Assessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence: A randomized controlled study in confinement.

Smoking conventional cigarettes (CCs) exposes smokers to harmful and potentially harmful constituents (HPHCs). The Tobacco Heating System 2.2 (THS 2.2), a candidate modified risk tobacco product, was developed to reduce or eliminate the formation of HPHCs, while preserving as much as possible the taste, sensory experience, nicotine delivery profile and ritual characteristics of CC. This randomized, controlled, open-label study in confinement for 5 day exposure aimed to demonstrate the reduction in exposure to selected HPHCs, to assess nicotine uptake and subjective effects, in participants switching to THS 2.2 (n = 80) compared to participants continuing smoking CCs (n = 40) and abstaining from smoking (n = 40). The subjects were randomized according to sex and daily CC consumption. The levels of biomarkers of exposure to HPHCs were significantly reduced in participants switching to THS 2.2, compared to CC use. More importantly, the magnitude of exposure reduction observed was close to that which was seen in participants who abstained from smoking for 5 days, while nicotine uptake was maintained. Reduction in urge-to-smoke was comparable between THS and CC groups, however THS 2.2 was slightly less satisfactory than CCs. The new, alternative tobacco product THS 2.2 was well tolerated.

Effect of Switching to the Tobacco Heating System Versus Continued Cigarette Smoking on Chronic Generalized Periodontitis Treatment Outcome: Protocol for a Randomized Controlled Multicenter Study.

BACKGROUND: Smoking is a significant risk factor for periodontal disease and tooth loss, as shown in several clinical studies comparing smokers and nonsmokers. Although only a few longitudinal studies have assessed the outcome of periodontal disease after smoking cessation, they indicated that recovery after nonsurgical treatment was more successful in those who had quit smoking. As part of tobacco harm reduction strategies, substituting cigarettes with alternative, less harmful tobacco products is an approach complementary to cessation for smokers who would otherwise continue to smoke. The Tobacco Heating System (THS), developed by Philip Morris International (commercialized as IQOS), is part of the heat-not-burn product category. The IQOS device electrically heats tobacco instead of burning it, at much lower temperatures than cigarettes, thereby producing substantially lower levels of harmful and potentially harmful constituents, while providing the nicotine, taste, ritual, and a sensory experience that closely parallel those of cigarettes. Phillip Morris International has published the results from a broad clinical assessment program, which was established to scientifically substantiate the harm reduction potential of the THS among adult healthy smokers switching to the THS. The program is now progressing toward including adult smokers with smoking-related diseases. OBJECTIVE: The goal of this study is to demonstrate favorable changes of periodontal endpoints in response to mechanical periodontal therapy in patients with generalized chronic periodontitis who completely switched to THS use compared with continued cigarette smoking. METHODS: This is a randomized controlled two-arm parallel-group multicenter Japanese study conducted in patients with chronic generalized periodontitis who switch from cigarettes to THS compared with smokers continuing to smoke cigarettes for 6 months. The patients were treated with mechanical periodontal therapy as per standard of care in Japan. The primary objective of the study is to demonstrate the beneficial effect of switching to THS use compared with continued cigarette smoking on pocket depth (PD) reduction in all sites with an initial PD≥4 mm. The secondary objectives include evaluation of other periodontal parameters (eg, clinical attachment level or gingival inflammation) and overall oral health status upon switching to THS. Safety was monitored throughout the study. RESULTS: In total, 172 subjects were randomized to the cigarette (n=86) or THS (n=86) groups, and all 172 completed the study. The conduct phase of the study is completed, while data cleaning and analyses are ongoing. CONCLUSIONS: This study is the first to test a heat-not-burn tobacco product in smokers with an already established disease. The results should further strengthen the evidence that switching to THS can significantly reduce the risk of smoking-related diseases if favorable changes in the evolution of chronic generalized periodontitis after mechanical therapy are found when compared with continued cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov NCT03364751; https://clinicaltrials.gov/ct2/show/NCT03364751. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15350.

Exposure to harmful and potentially harmful constituents decreased in smokers switching to Carbon-Heated Tobacco Product.

BACKGROUND: "Heat-not-burn" tobacco products are designed to heat processed tobacco instead of combusting it, thus significantly reducing the formation of harmful and potentially harmful constituents (HPHCs) found in cigarette smoke, and ultimately reducing the risk of smoking-related diseases. The Carbon-Heated Tobacco Product (CHTP), a heat-not-burn tobacco product similar in appearance and use ritual to cigarettes, has been developed for smokers who would otherwise continue smoking as an alternative to cigarettes. To evaluate reduced risk of harm potential of CHTP, it is critical to quantify exposure to HPHCs and consequent biological pathway disturbances involved in disease onset in smokers who switch to CHTP. METHODS: In this 2-arm, parallel-group study, adult healthy smokers, not willing to quit, were randomized to switch to CHTP 1.2 (n = 80) or to continue using cigarettes (n = 40) for 5 days in confinement followed by 85 days in an ambulatory setting. Endpoints included biomarkers of exposure (BoExp) to HPHCs, and to nicotine, urinary excretion of mutagenic constituents (Ames assay), CYP1A2 activity, biomarkers of effect, and safety. RESULTS: In switchers to CHTP, BoExp were 40%-95% lower compared to smokers after 5 days of product use, with sustained reductions (36%-93%) observed on Day 90. Urine mutagenicity and CYP1A2 activity were also lower in the CHTP group. Exposure to nicotine was higher in the CHTP group at Day 5, but was similar between the two groups at Day 90. Favorable changes in some biomarkers of effect were observed in the CHTP group showing reductions in white blood cell count, soluble intracellular adhesion molecule-1, and 11-dehydro-thromboxane B2, respectively, indicative of reduced inflammation, endothelial dysfunction, and platelet activation. CONCLUSIONS: Switching from cigarettes to CHTP resulted in significantly reduced exposure to HPHCs and was associated with observed improvements in some biomarkers of effect representative of pathomechanistic pathways underlying the development of smoking-related diseases.