Heat-not-burn Tobacco Research Articles

Heat-not-burn tobacco products and cardiovascular risk reduction: A systematic review of randomized controlled trials.

Heat-not-burn (HNB) technology by the U.S. Food and Drug Administration has been classified as a modified risk tobacco product, which can be a better option for those populations who cannot give up the habit of smoking. The outlook on the effects of these products is quite controversial in the scientific world. To present the effect of HNB tobacco products on the cardiovascular system, with reference to the existence of possible benefits of the technology. The literature search was conducted in PubMed/Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases, with reliance on a well-defined guiding research statement. Quality appraisal was performed using the CASP checklist for randomized controlled trials. The search of three databases identified 167 records, and after selection process, 25 randomized controlled trials were eligible for our study's criteria. Twenty studies investigated the effects of HNB products on biomarkers of clinical relevance. Five studies evaluated other functional heart parameters rather than biomarkers. With HNB tobacco products, significant reductions were found in biomarkers of exposure and biological effect related to pathways involved in cardiovascular disease, including inflammation, oxidative stress, lipid metabolism, platelet function, and endothelial dysfunction.

Toxic mechanisms of cigarette smoke and heat-not-burn tobacco vapor inhalation on rheumatoid arthritis

Tobacco combustion exposure worsens rheumatoid arthritis (RA). Non-combustible tobacco devices, as heat-not-burn tobacco (HNBT), are emerging as harm reduction to smokers by releasing nicotine and lower combustible tobacco products. Nevertheless, HNBT toxicity remains unclear. Hence, here we investigated the impacts of the tobacco combustible product (cigarette smoke; CS) or HNBT vapor exposures on antigen-induced arthritis (AIA) in C57BL/6 mice. Animals were exposed to airflow, HNBT vapor, or CS during 1 h/twice a day, under the Health Canada Intense (HCI) smoking regime, between days 14 to 20 after the first immunization. At day 21, 16 h after the last exposures, mice were i.a. challenged and the AIA effects were evaluated 24 h later. CS- or HNBT-exposed mice presented equivalent blood nicotine levels. CS exposure worsened articular symptoms, pulmonary inflammation, and expression of lung metallothioneins. Nevertheless, CS or HNBT exposures reduced lymphoid organs' cellularity, splenocyte proliferation and IL-2 secretion. Additional in vitro CS or HNBT exposures confirmed the harmful effects on splenocytes, which were partially mediated by the activation of nicotine/α7nAchR pathway. Associated, data demonstrate the toxic mechanisms of CS or HNBT inhalation at HCI regime on RA, and highlight that further investigations are fundamental to assure the toxicity of emerging tobacco products on the immune system during specific challenges.

Exposure of heat-not-burn tobacco effect on the quality of air and expiratory plume

The increasing interest to avoid the consumption of regular tobacco has lead in the development of several types of devices to decrease the effects of this practice on active and bystanders. In this work, the impact of the use of new heat-not-burn (HnB) devices has been evaluated and compared with that of regular cigarettes and electronic cigarettes (e-cigs). Portable monitoring devices were employed for CO, CO2, particulate matter (PM) and volatile organic compounds (VOCs) to evaluate the quality of indoor air and expiratory plume of both, active and passive, users during these practices. It can be noticed that the levels of VOCs in active HnB smokers expiratory air are five times lower in particular cases than those provided by regular tobacco and three times lower than those obtained for e-cigs, while the contribution of particulate matter to air pollution decreases between 200 and 600 times regarding the values obtained for e-cig vaping and regular tobacco smoking. The level of contaminants as CO decreases significantly in both, active and passive HnB smokers, in comparison with active and passive regular tobacco smokers, due to the absence of organic material combustion.Regarding passive HnB smokers, the exposure to HnB smoke do not increases the level of VOCs in ambient air nor in expiratory plume, remaining at the basal levels, being three times lower than values obtained to an exposure to regular tobacco smoke and two times lower than exposure to e-cigs vapours. On the other hand, the use of HnB devices decreases the concentration of PM in bystanders around thirty five times in relation with values obtained for passive regular tobacco smokers. Concerning the nicotine content delivered by HnB tobacco, data shown that HnB tobacco provides values from 0.5 to 1.7 mg of nicotine to the mainstream, being these values similar to those found in conventional tobacco.

Fabrication and Properties of Electrospun and Electrosprayed Polyethylene Glycol/Polylactic Acid (PEG/PLA) Films

Polylactic acid (PLA) film is an alternative filter material for heat-not-burn (HNB) tobacco, but its controllability in cooling performance is limited. In this work, polyethylene glycol (PEG) was introduced to form a polyethylene glycol/polylactic acid (PEG/PLA) film by electrospinning or electrospraying techniques to enhance the cooling performance, due to its lower glass transition and melting temperatures. The PEG/PLA films with typical electrospun or electrosprayed morphologies were successfully fabricated. One typical endothermic peak at approximately 65 °C was clearly observed for the melting PEG phase in the heating process, and the re-crystallization temperature represented by an exothermic peak was effectively lowered to 90–110 °C during the cooling process, indicating that the cooling performance is greatly enhanced by the introduction of the PEG phase. Additionally, the wetting properties and adsorption properties were also intensively studied by characterizing the contact angles, and the as-prepared PEG/PLA films all showed good affinity to water, 1,2-propandiol and triglyceride. Furthermore, the PEG/PLA film with a PLA content of 35 wt.% revealed the largest elasticity modulus of 378.3 ± 68.5 MPa and tensile strength of 10.5 ± 1.1 MPa. The results achieved in this study can guide the development of other filter materials for HNB tobacco application.

Ceramide ratios are affected by cigarette smoke but not heat-not-burn or e-vapor aerosols across four independent mouse studies

AimsSmoking is an important risk factor for the development of chronic obstructive pulmonary disease and cardiovascular diseases. This study aimed to further elucidate the role of ceramides, as a key lipid class dysregulated in disease states. Main methodsIn this article we developed and validated LC–MS/MS method for ceramides (Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1(15Z)) for the absolute quantification. We deployed it together with proteomics and transcriptomic analysis to assess the effects of cigarette smoke (CS) from the reference cigarette as well as aerosols from heat-not-burn (HnB) tobacco and e-vapor products in apolipoprotein E-deficient (ApoE−/−) mice over several time points. Key findingsIn the lungs, CS exposure substantially elevated the ratios of Cer(d18:1/24:0) and Cer(d18:1/24:1) to Cer(d18:1/18:0) in two independent ApoE−/− mouse inhalation studies. Data from previous studies, in both ApoE−/− and wild-type mice, further confirmed the reproducibility of this finding. Elevation of these ceramide ratios was also observed in plasma/serum, the liver, and—for the Cer(d18:1/24:1(15Z)) to Cer(d18:1/18:0) ratio—the abdominal aorta. Also, the levels of acid ceramidase (Asah1) and glucocerebrosidase (Gba)—lysosomal enzymes involved in the hydrolysis of glucosylceramides—were consistently elevated in the lungs after CS exposure. In contrast, exposure to HnB tobacco product and e-vapor aerosols did not induce significant changes in the ceramide profiles or associated enzymes. SignificanceOur work in mice contributes to the accumulating evidence on the importance of ceramide ratios as biologically relevant markers for respiratory disorders, adding to their already demonstrated role in cardiovascular disease risk assessment in humans.

Passive Exposure to Pollutants from a New Generation of Cigarettes in Real Life Scenarios.

The use of electronic cigarettes (e-cigarettes) and heat-not-burn tobacco (HNBT), as popular nicotine delivery systems (NDS), has increased among adult demographics. This study aims to assess the effects on indoor air quality of traditional tobacco cigarettes (TCs) and new smoking alternatives, to determine the differences between their potential impacts on human health. Measurements of particulate matter (PM1, PM2.5 and PM10), black carbon, carbon monoxide (CO) and carbon dioxide (CO2) were performed in two real life scenarios, in the home and in the car. The results indicated that the particle emissions from the different NDS devices were significantly different. In the home and car, the use of TCs resulted in higher PM10 and ultrafine particle concentrations than when e-cigarettes were smoked, while the lowest concentrations were associated with HNBT. As black carbon and CO are released by combustion processes, the concentrations of these two pollutants were significantly lower for e-cigarettes and HNBT because no combustion occurs when they are smoked. CO2 showed no increase directly associated with the NDS but a trend linked to a higher respiration rate connected with smoking. The results showed that although the levels of pollutants emitted by e-cigarettes and HNBT are substantially lower compared to those from TCs, the new smoking devices are still a source of indoor air pollutants.

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.

Association of alcohol and drug use with use of electronic cigarettes and heat-not-burn tobacco products among Korean adolescents

BackgroundThe tobacco industry has aggressively introduced new and diverse products in the market, including electronic cigarettes (e-cigarettes) and heat-not-burn (HNB) tobacco products, to which adolescents are readily susceptible. Conventional cigarettes have a well-established relationship with adolescent risky behaviors such as alcohol and drug use; however, no studies exist on the association between alcohol consumption and use of e-cigarettes or HNB tobacco products among Korean adolescents. This study evaluated alcohol-related behaviors and drug use in relation to whether a Korean nationally representative adolescent sample had ever used e-cigarettes and HNB tobacco products.MethodsData from the 2018 Korean Youth Risk Behavior Web-based Survey were analyzed. The final study sample comprised 60,040 adolescents. Chi-square and logistic regression were used to examine whether the ever having used e-cigarettes and HNB tobacco products was associated with alcohol-related behaviors and drug use. P-values for trends were calculated to examine the dose-response relationship for each variable.ResultsRespondents with higher drinking frequency, drinking quantity, alcohol intoxication, alcohol availability, and drug use were more likely to report having used e-cigarettes and HNB tobacco products, thus implying a significant relationship between substance use and novel tobacco product (P < .001).ConclusionsOur findings suggest that at-risk adolescents who are engaged in other forms of risk-taking behaviors are prone to attract the experimentation with e-cigarettes or HNB tobacco products. Thus, smoking cessation programs related to substance use should be implemented, and there is an urgent need to monitor and regulate these products effectively.

Heat-Not-Burn Tobacco Products: The Devil in Disguise or a Considerable Risk Reduction?

Background: Heat-not-burn (HNB) tobacco products are not burnt but instead are inserted into a tobacco-heating system, which heats the tobacco at temperatures below that required to initiate combustion. This mechanism potentially results in significantly reduced concentrations of heat-generated toxicants in the inhalable aerosol.Method: The margin of exposure (MOE) approach was applied for quantitative risk assessment. The MOE is defined as the ratio between the toxicological threshold and the estimated human intake of the same compound. The higher the MOE, the lower the risk of a compound.Findings: The MOEs were increased by factors of 3 to 415 for the most toxic compounds in tobacco smoke, comparing use of HNB with smoking conventional tobacco products. The combined MOE for all compounds was increased 23-fold, excluding nicotine, or 10-fold including nicotine. Thus, the overall risk for cumulative toxic effects was markedly lower for HNB products.Conclusions: HNB tobacco reduced the risk of exposure to 9 out of the 20 most toxic compounds in tobacco beyond an MOE threshold of 10,000. While our results show that use of HNB products leads to a considerable risk reduction compared to conventional tobacco, the products cannot be considered completely “risk-free” due to risk of exposure to the remaining toxicants with MOE below the threshold.

Heat-Not-Burn Tobacco Products: The Devil in Disguise or a Considerable Risk Reduction?

Background: Heat-not-burn (HNB) tobacco products are not burnt but instead are inserted into a tobacco-heating system, which heats the tobacco at temperatures below that required to initiate combustion. This mechanism potentially results in significantly reduced concentrations of heat-generated toxicants in the inhalable aerosol.Method: The margin of exposure (MOE) approach was applied for quantitative risk assessment. The MOE is defined as the ratio between the toxicological threshold and the estimated human intake of the same compound. The higher the MOE, the lower the risk of a compound.Findings: The MOEs were increased by factors of 3 to 415 for the most toxic compounds in tobacco smoke, comparing use of HNB with smoking conventional tobacco products. The combined MOE for all compounds was increased 23-fold, excluding nicotine, or 10-fold including nicotine. Thus, the overall risk for cumulative toxic effects was markedly lower for HNB products.Conclusions: HNB tobacco reduced the risk of exposure to 9 out of the 20 most toxic compounds in tobacco beyond an MOE threshold of 10,000. While our results show that use of HNB products leads to a considerable risk reduction compared to conventional tobacco, the products cannot be considered completely “risk-free” due to risk of exposure to the remaining toxicants with MOE below the threshold.

Chemical Analysis and Simulated Pyrolysis of Tobacco Heating System 2.2 Compared to Conventional Cigarettes.

Tobacco Heating System 2.2 (THS 2.2, marketed as iQOS) is a heat-not-burn (HNB) tobacco product that has been successfully introduced to global markets. Despite its expanding market, few independent and systematic researches into THS 2.2 have been carried out to date. We tested a comprehensive list of total particulate matter (TPM), water, tar, nicotine, propylene glycol, glycerin, carbon monoxide, volatile organic compounds, aromatic amines, hydrogen cyanide, ammonia, N-nitrosamines, phenol, and polycyclic aromatic hydrocarbon under both ISO and HCI regimes. We also simulated pyrolysis of THS 2.2 heating sticks and made comparisons with conventional cigarette tobacco fillers using comprehensive gas chromatography-mass spectrometry (GC × GC-MS) to determine whether the specially designed ingredients help reduce harmful constituents. Other than some carbonyls, ammonia, and N-nitrosoanabasine (NAB), the delivered releases from THS 2.2 were at least 80% lower than those from 3R4F. Tar and nicotine remained almost the same as 3R4F. Interestingly, the normalized yield of THS 2.2 to 3R4F under the HCI regime was lower than that under the ISO regime. THS 2.2 delivered fewer harmful constituents than the conventional cigarette 3R4F. Simulated pyrolysis results showed that the lower temperature instead of specially designed ingredients contributed to the distinct shift. In particular, if smoking machines are involved to evaluate the HNB products, smoking regimes of heat-not-burn tobacco products should be carefully chosen. To our knowledge, few independent studies of HNB products have been published. In this paper, a comprehensive list of chemical releases was tested systematically and compared to those from 3R4F. Although THS 2.2 generates lower levels of harmful constituents, the nicotine and tar levels were almost identical to 3R4F.The results should be discussed carefully in the future when assessing the dual-use with other conventional cigarettes, nicotine dependence of HNB products, etc. This study also suggests that regulatory agencies should pay attention to the smoking regimes that are adopted to evaluate HNB tobacco products.

Heat-not-Burn Tobacco Products: Tobacco Industry Claims No Substitute for Science.

* Abbreviations: FDA — : US Food and Drug Administration HNB — : heat-not-burn IQOS — : I Quit Ordinary Smoking In the wake of the rapid rise of e-cigarettes over the past decade, the tobacco industry has launched its latest response to the documented harms of cigarette smoking: heat-not-burn (HNB) tobacco products. Philip Morris International created and is heavily marketing their version of these products, called the IQOS (I Quit Ordinary Smoking), which involves disposable tobacco sticks soaked in propylene glycol that are inserted into a holder in the HNB cigarette. Philip Morris markets these products as being “designed to create a flavorful and satisfying nicotine-containing vapor, without burning and without smoke.”1 Advertisements claim this product releases no smoke because the tobacco leaves are heated rather than burned, with no tobacco combustion. Claims and distracting wording, however, are no substitute for science. The authors of a recent report have shown that these tobacco products release cancer-causing chemicals.2 The IQOS is not yet sold in the United States, but in December 2016, Philip Morris submitted a modified risk tobacco product application to the US Food and Drug Administration (FDA). If its application is successful, Philip Morris will face looser restrictions in marketing HNB tobacco products than it does for conventional tobacco cigarettes. Moreover, Philip Morris seeks to make affirmative safety statements on packaging and advertising for IQOS, including “Scientific studies have shown that switching completely from conventional cigarettes to the IQOS system can reduce the risks of tobacco-related diseases.”3 … Address correspondence to Brian P. Jenssen, MD, MSHP, Department of Pediatrics, PolicyLab, The Children’s Hospital of Philadelphia, 2716 South St, Philadelphia, PA 19146. E-mail: jenssenb{at}email.chop.edu