A Screening Method by Gas Chromatography-Mass Spectrometry for the Quantification of 24 Aerosol Constituents from Heat-Not-Burn Tobacco Products

Summary Based on the knowledge gained from published studies, a new analytical method has been developed for the quantification of mercury (Hg) in the gas-vapor phase of mainstream cigarette smoke and in heated tobacco aerosol generated by a tobacco heating system (THS) using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). From a preliminary test, the mercury concentration in the particulate matter of mainstream smoke from Kentucky reference cigarettes 3R4F generated under the International Organization for Standardization (ISO) smoking regimen was compared with the mercury concentration in the gasvapor phase to assure that mercury is only measurable in the gas-vapor phase, as reported in an earlier published study. The particulate matter was collected using an electrostatic precipitation trap and was analyzed by ICP-MS after a mineralization step. The gas-vapor phase was trapped in the same smoking run as for the particulate matter using two impingers containing a nitric acid-hydrochloric acid-gold solution. The impingers were connected in series behind the electrostatic precipitation trap and the combined impinger solution was analyzed by ICP-MS after sample dilution without further sample treatment. The addition of gold has shown to be efficient for maintaining mercury in an ionized form in the impinger solution and to minimize the mercury memory effect in the sample introduction system of the ICP-MS. Only mercury in the gas-vapor phase could be quantified whereas the signal for mercury in the particulate matter was found close to those of blank solutions and was not measurable, as already mentioned in an earlier study. Following this preliminary test, the electrostatic precipitation trap was replaced by a Cambridge filter pad for the separation of the gas-vapor phase from the particulate matter where only mercury in the gas-vapor phase was quantified. The method for the quantification of mercury in the gas-vapor phase of aerosols obtained under Health Canada (HC) and ISO smoking regimens was validated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and Association of Official Analytical Chemists (AOAC) guidelines. Accuracy profiles were evaluated as described in Association Française de Normalisation (AFNOR). The regression curve was shown to be linear within the evaluated concentration range from 25 pg/mL to 1000 pg/mL with a weighting factor 1/x. The coefficients of variation for repeatability (r) were 3.6% for 3R4F and 4.8% for THS under HC smoking regimen and 3.6% for 3R4F and 4.6% for THS under ISO smoking regimen. The coefficients of variation for intermediate precision (IP) were 7.7% for 3R4F and 7.7% for THS under HC smoking regimen and 4.7% for 3R4F and 4.6% for THS under ISO smoking regimen. The nominal mercury concentrations for 3R4F obtained during the validation under both HC and ISO smoking regimens were found to be in line with results reported in a previously published CORESTA study.

The objective of the study was to establish a method to determine the gas/particle nicotine in mainstream cigarette smoke with denuder technology. The mainstream smoke from a lit cigarette was passed through a coated denuder in laminar flow by a pump and the remaining smoke was collected by a Cambridge filter pad attached to the exit of the denuder. The interior of the denuder and the filter were extracted by dichloromethane before internal standards were added. The extracts were analyzed by gas chromatography-mass spectrometry. The results show that the gas phase nicotine proportion (fgas) increased with the exit smoke temperature (ranging from 293 K to 323 K). The determined fraction (fgas) was ca. 0.094 8% at 308 K. The method can be used to understand potential effects of gas/particle nicotine partitioning from cigarette designs, next generation nicotine and tobacco products such as electronic cigarettes and tobacco heating products.

Markets for nicotine vaping products (NVPs) and heated tobacco products (HTPs) have grown as these products became positioned as harm-reduction alternatives to combusted tobacco products. Herein, we present a public health decision-theoretic framework incorporating different patterns of HTP, NVP, and cigarette use to examine their impacts on population health. Our framework demonstrates that, for individuals who would have otherwise smoked, HTP use may provide public health benefits by enabling cessation or by discouraging smoking initiation and relapse. However, the benefits are reduced if more harmful HTP use replaces less harmful NVP use. HTP use may also negatively impact public health by encouraging smoking by otherwise non-smokers or by encouraging initiation or relapse into smoking. These patterns are directly influenced by industry behavior as well as public policy towards HTPs, NVPs, and cigarettes. While substantial research has been devoted to NVPs, much less is known about HTPs. Better information is needed to more precisely define the health risks of HTPs compared to cigarettes and NVPs, the relative appeal of HTPs to consumers, and the likelihood of later transitioning to smoking or quitting all products. While our analysis provides a framework for gaining that information, it also illustrates the complexities in distinguishing key factors.

Although smoking rates have been declining worldwide, new types of tobacco products have been gradually spreading in recent years, especially in Japan, where heated tobacco products (HTPs) users are rapidly increasing. Oxidative stress caused by reactive oxygen species (ROS) is one of the causes of smoking-induced carcinogenesis, respiratory diseases, and cardiovascular diseases. However, information on the amount of ROS contained in mainstream smoke from HTPs is limited. In this study, we measured the amount of ROS generated from HTPs to evaluate the oxidative stress-related toxicity of HTPs. IQOS ILUMA, glo hyper+, and Ploom X ADVANCED were used as the HTP devices. Mainstream smoke was collected from each HTP according to Health Canada Intense regime (smoke volume, 55 mL; smoke duration, 2 s). The collected ROS were reacted with 2,7'-dichlorodihydrofluorescein reagents, and the amount of ROS was calculated as H2O2 equivalent from the fluorescence intensity obtained. The ROS in the mainstream smoke from IQOS ILUMA, glo hyper+ (high-temperature mode), and Ploom X ADVANCED was found to be 48.8 ± 8.6, 86.6 ± 12.6, and 40.8 ± 5.7 nmol H2O2/stick, respectively (n = 6, mean ± standard deviation), with the highest being from glo hyper+ (high-temperature mode). The amount of ROS was significantly higher in the high-temperature mode of glo hyper+ than in the standard mode of glo hyper+. Additionally, the estimated amount of ROS from smoking 20 heated sticks per day (674-2160 nmol H2O2/day) was equivalent to 2.2-96 times the amount of daily exposure to ROS in the urban atmosphere (approximately 22-300 nmol H2O2/day). We found that ROS is generated from HTPs of different devices. This study suggests that HTPs users may be exposed to much more ROS than they are exposed to in normal life.

Information on the use of multiple tobacco and tobacco-like products (hereafter multiple tobacco products use, i.e., use of more than one product) is important for tobacco control. Use of heated tobacco products (HTPs), which first became popular in Japan, has been spreading over the world, while information about use of multiple tobacco products, including HTPs, is insufficient. We analyzed data of 10,114 responders from the 2017 Japan “Society and New Tobacco” Internet Survey (JASTIS) study. The prevalence and adjusted odds ratio (aOR) of multiple tobacco products use were estimated with inverse probability weighting using multivariable logistic regression models to approximate the results to whole Japanese estimates. Tobacco and tobacco-like products included cigarettes, cigars, e-cigarettes, HTPs, pipes/water pipes, and smokeless tobacco products. Among Japanese adults, 18.4% were single tobacco product users and 3.2% were multiple tobacco product users in 2017. Among current product users (100%), cigarettes were the most popular product in single (78.8%) and multiple (14.2%) tobacco products use, while HTPs were the second most popular product in single (5.2%) and multiple (10.6%) tobacco products use. People with no perception of risk regarding e-cigarettes/HTPs were more likely to use multiple tobacco products (aOR = 1.47, 95% CI = 1.12–1.92) than those who perceived a risk. Prevalence rates and predictors of multiple tobacco products use, including HTPs, were studied first. In multiple tobacco products use, high popularity of HTPs among current product users was revealed. Risk perception of e-cigarettes/HTPs was associated with multiple tobacco products use. This study provides baseline information on multiple tobacco products use in Japan, which will enable the examination of trends in the future.

Summary 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.

The Tobacco Endgame-Eradicating a Worsening Epidemic: A Joint Opinion From the American Heart Association, World Heart Federation, American College of Cardiology, and the European Society of Cardiology.

Heated tobacco products (HTPs) are marketed as lower-risk alternatives to conventional cigarettes; however, their toxicological impacts remain insufficiently characterized. This study evaluated the effects of HTP emissions on gene expression and mitochondrial function in comparison with conventional cigarettes. Whole cigarette smoke condensates (WCSCs), comprising both gas and particulate phases, were prepared from three commercially available HTPs and from 3R4F reference cigarettes. Human lung epithelial BEAS-2B cells were exposed to WCSCs at 3 μg nicotine/mL for 24 h, followed by transcriptome profiling using RNA sequencing. Principal component analysis demonstrated that HTP-WCSCs induced weaker gene expression changes than 3R4F-WCSC, with only modest variation among HTPs. Gene set enrichment analysis revealed that both HTP- and 3R4F-WCSCs significantly downregulated oxidative phosphorylation (OXPHOS)–related pathways, indicating potential mitochondrial impairment. Functional assays confirmed that both exposures elevated mitochondrial reactive oxygen species (ROS), while mitochondrial morphology, ATP production, membrane potential, and cytosolic ROS were largely unaffected. Collectively, these results show that although HTP emissions elicit weaker transcriptomic perturbations than conventional cigarette emissions, both converge on mitochondrial targets by suppressing OXPHOS gene expression and increasing mitochondrial ROS. Mitochondrial dysfunction may therefore represent a common mechanism underlying tobacco product toxicity.

Assessment of tobacco heating product THP1.0. Part 5: In vitro dosimetric and cytotoxic assessment

BackgroundFor novel tobacco products that potentially reduce the risk of tobacco harm, post-market surveillance is important to observe population usage and behaviours associated with everyday use. This pilot study was performed to examine the use of tobacco products in three Japanese urban regions.MethodsThis study was a cross-sectional epidemiological survey administered in Sendai, Tokyo and Osaka, Japan, from May 19th to June 25th, 2018. Participants were selected with a three-stage probability random sampling process that first identified primary sampling units, then households and finally individuals. Eligible participants were aged at least 20 years who were willing to participate after information about the study was provided. People younger than 20 years and those living in institutions were excluded. Questionnaires were paper based and administered door to door.ResultsResponses were obtained from 4154 participants. Sixty-five percent self-reported being never, 19% current and 16% former users of any tobacco product at the time of the survey. Combustible tobacco products (almost all being cigarette) were used most (16%) followed by HTPs (5%). In the categories of combustible tobacco users and HTP users, 70% and 16%, respectively, used these products exclusively. Dual use was reported by 11% of respondents. Compared with 12 months before the survey, 12% of sole combustible tobacco products users were using HTPs exclusively or as dual users and 6% had quit tobacco products completely; 94% of sole HTP users remained sole users and 4% had quit tobacco products completely; and amongst dual users 12% had reverted to exclusive use of combustible tobacco products, 14% had switched to sole use of HTPs and 4% had quit tobacco products completely.ConclusionHTPs seem to be accepted as an alternative tobacco product amongst combustible tobacco users. Given complex findings for dual use, improved understanding of the motivations underlying this behaviour would be of interest.

IntroductionEmerging tobacco and nicotine products, such as e-cigarettes and heated tobacco products (HTPs), are gaining popularity, particularly among young people. This study examines the perceptions of e-cigarettes and HTPs among nicotine-naive individuals and their variations across sociodemographic subgroups.MethodsWe conducted a cross-sectional analysis of the Special Eurobarometer 99.3 (May–June 2023) among never users of tobacco or nicotine products in the European Union (EU) (n = 13 436). We estimated the weighted prevalence of perceptions of e-cigarettes and HTPs: appeal, perceived effectiveness for smoking cessation, support for them being regulated like cigarettes, and support for keeping them out of sight in points of sale. Multi-level Poisson regression models examined associations of sociodemographic factors with these perceptions.ResultsAmong never users in the EU, 2.6% found e-cigarettes appealing, while 2.0% found HTPs appealing. Fifty-point eight percent and 58.8% of participants supported strict regulations and point-of-sale restrictions for these products, respectively. Younger age groups were more likely to find e-cigarettes (prevalence ratio [PR] = 1.70, for ages 15–39 vs. ≥55) and HTPs (PR = 1.88, PR = 1.54 for ages 15–24 and 25–39) appealing and view them as effective for smoking cessation. Support for regulations similar to cigarettes was higher among women, individuals with higher education, those living with children, and those without financial difficulties.ConclusionWhile the appeal of these products to never users remained low overall, the study found that young people were more likely to find them appealing, posing a risk for experimentation. Meanwhile, over 50% of respondents supported stricter regulations, which could influence policy changes in this area.ImplicationsAlthough appeal of e-cigarettes and Heated Tobacco Products (HTPs) was relatively low among people who have never used e-cigarettes, HTPs, or smoking tobacco in the EU, appeal was higher among younger age groups, which are often targeted by the industry. We also found substantial support for stricter regulatory policies for e-cigarettes and HTPs across the EU. These findings might encourage governments to increase restrictions around these emerging nicotine and tobacco products.

Tobacco companies have devoted increased resources in recent years to developing and marketing heated tobacco products (HTPs) as alternatives to combustible products like cigarettes. However, little is known about correlates of awareness and use of these products in American young adults. Two thousand four hundred ninety-seven young adults (mean age = 21.6) completed survey items on HTP awareness and lifetime use in 2018-2019. Logistic regression models compared young adults who were (1) unaware of HTPs (reference group) with those who were, (2) aware of HTPs, and (3) had ever used HTPs on demographic, tobacco, and other substance use characteristics. Among current smokers, these groups were compared on cigarette use, dependence, and readiness to quit. Approximately 12% of respondents (n = 293) were aware of HTPs, and 5% (n = 134) reported lifetime HTP use. Controlling for demographics, HTP awareness and use were both associated with greater use of all types of tobacco products, number of different tobacco products, and use of marijuana and other drugs. Among current smokers, HTP awareness and use correlated with heavier cigarette consumption, greater dependence, and past-month marijuana use, but not with recent quit attempts or thinking about quitting cigarettes. Awareness and use of HTPs among young adults were associated with greater use of tobacco products and other substances and, among current smokers, with greater cigarette dependence (but not cessation-related factors). As these products become increasingly available in the United States, additional surveillance and monitoring activities are needed to better understand use patterns, consequences, and reasons for using HTPs. Few studies have examined factors associated with awareness and use of heated tobacco products (HTPs) among US young adults. HTP awareness and lifetime use correlated with a range of factors, including male gender, white race/ethnicity, and tobacco and other substance use. Lifetime use of HTPs was low (5%); most lifetime HTP users reported history of other tobacco use, but a sizeable minority (14%) reported no other tobacco product use history. Among current cigarette smokers, cigarette dependence, poly-tobacco use, and marijuana use-but not cigarette cessation attempts or contemplation-were associated with greater likelihood of awareness and use of HTPs.

Objectives: Heated tobacco products (HTPs) constitute a novel and emerging type of tobacco product. Actual puffing topography and nicotine exposure studies are indispensable in tobacco and nicotine products risk assessment. In this study, we aimed to collect and compare usage behavioural data on HTPs to those of conventional cigarettes (CCs) by recording the puffing topography parameters of users under laboratory conditions. Methods: Two hundred voluntary adult cigarette users (164 male, 36 female) from 4 Chinese cities were recruited and randomly divided into 3 groups: the tobacco flavoured HTP (Original-HTP) group, the menthol-flavoured HTP (Menthol-HTP) group, and the CC group. The volunteers were acclimatized to the 3 tobacco products with a nicotine content of 1.0 mg/stick, for 1 week. Data on the 8 types of puffing parameters were collected for every participant via a commercial calibrated puff behaviour recorder. These data were analysed alongside the levels of 8 urinary nicotine metabolites after product usage. Results: When using the same type of nicotine stick, the volunteers in the two HTP groups had significantly higher puff numbers, puff volumes, flow velocities and peak flow rates than those in the CC group. Conversely, participants in the CC group had longer interpuff intervals and higher urinary nicotine concentrations. Differences in the puffing topography among the four cities were not significant. Conclusion: There were substantial differences in the overall puffing volume and urinary nicotine metabolite levels between Chinese smokers who used HTPs and those who used CCs. These findings indicate that assessments of risk associated with the use of tobacco and nicotine products need to adequately assess the actual use patterns and nicotine exposure levels of users of different types of products.

Summary In order to assess robustness for the reduction of harmful and potentially harmful constituent (HPHC) levels generated by the Tobacco Heating System 2.2 (THS 2.2), a heated tobacco product, we compared the aerosol of this product with mainstream smoke from the 3R4F reference cigarette under different conditions of temperature and humidity. The desired climatic conditions were achieved by using an air-conditioning system coupled with the smoking-machine housing. Two extreme climatic conditions were selected, representing a “Hot and Dry” climate (30 °C and 35% relative humidity RH) and a “Hot and Very Humid” climate (30 °C and 75% RH). In addition, aerosol and smoke were generated using the standard conditions recognized for smoking-machine analyses of tobacco products (22 °C and 60% RH), which were close to the climatic conditions defined for “Subtropical and Mediterranean” environments (25 °C and 60% RH). The experimental conditions were chosen to simulate the use of THS 2.2 and cigarettes under extreme conditions of temperature and humidity. HeatSticks and cigarettes taken from freshly opened packs were subjected to short-term conditioning from two to a few more days under the same experimental conditions. We analyzed 54 HPHCs in THS 2.2 aerosol and 3R4F cigarette smoke, generated in accordance with the Health Canada Intense (HCI) standard, using modified temperature and humidity conditions for sample conditioning and machine-smoking experiments. We used a volume-adjusted approach for comparing HPHC reductions across the different climatic conditions investigated. Although a single puffing regimen was used, the total puff volume recorded for the 3R4F cigarette smoke varied due to the influence of temperature and humidity on combustion rate, which justified the use of a volume-adjusted approach. Volume-adjusted yields were derived from HPHC yields expressed in mass-per-tobacco stick normalized per total puff volume. The results indicated that, regardless of the considered climatic conditions, the HPHC levels investigated in THS 2.2 aerosol were reduced by at least 90%, on average, when compared with the concentrations in 3R4F cigarette mainstream smoke. This confirmed the robustness in performance for THS 2.2 to deliver reduced levels of HPHCs under the extreme climatic conditions investigated in this study. In order to further characterize the robustness of these reductions, the lowest reduction performance achieved for individual HPHCs across all climatic conditions was used to define the threshold for a robust reduction. The majority of the 54 HPHCs investigated in THS 2.2 aerosol showed more than 90% reduction. Calculations derived from nicotine-adjusted yields also confirmed robust reductions for all investigated HPHCs. The small differences in absolute reduction between the volume- and nicotine-adjusted approaches were predominantly attributed to a combination of the differences in both nominal nicotine deliveries and total puff volumes between THS 2.2 and 3R4F cigarettes; however, this did not influence the determination of robustness. Our findings confirm the value of this approach for assessing the robustness of a product’s performance under different climatic conditions.

Heated tobacco products (HTPs) have been advertised as "reduced-harm" tobacco products compared to conventional cigarettes (CC); however, no direct evidence supporting HTPs being desirable for human health exists. A previous systematic review reported that evidence on HTPs published in 2017 or earlier was primarily drawn from industry-related papers. We aimed to investigate whether tobacco industry-affiliated studies are more likely to conclude that HTPs are more desirable than CC. PubMed and Ichushi-Web were searched up to March 15, 2022, for studies on HTPs published in 2017 or after. We selected studies that assessed any measures of HTPs and CC, including secondary analyses using gray literature in English or Japanese. We excluded review articles except for a meta-analysis that met the aforementioned criteria. Data on the authors' affiliations, grant, conflict of interest, category of research subjects, and interpretation were extracted. Research members in two groups independently assessed the papers; discrepancies were solved by discussion between the groups. Overall, 134 studies met the criteria. Eighty-seven (64.9%) of them were affiliated with the tobacco industry. Of the 134 studies, 56.3% (49/87) of the industry-affiliated studies versus 19.1% (9/47) of nonindustry-affiliated studies concluded that HTPs were more desirable than CC (p < .01). No study investigated clinically relevant outcomes, such as disease occurrence. Publications on HTPs in the biomedical literature from January 2017 to March 2022 were dominated by tobacco industry-affiliated studies. More than half of them concluded that HTPs were more desirable than CC compared to independent studies. Tobacco industry advertises HTPs as "reduced-harm" tobacco products compared to CC. HTP users tend to consider HTPs as alternative tobacco products less harmful than CC (ie, products for "harm reduction"). Our results demonstrated that papers written by tobacco industry-affiliated authors concluded that HTPs were more desirable than CC compared to papers by independent authors. However, all their judgments were based on surrogate outcomes. Surrogate outcomes are not necessarily linked to clinically relevant outcomes such as disease occurrence. Further studies on HTPs using clinically relevant outcomes are warranted by independent authors from tobacco industry.