E-Cigarettes & Heated Tobacco Products: Latest Developments
Transcript of E-Cigarettes & Heated Tobacco Products: Latest Developments
E-Cigarettes & Heated Tobacco Products:Latest Developments
Robert M. Anthenelli, M.D.
Professor and Interim Chair
Director, Pacific Treatment and Research Center
Department of Psychiatry
University of California, San Diego, Health Sciences
Acknowledgements
• Dr. Anthenelli’s research is supported by:
– National Institute on Alcohol Abuse and Alcoholism (NIAAA) Award # R44 AA024643
– UCOP Tobacco-Related Disease Research Program Award# T29IPO379
– National Institute on Drug Abuse (NIDA) Award# UO1 DA041731
– NIAAA’s Collaborative Study on the Genetics of Alcoholism Award # U10 AA008401
– …and thanks to Lindsay Gomez and Dr. Natassia Gaznick for help with slides and visuals
Disclosures
• Consulting Agreements: Astraea Therapeutics; Pfizer
• Other Research Support: Pfizer (drug supply for UCOP TRDRP Award # T29IPO379)
• Discussion of Off-Label Drug Use: Electronic nicotine delivery systems (ENDS) and Heated Tobacco Products (HTPs) are not U.S. FDA-approved for smoking cessation
• The opinions expressed in this talk are Dr. Anthenelli’s own and do not necessarily reflect the views of the University of California
Objectives
• Examine the rapid growth of electronic nicotine delivery systems (ENDS) aka E-cigarettes and Heated Tobacco Products (HTPs) aka Heat-not-Burn Tobacco Products
• Describe evolution of e-cigarettes and Heat-not-Burn (HnB) Tobacco Products
• Discuss evidence whether they aid smoking cessation
• Describe alarming trend of greater use in teens
• Describe the effects of nicotine on the brain’s reward circuit and how that contributes to an addicted brain
Global Trends and Projections for Tobacco Use 1990-2025
First, the good news…
• For 2000-2010, smoking prevalence ↓ in 72% of countries in men and 87% of countries in women
But, the bad news…
• Only 21% of countries for men and 49% for women are on track to achieve targeta reductions
• Smoking burden projected to shift geographically
• Estimated 1.1 billion smokers in 2025
aWHO target 30% relative reduction in tobacco smoking from baseline 2010 to 2025 (i.e., 2% reduction per year). From Bilano V et al. Lancet 2015; 385: 966-976
While Smoking Combustible Cigarettes Is On The Decline, Use of ENDS is Increasing
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Global E-Cigarette Market Projections
a Compound Annual Growth Rate (CAGR) estimate = 23.8%
b CAGR estimate = 8.3%
a https://www.askthetrainer.com/global-trends-in-e-cigarette-use/ accessed October 9, 2019; bhttps://www.mordorintelligence.com/industry-reports/global-e-cigarettes-market-industry accessed October 9, 2019
Current Use (2013-2017) of Nicotine Vaping Products from 14 International Tobacco Control Policy Evaluation Project (ITC Project)
Gravely S. et al. Addiction 2019
Electronic Cigarettes (E-cigarettes)
• Battery-operated nicotine delivery devices gaining popularity as a ‘safer’ alternative to smoking conventional tobacco cigarettes
• Generally comprised of 3 components
– A cartridge holding a liquid solution containing nicotine, flavorants and other chemicals
– A heating device (vaporizer)
– A power source (usually a battery)
First Generation“Cig-a-likes”
Small lithium batteryCartridge with atomizer
limited flavor assortments
Second Generation“Vape pens”
Improved lithium batteryAdjustable voltage
Refillable cartridges
Third Generation“Mods”
Largest lithium batteryAdjustable voltage/wattage
Various shapes/sizes
E-Cigarette Designs Have Evolved
Adapted from Farsalinos and Polasa. Ther Adv Drug Saf 2014; 5: 67-86
Authors, Year
# of Subjects
Intervention Length of Intervention
Outcome Significant Differences?
Bullen, et al,2013
N = 657 E-cig vs. nicotine patch vs. placebo e-cig
13 weeks Modestly increased smoking abstinence at 6 months in e-cig users as compared to patch or placebo
No
Caponnetto et al, 2013
N = 300 2 levels of nicotine e-cigarette vs. no nicotine e-cigarette
12 weeks Reduction in expired CO levels and reported #cigs/day across all study groups vs. baseline use
p < .001
Adriaens et al, 2014
N = 48 E-cig vs. smoking as usual
8 weeks Reduction in cigarettes per day throughout 8 week study, but no difference at 8 monthfollow up
p < 0.001 at 8 weeks; not significant at 8 months
Tseng et al, 2016 N = 99 E-cig vs. placebo e-cig
3 weeks Greater reduction in the number of cigarettes smoked per day in users of e-cigs with nicotine
p = .025
Meier et al, 2016
N = 24 E-cig vs placebo e-cig crossover
3 weeks No reduction in cigarettes per day
No
Are e-Cigarettes Effective Smoking Cessation Aids?
From Gaznick NV and Anthenelli RM. Current Psychiatry, 2017; 16(5): 31-39
The Largest RCT To Date
• Compared 2nd-Gen Refillable E-Cig versus NRT (incl. combo)
• 886 adult smokers; U.K. NHS stop-smoking service– 75% failed NRT in past
– 42% had also tried e-cigs
• 1º efficacy outcome = abstinence at 52 wk
• Among quitters, also examined n(%) of those still using e-cigs versus NRT
Hajek P et al. NEJM 2019; 380(7): 629-637.
E-Cigs versus NRT as Cessation Aids
• Combustible Cig Abstinence at 52 wk
– E-Cigs = 18%, NRT = 9%
• Combustible Cig Abstainers still using product
– E-Cigs = 80%, NRT = 9%; RR = 1.83; 95% CI = 1.3-2.6
– Thus, Substituted Dependence
• Most frequent adverse events
– Nausea: NRT = 38%, E-Cig = 31%
– Throat or Mouth Irritation: NRT = 51%, E-Cig = 65%
Hajek P et al. NEJM 2019; 380(7): 629-637.
So What’s the Harm in Harm Reduction? Percentage of U.S. Middle-Schoolers
Using Tobacco Products -- NYTS 2011-2015
NYTS = National Youth Tobacco Survey. U.S. Department of Health and Human Services. E-cigarette use among youth and young adults. A report of the Surgeon General, 2016.
ENDs Being Used by Teenagers and Transitional Age Youth: Percentage of U.S. High-Schoolers
Using Tobacco Products -- NYTS 2011-2015
NYTS = National Youth Tobacco Survey. U.S. Department of Health and Human Services. E-cigarette use among youth and young adults. A report of the Surgeon General, 2016.
The Advent of High-Tech, Pod-Based E-Cigs
• Trade names: JUUL, Suorin Air, EnviiFITT, MYLE
• Smaller, concealable; mimics USB flash drive
• Delivers nicotine at concentrations akin to cigarettes
• JUUL flavor pods produce less harsh aerosol but high plasma nicotine concentrations
• Flavors, sleek high-tech design, and misperceptions that safe attract youth smokers
Current e-cigarette use among middle and high school students increased markedly
between 2017-2018 in the U.S.
Cullen KA et al. MMWR. Nov. 16, 2018; 67(45): 1276-1277
The Market for Pod-Based e-Cigarettes
• Juul Labs Inc. flavored products make up > 80% of sales
• Was on track for $2 Billion in sales in 2019 before CDC warning of lung injury associated with vaping
• Altria Group invested $12.8 Billion in JLI in 2018; $38 billion valuation (35% stake)
• Federal (White House), State (MA, MI), County, City (San Francisco), Commercial (Walmart) regulatory actions planned Maloney J. The Wall Street Journal; Wednesday, September 25, 2019: B1-B2
U.S. Outbreak of Vaping-Induced Lung Injury
• As of November 5 -- Over 2000 cases reported across 49 states with 39 deaths and counting
• 70% are men; median age = 24 years
• Patients typically present with hypoxemia following several days to a few weeks of respiratory symptoms
• Most (>80%) have reported using e-cigs containing cannabinoids, with or without nicotine, but some cases involve only nicotine e-cigs
• No single device or compound identified
• E-cig fluids have been shown to contain at least 6 groups of potentially toxic compounds: nicotine, carbonyls, volatile organic compounds (such as benzene and toluene), particles, trace metal elements according to flavor, and bacterial endotoxins and fungal glucans
https://www.cdc.gov/tobacco/basic information/e-cigarettes/severe-lung-disease.html accessed November 7, 2019; Schier et al MMWR 2019;68(36):787-790; Christiani NEJM 2019
Heated Tobacco Products (HTPs)• aka Heat-not-Burn (HnB) Tobacco Products
• Heat tobacco at lower temperatures using battery-powered electronic heating elements
• Inhalable nicotine aerosol
• ‘Authentic tobacco taste'
• Latest effort at ‘safer cigarette’
• U.S. FDA granted IQOS® Pre-Market Approval as cigarette, but not as Modified Risk Tobacco Product
• Reduced exposure to toxicants
Modified from Glantz SA TobControl 2018; 27: s1-s6; Lempert & Glantz TobControl 2018; 27: s118-s125
Marketed Heated Tobacco Products
Brand Company Year Launched Countries
glo iFuse;glo
British American Tobacco
20152016
6 including Japan, Canada,
South Korea
PloomTECH Japan Tobacco International
2016 Japan, Switzerland
lila KT & G Corp 2017 South Korea
IQOS Phillip Morris International
2014 ~30 including Spain,
South Korea, USA (limited)
Modified from Bialous & Glantz Tob Control 2018; 27: s111-s117; Glantz SA Tob Control 2018; 27: s1-s6. alil (“a little is a lot”)
The Philip Morris International IQOS Charger, Holder and Heet-Stick (tobacco stick)
from Glantz SA. Tob Control 2018;27:s1-s6; ©2018 by BMJ Publishing Group Ltd
Lessons Learned: Combustible Tobacco’s Addiction Potential
Lifetime prevalence of DEPENDENCE
overall: 26% in men and 23% in womena
among one-time users: 33% in men and 31% in womena
among daily users: as high as 90%
Among last year users of alcohol, tobacco, cannabis and cocaine, TOBACCO USERS WERE MORE LIKELY TO BE NICOTINE DEPENDENT (28%) than alcohol (5.2%), cannabis (8.2%) or cocaine (11.6%) usersb
aNational Comorbidity Study (DSM-III-R)bNational Household Survey on Drug Abuse; Kandel D et al. Drug Alcohol Depend 1997
Combustible Cigarettes: The Model Nicotine Delivery System
• Inhaled route of administration
• Lungs → arterial blood → brain (10-20 secs.)
• Rapid elimination & distribution to peripheral tissues
• Rapid onset/offset → frequent re-administration
Venous Blood Nicotine Concentrations After Smoking a Cigarette vs. Various Forms of NRT
Mitrouska I et al. Pulmonary Pharmacology & Therapeutics 2007
Blood Nicotine Concentrations Vary Based On E-Liquid Nicotine Concentrations and Device &
Approach or Surpass Combustibles
Ramôa CP et al. Tob Control 2016; 25: e6-e9.
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muscle typenicotinic receptor
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neuronal typenicotinic receptors
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Nicotine Hijacks Nicotinic ACh Receptors
Picciotto, Marina; Emerging Neuronal Nicotinic Receptor Targets; SRNT 9th Annual Meeting, Feb. 2003, New Orleans, LA
Brain Saturation of nAChRs -- High-Dose Vaping Equivalent to Combustible Cigarette Smoking!
Baldassari SR et al. Nicotine Tob Res. April 21, 2017; 430
Too Much of a Bad Thing: How Nicotine Receptors Adapt to Too Much Nicotine
The Metabolism of Nicotine - www.chm.bris.ac.uk/motm/nicotine/E-metabolisme.html accessed October 09, 2019
Up-Regulation of nAChRs with Chronic Cigarette Smoking
Brody AL et al. Intl J Neuropsychopharmacology 2013
Likely Effects of Chronic Vaping
They’ll Learn to Vape: Nicotine enhances brain mechanisms undergirding
memory formation; vaping gets yoked to environmental cues (e.g., drinking)
They’ll Want to Vape: Nicotine modulates activity of dopamine in the
brain’s reward center; vaping behavior reinforced
They’ll Need to Vape or Smoke: Chronic nicotine use up-regulates
nicotinic acetylcholine receptors (nAChRs)
- nAChR activity returns when nicotine absent (e.g., person quits vaping or smoking)
- Increased receptor number and activity contribute to nicotine withdrawal dysphoria;
Vaper / smoker relapses to “feel normal” again
Summary on E-Cigarettes
• Probably ‘safer’ than conventional cigarettes, but insufficient information available regarding long-term use and health risks
• Vapor contains nicotine which is highly addictive and other potentially harmful chemicals
• Modest evidence for potential use as aid to smoking cessation, but really more a harm reduction tool providing substituted dependence
• Current e-cig use among middle and high school students increased alarmingly between 2017-18
Read More About It
• National Academies of Sciences, Engineering, and Medicine, 2018. Public health consequences of e-cigarettes, Washington, DC: The National Academies Press. doi:https//doi.org/10.17226/24952
• Gaznick NV and Anthenelli RM. E-cigarettes and vapes: do they work for smoking cessation and should we be recommending their use? Current Psychiatry, 2017; 16(5): 31-39.