1. JUUL In The Crown? Emerging Nicotine Delivery Systems
Douglas E Jorenby, PhD
Professor of Medicine, Center for Tobacco Research and Intervention
UW School of Medicine and Public Health
14 Feb 2019

2. I have received research grant support from the US Food and Drug Administration, the National Cancer Institute, and the National Heart, Lung, and Blood Institute.

3. Objectives Today’s goals are to:
Understand multiple generations of ENDS technology and the implications for use;
Be able to critically evaluate harm reduction/dual use claims regarding ENDS;
Learn how product flavorings and developmental factors may place adolescents at increased risk.

4. Drug Delivery Mission Parameters
Easy to use
Available in many environments
Variable dosing
Low latency to drug onset

5. First Generation
Disposable

6. First/Second Generation
Rechargeable

7. Second Generation
Vape pen

8. Second Generation
Tank systems

9. Second Generation
Mod systems

10. Third Generation Resembles a USB drive Minimal vapor cloud Pod units
Nicotine salt-based delivery system

11. Imitation is the sincerest form of marketing
Vuse Alto Pod System Kit- Key Features
Pod mod system from Vuse
Includes a mixed pack of Alto Pods
Pod flavors: Original, Menthol, Mixed Berry, Rich Tobacco

12. Suorin ‘Til You Drop

13. Less Than Meets The Eye Images courtesy of ClearWay MN Forest….
….or Trees?
Images courtesy of ClearWay MN

14. New Challenges Evolving technology Improved nicotine delivery
New form factors/difficult identification
Change in output

15. So Why Should We Care?
Vaping is safe, right?

16. Context Matters
“However, the absolute magnitude of any risk attributable to e-cigarette use is likely to be very small in absolute terms, and hence substantially smaller than that arising from tobacco smoking.”
Royal College of Physicians, Nicotine Without Smoke. 28 April 2016.

17. An Alternate View
Conclusion 5-1. There is conclusive evidence that in addition to nicotine, most e-cigarette products contain and emit numerous potentially toxic substances.
Conclusion There is conclusive evidence that e-cigarette devices can explode and cause burns and projectile injuries. Such risk is significantly increased when batteries are of poor quality, stored improperly, or modified by users.
Conclusion There is conclusive evidence that intentional or accidental exposure to e-liquids (from drinking, eye contact, or dermal contact) can result in adverse health effects including but not limited to seizures, anoxic brain injury, vomiting, and lactic acidosis.
Conclusion There is conclusive evidence that intentionally or unintentionally drinking or injecting e-liquids can be fatal.
National Academies of Sciences, Engineering, and Medicine Public Health Consequences of E-Cigarettes. Washington, DC: The National Academies Press.

18. An Alternate View
Conclusion 5-4. There is substantial evidence that e-cigarette aerosol contains metals. The origin of the metals could be the metallic coil used to heat the e-liquid, other parts of the e-cigarette device, or e-liquids. Product characteristics and use patterns may contribute to differences in the actual metals and metal concentrations measured in e- cigarette aerosol.
Conclusion 7-1.There is substantial evidence that e-cigarette aerosols can induce acute endothelial cell dysfunction, although the long-term consequences and outcomes on these parameters with long-term exposure to e-cigarette aerosol are uncertain.
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. Whether or not the levels of exposure are high enough to contribute to human carcinogenesis remains to be determined.
National Academies of Sciences, Engineering, and Medicine Public Health Consequences of E-Cigarettes. Washington, DC: The National Academies Press.

19. E-cigarettes help people stop smoking.
So Why Should We Care?
E-cigarettes help people stop smoking.

20. Cochrane Review
Based upon two RCTs
Participants using an EC were more likely to have abstained from smoking for at least six months compared with participants using placebo EC (RR 2.29, 95% CI 1.05 to 4.96; placebo 4% versus EC 9%; 2 studies; 662 participants. GRADE: low). The one study that compared EC to nicotine patch found no significant difference in six-month abstinence rates, but the confidence intervals do not rule out a clinically important difference (RR 1.26, 95% CI to 2.34; 584 participants. GRADE: very low).
Hartmann-Boyce J, et al. Cochrane Database of Systematic Reviews. 2016

21. Population Survey Results
“The adjusted odds of quitting smoking were lower for those that used ENDS at baseline (9.4%, 95% CI = 5.22%-16.38%; AOR = 0.30, 95% CI = 0.13–0.72) compared to smokers who did not use at ENDS (18.9%, 95% CI = 14.24%-24.68%). Smokers who used ENDS daily at some point during the study period were also less likely to quit smoking than nonusers (AOR = 0.17; 95% CI = 0.04–0.82).”
Weaver SR, Huang J, Pechacek TF, Heath JW, Ashley DL, Eriksen MP (2018) Are electronic nicotine delivery systems helping cigarette smokers quit? Evidence from a prospective cohort study of U.S. adult smokers, 2015–2016. PLoS ONE 13(7): e

22. Breaking News!
N=886
“The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001).”
Conducted in three UK NHS service sites between 2015 and 2018
Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. DOI: /NEJMoa

23. Pros and Cons Large study with randomized assignment to treatment
Relevant real-world comparison
Biochemical confirmation
Decent follow-up rate (78.8% at 12 mos.)
No placebo control
Weekly behavioral support from trained staff
Non-trivial crossover use of products
80% of quitters vaping at 1 year (vs. 9% NRT)
Used 2nd generation devices

24. Vaping is a harm reduction strategy.
So Why Should We Care?
Vaping is a harm reduction strategy.

25. Pop Quiz
Remember the conclusions of the Academies of Sciences, Engineering, and Medicine.
While vaping may cause less harm, it is not harmless.

26. The Proof of the Pudding….

27. More Pudding

28. And More

29. Marketing Is Effective
Data from WI Dept of Health Services, Youth Tobacco Survey 2018, P (Rev 01/2019)

30. Gateway Effects
“The positive association between baseline vaping and follow-up smoking frequency was stronger among baseline nonsmokers (n = 2966; OR, 2.51; 95% CI, ) than baseline infrequent (n = 63; OR, 1.47; 95% CI, ) and frequent (n = 53; OR, 1.06; 95% CI, ) smokers (P < .001 for interaction; Table 1 and Table 2). Similar trends were found for smoking heaviness (Table 1).”
Leventhal AM, et al. JAMA ;316:
A recent meta-analysis concluded that adolescents who first tried e-cigarettes were 3.6 times more likely to be smoking at follow-up.
Soneji S, Barrington-Trimis JL, Wills TA, et al. Association between initial use of e-cigarettes and subsequent cigarette smoking among adolescents and young adults: a systematic review and meta-analysis. JAMA Pediatr. 2017;171(8):788–797

31. Dual Use
59% of e-cigarette users (as of 2015) are actually dual users (vaping + smoking)
Centers for Disease Control and Prevention. QuickStats: Cigarette smoking status among current adult e-cigarettes users by age group - National Health Interview Survey, United States,

32. Tobacco Specific Nitrosamines
Shahab L, et al. Annals of Internal Medicine ;166:

33. Carbon Monoxide
Jorenby DE, et al. Drug and Alcohol Dependence ;170:

34. Public Health Implications
E-cigarette use has eclipsed traditional smoking
Marketing provides attractive flavors and reinforces lowered perceptions of risk
Early use increases risk of dependence and progression to smoking
Dual use is very common among adults

35. Summary ENDS technology is evolving rapidly
While vaping may cause less harm, it is not harmless
Marketing (particularly of non-tobacco flavors) increases youth adoption
Early vaping more than triples risk of progression to smoking
Dual use carries significant health risks

36. https://ctri.wisc.edu/providers/e-cigs-and-vaping/
Additional Resources