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Electronic Nicotine Delivery Systems (ENDS):
Friends or Foes in Smoking Cessation to Reduce Risk of ASCVD?
Pamela B. Morris, MDFACC, FAHA, FASPC, FNLA
Chair, ACC Prevention of Cardiovascular Disease Leadership Council and Section
The Medical University of South CarolinaCharleston, SC
Disclosures Advisory board/Consultant: Amgen, AstraZeneca, Sanofi Regeneron
Do you remember… Mindset pre-1950’s?
How could a behavior as widespread as cigarette smoking with so little apparent acute toxicity, cause major chronic health problems?
Oh, so glamorous….
And so rugged…
50% of doctors were smoking cigarettes in 1950…
• 1964: Publication of first USPHS Surgeon General’s report on smoking more than half a century ago.
• Identified tobacco smoking as a principle cause of lung and laryngeal cancer and major contributing factor in CHD, PAD, HTN.
• Heralded one of the most successful public health campaigns in the 20th century.
https://www.cdc.gov/statesystem/cigaretteuseadult.html.https://www.cdc.gov/statesystem/cigaretteuseyouth.html.
Worldwide cigarette consumption is still increasing…
http://www.tobaccoatlas.org/topic/cigarette-use-globally/
Enter new, rapidly evolving, disruptive technology…
Introduction of the e-cig or Electronic Nicotine Delivery System (ENDS)
First patented by Mr. Hon Lik in 2003 and first commercially marketed e-cigarette introduced in Chinese market in 2004
Available in the U.S. in 2007 Initially via internet Then mall kiosks Then tobacco retail outlets Print advertisements
Awareness of e-cigarettes
Doubled among adults and adolescents from 2008 to 2012
In US awareness is higher among men but trying e-cigs is more prevalent among women.
Highest e-cig use is among current smokers, followed by formers smokers, with little use among non-smokers.
U.S. Sales
0
200
400
600
800
1,000
1,200
1,400
1,600
1,800
2008 2009 2010 2011 2012 2013 2014
$ M
illio
ns
Reynolds American
Philip Morris
Source: UBS, Wells Fargo (Feb 2015)
Lorillard
02468
101214161820
2010 2011 2012 2013
% U
se
Ever UseCurrent
Overall Prevalence
Source: McMillen et al. (2015). NTR. 17:1195.
https://www.cdc.gov/nchs/data/databriefs/db217.pdf
https://www.cdc.gov/nchs/data/databriefs/db217.pdf
Prevalence of Electronic Cigarette Use: Smoking Status
Source: McMillen et al. (2015). Nicotine & Tobacco Research, 17 (10), 1195-1202
EVER Use Past 30 Day Use
0102030405060708090
100
2010 2011 2012 2013
% U
se
Never SmokerFormer SmokerNonDaily SmokerDaily Smoker
0102030405060708090
100
2010 2011 2012 2013
% U
se
In 2015 (CDC)
• 58.5% of users also use tobacco cigarettes (dual users)
• 29.8% former smokers
• 11.4% never smoked
https://www.cdc.gov/nchs/data/databriefs/db217.pdf
E-cigarettes
Rapid market penetration
“Smoke-like” inhaled aerosol imitates tobacco smoke visually
Replicates sensation in mouth and throat
Same hand-to-mouth behaviors
E-cigarettes and marketing
Tobacco advertising banned on TV/radio since 1970s
Celebrities used to market e-cigs since 2009
Claims Healthier than cigarettes Cheaper than cigarettes Cleaner than cigarettes Smoke anywhere Circumvent smoke-free policies No secondhand smoke Modern Cessation claims Harmless water vapor
2014 Sports Illustrated swimsuit issue (February 2014)
Magazine Advertising
blu e-cigarettes, Car and Driver (April 2015), Men's Journal (April & May 2015, Playboy (April & June 2015), Maxim (June/July 2015), http://trinketsandtrash.org/detail.php?artifactid=9859&page=1; http://trinketsandtrash.org/detail.php?artifactid=9882&page=1
blu e-cigarettes, Car and Driver, Playboy (May 2015); Men's Journal and Popular Mechanics (June 2015), http://trinketsandtrash.org/detail.php?artifactid=9993&page=1; Also appeared in Cosmopolitan (April 2015)
Magazine Advertising with actors
2. Magazine Advertisements Like old cigarette ads, e-cigarette magazine ads feature rugged men ...
... and glamorous women…and glamorous women
Billboard on I-95 South in Miami, FL, December 2013
Billboard Advertisements
Sports/event sponsorships
Bank of America 500, Charlotte, NC, October 2014
Mistic Facebook Post, May 10, 2014 https://www.facebook.com/MisticElectronicCigarettes/photos/a.511099415652844.1073741825.350217771741010/603283403101111/?type=3&theater
Point of Sale / Sales Near Candy
E-cigarette counter display near candy. Taken January 20, 2014 in Yanceyville, NC E-cigarette counter display near candy. Taken
August 2, 2013 in Denver, CO
ENDS: an infinite number of new questions
What are ENDS?
What harms do ENDS pose to users and bystanders?
Can ENDS help tobacco smokers quit?
Are ENDS a gateway to tobacco smoking, addicting new users, particularly the young, to nicotine?
Should ENDS be tolerated or even favored over tobacco, as a less harmful substitute for those unable to stop smoking?
US Patent Application
“An electronic atomization cigarette that functions as substitute for quitting smoking and cigarette substitute” (patent No. 8,490,628 B2)
Grana, et al. Circulation. 2014;129:1972-86
Basic Anatomy of ENDS
Image Sources: Legacy Factsheet
Indicator Tip
Battery
Vaporizer
Mouthpiece
Devices Manufactured mainly in China Wide variability in product engineering Varying solutions used to generate nicotine aerosol
Volume of solution Carrier compounds (usually propylene glycol with or without
glycerin/glycerol) Additives Flavors
Varying battery voltage Users can modify products (eg, to deliver marijuana) Variability in heating, conversion of nicotine solution to
aerosol, levels of nicotine and other chemicals delivered to use and environment
Four generations First generation:
cigalikes Heavier than tobacco
cigarettes LED light simulates
when inhaling Some disposable,
some rechargeable Cheap, easy to use Battery and cartridge
with atomizer
Four generations
Second generation:Mid-size electronic cigarettes
Larger Look like pens or laser pointers Pre-filled or refillable cartridge Push “fire” button when you
inhale (regulate length/frequency of puffs)
Improved battery capacity (1-2 days)
Four generations Third generation:Advanced personal vaping device
Favorite of advanced users Large, refillable cartridge Can easily modify voltage,
wattage output Design more effective
delivery of desired vapor Manual “fire” button Much larger
Four generations
Fourth generation:Innovative regulated mods Automatic temperature
control Adjustable and dual
air-flow
ENDS liquids
Basic Ingredients of e-liquid:• Water• Humectant(s)
• Propylene Glycol (base or carrier for nicotine and flavorings)• Vegetable Glycerin (base or carrier for nicotine and
flavorings)• Nicotine
• Various concentrations• 0-36 mg/mL in cartridges/cartomizers• Up to 100 mg/mL in refill fluids
• Flavoring agents (food flavorings to create specific taste)
http://www.veppocig.com/how-to-choose-nicotine-strength/
ENDS liquids: propylene glycol
Wieslander et al. 2001, Occup Environ MedVardavas et al. 2012, Chest
Choi et al. 2010, PlosOne
Inhalation exposure Short-term: eye, throat, airway irritation Long-term: can result in asthma in children
Used in theatrical fog/smoke machines Respiratory, throat, nose irritation
Supports possible respiratory irritation in some individuals
ENDS liquid: glycerin Humectant used instead of or in combination
with propylene glycol for aerosol production Most common is vegetable glycerin
Material Safety Data Sheet Slightly hazardous in case of skin or eye contact,
ingestion, and inhalation Prolonged exposure may cause organ damage
http://www.sciencelab.com/msds.php?msdsId=9927350
ENDS liquid:
http://www.sciencelab.com/msds.php?msdsId=9926222
• Large amounts of nicotine are lethal.• Is also insecticide and toxicant• 60 mg adult• 6 mg children
• Some ENDS manufacturers include caution labels for nicotine use.
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Nicotine Delivery Potential to deliver nicotine directly to
pulmonary system for rapid absorption (unlike NRT)
Nicotine delivery varies By product Less nicotine is delivered in original ENDS than
tobacco cigarettes, but newer options improve delivery Experience with the product Differential nicotine delivery novice vs. experienced users
Nicotine content of cartridge e-liquid had poor concordance of labeled and actual nicotine content
Secondhand exposure
ENDS do not burn or smolder Do not emit side-stream smoke
Bystanders are exposed to aerosol exhaled by user Low levels of nicotine, toxins, metals Much lower levels compared with
conventional cigarette emissions Particulate matter also exhaled Not “harmless water vapor”
ENDS: aerosol
ENDS vapor contains known carcinogens and toxic chemicals (formaldehyde and acetaldehyde), Also potentially toxic metal nanoparticles from the vaporizing
mechanism
Minor adverse events Headache, chest pain, nausea, cough, mouth irritation
Major adverse events Singular case reports of hospitalizations for pneumonia,
congestive heart failure, seizure, rapid heart rate, burns
Bottom line Long term risks largely unknown--more research needed
~trace levels of∧
Toxic compound Conventional cigarette [µg]
Electronic cigarette[µg per 15 puffs]
Conventional vs. electronic cigarette
Formaldehyde 1.6-52 0.20-5.61 9
Acetaldehyde 52-140 0.11-1.36 130
Acrolein 4.6-14 0.07-4.19 4
Toluene 6.4-9.0 0.02-0.63 23
NNN 0.012-0.37 0.00008-0.00043 145
NNK 0.009-0.08 0.00011-0.00283 30
Cd 0.03-0.35 0.001-0.022 16
Ni 0.003-0.60 0.011-0.029 15
Toxicants in vapor
Goniewicz et al., 2013, Tob Control
Health risks of tobacco products
Highly addictive
Cancers
Cardiovascular disease
Respiratory disease
Harm to others
Addictiveness dependent on delivery
Theoretical, no evidence
Risk low in those without CVD, but some risk in those with CVD
No
No
Adverse reproductive effects Some risk, but likely less than smoking
CIGARETTE SMOKE • >7000 different chemicals• >69 cause cancer• Many others are toxic
NICOTINE• 1 chemical• Neuroadaptive effects• Very high levels (>500 mg)
can be fatal
Calls to poison control centers
http://www.tobaccoatlas.org/topic/cigarette-use-globally/
Summary: not an obvious answer…….
Effects on youth…
Primary Concerns:1. Stem cell pulmonary cytotoxicity2. Nicotine initiation3. Gateway to other tobacco use4. Renormalizing smoking behavior
E-Cig Use among Adolescents: Concerning Trend?
In 2014, more high school seniors used e-cigarettes (17.1%) than traditional cigarettes (13.6%)
Among those who had used e-cigarettes, 20.3%reported never smoking conventional cigarettes
Dual use with conventional cigarettes is most common: 61% in MS, 80% in HS students
Johnson et al., 2015
0
5
10
15
20
25
30
35
6 Month Follow-up 12 Month Follow-up 6 Month Follow-up 12 Month Follow-up
%
% Ecig Never Use
% Ecig Ever Use
Risk difference = 22.7 (95% CI: 16.4 - 28.9)
Risk difference = 15.9 (95% CI: 10.0 - 21.8)
Risk difference = 6.7 (95% CI: 2.7 -
10.7) Risk difference = 4.7 (95% CI: 1.0 -
8.4)
Does E-Cigarette Use Lead to Other Tobacco Use?Prevalence of Combustible Tobacco Product Use During Past 6 Months Among Baseline E-cig (Non)Users
Overall Follow-Up AOR = 2.73 (95% CI: 2.00 - 3.73)
Overall Follow-Up AOR = 1.75(95% CI: 1.10 - 2.77)
Leventhal et al. (2015). Association of Electronic Cigarette Use With Initiation of Combustible Tobacco Product Smoking in Early Adolescence. JAMA, 314(7), 700-707.
New tools in the tobacco control intervention toolbox:
What is the role of e-cigs?
Two Different Approaches
Less Harm Nicotine is the highly
addictive component of tobacco smoke
Not the primary ingredient in tobacco that causes cancer, respiratory, and cardiovascular diseases
End the Addiction Risks of maintaining nicotine
addiction
Uncertain long-term personal and public health consequences
Unproven efficacy as cessation aid
versus
Show me the evidence…
ENDS in smoking cessation: clinical trials
Four clinical trials 2 very small sample sizes 3 did not have control group One compared e-cig to SOC with 21 mg
nicotine patch None with behavioral support Early generation devices that are no longer
widely used
Pragmatic RCT in Auckland, NZ (2011-2013)
657 smokers who wanted to quit
Randomized 4:4:1 ratio 16 mg nicotine e-cigs 21 mg nicotine patch daily Placebo e-cigs Low intensity behavioral
support with voluntary telephone counseling
Outcome: biochemically verified abstinence at 6 months
Bullen, et al. Lancet. 2013;382:1629-37
Results Very low rates of abstinence overall Insufficient power to conclude superiority of
nicotine e-cigarettes to patches or to placebo e-cigarettes.
No significant differences in adverse events
ECLAT (Italy)
Prospective 12-month RCT of 300 smokers not intending to quit
2 nicotine strengths of a popular e-cigarette model (‘Categoria’; Arbi Group Srl, Italy) compared to its non-nicotine choice. Group A (n = 100): 7.2 mg nicotine cartridges for 12 weeks; Group B (n = 100): 6-weeks 7.2 mg nicotine cartridges followed
by 6-weeks 5.4 mg nicotine cartridges Group C (n = 100): no-nicotine cartridges for 12 weeks
PLOS ONE. 2013;8:e66317
Cochrane Review 2014McRobbie et al
• Two trials suggest that ECs may help smokersto stop smoking long-term
• Small number of trials, low event rates, andwide confidence intervals
• Lack of biochemical assessment of actualreduction in smoke intake
• No evidence emerged that short-term ECuse is associated with health risk.
• Lack of difference between the effect ofECs compared with nicotine patches
USPSTF Recommendation Statement: 10/2015
Identified only 2 RCTs that evaluated the effect of e-cigs on smoking abstinence and found mixed results.
Neither reported adverse events.
How they may affect fetus is unknown.
Annals of Internal Medicine. 2015;163:622-34
USPSTF Recommendation Statement: 10/2015
“The USPSTF concludes that the current evidence is insufficient to recommend ENDS for tobacco cessation in adults, including pregnant women.”
“The USPSTF recommends that clinicians direct patients who smoke tobacco to other cessation interventions with established effectiveness and safety.”
Annals of Internal Medicine. 2015;163:622-34
2016 Cochrane Review Update Combined results from two studies, involving
662 people, showed that using an EC containing nicotine increased the chances of stopping smoking in the long term compared to using an EC without nicotine.
We could not determine if EC was better than a nicotine patch in helping people stop smoking, because the number of participants in the study was low. More studies are needed to evaluate this effect.
None of the studies found that smokers who used EC short- to mid-term (for two years or less) had an increased health risk compared to smokers who did not use ECs.
E-Cigs in real world: Systematic review and meta-analysis (Kalkhoran, Glantz)
38 studies included in systematic review 20 with control groups included in meta-
analysis Odds of quitting conventional cigarettes were
28% LOWER in those who used e-cigs compared with those who did not OR 0.72 (95% CI 0.57 to 0.91)
No difference in studies of smokers interested in smoking cessation
Lancet Respir Med. 2016;4:116-28
E-Cigs in real world: Systematic review and meta-analysis
Lancet Respir Med. 2016;4:116-28
As currently being used, e-cigarettes are associated
with significantly less quitting among smokers.
Review new tobacco products not yet on the market Registering manufacturing establishments and providing product
listings to the FDA Report ingredients, and harmful and potentially harmful constituents Requires premarket review and authorization of new tobacco products
by the FDA Places health warnings on product packages and advertisements Requires age verification by photo ID for purchase; No sales under
age 18 Disallows vending machine sales Disallows free samples
This final rule went into effect on August 8, 2016.
FDA and ENDS regulation
Public Health:Hope or Caution?
Effects on Individual Pros
Decrease toxicant exposure
Promote quitting? Cons
Dual Use Maintenance of long term
nicotine dependence
Effects on Population Pros
Lower smoking prevalence
Reduced healthcare burden of disease
Cons Youth initiation Undermine smoking
restrictions Renormalizing smoking
What to tell patients… Support a smoker’s quit attempt Ask, advise, assess, assist, arrange If appropriate, consider conventional smoking
cessation medications. Safest, most proven are
Varenicline Bupropion NRT
Referral to QUIT line Counseling support program
What to tell patients… If patient fails initial treatment, intolerant or refuses
conventional smoking cessation medication, and wishes to try e-cigs to aid quitting, it is reasonable to support the attempt.
Explain Likely much less toxic Unregulated Contain toxic chemicals Not proven Quit conventional cigarettes as soon as possible Do not use indoors or around children because others
exposed to nicotine and other toxins Urge to set quite date for e-cigs, do not use indefinitely
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