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Electronic Nicotine Delivery Systems(ENDS)

Jon O. Ebbert, MD, FASAMProfessor of MedicineMayo ClinicRochester, MNEmail: ebbert.jon@mayo.edu

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Goals & Objectives

• Understand the mechanics of ENDS

• Summarize the data regarding ENDS & nicotine delivery

• Define the known health risks of ENDS

• Know the rates of ENDS use of among adolescents

• Recall what summary reports expert recommendations exist on ENDS

DisclosuresRelevant Financial Relationship(s)Name Nature of Relationship Company NameJon Ebbert, M.D. Consultant Nesmah

Stock Shareholder (self-managed) Al Kaif

Off Label/Investigational UsageNone

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“Vaping” - Technically Aerosolization

NiCadNiMh

Li-polyLiMn

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ENDS Evolution

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Vape Pens

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Mod Systems

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Pod Systems

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Pod Systems

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Pod System - Juul

Vaping “Archetypes”

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Sub-Ohm Vapingwith

Mod Systems

“Low-profile” Vapingwith

Pod Systems

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Aerosolization With Heat: “It’s All About The Coil”1. Kanthal (chromium-iron-

aluminum)2. Nichrome (nickel-chrome)3. Stainless steel4. Nickel5. Titanium

Pod Systems

ModSystems

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Mod SystemCoils

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Pod System Coil

Coil Mechanics Drive Aerosol Production

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E-Juice or E-Liquid (7,700

Flavors*)

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E-liquid Flavorings

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Stratton KR, Kwan LY, Eaton DL, National Academies of Sciences Engineering and Medicine (U.S.). Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems. Public health consequences of e-cigarettes. Washington, DC: The National Academies Press; 2018.

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Solvent Carrier: Vegetable Glycerin (“VG”)

• Glycerol from vegetables

• Sweetener - 60% as sweet as sucrose

• Food preservative

• Gel capsule component

• Personal care products to make them “smooth”

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Solvent Carrier: Propylene glycol (“PG”)

• Pharmaceutical solvent

• Food additive

• Additive in moisturizer, cosmetics toothpaste, hand sanitizer

• Non-toxic antifreeze (toxic = ethylene glycol)

• Asthma inhaler & nebulizer component

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Fearon IM, et al. Regul Toxicol Pharmacol. 2018;100:25-34.

Nicotine Delivery By Device Type

What is a “Nicotine Salt”?

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Free Base:

• Harsher taste• Limits

concentration delivered

Salt:

• Smoother taste• Higher

concentration delivered

Add:Benzoic acidSalicylic acid

Malic acid

Make:Nicotine benzoateNicotine salicylate

Nicotine malate

Lower pH

Nicotine Salt Delivers More Nicotine

• Requires a higher temperature to properly vaporize (Pod system)

• Relative nicotine content• E-liquids (non salts)

• 0, 3, 6, 12, and 18 mg/mL• Juul

• 5% nicotine by weight (59 mg/mL)• 3% nicotine by weight (35 mg/mL)

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Mean blood serum nicotine levels for cigarette and ENDDs users

Yingst JM, Foulds J, Veldheer S, Hrabovsky S, Trushin N, et al. (2019) Nicotine absorption during electronic cigarette use among regular users. PLOS ONE 14(7): e0220300. https://doi.org/10.1371/journal.pone.0220300

Nicotine Salt Delivery in Pod Systems

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Goniewicz ML, et al. Tob Control. 2018.

“Median urinary cotinine concentration measured in participants who used pods was 244.8 ng/mL (IQR 8.4–1255.8), higher than 155.2 ng/mL (IQR: 68.8–579.2) in 55 adolescents (ages 13–19 years) who regularly smoked conventional tobacco cigarettes.”

Health Effects of

ENDS

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TSNAs Levels in 105 ENDS Replacement Liquids

Kim , et al. Journal of Chromatography A Volume 1291 2013 48 – 55.

ENDS Fluid & Cytotoxicity• Embryonic and adult cells & refill fluids

• Cytotoxicity varied among fluids and was correlated with the number and concentration of chemicals used to flavor fluids

• Cytotoxicity was not due to nicotine

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Bahl V, et al. Reprod Toxicol. 2012 Dec;34(4):529-37.

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Carbonyl Compounds Created By Oxidation of E-Juice From Contact with the Heated Nichrome Wire (>350ºC)

Bekki K, et al. Int J Environ Res Public Health. 2014 Oct 28;11(11):11192-200.

**Aerosolization - Up to 18 additional compounds

Carbonyl Compounds in Ecig Vapor by Voltage & Heat

Kosmider L, et a. Nicotine Tob Res. 2014;16(10):1319-1326.

Flora JW, et al. J Chromatogr Sci. 2017;55(2):142-148.

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Williams M, Bozhilov KN, Talbot P. Analysis of the elements and metals in multiple generations of electronic cigarette atomizers. Environmental research. 2019;175:156-166.

Carbonyl Production Associated with Coil Metal & Coil Age

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Saliba NA, etl al . J

Anal Appl Pyrolysis.

2018;134:520-525.

Formaldehyde (FA), acetaldehyde (AA), acetone (Acet), acrolein (Acr), propionaldehyde (PA), butyraldehyde (BA), glyoxal (GA), and methylglyoxal (MGA)

Heating & Reactive Oxidative Species

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Son Y, Mishin V, Laskin JD, et al. Hydroxyl Radicals in E-cigarette Vapor and E-vapor Oxidative Potentials under Different Vaping Patterns. Chem Res Toxicol. 2019.

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ENDS: Health Effects• 30 healthy smokers (Athens, Greece)

• Minimum of 5 pack-years • Aged 19-56 years • 14 male

• Ecigarettes for 5 minutes• Ecigarettes associated with a significant

increase in airway resistance

Vardavas CI, et al. Chest. 2011 Dec 22. PubMed PMID: 22194587.

ENDS & Lipoid Pneumonia• Ecigarettes x 7 months • SOB, fevers, cough• Chest CT showed opacities

consistent with lipoid pneumonia. • Macrophages in bronchoalveolar

lavage fluid were loaded with lipid. • Patient stopped Ecigarettes • Hypothesized condition may have

been caused by inhaling Ecigarette aerosol.

©2012 MFMER | 3136985-39McCauley L, et al. Chest. 2012 Apr;141(4):1110-3.

Lithium Battery Explosions “Thermal Runaway”

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Shastry S, Langdorf MI. West J Emerg Med. 2016 Mar;17(2):177-80. PubMed PMID:

26973744.

Brownson EG, et al. . N Engl J Med. 2016 Oct 6;375(14):1400-1402. PubMed PMID: 27705271.

Injury types:• Flame• Chemical• Blast

ENDS & Health RiskConclusion 7-2. There is substantial evidence that components of e-cigarette aerosols can promote formation of reactive oxygen species/oxidative stress. Although this supports the biological plausibility of tissue injury and disease from long-term exposure to e-cigarette aerosols, generation of reactive oxygen species and oxidative stress induction is generally lower from e-cigarettes than from combustible tobacco cigarette smoke.

Conclusion 10-4. There is substantial evidence that some chemicals present in e-cigarette aerosols (e.g., formaldehyde, acrolein) are capable of causing DNA damage and mutagenesis. This supports the biological plausibility that long-term exposure to e-cigarette aerosols could increase risk of cancer and adverse reproductive outcomes.

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ENDS Prevalence & Impact

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Conceptual Framework for Transition from ENDS Use Initiation and Progression

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National Academies of Sciences, Engineering, and Medicine. 2018. Public health consequences of e-cigarettes. Washington, DC: The National Academies Press.

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Gentzke AS, Creamer M, Cullen KA, et al. Vital Signs: Tobacco Product Use Among Middle and High School Students — United States, 2011–2018. MMWR Morb Mortal Wkly Rep

2019;68:157–164.

Estimated percentage of high school students who currently use any tobacco product,* any combustible tobacco product,† ≥2 tobacco product types,§ and selected

tobacco products — National Youth Tobacco Survey, 2011–2018¶,**,††

**Juul released June, 2015

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Gentzke AS, Creamer M, Cullen KA, et al. Vital Signs: Tobacco Product Use Among Middle and High School Students — United States, 2011–2018. MMWR Morb Mortal Wkly Rep

2019;68:157–164.

Estimated percentage of middle school students who currently use any tobacco product,* any combustible tobacco product,† ≥2 tobacco product types,§ and selected

tobacco products — National Youth Tobacco Survey, 2011–2018¶,**,†

**Juul released June, 2015

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SOURCE: Tobacco Product Use Among Middle and High School Students — United States, 2011-2018. Morbidity and Mortality Weekly Report (MMWR), February 2019.

Tobacco product use among high school students—2018

Cigarette Smoking Initiation Among Adolescents & Young Adults

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Soneji S, et al. JAMA Pediatr. 2017 Aug 1;171(8):788-797. PubMed PMID: 28654986.

ENDS and Conventional Cigarette Use

Substantial evidence: good-quality observational studies or controlled trials with few or no credible opposing findings.

• Conclusion 16-1. There is substantial evidence that e-cigarette use increases risk of ever using combustible tobacco cigarettes among youth and young adults.

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Reasons for ENDS Use Among Adolescents: Characteristics of 12th Graders With a History of Vaping • Monitoring the Future (MTF)

study: annual cross-sectional surveys of nationally representative samples of 12th grade students in public and private schools across the contiguous United States

• Completed 2015 and 2016 surveys

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Evans-Polce RJ, et al. J Adolesc Health. 2017 Dec 20. PubMed PMID: 29273302.

Summary Reports & Expert Recommendations

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Expert Panel Conclusions & Recommendations

• American Cancer Society• “…switching to the exclusive use of e-cigarettes is preferable

to continuing to smoke combustible products.”• American Heart Association

• “If a patient has failed initial treatment, has been intolerant to or refuses to use conventional smoking cessation medication, and wishes to use e-cigarettes to aid quitting, it is reasonable to support the attempt.”

• American Lung Association• “If smokers are ready to quit smoking for good, they should call

1-800-QUITNOW or talk with their doctor about finding the best way to quit using proven methods and FDA-approved treatments and counseling.”

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“Smokers who have tried other methods of quitting without success could be encouraged to try e-cigarettes (EC) to stop smoking and stop smoking services should

support smokers using EC to quit by offering them behavioral support.” – Public Health England

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Published August 2015

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Goals & Objectives

• Understand the mechanics of ENDS

• Summarize the data regarding ENDS & nicotine delivery

• Define the known health risks of ENDS

• Know the rates of ENDS use of among adolescents

• Recall what summary reports expert recommendations exist on ENDS