Tobacco Harm Reduction Research Articles

Tobacco harm reduction in the 21st century

Purpose This paper aims to overview the need for tobacco harm reduction, the consumer products that facilitate tobacco harm reduction and the barriers to its implementation. The worldwide endemic of tobacco smoking results in the death of over seven million smokers a year. Cigarette quit rates are very low, from 3%–12%, and relapse rates are high, from 75%–80% in the first six months and 30%–40% even after one year of abstinence. In addition, some smokers do not desire to quit. Cigarette substitution in tobacco harm reduction is one strategy that may reduce the burden of morbidity and mortality. Design/methodology/approach This review examines the displacement of smoking through substitution of non-combustible low-risk products such as snus, heated tobacco products and e-cigarettes. Findings Toxicological testing, population studies, clinical trials and randomized controlled trials demonstrate the potential reductions in exposures for smokers. Many barriers impede the implementation of product substitution in tobacco harm reduction. These products have been subjected to regulatory bans and heavy taxation and are rejected by smokers and society based on misperceptions about nicotine, sensational media headlines and unsubstantiated fears of youth addiction. These barriers will need to be addressed if tobacco harm reduction is to make the maximum impact on the tobacco endemic. Originality/value This review provides the rationale for tobacco harm reduction, evaluates the current products available and identifies the barriers to implementation.

Overcoming barriers to disseminate effective smoking cessation treatments globally

Purpose The purpose of this paper is to review the barriers in the dissemination of effective smoking cessation treatments and services globally. Offering tobacco users help to stop using tobacco is a key demand reduction measure outlined under Article 14 of the World Health Organisation (WHO) Framework Convention on Tobacco Control (FCTC). Implementing Article 14 can reap great dividends for the billion plus tobacco users around the world and their families, friends and societies. Design/methodology/approach A review of the status of the global implementation of Article 14 using available literature on smoking cessation products, services and national guidelines. Discussing innovative approaches being currently explored in South Asia that can lead to faster adoption and implementation of Article 14 globally. Findings Major gaps remain in cessation products’ availability and resource allocation for cessation services globally. Current licensed products are falling short on delivering and sustaining smoking cessation. Innovation in cessation products and services needs to build on learnings in nicotine pharmacokinetics, behavioural insights from consumer research and tap into 21st century tools such as mobile based apps. National implementation of FCTC’s Article 14 needs to follow guidelines that encourage integration into existing health programmes and health-care practitioners’ (HCPs) upskilling. Originality/value Smoking cessation is a desirable health outcome and nicotine replacement products are a means of achieving cessation through tobacco harm reduction. E-cigarettes are sophisticated nicotine replacement products. Innovation is urgently needed to fill the gaps in smoking cessation products and services, and for converting global policy into local practice. In low- and middle-income countries (LMICs), HCPs’ knowledge, attitudes and practice regarding tobacco use and cessation may hold the key to rapidly scaling up cessation support and delivery to achieve FCTC objectives sooner. Additionally, HCPs can play an important role in offering smoking cessation support in existing national health programmes for TB, cancer screening and maternal and child health. Also, widely prevalent smartphone devices may deliver smoking cessation through telemedicine in LMICs sooner, leapfrogging the hurdles of the existing health-care infrastructure.

Perceptions of nicotine in current and former users of tobacco and tobacco harm reduction products from seven countries

Purpose Nicotine is widely known as a tobacco constituent and for its use as a tobacco cessation aid. The development of new devices for nicotine delivery in recent years has led to uncertainty among consumers regarding the health risks of nicotine relative to tobacco. The purpose of this study was to discover if current and former consumers of tobacco and tobacco harm reduction (THR) products could distinguish between “nicotine” and “cigarettes” and examined the preceding media dialogue to determine if conflicting messages by the media influence public perceptions. Design/methodology/approach A quantitative survey was administered online in Norway (NO), Japan (JP), the United Kingdom (UK) and the United States (US), while face-to-face computer-aided interviews were conducted with randomly selected samples in India (IN), Greece (GR) and South Africa (SA). Participants were between 18 and 69 years of age and either current users of tobacco and THR products or previous users who quit within the past five years. Questions assessed beliefs about harmfulness of nicotine. Nicotine and other products and substances were also independently rated for harmfulness on a scale of 1–10 and subsequently compared. In addition, the authors examined the media dialogue of top media outlets in four countries to assess the potential influence on people’s beliefs. Findings A total of 54,267 participants (NO: 1,700, JP: 2,227, UK: 2,250, USA: 2,309, IN: 41,633, GR: 1,801, SA: 2,359) were sampled with the percentage of women participants ranging from 14.8% (IN) to 53.8% (UK). Between 68.3% (men, IN) and 88.7% (men, USA) of current consumers believed nicotine is harmful. Current consumers who agreed with the statement that nicotine is the primary cause of tobacco-related cancer ranged from 43.7% (men, UK) to 78.0% (men, SA). In six countries nicotine was rated nearly as harmful as cigarettes and alcohol, while other substances such as sugar, salt or caffeine, were usually rated as less harmful. Research limitations/implications A large proportion of consumers across all surveyed countries view nicotine and cigarettes similarly. Clearer communication on the harmful properties of both by the media is needed to help consumers make informed decisions about products across the continuum of risk. Messaging to consumers, especially via the media, propagates misinformation about the relative harms of tobacco and nicotine through reporting that is often incomplete and biased toward more negative aspects. Originality/value This study specifically assessed public perceptions of nicotine as opposed to products containing nicotine, which is the focus of previous studies. Apart from showing that consumers often incorrectly perceive nicotine and cigarettes as similar in terms of harmfulness, the authors highlight the need for more accurate and complete reporting by the media to clarify widespread misunderstandings and mitigate public uncertainty.

The effect of tobacco- and electronic cigarettes use on the olfactory function in humans

Electronic cigarettes are a recent development in tobacco harm reduction. They are marketed as a “healthier alternative” to conventional cigarettes but their health impact is unknown. Therefore, the aim of this study was to investigate the odor perception of smokers and vapers (e-cigarette consumers) in comparison to non-smokers. For the study 181 study participants aged 18 to 46 years were selected and divided into three groups including the control group (n = 70 non-smokers; 40 women, 30 men), as well as two investigated groups consisted of smokers (n = 66; 32 women, 34 men) and vapers (n = 45; 18 women, 27 men). The individuals were evaluated by applying the “Sniffin‘ Sticks” odor threshold (T), discrimination (D), and identification (I) test. To express the overall results a composite threshold-discrimination-identification (TDI) score was calculated. The results of the threshold test showed a significant difference (p ≤ 0.05) between non-smokers and smokers, as well as smokers and vapers. The data of odor discrimination- and odor identification, as well as the TDI-score revealed a significant difference (p ≤ 0.05) between all three evaluated groups. Furthermore, according to the Pearson test, there was a significant correlation (p ≤ 0.05) between the “pack-years” and odor threshold and the TDI-score. However, the correlation between the “pack-years” and the results of the odor discrimination and identification was not statistically significant (p > 0.05). Besides, the duration of vaping (in years) and amount of consumed liquid (ml) did not correlate (p > 0.05) with the odor threshold, discrimination, identification as well as the TDI-score. Finally, it can be stated that the non-smoker group exhibited the best performance in the conducted olfactory tests, closely followed by the vapers. In contrast, the consumption of cigarettes had a negative impact on the olfactory perception of smokers.

E-vapor aerosols do not compromise bone integrity relative to cigarette smoke after 6-month inhalation in an ApoE\u2013/\u2013 mouse model

Cigarette smoke (CS) exposure is one of the leading risk factors for human health. Nicotine-containing inhalable products, such as e-cigarettes, can effectively support tobacco harm reduction approaches. However, there are limited comparative data on the effects of the aerosols generated from electronic vapor products (e-vapor) and CS on bone. Here, we report the effects of e-vapor aerosols and CS on bone morphology, structure, and strength in a 6-month inhalation study. Eight-week-old ApoE–/– mice were exposed to aerosols from three different e-vapor formulations—CARRIER (propylene glycol and vegetable glycerol), BASE (CARRIER and nicotine), TEST (BASE and flavor)—to CS from 3R4F reference cigarettes at matched nicotine concentrations (35 µg/L) or to fresh air (Sham) (N = 10 per group). Tibiae were analyzed for bone morphology by µCT imaging, biomechanics by three-point bending, and by histological analysis. CS inhalation caused a significant decrease in cortical and total bone volume fraction and bone density relative to e-vapor aerosols. Additionally, CS exposure caused a decrease in ultimate load and stiffness. In contrast, bone structural and biomechanical parameters were not significantly affected by e-vapor aerosol or Sham exposure. At the dissection time point, there was no significant difference in body weight or tibia bone weight or length among the groups. Histological findings revealed microcracks in cortical bone areas among all exposed groups compared to Sham control. In conclusion, because of the bone-preserving effect of e-vapor aerosols relative to CS exposure, e-vapor products could potentially constitute less harmful alternatives to cigarettes in situations in which bone health is of importance.

Tobacco harm reduction: are smokers becoming more hardcore?

We undertook a systematic review to identify and summarise studies on hardcore smoking and hardening to: determine the degree of variability in definitions of hardcore smoking and hardening; assess the evidence for claims that smokers are becoming increasingly hardened within the context of harm reduction as a policy initiative; and identify the determining characteristics of a hardcore smoker. We searched five electronic databases from 1970 to mid-April 2018 using the search term "smok* AND hard* AND (tobacco OR cigar* OR nicotin*)". We included studies if they included a definition of hardcore smokers and/or hardening, and provided a prevalence rate for hard core smokers or empirical evidence for hardening. Definitions of hardcore smoker varied substantially across studies. Hardening was not evident in the general smoking population and we found mounting evidence of softening occurring in smoking populations. These results indicate that hardening of smokers is not occurring and that calls for policy interventions on this basis should be challenged.

Tobacco harm reduction: Past history, current controversies and a proposed approach for the future

Tobacco harm reduction remains a controversial topic in tobacco control. Tobacco harm reduction involves providing tobacco users who are unwilling or unable to quit using nicotine products with less harmful nicotine-containing products for continued use. The skepticism towards harm reduction is based in part on the experience with low-yield tar/nicotine cigarettes, which were presumed to be associated with lower health risks than higher yield cigarettes and marketed as such by cigarette manufacturers. Only later did the field learn that these cigarettes were a deceptive way for cigarette manufacturers to allay the health concerns over cigarette smoking. Since this experience, there has been a proliferation of tobacco products that might potentially serve as a means to reduce tobacco harm. Some members of the tobacco control community believe that these products have great potential to reduce mortality and morbidity among smokers who completely switch to them. Others believe that we will be addicting another generation to tobacco products. This paper reviews the past history, the current tobacco landscape and controversies, and an approach that might rapidly reduce the yearly half-million deaths associated with cigarette smoking in the U.S.

Perception of E-cigarette Use among Adult Users in China: A Mixed-method Study.

The use of electronic cigarettes (ECs) is increasing rapidly in China, but the perception of these products and their health impact among Chinese users have received little research attention. This study collected semi-structured in-depth interview data from experienced adult EC (including heated tobacco products also named ECs on the Chinese market) users in the Shanghai area. The subjects were recruited from those who participated in a previous online survey on EC use. A thematic narrative approach was used to analyze the data. Thirty current EC users were interviewed for evaluation of their perception of EC use in a variety of categories, including reasons for using, concerns, social acceptance, satisfaction, and health impacts. Participants’ common reasons for using ECs were the ease of use and carrying, hygiene, no fire hazard, reduced smoke exposure, aiding quitting smoking, reduced health hazard, palatable flavor, being fashionable, and substituting cigarettes in non-smoking areas. Most (90%; 27/30) participants reduced (77%) or quit smoking (13%) after using ECs, and 80% were willing to recommend these products to others. Most (90%) of the participants reportedly noticed positive health changes after using ECs. Regulatory concerns were expressed by 33% participants. Participants predominately viewed ECs as a viable substitute for smoking, with substantial effects on tobacco harm reduction. These findings lend support to EC use as a promising opportunity for public health promotion in China through engaging smokers in smoking cessation attempts. However, overall public health benefits/risks of EC use, and its regulatory affairs need to be considered.

E-Cigarette Use and Regular Cigarette Smoking Among Youth: Population Assessment of Tobacco and Health Study (2013–2016)

This study examines the association between current e-cigarette use at baseline and regular cigarette smoking at follow-up among U.S. youth. A longitudinal analysis of youth (aged 12-17 years) data from Waves 1-3 of the Population Assessment of Tobacco and Health Study (2013-2016) was conducted between January 2019 and December 2019. Youth who reported past-30-day current e-cigarette use at baseline were identified and followed for regular cigarette smoking (≥20 days) at follow-up. Compared with noncurrent e-cigarette users at baseline, current e-cigarette users (cigarette nonsmokers) had 5.0 (95% CI=1.9, 12.8) times higher odds of becoming regular cigarette smokers 1 year later. Additionally, there was a direct linear relationship between the number of days of e-cigarette use at baseline and the number of days of cigarette smoking 1 year later. Current e-cigarette use among U.S. youth is associated with higher odds of transitioning to regular cigarette smoking, likely reflecting robust transitions rather than experimentation. These results suggest that promoting e-cigarettes as the current practice for tobacco harm reduction will likely have the unintended consequence of initiating youth cigarette smokers.

전자담배 규제와 담배위해 감축: 미국의 정책과 시사점을 중심으로

전자담배 규제와 담배위해 감축: 미국의 정책과 시사점을 중심으로

Statistical analysis plan for “A randomised, controlled study to evaluate the effects of switching from cigarette smoking to using a tobacco heating product on health effect indicators in healthy subjects”

Tobacco harm reduction strategies aim to substitute smoking with potentially reduced risk products (PRRPs) such as e-cigarettes and tobacco-heating products (THPs). The health benefits of switching from smoking to PRRPs is unknown. A randomised controlled trial is being conducted to increase understanding of the health effects of switching from smoking to a THP in a 12-month long ambulatory study (ISRCTN81075760). Here we describe the study endpoints and the statistical analysis plan. Endpoints are divided into biomarkers of exposure (BoE) to tobacco smoke constituents and health effect indicators related to risk of lung cancer, cardiovascular and obstructive lung disease. These have been selected on the basis of extensive literature evidence. Three primary endpoints, augmentation index (risk factor for cardiovascular disease), total NNAL (linked to lung cancer) and 8-Epi-PGF2α type III (indicator of oxidative stress linked to various diseases), and multiple secondary endpoints will be analysed at 90, 180, and 360 days. Changes from baseline will be compared between study arms by specific contrasts in mixed models. Study wise multiple comparisons adjustments will be performed to account for multiplicity of timepoints and comparisons within timepoints. Generalisability of outcomes will be tested by a sensitivity analysis adjusting for age and gender. Importantly, an ancillary analysis will be performed to assess product compliance during the study based on plasma levels of CEVal, a surrogate marker for acrylonitrile exposure. The rationale underlying the selection of BoEs and health effect indicators, coupled with the statistical analysis plan will be central to understanding the potential health effects of replacing smoking with THP use for one year.

Non-inferiority trial comparing cigarette consumption, adoption rates, acceptability, tolerability, and tobacco harm reduction potential in smokers switching to Heated Tobacco Products or electronic cigarettes: Study protocol for a randomized controlled trial

BackgroundDespite the introduction of tobacco control measures, smoking remains highly prevalent in most EU countries. In Italy, one in four adults were still regular smokers in 2017. Increasing use of combustion-free delivering nicotine technologies for cigarette substitution may accelerate the current downward trends in smoking prevalence. Whether Heated Tobacco Products (HTPs) are more effective tobacco smoking substitutes that may potentially facilitate adoption and full conversion compared to e-cigarettes (ECs) is not known.We have designed a prospective study to compare changes in cigarette consumption and adoption rates among smokers randomized to either HTPs or ECs. Product acceptability, tolerability, and their tobacco harm reduction potential will be also compared. Methods220 healthy smokers, not motivated to quit, will be randomized into a 12-weeks single-center, open label, non-inferiority trial comparing study outcomes from HTPs vs. ECs use. The primary outcome will be biochemically verified self-reported continuous abstinence at 12-weeks from the previous visit. Secondary outcomes will include: smoking reduction from baseline, adoption rates and product acceptability, tolerability, changes in step test values and in the level of selected biomarkers of exposure in exhaled breath (i.e. eCO) and in spot urine samples. A follow-up visit will be also included at 24-weeks to review product usage and smoking behavior under naturalistic condition of use.Recruitment of participants started in May 2019 and enrolment is expected to be completed in November 2019. DiscussionThis will be the first study directly comparing Heated Tobacco Products with Electronic Cigarettes in term of reduction in cigarette consumption, adoption rates, product acceptability, tolerability, and tobacco harm reduction potential. This knowledge can contribute to a better understanding of the potential role of this new technology in the evolving nicotine consumer market. Trial registrationClinicalTrials.gov ID: NCT03569748.Registered June 25, 2018.https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4.

A038 Assessing the Impact of Switching to the Tobacco Heating System on Cardiovascular Disease: Translating Basic Science Into Clinical Benefit

Cigarette smoke (CS) is causally linked to the development of cardiovascular diseases (CVD). Tobacco harm reduction, by virtue of substituting cigarettes with less harmful products, is a complementary approach to current strategies for smokers who would otherwise continue to smoke. The Tobacco Heating System (THS) 2.2 is a novel tobacco product that heats tobacco instead of burning it, never allowing the temperature to exceed 350°C, thereby preventing the combustion process from occurring and producing substantially lower levels of toxicants than CS. The program includes in vitro/in vivo toxicology testing methods that follow OECD guidelines and Good Laboratory Practice, a systems toxicology approach, and randomised, controlled clinical studies that follow the principles of Good Clinical Practice. The effects of THS aerosol on the adhesion of monocytic cells to human coronary endothelial cells in vitro are significantly reduced. Switching to THS halted the progression of CS-induced atherosclerotic changes in ApoE-/- mice in vivo. Biomarkers linked to the development of smoking-related diseases were analysed following a 6-month randomised, controlled clinical study with THS, which demonstrated a consistent improvement of biomarkers in different pathophysiologic pathways leading to atherosclerosis. The evidence available to date indicates that switching to THS has the potential to reduce the risk of smoking-related diseases such as CVD.

State-of-the-art methods and devices for the generation, exposure, and collection of aerosols from heat-not-burn tobacco products

Tobacco harm reduction is increasingly recognized as a promising approach to accelerate the decline in smoking prevalence and smoking-related population harm. Potential modified risk tobacco products (MRTPs) must undergo a rigorous premarket toxicological risk assessment. The ability to reproducibly generate, collect, and use aerosols is critical for the characterization, and preclinical assessment of aerosol-based candidate MRTPs (cMRTPs), such as noncombusted cigarettes, also referred to as heated tobacco products, tobacco heating products, or heat-not-burn (HNB) tobacco products. HNB tobacco products generate a nicotine-containing aerosol by heating tobacco instead of burning it. The aerosols generated by HNB products are qualitatively and quantitatively highly different from cigarette smoke (CS). This constitutes technical and experimental challenges comparing the toxicity of HNB aerosols with CS. The methods and experimental setups that have been developed for the study of CS cannot be directly transposed to the study of HNB aerosols. Significant research efforts are dedicated to the development, characterization, and validation of experimental setups and methods suitable for HNB aerosols. They are described in this review, with a particular focus on the Tobacco Heating System version 2.2. This is intended to support further studies, the objective evaluation and verification of existing evidence, and the development of scientifically substantiated HNB MRTPs.

Combination of E-cigarettes and Varenicline for Tobacco Harm Reduction

Combination of E-cigarettes and Varenicline for Tobacco Harm Reduction

ERJ December Podcast: Tobacco harm reduction.

As part of the December issue, the European Respiratory Journal presents the latest in its series of podcasts. Chief Editor Martin Kolb interviews Jørgen Vestbo (ERS Advocacy Council Chair) about the European Respiratory Society's position on tobacco harm reduction published in this issue.

Effects of Switching to a Heat-Not-Burn Tobacco Product on Biologically Relevant Biomarkers to Assess a Candidate Modified Risk Tobacco Product: A Randomized Trial.

Cigarette smoking increases the risk of chronic diseases; heating instead of burning tobacco can lower these risks, contributing to tobacco harm reduction. This study (with 984 adult American smokers) examined whether favorable changes occur in 8 co-primary endpoints (HDL-C, WBC, FEV1%pred, COHb, Total NNAL, sICAM-1, 11-DTX-B2, 8-epi-PGF2α) indicative of biological and functional effects when cigarette smokers switch to the heat-not-burn Tobacco Heating System 2.2 (THS). Additionally, these biomarkers of exposure (BoExp) were quantified: MHBMA, 3-HPMA, Total NNN, CEMA, 3-OH-B[a]P, HMPMA, Total 1-OHP, NEQ, and CO exhaled. Participants were randomized to continued smoking of their preferred cigarette brand (n = 496) or to using THS (IQOS brand; n = 488) for 6 months. THS has a maximum heating temperature of 350°C, delivering 1.21 mg nicotine/stick and 3.94 mg glycerin/stick under the Health Canada Intense smoking regimen. The main outcome was a favorable change 6 months after baseline, with statistically significant improvements in 5 of 8 biomarkers of effect (HDL-C, WBC, FEV1%pred, COHb, Total NNAL) when smokers switched to THS compared with those who continued to smoke cigarettes. Likewise, BoExp were markedly reduced. All endpoints showed favorable changes in the same direction as with smoking cessation and improved biological effects were observed in smokers who predominantly used THS compared with continued cigarette smoking, with similar nicotine levels in both groups. Improvements in 5 of 8 biomarkers of effect are supportive of the research hypothesis, suggestive of disease risk reduction potential for smokers switching to THS instead of continuing to smoke cigarettes.

Exhaled Carbon Monoxide Levels in Forty Resistant to Cessation Male Smokers after Six Months of Full Switch to Electronic Cigarettes (e-Cigs) or to A Tobacco Heating Systems (THS).

Cigarette smoke releases several toxic chemicals and carcinogens including carbon monoxide (CO). This study examined the levels of exhaled CO in smokers switching to electronic cigarettes (e-Cigs) or a tobacco heating system (THS) and their level of compliance six months after switching. On the basis of their own preferences, 40 male smokers unwilling or unable to stop smoking were switched to e-Cigs or THSs for six months (20 subjects in each group). Nicotine addiction and levels of carbon monoxide in the exhaled breath (eCO) were measured at baseline (the latter also at six months). The Shapiro Wilk test, graphical methods, Student T test or Mann–Whitney test were used to assess the normal distribution of variables and differences between the two groups after six months. The two groups showed no difference at baseline, but a significant higher addiction score in smokers choosing THS. E-Cig and THS showed significant reduced levels of eCO (both %COHb and COppm) after six months, which were within the range of non-smoker status. Reduced levels of %COHb did not significantly differ between the two groups, whilst the THS group had a significantly lower reduction in levels of COppm vs the e-Cig group (p < 0.05). Both e-Cigs and THSs are capable of significantly reducing eCO at least in the medium term, hence constituting a viable tobacco harm reduction approach in smokers who are unwilling or unable to stop smoking.

A systematic review of the effectiveness of digital interventions for illicit substance misuse harm reduction in third-level students

BackgroundIllicit substance misuse is a growing public health problem, with misuse peaking among 18–25 year-olds, and attendance at third-level education identified as a risk factor. Illicit substance misuse has the potential to harm mental and physical health, social relationships, and impact on academic achievements and future career prospects. Digital interventions have been identified as a vehicle for reaching large student populations and circumventing the limited capacity of student health services for delivering face-to-face interventions. Digital interventions have been developed in the area of alcohol and tobacco harm reduction, reporting some effectiveness, but the evidence for the effectiveness of digital interventions targeting illicit substance misuse is lacking. This review aims to systematically identify and critically appraise studies examining the effectiveness of digital interventions for illicit substance misuse harm reduction in third-level students.MethodsWe systematically searched ten databases in April 2018 using keywords and database specific terms under the pillars of “mHealth,” “substance misuse,” and “student.” To be eligible for inclusion, papers had to present a measure of illicit substance misuse harm reduction. Included articles were critically appraised and included in the qualitative synthesis regardless of quality.ResultsA total of eight studies were included in the qualitative synthesis. Studies reported harm reduction in terms of substance misuse or initiation, as consequences or problems associated with substance misuse, or as correction of perceived social norms. Overall, five out of the eight studies reported at least one positive outcome for harm reduction. The critical appraisal indicated that the study quality was generally weak, predominantly due to a lack of blinding of study participants, and the use of self-reported substance misuse measures. However, results suggest that digital interventions may produce a modest reduction in harm from illicit substance misuse.ConclusionsThe results of this review are positive, and support the need for further high-quality research in this area, particularly given the success of digital interventions for alcohol and tobacco harm reduction. However, very few studies focused solely on illicit substances, and those that did targeted only marijuana. This suggests the need for further research on the effectiveness of this type of intervention for other illicit substances.Trial registrationThis review is registered on PROSPERO, ID number: CRD42018097203.

Application of a multi-layer systems toxicology framework for in vitro assessment of the biological effects of Classic Tobacco e-liquid and its corresponding aerosol using an e-cigarette device with MESH\u2122 technology

We previously proposed a systems toxicology framework for in vitro assessment of e-liquids. The framework starts with the first layer aimed at screening the potential toxicity of e-liquids, followed by the second layer aimed at investigating the toxicity-related mechanism of e-liquids, and finally, the third layer aimed at evaluating the toxicity-related mechanism of the corresponding aerosols. In this work, we applied this framework to assess the impact of the e-liquid MESH Classic Tobacco and its aerosol compared with that of cigarette smoke (CS) from the 3R4F reference cigarette. In the first layer, we evaluated the cytotoxicity profile of the MESH Classic Tobacco e-liquid (containing humectants, nicotine, and flavors) and its Base e-liquid (containing humectant and nicotine only) in comparison with total particulate matter (TPM) of 3R4F CS using primary bronchial epithelial cell cultures. In the second layer, the same culture model was used to explore changes in specific markers using high-content screening assays to identify potential toxicity-related mechanisms induced by the MESH Classic Tobacco and Base e-liquids beyond cell viability in comparison with the 3R4F CS TPM-induced effects. Finally, in the third layer, we compared the impact of exposure to the MESH Classic Tobacco or Base aerosols with 3R4F CS using human organotypic air–liquid interface buccal and small airway epithelial cultures. The results showed that the cytotoxicity of the MESH Classic Tobacco liquid was similar to the Base liquid but lower than 3R4F CS TPM at comparable nicotine concentrations. Relative to 3R4F CS exposure, MESH Classic Tobacco aerosol exposure did not cause tissue damage and elicited lower changes in the mRNA, microRNA, and protein markers. In the context of tobacco harm reduction strategy, the framework is suitable to assess the potential-reduced impact of electronic cigarette aerosol relative to CS.