1. Addressing E-cigarettes and vaping in your practice
American Academy of Pediatrics
NY Chapter 2 meeting
June 18, 2018
Karen M. Wilson, MD, MPH, FAAP
Debra and Leon Black Professor and Division Chief of General Pediatrics
Vice-Chair for Clinical and Translational Research
Icahn School of Medicine at Mount Sinai

2. Disclosure: In the past 12 months, I have had no relevant financial relationships with the manufacturers of any commercial product or providers of commercial services discussed in this CME activity.  I do intend to discuss an unapproved or investigative use of a commercial product or device.
Reference discussion of electronic cigarette products
Illustrated Surgeon General’s Report on Smoking - Alfred Gescheidt, 1964

3. Support
R01CA A1
Intervening with smoking parents of inpatients to reduce exposure (INSPIRE)
Flight Attendant Medical Research Institute through a grant to the American Academy of Pediatrics Julius B. Richmond Center of Excellence
Icahn School of Medicine at Mount Sinai

4. Julius B. Richmond Center of Excellence
…dedicated to protecting children from secondhand smoke, and
ensuring that all clinicians ask the right questions about tobacco and SHS exposure
Established at the American Academy of Pediatrics (AAP) in 2006 in recognition of the serious health risks that children and families face from exposure to SHS
Overarching goal of RCE: to improve child and family health by engaging and activating clinicians in efforts to prevent exposure to SHS and tobacco
Accomplish goal through: research and translation of research evidence into policy and practice for clinical practice and health care systems

5. Objectives At the end of the session, participants will be able to:
State what e-cigarettes are and how they are used
Describe new information on the composition of electronic cigarette aerosol, and potential harms
Counsel teens and parents about the risks of adolescent electronic cigarette use, and how electronic cigarettes may lead to combusted tobacco use
Describe the current regulatory environment around electronic cigarettes

6. Definitions and terms Electronic cigarettes
Electronic Nicotine Delivery Systems
E-Hookah
Vape pens
Personal vaporizer
E-cigar
There are many terms that are used to describe electronic cigarettes…

7. First Generation “Cigalikes”
AKA: minis
Examples: Blu, Logic, Vuse, Mark 10
Can have manual or automatic heating
Disposable or Rechargeable
Original e-cigarette design
Made up of an LED, battery and cartridge which houses the e-liquid and atomizer
The atomizer is where aerosolization occurs as e-liquid is fed via a wick.

8. Second Generation “Tank Systems”
AKA: Personal Vaporizers, Mid-size, Vape Pens
Examples: eGo, EVOD, Apollo, Halo, Vapor Fi
Available with many types of atomizers, batteries and mouthpieces
All rechargeable
Most have manual heating button
Available in tunable and non-tunable voltage batteries
Usually come in a kit for customization
Tank systems – the 2nd generation improves design to consistently deliver more “aresol”
Made up of a battery, atomizer and a tank which holds a large volume (usually 5-10 mL of e-liquid)
Also has a manual heating button to preheat the atomizer coil.
May have tunable voltage
Purchased in “kit” form
Allows users the ability to manipulate deliver and nicotine “dose”

9. Third Generation “Mods”
AKA: Advanced Personal Vaporizers (APVs)
Examples: Apollo, Henley, Volcano
Most advanced form of e-Cigarettes – preferred by hobbyists and eCig pros
Fully rebuildable and customizable
Rechargeable lithium ion battery
Most have manual heating button
Many customizable functions including:
integral liquid feed
multiple style tanks
digital readouts
variable voltage (voltage amplifiers)
full electronic control
Most advanced form of e-cigarette.
Usually look nothing like a traditional cigarette.
Typically highly “customized”

10. Heat not burn

12. Dripping “New” method of using electronic cigarette liquid
Recent study- 26% of teen Ecig users (CT) have tried it
Placing liquid directly on coil and inhaling vapor
May increase amount of nicotine and toxic chemicals

13. IMAGE CITATION:
S. Tanski, personal photo, April 2014.
This iPhone case, which is also a tank-style vaping device.

14. An electronic cigarette that has been bedazzled.

15. Some examples of how e cigarettes are packaged and marketed

16. 2014 Adults and ENDS Use Schoenborn & Gindi, 2015
In 2010, a total of 1.8% of U.S. adults reported having used an e-cigarette at some time, a rate that rose to 13.0% by 2013; reports of “current use” increased from 0.3% to 6.8% during this period. In this slide, you can see that while most adults who use e cigarettes are current or former smokers, there’s are some who are either never smokers or who quit some time ago.
Schoenborn & Gindi, 2015

17. Teen vaping
What about teenagers?

18. First time in almost 2 decades
High school student current tobacco use National Youth Tobacco Survey (NYTS)
No decline in cig use:
First time in almost 2 decades
E-cigarette
Use triples
CITATION: Singh T et al MMWR April 2016
- Between 2013 and 2014, e cigarette use tripled, then increased again in 2015 to about 17%. On the other hand, cigarette smoking rates, which have been declining for 20 years, leveled off in Electronic cigarette use is now higher than smoking tobacco.
Singh T et al, MMWR April 2016

19. 2015-16: drop in overall tobacco use;
High school student current tobacco use National Youth Tobacco Survey (NYTS)
: drop in overall tobacco use;
Leveled off in 2017
CITATION: Singh T et al MMWR April 2016
- Between 2013 and 2014, e cigarette use tripled, then increased again in 2015 to about 17%. On the other hand, cigarette smoking rates, which have been declining for 20 years, leveled off in Electronic cigarette use is now higher than smoking tobacco.
Singh T et al, MMWR April 2016

20. Percentage of High School Students Who Ever Used Electronic Vapor Products,* by Sex, Grade,† and Race/Ethnicity,† 2015
Data for this slide are from the 2015 National Youth Risk Behavior Survey. This slide shows the percentage of high school students who ever used electronic vapor products (e-cigarettes, e-cigars, e-pipes, vape pipes, vaping pens, e-hookahs, and hookah pens such as blu, NJOY, or Starbuzz).
*E-cigarettes, e-cigars, e-pipes, vape pipes, vaping pens, e-hookahs, and hookah pens such as blu, NJOY, or Starbuzz
†10th > 9th, 11th > 9th, 11th > 10th, 12th > 9th, 12th > 10th; H > B, H > W (Based on t-test analysis, p < 0.05.)
All Hispanic students are included in the Hispanic category. All other races are non-Hispanic.
Note: This graph contains weighted results.
National Youth Risk Behavior Survey, 2015

21. Why? Bold et al, Pediatrics, 2016
This slide shows the reasons that middle and high school tried electronic cigarettes- the highest percentage was curiosity, followed by good flavors, friends use, and that they were healthier than cigarettes.
Bold et al, Pediatrics, 2016

22. Gateway to smoking?
The adolescent brain appears uniquely susceptible to nicotine addiction
Animal studies have demonstrated that nicotine exposure during the adolescent period has long-standing effects in the brain including cell damage that leads to both immediate and persistent behavior changes.
These effects are not found with nicotine exposure to the adult, supporting the idea that the adolescent is uniquely susceptible to nicotine addiction.
Are electronic cigarettes truly a gateway to smoking combusted tobacco?
Slottkin, Neurotox & Teratol 2002

25. E-cigarette use among California Cohorts, 1994-2014 by grade and gender
This slide reports on tobacco use rates in a cohort of southern California teens- while you can see a steady decrease in smoking rates through 2005, when you combine cigarette and e cigarette use, the rates are significantly higher than the smoking rate in 2005, and in fact are back at about 2000 levels.
Jessica L. Barrington-Trimis et al. Pediatrics 2016;138:e
©2016 by American Academy of Pediatrics

26. Low risk are more likely to transition
In this study the investigators followed a cohort of high school students in California; they were categorized at baseline into susceptive and not susceptible to future tobacco use, and by baseline electronic cigarette use.
Barrington-Trimis et al, Pediatrics 2016

27. Low risk are more likely to transition
You can see that while there is no significant relationship between electronic cigarette use and cigarette use among those who already report susceptibility to tobacco, there is a 9 fold increase in smoking for those who report susceptibility. This suggests that electronic cigarettes are most likely to lead to smoking in kids who were not previously contemplating becoming smokers, and strong evidence for the gateway theory.
Barrington-Trimis et al, Pediatrics 2016

28. E-cigarette liquid IMAGE CITATION:
S. Tanski, personal photo, April 2014.
-I’m now going to spend a little time talking about electronic cigarette liquid, and new studies that have shed light on the potential harms.

29. Constituents of e-liquids
Propylene glycol: general recognized as safe
Acceptable for use in flavorings, drugs, cosmetics and as direct food additive
Few human studies for inhalation, however has been used as a tobacco humectant historically
Can cause eye and respiratory irritation
MSDS from Dow Chemical states “inhalation exposure to [propylene glycol] mists should be avoided”
EPA cites a single rat study from 1947 for their inhalation effects)
Werley et al, Toxicology 2011

30. Other humectants Vegetable glycerin: generally recognized as safe
When heated and vaporized, can form acrolein, which can cause upper respiratory irritation
For all: unknown long-term health impacts from repeated inhalation

31. Humectant Toxicity – recent evidence
When an EC user takes a puff, it activates a heating element to vaporize the e-liquid. This can achieve temperatures of 350 C, which is high enough to physically change the e-liquids and change the chemical reactions between the chemical constituents – this can lead to thermal decomposition, leading to formation of potentially harmful compounds. VG and PG have been shown to decompose, creating carbonyl compounds.
These findings show that increasing voltage from 3.2 to 4.8 V resulted in 4 to over 200 times increase in formaldehyde, acetaldehyde, and acetone levels. The levels of formaldehyde in vapors from high-voltage devices were in the range of levels reported in tobacco smoke (1.6–52 μg/cigarette; Counts, Morton, Laffoon, Cox, & Lipowicz, 2005). This finding suggests that in certain conditions ECs might expose their users to the same or even higher levels of carcinogenic formaldehyde
than tobacco smoke.
Kosmider et al, Nicotine & Tobacco Research 2014

32. Nicotine Not present in all e-liquids Nicotine effects: low doses
Complex pharmacodynamics – neural stimulant at low doses and a depressant at high doses
Nicotine overdose
Excess: nausea and vomiting, excessive salivation, abdominal pain, pallor, sweating, hypertension, tachycardia, ataxia, tremor, headache, dizziness, muscle fasciculations, and seizures
Death: several case reports of suicide by nicotine
One child death in the US
New regulations for child safe packaging
There are targets for nicotine (receptors) throughout the body, however,
allowing nicotine to have broad physiological effects. With repeated exposure to nicotine,
tolerance to some of the effects of nicotine develops, and leads to needing more nicotine.
Insufficient nicotine in someone who is dependent leads to craving and withdrawal
symptoms of irritability, anxiety, restlessness, and anhedonia. The basis of nicotine
addiction is reinforcement of behavior that restores nicotine and makes the user feel good
and avoid withdrawal.4 Regular users develop habits associated with nicotine use that also
become connected with the rewarding feelings of nicotine use, creating cues for use. This is
how smokers become cued to want a cigarette after a meal, or with coffee, or in certain
locations, for example. Cigarettes are carefully engineered to deliver nicotine quickly and
efficiently to the brain to reinforce addiction. The cigarette is the delivery device, but the
nicotine is the basis of the psychoactive effects.

33. How much do you get per puff?
HIGHLY variable
2013 study found 0-35 μg/puff, so minimum of 30 puffs to deliver the 1mg nicotine inhaled from a traditional cigarette
Only part of the nicotine is vaporized, and of that 50-60% of nicotine is inhaled
Wide variability in vaping behavior of ten volunteers:
Puff duration 1.8 +/- 0.9s, puff volume 70 +/- 68 ml, puffs/session 15 +/- 6.
Goniewicz, et al. Nicotine and Tobacco Research 2013

34. Factors that affect aerosol delivery
USER FACTORS
Puff duration
Puff volume
Puff profile (i.e. bell vs. square – machine smoking)
User’s experience
DEVICE FACTORS
Solvent (Propylene Glycol/Glycerin)
Voltage
Wick design/efficiency
Draw resistance
Atomizer design (single vs. dual coil)
Heating element resistance
Manual versus automatic activation
Overview of factors that affect exposure.
Major factors are user based or device based.
The user has control over the puffing parameters and sometimes control setting on the device.
Many of the device components are optimized to deliver consistent aerosol
The design is rapidly changing as new products emerge and much work is need to understand how the design impacts delivery as the products evolve.
Each of these topics is a talk on its own.

35. Design has large impact on aerosol delivery: Time dependent comparison of plasma nicotine
As E-cigarette “evolve” the devices have become more efficient in nicotine delivery.
Green line represents a traditional cigarette.
Blue line represents a 1st generation or “cigalike” device
Red line represents a 2nd generation or Tank device.
Comparable nicotine plasma concentrations can now be achieved using an e-cigarette device, although it takes longer.
This study is slightly dated due to the rapid evolution of e-cig products, new products likely deliver nicotine even faster.
The likely goal is to develop a device that rapidly delivers sufficient nicotine comparable to a cigarette.
Farsalinos, K.E., Scientific Reports, 2014, doi: /srep04133

36. Flavors V2: Eucalyptol, Camphor, Menthol, Pulegone, Cinnamaldehyde
Premium: Eucalyptol, Camphor, Menthol, Pulegone, Cinnamaldehyde, Ethyl Salicylate
eSmoke: Eucalyptol, Camphor, Menthol, Pulegone
South Beach Smoke: Eucalyptol, Camphor, Menthol, Pulegone, Cinnamaldehyde
Flavors are added to give e-cigarettes their characteristic and unique flavor
Thousands of unique e-liquid flavors are available, and that number continues to grow.
Flavors often contain images that are enticing to youth (candy, sweets) as well as adults (alcohol)
Flavors used in eCigs are quite different than smokeless and traditional cigarette products.

37. It’s just water vapor, after all
CITATION:

38. What are the harms of the aerosol?
Second-hand vapor is NOT just water vapor
Emit variable levels of nicotine (1/10th that of cigarettes), plus fine particles of similar size to that of cigarettes, and comparable concentration of fine particles
Emit low levels of other toxins: formaldehyde, acetaldehyde, metals
Czogala et al, Nicotine and Tobacco Research 2013
Fuoco et al, Environmental Pollution 2014

39. Role of surface contamination
Nicotine, which combines with indoor substances such as ozone and nitrous oxide to make irritants and carcinogens (TSNAs), collects on surfaces from e-cigarette use
The aerosol can also deposit on surfaces – and nicotine can react with ozone to create TSNAs
Goniewicz and Lee, Nicotine and Tobacco Research 2014

40. Impact of secondhand aerosol
Alveolar growth is impaired in newborn mice exposed to E-cigarette emissions
Several studies by our colleagues at Johns Hopkins have used mouse models to simulate exposure to secondhand electronic cigarette aerosol. In this study, they demonstrated significantly impaired alveolar growth in newborn mice exposed to emissions- interestingly, the aerosol without nicotine also impacted alveolar growth.
McGrath-Morrow, 2015 et al PLOS One

41. Overall growth is impaired in newborn mice exposed to E-cigarette emissions
Similarly, overall growth was impaired in newborn mice exposed to ecigarette aerosol; in this case, the nicotine containing liquid was the significant contributor.
McGrath-Morrow, 2015 et al PLOS One

42. Behavioral effects Mice exposed to e-cigarette aerosol neonatally:
More head dips
Higher levels of rearing activity
Increased markers of locomotor activity
But: increased time in new location in water maze
Marker of cognitive flexibility
Finally, they followed a cohort of exposed mice into mouse adulthood, and did a series of behavioral tests. Mice exposed to ecigarette aerosol showed…
Smith, et al PLOS One 2015

43. Cardiovascular effects
E cigarette aerosol induces reactive oxygen species and DNA damage in vitro
Nicotine and other components of e cigarette aerosol disrupted endothelial barrier function
E-cigarette use independent of combusted tobacco use is associated with a 42% higher risk of heart attack

44. Exploding batteries
The dangers of electronic cigarettes are not only in the aerosol…
Feb 29, 2016

45. The harm is not just chemical
Re-normalizing the image of smoking
Allowed in places where smoking is not allowed
Advertising is unrestricted, with TV ads for the first time since 1971
Largely indistinguishable from cigarettes
And bringing us back to the conversation about teens, there is a significant concern that the use of electronic cigarettes is renormalizing the image of smoking…

46. CITATION:

47. FDA Deeming rule May 16, 2016 Extended FDA’s jurisdiction to include:
E-cigarettes
Cigars
Hookah
DOES NOT include e-liquids without nicotine
Went into effect on August 8, 2016
Well, some of the rules, anyway
Finally, I wanted to spend a few minutes discussing the FDA new deeming rule

48. Covered in Deeming Pre-market review of all new products
Minimum age of sale of 18 years
Free samples prohibited
False or misleading advertising prohibited
Required disclosure of ingredients
Registration of manufacturers
Warning labels
Disclosure of potentially harmful ingredients

49. NOT covered in Deeming
Marketing and advertising
Use of flavors

50. CITATION:
But of course we know that they are not advertising electronic cigarettes inappropriately.

51. Lawsuits Nicopure Labs v FDA Global Premium Cigars v. FDA
Lost Art Liquids v. FDA
Larry Faircloth v. FDA
Cyclops Vapor v. FDA
Cigar Association of America v. FDA
Currently, several e-cigarette companies have filed suit against the Food and Drug Administration (FDA). Of note, Nicopure Labs, LLC., an e-cigarette manufacturer, sued the FDA this past summer in federal court over the deeming rule, arguing that the deeming rule is “arbitrary and capricious” and that the FDA is violating the company’s First Amendment rights by preventing the company from making “truthful and nonmisleading statements” about the products’ safety. The AAP joined an amicus brief in the case in September. Oral arguments were heard a few days ago, and the Judge seemed to act favorably to the FDA’s defense of the deeming rule. More to come…

52. Lung juice Elecampane Root and Flower Mulletein leaf Osha Root
Yerba Mansa(whole Plant)
Yerba Santa Leaf
Dandelion Leaf
Licorice root
Lobieala Root
Water extraction tincture of Cordyceps
Reishi Mushroom Alcohol Extraction
Base of pure grain alcohol, distilled water and vegetable glycerin
And finally, a couple of slides that should keep us all on our toes…

53. Marijuana

54. www.aap.org/richmondcenter Audience-Specific Resources
State-Specific Resources
Cessation Information
Funding Opportunities
Reimbursement Information
Tobacco Control List
Pediatric Tobacco Control Guide
Tobacco Prevention Policy Tool
Second to last slide

55. Legal resources

56. AAP Policy Statement

57. Acknowledgements Julius B. Richmond Center of Excellence
Jonathan Klein, MD, MPH
Susanne Tanski, MD, MPH
Robert McMillen, PhD
Julie Gorzkowski, MSW
Mark Gottlieb, JD
James Baumberger
Tobacco Product Laboratory Group at CDC
Pat Breysse, MHS, PhD
Benjamin Blount, PhD
Joe Lisko
I’d like to thank the AAP’s Richmond Center of Excellent and the Tobacco Products group