Committee on the Review of the Health Effects of
Electronic Nicotine Delivery Systems
Kathleen Stratton, Leslie Y. Kwan, and David L. Eaton, Editors
Board on Population Health and Public Health Practice
Health and Medicine Division
A Consensus Study Report of
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International Standard Book Number-13: 978-0-309-46834-3
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Public health consequences of e-cigarettes. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24952.
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COMMITTEE ON THE REVIEW OF THE HEALTH EFFECTS OF ELECTRONIC NICOTINE DELIVERY SYSTEMS
DAVID L. EATON (Chair), Dean and Vice Provost, Graduate School, University of Washington
ANTHONY J. ALBERG, Professor and Chair, Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina
MACIEJ GONIEWICZ, Associate Professor of Oncology, Roswell Park Comprehensive Cancer Center
ADAM LEVENTHAL, Director, USC Health, Emotion, & Addiction Laboratory, Professor of Preventive Medicine and Psychology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
JOSÉ E. MANAUTOU, Professor of Pharmacology & Toxicology, Interim Head, Department of Pharmaceutical Sciences, University of Connecticut
SHARON McGRATH-MORROW, Professor, Department of Pediatrics, Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine
DAVID MENDEZ, Associate Professor, Health Management and Policy, University of Michigan
RICHARD MIECH, Research Professor, Department of Youth and Social Issues, University of Michigan
ANA NAVAS-ACIEN, Professor, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University
KENT E. PINKERTON, Professor and Director, Center for Health and the Environment, Department of Anatomy, Physiology, and Cell Biology, University of California, Davis
NANCY A. RIGOTTI, Professor of Medicine, Harvard Medical School; Director, Tobacco Research and Treatment Center; Associate Chief, Division of General Internal Medicine, Massachusetts General Hospital
DAVID A. SAVITZ, Professor of Epidemiology, School of Public Health, Professor of Obstetrics and Gynecology and Pediatrics, Warren Alpert Medical School, Brown University
GIDEON St.HELEN, Assistant Professor of Medicine, Division of Clinical Pharmacology, Department of Medicine, University of California, San Francisco
KATHLEEN STRATTON, Study Director
LESLIE Y. KWAN, Associate Program Officer
AIMEE MEAD, Research Associate (from July 2017)
ALEXIS WOJTOWICZ, Senior Program Assistant
JORGE MENDOZA-TORRES, Senior Research Librarian
REBECCA MORGAN, Senior Research Librarian
DORIS ROMERO, Financial Associate (until March 2017)
MISRAK DABI, Financial Associate (from April 2017)
HOPE HARE, Administrative Assistant
ROSE MARIE MARTINEZ, Senior Director, Board on Population Health and Public Health Practice
Christine Mirzayan Science and Technology Policy Graduate Fellow
ANDREW MERLUZZI, Ph.D. Candidate at the University of Wisconsin–Madison (until April 2017)
This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following individuals for their review of this report:
R. GRAHAM BARR, Columbia University Medical Center
NEAL L. BENOWITZ, University of California, San Francisco
JOHN BRITTON, University of Nottingham
CRISTINE D. DELNEVO, Rutgers, The State University of New Jersey
JOANNA S. FOWLER, Brookhaven National Laboratory and National Institutes of Health
MARIANNA D. GAÇA, British American Tobacco Research and Development Centre
STEPHEN S. HECHT, University of Minnesota
HARLAN R. JUSTER, New York State Department of Health
PAULA M. LANTZ, University of Michigan
RAFAEL MEZA, University of Michigan
MEIR STAMPFER, Harvard Medical School and Harvard T.H. Chan School of Public Health
THOMAS A. WILLS, University of Hawaii Cancer Center
JUDITH T. ZELIKOFF, New York University School of Medicine
SHU-HONG ZHU, University of California, San Diego
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by ERIC B. LARSON, Kaiser Permanente Washington Health Research Institute, and HUDA AKIL, University of Michigan. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
On May 10, 2016, the Food and Drug Administration (FDA) issued a rule to extend regulatory authority to all tobacco products, including e-cigarettes, that meet the statutory definition of a tobacco product. This so-called “Deeming Regulation” allows FDA to regulate the manufacturing, distribution, and marketing of tobacco products such as e-cigarettes and includes automatic provisions such as youth access restrictions on sales. Although various forms of battery-powered “electronic nicotine delivery systems” (ENDS) devices have existed for more than a decade, their popularity, especially among youth, has increased in the past 5 years, although most recent data show a slight decline. In contrast to combustible tobacco cigarettes, e-cigarettes do not “burn,” and do not contain most of the estimated 7,000 chemical constituents present in tobacco smoke. Thus, it is generally believed that e-cigarettes are “safer” than combustible tobacco cigarettes, yet exposures to nicotine and a variety of other potentially harmful constituents do occur. Harm might also occur if youth who begin their “tobacco” use with e-cigarettes then transition to combustible tobacco cigarettes or if adult cigarette smokers use e-cigarettes to supplement their smoking, rather than quitting combustible tobacco cigarettes completely.
In order to inform the public about the consequences of e-cigarettes and in support of future FDA and congressional action, a thorough and objective analysis of the state of scientific evidence relating to e-cigarettes and public health is needed. To that end, the ENDS Committee was established in December 2016 under the National Academies of Sciences, Engineering, and Medicine, with an ambitious timeline to complete a
review of the science that can inform the understanding of public health risks and benefits of e-cigarettes. What are the short- and long-term health risks of regular use of e-cigarettes? What variables of the numerous types of devices and use patterns are important determinants of risk? Are e-cigarettes an effective means to quit smoking combustible tobacco cigarettes? Are e-cigarettes an “initiation pathway” of youth to smoking combustible tobacco cigarettes? These are just some of the important questions addressed by the committee in this report. Where feasible, the committee applied the most important attributes of systematic review methodology to the scientific literature to establish the strength of evidence surrounding the health risks (e.g., direct harmful effects, initiation of smoking) and benefits (e.g., smoking cessation) associated with e-cigarette use. Although the use of these products is relatively new, the committee identified more than 800 peer-reviewed scientific studies in this report. Based on this review, the committee has provided a summary of the current state of knowledge about the health risks and benefits of e-cigarette use, and has provided a series of research recommendations.
I am deeply gratified by the remarkable hard work and insights provided by my fellow committee members and indebted to the tireless and thoughtful work of the National Academies staff that so ably kept us on task throughout the duration of this study.
David L. Eaton, Chair
Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems
Boxes, Figures, and Tables
1-2 Major Provisions of the Food and Drug Administration Deeming Tobacco Products to Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act
3-3 Temporal evolution of the number/size distribution of inhaled combustible tobacco cigarette smoke particles (panel A) and e-cigarette droplets (panel B) during puffing, mouth-hold (MH), inhalation, and exhalation, based on the same initial size distribution
5-2 Effects of nicotine solvent and battery output voltage on levels of carbonyl compounds released from e-cigarettes (µg/15 puffs; n = 3; puff duration = 1.8 seconds, puff volume = 70 ml, puff intervals = 17 seconds)
7-3 Proposed signaling cascade triggered by nicotine that partially overlaps with that used by combustible tobacco cigarette smoke extracts to disrupt the endothelial cell barriers and cell proliferation
16-2 Meta-analysis of adjusted odds of current (past 30-day) combustible tobacco cigarette smoking at follow-up among non-current combustible tobacco cigarette smokers at baseline and current e-cigarette users at baseline compared with non-current e-cigarette users at baseline
18-4 Changes in diastolic blood pressure from baseline, follow-up 1 (6 ± 1 month) and follow-up 2 (12 ± 2 months) separately for e-cigarette users (exclusive and dual) and exclusive combustible tobacco cigarette smokers
18-5 Changes in the number of chronic obstructive pulmonary disease exacerbations from baseline, at follow-up visit 1 (12 ± 1.5 months) and visit 2 (24 ± 2.5 months) separately for e-cigarette users and controls
8-3 Tobacco Dependence Instruments and Questions Included, Examined in Response Models, and Retained on a Final Common Tobacco Dependence Instrument in the Population Assessment on Tobacco and Health Study Wave 1
16-1 INITIATION: Summary of Prospective Cohort Studies of the Association Between Ever Use of E-Cigarettes (Versus Never Use) and Subsequent Risk of Ever Smoking of Combustible Tobacco Cigarettes Among Youth/Young Adults Who Were Non-Smokers at Baseline
16-2 PROGRESSION: Summary of Prospective Cohort Studies of the Association Between E-Cigarette Use and Subsequent Risk of Recent Smoking/Heavier Smoking of Combustible Tobacco Cigarettes Among Youth/Young Adults
16-3 DOSE–RESPONSE: Summary of Prospective Cohort Studies of the Association Between E-Cigarette Use Frequency and Subsequent Risk of Smoking of Combustible Tobacco Cigarettes Among Youth/Young Adults
16-4 Meta-Analysis of Unadjusted and Adjusted Odds of Ever Smoking Combustible Tobacco Cigarettes Among Combustible Tobacco Cigarette–Never Smokers at Baseline and E-Cigarette–Ever Users at Baseline Compared with E-Cigarette–Never Users at Baseline