E-cigarettes: Miracle or Menace ?

1. E-cigarettes: Miracle or Menace ? Constantine Vardavas MD, RN, MPH, PhD Center for Global Tobacco Control, Harvard School of Public Health Smoking and Lung Cancer Research Center, Hellenic Cancer Society Co-Editor in Chief, Tobacco Induced Diseases

2. Acknowledgements and COI • No conflict of interest to declare. • The positions presented here are solely my own, and do not necessarily represent the positions of any of the institutions, organizations or journal with which I am affiliated. • This is not a “Pro-Con” Debate

3. Product evolution

4. of the “healthier” tobacco product Combustible MRTP Premier (RJR) Eclipse Accord Electronic cigarettes Digital cigarettes • Filtered cigarettes • Lights • Menthol • Slims Smokeless • Low TSNA snus • Dissolvables

5. Electronic cigarettes E-cigarettes are a class of battery-operated electronic nicotine delivery system (ENDS) designed to provide nicotine through inhalation of nicotine/humectant Cobb & Abrams. N Engl J Med. 2011;

6. Innovative aspects • Neurobiological basis of addiction • Habitual addictions which reinforce behavior. • “vapor” (propylene glycol), • hand-to-mouth • Chemosensory stimulus • Lack of combustion

7. Effects on Tobacco Craving • ECs can reduce craving in deprived smokers but not as effectively as tobacco cigarette (Bullen et al., 2010; Vansickel et al., 2010) • Placebo (0mg/ml) EC also associated with decline in craving after 5 mins and.. • Further reduction in craving with nicotine EC after 20 mins (Dawkins et al., 2012)

8. Chemosensory Stimulants • trace amounts of heavy metals during use. • trace amounts of impurities and tobacco-specific nitrosamines. • Electronic cigarette cartridge nicotine content may yield inconsistently. • Ranging cytotoxicity: human embryonic stem cells (hESC), mouse neural stem cells (mNSC). Flavors. • Propylene glycol and/or Vegetable glycerine (glycerol) US FDA; Goniewicz et al; Bahl et al; Flouris et al.

9. Pulmonary System I • No impact on FEV/FVC (n=15), (n=30), (n=58) • Case reports (Pneumonitis, pneumonia, etc.) • Increase in respiratory resistance • Decrease in Exhaled FeNO • The health impact from long-term inhalation of PG? Vardavas et al., 2012; Flouris et al 2013, Gratsiou et al, 2012; Thotis, et al 2014, and unpublished data

10. RESPIRATORY RESISTANCE CONTROL GROUP Table 3. Experimental group subject Respiratory Resistance (R 5-10 -20Hz) tests before and after exposure to an e-cig. 1: p values based on paired student t-tests, p<0.05 classified as statistically significant.

11. Medical Licensing? The MHRA says any application must have: 1. Dosage data — to ensure the product delivers a reasonably consistent dose of nicotine 2. Quality and safety assurances — part of this is to ensure the product is manufactured to cGMP standards, but also that it is designed to overcome potential dangers, for example if the product overheats. “We expect BAT to launch 2 new products with medical licenses within 12-24 months…..We are not aware that any other tobacco company has made an application for an MA in the UK or elsewhere, or is close to doing so, and so we think BAT will gain a first mover advantage in what we see as the long-term future of NextGen nicotine products in Europe” CITI Bank Equity Research, Oct 201

12. Medicine or Tobacco?

13. To trust or not to trust ??? • Tobacco industry has significantly invested • Altria CEO Mr. Barrington described MarkTen as “a familiar draw with an appealing taste.” • Include a microprocessor • “VUSE is powered by Smart Technology which is designed to monitor and regulate the power, heat and cartridge performance to ensure a perfect puff first time, every time”.

16. Heated tobacco products

17. Innovative aspects 3 • Neurobiological basis of addiction • Habitual addictions which reinforce behavior. • “vapor” (propylene glycol), • hand-to-mouth • Chemosensory stimulus • Lack of combustion harm reduction

18. Methods I Eurobarometer 385 survey (77.1) • 27 EU countries • ≥15 years of age • February-March 2012 • N= 26,566 participants • N= 7,352 smokers • N= 5,782 ex-smokers Ethics waiver: HSPH IRB14-0346 Special Eurobarometer 385. ATTITUDES OF EUROPEANS TOWARDS TOBACCO. Accessed 8/23, 2013

19. Eurobarometer analysis Special Eurobarometer 385. ATTITUDES OF EUROPEANS TOWARDS TOBACCO.

20. Population Extrapolations • 20.3% (95%C.I: 18.9-21.8) of smokers. 23.1 million • 4.4% (95%CI: 3.6-5.3) of former smokers. 3.9 million • 1.1% (95%CI: 0.8-1.4) of never smokers. 2.3 million

21. European Ex-Smokers 4.4% (95%CI: 3.6-5.3) of former smokers. 3.9 million • No significant differences in the ever use of e-cigarettes were observed by gender, place of residence, marital status or SES. Vardavas et al., Tobacco Control, 2014

22. Cessation ??? • Past year quit attempt aOR=2∙08; 95%CI: 1∙67-2.58. • Any quit attempt (lifetime): • 65∙7% had attempted to quit cold turkey • 22∙5% reported use of nicotine replacement therapy, • 7∙3% reported use of smoking cessation counseling, • 7∙1% had tried electronic cigarettes. • However, given that e-cigarettes have only been in the market for a few years, while respondents provided feedback on lifetime quit attempts, it is possible that the prevalence of use of e-cigarettes as harm reduction strategy may even be higher, • Success ? Duration? Relapse? comparative effectiveness ? • To date, the role as an cigarette cessation device/harm reduction strategy is potentially promising however research is limited. Vardavas et al., Tobacco Control, 2014

23. Randomised Controlled Trials • ‘Categoria’ 7.2mg nicotine EC vs. 4.8mg nicotine EC vs. no nicotine EC • 300 smokers (unwilling to quit) • 1 year abstinence rates: 13%, 9% and 4% (Caponnetto et al. 2013) • ‘Elusion’ 16mg nicotine EC vs. nicotine patch vs. no nicotine EC • 657 participants • 6 month abstinence rates: 7.3%, 5.8% and 4.1% (Bullen et al. 2013)

24. Acute vs. Long term effects Acute: Some studies available • All on earlier generation e-cigarettes • Limitations related to knowledge of use “naïve vs. experienced vapers”, small sample size. • No population based studies with health outcomes Long term: NO STUDIES available Projections? Industry vs. researcher?

26. A wolf in sheep's clothing ? • Tobacco product ? • Huge investment by the tobacco industry (PM, RJR etc) • Trojan horse? • Classical tobacco industry marketing tactics • Re-normalising of smoking? • Key issue of TC in the 21st century • Legislate for use in public areas? • Promote(d) dual use?

27. A sheep in wolf’s clothing ? • Medicine ? • Potentially Reduced Exposure Product (PREP) • Harm reduction strategy • May have a role as a cigarette cessation device • Has nicotine • Medical regulation would control for constituents. • EU Pharmacopeia, i.e. UK

30. Discussion points

31. Tobacco Product: from design to disease

32. US market

35. Investor predictions

36. Blue • The first major tobacco company to enter the market • “Blu is not a tobacco product; It does not burn; And it does not produce odor. For this reason, a blu electronic cigarette can often be smoked in places where tobacco cigarettes are banned. (i.e. bars, restaurants, stadiums)” • Cigarette pack case (battery)

37. Tobacco Product: from design to disease

38. E-cig industry advertising