Heated tobacco products (HTPs) are electronic devices that heat tobacco sticks to temperatures much lower than those which cause pyrolysis and combustion in cigarettes. While this electrical heating causes the formation of an inhalable aerosol which contains nicotine, the aerosol from HTPs contains significantly fewer and lower levels of the harmful and potentially harmful chemicals found in cigarette smoke. As a result, HTP use potentially conveys reduced risks to health compared to cigarette smoking. While this relative reduction in individual health risk is becoming clearer, what is less certain is the impact of HTPs on overall population‑level health, taking into account both the potential positive impact on adult smokers who completely switch to using HTPs and any unintended impacts such as use by tobacco non‑users and particularly by youth. The aim of this scoping review was to collate and evaluate the published scientific evidence to date, with a cut‑off of 1 January 2024, investigating the impact of HTPs on population‑level health. This evaluation suggests that HTP use is almost exclusively observed among those with a history of cigarette smoking, and there is a growing body of evidence for the ability of HTPs to provide support for adult smokers to transition away from cigarette smoking, in the absence of any significant \"gateway\" into tobacco use initiation. Many studies have reported a significant degree of dual use of cigarettes and HTPs, and efforts to assess the reasons for such patterns of use, whether these provide overall exposure reductions, and whether dual use acts as a bridge towards a complete transition away from cigarette smoking, requires further investigation. In addition, correction of the widespread and increasing misperceptions of HTPs among adult smokers is recommended to promote HTP uptake as a potentially less harmful alternative to smoking in this population.

New types of nicotine and tobacco products like electronic cigarettes (ECs), heated tobacco products or nicotine pouches have been discussed as less harmful alternatives to combustible cigarettes and other toxic forms of tobacco products. Their harm reduction potential lay in the efficient transition away from smoking to those new products. Numerous studies addressing the cessation efficacy of ECs have been published with contradictory outcomes. Yet, a comprehensive Cochrane review concluded with high certainty on the cessation efficacy of ECs. This prompted us to perform a review to identify weaknesses in common study designs and to summarize best practices for the study design on the potential of new nicotine products as cessation aids. 120 articles retrieved from Medline were found to be eligible. Most of the studies in the field were interventional trials while observational studies played a minor role in the evaluation of smoking cessation. Efficacy was predominantly assessed for ECs in 77% of the reports while heated tobacco (17%) and non-combustible products (11%) were less frequently investigated up to now. Measures to determine the efficacy were questionnaire-based assessments as well as use documentation/prevalence and abstinence rates. Studies varied largely in their duration and sample size with medians of 3 months and 156.5 participants, respectively.With the help of this review, we identified several weaknesses in the common study designs. One major limitation in longitudinal trials was the lack of compliance measures suited to verify the use status over longer time periods, relying solely on self-reports. Moreover, the motivation of the participants to quit was rarely defined and a profound familiarization period was not taken into account for the majority of the studies. To what extent such weaknesses influence the outcome of the studies was beyond the scope of this review. We encourage researchers to consider the recommendations which resulted from this review in order to determine the abuse liability and cessation efficacy of the products in a more robust manner. Finally, we like to call attention to the missing data for low- and middle-income countries which would require quitting strategies most urgently to combat the tobacco smoking epidemic.

Heated tobacco products represent a novel category of tobacco products in which a tobacco consumable is heated to a temperature that releases nicotine from the tobacco leaf but not to a temperature sufficient to cause combustion. Heated tobacco products may therefore have the potential to be a less harmful alternative for adult smokers who would otherwise continue to smoke cigarettes, as their use should result in exposure to substantially fewer and lower levels of toxicants. This update represents a two-year extension to our previous narrative review, which covered peer-reviewed journal articles published up to August 31, 2021. The scientific evidence published between 2021 and 2023 continues to indicate that aerosols produced from heated tobacco products contain fewer and substantially lower levels of harmful and potentially harmful constituents and that these observed reductions consistently translate to reduced biological effects in both in vitro and in vivo toxicological studies. Biomarker and clinical data from studies in which product use is controlled within a clinical setting continue to suggest changes in levels of biomarkers of exposure, biomarkers of potential harm, and clinical endpoints indicating the potential for reduced harm with switching to exclusive use of heated tobacco products in adult smokers. Overall, the available peer-reviewed scientific evidence continues to indicate that heated tobacco products offer promise as a potentially less harmful alternative to cigarettes, and as such, the conclusions of our original narrative review remain valid.

Emerging tobacco products such as electronic nicotine delivery systems (ENDS) and heated tobacco products (HTPs) have a dynamic landscape and are becoming widely popular as they claim to offer a low-risk alternative to conventional smoking. Most pre-clinical laboratories currently exploit in vitro, ex vivo, and in vivo experimental models to assess toxicological outcomes as well as to develop risk-estimation models. While most laboratories have produced a wide range of cell culture and mouse model data utilizing current smoke/aerosol generators and standardized puffing profiles, much variation still exists between research studies, hindering the generation of usable data appropriate for the standardization of these tobacco products. In this review, we discuss current state-of-the-art in vitro and in vivo models and their challenges, as well as insights into risk estimation of novel products and recommendations for toxicological parameters for reporting, allowing comparability of the research studies between laboratories, resulting in usable data for regulation of these products before approval by regulatory authorities.

This work aims to summarize the current evidence on the toxicity and health impact of IQOS, taking into consideration the data source. On 1 June 2022, we searched PubMed, Web of Science, and Scopus databases using the terms: \'heated tobacco product\', \'heat-not-burn\', \'IQOS\', and \'tobacco heating system\'. The search was time-restricted to update a previous search conducted on 8 November 2021, on IQOS data from 2010-2021. The data source [independent, Philip Morris International (PMI), or other manufacturers] was retrieved from relevant sections of each publication. Publications were categorized into two general categories: 1) Toxicity assessments included in vitro, in vivo, and systems toxicology studies; and 2) The impact on human health included clinical studies assessing biomarkers of exposure and biomarkers of health effects. Generally, independent studies used classical in vitro and in vivo approaches, but PMI studies combined these with modeling of gene expression (i.e. systems toxicology). Toxicity assessment and health impact studies covered pulmonary, cardiovascular, and other systemic toxicity. PMI studies overall showed reduced toxicity and health risks of IQOS compared to cigarettes, but independent data did not always conform with this conclusion. This review highlights some discrepancies in IQOS risk assessment regarding methods, depth, and breadth of data collection, as well as conclusions based on the data source.

We provide an extensive review of 17 independent and industry-funded studies targeting carbonyls in aerosol emissions of Heated Tobacco Products (HTPs), focusing on quality criteria based on the reproducibility of experiments, appropriate analytic methods, and puffing regimes. Most revised studies complied with these requirements, but some were unreproducible, while others failed to consider analytical variables that may have affected the results and/or produced unrealistic comparisons. We also provide a review of the literature on the physicochemical properties of heated tobacco and HTP aerosols, as well as the evaluation of HTPs by regulatory agencies, addressing various critiques of their relative safety profile. The outcomes from the revised studies and regulatory evaluations tend to agree with and converge to a general consensus that HTP aerosols expose users to significantly lower levels of toxicity than tobacco smoke.

Heated tobacco products (HTPs) are electronic devices that heat process tobacco to release an aerosol containing nicotine and other chemicals. Limited data exist on world-wide HTP use prevalence. This meta-analytic review estimated the prevalence of HTP use by country, World Health Organization (WHO) region, year, sex/gender and age.
Five databases (Web of Science, Scopus, Embase, PubMed and PsycINFO) were searched between January 2015 and May 2022. Included studies reported the prevalence of HTP use in nationally representative samples post-modern HTP device market entry (2015). A random-effects meta-analysis was used to estimate overall prevalence for life-time, current and daily HTP use.
Forty-five studies (n = 1 096 076) from 42 countries/areas from the European Region (EUR), Western Pacific Region (WPR), Region of the Americas (AMR) and African Region (AFR) met inclusion criteria. Estimated pooled prevalence for life-time, current and daily HTP use was 4.87% [95% confidence interval (CI) = 4.16, 5.63], 1.53% (95% CI = 1.22, 1.87) and 0.79% (95% CI = 0.48, 1.18), respectively, across all years (2015-22). Life-time HTP use prevalence significantly increased by 3.39% for WPR [0.52% (95% CI = 0.25, 0.88) in 2015 to 3.91% (95% CI = 2.30, 5.92) in 2019] and 5.58% for EUR [1.13% (95% CI = 0.59, 1.97) in 2016 to 6.98% (95% CI = 5.69, 8.39) in 2020]. Current HTP use increased by 10.45% for WPR [0.12% (95% CI = 0, 0.37) in 2015 to 10.57% (95% CI = 5.59, 16.88) in 2020] and 1.15% for EUR [0% (95% CI = 0, 0.35) in 2016 to 1.15% (95% CI = 0.87, 1.47) in 2020]. Meta-regression revealed higher current HTP use in WPR [3.80% (95% CI = 2.88, 4.98)] compared with EUR [1.40% (95% CI = 1.09, 1.74)] and AMR [0.81% (95% CI = 0.46, 1.26)] and for males [3.45% (95% CI = 2.56, 4.47)] compared with females [1.82% (95% CI = 1.39, 2.29)]. Adolescents had higher life-time HTP use prevalence [5.25% (95% CI = 4.36, 6.21) than adults [2.45% (95% CI = 0.79, 4.97)]. Most studies scored a low risk of sampling bias due to their nationally representative sampling.
The prevalence of HTPs use increased in the EUR and WPR between 2015 and 2020, with nearly 5% of the included populations having ever tried HTP and 1.5% identifying as current users during the study period.

Approximately 100 million people globally smoke cigarettes, making it a significant and quickly spreading global tobacco epidemic. Substance use disorders are frequently evaluated by non-randomized studies. Tobacco use and its impacts on the cardiovascular system were the subjects of a comprehensive search across five electronic databases: Cochrane, MEDLINE, Scopus, Embase, and PubMed. The findings demonstrated that waterpipe smokers in comparison to non-smokers have immediate elevations in heart rate and blood pressure, lower levels of high-density lipoprotein, higher levels of low-density lipoprotein, higher levels of triglycerides, higher levels of fasting blood glucose, and a higher heart rate. Users of waterpipes and cigarettes had similar average heart rates, blood pressure, and lipid levels, with the exception that waterpipe smokers had greater total cholesterol. Smoking a waterpipe has significant negative effects on the cardiovascular system comparable to cigarette smoking, and non-randomized studies proved to yield substantial evidence related to its cardiovascular effects. Such study designs can be used to evaluate substance use and its cardiovascular impact.

Heated tobacco products (HTP) have become increasingly common in many countries worldwide. The principle of heating tobacco, without combustion, to produce a nicotine-containing aerosol with remarkably reduced levels of other known toxins, compared to combusted tobacco cigarettes, is now well established. As these products are intended as alternatives to traditional combusted products, during the early stages of their development, it is important for manufacturers to ensure that the design of the product does not lead to any unintentionally increased or new risk for the consumer, compared to the traditional products that consumers seek to replace. There is limited guidance from tobacco product regulations concerning the requirements for performing such preliminary toxicological assessments. Here, we review the published literature on studies performed on HTPs in the pursuit of such data, outline a proposed approach that is consistent with regulatory requirements, and provide a logical approach to the preliminary toxicological assessment of HTPs.

Disparities in exposure to and density of tobacco advertising are well established; however, it is still unclear how e-cigarette and heated tobacco product (HTP) advertising vary by age, education, sex, gender identity, race/ethnicity, sexual orientation, socioeconomic status (SES), and/or urban/rural area. Through a scoping review, we sought to identify potential disparities in exposure to e-cigarette and HTP advertising and promotion across populations.
In January 2020, a systematic literature search was conducted in five databases: PubMed, Scopus, Embase, Web of Science, and the Cochrane Library. The search was updated in October 2020. Articles reporting on exposure to e-cigarette and/or HTP advertising and promotion across age, education, sex, gender identity, race/ethnicity, sexual orientation, SES, and/or urban/rural areas were included for full-text review (n = 25). Of those, 15 were deemed relevant for data extraction.
The majority of the studies were from the U.S. (n = 12) and cross-sectional (n = 14). Studies were published between 2014 and 2020 and focused on determining causal relationships that underlie disparities; only one study assessed HTP advertising and promotion. Exposure to e-cigarette and HTP advertising was assessed at the individual-level (e.g., recall seeing ads on television) and at the neighborhood-level (e.g., ad density at the point-of-sale). Studies addressed differences across age (n = 6), education (n = 2), sex (n = 6), gender identity and sexual orientation (n = 3), race/ethnicity (n = 11), SES (n = 5), and urban/rural (n = 2). The following populations were more likely to be exposed to e-cigarette advertising: youth, those with more than a high school diploma, males, sexual and gender minorities, Whites, and urban residents. At the neighborhood-level, e-cigarette advertisements were more prevalent in non-White neighborhoods.
Exposure to e-cigarette/HTP advertising varies based on sociodemographic characteristics, although the literature is limited especially regarding HTPs. Higher exposure among youth might increase tobacco-related disparities since it can lead to nicotine/tobacco use. Research should incorporate and apply a health equity lens from its inception to obtain data to inform the elimination of those disparities.