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.

BACKGROUND: 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.
CONCLUSIONS: 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.

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

BACKGROUND: 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.
CONCLUSIONS: 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.

OBJECTIVE: 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).
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.
CONCLUSIONS: 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.

BACKGROUND: 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.

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.

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.

BACKGROUND: 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.

BACKGROUND: Heated tobacco products (HTPs), like IQOS, are marketed as innovative, stylish, harm-reduction products distinct from cigarettes and e-cigarettes. Research is needed to better understand how adults who are newly introduced to HTPs perceive them relative to cigarettes and e-cigarettes, and the impact of these perceptions on use outcomes.
METHODS: We analyzed 2021 cross-sectional survey data from 1,914 adults who never used HTPs from the United States and Israel, two countries where IQOS has unique histories and markets. Exploratory factor analysis examined perceptions of HTPs (vs. cigarettes and e-cigarettes) across 12 perception measures (e.g., innovative, trendy, harmful, addictive). Multivariable linear regression examined these factors in relation to self-reported likelihood to: 1) \"try HTPs in the next year\" (1=not-7=extremely); and 2) \"suggest IQOS to a friend who smokes cigarettes\" (1=not-5=very), controlling for demographics and past-month cigarette and e-cigarette use (10.1% dual use, 15.4% cigarette-only, 5.7% e-cigarette-only, 68.8% neither).
RESULTS: Four factors were identified: HTPs\' health and utility (\'health-utility\') and design and appeal (\'design-appeal\') vs. cigarettes and vs. e-cigarettes, separately. More favorable perceptions of HTP vs. e-cigarette design-appeal (B=0.30, 95%CI=0.18, 0.41) was associated with greater likelihood to try HTPs. More favorable perceptions of HTP vs. cigarette design-appeal (B=0.38, 95%CI=0.26, 0.51) and health-utility (B=0.25, 95%CI=0.13, 0.36), and HTP vs. e-cigarette design-appeal (B=0.32, 95%CI=0.20, 0.45) were associated with greater likelihood to suggest HTPs to smokers.
CONCLUSIONS: Monitoring perceptions of HTPs vs. cigarettes and e-cigarettes is critical given the role of such perceptions in HTP use and their population-level impact.
CONCLUSIONS: This study examined the relationship of perceptions of HTPs relative to cigarettes and e-cigarettes, with regard to adults\' self-reported likelihood to use HTP or to suggest HTPs to those who smoke cigarettes. Favorable perceptions of HTPs\' design and appeal versus e-cigarettes correlated with greater likelihood to try HTPs. Favorable perceptions of HTPs\' design and appeal, as well as health and utility, versus cigarettes and e-cigarettes correlated with greater likelihood to suggest HTPs to those who smoke. Findings underscore the need for ongoing surveillance of HTP marketing and consumer perceptions to inform regulatory efforts and estimate the population-level impact of HTPs and other tobacco products.