Heated Tobacco Products Research Articles

Vascular Stress Markers Following Inhalation of Heated Tobacco Products: A Study on Extracellular Vesicles.

The advent of heated tobacco products (HTPs) has introduced new variables in the study of nicotine delivery systems and their health implications. Amidst concerns over cardiovascular effects, this study aims to elucidate the acute impact of HTP inhalation on extracellular vesicles (EV) levels in young, healthy individuals. In this controlled, acute exposure study, 23 young, healthy volunteers were subjected to HTP inhalation. EV levels of endothelial and platelet origin were quantified through flow cytometry before and after exposure. Data analysis was performed using multiple measures ANOVA to assess changes in EV concentrations. Our findings reveal a significant increase in EVs of endothelial and platelet origin following short-term HTP inhalation with nicotine. Notably, no significant change was observed in leukocyte- and neutrophil-derived EVs. This increase in EVs suggests acute vascular stress, with peak levels observed 4h post-exposure. The rise in endothelial and platelet-derived EVs aligns with documented responses to acute vascular injury, paralleling the effects seen with traditional cigarette and e-cigarette use. Despite HTPs being marketed as safer alternatives, our results indicate that nicotine-containing HTPs may still pose significant vascular risks. These findings contribute to the growing body of evidence cautioning against the perceived safety of HTPs and reinforce the importance of regulatory oversight and public health initiatives targeting nicotine delivery technologies. Trial Registrations: ClinicalTrials.gov ID: NCT04824495, registered 2021-01-07.

Transformation of the tobacco product market in Japan, 2011–2023

ObjectiveThis study updates a previous paper that examined trends in the sale of cigarettes and heated tobacco products (HTPs) in Japan between 2011 and part way through 2019. The current study includes complete unit sales data through 2023.MethodsData on cigarette and HTP sales were obtained from public sources available from the websites and stockholder reports for the Tobacco Institute of Japan, Philip Morris International and Japan Tobacco. We used joinpoint regression using the parametric method to test for trends in both per capita and total sales for the three outcome variables assessed between 2011 and 2023: (1) cigarette sales, (2) HTP sales and (3) combined cigarette and HTP sales. Joinpoint regression identifies changes in trends and estimates the annual per cent change (APC) for each trend segment.ResultsBetween 2011 and 2023, per capita and total cigarette sales declined by 52.6% and 52.7%, respectively. From 2011 to 2015, per capita cigarette sales in Japan decreased −1.5% APC; from 2015 to 2018, the decline accelerated to −10.5% APC and continued to fall −7.3% APC between 2018 and 2023. Between 2016 and 2018, per capita HTP sales increased by 149.0% APC, and since 2018, they have increased by 8.1% APC.ConclusionWhile many factors may account for the decreased sale of cigarettes in Japan over the past 12 years, the increased sale of HTPs appears to be a factor.

Level of tobacco dependence and beliefs towards heated tobacco products

Abstract Nicotine dependence affects not only behaviors related directly to smoking, quit attempts or looking for alternative products but also beliefs about smoking. We sought to assess whether the level of tobacco dependence is associated with beliefs and feelings towards heated tobacco products (HTP) and to assess the relationship between tobacco dependence and the motivators to quit HTP use. Random population sample of Polish citizens aged 18+ years, former smokers, current HTP users was recruited. Tobacco dependence was assessed using 5 question; participants were classified into two groups of tobacco dependence (low or high) using a two-stage cluster analysis. An extensive questionnaire on beliefs on HTP use was administered. The χ2 test and logistic regression were used. There were 2,500 participants (62.6% women) of median age=36 years (Q1=29, Q3=45). The median number of years of smoking was 10 (Q1=5, Q3=15) and median number of years of HTP use was 2 (Q1=1, Q3=3). High tobacco dependence was found in 958 (38,3%) participants. Compared to low dependence, high tobacco dependence was related with feeling of strong need for HTP use (69.7% vs. 47.6%, p < 0,001). High level of tobacco dependence was positively related to perceived social pressure against smoking (72.9% vs. 44.9%, p < 0,001), but it did not differentiate perceived social pressure against HTP use. Compared to low tobacco dependence, participants with high tobacco dependence more often indicated fear of illness OR = 1,73 95%CI=1,46-2,07, own resolution OR = 1,32 95%CI =1,12-1,55 and price OR = 1,34 95%CI=1,13-1,59 as possible motivators to quit HTP use. Level of tobacco dependence in former smokers shaped beliefs and feelings towards HTP use. High tobacco dependence contributed to strong need to use HTP and also increased perception of social pressure against smoking, but not against using HTP. It also increased the importance of fear of illness, price and one’s own resolution as motivators to quit HTP use. Key messages • High level of tobacco dependence in former smokers results in stronger perceived social pressure against smoking but not against HTP use. • High tobacco dependence in former smokers is related with stronger need to use HTP.

Tobacco and nicotine products use among adolescents in Serbia – Latent class analysis

Abstract Background In parallel with a decline in cigarette smoking in the previous decade, other tobacco and nicotine products (TNPs), that are often used concurrently, have gained popularity among adolescents. The purpose of this study was to identify patterns of tobacco and nicotine product use among Serbian adolescents. Methods Data for this study were obtained from Health Behavior in School-aged Children (HBSC), a WHO collaborative cross-national study of adolescent health and well-being, that was conducted in Serbia in 2022 on a sample of 3713 students 11,13 and 15 years old. Descriptive statistics was used as well as latent class analysis to classify students based on their past-month use of cigarettes, e-cigarettes, heated tobacco products, waterpipes, and oral tobacco/nicotine products. Results Among students 11,13 and 15 years old, 10.2% smoke cigarettes, 13% use e-cigarettes, 11.1% waterpipes, 3.7% oral tobacco/nicotine products, and 4.5% heated tobacco products with differences by age and sex. We found high percentages of dual use of TNPs among cigarette smokers. Among students who smoke cigarettes, 61.6% also use e-cigarettes, 36.2% smoke waterpipes, 30.2% heated tobacco products, and 24.1% oral tobacco/nicotine products. Latent class analysis identified three classes as optimal solution: (1) dual e-cigarette and cigarette users (6.9%); (2) minimal/non-users (83.2%) and (3) poly tobacco and nicotine products users (9.9%). Statistically significant differences between classes were found in age and sex. Conclusions Dual and poly-tobacco and nicotine use is common among Serbian adolescents and presents a challenge for monitoring and public health response. Findings contribute to a better understanding of patterns and heterogeneity of TNPs use among adolescents and might have implications for prevention and cessation interventions for youth. Key messages • Among students 11,13 and 15 years old, tobacco and nicotine products, other than cigarettes is gaining popularity and with the e-cigarettes being the most popular product. • Dual and poly tobacco and nicotine products use is new challenged that should be taken into account in tobacco and nicotine monitoring, cessation and prevention.

Nicotine use in Polish adolescents and sociodemographic factors correlations - PolNicoYouth study

Abstract Background & aim Almost 36% of Polish smokers started their addiction before the age of 17. Polish youth exhibit a higher prevalence of e-cigarette use (29.5%) than traditional cigarettes (26.2%). This study aimed to outline the prevalence of tobacco and nicotine product use based on usage frequency, poly-product use patterns among ever/former/naive users. Methods In the 2020 cross-sectional study, secondary school students from 200 schools, were selected nationwide using a stratified and random approach, making the sample representative of the entire Polish population. Data were collected through Computer-Assisted Web Interviews, using a questionnaire based on the Global Youth Tobacco Survey. Bayesian linear regression was used to assess correlations. Results The study consisted of 16,712 pupils aged 15-18. Almost 30% of participants admitted to current e-cigarette usage. Questions on parental smoking habits showed that 45.95% of parents smoke traditional cigarettes, 13.89% use e-cigarettes, and 13.80% use heated tobacco products (HTP). There was a very strong positive correlation between the female gender and the initiation of smoking with regular cigarettes (log[BF]=10.76). A very strong positive correlation between those studying in vocational schools and with initiation with regular cigarettes during initiation (log[BF]=18.13), while high school students had a greater association with e-cigarettes (log[BF]=11.08). There was also a very strong positive correlation between adolescents initiating smoking with regular cigarettes when their parents are also regular cigarette smokers (log[BF]=8.11) - no corresponding correlations were observed for e-cigarettes and HTP. There is a moderate positive correlation indicating a relationship between younger age (15 vs 18) and initiation by e-cigarette (log[BF]=1.8). Key messages • The type of nicotine product used by adolescents for nicotine initiation correlates differently with various socio-demographic factors and the type of nicotine product used by parents. • Taking these relationships into consideration enables the development of tailored nicotine prevention.

Future of nicotine pouches – users’ perspective

Abstract Background Nicotine pouches (NPs) are gaining popularity. They are a rapidly developing category with little research or regulatory oversight. Studies have shown that the descriptor ‘tobacco-free’ may impact risk perceptions and the appeal of nicotine pouches among young adults and thus shape their position on the market. The aim of the study was to broaden the knowledge on NP users’ perspective about the future of this products. Methods Qualitative approach was utilized. In December 2022 there were seventeen structured In-depth Interviews (IDIs) conducted. The sample included of adults aged 18-22, both male and female. The respondents were asked how they see NPs in the context of aim group and competition with other nicotine products. Results We found that from NPs users’ perspective, these products are aimed at those who want give up smoking, do not want to play with electronic devices (such us e-cigarettes of heated tobacco products) or just seek for discretion (such as office workers who do want to go outside for a smoke or vape). Special aim group are children who want to hide their nicotine product use. Respondents believe that they will not force traditional cigarettes out of the market but will be a popular alternative for young people. Some suggest they need popularization to help exclude products that produce smelly smoke or vape. Conclusions Nicotine pouches as smokeless products will probably fill the market space with product aimed at young people who seek discretion of their nicotine addiction as well as those who do not want to inhale smoke. Key messages • Nicotine pouches users see value of these products. • Nicotine pouches future seems to be bright unless regulations disrupt their market development.

Exposure to e-cigarette and heated tobacco product advertisements via digital, traditional media, and points-of-sale: An examination of associations with use intentions and perceived risk among adults in Armenia and Georgia.

E-cigarette and heated tobacco product (HTP) marketing often leverages digital media and points-of-sale (POS) and advertises risk reduction, including in Armenia and Georgia where male cigarette use rates are high. Using 2022 survey data from Armenian and Georgian adults (n=1468, mean age=42.92 years, 51.4% female; and past-month use of e-cigarettes 3.2%, HTPs 2.7%, and cigarettes 31.6%), multivariable linear regression examined 4 outcomes - e-cigarette and HTP use intentions and perceived risk (1=not at all, to 7=extremely) - in relation to past-month e-cigarette or HTP advertisement exposure via digital media, traditional media, and POS, controlling for covariates (country, age, gender, education level, relationship status, children, past-month cigarette and e-cigarette/HTP use). E-cigarette and HTP use intentions were low (mean score=1.47, SD=1.39 each), while perceived risk was high (mean score=5.83, SD=1.6, and mean score=5.87, SD=1.56, respectively). Past-month exposure to e-cigarette and HTP advertisements, respectively, were 12.9% and 11.2% via digital media, 6.1% and 4.8% traditional media, and 22.5% and 21.1% POS. For e-cigarettes, ad exposure via digital media was associated with greater use intentions (β=0.24; 95% CI: 0.03-0.44), ad exposure via traditional media (β= -0.32; 95% CI: -0.55 - -0.09) and POS (β= -0.30; 95% CI: -0.60 - -0.004) was associated with lower risk perceptions. For HTPs, ad exposure via digital media (β=0.35; 95% CI: 0.14-0.56) and POS (β=0.21; 95% CI: 0.04-3.63) was associated with greater use intentions, and ad exposure at POS was associated with lower risk perceptions (β= -0.23; 95% CI: -0.42 - -0.03). Tobacco control efforts should monitor and regulate e-cigarette and HTP marketing, particularly via digital media which may effectively promote use, and via POS which may target and influence risk perceptions.

Association of food insecurity with the use of tobacco products and urine cotinine-measured smoking intensity: evidence from a population-based study in South Korea, 2019–2021

IntroductionThis study explored the association between food insecurity and tobacco product use and urine cotinine-measured smoking intensity.MethodsThis cross-sectional study included 13 705 adults representative of the Korean population. The 18-item...

Can switching from cigarettes to heated tobacco products reduce consequences of pulmonary infection?

While tobacco industry data suggests that switching from combustible cigarettes to heated tobacco products (HTPs), like IQOS, may reduce the users' exposure to respiratory toxicants, it is not known if using HTPs impacts the outcomes of acute respiratory infections. Does switching from cigarettes to HTPs improve responses to pulmonary infection. We conducted experiments in which 3 groups of mice were pre-exposed to cigarette smoke for 8 weeks, followed by 8-week exposure to (1) HTPs (tobacco product switching), (2) air (smoking cessation), or (3) continued exposure to cigarette smoke. Pulmonary bacterial clearance and surrogate markers of lung damage were assessed as study outcomes. Significantly compromised clearance of bacteria from the lungs post-acute challenge occurred in both the switching group and in mice continuously exposed to cigarette smoke. Bacterial clearance, inflammatory T-cell infiltration into the lungs, and albumin leak improved at 12h post-acute challenge in the switching group compared to mice continuously exposed to cigarette smoke. Bacterial clearance, total lung immune-cell infiltration, inflammatory T-cell infiltration into the lungs, the content of total proteins in the BAL, and albumin leak measured post-acute challenge were compromised in the switching group compared to mice in the cessation group. Switching from cigarettes to HTPs did not improve lung myeloperoxidase and neutrophil elastase levels (markers for lung inflammation and damage), which, however, were significantly reduced in the cessation group. This study reveals only a modest improvement in respiratory infection outcomes after switching exposure from cigarettes to HTPs and significantly compromised outcomes compared to a complete cessation of exposure to all tobacco products.

Impacts of revised smoke-free regulations under the 2020 Japan Health Promotion Act on cigarette smoking and heated tobacco product use in indoor public places and homes: findings from 2018 to 2021 International Tobacco Control (ITC) Japan Surveys

BackgroundIn April 2020, Japan’s revised Health Promotion Act (HPA) banned cigarette smoking and heated tobacco products (HTP) use in indoor public places but exempted small establishments and permitted smoking-designated/HTP-designated rooms....

Tobacco Product Use Among Middle and High School Students - National Youth Tobacco Survey, United States, 2024.

Use of tobacco products in any form is unsafe, and nearly all tobacco product use begins during adolescence. CDC and the Food and Drug Administration (FDA) analyzed data from the 2024 National Youth Tobacco Survey to determine tobacco product use among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2024, current (previous 30-day) use of any tobacco product was reported by 10.1% of high school students (representing 1.58 million students) and 5.4% of middle school students (representing 640,000 students). Among all students, e-cigarettes were the most commonly reported tobacco product currently used (5.9%), followed by nicotine pouches (1.8%), cigarettes (1.4%), cigars (1.2%), smokeless tobacco (1.2%), other oral nicotine products (1.2%), heated tobacco products (0.8%), hookahs (0.7%), and pipe tobacco (0.5%). During 2023-2024, among all students, the estimated number who reported current use of any tobacco product decreased from 2.80 to 2.25 million students; e-cigarette use decreased (from 2.13 to 1.63 million students); and hookah use decreased (from 290,000 to 190,000 students). Among high school students, current use of any tobacco product decreased from 12.6% to 10.1% of students, and e-cigarette use decreased from 10.0% to 7.8%. Among middle school students, no statistically significant changes occurred. Evidence-based strategies can help prevent initiation and promote cessation of tobacco product use among U.S. youths.

Social media monitoring as a tool for advocacy: analyzing advertisements for Heated Tobacco Products (HTPs) and e-cigarettes in Germany

Social media monitoring as a tool for advocacy: analyzing advertisements for Heated Tobacco Products (HTPs) and e-cigarettes in Germany

Tobacco- and Nicotine-Containing Product Use in Italy: Results From Two Cross-Sectional Studies

BACKGROUND: Heated tobacco products (HTPs) are alternatives to cigarettes that heat rather than burn tobacco. The first HTP sold in Italy was _IQOS®_ (I-HTP), and while it has been available for nearly a decade, limited data are available on the use of these products. OBJECTIVE: To characterize how Italian adults (users of legal age) use tobacco- and nicotine-containing products (TNPs), including smoke-free products (SFPs), we surveyed this population about their current and past use of TNPs from 2018 to 2020. METHODS: Two consecutive cross-sectional surveys were conducted in representative samples of the general adult population (6,095 subjects from 2018 to 2019 and 6,118 from 2019 to 2020) and among adult I-HTP users (1,371 subjects from 2018 to 2019 and 1,401 from 2019 to 2020) in Italy. We assessed the prevalence of current TNP use in the general population sample and use patterns in the I-HTP_ _users sample. RESULTS: In the first cross-sectional study (2018-2019), cigarettes were the most used TNP (24.3%), while only a small proportion of the surveyed general population sample used e-cigarettes or I-HTPs (1.4% and 0.7%, respectively). Nearly all current I-HTP users were current adult cigarette smokers when they started using I-HTPs (98.0%). Both surveys showed low initiation, re-initiation, and relapse with I-HTPs, with the majority of current I-HTP users belonging to the intended audience of adults who already used TNPs. Some participants used both I-HTPs and combustible TNPs (38.6%); however, most (59.2%) used I-HTPs exclusively. I-HTP_ _users perceived the health risk (score 0 = no risk; score 100 = very high risk) associated with cigarette smoking higher (63.7) than that for I-HTP_ _use (42.6). Exclusive I-HTP users reported improved respiratory symptoms (reduced cough and phlegm) and exercise capacity compared to a year before they started using I-HTPs. Most current I-HTP users also reported improved smell and taste, better breath smell, and reduced stains or yellowing teeth. Overall, these results were more pronounced among exclusive I-HTP users. The results of the second cross-sectional study (2019-2020) were similar, except for an increase in I-HTP_ _use_ _(1.1% vs. 0.7% in 2018 to 2019). CONCLUSIONS: These studies show that most TNP users in Italy smoke cigarettes. The uptake of I-HTPs suggests that they are a viable alternative to cigarettes. Nearly all I-HTP users switched from cigarettes to I-HTPs. Furthermore, most I-HTP_ _users exclusively use the product. I-HTP users considered the health risk associated with I-HTP_ _use to be lower compared to cigarette smoking, but they did not perceive I-HTPs_ _as risk free. Study participants reported improvements on some health, hygiene, and appearance aspects after switching from cigarettes to I-HTPs. Our results suggest that SFPs can play a role in a harm reduction approach. Further studies are needed to continually monitor the prevalence of SFP use to provide long-term evidence of their impact.

Identification of Specific Hemoglobin Adduct Patterns in Users of Different Tobacco/nicotine Products by Nontargeted GC-MS/MS Analysis.

Tobacco smoke contains several electrophilic constituents which are capable of forming adducts with nucleophilic sites in DNA and proteins like hemoglobin (Hb) and albumin. New nicotine and tobacco products are discussed as less harmful forms of tobacco use compared to smoking combustible cigarettes (CC) due to reduced exposure to harmful constituents. Hence, the adduct profile in users of various tobacco/nicotine products is expected to differ characteristically. In this article, we present a novel nontargeted screening strategy using GC-MS/MS for Hb adducts based on the analysis of the respective derivatized N-terminal valine adducts after modified Edman degradation. We analyzed blood samples from a clinical study with habitual users of CCs, electronic cigarettes, heated tobacco products (HTPs), oral tobacco, nicotine replacement therapy products and nonusers of any tobacco/nicotine products. Our nontargeted approach revealed significant differences in the Hb adduct profiles of the investigated tobacco/nicotine product user groups. Adduct identification was performed by means of an internal database, retention time estimations based on the theoretical boiling points, as well as in-house synthesized reference compounds. Several chemicals that form adducts with Hb could be identified: methylating and ethylating agents, ethylene oxide, acrylonitrile, acrylamide, glycidamide and 4-hydroxybenzaldehyde. Levels were elevated in smokers compared to all other groups for Hb adducts from methylating agents, ethylene oxide, acrylonitrile, acrylamide and glycidamide. Our approach revealed higher concentrations of Hb adducts formed by ethylation, acrylamide and glycidamide in users of HTPs compared to nonusers. However, concentrations for the latter two were still lower than in smokers. Due to their long half-lives, Hb adducts related to acrylonitrile, acrylamide (glycidamide), and ethylene oxide exposure may be useful for the biochemical verification of subjects̀ compliance in longitudinal and cross-sectional studies with respect to smoking and HTP use/abstinence.

Association between use of heated tobacco products and long-term respiratory effects considering smoking history: internet-based cross-sectional study in Japan

BackgroundWith 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.MethodsThe 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.ResultsOf 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.ConclusionsThese 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.

Comparative evaluation of cigarette smoke and a heated tobacco product on microglial toxicity, oxidative stress and inflammatory response

BackgroundTobacco 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.MethodsWe 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.ResultsOur 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.ConclusionThese 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.

Gender-Based Socioeconomic Inequality of Electronic Cigarettes and Heated Tobacco Products in Korea

Gender-Based Socioeconomic Inequality of Electronic Cigarettes and Heated Tobacco Products in Korea

Exposure to smoking tobacco, roll your own tobacco, heated tobacco products, and e-cigarette advertising in 28 European countries.

Exposure to smoking tobacco, roll your own tobacco, heated tobacco products, and e-cigarette advertising in 28 European countries.

Development of an LC-HRMS non-targeted method for comprehensive profiling of the exposome of nicotine and tobacco product users – A showcase for cigarette smokers

The global prevalence of electronic cigarettes, heated tobacco products, and other smokeless alternatives has grown significantly in the last ten years. These products have been suggested as combustion-free alternatives for conventional tobacco products like cigarettes, aiming to reduce the negative health impacts associated with smoking. However, the impact of those products on the health and safety of the general population are still unclear, as the absolute exposure from those products has not been thoroughly studied, yet. In this project, a non-targeted LC-HRMS method was developed comprising four different analytical modes for the investigation of the exposure profile in urine of the product users. The method is characterized by its high sensitivity and reproducibility, as shown during method validation. As a proof of concept, we first applied this method to detect significant differences in biomarkers of exposure (BoEs) between smokers and non-smokers. We observed a total of 171 BoEs significantly elevated in smokers, including several well-known biomarkers of smoke exposure like nicotine and its metabolites, mercapturic acid derivatives, and phenolic compounds. Some of the detected biomarkers are present at low ng/mL concentrations in urine, proving the high sensitivity needed for a holistic exploration of the exposome. Moreover, we were able to identify BoEs that have not been reported previously for smoking, such as 2,6-dimethoxyphenol and 7-methyl-1-naphthol glucuronide.

Switching from Cigarettes to Heated Tobacco Products in Japan-Potential Impact on Health Outcomes and Associated Health Care Costs.

Japan's rising health expenditure, driven by an aging population, coincides with growing demands for increased spending. Reducing smoking-related costs could alleviate the burden on the health care system. Despite efforts to promote smoking cessation, success has been limited, indicating a need for strategies beyond cessation. Using a status quo simulation based on hospital resource data from the Japanese Ministry of Health, Labor, and Welfare, we examine the impact of heated tobacco products (HTPs) on the prevalence of four smoking-attributable diseases (chronic obstructive pulmonary disease, ischemic heart disease, stroke, and lung cancer) and the related direct health care costs. The baseline scenario assumes a 50% switch from combustible cigarettes to HTPs, with a 70% risk reduction. A sensitivity analysis was conducted to assess the effects of parameter variations. If 50% of smokers replaced combustible tobacco products with HTPs, 12 million patients could be averted equivalent to JPY 454 billion in health care savings. Prefectures located in the north and south of Japan would benefit the most. Considering the heterogeneous prevalence rates, a one-size-fits-all tobacco control approach is ineffective. Japan should prioritize cost-efficient measures that promote public health and economic benefits. Encouraging smokers to switch to reduced-risk products, raising awareness of health risks, and adopting a harm-based taxation model can drive positive change. Public-private partnerships can further enhance harm reduction efforts. With a combination of tax reforms, revised regulations, collaborations, and ongoing research, Japan can create a more effective and comprehensive approach to tobacco control.