Public Health Consequences of E-Cigarettes January 23, 2018 1 2 - PowerPoint PPT Presentation

HEALTH AND MEDICINE DIVISION Public Health Consequences of E-Cigarettes January 23, 2018 1

2 Committee • David L. Eaton (Chair) • David Mendez • Anthony J. Alberg • Richard Miech • Maciej Goniewicz • Ana Navas-Acien • Adam Leventhal • Kent E. Pinkerton • José E. Manatou • Nancy A. Rigotti • S • David A. Savitz haron McGrath-Morrow • Gideon S t.Helen

3 Statement of Task • Evaluate the available evidence of the health effects related to the use of electronic nicotine delivery systems (ENDS ) • Identify future federally funded research needs

4 Terminology: What are E-Cigarettes? • Heterogeneous group of products that are referred to using a widely variably terminology (e.g., ENDS , electronic cigarettes, vaporizers, mods, tanks) • May or may not contain nicotine* • Excludes heat-not-burn products* *As clarified by Mitchell Zeller, Director of FDA Center for Tobacco Products, at the committee’s first meeting

5 Report Organization S ection I: E-Cigarette Devices, Constituents, and Exposures S ection II: Effects of E-Cigarettes on Health S ection III: Public Health Implications of E-Cigarettes

6 Committee Approach • Literature S earch – February 1, 2017 to August 31, 2017 – 6 databases – Approximately 4,200 unique results identified; over 800 reviewed for the report • Literature Review and Quality Assessment • Approach to Assessing Causality – Evidence S ynthesis (Hill’s criteria) • Levels of Evidence and Conclusions

7 Approach to Assessing Causality • First examined evidence on distal health outcomes [E], then moved up the causal chain to intermediate/ short-term outcomes, mechanisms/ modes of action, and exposures General and • Considered human data most relevant simplified conceptual and animal data supportive framework of potential • In vitro data useful for hypothesis causal pathways by generation and understanding which mechanisms, but relevance for e-cigarettes could affect establishing human health risk uncertain health Source: Figure 2-1

8 Levels of Evidence Framework • Conclusive • More, higher quality studies (e.g., randomized and non- • S ubstantial randomized controlled studies) • Moderate • Conclusions can be made • Limited • Greater confidence that limitations (including chance, • Insufficient bias, and confounding factors) • No available can be ruled out) (not evidence of no effect)

9 Devices, Uses, and Exposures Source: Figure 3-1

10 Toxicology of Constituents • Conclusive evidence that … – most e-cigarette products contain and emit numerous potentially toxic substances. [ 5-1] – the number, quantity, and characteristics of [ these] substances emitted … is highly variable and depends on product characteristics … and how the device is operated. [ 5-2] • Substantial evidence that … under typical conditions of use, exposure to potentially toxic substances from e-cigarettes is significantly lower compared with combustible tobacco cigarettes. [ 5-3]

11 Nicotine • Conclusive evidence t hat exposure t o nicot ine f rom e-cigaret t es is highly variable and depends on product charact erist ics … and how t he device is operat ed. [4-1] • Substantial evidence t hat nicot ine int ake f rom e-cigaret t e devices among experienced adult e- cigaret t e users can be comparable t o t hat f rom combust ible t obacco cigaret t es.[4-2]

12 Metals • Substantial evidence t hat e-cigaret t e aerosol cont ains met als [5-4] • Limited evidence t hat t he number of met als in e-cigaret t e aerosol could be great er t han t he number of met als in combust ible t obacco cigaret t es.* [5-5] * Except for cadmium, which is markedly lower in e-cigarettes compared with combustible tobacco cigarettes

13 Health Effects Evaluated • Modes of Action • Cancers – Endothelial Cell • Respiratory Diseases Dysfunction • Oral Diseases – Oxidative S tress • Reproductive & • Dependence & Abuse Developmental Effects Liability • Inj uries & Poisonings • Cardiovascular Diseases

14 Approach to Evaluation of Health Effects • Characterization of Disease Endpoints and Intermediate Outcomes • Optimal S tudy Design • Questions Addressed by the Literature • Considered comparisons to unexposed and to smokers as appropriate • Evidence Review • S ynthesis and Conclusions • Vulnerable/ S uscept ible Populations

15 Dependence & Abuse Liability • Substantial evidence t hat e-cigaret t e use result s in sympt oms of dependence on e-cigaret t es[8-1] • Moderate evidence t hat – risk and severit y of dependence are lower for e- cigaret t es t han combust ible t obacco cigaret t es [8-2] – variabilit y in e-cigaret t e product charact erist ics … is an import ant det erminant of risk and severit y [8-3]

16 Cardiovascular Diseases • No available evidence whet her or not e- cigaret t e use is associat ed wit h clinical cardiovascular out comes … and subclinical at herosclerosis [9-1] • S ubst ant ial evidence t hat heart rat e increases af t er nicot ine int ake f rom e-cigaret t es [9-2] • Moderat e evidence t hat diast olic blood pressure increases af t er nicot ine int ake f rom e-cigaret t es [9-3]

17 Cardiovascular Diseases • Limit ed evidence t hat e-cigaret t e use is associat ed wit h a short -t erm increase in syst olic blood pressure, changes in biomarkers of oxidat ive st ress, increased endot helial dysf unct ion and art erial st if f ness, and aut onomic cont rol. [9-4] • Insuf f icient evidence t hat e-cigaret t e use is associat ed wit h long- t erm changes in heart rat e, blood pressure, and cardiac geomet ry and f unct ion. [9-5]

18 Cancers • Limited evidence from in vivo animal st udies using int ermediat e biomarkers of cancer t o support t he hypot hesis t hat long-t erm e-cigaret t e use could increase t he risk of cancer [but ] no available evidence whet her or not e-cigaret t e use is associat ed wit h int ermediat e cancer endpoint s in humans* [10-1, 10-2] *True for comparisons with both combustible tobacco cigarettes and with no use of tobacco products

19 Cancers • No available evidence from adequat e long-t erm animal bioassays of e- cigaret t e aerosol exposures t o inform cancer risk [10-2] • Limited evidence t hat e-cigaret t e aerosol can be mut agenic or cause DNA damage in humans, animal models, and human cells in cult ure [10-3] • Substantial evidence that some chemicals present in e-cigarette aerosols are capable of causing DNA damage and mutagenesis* … Whether or not the levels of exposure are high enough to contribute to human carcinogenesis remains to be determined [ 10-4] * Supports the biological plausibility that long-term exposure to e-cigarette aerosols could increase risk of cancer and adverse reproductive outcomes

20 Respiratory Diseases • No available evidence whether or not e- cigarettes cause respiratory diseases in humans [ 11-1] • Moderat e evidence f or increased cough and wheeze in adolescent s who use e-cigaret t es and an associat ion wit h e-cigaret t e use and an increase in ast hma exacerbat ions [11-4] • Limit ed evidence of adverse eff ect s of e-cigaret t e exposure on t he respirat ory syst em f rom animal and in vit ro st udies [11-5]

21 Respiratory Diseases • Limit ed evidence f or – improvement in lung f unct ion and respirat ory sympt oms among adult smokers wit h ast hma who swit ch t o e-cigaret t es complet ely or in part (dual use) [11-2] – reduct ion of COPD exacerbat ions among adult smokers wit h COPD who swit ch t o e-cigaret t es complet ely or in part (dual use) [11-3]

22 Inj uries & Poisonings • Conclusive evidence that … – e-cigarette devices can explode and cause burns and projectile injuries … [ especially] when batteries are of poor quality, stored improperly, or are being modified by users [ 14-1] – intentional or accidental exposure to e-liquids (from drinking, eye contact, or dermal contact) can result in adverse health effects … and can be fatal [ 14-2, 14-3]

23 Public Health Implications of E-Cigarettes • S moking among Y outh and Y oung Adults • S moking Cessation among Adults • Harm Reduction • Modeling of E-Cigarette Use

24 Y outh & Y oung Adult Smoking: Ever Use • Substantial evidence t hat e-cigaret t e use increases risk of ever using combust ible t obacco cigaret t es among yout h and young adult s [16-1]

25 Y outh & Y oung Adult S moking: S moking Progression Among yout h and young adult e-cigaret t e users who ever use combust ible t obacco cigaret t es: • Moderate evidence t hat e-cigaret t e use increases t he frequency and int ensit y of subsequent combust ible t obacco cigaret t e smoking [16-2] • Limited evidence t hat e-cigaret t e use increases, in t he near t erm, t he durat ion of subsequent combust ible t obacco cigaret t e smoking [16-3]

26 Adult Smoking Cessation Limited evidence t hat e-cigaret t es may be effect ive aids t o promot e smoking cessat ion overall a,b [17-1] a Very little data from randomized controlled trials b Results of trials and observational studies often differ