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Smoking is a leading cause of numerous human disorders including pulmonary disease, cardiovascular disease, and cancer. Disease development is primarily caused by exposure to cigarette smoke constituents, many of which are known toxicants. Switching smokers to modified risk tobacco products (MRTPs) has been suggested as a potential means to reduce the risks of tobacco use, by reducing such exposure. This randomized, controlled study investigated whether biomarkers of toxicant exposure (BoE) were reduced when smokers switched from smoking combustible cigarettes to using a novel (glo™/THP1.0) or in-market comparator (iQOS/THS) tobacco heating product (THP). One hundred eighty Japanese smokers smoked combustible cigarettes during a 2-day baseline period, followed by randomization to either continue smoking cigarettes, switch to using mentholated or non-mentholated variants of glo™, switch to using a non-mentholated variant of iQOS, or quit nicotine and tobacco product use completely for 5 days. Baseline and post-randomization 24-h urine samples were collected for BoE analysis. Carbon monoxide was measured daily in exhaled breath (eCO). On day 5 after switching, urinary BoE (excluding for nicotine) and eCO levels were significantly (p < .05) reduced by medians between 20.9% and 92.1% compared with baseline in all groups either using glo™ or iQOS or quitting tobacco use. Between-group comparisons revealed that the reductions in the glo™ groups were similar (p > .05) to quitting in many cases. glo™ or iQOS use for 5 days reduced exposure to smoke toxicants in a manner comparable to quitting tobacco use. THPs are reduced exposure tobacco products with the potential to be MRTPs. This clinical study demonstrates that when smokers switched from smoking combustible cigarettes to using tobacco heating products their exposure to smoke toxicants was significantly decreased. In many cases, this was to the same extent as that seen when they quit smoking completely. This may indicate that these products have the potential to be reduced exposure and/or reduced risk tobacco products when used by smokers whose cigarette consumption is displaced completely. ISRCTN14301360 and UMIN000024988.

Smokers who switch completely to e-cigarettes may reduce their relative risk of tobacco-related disease. Effective nicotine delivery from e-cigarettes is important in consumer acceptance. We assessed whether protonated nicotine and e-cigarette devices delivering greater aerosol mass increase nicotine delivery and product liking. A randomised controlled non-blinded eight-arm crossover study was used to assess plasma nicotine pharmacokinetics and product liking for two e-cigarettes (Vype ePen3 and Vype ePen) with various nicotine e-liquid formulations and a conventional cigarette among 24 healthy dual-users of cigarettes and e-cigarettes. Product use and puff count were also assessed. Results show that nicotine bioavailability was greater for Vype ePen3 with greater aerosol mass delivery than for Vype ePen (C max , p  = 0.0073; AUC 0–120 min , p  = 0.0102). Protonated nicotine (18 mg/mL, medium protonation) e-liquid yielded higher nicotine bioavailability than unprotonated nicotine (18 mg/mL) e-liquid (C max , p  = 0.0001; AUC 0–120 min , p  = 0.0026). There was no significant difference in T max between e-liquids. Nicotine bioavailability did not differ between nicotine benzoate formulation (30 mg/mL nicotine, high protonation) and combustible cigarettes (C max , p  = 0.79; AUC 0–120 min , p  = 0.13). Vype ePen3 with protonated nicotine delivers nicotine more efficiently with the potential to increase product liking relative to earlier devices using unprotonated e-liquid.

Tobacco heating products (THPs) have reduced emissions of toxicants compared with cigarette smoke, and as they expose user to lower levels than smoking, have for a role to play in tobacco harm reduction. One key concern of Public Health is that new tobacco and nicotine products should not be more addictive than cigarettes. To assess their abuse liability, we determined nicotine pharmacokinetics and subjective effects of two THPs compared with conventional cigarettes and a nicotine replacement therapy (Nicotine inhaler). In a randomised, controlled, open-label, crossover study healthy adult smokers used a different study product in a 5 min ad libitum use session in each of four study periods. Product liking, overall intent to use again, urge for product and urge to smoke questionnaires were utilised to assess subjective effects. Nicotine uptake was greater for the cigarette (C max  = 22.7 ng/mL) than for either THP (8.6 and 10.5 ng/mL) and the NRT (2.3 ng/mL). Median T max was significantly longer for the NRT (15.03 min) than for the tobacco products (4.05–6.03 min). Product liking and overall intent to use again was highest for the cigarette, and higher for the THPs than the NRT. Urge to smoke was reduced more by the cigarette than by the other three products. Urge to use the THPs was greater than the NRT. These findings suggest that the abuse liability of the THPs lies between that of subjects usual brand cigarettes and the NRT.

Background Smoking is a leading cause of numerous human disorders including lung cancer, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease. The development of modified risk tobacco products (MRTPs) has been suggested as a possible way to reduce the risks of tobacco smoking by reducing exposure to cigarette smoke toxicants. This study is designed to investigate whether biomarkers of such exposure are reduced when smokers switch from smoking commercial cigarettes to using either a novel or a commercially-available tobacco heating product (THP). Design and Methods This study will assess biomarkers of exposure in current smokers who either remain smoking, switch to THP use, or quit all tobacco use completely, for 5 days. The study is an in-clinic (confinement) two-centre, randomised controlled clinical study with a forced-switching design. Subjects of either gender will be aged 23–55 years (minimum legal smoking age plus 3 years), of Japanese origin and with a verified smoking status (assessed by exhaled breath carbon monoxide and urinary cotinine levels). Subjects will have a usual brand cigarette within the International Organisation for Standardisation (ISO) tar band of 6-8 mg and will be judged to be healthy by medical history, physical examination, vital signs, electrocardiography (ECG), clinical biochemistry and lung function tests. The primary objective of this study is to assess changes within groups in selected biomarkers of exposure (BoE) and of biological effect (BoBE) after a forced switch from a commercial control cigarette to either a menthol or a non-menthol THP. Secondary objectives are to assess between-group differences, to determine nicotine pharmacokinetics for cigarettes and THPs, to assess subject’s satisfaction with the study products, and to monitor additional endpoints related to safety and product use. Discussion Data from this study will advance our scientific understanding of the changes in exposure to cigarette smoke toxicants in smokers who switch to using a THP. Trial registrations UMIN000024988 (25th November 2016); ISRCTN14301360 (14th December 2016)

The aim of this study was to investigate whether biomarkers of exposure (BoE) and potential harm (BoPH) are modified when smokers either continue to smoke or switch from smoking cigarettes to exclusive use of a tobacco heating product (THP) in an ambulatory setting over the period of a year, and to compare any changes with smokers who quit tobacco use completely and with never smokers’ biomarker levels. Participants in this year-long ambulatory study were healthy smokers with a self-reported low intent to quit assigned either to continue smoking or switch to a THP; a group of smokers with a self-reported high intent to quit who abstained from tobacco use; and a group of never smokers. Various BoE and BoPH related to oxidative stress, cardiovascular and respiratory diseases and cancer were assessed at baseline and up to 360 days. Substantial and sustained reductions in BoE levels were found at 360 days for both participants who switched from smoking to THP use and participants who quit smoking, in many cases the reductions being of a similar order for both groups. The never smoker group typically had lower levels of the measured BoEs than either of these groups, and much lower levels than participants who continued to smoke. Several BoPHs were found to change in a favourable direction (towards never smoker levels) over the year study for participants who completely switched to THP or quit, while BoPHs such as soluble intercellular adhesion molecule-1 were found to change in an unfavourable direction (away from never smoker levels) in participants who continued to smoke. Our findings, alongside chemical and toxicological studies undertaken on the THP used in this study, lead to the conclusion that smokers who would have otherwise continued to smoke and instead switch entirely to the use of this THP, will reduce their exposure to tobacco smoke toxicants and as a consequence are reasonably likely to reduce disease risks compared to those continuing to smoke.

BackgroundCigarette smoking is a well recognized cause of diseases such as lung cancer, chronic obstructive pulmonary disease and cardiovascular disease. Of the more than 5000 identified species in cigarette smoke, at least 150 have toxicological activity. For example, formaldehyde and acetaldehyde have been assigned as Group 1 and Group 2B carcinogens by IARC, and hydrogen cyanide has been identified as a respiratory and cardiovascular toxicant. Active carbon has been shown to be an effective material for the physical adsorption of many of the smoke volatile species. However, physical adsorption of acetaldehyde, formaldehyde and also hydrogen cyanide from smoke is less effective using carbon. Alternative methods for the removal of these species from cigarette smoke are therefore of interest. A macroporous, polystyrene based ion-exchange resin (Diaion®CR20) with surface amine group functionality has been investigated for its ability to react with aldehydes and HCN in an aerosol stream, and thus selectively reduce the yields of these compounds (in particular formaldehyde) in mainstream cigarette smoke.ResultsResin surface chemistry was characterized using vapour sorption, XPS, TOF-SIMS and 15N NMR. Diaion®CR20 was found to have structural characteristics indicating weak physisorption properties, but sufficient surface functionalities to selectively remove aldehydes and HCN from cigarette smoke. Using 60 mg of Diaion®CR20 in a cigarette cavity filter gave reductions in smoke formaldehyde greater than 50% (estimated to be equivalent to >80% of the formaldehyde present in the smoke vapour phase) independent of a range of flow rates. Substantial removal of HCN (>80%) and acetaldehyde (>60%) was also observed. The performance of Diaion®CR20 was found to be consistent over a test period of 6 months. The overall adsorption for the majority of smoke compounds measured appeared to follow a pseudo-first order approximation to second order kinetics.ConclusionsThis study has shown that Diaion®CR20 is a highly selective and efficient adsorbent for formaldehyde, acetaldehyde and HCN in cigarette smoke. The reductions for these compounds were greater than those achieved using an active carbon. The results also demonstrate that chemisorption can be an effective mechanism for the removal of certain vapour phase toxicants from cigarette smoke.

The aim of this study was to investigate whether biomarkers of exposure (BoE) and potential harm (BoPH) are modified when smokers switch from smoking cigarettes to exclusive use of a tobacco heating product (THP) in an ambulatory setting. Participants in this randomised, controlled study were healthy volunteer smokers assigned either to continue smoking or switch to a THP, and a control group of smokers who abstained from cigarette smoking. Various BoE and BoPH related to oxidative stress, cardiovascular and respiratory diseases, and cancer were assessed at baseline and up to 180 days. In continuing smokers, BoE and BoPH remained stable between baseline and day 180, while THP users’ levels of most BoE reduced significantly, becoming similar to those in controls abstaining from cigarette smoking. Also at 180 days, significant changes in numerous BoPH, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, 8-epi-prostaglandin F2α type III, fractional concentration of exhaled nitric oxide and white blood cell count, were directionally consistent with lessened health impact. Our findings support the notion that the deleterious health impacts of cigarette smoking may be reduced in smokers who completely switch to using THPs.

BackgroundCigarette smoke emissions are mainly produced by distillation, pyrolysis and combustion reactions when the tobacco is burnt. Some studies have shown that heating tobacco to temperatures below pyrolysis and combustion temperatures has the potential to reduce or eliminate some toxicants found in cigarette smoke. In this study, we designed a bench-top tube furnace that heats tobacco between 100-200°C and systematically studied the effects of heating temperatures on selected gas phase and aerosol phase compounds using an ISO machine-smoking protocol.ResultsAmong a list of target chemical compounds, seven toxicants (nicotine, carbon monoxide, acetaldehyde, crotonaldehyde, formaldehyde, NNN and NNK) were quantifiable but not at all temperatures examined. The levels of the compounds generally displayed an increasing trend with increasing temperatures. The observed carbon monoxide and aldehydes represented the initial thermal breakdown products from the tobacco constituents. Water was the largest measured component in the total aerosol phase collected and appeared to be mainly released by evaporation; nicotine release characteristics were consistent with bond breaking and evaporation. Quantifiable levels of NNK and NNN were thought to be the result of evaporative transfer from the tobacco blend.ConclusionsThese results demonstrate the practical utility of this tool to study low-temperature toxicant formation and emission from heated tobacco. Between 100 to 200°C, nicotine and some cigarette smoke compounds were released as a result of evaporative transfer or initial thermal decomposition from the tobacco blend.

Cigarette smoking causes serious diseases through frequent and prolonged exposure to toxicants. Technologies are being developed to reduce smokers’ toxicant exposure, including filter adsorbents, tobacco treatments and substitutes. This study examined the effect of modifications to filter ventilation, variations in cigarette circumference and active charcoal filter length and loading, as well as combinations of these features in a reduced-toxicant prototype (RTP) cigarette, on the yields of toxicants in cigarette smoke. An air-dilution mechanism, called split-tipping, was developed in which a band of porous paper in the centre of the filter tipping functions to minimise the loss of effective filter ventilation that occurs at the high flow rates encountered during human-smoking, and to facilitate the diffusional loss of volatile toxicants. As compared with conventional filter ventilation cigarettes, split-tipping reduced tar and volatile smoke constituent emissions under high flow rate machine-smoking conditions, most notably for products with a 1-mg ISO tar yield. Furthermore, mouth level exposure (MLE) to tar and nicotine was reduced among smokers of 1-mg ISO tar cigarettes in comparison to smokers of cigarettes with traditional filter ventilation. For higher ISO tar level cigarettes, however, there were no significant reductions in MLE. Smaller cigarette circumferences reduced sidestream toxicant yields and modified the balance of mainstream smoke chemistry with reduced levels of aromatic amines and benzo[a]pyrene but increased yields of formaldehyde. Smaller circumference cigarettes also had lower mainstream yields of volatile toxicants. Longer cigarette filters containing increased levels of high-activity carbon (HAC) showed reduced machine-smoking yields of volatile toxicants: with up to 97% removal for some volatile toxicants at higher HAC loadings. Split-tipping was combined with optimal filter length and cigarette circumference in an RTP cigarette that gave significantly lower mainstream (up to ~90%) and sidestream (predominately 20%–60%) smoke yields of numerous toxicants as compared with a commercial comparator cigarette under machine-smoking conditions. Significantly lower mainstream and sidestream smoke toxicant yields were observed for an RTP cigarette comprising several toxicant reducing technologies; these observations warrant further evaluation in clinical studies where real-world relevance can be tested using biomarkers of exposure and physiological effect.