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Tobacco habit still represents the leading preventable cause of morbidity and mortality worldwide. Heat-not-burn cigarettes (HNBCs) are considered as an alternative to traditional combustion cigarettes (TCCs) due to the lack of combustion and the absence of combustion-related specific toxicants. The aim of this observational study was to assess the effect of HNBC on endothelial function, oxidative stress and platelet activation in chronic adult TCC smokers and HNBC users. The results showed that both HNBC and TCC display an adverse phenotype in terms of endothelial function, oxidative stress and platelet activation. Future randomised studies are strongly warranted to confirm these data., Competing Interests: Competing interests: GB-Z has consulted for Cardionovum, InnovHeart, Meditrial and Replycare. All remaining authors declare no conflict of interest or financial disclosures., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

We conducted an inhalation study, in accordance with Organisation for Economic Co-operation and Development Test Guideline 453, exposing A/J mice to tobacco heating system (THS) 2.2 aerosol or 3R4F reference cigarette smoke (CS) for up to 18 months to evaluate chronic toxicity and carcinogenicity. All exposed mice showed lower thymus and spleen weight, blood lymphocyte counts, and serum lipid concentrations than sham mice, most likely because of stress and/or nicotine effects. Unlike THS 2.2 aerosol-exposed mice, CS-exposed mice showed increased heart weight, changes in red blood cell profiles and serum liver function parameters. Similarly, increased pulmonary inflammation, altered lung function, and emphysematous changes were observed only in CS-exposed mice. Histopathological changes in other respiratory tract organs were significantly lower in the THS 2.2 aerosol-exposed groups than in the CS-exposed group. Chronic exposure to THS 2.2 aerosol also did not increase the incidence or multiplicity of bronchioloalveolar adenomas or carcinomas relative to sham, whereas CS exposure did. Male THS 2.2 aerosol-exposed mice had a lower survival rate than sham mice, related to an increased incidence of urogenital issues that appears to be related to congenital factors rather than test item exposure. The lower impact of THS 2.2 aerosol exposure on tumor development and chronic toxicity is consistent with the significantly reduced levels of harmful and potentially harmful constituents in THS 2.2 aerosol relative to CS. The totality of the evidence from this study further supports the risk reduction potential of THS 2.2 for lung diseases in comparison with cigarettes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology.)

The awareness and use of the recently introduced heated product in the global tobacco market is rapidly increasing. Few studies have investigated the association of this product's use with health-related factors. To examine the association of the heated tobacco product (HTP)'s use with perceived stress, physical activity, and internet use, we analyzed data from the Korea Youth Risk Behavior Survey using multinomial logistic regression models. The participants included 60,040 students from middle school and high school. There were significant associations between high perceived stress and cigarette use only, dual use of cigarette and e-cigarette, triple use of cigarette, e-cigarette, and HTP; a negative association between HTP's use and perceived stress; positive association between physical activity and tobacco use; and not using the internet significantly increased the odds of use of all types of tobacco products. A smoking prevention program, tailored to meet the needs of different types of tobacco product users, is recommended. A program aimed at not only increasing awareness of perceived risk but also decreasing perceived benefits of risky behaviors, should also be considered. Further research using a longitudinal design to test the causal relationship of tobacco product use with perceived stress, physical activity, and internet use is warranted.

Providing data on usage patterns is key to assessing the reduced-risk potential of novel tobacco and nicotine products as compared to conventional cigarettes at a population level. A pilot cross-sectional survey was conducted in 2018 across 3 areas of Japan (Tokyo, Osaka, and Sendai) to assess tobacco and nicotine product use after the introduction of Heated Tobacco Products (HTPs). Following successful completion of the pilot study, two nationwide cross-sectional surveys were conducted using the general population in Japan to assess use patterns after the introduction of HTPs. The first (Wave 1) was conducted in 2019, and the second in 2020. In Wave 2, the concern of this publication, additional population-level data was obtained on use patterns and behaviour relating to tobacco and nicotine products in Japan. Eligible participants were Japanese residents, aged 20 years or older who consented to complete the survey. A 3-stage probability sampling method was applied that was geographically stratified by street blocks proportionate to population density. Respondents self-reported patterns of product use and reasons for HTP use. Complete responses were available from 5307 individuals, of whom 889 (16.7%) were current users, 1012 (19.1%) were former users, and 3407 (64.2%) were never users of tobacco products (weighted respondent totals). Of current tobacco users, 63.5% smoked cigarettes exclusively and 17.9% used HTPs exclusively. HTP dual use in combination with conventional cigarettes was 12.7%. The remaining 5.9% of users were categorised as poly users (i.e., use of 2 or more tobacco products). The most common reasons reported for HTP use were perceived reduction in harm to others and self - compared to cigarettes. These findings are consistent across pilot and Wave 1 conducted in Japan as part of this survey programme. Cigarettes were still the most frequent tobacco product used (13.4% in the pilot to 15.5% in Wave 1) within the general population, the usage prevalence for HTPs (5.3% to 5.4%) being considerable in comparison to other tobacco or nicotine-containing products like cigars, cigarillos, pipe, kiseru, and oral tobacco, where usage prevalence was close to zero. As with the previous Waves, no gateway effect (use of non-traditional combustible tobacco use – such as e-cigarettes and in this case HTP use – leading to subsequent tobacco smoking) was observed in this study. The findings presented here are indicative of the results from the initial study in 2018 and the nationwide Wave 1 study in 2019 but with a larger population, where the market is now more established with new-generation products. In conclusion, the prevalence of cigarette use in Japan is decreasing and HTPs seem to be increasingly used as an alternative to cigarette smoking. [ABSTRACT FROM AUTHOR]

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

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

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

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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

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. [ABSTRACT FROM AUTHOR]

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

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. This was a population-based cross-sectional study. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. We examined a biological sequence leading to EGFR activation by exposing bronchial epithelial cells from four different donors to cigarette smoke (CS) or aerosol from three in‐market heated tobacco products (HTPs). CS and HTP aerosols elicited oxidative stress and EGF ligand secretion, whereas higher concentrations of HTPs than CS were required for the same effects. EGFR activation was only observed after CS exposure. This is the first step in investigating the reduced‐risk potential of HTPs in EGFR signaling‐mediated adverse outcomes. [ABSTRACT FROM AUTHOR]

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

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

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

Transient receptor potential ankyrin-1 (TRPA1) is expressed in the trigeminal nerves in the nasal cavity. It detects irritant chemicals such as formalin and acrolein, induces respiratory depression to protect against further inhalation, and elicits avoidance behavior. Although tobacco smoke contains formalin, acrolein, and other irritant chemicals, the possible contribution of TRPA1 to protection against tobacco smoke has yet to be fully understood. In this study, we compared respiratory and behavioral responses to an aerosol of tobacco smoke between TRPA1 conditional knockout mice and the controls. We also compared the effect of aerosols from the smoke of traditional standard tobacco and a recently developed heated tobacco product. As expected, respiratory depression by tobacco aerosol was observed only in the TRPA1 intact mice and was associated with increased trigeminal activation. Meanwhile, mice did not avoid or even prefer tobacco aerosol in a TRPA1-independent manner, contrary to our expectations. Repeated exposure to tobacco aerosol resulted in lung inflammation in a TRPA1-independent manner. Aerosols from a heated tobacco product showed no significant effect as in traditional tobacco smoke. These results indicate that TRPA1 contributes to acute protection from tobacco smoke by inducing respiratory depression but not to the safety of the lungs in repeated exposure. Tobacco aerosol contains attractive substances for mice. Heated tobacco product aerosol contains less TRPA1 activating substances and less inflammation evoking than traditional tobacco smoke. [Display omitted] • TRPA1 conditional knockout mice lost the ability to detect formalin after 3 weeks. • TRPA1 protects from tobacco aerosol by inducing respiratory depression. • Tobacco aerosol contains TRPA1-independent attractive substances for mice. • TRPA1 does not contribute to the safety of the lungs in repeated tobacco exposure. • Heated tobacco product evokes less inflammation than traditional tobacco smoke. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

To identify biomarkers of exposure present in Heated Tobacco Products (HTPs) users' urine which are associated with bladder cancer and to compare quantitative biomarker levels to those seen in combustible cigarette users. A systematic literature review was conducted in December 2020 with no date limits. Relevant studies that reported quantitative urinary biomarker of exposure in HTP users were included. Biomarkers and their parent compounds were classified by carcinogenicity according to the International Agency for Research on Cancer Monographs and were cross-referenced with the Collaborative on Health and the Environment Toxicant and Disease Database to determine associations with bladder cancer. Our literature search identified 561 articles and 30 clinical trial reports. 11 studies met inclusion criteria. These studies identified 29 biomarkers of exposure present in HTP users' urine, which reflect exposure to 21 unique parent compounds. Of these parent compounds, 14 are carcinogens and 10 have a known link to bladder cancer. HTP users' biomarkers of exposure were present at lower levels than combustible cigarette users but higher than never-smokers. Biomarkers of exposure to bladder carcinogens are present in the urine of HTP users. While levels of these biomarkers appear to be lower than combustible cigarette users, chronic urothelial exposure to bladder carcinogens is concerning and degree of bladder cancer risk remains unknown. Further long-term study is needed to elucidate the bladder cancer risk of HTP use. [ABSTRACT FROM AUTHOR]

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

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

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

Aging and smoking are major risk factors for cardiovascular diseases (CVD). Our in vitro study compared, in the context of aging, the effects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribute to vascular pathomechanisms leading to CVD. Young and old human aortic smooth muscle cells (HAoSMC) were exposed to various concentrations of aqueous extracts (AE) from 3R4F CS [0.014–0.22 puffs/mL] or THS aerosol [0.11–1.76 puffs/mL] for 24 h. Key markers were measured by high-content imaging, transcriptomics profiling and multianalyte profiling. In our study, in vitro aging increased senescence, DNA damage, and inflammation and decreased proliferation in the HAoSMCs. At higher concentrations of 3R4F AE, young HAoSMCs behaved similarly to aged cells, while old HAoSMCs showed additional DNA damage and apoptosis effects. At 3R4F AE concentrations with the maximum effect, the THS AE showed no significant effect in young or old HAoSMCs. It required an approximately ten-fold higher concentration of THS AE to induce effects similar to those observed with 3R4F. These effects were independent of nicotine, which did not show a significant effect on HAoSMCs at any tested concentration. Our results show that 3R4F AE accelerates aging in young HAoSMCs and exacerbates the aging effect in old HAoSMCs in vitro, consistent with CS-related contributions to the risk of CVD. Relative to 3R4F AE, the THS AE showed a significantly reduced impact on HAoSMCs, suggesting its lower risk for vascular SMC-associated pathomechanisms leading to CVD. [ABSTRACT FROM AUTHOR]

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

Health risk associated with the use of combustible cigarettes is well characterized and numerous epidemiological studies have been published for many years. Since more than a decade, innovative non-combusted tobacco products have emerged like heated tobacco products (HTP) or electronic cigarettes (EC). Long-term effects of these new products on health remain, however, unknown and there is a need to characterize associated potential health risks. The time dedicated to epidemiological data generation (at least 20 to 40 years for cancer endpoint), though, is not compatible with innovative development. Surrogates need, therefore, to be developed. In this work, non-cancer and cancer risks were estimated in a range of HTP and commercial combustible cigarettes based upon their harmful and potentially harmful constituent yields in aerosols and smoke, respectively. It appears that mean lifetime cancer risk values were decreased by more than one order of magnitude when comparing HTPs and commercial cigarettes, and significantly higher margin of exposure for non-cancer risk was observed for HTPs when compared to commercial cigarettes. The same approach was applied to two commercial ECs. Similar results were also found for this category of products. Despite uncertainties related to the factors used for the calculations and methodological limitations, this approach is valuable to estimate health risks associated to the use of innovative products. Moreover, it acts as predictive tool in absence of long-term epidemiological data. Furthermore, both cancer and non-cancer risks estimated for HTPs and ECs highlight the potential of reduced risk for non-combusted products when compared to cigarette smoking. [ABSTRACT FROM AUTHOR]

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. • In vitro model of monocyte adhesion was developed using OoC. • Inflammatory cytokine-mediated endothelial activation by macrophages was reflected. • Effective doses of TNF-α and IL-1β were close to CVD pathogenesis. • Monocyte adhesion was less induced by HTPs than by cigarette. [ABSTRACT FROM AUTHOR]

We present a vacuum ultraviolet (VUV) lamp-based photoionization time-of-flight (TOF) mass spectrometer coupled with a capillary inlet and an aerodynamic lens to online analyze the chemical compositions of the gas- and particulate-phase of cigarette smoke of a heated tobacco product (HTP). Both phase compositions of the fresh cigarette smoke, without dilution and pretreatment, are softly photoionized and their mass spectra are measured with a time resolution of 1 s. It is shown that the gas-phase compositions with low mass are volatile organic compounds (VOCs), and the particulate-phase compositions are also clearly identified and cover the full mass range of the mass spectrometer. The time- or puff-by-puff resolved dynamic data are obtained for each species and provide abundant information to unravel the chemistry of the HTP smoke. In addition, the present results show that besides thermal vaporization, a couple of chemical reactions including pyrolysis and degradation have also occurred in the HTP smoking process, although its operation temperature is less than 350 °C. Even if not done here, this study paves the way to analyze the gas- and particulate-phase chemical compositions of a complex system in real time, like the cigarette smoke presented here, by using advanced soft ionization mass spectrometry. [Display omitted] • Particle-phase compositions of the HTP smoke measured online for the first time. • Gas-/particle-phase compositions of the HTP smoke analyzed with a resolution of 1 s. • Glycerol and nicotine mainly populated into the particle phase in the HTP smoking. • Besides vaporization, pyrolysis and degradation also occur in the HTP smoking. [ABSTRACT FROM AUTHOR]