Electronic Nicotine Delivery Systems (ENDS) Jon O. Ebbert, MD, FASAM Professor of Medicine Mayo Clinic Rochester, MN Email: [email protected] ©2012 MFMER | 3136985-1 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 ©2012 MFMER | 3136985-2 Disclosures Relevant Financial Relationship(s) Name Nature of Relationship Company Name Jon Ebbert, M.D. Consultant Nesmah Stock Shareholder (self-managed) Al Kaif Off Label/Investigational Usage None “Vaping” - Technically Aerosolization ©2012 MFMER | 3136985-4 NiCad NiMh Li-poly LiMn ENDS Evolution ©2012 MFMER | 3136985-6 ©2012 MFMER | 3136985-7 Vape Pens ©2012 MFMER | 3136985-8 Mod Systems ©2012 MFMER | 3136985-9 Pod Systems ©2012 MFMER | 3136985-10 Pod Systems ©2012 MFMER | 3136985-11 Pod System - Juul ©2012 MFMER | 3136985-12 Vaping “Archetypes” Sub-Ohm Vaping with Mod Systems “Low-profile” Vaping with Pod Systems ©2012 MFMER | 3136985-13 Aerosolization With Heat: “It’s All About The Coil” 1. Kanthal (chromium-iron- aluminum) 2. Nichrome (nickel-chrome) 3. Stainless steel 4. Nickel 5. Titanium Mod Systems Pod Systems ©2012 MFMER | 3136985-14 Mod System Coils ©2012 MFMER | 3136985-15 Pod System Coil ©2012 MFMER | 3136985-16 Coil Mechanics Drive Aerosol Production ©2012 MFMER | 3136985-17 E-Juice or E- Liquid (7,700 Flavors*) ©2012 MFMER | 3136985-18 ©2012 MFMER | 3136985-19 E-liquid Flavorings 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. ©2012 MFMER | 3136985-20 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” ©2012 MFMER | 3136985-21 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 ©2012 MFMER | 3136985-22 ©2012 MFMER | 3136985-23 Nicotine Delivery By Device Type Fearon IM, et al. Regul Toxicol Pharmacol. 2018;100:25-34. ©2012 MFMER | 3136985-24 What is a “Nicotine Salt”? Add: Benzoic acid Salicylic acid Malic acid Lower pH Make: Nicotine benzoate Nicotine salicylate Nicotine malate Salt: Free Base: • Smoother taste • Harsher taste • Higher • Limits concentration concentration delivered delivered ©2012 MFMER | 3136985-25 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) ©2012 MFMER | 3136985-26 ©2012 MFMER | 3136985-27 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 “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.” Goniewicz ML, et al. Tob Control. 2018. ©2012 MFMER | 3136985-29 Health Effects of ENDS ©2012 MFMER | 3136985-30 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 Bahl V, et al. Reprod Toxicol. 2012 Dec;34(4):529-37. ©2012 MFMER | 3136985-32 Carbonyl Compounds Created By Oxidation of E-Juice From Contact with the Heated Nichrome Wire (>350ºC) **Aerosolization - Up to 18 additional compounds Bekki K, et al. Int J Environ Res Public Health. 2014 Oct 28;11(11):11192-200. ©2012 MFMER | 3136985-33 Carbonyl Compounds in Ecig Vapor by Voltage & Heat Flora JW, et al. J Chromatogr Sci. Kosmider L, et a. Nicotine Tob Res. 2017;55(2):142-148. 2014;16(10):1319-1326. 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. ©2012 MFMER | 3136985-35 Carbonyl Production Associated with Coil Metal & Coil Age Saliba NA, etl al . J Anal Appl Pyrolysis. 2018;134:5 20-525. Formaldehyde (FA), acetaldehyde (AA), acetone (Acet), acrolein (Acr), propionaldehyde (PA), butyraldehyde (BA), glyoxal (GA), and methylglyoxal (MGA) ©2012 MFMER | 3136985-36 Heating & Reactive Oxidative Species 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. ©2012 MFMER | 3136985-37 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. ©2012 MFMER | 3136985-38 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. McCauley L, et al. Chest. 2012 Apr;141(4):1110-3. ©2012 MFMER | 3136985-39 Lithium Battery Explosions “Thermal Runaway” Shastry S, Langdorf MI. West J Emerg Med. 2016 Mar;17(2):177-80. PubMed PMID: 26973744. Injury types: • Flame • Chemical • Blast Brownson EG, et al. N Engl J Med. 2016 Oct 6;375(14):1400- 1402. PubMed PMID: 27705271. ©2012 MFMER | 3136985-40 ENDS & Health Risk Conclusion 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. ©2012 MFMER | 3136985-41 ENDS Prevalence & Impact ©2012 MFMER | 3136985-42 Conceptual Framework for Transition from ENDS Use Initiation and Progression National Academies of Sciences, Engineering, and Medicine. 2018. Public health consequences of e-cigarettes. Washington, DC: The National Academies Press. ©2012 MFMER | 3136985-43 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 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. ©2012 MFMER | 3136985-44 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 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. ©2012 MFMER | 3136985-45 Tobacco product use among high school students—2018 SOURCE: Tobacco Product Use Among Middle and High School Students — United States, 2011-2018. Morbidity and Mortality Weekly Report (MMWR), February 2019. ©2012 MFMER | 3136985-46 Cigarette Smoking Initiation Among Adolescents & Young Adults Soneji S, et al. JAMA Pediatr. 2017 Aug 1;171(8):788-797. PubMed PMID: 28654986. ©2012 MFMER | 3136985-47 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. ©2012 MFMER | 3136985-48 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 Evans-Polce RJ, et al. J Adolesc Health. 2017 Dec 20. PubMed PMID: 29273302. ©2012 MFMER | 3136985-49 Summary Reports & Expert Recommendations ©2012 MFMER | 3136985-50 ©2012 MFMER