Comparing the Effectiveness, Tolerability, and Acceptability of Heated Tobacco Products and Refillable Electronic Cigarettes for Cigarette Substitution (CEASEFIRE): Randomized Controlled Trial.

BACKGROUND: People who smoke and who face challenges trying to quit or wish to continue to smoke may benefit by switching from traditional cigarettes to noncombustible nicotine delivery alternatives, such as heated tobacco products (HTPs) and electronic cigarettes (ECs). HTPs and ECs are being increasingly used to quit smoking, but there are limited data about their effectiveness. OBJECTIVE: We conducted the first randomized controlled trial comparing quit rates between HTPs and ECs among people who smoke and do not intend to quit. METHODS: We conducted a 12-week randomized noninferiority switching trial to compare effectiveness, tolerability, and product satisfaction between HTPs (IQOS 2.4 Plus) and refillable ECs (JustFog Q16) among people who do not intend to quit. The cessation intervention included motivational counseling. The primary endpoint of the study was the carbon monoxide-confirmed continuous abstinence rate from week 4 to week 12 (CAR weeks 4-12). The secondary endpoints included the continuous self-reported ≥50% reduction in cigarette consumption rate (continuous reduction rate) from week 4 to week 12 (CRR weeks 4-12) and 7-day point prevalence of smoking abstinence. RESULTS: A total of 211 participants completed the study. High quit rates (CAR weeks 4-12) of 39.1% (43/110) and 30.8% (33/107) were observed for IQOS-HTP and JustFog-EC, respectively. The between-group difference for the CAR weeks 4-12 was not significant (P=.20). The CRR weeks 4-12 values for IQOS-HTP and JustFog-EC were 46.4% (51/110) and 39.3% (42/107), respectively, and the between-group difference was not significant (P=.24). At week 12, the 7-day point prevalence of smoking abstinence values for IQOS-HTP and JustFog-EC were 54.5% (60/110) and 41.1% (44/107), respectively. The most frequent adverse events were cough and reduced physical fitness. Both study products elicited a moderately pleasant user experience, and the between-group difference was not significant. A clinically relevant improvement in exercise tolerance was observed after switching to the combustion-free products under investigation. Risk perception for conventional cigarettes was consistently higher than that for the combustion-free study products under investigation. CONCLUSIONS: Switching to HTPs elicited a marked reduction in cigarette consumption among people who smoke and do not intend to quit, which was comparable to refillable ECs. User experience and risk perception were similar between the HTPs and ECs under investigation. HTPs may be a useful addition to the arsenal of reduced-risk alternatives for tobacco cigarettes and may contribute to smoking cessation. However, longer follow-up studies are required to confirm significant and prolonged abstinence from smoking and to determine whether our results can be generalized outside smoking cessation services offering high levels of support. TRIAL REGISTRATION: ClinicalTrials.gov NCT03569748; https://clinicaltrials.gov/ct2/show/NCT03569748.

Saccharin test: Methodological validation and systematic review of the literature.

OBJECTIVES: Saccharin test (ST) is a convenient method to assess the efficiency of mucociliary clearance, the primary defense mechanism of the upper airways' tract. The study objectives are to: (1) substantiate its short- (3 days) and long-term (30 days) repeatability; (2) assess its tolerability; (3) conduct a systematic literature review and to compare our results with the existing evidence. METHODS: Twenty-nine healthy subjects were enrolled in an observational prospective study to perform an ST on three separate visits (at baseline; at follow-up visits at day 3 and at day 30). Transit times were recorded and self-reported nasal and general symptoms noted. A systematic review of the literature was conducted to compare our results with the existing literature. RESULTS: The mean values (±SD) of ST transit time (STTT) were 7.085 (±2.19), 7.788 (±2.11), and 7.790 (±2.06) minutes at baseline, day 3, and day 30, respectively. Significant linear regression analysis was observed between day 3 and baseline (r = .193; P = .019) and day 30 and baseline (r = .182 P = .024). Significant agreement for the intrasession repeatability was observed with an ICC = .354 (P = .001). Outcomes' comparisons between baseline vs day 3 (P = .197) and baseline vs day 30 (P = .173) were not statistically significant. ST was well tolerated. Concordance with existing literature's data and high level of STTT repeatability were confirmed by the qualitative analysis. CONCLUSION: STTT reproducibility was good both in the short- and long-term. ST tolerability was very good. Our study data are consistent with the existing literature, indicating ST as a sound methodology for detection of early respiratory health changes and for specific regulatory application in respiratory research.

Short and Long Term Repeatability of Saccharin Transit Time in Current, Former, and Never Smokers.

Smoking progressively damages the efficiency of mucociliary clearance (MCC) defense mechanisms, thus contributing to increased susceptibility to respiratory infections. Prolonged mucociliary clearance transit time (MCCTT) caused by chronic smoking has been investigated by saccharin test, but little data is available about its short- and long-term reproducibility. Moreover, it is not known if MCC impairment can be reversed when stopping smoking. Objective of the study is to investigate and compare short (3 days) and long term (30 days) repeatability of baseline saccharin transit time (STT) among current, former, and never smokers. STT results were analyzed in 39 current, 40 former, and 40 never smokers. Significant (p < 0.0001) short-term and long-term repeatability of STT were observed in current (R squared = 0.398 and 0.672, for short- and long-term, respectively) and former smokers (R squared = 0.714 and 0.595, for short- and long-term, respectively). Significant differences in MCCTT were observed among the three study groups (p < 0.0001); the median (IQR) MCCTT being 13.15 (10.24-17.25), 7.26 (6.18-9.17), and 7.24 (5.73-8.73) minutes for current, former and never smokers, respectively. Comparison between current smokers and former smokers was significantly different (p < 0.0001). There was no significant difference between former and never smokers. The Saccharin test was well tolerated by all participants. We have shown for the first time high level repeatability in both current and former smokers. Moreover, MCC impairment can be completely reversed, former smokers exhibiting similar STT as never smokers. Measurement of STT is a sensitive biomarker of physiological effect for the detection of early respiratory health changes and may be useful for clinical research.

Smoking behavior and psychological dynamics during COVID-19 social distancing and stay-at-home policies: A survey.

During the COVID-19 pandemic, about 60 million of Italians stayed at home. These circumstances may generate exceptional challenges and stress for people who regularly use cigarettes, ecigarettes, heated tobacco products, dual users, former smokers and never smokers. Here, we present results from a study that was aimed at surveying smoking behaviour and psychological dynamics during the Italian COVID-19 social distancing and stay-at-home policies. Participants living in Italy were invited to complete an online brief questionnaire. A questionnaire was prepared and uploaded in an online survey tool. They were asked to participate regardless of their current smoking status and were divided in seven subgroups. In total, 1825 participants were included in the analysis. Exclusive cigarette smokers; Dual users of cigarette and ecigarettes; Dual users of cigarette and heated tobacco products; Former smokers; Exclusive users of e-cigarette; Exclusive users of heated tobacco products; never smoker. Dual users of cigarette and e-cigarette and exclusive cigarette smokers perceived that their daily consumption has slightly decreased. Exclusive cigarette smokers and exclusive e-cigarette users changed the way of purchasing products. Most exclusive cigarette smokers have considered quitting but most exclusive e-cigarette users have not considered stopping the use of e-cigarettes. In former smokers' group, about one third of participants declared thoughts about starting to smoke again and in never smokers' group few participants declared intention to start smoking. The COVID-19 era could be considered a "transition" phase and as such requires a search for a new balance. These changes in everyday habits can be a significant moment to use established and emerging strategies to create a definitive smoke-free world.

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.

BACKGROUND: Despite 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. METHODS: 220 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. DISCUSSION: This 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 REGISTRATION: ClinicalTrials.gov ID: NCT03569748.Registered June 25, 2018.https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4.

[Electronic cigarette: current overview and future perspectives]. / Sigaretta elettronica: panoramica attuale e prospettive future.

Electronic cigarettes (e-cigs) are experiencing a great popularity and their market has surprisingly grown in a few years. However, the rapidly evolving phenomenon is raising concerns about the safety and efficacy of these products. Opinions and information from the popular press, but also from the scientific community, are often divergent, confused, warning and sometimes purposely false, raising inconsistent doubts and disproportionate concerns for the public health. This can be easily overcome by the application of rational, plausible, evidence-based regulations for e-cigs. In this short article, we will consider the doubts, evaluate the evidence and formulate some proposals for a more equitable and balanced regulation of these products.