What are the respiratory effects of e-cigarettes?

Jeffrey E Gotts, Sven-Eric Jordt, Rob McConnell, Robert Tarran, Jeffrey E Gotts, Sven-Eric Jordt, Rob McConnell, Robert Tarran

Abstract

Electronic cigarettes (e-cigarettes) are alternative, non-combustible tobacco products that generate an inhalable aerosol containing nicotine, flavors, propylene glycol, and vegetable glycerin. Vaping is now a multibillion dollar industry that appeals to current smokers, former smokers, and young people who have never smoked. E-cigarettes reached the market without either extensive preclinical toxicology testing or long term safety trials that would be required of conventional therapeutics or medical devices. Their effectiveness as a smoking cessation intervention, their impact at a population level, and whether they are less harmful than combustible tobacco products are highly controversial. Here, we review the evidence on the effects of e-cigarettes on respiratory health. Studies show measurable adverse biologic effects on organ and cellular health in humans, in animals, and in vitro. The effects of e-cigarettes have similarities to and important differences from those of cigarettes. Decades of chronic smoking are needed for development of lung diseases such as lung cancer or chronic obstructive pulmonary disease, so the population effects of e-cigarette use may not be apparent until the middle of this century. We conclude that current knowledge of these effects is insufficient to determine whether the respiratory health effects of e-cigarette are less than those of combustible tobacco products.

Conflict of interest statement

Competing interests: We have read and understood the BMJ policy on the declaration of interests and declare that we have no conflicts of interest; SEJ has receiving personal fees from Hydra Biosciences LLC and Sanofi SA and non-financial support from GlaxoSmithKline Pharmaceuticals outside the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Fig 1
Fig 1
Reported effects of vaping on the human pulmonary system
Fig 2
Fig 2
Flowchart outlining proposed smoking cessation regimen that espouses counseling and nicotine cessation. Given the potential health risks associated with vaping, tobacco smokers looking to quit should first try nicotine patch or gum along with counseling (1, 2). If this approach fails, e-cigarettes could be used as a second attempt (3, 4). Given that nicotine is not risk-free, attempts should then be made to end nicotine dependence (5). As nicotine levels in e-liquids differ globally, the use of e-cigarettes as a smoking/nicotine cessation device may be more effective in countries with lower nicotine levels

References

    1. US Department of Health and Human Services The Health Consequences of Smoking–50 Years of Progress: A Report of the Surgeon General. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.
    1. Ochsner A, Debakey M. Primary pulmonary malignancy: treatment by total pneumonectomy; analysis of 79 collected cases and presentation of 7 personal cases. Ochsner J 1999;1:109-25.
    1. US Department of Health, Education, and Welfare. Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Health Service. Public Health Service Publication No 1103. 1964. .
    1. Eaton DL, Kwan LY, Stratton K, eds. Public Health Consequences of E-Cigarettes. National Academies Press, 2018.
    1. Walley SC, Wilson KM, Winickoff JP, Groner J. A Public Health Crisis: Electronic Cigarettes, Vape, and JUUL. Pediatrics 2019;143:e20182741. 10.1542/peds.2018-2741
    1. Pisinger C, Godtfredsen N, Bender AM. A conflict of interest is strongly associated with tobacco industry-favourable results, indicating no harm of e-cigarettes. Prev Med 2019;119:124-31. 10.1016/j.ypmed.2018.12.011
    1. Ahluwalia IB, Smith T, Arrazola RA, et al. Current Tobacco Smoking, Quit Attempts, and Knowledge About Smoking Risks Among Persons Aged ≥15 Years - Global Adult Tobacco Survey, 28 Countries, 2008-2016. MMWR Morb Mortal Wkly Rep 2018;67:1072-6. 10.15585/mmwr.mm6738a7
    1. Wang TW, Asman K, Gentzke AS, et al. Tobacco Product Use Among Adults - United States, 2017. MMWR Morb Mortal Wkly Rep 2018;67:1225-32. 10.15585/mmwr.mm6744a2
    1. Gottlieb MA. Regulation of E-Cigarettes in the United States and Its Role in a Youth Epidemic. Children (Basel) 2019;6:E40. 10.3390/children6030040
    1. Patrick ME, O’Malley PM, Kloska DD, et al. Novel psychoactive substance use by US adolescents: Characteristics associated with use of synthetic cannabinoids and synthetic cathinones. Drug Alcohol Rev 2016;35:586-90. 10.1111/dar.12372
    1. Miech R, Johnston L, O’Malley PM, Bachman JG, Patrick ME. Adolescent Vaping and Nicotine Use in 2017-2018 - U.S. National Estimates. N Engl J Med 2019;380:192-3. 10.1056/NEJMc1814130
    1. Barrington-Trimis JL, Gibson LA, Halpern-Felsher B, et al. Type of E-Cigarette Device Used Among Adolescents and Young Adults: Findings From a Pooled Analysis of Eight Studies of 2166 Vapers. Nicotine Tob Res 2018;20:271-4. 10.1093/ntr/ntx069
    1. Hsu G, Sun JY, Zhu SH. Evolution of Electronic Cigarette Brands From 2013-2014 to 2016-2017: Analysis of Brand Websites. J Med Internet Res 2018;20:e80. 10.2196/jmir.8550
    1. Pearson JL, Reed DM, Villanti AC. Vapes, e-cigs, and mods: what do young adults call e-cigarettes? Nicotine Tob Res 2018. 10.1093/ntr/nty223
    1. Galstyan E, Galimov A, Sussman S. Commentary: The Emergence of Pod Mods at Vape Shops. Eval Health Prof 2019;42:118-24. 10.1177/0163278718812976
    1. King BA, Gammon DG, Marynak KL, Rogers T. Electronic Cigarette Sales in the United States, 2013-2017. JAMA 2018;320:1379-80. 10.1001/jama.2018.10488
    1. Cullen KA, Ambrose BK, Gentzke AS, Apelberg BJ, Jamal A, King BA. Notes from the Field: Use of Electronic Cigarettes and Any Tobacco Product Among Middle and High School Students - United States, 2011-2018. MMWR Morb Mortal Wkly Rep 2018;67:1276-7. 10.15585/mmwr.mm6745a5
    1. Huang J, Duan Z, Kwok J, et al. Vaping versus JUULing: how the extraordinary growth and marketing of JUUL transformed the US retail e-cigarette market. Tob Control 2019;28:146-51. 10.1136/tobaccocontrol-2018-054382
    1. Jackler RK, Ramamurthi D. Nicotine arms race: JUUL and the high-nicotine product market. Tob Control 2019;tobaccocontrol-2018-054796. 10.1136/tobaccocontrol-2018-054796
    1. Tsunoda S, Fukaya H, Sugihara T, Martin CJ, Hildebrandt J. Lung volume, thickness of alveolar walls, and microscopic anisotropy of expansion. Respir Physiol 1974;22:285-96. 10.1016/0034-5687(74)90078-4
    1. Hua M, Alfi M, Talbot P. Health-related effects reported by electronic cigarette users in online forums. J Med Internet Res 2013;15:e59. 10.2196/jmir.2324
    1. Wang MP, Ho SY, Leung LT, Lam TH. Electronic Cigarette Use and Respiratory Symptoms in Chinese Adolescents in Hong Kong. JAMA Pediatr 2016;170:89-91. 10.1001/jamapediatrics.2015.3024
    1. McConnell R, Barrington-Trimis JL, Wang K, et al. Electronic Cigarette Use and Respiratory Symptoms in Adolescents. Am J Respir Crit Care Med 2017;195:1043-9. 10.1164/rccm.201604-0804OC
    1. Cho JH, Paik SY. Association between Electronic Cigarette Use and Asthma among High School Students in South Korea. PLoS One 2016;11:e0151022. 10.1371/journal.pone.0151022
    1. Schweitzer RJ, Wills TA, Tam E, Pagano I, Choi K. E-cigarette use and asthma in a multiethnic sample of adolescents. Prev Med 2017;105:226-31. 10.1016/j.ypmed.2017.09.023
    1. Choi K, Bernat D. E-Cigarette Use Among Florida Youth With and Without Asthma. Am J Prev Med 2016;51:446-53. 10.1016/j.amepre.2016.03.010
    1. Reid KM, Forrest JR, Porter L. Tobacco Product Use Among Youths With and Without Lifetime Asthma - Florida, 2016. MMWR Morb Mortal Wkly Rep 2018;67:599-601. 10.15585/mmwr.mm6721a2
    1. Wills TA, Pagano I, Williams RJ, Tam EK. E-cigarette use and respiratory disorder in an adult sample. Drug Alcohol Depend 2019;194:363-70. 10.1016/j.drugalcdep.2018.10.004
    1. Hedman L, Backman H, Stridsman C, et al. Association of Electronic Cigarette Use With Smoking Habits, Demographic Factors, and Respiratory Symptoms. JAMA Netw Open 2018;1:e180789. 10.1001/jamanetworkopen.2018.0789
    1. Wang JB, Olgin JE, Nah G, et al. Cigarette and e-cigarette dual use and risk of cardiopulmonary symptoms in the Health eHeart Study. PLoS One 2018;13:e0198681. 10.1371/journal.pone.0198681
    1. Centers for Disease Control and Prevention. Outbreak of Lung Injury Associated with E-Cigarette Use, or Vaping. 2019. .
    1. Layden JE, Ghinai I, Pray I, et al. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Preliminary Report. N Engl J Med 2019. 10.1056/NEJMoa1911614
    1. Centers for Disease Control and Prevention. Severe Pulmonary Disease Associated with Electronic-Cigarette–Product Use — Interim Guidance. 2019. .
    1. Hammond D. Outbreak of pulmonary diseases linked to vaping. BMJ 2019;366:l5445. 10.1136/bmj.l5445
    1. Itoh M, Aoshiba K, Herai Y, Nakamura H, Takemura T. Lung injury associated with electronic cigarettes inhalation diagnosed by transbronchial lung biopsy. Respirol Case Rep 2017;6:e00282. 10.1002/rcr2.282
    1. Viswam D, Trotter S, Burge PS, Walters GI. Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes. BMJ Case Rep 2018;2018:bcr-2018-224350. 10.1136/bcr-2018-224350
    1. Cibella F, Campagna D, Caponnetto P, et al. Lung function and respiratory symptoms in a randomized smoking cessation trial of electronic cigarettes. Clin Sci (Lond) 2016;130:1929-37. 10.1042/CS20160268
    1. Polosa R, Morjaria JB, Caponnetto P, et al. Persisting long term benefits of smoking abstinence and reduction in asthmatic smokers who have switched to electronic cigarettes. Discov Med 2016;21:99-108.
    1. Veldheer S, Yingst J, Midya V, et al. Pulmonary and other health effects of electronic cigarette use among adult smokers participating in a randomized controlled smoking reduction trial. Addict Behav 2019;91:95-101. 10.1016/j.addbeh.2018.10.041
    1. Hajek P, Phillips-Waller A, Przulj D, et al. A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy. N Engl J Med 2019;380:629-37. 10.1056/NEJMoa1808779
    1. Walele T, Bush J, Koch A, Savioz R, Martin C, O’Connell G. Evaluation of the safety profile of an electronic vapour product used for two years by smokers in a real-life setting. Regul Toxicol Pharmacol 2018;92:226-38. 10.1016/j.yrtph.2017.12.010
    1. D’Ruiz CD, O’Connell G, Graff DW, Yan XS. Measurement of cardiovascular and pulmonary function endpoints and other physiological effects following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers. Regul Toxicol Pharmacol 2017;87:36-53. 10.1016/j.yrtph.2017.05.002
    1. Cravo AS, Bush J, Sharma G, et al. A randomised, parallel group study to evaluate the safety profile of an electronic vapour product over 12 weeks. Regul Toxicol Pharmacol 2016;81(Suppl 1):S1-14. 10.1016/j.yrtph.2016.10.003
    1. Vardavas CI, Anagnostopoulos N, Kougias M, Evangelopoulou V, Connolly GN, Behrakis PK. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide. Chest 2012;141:1400-6. 10.1378/chest.11-2443
    1. Flouris AD, Chorti MS, Poulianiti KP, et al. Acute impact of active and passive electronic cigarette smoking on serum cotinine and lung function. Inhal Toxicol 2013;25:91-101. 10.3109/08958378.2012.758197
    1. Staudt MR, Salit J, Kaner RJ, Hollmann C, Crystal RG. Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes. Respir Res 2018;19:78. 10.1186/s12931-018-0778-z
    1. Ferrari M, Zanasi A, Nardi E, et al. Short-term effects of a nicotine-free e-cigarette compared to a traditional cigarette in smokers and non-smokers. BMC Pulm Med 2015;15:120. 10.1186/s12890-015-0106-z
    1. Boulay ME, Henry C, Bossé Y, Boulet LP, Morissette MC. Acute effects of nicotine-free and flavour-free electronic cigarette use on lung functions in healthy and asthmatic individuals. Respir Res 2017;18:33. 10.1186/s12931-017-0518-9
    1. Lappas AS, Tzortzi AS, Konstantinidi EM, et al. Short-term respiratory effects of e-cigarettes in healthy individuals and smokers with asthma. Respirology 2018;23:291-7. 10.1111/resp.13180
    1. Meo SA, Ansary MA, Barayan FR, et al. Electronic Cigarettes: Impact on Lung Function and Fractional Exhaled Nitric Oxide Among Healthy Adults. Am J Mens Health 2019;13:1557988318806073. 10.1177/1557988318806073
    1. Aurora P, Stanojevic S, Wade A, et al. London Cystic Fibrosis Collaboration Lung clearance index at 4 years predicts subsequent lung function in children with cystic fibrosis. Am J Respir Crit Care Med 2011;183:752-8. 10.1164/rccm.200911-1646OC
    1. Woodruff PG, Barr RG, Bleecker E, et al. SPIROMICS Research Group Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function. N Engl J Med 2016;374:1811-21. 10.1056/NEJMoa1505971
    1. Coxson HO, Leipsic J, Parraga G, Sin DD. Using pulmonary imaging to move chronic obstructive pulmonary disease beyond FEV1. Am J Respir Crit Care Med 2014;190:135-44. 10.1164/rccm.201402-0256PP
    1. Matthay MA, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. J Clin Invest 2012;122:2731-40. 10.1172/JCI60331
    1. Ghosh A, Coakley RC, Mascenik T, et al. Chronic E-Cigarette Exposure Alters the Human Bronchial Epithelial Proteome. Am J Respir Crit Care Med 2018;198:67-76. 10.1164/rccm.201710-2033OC
    1. Carter T, Tucker D, Kilic A, Papadimos TJ, Barlow A, Berry E. Life-threatening Vesicular Bronchial Injury Requiring Veno-venous Extracorporeal Membrane Oxygenation Rescue in an Electronic Nicotine Delivery System User. Clin Pract Cases Emerg Med 2017;1:212-7. 10.5811/cpcem.2017.3.33171
    1. Reidel B, Radicioni G, Clapp PW, et al. E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving Increased Neutrophilic Activation and Altered Mucin Secretion. Am J Respir Crit Care Med 2018;197:492-501. 10.1164/rccm.201708-1590OC
    1. Anderson WH, Coakley RD, Button B, et al. The Relationship of Mucus Concentration (Hydration) to Mucus Osmotic Pressure and Transport in Chronic Bronchitis. Am J Respir Crit Care Med 2015;192:182-90. 10.1164/rccm.201412-2230OC
    1. Kesimer M, Ford AA, Ceppe A, et al. Airway Mucin Concentration as a Marker of Chronic Bronchitis. N Engl J Med 2017;377:911-22. 10.1056/NEJMoa1701632
    1. Malerba M, Radaeli A, Olivini A, et al. Exhaled nitric oxide as a biomarker in COPD and related comorbidities. Biomed Res Int 2014;2014:271918. 10.1155/2014/271918
    1. Marini S, Buonanno G, Stabile L, Ficco G. Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide. Toxicol Appl Pharmacol 2014;278:9-15. 10.1016/j.taap.2014.04.004
    1. Muley T, Wiebel M, Schulz V, Ebert W. Elastinolytic activity of alveolar macrophages in smoking-associated pulmonary emphysema. Clin Investig 1994;72:269-76. 10.1007/BF00180039
    1. Harris JO, Olsen GN, Castle JR, Maloney AS. Comparison of proteolytic enzyme activity in pulmonary alveolar macrophages and blood leukocytes in smokers and nonsmokers. Am Rev Respir Dis 1975;111:579-86.
    1. Takahashi H, Ishidoh K, Muno D, et al. Cathepsin L activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers. Am Rev Respir Dis 1993;147:1562-8. 10.1164/ajrccm/147.6_Pt_1.1562
    1. Weitz JI, Crowley KA, Landman SL, Lipman BI, Yu J. Increased neutrophil elastase activity in cigarette smokers. Ann Intern Med 1987;107:680-2. 10.7326/0003-4819-107-5-680
    1. Shapiro SD, Goldstein NM, Houghton AM, Kobayashi DK, Kelley D, Belaaouaj A. Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol 2003;163:2329-35. 10.1016/S0002-9440(10)63589-4
    1. Churg A, Cosio M, Wright JL. Mechanisms of cigarette smoke-induced COPD: insights from animal models. Am J Physiol Lung Cell Mol Physiol 2008;294:L612-31. 10.1152/ajplung.00390.2007
    1. Antunes MA, Rocco PR. Elastase-induced pulmonary emphysema: insights from experimental models. An Acad Bras Cienc 2011;83:1385-96. 10.1590/S0001-37652011005000039
    1. Sohal SS, Reid D, Soltani A, et al. Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease. Respirology 2010;15:930-8. 10.1111/j.1440-1843.2010.01808.x
    1. Crystal RG. Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. J Clin Invest 1990;85:1343-52. 10.1172/JCI114578
    1. Stick SM, Brennan S, Murray C, et al. Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening. J Pediatr 2009;155:623-8.e1. 10.1016/j.jpeds.2009.05.005
    1. Mason SD, Joyce JA. Proteolytic networks in cancer. Trends Cell Biol 2011;21:228-37. 10.1016/j.tcb.2010.12.002
    1. Chaumont M, van de Borne P, Bernard A, et al. Fourth generation e-cigarette vaping induces transient lung inflammation and gas exchange disturbances: results from two randomized clinical trials. Am J Physiol Lung Cell Mol Physiol 2019;316:L705-19. 10.1152/ajplung.00492.2018
    1. Moazed F, Burnham EL, Vandivier RW, et al. Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation. Thorax 2016;71:1130-6. 10.1136/thoraxjnl-2015-207886
    1. Moazed F, Calfee CS. Environmental risk factors for acute respiratory distress syndrome. Clin Chest Med 2014;35:625-37. 10.1016/j.ccm.2014.08.003
    1. Viswam D, Trotter S, Burge PS, Walters GI. Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes. BMJ Case Rep 2018;2018:bcr-2018-224350. 10.1136/bcr-2018-224350
    1. Thota D, Latham E. Case report of electronic cigarettes possibly associated with eosinophilic pneumonitis in a previously healthy active-duty sailor. J Emerg Med 2014;47:15-7. 10.1016/j.jemermed.2013.09.034
    1. Agustin M, Yamamoto M, Cabrera F, Eusebio R. Diffuse Alveolar Hemorrhage Induced by Vaping. Case Rep Pulmonol 2018;2018:9724530. 10.1155/2018/9724530
    1. Khan MS, Khateeb F, Akhtar J, et al. Organizing pneumonia related to electronic cigarette use: A case report and review of literature. Clin Respir J 2018;12:1295-9. 10.1111/crj.12775
    1. Flower M, Nandakumar L, Singh M, Wyld D, Windsor M, Fielding D. Respiratory bronchiolitis-associated interstitial lung disease secondary to electronic nicotine delivery system use confirmed with open lung biopsy. Respirol Case Rep 2017;5:e00230. 10.1002/rcr2.230
    1. Sommerfeld CG, Weiner DJ, Nowalk A, Larkin A. Hypersensitivity Pneumonitis and Acute Respiratory Distress Syndrome From E-Cigarette Use. Pediatrics 2018;141:e20163927. 10.1542/peds.2016-3927
    1. Dicpinigaitis PV, Lee Chang A, Dicpinigaitis AJ, Negassa A. Effect of e-Cigarette Use on Cough Reflex Sensitivity. Chest 2016;149:161-5. 10.1378/chest.15-0817
    1. Carson JL, Zhou L, Brighton L, et al. Temporal structure/function variation in cultured differentiated human nasal epithelium associated with acute single exposure to tobacco smoke or E-cigarette vapor. Inhal Toxicol 2017;29:137-44. 10.1080/08958378.2017.1318985
    1. Martin EM, Clapp PW, Rebuli ME, et al. E-cigarette use results in suppression of immune and inflammatory-response genes in nasal epithelial cells similar to cigarette smoke. Am J Physiol Lung Cell Mol Physiol 2016;311:L135-44. 10.1152/ajplung.00170.2016
    1. Law SM, Gray RD. Neutrophil extracellular traps and the dysfunctional innate immune response of cystic fibrosis lung disease: a review. J Inflamm (Lond) 2017;14:29. 10.1186/s12950-017-0176-1
    1. Clapp PW, Pawlak EA, Lackey JT, et al. Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune cell function. Am J Physiol Lung Cell Mol Physiol 2017;313:L278-92. 10.1152/ajplung.00452.2016
    1. Proctor RN. The history of the discovery of the cigarette-lung cancer link: evidentiary traditions, corporate denial, global toll. Tob Control 2012;21:87-91. 10.1136/tobaccocontrol-2011-050338
    1. Lorenz E, Stewart HL, Daniel JH, et al. The effects of breathing tobacco smoke on strain A mice. Cancer Res 1943;3:123.
    1. Wynder EL, Graham EA, Croninger AB. Experimental production of carcinoma with cigarette tar. Cancer Res 1953;13:855-64.
    1. Larcombe AN, Janka MA, Mullins BJ, Berry LJ, Bredin A, Franklin PJ. 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. 10.1152/ajplung.00203.2016
    1. Lee HW, Park SH, Weng MW, et al. E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc Natl Acad Sci U S A 2018;115:E1560-9. 10.1073/pnas.1718185115
    1. Khosravi M, Lin RL, Lee LY. Inhalation of electronic cigarette aerosol induces reflex bronchoconstriction by activation of vagal bronchopulmonary C-fibers. Am J Physiol Lung Cell Mol Physiol 2018;315:L467-75. 10.1152/ajplung.00137.2018
    1. Lim HB, Kim SH. Inhallation of e-Cigarette Cartridge Solution Aggravates Allergen-induced Airway Inflammation and Hyper-responsiveness in Mice. Toxicol Res 2014;30:13-8. 10.5487/TR.2014.30.1.013
    1. Werley MS, Kirkpatrick DJ, Oldham MJ, et al. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats. Inhal Toxicol 2016;28:22-38. 10.3109/08958378.2015.1130758
    1. Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ 2016;353:i1585. 10.1136/bmj.i1585
    1. 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;71:1119-29. 10.1136/thoraxjnl-2015-208039
    1. Sussan TE, Gajghate S, Thimmulappa RK, et al. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS One 2015;10:e0116861. 10.1371/journal.pone.0116861
    1. Miyashita L, Suri R, Dearing E, et al. E-cigarette vapour enhances pneumococcal adherence to airway epithelial cells. Eur Respir J 2018;51:1701592. 10.1183/13993003.01592-2017
    1. Hwang JH, Lyes M, Sladewski K, et al. Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. J Mol Med (Berl) 2016;94:667-79. 10.1007/s00109-016-1378-3
    1. Webster MJ, Tarran R. Slippery When Wet: Airway Surface Liquid Homeostasis and Mucus Hydration. Curr Top Membr 2018;81:293-335. 10.1016/bs.ctm.2018.08.004
    1. Ghosh A, Boucher RC, Tarran R. Airway hydration and COPD. Cell Mol Life Sci 2015;72:3637-52. 10.1007/s00018-015-1946-7
    1. Shivalingappa PC, Hole R, Westphal CV, Vij N. Airway Exposure to E-Cigarette Vapors Impairs Autophagy and Induces Aggresome Formation. Antioxid Redox Signal 2016;24:186-204. 10.1089/ars.2015.6367
    1. Lee KM, Hoeng J, Harbo S, et al. Biological changes in C57BL/6 mice following 3 weeks of inhalation exposure to cigarette smoke or e-vapor aerosols. Inhal Toxicol 2018;30:553-67. 10.1080/08958378.2019.1576807
    1. Glynos C, Bibli SI, Katsaounou P, et al. Comparison of the effects of e-cigarette vapor with cigarette smoke on lung function and inflammation in mice. Am J Physiol Lung Cell Mol Physiol 2018;315:L662-72. 10.1152/ajplung.00389.2017
    1. Phillips B, Titz B, Kogel U, et al. Toxicity of the main electronic cigarette components, propylene glycol, glycerin, and nicotine, in Sprague-Dawley rats in a 90-day OECD inhalation study complemented by molecular endpoints. Food Chem Toxicol 2017;109:315-32. 10.1016/j.fct.2017.09.001
    1. Reinikovaite V, Rodriguez IE, Karoor V, et al. The effects of electronic cigarette vapour on the lung: direct comparison to tobacco smoke. Eur Respir J 2018;51:1701661. 10.1183/13993003.01661-2017
    1. Crotty Alexander LE, Drummond CA, Hepokoski M, et al. Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice. Am J Physiol Regul Integr Comp Physiol 2018;314:R834-47. 10.1152/ajpregu.00270.2017
    1. Kozlowski LT, Whetzel CA, Stellman SD, O’Connor RJ. Ignoring puff counts: another shortcoming of the Federal Trade Commission cigarette testing programme. Tob Control 2008;17(Suppl 1):i6-9. 10.1136/tc.2007.020602
    1. Dalhamn T. In vivo and in vitro ciliotoxic effects of tobacco smoke. Arch Environ Health 1970;21:633-4. 10.1080/00039896.1970.10667307
    1. Kaminski EJ, Fancher OE, Calandra JC. In vivo studies of the ciliastatic effects of tobacco smoke. Absorption of ciliastatic components by wet surfaces. Arch Environ Health 1968;16:188-93. 10.1080/00039896.1968.10665042
    1. Pettersson B, Curvall M, Enzell CR. Effects of tobacco smoke compounds on the ciliary activity of the embryo chicken trachea in vitro. Toxicology 1982;23:41-55. 10.1016/0300-483X(82)90040-3
    1. Agius AM, Smallman LA, Pahor AL. Age, smoking and nasal ciliary beat frequency. Clin Otolaryngol Allied Sci 1998;23:227-30. 10.1046/j.1365-2273.1998.00141.x
    1. Lin VY, Fain MD, Jackson PL, et al. Vaporized E-Cigarette Liquids Induce Ion Transport Dysfunction in Airway Epithelia. Am J Respir Cell Mol Biol 2019;61:162-73. 10.1165/rcmb.2017-0432OC
    1. Chung S, Baumlin N, Dennis JS, et al. Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors. Am J Respir Crit Care Med 2019. 10.1164/rccm.201811-2087OC
    1. Clapp PW, Lavrich KS, van Heusden CA, Lazarowski ER, Carson JL, Jaspers I. Cinnamaldehyde in flavored e-cigarette liquids temporarily suppresses bronchial epithelial cell ciliary motility by dysregulation of mitochondrial function. Am J Physiol Lung Cell Mol Physiol 2019;316:L470-86. 10.1152/ajplung.00304.2018
    1. Scott A, Lugg ST, Aldridge K, et al. Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages. Thorax 2018;73:1161-9. 10.1136/thoraxjnl-2018-211663
    1. Sassano MF, Davis ES, Keating JE, et al. Evaluation of e-liquid toxicity using an open-source high-throughput screening assay. PLoS Biol 2018;16:e2003904. 10.1371/journal.pbio.2003904
    1. Higham A, Rattray NJ, Dewhurst JA, et al. Electronic cigarette exposure triggers neutrophil inflammatory responses. Respir Res 2016;17:56. 10.1186/s12931-016-0368-x
    1. Schweitzer KS, Chen SX, Law S, et al. Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures. Am J Physiol Lung Cell Mol Physiol 2015;309:L175-87. 10.1152/ajplung.00411.2014
    1. Higham A, Bostock D, Booth G, Dungwa JV, Singh D. The effect of electronic cigarette and tobacco smoke exposure on COPD bronchial epithelial cell inflammatory responses. Int J Chron Obstruct Pulmon Dis 2018;13:989-1000. 10.2147/COPD.S157728
    1. Moses E, Wang T, Corbett S, et al. Molecular Impact of Electronic Cigarette Aerosol Exposure in Human Bronchial Epithelium. Toxicol Sci 2017;155:248-57. 10.1093/toxsci/kfw198
    1. Haswell LE, Baxter A, Banerjee A, et al. Reduced biological effect of e-cigarette aerosol compared to cigarette smoke evaluated in vitro using normalized nicotine dose and RNA-seq-based toxicogenomics. Sci Rep 2017;7:888. 10.1038/s41598-017-00852-y
    1. Rayner RE, Makena P, Prasad GL, Cormet-Boyaka E. Cigarette and ENDS preparations differentially regulate ion channels and mucociliary clearance in primary normal human bronchial 3D cultures. Am J Physiol Lung Cell Mol Physiol 2019;317:L295-302. 10.1152/ajplung.00096.2019
    1. Clunes LA, Davies CM, Coakley RD, et al. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. FASEB J 2012;26:533-45. 10.1096/fj.11-192377
    1. Patel W, Moore PJ, Sassano MF, et al. Increases in cytosolic Ca2+ induce dynamin- and calcineurin-dependent internalisation of CFTR. Cell Mol Life Sci 2019;76:977-94. 10.1007/s00018-018-2989-3
    1. Rasmussen JE, Sheridan JT, Polk W, Davies CM, Tarran R. Cigarette smoke-induced Ca2+ release leads to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. J Biol Chem 2014;289:7671-81. 10.1074/jbc.M113.545137
    1. Einarsson GG, Comer DM, McIlreavey L, et al. Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers. Thorax 2016;71:795-803. 10.1136/thoraxjnl-2015-207235
    1. Fodor AA, Klem ER, Gilpin DF, et al. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations. PLoS One 2012;7:e45001. 10.1371/journal.pone.0045001
    1. Yaucher NE, Fish JT, Smith HW, Wells JA. Propylene glycol-associated renal toxicity from lorazepam infusion. Pharmacotherapy 2003;23:1094-9. 10.1592/phco.23.10.1094.32762
    1. Blake DA, Whikehart DR, Yu H, Vogel T, Roberts DD. Common cryopreservation media deplete corneal endothelial cell plasma membrane Na+,K+ ATPase activity. Curr Eye Res 1996;15:263-71. 10.3109/02713689609007620
    1. Morshed KM, Jain SK, McMartin KE. Acute toxicity of propylene glycol: an assessment using cultured proximal tubule cells of human origin. Fundam Appl Toxicol 1994;23:38-43. 10.1006/faat.1994.1076
    1. Wieslander G, Norbäck D, Lindgren T. Experimental exposure to propylene glycol mist in aviation emergency training: acute ocular and respiratory effects. Occup Environ Med 2001;58:649-55. 10.1136/oem.58.10.649
    1. Dalton P, Soreth B, Maute C, Novaleski C, Banton M. Lack of respiratory and ocular effects following acute propylene glycol exposure in healthy humans. Inhal Toxicol 2018;30:124-32. 10.1080/08958378.2018.1470207
    1. Bessac BF, Jordt SE. Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology (Bethesda) 2008;23:360-70. 10.1152/physiol.00026.2008
    1. Niedermirtl F, Eberhardt M, Namer B, et al. Etomidate and propylene glycol activate nociceptive TRP ion channels. Mol Pain 2018;14:1744806918811699. 10.1177/1744806918811699
    1. Caceres AI, Brackmann M, Elia MD, et al. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc Natl Acad Sci U S A 2009;106:9099-104. 10.1073/pnas.0900591106
    1. Verkman AS. Aquaporins in clinical medicine. Annu Rev Med 2012;63:303-16. 10.1146/annurev-med-043010-193843
    1. Kreda SM, Gynn MC, Fenstermacher DA, Boucher RC, Gabriel SE. Expression and localization of epithelial aquaporins in the adult human lung. Am J Respir Cell Mol Biol 2001;24:224-34. 10.1165/ajrcmb.24.3.4367
    1. Madeira A, Moura TF, Soveral G. Aquaglyceroporins: implications in adipose biology and obesity. Cell Mol Life Sci 2015;72:759-71. 10.1007/s00018-014-1773-2
    1. Pocivavsek L, Gavrilov K, Cao KD, et al. Glycerol-induced membrane stiffening: the role of viscous fluid adlayers. Biophys J 2011;101:118-27. 10.1016/j.bpj.2011.05.036
    1. Zia S, Ndoye A, Nguyen VT, Grando SA. Nicotine enhances expression of the alpha 3, alpha 4, alpha 5, and alpha 7 nicotinic receptors modulating calcium metabolism and regulating adhesion and motility of respiratory epithelial cells. Res Commun Mol Pathol Pharmacol 1997;97:243-62.
    1. Macklin KD, Maus AD, Pereira EF, Albuquerque EX, Conti-Fine BM. Human vascular endothelial cells express functional nicotinic acetylcholine receptors. J Pharmacol Exp Ther 1998;287:435-9.
    1. Maus AD, Pereira EF, Karachunski PI, et al. Human and rodent bronchial epithelial cells express functional nicotinic acetylcholine receptors. Mol Pharmacol 1998;54:779-88. 10.1124/mol.54.5.779
    1. Conti-Fine BM, Navaneetham D, Lei S, Maus AD. Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity? Eur J Pharmacol 2000;393:279-94. 10.1016/S0014-2999(00)00036-4
    1. Maouche K, Medjber K, Zahm JM, et al. Contribution of α7 nicotinic receptor to airway epithelium dysfunction under nicotine exposure. Proc Natl Acad Sci U S A 2013;110:4099-104. 10.1073/pnas.1216939110
    1. Ahmad S, Zafar I, Mariappan N, et al. Acute pulmonary effects of aerosolized nicotine. Am J Physiol Lung Cell Mol Physiol 2019;316:L94-104. 10.1152/ajplung.00564.2017
    1. Armstrong LW, Rom WN, Martiniuk FT, Hart D, Jagirdar J, Galdston M. Nicotine enhances expression of the neutrophil elastase gene and protein in a human myeloblast/promyelocyte cell line. Am J Respir Crit Care Med 1996;154:1520-4. 10.1164/ajrccm.154.5.8912774
    1. Gomes JP, Watad A, Shoenfeld Y. Nicotine and autoimmunity: The lotus’ flower in tobacco. Pharmacol Res 2018;128:101-9. 10.1016/j.phrs.2017.10.005
    1. Egleton RD, Brown KC, Dasgupta P. Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis. Trends Pharmacol Sci 2008;29:151-8. 10.1016/j.tips.2007.12.006
    1. Caporaso N, Gu F, Chatterjee N, et al. Genome-wide and candidate gene association study of cigarette smoking behaviors. PLoS One 2009;4:e4653. 10.1371/journal.pone.0004653
    1. Hung RJ, McKay JD, Gaborieau V, et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 2008;452:633-7. 10.1038/nature06885
    1. Saccone NL, Wang JC, Breslau N, et al. The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. Cancer Res 2009;69:6848-56. 10.1158/0008-5472.CAN-09-0786
    1. Spitz MR, Amos CI, Dong Q, Lin J, Wu X. The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer. J Natl Cancer Inst 2008;100:1552-6. 10.1093/jnci/djn363
    1. Lam DC, Girard L, Ramirez R, et al. Expression of nicotinic acetylcholine receptor subunit genes in non-small-cell lung cancer reveals differences between smokers and nonsmokers. Cancer Res 2007;67:4638-47. 10.1158/0008-5472.CAN-06-4628
    1. Paleari L, Catassi A, Ciarlo M, et al. Role of alpha7-nicotinic acetylcholine receptor in human non-small cell lung cancer proliferation. Cell Prolif 2008;41:936-59. 10.1111/j.1365-2184.2008.00566.x
    1. Babic M, Schuchardt M, Tölle M, van der Giet M. In times of tobacco-free nicotine consumption: The influence of nicotine on vascular calcification. Eur J Clin Invest 2019;49:e13077. 10.1111/eci.13077
    1. 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;8:10378. 10.1038/s41598-018-28723-0
    1. Klager S, Vallarino J, MacNaughton P, Christiani DC, Lu Q, Allen JG. Flavoring Chemicals and Aldehydes in E-Cigarette Emissions. Environ Sci Technol 2017;51:10806-13. 10.1021/acs.est.7b02205
    1. Holden VK, Hines SE. Update on flavoring-induced lung disease. Curr Opin Pulm Med 2016;22:158-64. 10.1097/MCP.0000000000000250
    1. Gerloff J, Sundar IK, 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. 10.1089/aivt.2016.0030
    1. Muthumalage T, Prinz M, Ansah KO, Gerloff J, Sundar IK, Rahman I. Inflammatory and Oxidative Responses Induced by Exposure to Commonly Used e-Cigarette Flavoring Chemicals and Flavored e-Liquids without Nicotine. Front Physiol 2018;8:1130. 10.3389/fphys.2017.01130
    1. Behar RZ, Luo W, Lin SC, et al. Distribution, quantification and toxicity of cinnamaldehyde in electronic cigarette refill fluids and aerosols. Tob Control 2016;25(Suppl 2):ii94-102. 10.1136/tobaccocontrol-2016-053224
    1. Park HR, O’Sullivan M, Vallarino J, et al. Transcriptomic response of primary human airway epithelial cells to flavoring chemicals in electronic cigarettes. Sci Rep 2019;9:1400. 10.1038/s41598-018-37913-9
    1. Allen JG, Flanigan SS, 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;124:733-9. 10.1289/ehp.1510185
    1. Erythropel HC, Jabba SV, DeWinter TM, et al. Formation of flavorant-propylene Glycol Adducts With Novel Toxicological Properties in Chemically Unstable E-Cigarette Liquids. Nicotine Tob Res 2019;21:1248-58. 10.1093/ntr/nty192
    1. Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med 2015;372:392-4. 10.1056/NEJMc1413069
    1. Salamanca JC, Meehan-Atrash J, Vreeke S, Escobedo JO, Peyton DH, Strongin RM. E-cigarettes can emit formaldehyde at high levels under conditions that have been reported to be non-averse to users. Sci Rep 2018;8:7559. 10.1038/s41598-018-25907-6
    1. Samburova V, Bhattarai C, Strickland M, et al. Aldehydes in Exhaled Breath during E-Cigarette Vaping: Pilot Study Results. Toxics 2018;6:E46. 10.3390/toxics6030046
    1. Sleiman M, Logue JM, Montesinos VN, et al. Emissions from Electronic Cigarettes: Key Parameters Affecting the Release of Harmful Chemicals. Environ Sci Technol 2016;50:9644-51. 10.1021/acs.est.6b01741
    1. Bein K, Leikauf GD. Acrolein - a pulmonary hazard. Mol Nutr Food Res 2011;55:1342-60. 10.1002/mnfr.201100279
    1. Haussmann HJ. Use of hazard indices for a theoretical evaluation of cigarette smoke composition. Chem Res Toxicol 2012;25:794-810. 10.1021/tx200536w
    1. Kalkhoran S, Glantz SA. Modeling the Health Effects of Expanding e-Cigarette Sales in the United States and United Kingdom: A Monte Carlo Analysis. JAMA Intern Med 2015;175:1671-80. 10.1001/jamainternmed.2015.4209
    1. Warner KE, Mendez D. E-cigarettes: Comparing the Possible Risks of Increasing Smoking Initiation with the Potential Benefits of Increasing Smoking Cessation. Nicotine Tob Res 2019;21:41-7. 10.1093/ntr/nty062
    1. Larcombe AN. Early-life exposure to electronic cigarettes: cause for concern. Lancet Respir Med 2019;S2213-2600(19)30189-4. 10.1016/S2213-2600(19)30189-4
    1. Visser WF, Klerx WN, Cremers HWJM, Ramlal R, Schwillens PL, Talhout R. The Health Risks of Electronic Cigarette Use to Bystanders. Int J Environ Res Public Health 2019;16:E1525. 10.3390/ijerph16091525
    1. Gentzke AS, Creamer M, Cullen KA, et al. Vital Signs: Tobacco Product Use Among Middle and High School Students - United States, 2011-2018. MMWR Morb Mortal Wkly Rep 2019;68:157-64. 10.15585/mmwr.mm6806e1
    1. Kulik MC, Lisha NE, Glantz SA. E-cigarettes Associated With Depressed Smoking Cessation: A Cross-sectional Study of 28 European Union Countries. Am J Prev Med 2018;54:603-9. 10.1016/j.amepre.2017.12.017
    1. Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med 2016;4:116-28. 10.1016/S2213-2600(15)00521-4
    1. Glantz SA, Bareham DW. E-Cigarettes: Use, Effects on Smoking, Risks, and Policy Implications. Annu Rev Public Health 2018;39:215-35. 10.1146/annurev-publhealth-040617-013757
    1. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet 2013;382:1629-37. 10.1016/S0140-6736(13)61842-5
    1. Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One 2013;8:e66317. 10.1371/journal.pone.0066317
    1. Borrelli B, O’Connor GT. E-Cigarettes to Assist with Smoking Cessation. N Engl J Med 2019;380:678-9. 10.1056/NEJMe1816406
    1. McNeill A, Brose L, Calder R, et al. E-Cigarettes: An Evidence Update. A Report Commissioned by Public Health England. Public Health England, 2015.
    1. Ferkol TW, Farber HJ, La Grutta S, et al. Forum of International Respiratory Societies Electronic cigarette use in youths: a position statement of the Forum of International Respiratory Societies. Eur Respir J 2018;51:1800278. 10.1183/13993003.00278-2018
    1. Livingston CJ, Freeman RJ, Costales VC, et al. Electronic Nicotine Delivery Systems or E-cigarettes: American College of Preventive Medicine’s Practice Statement. Am J Prev Med 2019;56:167-78. 10.1016/j.amepre.2018.09.010
    1. Douglas CE, Henson R, Drope J, Wender RC. The American Cancer Society public health statement on eliminating combustible tobacco use in the United States. CA Cancer J Clin 2018;68:240-5. 10.3322/caac.21455
    1. Royal College of Physicians. Nicotine without smoke: Tobacco harm reduction. 2016. .
    1. Leone FT, Carlsen KH, Chooljian D, et al. Recommendations for the Appropriate Structure, Communication, and Investigation of Tobacco Harm Reduction Claims. An Official American Thoracic Society Policy Statement. Am J Respir Crit Care Med 2018;198:e90-105. 10.1164/rccm.201808-1443ST
    1. European Public Health Association. Facts and fiction on e-cigs. 2018. .
    1. Bals R, Boyd J, Esposito S, et al. Electronic cigarettes: a task force report from the European Respiratory Society. Eur Respir J 2019;53:1801151. 10.1183/13993003.01151-2018
    1. Cummings KM, Morris PB, Benowitz NL. Another Article About E-Cigarettes: Why Should I Care? J Am Heart Assoc 2018;7:e009944. 10.1161/JAHA.118.009944
    1. Chadi N, Hadland SE, Harris SK. Understanding the implications of the “vaping epidemic” among adolescents and young adults: A call for action. Subst Abus 2019;40:7-10. 10.1080/08897077.2019.1580241
    1. Cooper EC, Hoyle PC. Guidance for Industry. 1989. .

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren