E-cigarettes for tobacco harm reduction School of Public Health and Community Medicine The University of New South Wales, Sydney Associate Professor Colin Mendelsohn E-cigarettes for tobacco harm reduction ACRA 2018 ASM Wednesday 1 August

What is the evidence? Is vaping an effective quitting aid and how does it compare to conventional therapies? Does switching to an e-cigarette reduce harm? What are the cardiovascular effects of vaping? Are e-cigarettes a gateway to smoking tobacco?

Effectiveness Population studies Best evidence is in real-world settings E-cig users have much higher quit rates than non-users Any use almost doubled quit rates 4.8% vs 8.2% 1 US Current Population Survey-Tobacco Use Supplement, 2014-15, n=24,684 Daily use increased quit rates 3-8x 2,3 PATH, 2013/4-2014/5, n=32,320 NHIS, 2014-15, n=15,532 Does the technology work in a real world environment: experiment with range of devices, strengths, flavours Zhu. Over a 12m period, smokers who used ecigs had twice quit rates for >3m Nationally representative population studies 1. Zhu S. BMJ 2017 2. Berry K. Tob Control 2018 3. Giovenco D. Addict Behav 2017

Effectiveness National surveys Millions of smokers have quit smoking by vaping Quit smoking by vaping Data Source 7.5 million Eurobarometer #458 2016 National Health Interview Survey 2016, CDC 2.62 million Some are vaping, some are not. But all have quit smoking Office of National Statistics 2017 2 million Most popular quitting aid in EU, US, UK

Effectiveness Clinical trials ‘The three higher quality reviews all reached similar conclusions… consistent with an approximate doubling of the likelihood of quitting smoking’ 1 Modern devices more effective 2,3 Clinical trials of approved therapies increase 50-288% 4 21 reviews of clinical trials of mixed methodological quality High quality: Cochrane, Malas, El Dib The remainder were rated as low or critically low quality RCTs are often not suited to public health research on complex consumer behaviors and are often misleading. Process of finding the right combination is not linear and not easily randomizable. Trials are limited duration. 1. Royal College of Physicians. June 2018 2. Hitchman SC. Nicotine Tob Res 2015 3. O’Leary R. Canadian Institute for Substance Use Research 2017 4. Cahill K. Cochrane review 2013

Harm reduction Far less harmful than smoking Not risk-free ‘the hazard to health arising from long-term vapour inhalation from the e-cigarettes available today is unlikely to exceed 5% of the harm from smoking tobacco’ 1,2 ‘no identified health risks of passive vaping to bystanders’ 1,2,3 The Glasser review: exposure to nicotine vapour but the level of exposure was low, and exposure to other compounds were also very low, or at trace or non-detectable levels when compared with second-hand smoke No sidestream vapour 1. Royal College of Physicians 2016 2. Public Health England 2018 3. British Heart Foundation. Position Statement 2017

The dose determines whether a substance is a poison 2 Harm reduction Why? ‘the constituents of cigarette smoke that harm health – including carcinogens – are either absent in e-cigarette vapour or, if present, they are mostly at levels much below 5% of smoking doses (mostly below 1% and far below safety limits for occupational exposure)’ 1 Philippus Theophrastus Aureolus Bombastus von Hohenheim, All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy. The dose determines whether a substance is a poison 2 1. Royal College of Physicians 2016 2. Paracelsus. Father of modern toxicology 1493-1541

Harm reduction Supporting evidence Biomarkers: toxins dramatically reduced 1 Clinical improvements Asthma2, COPD3, BP4, lung function5, pneumonia risk6 Nicotine has only relatively minor health effects Not a carcinogen7,8; does not cause lung disease7; only a small role in CVD9 Cancer risk <0.5% smoking10; Lung cancer 100,000x less11 No serious adverse events after 10 years 1. Public Health England 2018 2. Polosa R. BMC Med 2017 3. Polosa R. Resp Res 2016 4. Farsalinos K. Int Emerg Med 2016 5. Cibella F. Clin Sci 2016 6. Capagna D. Pneumonia 2016 7. The health consequences of smoking. US Surgeon General 2014 8. IARC 2012 9. Benowitz NL. Nature Rev Cardiology 2017 10. Stevens S. Tob Control 2017 11. Scungio M. J Aerosol Sci 2017

Cardiovascular effects Cause of CV effects Most CV effects of e-cigs are from nicotine 1 Low levels of toxic constituents 1 Benowitz NL. Nature Rev Cardiology 2017

Cardiovascular effects Evidence reviews ‘People with established CVD might incur some increased risk from e-cigarette use, the risk is certainly much less than that of smoking’ 1 ‘Risks of cardiovascular disease… are likely to be substantially below the risks of smoking’ 2 ‘Current research shows that e-cigarettes are significantly less harmful than tobacco products’ 3 1. Benowitz NL. Trends Cardiovasc Med 2016 2. Public Health England. Evidence Review 2018 3. British Heart Foundation. Evidence to UK Parliamentary Inquiry 2018

Gateway What is the gateway hypothesis? try vaping and… Young people who would not otherwise have smoked …as a result, become long- term smokers

Gateway Association or causation? Many studies show that young people who try vaping are more likely to also try smoking later 1 Cross sectional studies are unable to show causation 2 “Common liability” more plausible 3 Young people who are impulsive, rebellious and sensation-seeking are more likely to try both behaviours Smoking usually precedes vaping 2 This association does not mean that vaping causes the behaviour 1. Soneji SS. Pediatrics 2017 2. Etter JF. Addiction 2017 3. Vanyukov MM. Drug Alcohol Depend 2012

Gateway Regular use by non-smokers is rare UK US Bauld L. IJERPH 2017 n=60,000, 15-17yo National Youth Tobacco Survey 2015 (CDC) n=17,717, 11-18yo Never-smokers Regular use rare: 0.6% (≥ 10d per month) 1 Most don’t use nicotine 2 Most use is by smokers Kids experiment Never smokers ≥ weekly use rare 0.1-0.5% Most past 30-day users were experimenters and had very low prevalence of frequent use US Almost half 30d ever users used on 1-2d only 39%: past 30-day use Currently, fewer than 25% of youth ever cigarette users progress to daily cigarette use, indicating that a large proportion of tobacco product use that occurs in adolescence is experimental and does not lead to long-term regular use in adulthood 0.23% used 10 or more days in month NYTS: Never smokers: Last 30d use 5.4% 1. Farsalinos K. Am J Prev Med 2018 2. Miech R. Tob Control. 2017

Gateway Population effects Youth smoking rates are falling where vaping is available In US, decline accelerated after 2014 (peak vaping year) 1 Vaping is replacing—rather than encouraging—smoking 2 If there is a gateway IN, it is very small and is swamped by the gateway OUT Levy D. 6 national data sets 1. Levy D. Submitted for publication 2. Canadian Institute for Substance Use Research 2017