Cytotoxicity of the exhaled aerosol particles from the usage of conventional cigarette and heated tobacco product as determined by a novel "Cells-on-Particles" exposure model in vitro.

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.

Attitudes toward smoking cessation according to smoking status among dentists in the Aichi Dental Association in Japan.

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.

Assessing nicotine pharmacokinetics of new generation tobacco products and conventional cigarettes: a systematic review and meta-analysis.

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.

Impact of Heating Conventional Cigarettes with a Novel Device on Health-related Biomarkers and Cigarette Use Patterns among Chinese Adult Smokers Unwilling to Quit: A Pilot Randomized Controlled Trial.

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.

Urgent health concerns: Clinical issues associated with accidental ingestion of new metal-blade-containing sticks for heated tobacco products.

INTRODUCTION: Recently, a concerning pattern has emerged in clinical settings, drawing attention to the potential health risks associated with the accidental ingestion, mostly by children, of a new Heated Tobacco Product (HTP) stick, which contains a sharp metal blade inside. METHODS: Following a webinar of the Joint Action on Tobacco Control 2 project, where data on adverse health incidents related to novel tobacco and nicotine products from EU Member States were presented, the Milan Poison Control Center (PCC) conducted a case series study on the accidental ingestion of blade-containing HTP sticks in Italy, between July 2023 and February 2024. The data in the medical records were analyzed to identify the age distribution, clinical presentation symptoms, performed diagnostic procedures, and medical management. RESULTS: Overall, 40 cases of accidental ingestion of HTP sticks were identified and are described. A total of 33 (82.5%) children (infants and toddlers, mean age 12.3 ± 3.3 months) were hospitalized. Of these, 29 underwent abdominal X-rays, two children underwent esophagogastroduodenoscopy, and one child suffered from cut injuries to the tonsillar pillar and genian mucosa, requiring anesthesia for fibroscopy. The observed clinical cases associated with new HTP sticks containing a metal blade occurred over just eight months. This issue required the immediate implementation of corrective measures to mitigate health risks. The Ministry of Health issued an alert regarding the dangers related to the accidental ingestion of the stick and imposed more visible warnings on the package. CONCLUSIONS: It is of the utmost importance to raise awareness among both the general public and medical practitioners to prevent further cases of accidental ingestion of HTP sticks by infants and toddlers, and ensure a prompt and informed response in emergency situations.

Cytotoxic impact of nicotine products on periodontal ligament cells.

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.

Comparative toxicological assessment of cigarettes and new category products via an in vitro multiplex proteomics platform.

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-1ß levels, whilst ePen 3.0 affected IL-1ß 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.

Impact of exposures to Heated Tobacco Products in the media and through social connections on product perceptions and use.

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 (ß=0.35; 95% CI: 0.07-0.62) and non-advertising promotion via social media (ß=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 (ß=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.

Association of conventional cigarette smoking, heated tobacco product use, and dual use with hearing loss: A working population-based study.

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.

Three in four smokers want to quit tobacco (reference to reassessing the smoking target in Japan): findings from the JASTIS2021 study.

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.

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols.

With the use of in vitro new approach methodologies (NAMs) for the assessment of non-combustible next-generation nicotine delivery products, new extrapolation methods will also be required to interpret and contextualize the physiological relevance of these results. Quantitative in vitro to in vivo extrapolation (QIVIVE) can translate in vitro concentrations into in-life exposures with physiologically-based pharmacokinetic (PBPK) modelling and provide estimates of the likelihood of harmful effects from expected exposures. A major challenge for evaluating inhalation toxicology is an accurate assessment of the delivered dose to the surface of the cells and the internalized dose. To estimate this, we ran the multiple-path particle dosimetry (MPPD) model to characterize particle deposition in the respiratory tract and developed a PBPK model for nicotine that was validated with human clinical trial data for cigarettes. Finally, we estimated a Human Equivalent Concentration (HEC) and predicted plasma concentrations based on the minimum effective concentration (MEC) derived after acute exposure of BEAS-2B cells to cigarette smoke (1R6F), or heated tobacco product (HTP) aerosol at the air liquid interface (ALI). The MPPD-PBPK model predicted the in vivo data from clinical studies within a factor of two, indicating good agreement as noted by WHO International Programme on Chemical Safety (2010) guidance. We then used QIVIVE to derive the exposure concentration (HEC) that matched the estimated in vitro deposition point of departure (POD) (MEC cigarette = 0.38 puffs or 11.6 µg nicotine, HTP = 22.9 puffs or 125.6 µg nicotine) and subsequently derived the equivalent human plasma concentrations. Results indicate that for the 1R6F cigarette, inhaling 1/6th of a stick would be required to induce the same effects observed in vitro, in vivo. Whereas, for HTP it would be necessary to consume 3 sticks simultaneously to induce in vivo the effects observed in vitro. This data further demonstrates the reduced physiological potency potential of HTP aerosol compared to cigarette smoke. The QIVIVE approach demonstrates great promise in assisting human health risk assessments, however, further optimization and standardization are required for the substantiation of a meaningful contribution to tobacco harm reduction by alternative nicotine delivery products.

Tobacco usage in the home: a cross-sectional analysis of heated tobacco product (HTP) use and combustible tobacco smoking in Japan, 2023.

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.

Assessment of toxicological validity using tobacco emission condensates: A comparative analysis of emissions and condensates from 3R4F reference cigarettes and heated tobacco products.

The tobacco emission condensate, henceforth referred to as "tobacco condensate," plays a critical role in assessing the toxicity of tobacco products. This condensate, derived from tobacco emissions, provides an optimized liquid concentrate for storage and concentration control. Thus, the validation of its constituents is vital for toxicity assessments. This study used tobacco condensates from 3R4F cigarettes and three heated tobacco product (HTP) variants to quantify and contrast organic compounds (OCs) therein. The hazard index (HI) for tobacco emissions and condensates was determined to ascertain the assessment validity. The total particulate matter (TPM) for 3R4F registered at 17,667 µg cig-1, with its total OC (TOC) at 3777 µg cig-1. HTPs' TPM and TOC were 9342 ± 1918 µg cig-1 and 5258 ± 593 µg stick-1, respectively. 3R4F's heightened TPM likely arises from tar, while HTPs' OC concentrations are influenced by vegetable glycerin (2236-2688 µg stick-1) and propylene glycol (589-610 µg stick-1). During the condensation process, a substantial proportion of OCs in 3R4F smoke underwent significant concentration decreases, in contrast to HTPs, where fewer than half of the examined OCs exhibited notable concentration declines. The HI for tobacco emissions exhibited a marginally higher value compared to tobacco condensate, with variations ranging from 7.92% (HTPs) to 18.6% (3R4F), denoting a minimal differential. These observations emphasize the importance of accurate OC recovery techniques to maintain the validity and reliability of toxicity assessments based on tobacco condensates. This study not only deepens the comprehension of chemical behaviors in tobacco products but also establishes a novel benchmark for their toxicity evaluation, with profound implications for public health strategies and consumer protection.

Associations of Individual Characteristics and Socioeconomic Status With Heated Tobacco Product Harmfulness Perceptions in Japan: A Nationwide Cross-sectional Study (INFORM Study 2020).

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.

Is heated tobacco a harm reduction tool? / Le tabac chauffé est-il un outil de réduction des risques ?

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.

Le tabac chauffé (TC), nouveau produit du tabac, est présenté par l'industrie du tabac comme une alternative efficace et sûre à la cigarette. Même si les quantités de composés nocifs pour la santé émises par le TC sont inférieures à celles trouvées dans la fumée de cigarette, cette diminution d'exposition ne peut être assimilée à une réduction des risques. Aucune étude n'a apporté la preuve que le passage de la cigarette au TC réduisait le risque des maladies liées au tabac. Le TC ne peut pas être considéré comme un produit de sevrage de la cigarette et a même été conçu comme un produit pour entrer dans la consommation de tabac ou y revenir. Pour faire la promotion de ce produit, l'industrie du tabac exploite essentiellement le concept de réduction des risques et, à ce titre, essaie dans sa communication commerciale de créer la confusion entre le TC et la cigarette électronique alors que ces deux produits n'ont rien à voir. Cette promotion s'appuie, d'une part, sur les données d'études internes contradictoires avec celles d'études indépendantes, d'autre part, de façon illégale, sur les réseaux sociaux et une communication en contradiction avec les avis des autorités de régulation. Le TC est un nouveau leurre de l'industrie du tabac, destiné à assurer le maintien de ses profits dans un monde qui s'éloigne de la cigarette « traditionnelle ¼. Il doit être formellement déconseillé, tant aux non-fumeurs qu'aux fumeurs.

Foods and beverages associated with smoking craving in heated tobacco product and cigarette smokers: A cross-sectional study.

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.

Mechanism of cytotoxicity induced by the cigarette smoke extract (CSE) of heated tobacco products in vascular smooth muscle cells: A comparative study of the cytotoxic effects of CSE and the ferroptosis inducer, erastin.

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.

Non-targeted analytical comparison of a heated tobacco product aerosol against mainstream cigarette smoke: does heating tobacco produce an inherently different set of aerosol constituents?

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.

Liver toxicity in rats after subchronic exposure to HTP aerosol and cigarette smoke.

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_10, 23 and 50 µg nicotine/L aerosol) and Cig_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_50 and Cig_23 led to abnormality of ALT for male rats. CS and HTP exposure reduced the expression of IL-1ß, IL-6 and TNF-α and mitochondrial medicated oxidative stress. In addition, the ATP production was reduced in Cig_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_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.

Exploring the association between the proximity to and density around schools of retailers selling IQOS products and youth use of heated tobacco products: evidence from the 2020-2021 COMPASS study. / Exploration de l'association entre la proximité et la densité des détaillants de produits IQOS autour des écoles et l'utilisation de produits de tabac chauffé chez les adolescents : données de l'étude COMPASS 2020-2021.

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.