative to cigarettes, among current IQOS TM 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 IQOS TM users from local registers of IQOS TM users. The health RPs of cigarettes and IQOS TM were assessed using the ABOUT™-Perceived Risk instrument, and their difference was described as the relative RP of IQOS TM to cigarettes (RP Cig: IQOS TM )., Results: After adjustment for covariates, the relative RP Cig: IQOS TM 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 IQOS TM 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 IQOS TM decreased over time, driven by an increase in the RP of IQOS TM , 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., Competing Interests: All authors except M.B., G.K. and B.Z. are employees of Philip Morris International. G.K. and B.Z. are employees of ARGUS, a consulting company contracted by Philip Morris International. M.B. is employed by Bajec Senseworks consulting, a consulting company contracted by Philip Morris International., (© 2022 The Authors.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

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.