Visualising possible scenarios with ENDS (Electronic Nicotine Delivery Systems)Barcelona, July 2014

School of Public Health, University of SydneySimon Chapman AO PhD FASSA

Insert Partner Logo - Delete if not required

World’s lowest smoking prevalence

Plain Packs Dec 2012

Great moments in tobacco harm reduction hype

What will be net effect of ENDS across the whole population?

› Across 40 years, many hyped claims for HR products (filters, “lights & milds”, reduced carcinogens, heat rods).

› All fraudulent and/or market failures.› 80% of smokers switched to lights & milds› Revealed as fraudulent in reducing harm› What should we have learned from the lights/milds issue?› Because all previous efforts have failed, does not follow all future

ones will also fail.

5

Evidence already in? Open the deregulatory floodgates?

Lord Bertrand Russell

6

The vaping industry’s agenda

› No pharmaceutical regulation› Vaping in all public places› Self-regulated advertising› No restrictions on kiddie flavours› High yield nicotine e-juice › If kids start vaping, so what? ..

far better than smoking & nicotine “just like coffee” .. even good for you!

› http://www.clivebates.com/?p=2257

› “Controls on  advertising  to  non- smokers,  and  particularly  to  young  people  are  certainly  justified,  but  a  total  ban would have  many  negative  effects,  including  protection  of  the  cigarette  market and  implicit support  for  tobacco  companies. It  is  possible  to  target  advertising  at  existing  smokers  where  the  benefits  are  potentially  huge  and  the  risks minimal.”

Also articulated by Clive Bates

7

As well as, not instead of cigarettes.

› Widespread dual use › Retarding smoking cessation› Resocialising public smoking back into fashion from forlorn exile outside buildings

› Conveying to young, apprehensive would-be smokers that nicotine is a benign drug

› Welcoming back ex-smokers as customers› Cross-promoting cigarettes via same name brands

6 goals for Big Tobacco

8

Peter Hajek: Mike Russell Lecture 2014

“Many smokers want to access e-cigarettes to quit or reduce risk, and they should not be denied this opportunity. But the needs of often desperate smokers must not become the tail that wag the dog of tobacco control policy, putting at risk the massive gains we have achieved.”

What Hajek says I wrote What I wrote

9

Peter Hajek: Mike Russell Lecture 2014

“So tobacco control is not there for people not to die .. It is there for some much higher and much more important purpose”

10

› Imagine claims for a cancer or HIV/AIDS preventive or curative drug …

›Advocates (many financially conflicted) urge by-passing of all therapeutic goods assessment oversight, direct-to-consumer advertising all on the ethical imperative of exceptionalist rhetoric to save lives

11

Utopian vision: best case scenario

› Mass & rapid migration of significant proportion of smokers to ENDS. A “disruptive technology” like digital vs film cameras

› Most ENDS users use them to quit smoking, succeed, & do not return to smoking› Trivial uptake of ENDS by returning ex-smokers & never smokers (esp. kids)› Negligible evidence after several years of ENDS use as gateway to smoking (esp.

kids)› Prolonged, frequent, deep inhalation of nicotine over decades turns out to be

benign (IARC affirms) › Secondhand vape assessed as inconsequential to health (IARC affirms)› Tobacco industry sees sales, profits from tobacco deeply eroded. It actively

accelerates this decline as new “partner” in public health› Tobacco industry voluntarily stops all promotion of tobacco; stops opposing

effective tobacco control› Millions of lives saved

12

And pigs might fly …

13

Dystopian threat: worst case scenario

› Global uptake of ENDS on the scale of cell phones› Includes many kids who would have never used any nicotine product› Smoking cessation rates via ENDS little different to current methods› Population smoking cessation permanently stalls: most smokers dual using› Widespread evidence of would-be quitters remaining smokers (prevarication)› Smoking cessation volumes soon eclipsed by new ENDS user uptake› Significant drift of new ENDS users into smoking as well (gateway)› Net impact on smoking = increase› ENDS advertising & promotion massively proliferates, esp in social media› The smoking “performance” is rapidly re-socialised, renormalised as all indoor smoke free

areas allow vaping› Same name vape/tobacco products cross-promote› Long term use of inhaled nicotine confirmed in research to have important role in pre-

cancerous cell biology; heart disease› Falling smoking disease rates begin to climb again

14

Today: What does the evidence to date suggest?

› Health risks of vaping? As benign as coffee? No› Health risks of secondhand vaping? Not negligible› How effective in smoking cessation? Too early› How much dual use? Lots› Health benefits of reduced smoking? Poor› Uptake of vaping by non-smoking kids? Rapid› Tobacco industry goals? Mendacious› Renormalisation of the “smoking performance”? Major

MAIN CONCERNS

15

1. Health risks of vaping?

› No one sensible argues vaping is or is likely to be as remotely risky as smoking

› “Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy.” (Paracelsus 1493-1541)

› Average exclusive vaper takes 220 inhalations per day (80,355/year) (Etter, Addiction 2014)

› Vape is NOT just water vapour› Are there health risks in prolonged, frequent inhalation of nicotine,

fine & ultra-fine particles, vapourised flavourants & propylene glycol?

16

So is nicotine benign?

› “If they're people who would never have smoked but they've taken up e-cigarettes, frankly in public health terms it's not really an issue - it's like drinking coffee or something, there's no real risk associated with it.”

› Av coffee drinker: 3.1 cups/day

Prof Robert West

17

Nicotine in angiogenesis, cell proliferation, apoptosis

› “Nicotine .. deregulates essential biological processes like regulation of cell proliferation, apoptosis, migration, invasion, angiogenesis, inflammation and cell-mediated immunity in a wide variety of cells, including foetal, embryonic and adult stem cells, adult tissues as well as cancer cells.”

Emerging evidence that nicotine far from benign

› Grando SA. Connections of nicotine to cancer. Nature Reviews Cancer 14, 419–29. Published online 15 May 2014

› The list of cancers reportedly connected to nicotine is expanding and presently includes small-cell and non-small-cell lung carcinomas, as well as head and neck, gastric, pancreatic, gallbladder, liver, colon, breast, cervical, urinary bladder and kidney cancers. The mutagenic and tumour-promoting activities of nicotine may result from its ability to damage the genome, disrupt cellular metabolic processes, and facilitate growth and spreading of transformed cells. The nicotinic acetylcholine receptors (nAChRs), which are activated by nicotine, can activate several signalling pathways that can have tumorigenic effects, and these receptors might be able to be targeted for cancer therapy or prevention. There is also growing evidence that the unique genetic makeup of an individual, such as polymorphisms in genes encoding nAChR subunits, might influence the susceptibility of that individual to the pathobiological effects of nicotine. The emerging knowledge about the carcinogenic mechanisms of nicotine action should be considered during the evaluation of regulations on nicotine product manufacturing, distribution and marketing.

18

19

“

“nicotine stress on the transcriptome of normal breast epithelial cells”

PLACE IMAGE HERE

20

But … Sweden & snus?

› Many years of prolonged snus use by men .. little evidence of high levels of any smoking-related or other cancers

› But: different exposure pathways -- ingestion vs inhalation (buccal absorbed nicotine vs deeply inhaled vapourised nicotine). Plus deep inhalation of flavourants, propylene glycol.

21

336,381 Swedish construction workers followed 1971-1992 (40,230 cases of cancer)

Source: Nordenvall et al. Int J Cancer (2013)

› “history of tobacco use, even exclusive use of the seemingly benign snus, is associated with moderately increased cancer-specific mortality.”

› “our results concerning snus users seem to narrow in on nicotine as a conceivable culprit.”

22

336,381 Swedish construction workers followed 1971-1992 (40,230 cases of cancer)

Source: Nordenvall et al. Int J Cancer (2013)

23

Chemical hazards in electronic cigarettes?

› Besides nicotine, hazards can also arise from solvents, flavours, additives & contaminants.

› Analysis: 28 liquids of 7 manufacturers (Germany) › Glycerol & propylene glycol in all samples, but ethylene glycol was

dominant compound in 5 products. Ethylene glycol is associated with markedly enhanced toxicological hazards.

› Coumarin, acetamide, formaldehyde detected in certain samples.› 141 different volatile flavour compounds found in 28 liquids› 7/10 “free-of-nicotine” products contained nicotine› Hutzler et al. Chemical hazards present in liquids ad vapors of electronic cigarettes.

Arch Toxicology (2014);88:1295-1308

24

Fine & ultra-fine particles in vape

“Particle number distribution modes of the e-cigarette aerosol were in the 120-165nm range, then similar to the conventional cigarette.”

25

9 vapers, 6 vaping sessions, 2 hours, in ventilated room

› substantial amounts of 1,2-propanediol, glycerine and nicotine were found in the gas-phase, as well as high concentrations of PM2.5 (mean 197μg/m(3)). The concentration of putative carcinogenic PAH in indoor air increased by 20% to 147ng/m(3), and aluminum showed a 2.4-fold increase. PNC ranged from 48,620 to 88,386 particles/cm(3) (median), with peaks at diameters 24-36nm. FeNO increased in 7 of 9 individuals.

› Our data confirm that e-cigarettes are not emission-free and their pollutants could be of health concern for users and secondhand smokers. In particular, ultrafine particles formed from supersaturated 1,2-propanediol vapor can be deposited in the lung, and aerosolized nicotine seems capable of increasing the release of the inflammatory signaling molecule NO upon inhalation. In view of consumer safety, e-cigarettes and nicotine liquids should be officially regulated and labeled with appropriate warnings of potential health effects, particularly of toxicity risk in children.

Schober et al. Int J Hygiene Environ Health (2014)

FeNO = Fractional exhaled nitric oxide.A measure of airway inflammation

26

Dow Chemical on breathing propylene glycol mists

› “Prolonged inhalation of saturated vapors of PG have produced only minor effects in animals (irritation). However, such concentrations may be irritating to the upper respiratory tract and eyes of humans.

› Therefore breathing spray mists of these materials should be avoided. In general, Dow does not support or recommend the use of Dow’s glycols in applications where breathing or human eye contact with the spray mists of these materials is likely, such as fogs for theatrical productions or antifreeze solutions for emergency eye wash stations.

http://msdssearch.dow.com/PublishedLiteratureDOWCOM/dh_0047/0901b803800479d9.pdf#page=36

27

Many studies on cessation via e-cigs have major selection bias problems

› “As a fortunate survivor of extended tobacco addiction, 40 years of a pack a day, I have not smoked a single bit of tobacco since I started vaping 5 months ago. I was able to finally give up tobacco after failed attempts at cold turkey, patches, and gum as NRT

› As far as your "dual use" argument, I know about 200 people in our small town of 3000 that vape, and only about 3 of those still smoke some cigarettes, and those that do have cut consumption by about 90%.”

› Aussie Vapers: 7945 ever members 1137 active members

Farsalinos et al (2014): 19,414 vapers, on-line QA: 81% quit!!!!!

28

Cessation in “real world” populations?

› Methods: Representative cross-sectional survey, England. 5863 smokers within the last 12 months who made at least 1 quit attempt with either an e-cigarette only (n=464), NRT bought over-the-counter only (n=1922) or no aid in their most recent quit attempt (n=3477).

› Results: E-Cig users more likely still to be abstinent than either those who used NRT bought over-the-counter (OR=2.23, 95%CI=1.70- 2.93, 20% vs. 10.1%) or no aid (OR=1.38, 95%CI=1.08-1.76, 20% vs. 15.4%).

› Note difference with unassisted cessation: 20%-15.4% = 4.6% more quit with eCigs

› Thus: 80% attempted quitters with eCigs failed to quit› Point prevalence measure, no account of relapse.

Brown et al: Real-world effectiveness of e-cigarettes (Addiction 2014)

29

So what does a 60% relative improvement on “no aid” mean?

› Cross-sectional, with no account of relapse. › We know unassisted cessation or OTC NRT = 4% continuous

abstinence at 12 months› So: 60% improvement on 4%? = 6.4% quit per year with eCigs ??› ie: 93.6% still smoking a year later? How many dual using?› Longitudinal data needed on comparative shape of relapse curve

(smoking vs ENDS vs NRT vs Champix)

Adjusted OR = 60% improvement

Health benefits of cutting down, but not quitting ?

Source: Godtfredsen et al, Am J Epidemiol 2002;156: 994-1001

2002 review: little or no health benefits to cutting down

31

Norway: 51,210 adults followed-up 1970s-2003

› “Long term follow-up provides no evidence that smokers who cut down their daily cigarette consumption by >50% reduce their risk of premature death significantly”

Renfrew and Paisley study: Hazard ratios of all-cause mortality

Collaborative Renfrew & Paisley

Increased 1.15 (0.97-1.35)15 (0..9 7 – 1.35)

1.17 (1.04 – 1.32)

Maintained 1 1

Reduced 0.91 (0.75 – 1.10)

1.08 (0.97 – 1.20)

Quit 0.66 (0.56 – 0.78)

0.75 (0.67-0.84)– 0.84)

Adjusted for age, sex, social class, cigarettes, cholesterol, systolic blood pressure, body mass index, diabetes, pre-existing CHD

Source: Hart, Bauld and Gruer, AmJEpi, 2013.

33

Korea 479,156 men: 1992-2003 follow-up

› No association between smoking reduction & all cancer risk

› “Smoking reduction associated with significant decrease in risk of lung cancer, but size of risk reduction was disproportionately smaller than expected”

34

US: 2011-2012 increases

› Middle School %› Ever: 1.4 - 2.7› Current: 0.6 - 1.1› 20.3 never smoked› High School %› Ever: 4.7 - 10› Current: 1.5 - 2.8› 7.2 never smoked

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6235a6.htm

1.78m have used

35

Rapid uptake by youth (Utah)

› The percentage of Utah students in grades 8, 10, &12 who reported they had tried electronic cigarettes more than doubled from 2011 to 2013.

› Despite having no legal access to e-cigarettes, Utah youth are 3x more likely to report current use than adults.

› Nearly one third of Utah youth using e-cigarettes in past 30 days report they never tried conventional cigarettes.http://health.utah.gov/opha/publications/hsu/

1312_ECig.pdf

36

What might happen vs what is happening

› what is actually happening in the real world:› The large majority of e-cigarette users continue to smoke cigarettes. 

“Dual use" is projected in all investment analysts' reports and is exactly what one would expect as cigarette companies rapidly take over the e-Cig business.

› Signs of explosive growth in e-Cig use, with many kids initiating nicotine addiction with e-Cigs.

› Nicotine “training wheels” just like alcopops?› Marketing is back on TV and radio and product placement in movies

and TV is going wild. (USA)› Tobacco control community spending lots of time arguing with each

other

37

Adult flavours?

38

Re-normalising the smoking performance

My position

› ENDS may hold significant, game-changing promise for both cessation & HR. Current rapid growth, consumer interest

› But also hold potential to be a “weapon of mass distraction” that may stall cessation in population, re-normalise the smoking “performance”, draw attention from challenges of implementing known effective strategies

› I am not advocating for a ban› We urgently need quality, longitudinal evidence (but by definition, it

can’t happen quickly) › If eCig’s promise is delivered, focus should be on regulation for

access to smokers› Greatest concerns: holding smokers in smoking; addicting kids

E-cigs: Letting a benevolent or evil genie out of the bottle?

Possibly one of the most significant moments in tobacco control history or another fad?

Thank you!

41