Study on assisted use of electronic cigarette (e-cig) concerning reduction of healthrelated harm associated with tobacco addiction

Transcription

1 Study on assisted use of electronic cigarette (e-cig) concerning reduction of healthrelated harm associated with tobacco addiction Responsible for ISS Dr.ssa Roberta Pacifici Responsible for ASL TO2 Dr. Fabio Beatrice Reply of the Ethics Committee of ISS Prot. PRE 165/14 Prot. CE 14/418

2 SMOKING IN ITALY ( Source: Doxa- Iss 2014 ) Total Italian population ( aged over 15 ) : 51,3 millions SMOKERS: 11,3 MILLIONS ( 22%) EX-SMOKERS: 6,6 MILLONS ( 12,8%) NON-SMOKERS: 33,4 MILLONS (65,2%)

3 ANTI-SMOKING CENTERS IN ITALY By Pucchio A. et Al. Tabaccology 1:26-29, : 284 centers surveyed by ISS in Italy in smokers treated ( treated / smokers = % less than 1%! )

4 THE ISSUE ON HOW TO ACHIEVE SMOKERS POSES MANY QUESTIONS TO THE MEDICAL COMMUNITY.

5 RATIONAL Primary Objective This study proposes to show that the use of electronic cigarette, if supported and managed in a healthcare environment by a Team able to sustain and assist the smoker, is an useful means of reduction of damage to the respiratory system, with smokers that do not want to give up smoking, but wish to improve their health status.

6 Secondary objectives Monitoring of side effects associated with use of electronic cigarette. Monitoring of relapses. Expected benefits Persuading subjects «resistant» to cessation or unwilling to give up smoking to use the e-cig, in order to make them keep up the use of a device according to the principle of damage reduction. Observation Observation and objectification of smokers behaviour, by means of a comparison between clinical conditions and serological/urinary tests in a months follow up.

7 MATERIALS AND METHODS

8 THE RECRUITMENT OF SMOKERS Male and female aged between 35 and 60 years, smoking more than 15 cigarettes a day. These smokers are not interested in giving up smoking for various reasons. 34 individuals recruited. For each smoker we consider: real number of cigarettes smoked per day, the brand of the cigarette, the daily rate of nicotine absorbed, type and frequency of sport activities, weight, height and any pathology. SEX N AGE NIC/DAY CIG/DAY CO START MASCHI 18 40,72 0,67 21,11 2,43 FEMMINE 16 40,56 0,66 21,87 2,80

9 DEVICE AND LIQUIDS

10 WE HAVE PROPOSED TO ALL RECRUITED SMOKERS THE USE OF ELECTRONIC CIGARETTE INSTEAD OF TRADITIONAL TOBACCO.THE HEALTHCARE TEAM PROVIDED THE PARTICIPANTS WITH A COMPLETE ELECTRONIC DEVICE, THE CHARGERS AND A SELECTION OF LIQUIDS WITH NICOTINE, CHOSEN BY THE SMOKERS ACCORDING TO THEIR TASTE. EACH TECHNICAL AND EDUCATIONAL- BEHAVIOURAL ACTION TOOK PLACE ACCORDING TO A DETERMINED PROCEDURE AND TO DETERMINED FORMS, PREVIOUSLY AGREED BY THE TEAM ON THE BASIS OF THE INFORMATIONS GIVEN BY LITERATURE CALLED M.B.. THIS PROCEDURE INCLUDES TECHNICAL, EDUCATIONAL AND BEHAVIOURAL ASPECTS.

11 DEVICE Producer: PUFF CIGARETTE Corso Re Umberto 7, Torino European Conformity tested in italian Laboratory Content 1,5 ml, Average consumption /day 3 ml Average lifetime: 15 gg Impedance: OHM 2,2 BUTTON CARTOMIZER ACTIVATION Capacity m.a. 550 Voltage: Volt 3,9 Operating time : 4/5 h BATTERY RECHARGE Plug micro USB fast recharge 1 h. DIMENSIONS : mm 143 X 19 WEIGHT : gr. 40 ALIMENTARY PAINT

12 LIQUIDS Producer: Puff Cigarette Plant in Via Giuseppe di Vittorio 13/a Moncalieri (TO) Composition: Glycerol USP, Propylene glycol USP, Nicotine USP/EP, Deionised water, Aromas Nicotine rate: mg./g ( 10 ml and 20 ml bottles ) Titration of nicotine made in laboratory with analytical method validated by ACCREDIA Complies with UNI CEI EN ISO/IEC 17025:2005 General Requirements for the accreditation of testing and calibration laboratories» with Accreditation no. 0729, by means of gas chromatography with mass spectrometry ( GC-MS). Determination of metals : EPA 3550B EPA 6010C 2007 Determination of benzene : EPA 3550B EPA 5030C 2003 Determination of glycols : GAS CHROMATOGRAPHY WITH MASS SPECTROMETRY (GC-MS) Production unit : White room with a controlled environment, processings carried out in chemical hood series MA95 certified EN , technical balance for dosage LAB Mettler- Toledo, resolution 0,01 g., automated bottling line. Certifications: ISO 9001:2008 TUV

13 just to understand NICOTINE IN THE E-CIG Refills used 1 refill 4 mg (ml 1,5) = 6 mg 1 refill 8 mg ( ml 1,5) = 12 mg 1 refill 16 mg ( ml 1,5) = 24 mg NICOTINE IN CIGARETTES Example 20 MARLBORO 100S = 16 mg 20 MS BLU = 16 mg 20 PHILIP MORRIS BLU 100s = 8 mg

14 TOXICOLOGICAL ANALYSIS AVAILABLE ON THE EVAPORATED Analysis performed by: GSC Chemical Advice & Analyses (Olgiate Comasco CO) Parameters taken under study: research for heavy metals, determination of volatile organic compounds, identification of decomposition products of glycerol and propylene glycol. Comparison: saline solution Analysis typology : HPLC-DAD / HS GC MS / ICP - OES Metals analysed : Ca-Al-Mg-K-Na-As-B-Ba-Be-Bi-Cd-Co-Cr-Cu-Fe-Hg-Li- Mn-Mo-Ni-Pb-Sb-Se-Si-Sn-V-Zn

15 Available toxicological data There are no degradation products of glycerol present above the LOD of the technique used. The evaporated is comparable with that of the reference saline solution. There was no positivity regarding the presence of contaminants of the glycol base in the evaporated of liquid for electronic cigarette analysed within the limits of the techniques used. Metals detected Liquid (ppm) Saline solution (ppm) Aluminium 0,165 0,086 Arsenic 0,243 n.d. Boron n.d. Calcium 25,431 0,593 Iron n.d. 0,088 Potassium 0,282 0,383 Magnesium 5,923 0,032 Sodium 4, Arsenic / day 1Lt drinking water 20 traditional cigarettes 3 ml of liquid (max.limit set by European Union)) (source: INAIL) 10 µg 14 µg µg

16 RESULTS

17 SUMMARY TABLE OF SMOKERS/VAPERS DISTRIBUTION AFTER THE 1 MONTH FROM TRANSLATION (34 INDIVIDUALS) GREEN: COMPLETELY TRANSLATED BLUE: EX TRANSLATED RED: THOSE WHO KEEP SMOKING «MIXED» 34 smokers 1 month Nic mg Cig day T 0 Cig day 16/6 (month 1) Cig day (month 4) CO start T 0 CO 16/6 (month 1) CO 5/10 (month 4) 25 (73,5%) 5 (16%) 4 (10,5%) 0,65 19, ,38 0,31 0,33 0, ,25 2,4 2,46 0,46 0,72 0,7 31,25 7,11 14,75 4,18 4,50 1,65

18 4 months later

19 SUMMARY TABLE OF SMOKERS/VAPERS DISTRIBUTION AT THE 4 MONTH FROM TRANSLATION (34 INDIVIDUALS) GREEN: COMPLETELY TRANSLATED BLUE: EX TRANSLATED RED: THOSE WHO KEEP SMOKING «MIXED» 34 Smokers 4 month Nic mg Cig day T 0 Cig/day 16/6 (month 1) Cig/day (month 4) CO start T 0 CO 16/6 (month 1) CO 5/10 (month 4) 17 (50%) 8 (23,5%) 9 (26,5%) 0,68 18, ,07 0,27 0,33 0,6 21,87 0,25 2,37 2,93 0,43 0,72 0,71 26,11 7,11 5,66 3,33 1,95 1,65

20 Some numbers in detail

21 TABLE 1 AT TIME 0 34 volunteer smokers not interested in giving up smoking Average of 22 cigarettes a day CO nell espirato = 2,6 nettamente superiore al valore medio dei non fumatori Participants (n) men (%) women (%) Age 40.6 ± ± ± 11.9 Weight 70.9 ± ± ± 14.1 Daily cigarettes ( M ± DS) 21.5 ± ± ± 13.9 Years as smoker 22.0 ± ± ± 11.2 Education Primary school Intermediate school High school Degree Job Unemployed Partially qualified Qualified worker Manager

22 TABLE 2 AFTER 1 MONTH Very drastic reduction of smoked cigarettes, declared to TO by translated and «mixed». Very drastic reduction of CO exhaled by translated and (although minor) by «mixed». Translated to e-cig Mixed smokers Classic smokers % (n= 34) 73.5% (n=25) 17.6% (n= 6) 8.8% (n= 3) Age (years, M ± DS) 40.4 ± ± ± 8.3 Fagestrom ( M ± DS) 5.3 ± ± ± 2.5 Cigarettes at time T ± ± ± 25.7 Cigarettes at time T ± ± 18.5 p-test < Carbon monoxide exhaled at time T0 Carbon monoxide exhaled at timet1 2.4 ± ± ± ± ± ± 2.5 p-test < < Cotinine rates steady Plasmatic cotinine at time T0 Plasmatic cotinine at timet ± ± ± ± ± ± 88.7 p-test Trans-3-plasmatic idrossicotinine at time T0 Trans-3-plasmatic idrossicotinine at time T ± ± ± ± ± ± 52.0 p-test

23 TABLE 3 AFTER 4 MONTHS 50% of smokers confirms Translation. The declared smoke decreases significantly The average rates of CO exhaled decrease for all significantly according to different orders of magnitude Cotinine steady Translatied to e-cig Mixed smokers Classic smokers % (n= 34) 50 (n=17) 23.5 (n= 8) 26.5 (n= 9) Age (years, M ± DS) 40.8 ± ± ± 13.1 Fagestrom ( M ± DS) 5.1 ± ± ± 1.9 Cigarettes at time T ± ± ± 14.3 Cigarettes at time T ± ± 3.4 p-test < < Carbon monoxide exhaled at time T0 Carbon monoxide exhaled at time T1 2.1 ± ± ± ± ± ± 0.8 p-test < Plasmatic Cotinine at time T0 Plasmatic Cotinine at time T ± ± ± ± ± ± 63.6 p-test Trans-3-plasmatic idrossicotinine at time T0 Trans-3-plasmatic idrossicotinine at time T ± ± ± ± ± ± 21.6 p-test

24 CO EXHALED

25 NUMBER OF SMOKED CIGARETTES DECLARED AT THE 4 MONTH OF EXPERIMENTATION traslati misti fumatori

26 PLASMATIC COTININE

27 PLASMATIC COTININE -3-OH

28 CONCLUSIONS

29 CONCLUSION 1 (I MONTH) 74% of participants used just the e-cig 18% smoked both cigarettes ( 1 to 5) and e-cig 8% kept on smoking cigarettes Those who smoked just the e-cig and the mixed showed values of CO exhaled significantly lower, thus reaching the average rates (0,3-05%) present among the non-smoker population. There has been a collapse of the declared smoke in all groups of smokers. Cotinine was present in all groups at the same rate of the beginning; this means that e-cig smokers could absorb all the nicotine needed to avoid craving complications.

30 CONCLUSION 2 (IV MONTH) 50% of participants used just the e-cig 24% smoked both cigarettes ( 1 to 5) and e-cig 26% kept on smoking cigarettes Those who smoked just the e-cig and the mixed showed values of CO exhaled significantly lower, thus reaching the average rates (0,3-05%) present among the non-smoker population The drop of declared smoke has consolidated. In the «mixed» group and in pure smokers there was a significat reduction of daily smoked cigarettes with consequent significant reduction of exhaled CO, even in pure smokers. Cotinine rate remained almost the same of the beginning in all the three groups. In pure smokers the average rate of plasmatic cotinine and trans-3- idrossicotinine remained steady in comparison with the beginning of the study, in spite of the reduction of daily smoked cigarettes: it is plausible that this reduction, over 4 months, is so slow that the symptoms of craving can be avoided. Summer holidays have conditioned the support program for a period of 45 days.

31 CONCLUSION 3 Electronic cigarette proves to be an important means of approaching most part of smokers who, due to different reasons, are not interested in giving up smoking (the so-called «unreachable»). E-cig is a device of medical concern in the context of the operative clinical management of the so-called «risk reduction» in treating tobacco addiction with cessation-resistant smokers. The assisted medical approach to the use of this electronic device proves to be fundamental to understand how to use it and how to follow a «translation» process correctly. No significant adverse reaction took place in the present period of observation. Technical and behavioural support is very important and must follow several steps according to a logical sequence of actions supporting the «translation». The «replacement» can be done with a consolidated use of the electronic device during a period of at least three months. Technical and psychological support is very important, as well as the follow up. The clinical management of nicotine consumption reduction is still to be explored.