E-Cigarettes: Current Perspective

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1 E-Cigarettes: Current Perspective Aruni Bhatnagar, Ph.D. Professor of Medicine University of Louisville Louisville, KY

2 Electronic Cigarettes E-cigarettes are electronic nicotine delivery systems (ENDS), they produce a cloud of nicotine carrying vapor with none of the toxic by products of burning tobacco Patented in China by Ruyan Technology in International Patent 2007

3 A variety of e-cigarettes are available in the market Cigalikes Tankomizers Mods E-hookahs Vape-pens

4 E-cigarettes are selling like crazy Wells Fargo predicts that e-cigarettes would surpass conventional cigarette sales by 2017, approaching $10 billion by 2017 Advertising expenditures across all media outlets has surpassed $82 million in 2013

5 Profile of an adult e-cigarette users Most users are current and former smokers 6.2% US adults have tried e-cigarettes at least once Use of e-cigarettes has increased from 1 % in 2009 to 6% in 2011 Men (45-54 years) with college education are most aware of e-cigarettes Ever users tend to be female (18-34 years) with high school level of education About 20 % of smokers who try e-cigarettes become regular users Among recent former smokers 45.7% use e-cigarettes on a daily basis Ever users are more frequently white, have Midwestern residential status

6 Youth Use Use of e-cigarettes among never smoking young people has increased from 79,000 in 2011 to 263,00 in 2013 Ever e-cigarette use has increased from 3.3 to 6.8% Over 1.78 million high school and middle school students have tried e- cigarettes For those who ever used e-cigarette 9.3% reported never smoking conventional cigarettes, 76.3% e-cigarette users have also smoked conventional cigarette Almost 45% of non-smoking youth who have tried e-cigarettes indicated that they intend to smoke conventional cigarettes within the next year, compare with 20% of those who have never used e-cigarettes Restrict marketing and advertising of e-cigarettes to minors

7 E-cigarette constituents E-cigarettes contain nicotine derived from tobacco in propylene glycol and/or glycerol Nicotine is heated and vaporized, but not burned Levels of most chemicals with significant cancer and non-cancer risk are much lower in e-cigarettes than conventional cigarettes However, their yields vary with puff duration and voltage Aerosol contains low levels of aldehydes and particulate matter E-cigarette constituents should be regulated by the FDA with standards for contaminants

8 E-cigarette constituents Toxicant Range in Content in Aerosol From 12 E-Cigarette Samples per 15 Puffs* Range in Content in Conventional Cigarette Micrograms in Mainstream Smoke From 1 Cigarette Content in Nicotine Inhaler Mist per 15 Puffs* Formaldehyde, μg Acetaldehyde, μg Acrolein, μg ND o-methylbenzaldehyde, μg Toluene, μg ND ND p,m-xylene, μg ND 0.2 ND NNN, ng ND ND NNK, ng ND ND Cadmium, ng ND Nickel, ng Lead, ng Goniewicz et al., Tob Control (2014) 23:133

9 Nicotine and related alkaloids E-cigarettes contain very low levels of carcinogenic alkaloid NNK Trace levels of nornicotine, anatabine, and anabasine (1-2 % of nicotine) Variable doses of nicotine Nicotine is a psychoactive and vasoactive drug Increases heart rate and blood pressure Enhances cognition and suppresses appetite Affects release and metabolism of neurotransmitters such as dopamine, norepinephrine and epinephrine Relatively non-toxic, but long-term effects remain unknown

10 Propylene Glycol Generally considered non-toxic Approved by the FDA as a solubilizing agent for different types of medication It is used to generate theatre fog and in the aviation industry Prolonged exposure can cause eye and respiratory irritation Exposure could be of concern in susceptible individuals (e.g., asthmatics) Trace levels of the antifreeze ethylene glycol have been detected.

11 Aldehyde generation E-cigarettes contain trace levels of aldehydes; however, aldehyde generation is accelerated by increased air flow, and therefore release of aldehydes increases as the liquid in the cartridges is replaced by air After puffs, the levels of formaldehyde is comparable or higher than in conventional cigarettes Carbonyl released from e- cigarettes using a smoke machine First fraction = 50 puffs, each consecutive fraction = 10 puffs Hutzler et al., Arch Toxicol (2014) 88:1295

12 Particulate Matter (PM) E-cigarettes Main mode around 150 nm, smaller mode at 10 nm 20-27% particles are estimated to be deposited in the circulatory system and organs Higher e-liquid nicotine content associated with higher number of particles Longer puffing time results in more particles Conventional cigarettes Mainstream aerosol has a particle size distribution of 165 nm 25-35% particles are likely to be deposited in tissues No difference in particle number: 4.4 X10 9 versus 3.1 x 10 9 part. cm -3 Fuoco et al., Environ Pollution (2014) 84:523

13 Direct Acute Health Effects Acute exposure increases dynamic air resistance (18%) and decreased NO (16%) after puffing on e-cigarettes for 5 min No significant decrease in expired lung volume No change in white cell count or coronary reserve Elevated levels of NO attributed to pulmonary inflammation E-cigarette constituents - PM, aldehydes and nicotine have been linked to a variety of health effects No long-term studies are available yet E-cigarette use should be included in tobacco screening questions

14 Are e-cigarettes reduced harm products? Harm depends on the level of exposure, which might increase with persistent e- cigarette use For conventional cigarettes, the dose response for cardiovascular mortality is nonlinear Most of the risk of smoking is at low doses: 80 % of the harm at <3 cigarettes/day Pope et al., Circulation (2009) 120:941

15 E-cigarettes as cessation aids Many individuals who smoke e-cigarettes believe that it will help them quit conventional cigarettes There have been 5 longitudinal studies: Adkison et al: reduction in cigarettes smoked per day (20.1 to 16.3), however, e-cigarette users were no more likely to quit 1 year later than nonusers Vickerman et al: 31% quitline callers surveyed 7 months after enrollment reported ever e-cigarette use those who reported using e-cigarettes were likely to quit than those who had not used e-cigarettes Grana et al: Current e-cigarette use at baseline did not predict greater likelihood of quitting, 1 year later Choi and Forster: 11 % of those who used e-cigarettes at least 1 day in the past 30 days at baseline quit smoking at follow-up, compared with 17% of smokers who never used e-cigarettes Bullen: randomized controlled trial: At 6 months, quit rates were 7.3% with nicotine e-cigarettes, 5.8% with nicotine patches and 4.1 % with placebo e- cigarette treatment. E-cigarettes should not be currently used as a primary cessation aid

16 Secondhand Exposure There is no secondhand exposure due to smoldering, but only after the aerosol is exhaled Increased carbonyl formation, 5- to 40-times less than conventional cigarette After e-cigarette use the ambient PM2.5 concentration was 18% that seen with cigarette smoke Ambient nicotine levels 10% of that seen with smoking conventional cigarettes Exposure of 15 nonsmokers to 1 h of secondhand cigarette smoke or e- cigarette aerosol results in similar serum cotinine levels. E-cigarettes should be included in smoke-free laws

17 E-cigarettes and public health Acceptance of e-cigarettes has the potential to reverse social norm Prevalence of dual use not known Efficacy as cessation aid is unclear (some studies have shown that they are as effective as other nicotine replacement therapies) Some surveys report that a majority of e-cigarette users completely replaced tobacco cigarettes with e-cigarettes Dual use persists at moderately high levels As a last alternative physicians should not discourage e-cigarette use for cessation

18 Future Research Agenda Identifying any acute and chronic adverse health effects of e-cigarettes. Assessment of any health effects of second or third hand exposure to e-cigarette vapor and constituents. Evaluation of the efficacy of e-cigarettes as a smoking and nicotine cessation modality Understanding the addictive potential of e-cigarettes and their pattern of use, and withdrawal symptoms. Identification of cultural, social and economic factors (including regulation and taxation) that promote, sustain or discourage e-cigarette use. Identification and monitoring of manufacturing practices, e-cigarette constituents, their variation between different brands, pharmacokinetics, and modes of delivery. Assessment of the impact of marketing and communication on e-cigarette use and public health Monitor unintended use for delivery of other drugs and medications.

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