Reduced Exposure to Harmful and Potentially Harmful Smoke Constituents With the Tobacco Heating System 2.1.

INTRODUCTION: Heating rather than burning tobacco reduces levels of harmful and potentially harmful constituents, and consumer products using this approach aim to reduce exposure to tobacco toxicants. The Tobacco Heating System (THS) version 2.1 has been enhanced from earlier prototypes with an improved heat control and sensorial experience and thereby user acceptance. Exposure measurements are required to determine whether it may be possible to reduce the individual health risk compared to smoking combustible cigarettes (CCs). METHODS: This controlled clinical study randomly assigned 40 smokers to either a group continuing to use of their own CC brand (n = 20) or a group switching to THS 2.1 (n = 20) for 5 days. Biomarkers of exposure were measured at baseline and on day 1 through day 5. Product consumption, Human Puffing Topography, the occurrence of adverse events, and an assessment of subjective effects, such as smoking satisfaction and enjoyment of respiratory tract sensations, were also determined. RESULTS: The group of smokers who switched to THS 2.1 adapted their puffing behavior initially through longer puff duration and more puffs. During the duration of the study, total puff volume returned to baseline levels and the mean daily product consumption increased but with similar nicotine exposure compared to baseline CC use. Biomarkers of exposure to tobacco smoke toxicants which inform product risk assessment were significantly reduced with THS use compared to the CC group. THS 2.1 users experienced less reinforcing effects with THS 2.1 than with their own cigarette brand. CONCLUSIONS: THS 2.1 is a promising alternative to smoking CCs. Notwithstanding possible use adaption through consumption or puffing behavior, the exposure to harmful smoke constituents was markedly reduced with the new heated tobacco platform. IMPLICATIONS: Exposure markers to harmful and potentially harmful smoke constituents were lowered with the THS 2.1. Heating tobacco instead of burning can offer a potentially lower risk of delivering nicotine compared to CCs.

Evaluation of Biomarkers of Exposure in Smokers Switching to a Carbon-Heated Tobacco Product: A Controlled, Randomized, Open-Label 5-Day Exposure Study.

INTRODUCTION: Tobacco harm reduction aims to provide reduced risk alternatives to adult smokers who would otherwise continue smoking combustible cigarettes (CCs). This randomized, open-label, three-arm, parallel-group, single-center, short-term confinement study aimed to investigate the effects of exposure to selected harmful and potentially harmful constituents (HPHCs) of cigarette smoke in adult smokers who switched to a carbon-heated tobacco product (CHTP) compared with adult smokers who continued to smoke CCs and those who abstained from smoking for 5 days. METHODS: Biomarkers of exposure to HPHCs, including nicotine and urinary excretion of mutagenic material, were measured in 24-hour urine and blood samples in 112 male and female Caucasian smokers switching from CCs to the CHTP ad libitum use. Puffing topography was assessed during product use. RESULTS: Switching to the CHTP or smoking abstinence (SA) resulted in marked decreases from baseline to Day 5 in all biomarkers of exposure measured, including carboxyhemoglobin (43% and 55% decrease in the CHTP and SA groups, respectively). The urinary excretion of mutagenic material was also markedly decreased on Day 5 compared with baseline (89% and 87% decrease in the CHTP and SA groups, respectively). No changes in biomarkers of exposure to HPHCs or urinary mutagenic material were observed between baseline and Day 5 in the CC group. CONCLUSIONS: Our results provide clear evidence supporting a reduction in the level of exposure to HPHCs of tobacco smoke in smokers who switch to CHTP under controlled conditions, similar to that observed in SA. IMPLICATIONS: The reductions observed in biomarkers of exposure to HPHCs of tobacco smoke in this short-term study could potentially also reduce the incidence of cancer, cardiovascular and respiratory diseases in those smokers who switch to a heated tobacco product.

A Japanese cross-sectional multicentre study of biomarkers associated with cardiovascular disease in smokers and non-smokers.

We performed a cross-sectional, multicentre study in Japan to detect the differences in biomarkers of exposure and cardiovascular biomarkers between smokers and non-smokers. Several clinically relevant cardiovascular biomarkers differed significantly between smokers and non-smokers, including lipid metabolism (high-density lipoprotein cholesterol concentrations - lower in smokers), inflammation (fibrinogen and white blood cell count - both higher in smokers), oxidative stress (8-epi-prostaglandin F2α - higher in smokers) and platelet activation (11-dehydro-thromboxane B2 - higher in smokers) (p ≤ 0.0001). These results provide further evidence showing that cardiovascular biomarkers can discriminate smokers from non-smokers, and could be used to evaluate the risks associated with tobacco products.

Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 7: A one-month, randomized, ambulatory, controlled clinical study in Poland.

This randomized, open-label, ambulatory, controlled clinical study investigated biomarkers associated with cardiovascular risk and biomarkers of exposure to 10 selected harmful and potentially harmful constituents (HPHC) in cigarette smoke in 316 male and female Polish smokers. Subjects were randomized to continue smoking conventional cigarettes (CC; N=79) or switch to smoking the Electrically Heated Cigarette Smoking System series-K cigarette (EHCSS-K6; N=237). Biomarker assessments were performed at several time points during the study at baseline and during the 1-month investigational period. The primary biomarkers were high-sensitivity C-reactive protein and white blood cell counts. No statistically significant differences in the two primary biomarkers were found between the study groups at the end of the study. End-of-study comparisons of secondary biomarkers between study groups indicated an increase in high-density lipoprotein cholesterol, and reductions in red blood cell count, hemoglobin, and hematocrit levels in the EHCSS-K6 group. All biomarkers of exposure to cigarette smoke HPHC were decreased in the EHCSS-K6 group, despite an increase in cigarette consumption, compared to the CC group. There were no apparent differences in any of the safety assessment parameters between the groups, and the overall incidence of study-related adverse events was low.

The efficacy and safety of low-dose diclofenac sodium 0.1% gel for the symptomatic relief of pain and erythema associated with superficial natural sunburn.

A randomised, double-blind, single-centre, vehicle-controlled clinical trial was conducted to assess the efficacy and tolerability of diclofenac-Na 0.1% gel in 172 subjects suffering from acute first-degree natural sunburn. Overall 172 subjects with skin phototypes II-IV were randomised in a ratio of 2:1 to receive two applications of either diclofenac-Na 0.1% Emulgel gel or its vehicle Emulgel gel, 6 and 10 hours after the end of sun exposure. Subjects were drawn from a target population of healthy volunteers and well outdoor sunbathers with normal tolerance to ultraviolet light and the sun. Previously untanned areas were exposed to carefully determined standardised doses of sun (2.8 individual minimal erythema doses) on 15% body surface area to induce first-degree sunburn. After administration of diclofenac-Na 0.1% gel, subjects reported a significant reduction in spontaneous pain intensity compared with those on vehicle. Pain relief was rapid with a reduction in erythema, which was apparent within the first few hours after the first application of the trial medication with a maximum effect observed up to 30 hours after sun exposure. A good', very good', or excellent' cooling effect was recorded by 85% of subjects after treatment. Reported treatment-emergent adverse effects were infrequent, generally mild and none were considered to be related to the trial medication. Only one severe treatment emergent adverse event (abdominal pain) was recorded in the active group, and another (burning sensation) with vehicle.