Advertisement
Canadian Journal of Cardiology

E-Cigarettes Reexamined: Product Toxicity

      Abstract

      The introduction of e-cigarettes, or electronic nicotine delivery systems (ENDS), has been accompanied by controversy regarding their safety and effectiveness as a cessation aid and by an explosion in their use by youth. Their use does not involve the combustion of tobacco and the creation of harmful combustion products; they have been seen as a “harm reduction” tool that may be of assistance in promoting smoking cessation. Recognition that ENDS can deliver an array of chemicals and materials with known adverse consequences has spurred more careful examination of these products. Nicotine, nitrosamines, carbonyl compounds, heavy metals, free radicals, reactive oxygen species, particulate matter, and “emerging chemicals of concern” are among the constituents of the heated chemical aerosol that is inhaled when ENDS are used. They raise concerns for cardiovascular and respiratory health that merit the attention of clinicians and regulatory agencies. Frequently cited concerns include evidence of disordered respiratory function, altered hemodynamics, endothelial dysfunction, vascular reactivity, and enhanced thrombogenesis. The absence of evidence of the consequences of their long-term use is of additional concern. Their effectiveness as cessation aids and beneficial impact on health outcomes continue to be examined. It is important to ensure that their production and availability are thoughtfully regulated to optimise their safety and permit their use as harm reduction devices and potentially as smoking-cessation aids. It is equally vital to effectively prevent them from becoming ubiquitous consumer products with the potential to rapidly induce nicotine addiction among large numbers of youth. Clinicians should understand the nature of these products and the implications of their use.

      Résumé

      L’introduction de la cigarette électronique, ou des inhalateurs électroniques de nicotine (ENDS, de l’anglais electronic nicotin delivery systems), a suscité la controverse quant à son innocuité et son efficacité pour faciliter la désaccoutumance et connu une explosion de son utilisation par les jeunes. L’utilisation des ENDS n’implique pas la combustion de tabac et ne génère pas de produits de combustion nocifs; ils ont été considérés comme des outils de « réduction des dommages » qui peuvent aider à favoriser la désaccoutumance au tabac. Le fait d’avoir constaté que les ENDS peuvent présenter un éventail de produits chimiques et de substances dont les conséquences néfastes sont connues a poussé à mener un examen plus approfondi de ces produits. La nicotine, les nitrosamines, les composés carbonylés, les métaux lourds, les radicaux libres, les espèces réactives de l’oxygène, la matière particulaire et « les nouveaux produits chimiques préoccupants » comptent parmi les constituants des aérosols chimiques chauffés qui sont inhalés lorsque les ENDS sont utilisés. Les inquiétudes en lien avec la santé cardiovasculaire et respiratoire qu’ils ont suscitées méritent l’attention des cliniciens et des organismes de réglementation. Les préoccupations les plus fréquemment citées sont notamment les données probantes sur les troubles respiratoires, les perturbations hémodynamiques, la dysfonction endothéliale, la réactivité vasculaire et l’augmentation de la thrombogenèse. L’absence de données probantes sur les conséquences de leur utilisation à long terme est en outre préoccupante. Leur efficacité pour faciliter la désaccoutumance au tabac et leurs répercussions bénéfiques sur les résultats cliniques continuent de faire l’objet d’études. Il est important de s’assurer que leur production et leur disponibilité sont soumises à une réglementation réfléchie de façon à optimiser leur innocuité, à permettre leur utilisation comme dispositifs de « réduction des dommages » et à potentiellement faciliter la désaccoutumance au tabac. Il est également essentiel de prévenir efficacement l’omniprésence de ces produits de consommation qui ont le potentiel d’induire rapidement la dépendance à la nicotine chez un grand nombre de jeunes. Les cliniciens doivent comprendre les spécificités de ces produits et les conséquences de leur utilisation.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Wilson N.
        • Summers J.A.
        • Ait Ouakrim D.
        • et al.
        Improving on estimates of the potential relative harm to health from using modern ENDS (vaping) compared to tobacco smoking.
        BMC Public Health. 2021; 21: 2038
        • Nayeri A.
        • Middlekauff H.R.
        Vaping instead of cigarette smoking: a panacea or just another form of cardiovascular risk?.
        Can J Cardiol. 2021; 37: 690-698
        • Ikonomidis I.
        • Vlastos D.
        • Kourea K.
        • et al.
        Electronic cigarette smoking increases arterial stiffness and oxidative stress to a lesser extent than a single conventional cigarette: an acute and chronic study.
        Circulation. 2018; 137: 303-306
        • Ikonomidis I.
        • Katogiannis K.
        • Kostelli G.
        • et al.
        Effects of electronic cigarette on platelet and vascular function after four months of use.
        Food Chem Toxicol. 2020; 141111389
        • Kelesidis T.
        • Zhang Y.
        • Tran E.
        • et al.
        Expression of key inflammatory proteins is increased in immune cells from tobacco cigarette smokers but not electronic cigarette vapers: implications for atherosclerosis.
        J Am Heart Assoc. 2021; 10e019324
        • Haptonstall K.P.
        • Choroomi Y.
        • Moheimani R.
        • et al.
        Differential effects of tobacco cigarettes and electronic cigarettes on endothelial function in healthy young people.
        Am J Physiol Heart Circ Physiol. 2020; 319: H547-H556
        • Biondi-Zoccai G.
        • Sciarretta S.
        • Bullen C.
        • et al.
        Acute effects of heat-not-burn, electronic vaping, and traditional tobacco combustion cigarettes: the Sapienza University of Rome—Vascular Assessment of Proatherosclerotic Effects of Smoking (SUR-VAPES ) 2 randomized trial.
        J Am Heart Assoc. 2019; 8e010455
        • Peruzzi M.
        • Biondi-Zoccai G.
        • Carnevale R.
        • et al.
        Vaping cardiovascular health risks: an updated umbrella review.
        Curr Emerg Hosp Med Rep. 2020; 8: 103-109
        • Mayer M.
        • Reyes-Guzman C.
        • Grana R.
        • et al.
        Demographic characteristics, cigarette smoking, and e-cigarette use among US adults.
        JAMA Netw Open. 2020; 3e2020694
        • Gilbert H.A.
        USA patent US3200819A.
        August 17, 1965
        • Dutra L.M.
        • Grana R.
        • Glantz S.A.
        Philip Morris research on precursors to the modern e-cigarette since 1990.
        Tob Control. 2017; 26: e97-105
        • Benowitz N.L.
        • St Helen G.
        • Liakoni E.
        Clinical pharmacology of electronic nicotine delivery systems (ENDS): implications for benefits and risks in the promotion of the combusted tobacco endgame.
        J Clin Pharmacol. 2021; 61: S18-36
        • Sanford Z.
        • Goebel L.
        E-cigarettes: an up to date review and discussion of the controversy.
        W V Med J. 2014; 110: 10-15
        • Chatterjee K.
        • Alzghoul B.
        • Innabi A.
        • et al.
        Is vaping a gateway to smoking: a review of the longitudinal studies.
        Int J Adolesc Med Health. 2018; 3020160033
        • Pepper J.K.
        • Ribisl K.M.
        • Brewer N.T.
        Adolescents’ interest in trying flavoured e-cigarettes.
        Tob Control. 2016; 25: ii62-i66
        • Watkins S.L.
        • Glantz S.A.
        • Chaffee B.W.
        Association of noncigarette tobacco product use with future cigarette smoking among youth in the Population Assessment of Tobacco and Health (PATH) study, 2013-2015.
        JAMA Pediatr. 2018; 172: 181-187
        • Hammond D.
        • Rynard V.L.
        • Reid J.L.
        Changes in prevalence of vaping among youths in the United States, Canada, and England from 2017 to 2019.
        JAMA Pediatr. 2020; 174: 797-800
        • King B.A.
        Flavors are a major driver of the youth e-cigarette epidemic.
        Am J Public Health. 2020; 110: 773-774
        • Kong G.
        • Morean M.E.
        • Cavallo D.A.
        • et al.
        Reasons for electronic cigarette experimentation and discontinuation among adolescents and young adults.
        Nicotine Tob Res. 2015; 17: 847-854
        • Leventhal A.M.
        • Goldenson N.I.
        • Cho J.
        • et al.
        Flavored e-cigarette use and progression of vaping in adolescents.
        Pediatrics. 2019; 144e20190789
        • Ambrose B.K.
        • Day H.R.
        • Rostron B.
        • et al.
        Flavored tobacco product use among US youth aged 12-17 years, 2013-2014.
        JAMA. 2015; 314: 1871-1873
        • Leventhal A.M.
        • Barrington-Trimis J.L.
        New tobacco products with fewer advertising restrictions and consequences for the current generation of youths.
        JAMA Pediatr. 2018; 172: 414-416
        • Doran N.
        • Brikmanis K.
        • Petersen A.
        • et al.
        Does e-cigarette use predict cigarette escalation? A longitudinal study of young adult nondaily smokers.
        Prev Med. 2017; 100: 279-284
        • Loukas A.
        • Marti C.N.
        • Harrell M.B.
        Electronic nicotine delivery systems use predicts transitions in cigarette smoking among young adults.
        Drug Alcohol Depend. 2022; 231109251
        • El-Hellani A.
        • El-Hage R.
        • Salman R.
        • et al.
        Electronic cigarettes are chemical reactors: implication to toxicity.
        Chem Res Toxicol. 2020; 33: 2489-2490
        • Talih S.
        • Balhas Z.
        • Eissenberg T.
        • et al.
        Effects of user puff topography, device voltage, and liquid nicotine concentration on electronic cigarette nicotine yield: measurements and model predictions.
        Nicotine Tob Res. 2015; 17: 150-157
        • Spindle T.R.
        • Eissenberg T.
        Pod mod electronic cigarettes—an emerging threat to public health.
        JAMA Netw Open. 2018; 1e183518
        • Wang T.W.
        • Gentzke A.S.
        • Neff L.J.
        • et al.
        Disposable e-cigarette use among U.S. youth—an emerging public health challenge.
        N Engl J Med. 2021; 384: 1573-1576
        • Rosenthal H.
        • Chow N.
        • Mehta S.
        • et al.
        Puff bars: a dangerous trend in adolescent disposable e-cigarette use.
        Curr Opin Pediatr. 2022; 34: 288-294
        • Groner J.
        Health effects of electronic cigarettes.
        Curr Probl Pediatr Adolesc Health Care. 2022; 101202
        • Kaur G.
        • Muthumalage T.
        • Rahman I.
        Mechanisms of toxicity and biomarkers of flavoring and flavor enhancing chemicals in emerging tobacco and nontobacco products.
        Toxicol Lett. 2018; 288: 143-155
        • Laverty A.A.
        • Vardavas C.I.
        • Filippidis F.T.
        Design and marketing features influencing choice of e-cigarettes and tobacco in the EU.
        Eur J Public Health. 2016; 26: 838-841
        • Russell M.A.
        The nicotine addiction trap: a 40-year sentence for four cigarettes.
        Br J Addict. 1990; 85: 293-300
        • Ren M.
        • Lotfipour S.
        • Leslie F.
        Unique effects of nicotine across the lifespan.
        Pharmacol Biochem Behav. 2022; 214173343
        • Kandel E.R.
        • Kandel D.B.
        Shattuck lecture: A molecular basis for nicotine as a gateway drug.
        N Engl J Med. 2014; 371: 932-943
        • Ren M.
        • Lotfipour S.
        Nicotine gateway effects on adolescent substance use.
        West J Emerg Med. 2019; 20: 696-709
        • Owens D.K.
        • Davidson K.W.
        • Krist A.H.
        • et al.
        Primary care interventions for prevention and cessation of tobacco use in children and adolescents: US Preventive Services Task Force recommendation statement.
        JAMA. 2020; 323: 1590-1598
        • Primack B.A.
        • Shensa A.
        • Sidani J.E.
        • et al.
        Initiation of traditional cigarette smoking after electronic cigarette use among tobacco-naïve US young adults.
        Am J Med. 2018; 131: 443.e1-443.e9
        • Wills T.A.
        • Sargent J.D.
        • Knight R.
        • et al.
        E-cigarette use and willingness to smoke: a sample of adolescent nonsmokers.
        Tob Control. 2016; 25: e52-e59
        • Hammond D.
        • Reid J.L.
        • Cole A.G.
        • et al.
        Electronic cigarette use and smoking initiation among youth: a longitudinal cohort study.
        CMAJ. 2017; 189: e1328-e1336
        • Chadi N.
        • Hadland S.E.
        • Harris S.K.
        Understanding the implications of the “vaping epidemic” among adolescents and young adults: a call for action.
        Subst Abus. 2019; 40: 7-10
        • DiFranza J.R.
        • Rigotti N.A.
        • McNeill A.D.
        • et al.
        Initial symptoms of nicotine dependence in adolescents.
        Tob Control. 2000; 9: 313-319
        • Leventhal A.M.
        • Stone M.D.
        • Andrabi N.
        • et al.
        Association of e-cigarette vaping and progression to heavier patterns of cigarette smoking.
        JAMA. 2016; 316: 1918-1920
        • Culbreth R.E.
        • Spears C.A.
        • Brandenberger K.
        • et al.
        Dual use of electronic cigarettes and traditional cigarettes among adults: psychosocial correlates and associated respiratory symptoms.
        Respir Care. 2021;
        • Czoli C.D.
        • Fong G.T.
        • Goniewicz M.L.
        • et al.
        Biomarkers of exposure among “dual users” of tobacco cigarettes and electronic cigarettes in Canada.
        Nicotine Tob Res. 2019; 21: 1259-1266
        • Olfson M.
        • Wall M.M.
        • Liu S.M.
        • et al.
        E-cigarette use among young adults in the U.S.
        Am J Prev Med. 2019; 56: 655-663
        • Osibogun O.
        • Bursac Z.
        • Maziak W.
        Longitudinal transition outcomes among adult dual users of e-cigarettes and cigarettes with the intention to quit in the United States: PATH study (2013-2018).
        Prev Med Rep. 2022; 26101750
        • Everard C.D.
        • Silveira M.L.
        • Kimmel H.L.
        • et al.
        Association of electronic nicotine delivery system use with cigarette smoking relapse among former smokers in the United States.
        JAMA Netw Open. 2020; 3e204813
        • Soneji S.S.
        • Sung H.Y.
        • Primack B.A.
        • et al.
        Quantifying population-level health benefits and harms of e-cigarette use in the United States.
        PloS one. 2018; 13e0193328
        • Park-Lee E.
        • Ren C.
        • Sawdey M.D.
        • et al.
        Notes from the field: e-cigarette use among middle and high school students—National Youth Tobacco Survey, United States, 2021.
        MMWR Morb Mortal Wkly Rep. 2021; 70: 1387-1389
        • Counotte D.S.
        • Smit A.B.
        • Pattij T.
        • et al.
        Development of the motivational system during adolescence, and its sensitivity to disruption by nicotine.
        Dev Cogn Neurosci. 2011; 1: 430-443
        • England L.J.
        • Bunnell R.E.
        • Pechacek T.F.
        • et al.
        Nicotine and the developing human: a neglected element in the electronic cigarette debate.
        Am J Prev Med. 2015; 49: 286-293
        • Goriounova N.A.
        • Mansvelder H.D.
        Nicotine exposure during adolescence alters the rules for prefrontal cortical synaptic plasticity during adulthood.
        Front Synaptic Neurosci. 2012; 4: 3
        • Leslie F.M.
        Unique, long-term effects of nicotine on adolescent brain.
        Pharmacol Biochem Behav. 2020; 197173010
        • Smith R.F.
        • McDonald C.G.
        • Bergstrom H.C.
        • et al.
        Adolescent nicotine induces persisting changes in development of neural connectivity.
        Neurosci Biobehav Rev. 2015; 55: 432-443
        • Yuan M.
        • Cross S.J.
        • Loughlin S.E.
        • et al.
        Nicotine and the adolescent brain.
        J Physiol. 2015; 593: 3397-3412
        • Marczylo T.
        How bad are e-cigarettes? What can we learn from animal exposure models?.
        J Physiol. 2020; 598: 5073-5089
        • Garcia-Arcos I.
        • Geraghty P.
        • Baumlin N.
        • et al.
        Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner.
        Thorax. 2016; 71: 1119-1129
        • Larcombe A.N.
        • Janka M.A.
        • Mullins B.J.
        • et al.
        The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice.
        Am J Physiol Lung Cell Mol Physiol. 2017; 313: L67-79
        • Ganguly K.
        • Nordstrom A.
        • Thimraj T.A.
        • et al.
        Addressing the challenges of e-cigarette safety profiling by assessment of pulmonary toxicological response in bronchial and alveolar mucosa models.
        Sci Rep. 2020; 1020460
        • Olfert I.M.
        • DeVallance E.
        • Hoskinson H.
        • et al.
        Chronic exposure to electronic cigarettes results in impaired cardiovascular function in mice.
        J Appl Physiol. 2018; 124: 573-582
        • Martinez-Morata I.
        • Sanchez T.R.
        • Shimbo D.
        • et al.
        Electronic cigarette use and blood pressure end points: a systematic review.
        Curr Hypertens Rep. 2020; 23: 2
        • Espinoza-Derout J.
        • Hasan K.M.
        • Shao X.M.
        • et al.
        Chronic intermittent electronic cigarette exposure induces cardiac dysfunction and atherosclerosis in apolipoprotein-E knockout mice.
        Am J Physiol Heart Circ Physiol. 2019; 317: H445-H459
        • Larue F.
        • Tasbih T.
        • Ribeiro P.A.B.
        • et al.
        Immediate physiological effects of acute electronic cigarette use in humans: a systematic review and meta-analysis.
        Respir Med. 2021; 190106684
        • Chaumont M.
        • de Becker B.
        • Zaher W.
        • et al.
        Differential effects of e-cigarette on microvascular endothelial function, arterial stiffness and oxidative stress: a randomized crossover trial.
        Sci Rep. 2018; 810378
        • Kerr D.M.I.
        • Brooksbank K.J.M.
        • Taylor R.G.
        • et al.
        Acute effects of electronic and tobacco cigarettes on vascular and respiratory function in healthy volunteers: a cross-over study.
        J Hypertens. 2019; 37: 154-166
        • Morris P.B.
        • Ference B.A.
        • Jahangir E.
        • et al.
        Cardiovascular effects of exposure to cigarette smoke and electronic cigarettes: clinical perspectives from the Prevention of Cardiovascular Disease Section Leadership Council and Early Career Councils of the American College of Cardiology.
        J Am Coll Cardiol. 2015; 66: 1378-1391
        • Gordon T.
        • Karey E.
        • Rebuli M.E.
        • et al.
        E-cigarette toxicology.
        Annu Rev Pharmacol Toxicol. 2022; 62: 301-322
        • Azimi P.
        • Keshavarz Z.
        • Lahaie Luna M.
        • et al.
        An unrecognized hazard in e-cigarette vapor: preliminary quantification of methylglyoxal formation from propylene glycol in e-cigarettes.
        Int J Environ Res Public Health. 2021; 18: 385
        • Kosmider L.
        • Sobczak A.
        • Fik M.
        • et al.
        Carbonyl compounds in electronic cigarette vapors: effects of nicotine solvent and battery output voltage.
        Nicotine Tob Res. 2014; 16: 1319-1326
        • Farsalinos K.E.
        • Voudris V.
        • Poulas K.
        E-cigarettes generate high levels of aldehydes only in “dry puff” conditions.
        Addiction. 2015; 110: 1352-1356
        • Park Y.S.
        • Taniguchi N.
        Acrolein induces inflammatory response underlying endothelial dysfunction: a risk factor for atherosclerosis.
        Ann N Y Acad Sci. 2008; 1126: 185-189
        • Jensen R.P.
        • Luo W.
        • Pankow J.F.
        • et al.
        Hidden formaldehyde in e-cigarette aerosols.
        N Engl J Med. 2015; 372: 392-394
        • Allaman I.
        • Bélanger M.
        • Magistretti P.J.
        Methylglyoxal, the dark side of glycolysis.
        Front Neurosci. 2015; 9: 23
        • Sleiman M.
        • Logue J.M.
        • Montesinos V.N.
        • et al.
        Emissions from electronic cigarettes: key parameters affecting the release of harmful chemicals.
        Environ Sci Technol. 2016; 50: 9644-9651
        • Zhu S.H.
        • Sun J.Y.
        • Bonnevie E.
        • et al.
        Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation.
        Tob Control. 2014; 23: iii3-9
        • Barrington-Trimis J.L.
        • Samet J.M.
        • McConnell R.
        Flavorings in electronic cigarettes: an unrecognized respiratory health hazard?.
        JAMA. 2014; 312: 2493-2494
        • Kaur G.
        • Gaurav A.
        • Lamb T.
        • et al.
        Current perspectives on characteristics, compositions, and toxicological effects of e-cigarettes containing tobacco and menthol/mint flavors.
        Front Physiol. 2020; 11613948
        • Dinu V.
        • Kilic A.
        • Wang Q.
        • et al.
        Policy, toxicology and physicochemical considerations on the inhalation of high concentrations of food flavour.
        NPJ Sci Food. 2020; 4: 15
        • Morris A.M.
        • Leonard S.S.
        • Fowles J.R.
        • et al.
        Effects of e-cigarette flavoring chemicals on human macrophages and bronchial epithelial cells.
        Int J Environ Res Public Health. 2021; 1811107
        • Allen J.G.
        • Flanigan S.S.
        • LeBlanc M.
        • et al.
        Flavoring chemicals in e-cigarettes: diacetyl, 2,3-pentanedione, and acetoin in a sample of 51 products, including fruit-, candy-, and cocktail-flavored e-cigarettes.
        Environ Health Perspect. 2016; 124: 733-739
        • Kreiss K.
        Flavoring-related bronchiolitis obliterans.
        Curr Opin Allergy Clin Immunol. 2007; 7: 162-167
        • Rose C.S.
        Early detection, clinical diagnosis, and management of lung disease from exposure to diacetyl.
        Toxicology. 2017; 388: 9-14
        • White A.V.
        • Wambui D.W.
        • Pokhrel L.R.
        Risk assessment of inhaled diacetyl from electronic cigarette use among teens and adults.
        Sci Total Environ. 2021; 772145486
        • Morgan D.L.
        • Jokinen M.P.
        • Price H.C.
        • et al.
        Bronchial and bronchiolar fibrosis in rats exposed to 2,3-pentanedione vapors: implications for bronchiolitis obliterans in humans.
        Toxicol Pathol. 2012; 40: 448-465
        • Landry R.L.
        • Groom A.L.
        • Vu T.T.
        • et al.
        The role of flavors in vaping initiation and satisfaction among U.S. adults.
        Addict Behav. 2019; 99106077
        • Leventhal A.M.
        • Mason T.B.
        • Cwalina S.N.
        • et al.
        Flavor and nicotine effects on e-cigarette appeal in young adults: moderation by reason for vaping.
        Am J Health Behav. 2020; 44: 732-743
        • Gerloff J.
        • Sundar I.K.
        • Freter R.
        • et al.
        Inflammatory response and barrier dysfunction by different e-cigarette flavoring chemicals identified by gas chromatography-mass spectrometry in e-liquids and e-vapors on human lung epithelial cells and fibroblasts.
        Appl In vitro Toxicol. 2017; 3: 28-40
        • Ween M.P.
        • Whittall J.J.
        • Hamon R.
        • et al.
        Phagocytosis and Inflammation: exploring the effects of the components of e-cigarette vapor on macrophages.
        Physiol Rep. 2017; 5e13370
        • Jabba S.V.
        • Erythropel H.C.
        • Torres D.G.
        • et al.
        Synthetic cooling agents in US-marketed e-cigarette refill liquids and popular disposable ecigarettes: chemical analysis and risk assessment.
        Nicotine Tob Res. 2022; 24: 1037-1046
      1. Leventhal AM, Tackett AP, Whitted L, et al. Ice flavours and nonmenthol synthetic cooling agents in e-cigarette products: a review [e-pub ahead of print]. Tob Control 2022 Apr 28. doi:10.1136/tobaccocontrol-2021-057073

        • Flake G.P.
        • Morgan D.L.
        Pathology of diacetyl and 2,3-pentanedione airway lesions in a rat model of obliterative bronchiolitis.
        Toxicology. 2017; 388: 40-47
        • Wallace K.B.
        Future perspective of butter flavorings–related occupational lung disease.
        Toxicology. 2017; 388: 7-8
        • Krishnan-Sarin S.
        • Green B.G.
        • Kong G.
        • et al.
        Studying the interactive effects of menthol and nicotine among youth: an examination using e-cigarettes.
        Drug Alcohol Depend. 2017; 180: 193-199
        • Zhao D.
        • Aravindakshan A.
        • Hilpert M.
        • et al.
        Metal/metalloid levels in electronic cigarette liquids, aerosols, and human biosamples: a systematic review.
        Environ Health Perspect. 2020; 12836001
        • Zhao D.
        • Ilievski V.
        • Slavkovich V.
        • et al.
        Effects of e-liquid flavor, nicotine content, and puff duration on metal emissions from electronic cigarettes.
        Environ Res. 2022; 204112270
        • Williams M.
        • Bozhilov K.
        • Ghai S.
        • et al.
        Elements including metals in the atomizer and aerosol of disposable electronic cigarettes and electronic hookahs.
        PLoS One. 2017; 12e0175430
        • Saffari A.
        • Daher N.
        • Ruprecht A.
        • et al.
        Particulate metals and organic compounds from electronic and tobacco-containing cigarettes: comparison of emission rates and secondhand exposure.
        Environ Sci Process Impacts. 2014; 16: 2259-2267
        • Olmedo P.
        • Goessler W.
        • Tanda S.
        • et al.
        Metal concentrations in e-cigarette liquid and aerosol samples: the contribution of metallic coils.
        Environ Health Perspect. 2018; 126027010
        • Navas-Acien A.
        • Martinez-Morata I.
        • Hilpert M.
        • et al.
        Early cardiovascular risk in e-cigarette users: the potential role of metals.
        Curr Environ Health Rep. 2020; 7: 353-361
        • Fowles J.
        • Barreau T.
        • Wu N.
        Cancer and non-cancer risk concerns from metals in electronic cigarette liquids and aerosols.
        Int J Environ Res Public Health. 2020; 17: 7
        • Nordberg M.
        • Nordberg G.
        • Friberg L.
        Handbook on the Toxicity of Metals.
        Academic Press, Amsterdam2014
        • Aherrera A.
        • Olmedo P.
        • Grau-Perez M.
        • et al.
        The association of e-cigarette use with exposure to nickel and chromium: a preliminary study of noninvasive biomarkers.
        Environ Res. 2017; 159: 313-320
        • Navas-Acien A.
        • Guallar E.
        • Silbergeld E.K.
        • et al.
        Lead exposure and cardiovascular disease—a systematic review.
        Environ Health Perspect. 2007; 115: 472-482
        • Wei B.
        • O’Connor R.J.
        • Goniewicz M.L.
        • et al.
        Emerging chemicals of health concern in electronic nicotine delivery systems.
        Chem Res Toxicol. 2020; 33: 2637-2646
        • Ospina M.
        • Jayatilaka N.K.
        • Wong L.Y.
        • et al.
        Exposure to organophosphate flame retardant chemicals in the U.S. general population: data from the 2013-2014 National Health and Nutrition Examination Survey.
        Environ Int. 2018; 110: 32-41
        • Koch H.M.
        • Calafat A.M.
        Human body burdens of chemicals used in plastic manufacture.
        Philos Trans R Soc Lond B Biol Sci. 2009; 364: 2063-2078
        • Meeker J.D.
        • Stapleton H.M.
        House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality parameters.
        Environ Health Perspect. 2010; 118: 318-323
        • Wei B.
        • Goniewicz M.L.
        • O’Connor R.J.
        • et al.
        Urinary metabolite levels of flame retardants in electronic cigarette users: a study using the data from NHANES 2013-2014.
        Int J Environ Res Public Health. 2018; 15: 201
        • Wei B.
        • O’Connor R.
        • Goniewicz M.
        • et al.
        Association between urinary metabolite levels of organophosphorus flame retardants and serum sex hormone levels measured in a reference sample of the US general population.
        Expo Health. 2020; 12: 905-916
        • Philippat C.
        • Mortamais M.
        • Chevrier C.
        • et al.
        Exposure to phthalates and phenols during pregnancy and offspring size at birth.
        Environ Health Perspect. 2012; 120: 464-470
        • Messerlian C.
        • Williams P.L.
        • Mínguez-Alarcón L.
        • et al.
        Organophosphate flame-retardant metabolite concentrations and pregnancy loss among women conceiving with assisted reproductive technology.
        Fertil Steril. 2018; 110: 1137-11344.e1
        • Ehrlich S.
        • Williams P.L.
        • Missmer S.A.
        • et al.
        Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF.
        Hum Reprod. 2012; 27: 3583-3592
        • Silva M.J.
        • Barr D.B.
        • Reidy J.A.
        • et al.
        Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000.
        Environ Health Perspect. 2004; 112: 331-338
        • Gotts J.E.
        • Jordt S.E.
        • McConnell R.
        • et al.
        What are the respiratory effects of e-cigarettes?.
        BMJ. 2019; 366: l5275
        • Tierney P.A.
        • Karpinski C.D.
        • Brown J.E.
        • et al.
        Flavour chemicals in electronic cigarette fluids.
        Tob Control. 2016; 25: e10-e15
        • Xie W.
        • Kathuria H.
        • Galiatsatos P.
        • et al.
        Association of electronic cigarette use with incident respiratory conditions among US adults from 2013 to 2018.
        JAMA Netw Open. 2020; 3e2020816
        • Park J.A.
        • Crotty Alexander L.E.
        • Christiani D.C.
        Vaping and lung inflammation and injury.
        Annu Rev Physiol. 2022; 84: 611-629
        • Hua M.
        • Alfi M.
        • Talbot P.
        Health-related effects reported by electronic cigarette users in online forums.
        J Med Internet Res. 2013; 15: e59
        • McConnell R.
        • Barrington-Trimis J.L.
        • Wang K.
        • et al.
        Electronic cigarette use and respiratory symptoms in adolescents.
        Am J Respir Crit Care Med. 2017; 195: 1043-1049
        • Wills T.A.
        • Pagano I.
        • Williams R.J.
        • et al.
        E-cigarette use and respiratory disorder in an adult sample.
        Drug Alcohol Depend. 2019; 194: 363-370
        • Baines D.L.
        A nasty case of the vapours—e-cigarettes friend or foe?.
        J Physiol. 2020; 598: 5025
        • Miyashita L.
        • Foley G.
        E-cigarettes and respiratory health: the latest evidence.
        J Physiol. 2020; 598: 5027-5038
        • Tsai M.
        • Byun M.K.
        • Shin J.
        • et al.
        Effects of e-cigarettes and vaping devices on cardiac and pulmonary physiology.
        J Physiol. 2020; 598: 5039-5062
        • McAlinden K.D.
        • Lu W.
        • Eapen M.S.
        • et al.
        Electronic cigarettes: modern instruments for toxic lung delivery and posing risk for the development of chronic disease.
        Int J Biochem Cell Biol. 2021; 137106039
        • Tarran R.
        • Barr R.G.
        • Benowitz N.L.
        • et al.
        E-cigarettes and cardiopulmonary health.
        Function. 2021; 2: zqab004
        • Chung S.
        • Baumlin N.
        • Dennis J.S.
        • et al.
        Electronic cigarette vapor with nicotine causes airway mucociliary dysfunction preferentially via TRPA1 receptors.
        Am J Respir Crit Care Med. 2019; 200: 1134-1145
        • Vardavas C.I.
        • Anagnostopoulos N.
        • Kougias M.
        • et al.
        Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide.
        Chest. 2012; 141: 1400-1406
        • Flouris A.D.
        • Chorti M.S.
        • Poulianiti K.P.
        • et al.
        Acute impact of active and passive electronic cigarette smoking on serum cotinine and lung function.
        Inhal Toxicol. 2013; 25: 91-101
        • Staudt M.R.
        • Salit J.
        • Kaner R.J.
        • et al.
        Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes.
        Respir Res. 2018; 19: 78
        • Boulay M.
        • Henry C.
        • Bossé Y.
        • et al.
        Acute effects of nicotine-free and flavour-free electronic cigarette use on lung functions in healthy and asthmatic individuals.
        Respir Res. 2017; 18: 33
        • Kizhakke Puliyakote A.S.
        • Elliott A.R.
        • Sá R.C.
        • et al.
        Vaping disrupts ventilation-perfusion matching in asymptomatic users.
        J Appl Physiol. 2021; 130: 308-317
        • Osei A.D.
        • Mirbolouk M.
        • Orimoloye O.A.
        • et al.
        Association between e-cigarette use and chronic obstructive pulmonary disease by smoking status: Behavioral Risk Factor Surveillance System 2016 and 2017.
        Am J Prev Med. 2020; 58: 336-342
        • Bhatta D.N.
        • Glantz S.A.
        Association of e-cigarette use with respiratory disease among adults: a longitudinal analysis.
        Am J Prev Med. 2020; 58: 182-190
        • Xie W.
        • Tackett A.P.
        • Berlowitz J.B.
        • et al.
        Association of electronic cigarette use with respiratory symptom development among US young adults.
        Am J Respir Crit Care Med. 2022; 205: 1320-1329
        • McAlinden K.D.
        • Eapen M.S.
        • Lu W.
        • et al.
        The rise of electronic nicotine delivery systems and the emergence of electronic-cigarette–driven disease.
        Am J Physiol Lung Cell Mol Physiol. 2020; 319: L585-L595
        • Lappas A.S.
        • Tzortzi A.S.
        • Konstantinidi E.M.
        • et al.
        Short-term respiratory effects of e-cigarettes in healthy individuals and smokers with asthma.
        Respirology. 2018; 23: 291-297
        • Gilpin D.F.
        • McGown K.A.
        • Gallagher K.
        • et al.
        Electronic cigarette vapour increases virulence and inflammatory potential of respiratory pathogens.
        Respir Res. 2019; 20: 267
        • Sussan T.E.
        • Gajghate S.
        • Thimmulappa R.K.
        • et al.
        Exposure to electronic cigarettes impairs pulmonary antibacterial and antiviral defenses in a mouse model.
        PLoS One. 2015; 10e0116861
        • Tang M.S.
        • Wu X.R.
        • Lee H.W.
        • et al.
        Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice.
        Proc Natl Acad Sci U S A. 2019; 116: 21727-21731
        • Tzortzi A.
        • Teloniatis S.
        • Matiampa G.
        • et al.
        Passive exposure of nonsmokers to e-cigarette aerosols: sensory irritation, timing and association with volatile organic compounds.
        Environ Res. 2020; 182108963
        • Islam T.
        • Braymiller J.
        • Eckel S.P.
        • et al.
        Secondhand nicotine vaping at home and respiratory symptoms in young adults.
        Thorax. 2022; 77: 663-668
        • Bhatnagar A.
        Cardiovascular perspective of the promises and perils of e-cigarettes.
        Circ Res. 2016; 118: 1872-1875
        • Shahandeh N.
        • Chowdhary H.
        • Middlekauff H.R.
        Vaping and cardiac disease.
        Heart. 2021; 107: 1530-1535
        • Qasim H.
        • Karim Z.A.
        • Rivera J.O.
        • et al.
        Impact of electronic cigarettes on the cardiovascular system.
        J Am Heart Assoc. 2017; 6e006353
        • Berlowitz J.B.
        • Xie W.
        • Harlow A.F.
        • et al.
        E-cigarette use and risk of cardiovascular disease: a longitudinal analysis of the PATH study, 2013-2019.
        Circulation. 2022; 145: 1557-1559
        • Kennedy C.D.
        • van Schalkwyk M.C.I.
        • McKee M.
        • et al.
        The cardiovascular effects of electronic cigarettes: a systematic review of experimental studies.
        Prev Med. 2019; 127105770
        • Moheimani R.S.
        • Bhetraratana M.
        • Yin F.
        • et al.
        Increased cardiac sympathetic activity and oxidative stress in habitual electronic cigarette users: implications for cardiovascular risk.
        JAMA Cardiol. 2017; 2: 278-284
        • Moheimani R.S.
        • Bhetraratana M.
        • Peters K.M.
        • et al.
        Sympathomimetic effects of acute e-cigarette use: role of nicotine and non-nicotine constituents.
        J Am Heart Assoc. 2017; 6e006579
        • Benowitz N.L.
        • Burbank A.D.
        Cardiovascular toxicity of nicotine: implications for electronic cigarette use.
        Trends Cardiovasc Med. 2016; 26: 515-523
        • Middlekauff H.R.
        • Park J.
        • Moheimani R.S.
        Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: mechanisms and implications for cardiovascular risk.
        J Am Coll Cardiol. 2014; 64: 1740-1750
        • Chatterjee S.
        • Caporale A.
        • Tao J.Q.
        • et al.
        Acute e-cig inhalation impacts vascular health: a study in smoking naïve subjects.
        Am J Physiol Heart Circ Physiol. 2021; 320: H144-H158
        • Darville A.
        • Hahn E.J.
        E-cigarettes and atherosclerotic cardiovascular disease: what clinicians and researchers need to know.
        Curr Atheroscler Rep. 2019; 21: 15
        • El-Mahdy M.A.
        • Mahgoup E.M.
        • Ewees M.G.
        • et al.
        Long-term electronic cigarette exposure induces cardiovascular dysfunction similar to tobacco cigarettes: role of nicotine and exposure duration.
        Am J Physiol Heart Circ Physiol. 2021; 320: H2112-H2129
        • Antoniewicz L.
        • Brynedal A.
        • Hedman L.
        • et al.
        Acute effects of electronic cigarette inhalation on the vasculature and the conducting airways.
        Cardiovasc Toxicol. 2019; 19: 441-450
        • Caporale A.
        • Langham M.C.
        • Guo W.
        • et al.
        Acute effects of electronic cigarette aerosol inhalation on vascular function detected at quantitative MRI.
        Radiology. 2019; 293: 97-106
        • Rao P.
        • Han D.D.
        • Tan K.
        • et al.
        Comparable impairment of vascular endothelial function by a wide range of electronic nicotine delivery devices.
        Nicotine Tob Res. 2022; 24: 1055-1062
        • Rao P.
        • Liu J.
        • Springer M.L.
        Juul and combusted cigarettes comparably impair endothelial function.
        Tob Regul Sci. 2020; 6: 30-37
        • Qasim H.
        • Karim Z.A.
        • Silva-Espinoza J.C.
        • et al.
        Short-term e-cigarette exposure increases the risk of thrombogenesis and enhances platelet function in mice.
        J Am Heart Assoc. 2018; 7e009264
        • Metzen D.
        • M’Pembele R.
        • Zako S.
        • et al.
        Platelet reactivity is higher in e-cigarette vaping as compared to traditional smoking.
        Int J Cardiol. 2021; 343: 146-148
        • Kuntic M.
        • Oelze M.
        • Steven S.
        • et al.
        Short-term e-cigarette vapour exposure causes vascular oxidative stress and dysfunction: evidence for a close connection to brain damage and a key role of the phagocytic NADPH oxidase (NOX-2).
        Eur Heart J. 2020; 41: 2472-2483
        • Hecht S.S.
        • Carmella S.G.
        • Kotandeniya D.
        • et al.
        Evaluation of toxicant and carcinogen metabolites in the urine of e-cigarette users versus cigarette smokers.
        Nicotine Tob Res. 2015; 17: 704-709
        • Henning R.J.
        • Johnson G.T.
        • Coyle J.P.
        • et al.
        Acrolein can cause cardiovascular disease: a review.
        Cardiovasc Toxicol. 2017; 17: 227-236
        • Luo J.
        • Hill B.G.
        • Gu Y.
        • et al.
        Mechanisms of acrolein-induced myocardial dysfunction: implications for environmental and endogenous aldehyde exposure.
        Am J Physiol Heart Circ Physiol. 2007; 293: H3673-H3684
        • Zhang X.
        • Pu J.
        E-cigarette use among US adolescents: secondhand smoke at home matters.
        Int J Public Health. 2016; 61: 209-213
        • Goniewicz M.L.
        • Knysak J.
        • Gawron M.
        • et al.
        Levels of selected carcinogens and toxicants in vapour from electronic cigarettes.
        Tob Control. 2014; 23: 133-139
        • Hutzler C.
        • Paschke M.
        • Kruschinski S.
        • et al.
        Chemical hazards present in liquids and vapors of electronic cigarettes.
        Arch Toxicol. 2014; 88: 1295-1308
        • Anderson J.O.
        • Thundiyil J.G.
        • Stolbach A.
        Clearing the air: a review of the effects of particulate matter air pollution on human health.
        J Med Toxicol. 2012; 8: 166-175
        • Fernández E.
        • Ballbè M.
        • Sureda X.
        • et al.
        Particulate matter from electronic cigarettes and conventional cigarettes: a systematic review and observational study.
        Curr Environ Health Rep. 2015; 2: 423-429
        • Nelin T.D.
        • Joseph A.M.
        • Gorr M.W.
        • et al.
        Direct and indirect effects of particulate matter on the cardiovascular system.
        Toxicol Lett. 2012; 208: 293-299
        • Peters A.
        • Dockery D.W.
        • Muller J.E.
        • et al.
        Increased particulate air pollution and the triggering of myocardial infarction.
        Circulation. 2001; 103: 2810-2815
        • Sullivan J.
        • Sheppard L.
        • Schreuder A.
        • et al.
        Relation between short-term fine-particulate matter exposure and onset of myocardial infarction.
        Epidemiology. 2005; 16: 41-48
        • Wang T.
        • Lang G.D.
        • Moreno-Vinasco L.
        • et al.
        Particulate matter induces cardiac arrhythmias via dysregulation of carotid body sensitivity and cardiac sodium channels.
        Am J Respir Cell Mol Biol. 2012; 46: 524-531
        • Osei A.D.
        • Mirbolouk M.
        • Orimoloye O.A.
        • et al.
        Association between e-cigarette use and cardiovascular disease among never and current combustible-cigarette smokers.
        Am J Med. 2019; 132 (-54.e2): 949
        • Fetterman J.L.
        • Keith R.J.
        • Palmisano J.N.
        • et al.
        Alterations in vascular function associated with the use of combustible and electronic cigarettes.
        J Am Heart Assoc. 2020; 9e014570
        • George J.
        • Hussain M.
        • Vadiveloo T.
        • et al.
        Cardiovascular effects of switching from tobacco cigarettes to electronic cigarettes.
        J Am Coll Cardiol. 2019; 74: 3112-3120
        • Dai H.
        • Benowitz N.L.
        • Achutan C.
        • et al.
        Exposure to toxicants associated with use and transitions between cigarettes, e-cigarettes, and no tobacco.
        JAMA Netw Open. 2022; 5e2147891
        • Benowitz N.L.
        • St Helen G.
        • Nardone N.
        • et al.
        Twenty-four-hour cardiovascular effects of electronic cigarettes compared with cigarette smoking in dual users.
        J Am Heart Assoc. 2020; 9e017317
        • Benowitz N.L.
        • Liakoni E.
        Tobacco use disorder and cardiovascular health.
        Addiction. 2022; 117: 1128-1138
        • Rezk-Hanna M.
        • Warda U.S.
        • Stokes A.C.
        • et al.
        Associations of smokeless tobacco use with cardiovascular disease risk: insights from the Population Assessment of Tobacco and Health study.
        Nicotine Tob Res. 2022; 24: 1063-1070
        • Eissenberg T.
        • Bhatnagar A.
        • Chapman S.
        • et al.
        Invalidity of an oft-cited estimate of the relative harms of electronic cigarettes.
        Am J Public Health. 2020; 110: 161-162
        • Nutt D.J.
        • Phillips L.D.
        • Balfour D.
        • et al.
        Estimating the harms of nicotine-containing products using the MCDA approach.
        Eur Addict Res. 2014; 20: 218-225
        • Feeney S.
        • Rossetti V.
        • Terrien J.
        E-Cigarettes-a review of the evidence-harm versus harm reduction.
        Tob Use Insights. 2022; 151179173X221087524
        • Cohen J.E.
        • Krishnan-Sarin S.
        • Eissenberg T.
        • et al.
        Balancing risks and benefits of e-cigarettes in the real world.
        Am J Public Health. 2022; 112: e1-2
        • Flacco M.E.
        • Fiore M.
        • Acuti Martellucci C.
        • et al.
        Tobacco vs electronic cigarettes: absence of harm reduction after six years of follow-up.
        Eur Rev Med Pharmacol Sci. 2020; 24: 3923-3934
        • Adriaens K.
        • Belmans E.
        • van Gucht D.
        • et al.
        Electronic cigarettes in standard smoking cessation treatment by tobacco counselors in Flanders: e-cigarette users show similar if not higher quit rates as those using commonly recommended smoking cessation aids.
        Harm Reduct J. 2021; 18: 28
        • Cook R.
        • Davidson P.
        • Martin R.
        E-cigarettes helped more smokers quit than nicotine replacement therapy.
        BMJ. 2019; 365: l2036
        • Eisenberg M.J.
        • Hebert-Losier A.
        • Windle S.B.
        • et al.
        Effect of e-cigarettes plus counseling vs counseling alone on smoking cessation: a randomized clinical trial.
        JAMA. 2020; 324: 1844-1854
        • Hajek P.
        • Phillips-Waller A.
        • Przulj D.
        • et al.
        A randomized trial of e-cigarettes versus nicotine-replacement therapy.
        N Engl J Med. 2019; 380: 629-637
        • Levy D.T.
        • Yuan Z.
        • Luo Y.
        • et al.
        The relationship of e-cigarette use to cigarette quit attempts and cessation: insights from a large, nationally representative U.S. survey.
        Nicotine Tob Res. 2018; 20: 931-939
        • Hartmann-Boyce J.
        • McRobbie H.
        • Butler A.R.
        • et al.
        Electronic cigarettes for smoking cessation.
        Cochrane Database Syst Rev. 2021; 9: CD010216
        • Chan G.C.K.
        • Stjepanović D.
        • Lim C.
        • et al.
        A systematic review of randomized controlled trials and network meta-analysis of e-cigarettes for smoking cessation.
        Addict Behav. 2021; 119106912
        • Wang R.J.
        • Bhadriraju S.
        • Glantz S.A.
        E-cigarette use and adult cigarette smoking cessation: a meta-analysis.
        Am J Public Health. 2021; 111: 230-246
        • Borrelli B.
        • O’Connor G.T.
        E-cigarettes to assist with smoking cessation.
        N Engl J Med. 2019; 380: 678-679
        • Famiglietti A.
        • Memoli J.W.
        • Khaitan P.G.
        Are electronic cigarettes and vaping effective tools for smoking cessation? Limited evidence on surgical outcomes: a narrative review.
        J Thorac Dis. 2021; 13: 384-395
        • Grabovac I.
        • Oberndorfer M.
        • Fischer J.
        • et al.
        Effectiveness of electronic cigarettes in smoking cessation: a systematic review and meta-analysis.
        Nicotine Tob Res. 2021; 23: 625-634
        • Hedman L.
        • Galanti M.R.
        • Ryk L.
        • et al.
        Electronic cigarette use and smoking cessation in cohort studies and randomized trials: a systematic review and meta-analysis.
        Tob Prev Cessat. 2021; 7: 62
        • Ibrahim S.
        • Habiballah M.
        • Sayed I.E.
        Efficacy of electronic cigarettes for smoking cessation: a systematic review and meta-analysis.
        Am J Health Promot. 2021; 35: 442-455
        • Kaplan B.
        • Galiatsatos P.
        • Breland A.
        • et al.
        Effectiveness of ENDS, NRT and medication for smoking cessation among cigarette-only users: a longitudinal analysis of PATH study wave 3 (2015-2016) and 4 (2016-2017), adult data [e-pub ahead of print].
        Tob Control. 2021 Sep 15; https://doi.org/10.1136/tobaccocontrol-2020-056448
        • Lanspa M.J.
        • Blagev D.P.
        • Callahan S.J.
        Use of e-cigarettes for smoking cessation.
        JAMA. 2021; 325: 1006
        • Miech R.
        • Leventhal A.M.
        • O’Malley P.M.
        • et al.
        Failed attempts to quit combustible cigarettes and e-cigarettes among US adolescents.
        JAMA. 2022; 327: 1179-1181
      2. Banks E, Yazidjoglou A, Brown S, et al. Electronic cigarettes and health outcomes: systematic review of global evidence. Australian National University; April 7, 2022. Available at: https://apo.org.au/node/317300.

        • Chen R.
        • Pierce J.P.
        • Leas E.C.
        • et al.
        Effectiveness of e-cigarettes as aids for smoking cessation: evidence from the PATH study cohort, 2017-2019 [e-pub ahead of print].
        Tob Control. 2022 Feb 7; https://doi.org/10.1136/tobaccocontrol-2021-056901
        • Hanewinkel R.
        • Niederberger K.
        • Pedersen A.
        • et al.
        E-cigarettes and nicotine abstinence: a meta-analysis of randomised controlled trials.
        Eur Respir Rev. 2022; 31210215
        • Morphett K.
        • Fraser D.
        • Borland R.
        • et al.
        A pragmatic randomised comparative trial of e-cigarettes and other nicotine products for quitting or long-term substitution in smokers.
        Nicotine Tob Res. 2022; 24: 1079-1088
        • Balfour D.J.K.
        • Benowitz N.L.
        • Colby S.M.
        • et al.
        Balancing consideration of the risks and benefits of e-cigarettes.
        Am J Public Health. 2021; 111: 1661-1672
        • Samet J.M.
        • Barrington-Trimis J.
        E-cigarettes and harm reduction: an artificial controversy instead of evidence and a well-framed decision context.
        Am J Public Health. 2021; 111: 1572-1574
        • Hammond D.
        • Reid J.L.
        • Burkhalter R.
        • et al.
        E-cigarette marketing regulations and youth vaping: cross-sectional surveys, 2017-2019.
        Pediatrics. 2020; 146e20194020