Participants
Healthy smokers 18-60 years old, smoking ≥ 15 factory-made cigarettes per day (cig/day) for at least the past 10 years and not currently attempting to quit smoking or wishing to do so in the next 30 days were recruited from the local Hospital staff in Catania, Italy. None of the participants reported a history of alcohol and illicit drug use, major depression or other psychiatric conditions. We also excluded subjects who reported recent myocardial infarction, angina pectoris, high blood pressure (BP > 140 mmHg systolic and/or 90 mmHg diastolic), diabetes mellitus, severe allergies, poorly controlled asthma or other airways diseases. The study protocol was discussed with the Chair of the local institutional ERB (Comitato Etico Azienda Vittorio Emanuele) in February 2010. In consideration of the fact that e-cigarette use is a widespread phenomenon in Italy, that many e-cigarette users are enjoying them as consumer goods, that this type of product is not regulated as a drug or a drug device in Italy (end users can buy e-cig almost anywhere - internet, tobacconists, pharmacies, restaurants, and shops), and that only healthy smokers not willing to quit smoking would participate, it was felt that the study fulfilled the criteria of an observational naturalistic investigation and was exempt from the requirement from ethical approval. Participants gave written informed consent prior to participation in the study.
Study Design and Baseline Measures
Eligible participants were invited to use an ENDD ('Categoria' e-Cigarette, Arbi Group Srl, Milano, Italy) and were followed up prospectively for 6 months. They attended a total of five study visits at our smoking cessation clinic (Centro per la Prevenzione e Cura del Tabagismo (CPCT), Università di Catania, Italy): a baseline visit and four follow-up visits, (at week-4, week-8, week-12 and week-24) (Figure 2).
At baseline (study visit 1), basic demographic and a detailed smoking history were taken and individual pack-years (pack/yrs) calculated together with scoring of their level of nicotine dependence by means of Fagerstrom Test of Nicotine Dependence (FTND) questionnaire [13]. Subjective ratings of depression were assessed with the Beck Depression Inventory (BDI) [14]. Additionally, levels of carbon monoxide in exhaled breath (eCO) were measured using a portable device (Micro CO, Micro Medical Ltd, UK). Participants were given a free e-Cigarette kit containing two rechargeable batteries, a charger, and two atomizers and instructed on how to charge, activate and use the e-Cigarette. Key troubleshooting were addressed and phone numbers were supplied for both technical and medical assistance. A full 4-weeks supply of 7.4 mg nicotine cartridges ("Original" cartridges; Arbi Group Srl, Milano, Italy) was also provided and participants were trained on how to load them onto the e-Cigarette's atomizer. Random checks confirmed that the nicotine content per cartridge was 7,25 mg. Detailed toxicology and nicotine content analyses of "Original" cartridges had been carried in a laboratory certified by the Italian Institute of Health and can be found at: http://www.liaf-onlus.org/public/allegati/categoria1b.pdf
Participants were permitted to use the study product ad libitum throughout the day (up to a maximum of 4 cartridges per day, as recommended by the manufacturer) in the anticipation of reducing the number of cig/day smoked, and to fill a 4-weeks' study diary recording product use, number of any tobacco cigarettes smoked, and adverse events.
Participants were invited to came back at week-4 (study visit 2), week-8 (study visit 3), and week-12 (visit 4), a) to receive further free supply of nicotine cartridges together with the study diaries for the residual study periods, b) to record their eCO levels, and c) to give back completed study diaries and unused study products.
Study participants attended a final follow-up visit at week-24 (study visit 5) to report product use (cartridges/day) and the number of any tobacco cigarettes smoked (from which smoking reduction and smoking abstinence could be calculated), to re-check eCO levels and to rate the degree of usefulness of the study product. In particular, participants were asked to rate their level of satisfaction with the products compared to their usual cigarettes using a visual analogue scale (VAS) from 0 to 10 points (0 = being 'completely unsatisfied', 10 being = 'fully satisfied'); on the same scale, they also rated helpfulness (in keeping them from smoking) and whether they would recommend it to a friend who wanted to stop/reduce smoking. Adverse events were obtained from their study diaries.
Given the observational nature of this study, no emphasis on encouragement, motivation and reward for the smoking cessation effort were provided since this study was intended to monitor the case of a smoker (unwilling to quit) trying out an unconventional nicotine delivery device in a real world setting. Although participants were allowed to smoke their own brand of cigarette as they wished, smoking cessation services were provided to those who would spontaneously ask for assistance with quitting. These subjects were excluded from the study protocol.
Study outcome measures
The primary efficacy measure was sustained 50% reduction in the number of cig/day at week-24 from baseline (reducers) [15]; defined as sustained self-reported 50% reduction in the number of cig/day compared to baseline for the 30 days period prior to week-24 study visit (eCO levels were measured to verify smoking status and confirm a reduction compared to baseline).
A secondary efficacy measure of the study was sustained 80% reduction in the number of cig/day at week-24 from baseline (heavy reducers); defined as sustained self-reported 80% reduction in the number of cig/day compared to baseline for the 30 days period prior to week-24 study visit (eCO levels were measured to verify smoking status and confirm a reduction compared to baseline).
An additional secondary efficacy measure of the study was sustained smoking abstinence at week-24 (quitters); defined as complete self-reported abstinence from tobacco smoking (not even a puff) for the 30 days period prior to week-24 study visit (eCO levels were measured to objectively verify smoking status with an eCO concentration of ≤10 ppm).
Those smokers who failed to meet the above criteria at the final week-24 follow-up visit (study visit 5) were categorized as reduction/cessation failures (failures).
Statistical Analyses
This was a proof-of-concept pilot study, the first of its kind, hence no previous data could be used for power calculation. However, using our previous experience in smoking cessation studies, we estimated that a sample of 40 subjects would have been adequate to acquire quit/reduction rates from 70-75% of the subjects enrolled [16]. Primary and secondary outcome measures were computed by including all enrolled participants - assuming that all those individuals who were lost to follow-up are classified as failures (intention-to-treat analysis). The changes from baseline (study visit 1) in number of cig/day and in eCO levels were compared with data recorded at subsequent follow-up visits using Wilcoxon Signed rank test as these data were non-parametric. Parametric and non-parametric data were expressed as mean (± SD) and median (interquartile range (IQR)) respectively. Correlations were calculated using Spearman's Rho Correlation. Statistical methods were 2-tailed, and P values of < 0.05 were considered significant.