E-cigarettes: Miracle or Menace ?

Constantine VardavasMD, RN, MPH, PhD

1.Center for Global Tobacco Control, Harvard School of Public Health2.Smoking and Lung Cancer Research Center, Hellenic Cancer Society3.Co-Editor in Chief, Tobacco Induced Diseases

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

Product evolution

of the “healthier” tobacco product

Combustible• Filtered cigarettes• Lights • Menthol • Slims

Smokeless• Low TSNA snus• Dissolvables

MRTP• Premier (RJR)

• Eclipse• Accord

• Electronic cigarettes• Digital cigarettes

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;

Innovative aspects

• Neurobiological basis of addiction • Habitual addictions which reinforce

behavior. – “vapor” (propylene glycol), – hand-to-mouth– Chemosensory stimulus

• Lack of combustion

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)

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.

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Vardavas et al., 2012; Flouris et al 2013, Gratsiou et al, 2012; Thotis, et al 2014, and unpublished data

RESPIRATORY RESISTANCE

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.

CONTROL GROUP

Medical Licensing?The MHRA says any application must have:1. Dosage data — to ensure the product delivers a reasonably consistent dose of nicotine2. 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

Medicine or Tobacco?

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”.

Heated tobacco products

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

Methods IEurobarometer 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

Eurobarometer analysis

Special Eurobarometer 385. ATTITUDES OF EUROPEANS TOWARDS TOBACCO.

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

• No significant differences in the ever use of e-cigarettes were observed by gender, place of residence, marital status or SES.

European Ex-Smokers4.4% (95%CI: 3.6-5.3) of former smokers. 3.9 million

Vardavas et al., Tobacco Control, 2014

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

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)

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?

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?

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

Discussion points

Tobacco Product: from design to disease

US market

Investor predictions

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)

Tobacco Product: from design to disease

E-cig industry advertising