Pulmonary toxicity of e-cigarettes

Lauren F Chun, Farzad Moazed, Carolyn S Calfee, Michael A Matthay, Jeffrey E Gotts, Lauren F Chun, Farzad Moazed, Carolyn S Calfee, Michael A Matthay, Jeffrey E Gotts

Abstract

Electronic cigarettes (e-cigarettes or e-cigs) are designed to heat and aerosolize mixtures of vegetable glycerin, propylene glycol, nicotine, and flavoring additives, thus delivering nicotine by inhalation in the absence of combustion. These devices were originally developed to facilitate smoking cessation and have been available in the United States for over a decade. Since 2010, e-cig use has expanded rapidly, especially among adolescents, despite a paucity of short- and long-term safety data. Patterns of use have shifted to include never smokers and many dual users of e-cigs and combustible tobacco products. Over the last several years, research into the potential toxicities of e-cig aerosols has grown exponentially. In the interim, regulatory policymakers across the world have struggled with how to regulate an increasingly diverse array of suppliers and products, against a backdrop of strong advocacy from users, manufacturers, and tobacco control experts. Herein we provide an updated review of the pulmonary toxicity profile of these devices, summarizing evidence from cell culture, animal models, and human subjects. We highlight the major gaps in our current understanding, emphasize the challenges confronting the scientific and regulatory communities, and identify areas that require more research in this important and rapidly evolving field.

Keywords: alveolar epithelium; bronchial epithelium; electronic cigarette; lung; smoking; toxicity.

Copyright © 2017 the American Physiological Society.

Figures

Fig. 1.
Fig. 1.
A: the three generations of e-cigarettes. Beginning with the early cig-a-like devices, e-cigs introduced to the market more recently incorporate increased user control over the physics of aerosolization and e-liquid composition. B: e-cigarette atomizers contain wicking materials to transfer e-liquids from a storage tank in close proximity to a heating filament made from one of several types of metal alloys. Many of the commonly employed materials have well-described health risks.
Fig. 2.
Fig. 2.
E-cigarettes impact multiple regions and functions of the respiratory system, including altering airflow through the conducting airways, increasing oxidative stress, interfering with lung development, and impairing host defense against bacterial and viral pathogens.

References

    1. Ambrose BK, Day HR, Rostron B, Conway KP, Borek N, Hyland A, Villanti AC. Flavored tobacco product use among US youth aged 12-17 years, 2013-2014. JAMA 314: 1871–1873, 2015. doi:10.1001/jama.2015.13802.
    1. American Nonsmokers’ Rights Foundation (ANRF) Overview List—How many Smokefree Laws? [Online]. 2017. [6 Apr. 2017].
    1. American Nonsmokers’ Rights Foundation (ANRF) States and Municipalities with Laws Regulating Use of Electronic Cigarettes [Online]. 2017. .
    1. Antoniewicz L, Bosson JA, Kuhl J, Abdel-Halim SM, Kiessling A, Mobarrez F, Lundbäck M. Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers. Atherosclerosis 255: 179–185, 2016. doi:10.1016/j.atherosclerosis.2016.09.064.
    1. Antonini JM, Krishna Murthy GG, Brain JD. Responses to welding fumes: lung injury, inflammation, and the release of tumor necrosis factor-alpha and interleukin-1 beta. Exp Lung Res 23: 205–227, 1997. doi:10.3109/01902149709087368.
    1. Antonini JM, Roberts JR. Chromium in stainless steel welding fume suppresses lung defense responses against bacterial infection in rats. J Immunotoxicol 4: 117–127, 2007. doi:10.1080/15476910701336953.
    1. Antonini JM, Taylor MD, Zimmer AT, Roberts JR. Pulmonary responses to welding fumes: role of metal constituents. J Toxicol Environ Health A 67: 233–249, 2004. doi:10.1080/15287390490266909.
    1. Atabai K, Ishigaki M, Geiser T, Ueki I, Matthay MA, Ware LB. Keratinocyte growth factor can enhance alveolar epithelial repair by nonmitogenic mechanisms. Am J Physiol Lung Cell Mol Physiol 283: L163–L169, 2002. doi:10.1152/ajplung.00396.2001.
    1. Audrain-McGovern J, Strasser AA, Wileyto EP. The impact of flavoring on the rewarding and reinforcing value of e-cigarettes with nicotine among young adult smokers. Drug Alcohol Depend 166: 263–267, 2016. doi:10.1016/j.drugalcdep.2016.06.030.
    1. Aug A, Altraja S, Kilk K, Porosk R, Soomets U, Altraja A. E-cigarette affects the metabolome of primary normal human bronchial epithelial cells. PLoS One 10: e0142053, 2015. doi:10.1371/journal.pone.0142053.
    1. Azzopardi D, Patel K, Jaunky T, Santopietro S, Camacho OM, McAughey J, Gaça M. Electronic cigarette aerosol induces significantly less cytotoxicity than tobacco smoke. Toxicol Mech Methods 26: 477–491, 2016. doi:10.1080/15376516.2016.1217112.
    1. Bahl V, Lin S, Xu N, Davis B, Wang YH, Talbot P. Comparison of electronic cigarette refill fluid cytotoxicity using embryonic and adult models. Reprod Toxicol 34: 529–537, 2012. doi:10.1016/j.reprotox.2012.08.001.
    1. Ballbè M, Martínez-Sánchez JM, Sureda X, Fu M, Pérez-Ortuño R, Pascual JA, Saltó E, Fernández E. Cigarettes vs. e-cigarettes: passive exposure at home measured by means of airborne marker and biomarkers. Environ Res 135: 76–80, 2014. doi:10.1016/j.envres.2014.09.005.
    1. Barrington-Trimis JL, Samet JM, McConnell R. Flavorings in electronic cigarettes: an unrecognized respiratory health hazard? JAMA 312: 2493–2494, 2014. doi:10.1001/jama.2014.14830.
    1. Barrington-Trimis JL, Urman R, Berhane K, Unger JB, Cruz TB, Pentz MA, Samet JM, Leventhal AM, McConnell R. E-cigarettes and future cigarette use. Pediatrics 138: e20160379, 2016. doi:10.1542/peds.2016-0379.
    1. Behar RZ, Davis B, Wang Y, Bahl V, Lin S, Talbot P. Identification of toxicants in cinnamon-flavored electronic cigarette refill fluids. Toxicol In Vitro pii: S0887-2333(13)00261-0, 2013. doi:10.1016/j.tiv.2013.10.006.
    1. Behar RZ, Hua M, Talbot P. Puffing topography and nicotine intake of electronic cigarette users. PLoS One 10: e0117222, 2015. doi:10.1371/journal.pone.0117222.
    1. Behar RZ, Luo W, Lin SC, Wang Y, Valle J, Pankow JF, Talbot P. Distribution, quantification and toxicity of cinnamaldehyde in electronic cigarette refill fluids and aerosols. Tob Control 25, Suppl 2: ii94–ii102, 2016. doi:10.1136/tobaccocontrol-2016-053224.
    1. Benowitz NL, Burbank AD. Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends Cardiovasc Med 26: 515–523, 2016. doi:10.1016/j.tcm.2016.03.001.
    1. Benowitz NL, Fraiman JB. Cardiovascular effects of electronic cigarettes. Nat Rev Cardiol; advance online publication, 2017. doi:10.1038/nrcardio.2017.36.
    1. Blonshine S, Goldman MD. Optimizing performance of respiratory airflow resistance measurements. Chest 134: 1304–1309, 2008. doi:10.1378/chest.06-2898.
    1. Calfee CS, Matthay MA, Eisner MD, Benowitz N, Call M, Pittet J-F, Cohen MJ. Active and passive cigarette smoking and acute lung injury after severe blunt trauma. Am J Respir Crit Care Med 183: 1660–1665, 2011. doi:10.1164/rccm.201011-1802OC.
    1. Calfee CS, Matthay MA, Kangelaris KN, Siew ED, Janz DR, Bernard GR, May AK, Jacob P, Havel C, Benowitz NL, Ware LB. Cigarette smoke exposure and the acute respiratory distress syndrome. Crit Care Med 43: 1790–1797, 2015. doi:10.1097/CCM.0000000000001089.
    1. CDC QuickStats: cigarette smoking status* among current adult e-cigarette users,(†) by age group—National Health Interview Survey,(§) United States, 2015. MMWR Morb Mortal Wkly Rep 65: 1177, 2016. doi:10.15585/mmwr.mm6542a7.
    1. CDC Electronic Cigarette Use Among Adults: United States, 2014; Products—Data Briefs—Number 217—October 2015 [Online]. [12 Oct. 2016].
    1. Cervellati F, Muresan XM, Sticozzi C, Gambari R, Montagner G, Forman HJ, Torricelli C, Maioli E, Valacchi G. Comparative effects between electronic and cigarette smoke in human keratinocytes and epithelial lung cells. Toxicol In Vitro 28: 999–1005, 2014. doi:10.1016/j.tiv.2014.04.012.
    1. Chausse P, Naughton G, Dutheil F. Electronic cigarettes: the resistance value of the heating filament could be the key to lung toxicity. Chest 148: e29–e30, 2015. doi:10.1378/chest.15-0497.
    1. Chen BC, Bright SB, Trivedi AR, Valento M. Death following intentional ingestion of e-liquid. Clin Toxicol (Phila) 53: 914–916, 2015. doi:10.3109/15563650.2015.1090579.
    1. Cheng T. Chemical evaluation of electronic cigarettes. Tob Control 23, Suppl 2: ii11–ii17, 2014. doi:10.1136/tobaccocontrol-2013-051482.
    1. Cho JH, Paik SY. Association between electronic cigarette use and asthma among high school students in South Korea. PLoS One 11: e0151022, 2016. doi:10.1371/journal.pone.0151022.
    1. Coleman BN, Apelberg BJ, Ambrose BK, Green KM, Choiniere CJ, Bunnell R, King BA. Association between electronic cigarette use and openness to cigarette smoking among US young adults. Nicotine Tob Res 17: 212–218, 2015. doi:10.1093/ntr/ntu211.
    1. Cummings KJ, Boylstein RJ, Stanton ML, Piacitelli CA, Edwards NT, LeBouf RF, Kreiss K. Respiratory symptoms and lung function abnormalities related to work at a flavouring manufacturing facility. Occup Environ Med 71: 549–554, 2014. doi:10.1136/oemed-2013-101927.
    1. Davis B, Dang M, Kim J, Talbot P. Nicotine concentrations in electronic cigarette refill and do-it-yourself fluids. Nicotine Tob Res 17: 134–141, 2015. doi:10.1093/ntr/ntu080.
    1. Dicpinigaitis PV, Lee Chang A, Dicpinigaitis AJ, Negassa A. Effect of e-cigarette use on cough reflex sensitivity. Chest 149: 161–165, 2016. doi:10.1378/chest.15-0817.
    1. Dutra LM, Glantz SA. Electronic cigarettes and conventional cigarette use among U.S. adolescents: a cross-sectional study. JAMA Pediatr 168: 610–617, 2014. doi:10.1001/jamapediatrics.2013.5488.
    1. Fang X, Song Y, Hirsch J, Galietta LJV, Pedemonte N, Zemans RL, Dolganov G, Verkman AS, Matthay MA. Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells. Am J Physiol Lung Cell Mol Physiol 290: L242–L249, 2006. doi:10.1152/ajplung.00178.2005.
    1. Farsalinos KE, Kistler KA, Gillman G, Voudris V. Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins. Nicotine Tob Res 17: 168–174, 2015. doi:10.1093/ntr/ntu176.
    1. Farsalinos KE, Romagna G, Allifranchini E, Ripamonti E, Bocchietto E, Todeschi S, Tsiapras D, Kyrzopoulos S, Voudris V. Comparison of the cytotoxic potential of cigarette smoke and electronic cigarette vapour extract on cultured myocardial cells. Int J Environ Res Public Health 10: 5146–5162, 2013. doi:10.3390/ijerph10105146.
    1. Farsalinos KE, Spyrou A, Stefopoulos C, Tsimopoulou K, Kourkoveli P, Tsiapras D, Kyrzopoulos S, Poulas K, Voudris V. Nicotine absorption from electronic cigarette use: comparison between experienced consumers (vapers) and naïve users (smokers). Sci Rep 5: 11269, 2015. doi:10.1038/srep11269.
    1. FDA Public Health Focus—Summary of Results: Laboratory Analysis of Electronic Cigarettes Conducted by FDA [Online]. [11 Oct. 2016].
    1. FDA Center for Tobacco Products Products, Ingredients & Components—Vaporizers, E-Cigarettes, and Other Electronic Nicotine Delivery Systems (ENDS) [Online]. [7 Nov. 2016].
    1. FDA Center for Tobacco Products Compliance, Enforcement & Training—Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke: Established List [Online]. [20 Apr. 2017].
    1. Ferrari M, Zanasi A, Nardi E, Morselli Labate AM, Ceriana P, Balestrino A, Pisani L, Corcione N, Nava S. Short-term effects of a nicotine-free e-cigarette compared to a traditional cigarette in smokers and non-smokers. BMC Pulm Med 15: 120, 2015. doi:10.1186/s12890-015-0106-z.
    1. Flouris AD, Chorti MS, Poulianiti KP, Jamurtas AZ, Kostikas K, Tzatzarakis MN, Wallace Hayes A, Tsatsakis AM, Koutedakis Y. Acute impact of active and passive electronic cigarette smoking on serum cotinine and lung function. Inhal Toxicol 25: 91–101, 2013. doi:10.3109/08958378.2012.758197.
    1. Garcia-Arcos I, Geraghty P, Baumlin N, Campos M, Dabo AJ, Jundi B, Cummins N, Eden E, Grosche A, Salathe M, Foronjy R. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax 71: 1119–1129, 2016. doi:10.1136/thoraxjnl-2015-208039.
    1. Gaworski CL, Oldham MJ, Coggins CRE. Toxicological considerations on the use of propylene glycol as a humectant in cigarettes. Toxicology 269: 54–66, 2010. doi:10.1016/j.tox.2010.01.006.
    1. Geiss O, Bianchi I, Barrero-Moreno J. Correlation of volatile carbonyl yields emitted by e-cigarettes with the temperature of the heating coil and the perceived sensorial quality of the generated vapours. Int J Hyg Environ Health 219: 268–277, 2016. doi:10.1016/j.ijheh.2016.01.004.
    1. Gennimata S-A, Palamidas A, Kaltsakas G, Tsikrika S, Vakali S, Gratziou C, Koulouris N. Acute effect of e-cigarette on pulmonary function in healthy subjects and smokers. Eur Respir J 40: 1053, 2012.
    1. Gerloff J, Sundar IK, Freter R, Sekera ER, Friedman AE, Robinson R, Pagano T, Rahman I. 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 3: 28–40, 2017. doi:10.1089/aivt.2016.0030.
    1. Gillman IG, Kistler KA, Stewart EW, Paolantonio AR. Effect of variable power levels on the yield of total aerosol mass and formation of aldehydes in e-cigarette aerosols. Regul Toxicol Pharmacol 75: 58–65, 2016. doi:10.1016/j.yrtph.2015.12.019.
    1. Goldenson NI, Kirkpatrick MG, Barrington-Trimis JL, Pang RD, McBeth JF, Pentz MA, Samet JM, Leventhal AM. Effects of sweet flavorings and nicotine on the appeal and sensory properties of e-cigarettes among young adult vapers: Application of a novel methodology. Drug Alcohol Depend 168: 176–180, 2016. doi:10.1016/j.drugalcdep.2016.09.014.
    1. Goldsmith KT, Listinsky CM, Garver RI Jr. Serum response heterogeneity among nonsmall cell lung cancer cell lines. Am J Pathol 139: 939–947, 1991.
    1. Goniewicz ML, Gupta R, Lee YH, Reinhardt S, Kim S, Kim B, Kosmider L, Sobczak A. Nicotine levels in electronic cigarette refill solutions: A comparative analysis of products from the U.S., Korea, and Poland. Int J Drug Policy 26: 583–588, 2015. doi:10.1016/j.drugpo.2015.01.020.
    1. Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, Kurek J, Prokopowicz A, Jablonska-Czapla M, Rosik-Dulewska C, Havel C, Jacob P III, Benowitz N. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control 23: 133–139, 2014. doi:10.1136/tobaccocontrol-2012-050859.
    1. Grana RP, Benowitz NM, Glantz SAP. Background Paper on E-cigarettes (Electronic Nicotine Delivery Systems) [Online]. eScholarship. [10 Oct. 2016].
    1. Herzog B, Gerberi J, Scott A. Equity Research: Tobacco—Nielsen C-store Data—E-cig $ Sales Decline Moderates [Online]. Wells Fargo Securities: 2014. [10 Oct. 2016].
    1. Herzog B, Gerberi J, Scott A. Equity Research, “Tobacco Talk”–Q4 U.S. Vapor Retailer Survey [Online]. Wells Fargo Securities: 2015. [25 Oct. 2016].
    1. Hess CA, Olmedo P, Navas-Acien A, Goessler W, Cohen JE, Rule AM. E-cigarettes as a source of toxic and potentially carcinogenic metals. Environ Res 152: 221–225, 2017. doi:10.1016/j.envres.2016.09.026.
    1. Hu R-S, Wang J, Li H, Ni H, Chen Y-F, Zhang Y-W, Xiang S-P, Li H-H. Simultaneous extraction of nicotine and solanesol from waste tobacco materials by the column chromatographic extraction method and their separation and purification. Separ Purif Tech 146: 1–7, 2015. doi:10.1016/j.seppur.2015.03.016.
    1. Husari A, Shihadeh A, Talih S, Hashem Y, El Sabban M, Zaatari G. Acute exposure to electronic and combustible cigarette aerosols: effects in an animal model and in human alveolar cells. Nicotine Tob Res 18: 613–619, 2016. doi:10.1093/ntr/ntv169.
    1. Hwang JH, Lyes M, Sladewski K, Enany S, McEachern E, Mathew DP, Das S, Moshensky A, Bapat S, Pride DT, Ongkeko WM, Crotty Alexander LE. Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. J Mol Med (Berl) 94: 667–679, 2016. doi:10.1007/s00109-016-1378-3.
    1. Javed F, Kellesarian SV, Sundar IK, Romanos GE, Rahman I. Recent updates on electronic cigarette aerosol and inhaled nicotine effects on periodontal and pulmonary tissues. Oral Dis, 2017. doi:10.1111/odi.12652.
    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 175: 1671–1680, 2015. doi:10.1001/jamainternmed.2015.4209.
    1. Kandel ER, Kandel DB. Shattuck Lecture. A molecular basis for nicotine as a gateway drug. N Engl J Med 371: 932–943, 2014. doi:10.1056/NEJMsa1405092.
    1. Khlystov A, Samburova V. Flavoring compounds dominate toxic aldehyde production during e-cigarette vaping. Environ Sci Technol 50: 13080–13085, 2016. doi:10.1021/acs.est.6b05145.
    1. Kim H, Lim J, Buehler SS, Brinkman MC, Johnson NM, Wilson L, Cross KS, Clark PI. Role of sweet and other flavours in liking and disliking of electronic cigarettes. Tob Control 25, Suppl 2: ii55–ii61, 2016. doi:10.1136/tobaccocontrol-2016-053221.
    1. Kim KJ, Borok Z, Crandall ED. A useful in vitro model for transport studies of alveolar epithelial barrier. Pharm Res 18: 253–255, 2001. doi:10.1023/A:1011040824988.
    1. Kite AC, Le BQ, Cumpston KL, Hieger MA, Feldman MJ, Pozez AL. Blast injuries caused by vape devices: 2 case reports. Ann Plast Surg 77: 620–622, 2016. doi:10.1097/SAP.0000000000000875.
    1. Konrádová V, Vávrová V, Janota J. Effect of the inhalation of a surface tension-reducing substance (propylene glycol) on the ultrastructure of epithelium of the respiratory passages in rabbits. Folia Morphol (Praha) 26: 28–34, 1978.
    1. Kosmider L, Sobczak A, Prokopowicz A, Kurek J, Zaciera M, Knysak J, Smith D, Goniewicz ML. Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde. Thorax 71: 376–377, 2016. doi:10.1136/thoraxjnl-2015-207895.
    1. Kreiss K, Gomaa A, Kullman G, Fedan K, Simoes EJ, Enright PL. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N Engl J Med 347: 330–338, 2002. doi:10.1056/NEJMoa020300.
    1. Krishnan-Sarin S, Morean ME, Camenga DR, Cavallo DA, Kong G. E-cigarette use among high school and middle school adolescents in Connecticut. Nicotine Tob Res 17: 810–818, 2015. doi:10.1093/ntr/ntu243.
    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 2016, 2017. doi:10.1152/ajplung.00203.2016.
    1. Lee YH, Gawron M, Goniewicz ML. Changes in puffing behavior among smokers who switched from tobacco to electronic cigarettes. Addict Behav 48: 1–4, 2015. doi:10.1016/j.addbeh.2015.04.003.
    1. Leigh NJ, Lawton RI, Hershberger PA, Goniewicz ML. Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). Tob Control 25, Suppl 2: ii81–ii87, 2016. doi:10.1136/tobaccocontrol-2016-053205.
    1. Lerner CA, Sundar IK, Yao H, Gerloff J, Ossip DJ, McIntosh S, Robinson R, Rahman I. Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung. PLoS One 10: e0116732, 2015. doi:10.1371/journal.pone.0116732.
    1. Leung CC, Yu ITS, Chen W. Silicosis. Lancet 379: 2008–2018, 2012. doi:10.1016/S0140-6736(12)60235-9.
    1. Leventhal AM, Strong DR, Kirkpatrick MG, Unger JB, Sussman S, Riggs NR, Stone MD, Khoddam R, Samet JM, Audrain-McGovern J. Association of electronic cigarette use with initiation of combustible tobacco product smoking in early adolescence. JAMA 314: 700–707, 2015. doi:10.1001/jama.2015.8950.
    1. Lieber M, Smith B, Szakal A, Nelson-Rees W, Todaro G. A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer 17: 62–70, 1976. doi:10.1002/ijc.2910170110.
    1. Lim HB, Kim SH. Inhallation of e-cigarette cartridge solution aggravates allergen-induced airway inflammation and hyper-responsiveness in mice. Toxicol Res 30: 13–18, 2014. doi:10.5487/TR.2014.30.1.013.
    1. Lisko JG, Tran H, Stanfill SB, Blount BC, Watson CH. Chemical composition and evaluation of nicotine, tobacco alkaloids, pH, and selected flavors in e-cigarette cartridges and refill solutions. Nicotine Tob Res 17: 1270–1278, 2015. doi:10.1093/ntr/ntu279.
    1. Majeed BA, Dube SR, Sterling K, Whitney C, Eriksen MP. Opinions about electronic cigarette use in smoke-free areas among U.S. Adults, 2012. Nicotine Tob Res 17: 675–681, 2015. doi:10.1093/ntr/ntu235.
    1. Manigrasso M, Buonanno G, Fuoco FC, Stabile L, Avino P. Aerosol deposition doses in the human respiratory tree of electronic cigarette smokers. Environ Pollut 196: 257–267, 2015. doi:10.1016/j.envpol.2014.10.013.
    1. Manigrasso M, Buonanno G, Stabile L, Morawska L, Avino P. Particle doses in the pulmonary lobes of electronic and conventional cigarette users. Environ Pollut 202: 24–31, 2015. doi:10.1016/j.envpol.2015.03.008.
    1. Mao P, Wu S, Li J, Fu W, He W, Liu X, Slutsky AS, Zhang H, Li Y. Human alveolar epithelial type II cells in primary culture. Physiol Rep 3: 3, 2015. doi:10.14814/phy2.12288.
    1. Margham J, McAdam K, Forster M, Liu C, Wright C, Mariner D, Proctor C. Chemical composition of aerosol from an e-cigarette: a quantitative comparison with cigarette smoke. Chem Res Toxicol 29: 1662–1678, 2016. doi:10.1021/acs.chemrestox.6b00188.
    1. Maridet C, Atge B, Amici J-M, Taïeb A, Milpied B. The electronic cigarette: the new source of nickel contact allergy of the 21st century? Contact Dermat 73: 49–50, 2015. doi:10.1111/cod.12373.
    1. Marini S, Buonanno G, Stabile L, Ficco G. Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide. Toxicol Appl Pharmacol 278: 9–15, 2014. doi:10.1016/j.taap.2014.04.004.
    1. Maritz GS. Maternal nicotine exposure during gestation and lactation of rats induce microscopic emphysema in the offspring. Exp Lung Res 28: 391–403, 2002. doi:10.1080/01902140290092010.
    1. Martin EM, Clapp PW, Rebuli ME, Pawlak EA, Glista-Baker E, Benowitz NL, Fry RC, Jaspers I. 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 311: L135–L144, 2016. doi:10.1152/ajplung.00170.2016.
    1. Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol 88: 5–7, 2014. doi:10.1007/s00204-013-1127-0.
    1. McConnell R, Barrington-Trimis JL, Wang K, Urman R, Hong H, Unger J, Samet J, Leventhal A, Berhane K. Electronic cigarette use and respiratory symptoms in adolescents. Am J Respir Crit Care Med 195: 1043–1049, 2017. doi:10.1164/rccm.201604-0804OC.
    1. McGrath-Morrow SA, Hayashi M, Aherrera A, Lopez A, Malinina A, Collaco JM, Neptune E, Klein JD, Winickoff JP, Breysse P, Lazarus P, Chen G. The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice. PLoS One 10: e0118344, 2015. doi:10.1371/journal.pone.0118344.
    1. Mello S, Bigman CA, Sanders-Jackson A, Tan ASL. Perceived harm of secondhand electronic cigarette vapors and policy support to restrict public vaping: results from a national survey of US adults. Nicotine Tob Res 18: 686–693, 2016. doi:10.1093/ntr/ntv232.
    1. Mikheev VB, Brinkman MC, Granville CA, Gordon SM, Clark PI. Real-time measurement of electronic cigarette aerosol size distribution and metals content analysis. Nicotine Tob Res 18: 1895–1902, 2016. doi:10.1093/ntr/ntw128.
    1. Misra M, Leverette RD, Cooper BT, Bennett MB, Brown SE. Comparative in vitro toxicity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: e-liquids, extracts and collected aerosols. Int J Environ Res Public Health 11: 11325–11347, 2014. doi:10.3390/ijerph111111325.
    1. Moazed F, Burnham EL, Vandivier RW, O’Kane CM, Shyamsundar M, Hamid U, Abbott J, Thickett DR, Matthay MA, McAuley DF, Calfee CS. Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation. Thorax 71: 1130–1136, 2016. doi:10.1136/thoraxjnl-2015-207886.
    1. Morgan DL, Flake GP, Kirby PJ, Palmer SM. Respiratory toxicity of diacetyl in C57BL/6 mice. Toxicol Sci 103: 169–180, 2008. doi:10.1093/toxsci/kfn016.
    1. Mowry JB, Spyker DA, Brooks DE, Zimmerman A, Schauben JL. 2015 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 33rd Annual Report. Clin Toxicol (Phila) 54: 924–1109, 2016. doi:10.1080/15563650.2016.1245421.
    1. Neilson L, Mankus C, Thorne D, Jackson G, DeBay J, Meredith C. Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol. Toxicol In Vitro 29: 1952–1962, 2015. doi:10.1016/j.tiv.2015.05.018.
    1. Normandin PA, Benotti SA. Pediatric emergency update: lethality of liquid nicotine in e-cigarettes. J Emerg Nurs 41: 357–359, 2015. doi:10.1016/j.jen.2015.04.001.
    1. Patterson SB, Beckett AR, Lintner A, Leahey C, Greer A, Brevard SB, Simmons JD, Kahn SA. A novel classification system for injuries after electronic cigarette explosions. J Burn Care Res 38: e95–e100, 2017. doi:10.1097/BCR.0000000000000471.
    1. Pollard KM. Silica, silicosis, and autoimmunity. Front Immunol 7: 97, 2016. doi:10.3389/fimmu.2016.00097.
    1. RCP London Nicotine Without Smoke: Tobacco Harm Reduction [Online]. [7 Nov. 2016].
    1. Robinson RJ, Hensel EC, Morabito PN, Roundtree KA. Electronic cigarette topography in the natural environment. PLoS One 10: e0129296, 2015. doi:10.1371/journal.pone.0129296.
    1. Romagna G, Allifranchini E, Bocchietto E, Todeschi S, Esposito M, Farsalinos KE. Cytotoxicity evaluation of electronic cigarette vapor extract on cultured mammalian fibroblasts (ClearStream-LIFE): comparison with tobacco cigarette smoke extract. Inhal Toxicol 25: 354–361, 2013. doi:10.3109/08958378.2013.793439.
    1. Scheffler S, Dieken H, Krischenowski O, Förster C, Branscheid D, Aufderheide M. Evaluation of E-cigarette liquid vapor and mainstream cigarette smoke after direct exposure of primary human bronchial epithelial cells. Int J Environ Res Public Health 12: 3915–3925, 2015. doi:10.3390/ijerph120403915.
    1. Schober W, Szendrei K, Matzen W, Osiander-Fuchs H, Heitmann D, Schettgen T, Jörres RA, Fromme H. Use of electronic cigarettes (e-cigarettes) impairs indoor air quality and increases FeNO levels of e-cigarette consumers. Int J Hyg Environ Health 217: 628–637, 2014. doi:10.1016/j.ijheh.2013.11.003.
    1. Schweitzer KS, Chen SX, Law S, Van Demark M, Poirier C, Justice MJ, Hubbard WC, Kim ES, Lai X, Wang M, Kranz WD, Carroll CJ, Ray BD, Bittman R, Goodpaster J, Petrache I. Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures. Am J Physiol Lung Cell Mol Physiol 309: L175–L187, 2015. doi:10.1152/ajplung.00411.2014.
    1. Sekhon HS, Jia Y, Raab R, Kuryatov A, Pankow JF, Whitsett JA, Lindstrom J, Spindel ER. Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys. J Clin Invest 103: 637–647, 1999. doi:10.1172/JCI5232.
    1. Seo AD, Kim DC, Yu HJ, Kang MJ. Accidental ingestion of E-cigarette liquid nicotine in a 15-month-old child: an infant mortality case of nicotine intoxication. Korean J Pediatr 59: 490–493, 2016. doi:10.3345/kjp.2016.59.12.490.
    1. Sherwood CL, Boitano S. Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5-dimethypyrazine. Respir Res 17: 57, 2016. doi:10.1186/s12931-016-0369-9.
    1. Shi Y, Cummins SE, Zhu S-H. Use of electronic cigarettes in smoke-free environments. Tob Control 26: e19–e22, 2017. doi:10.1136/tobaccocontrol-2016-053118.
    1. Shivalingappa PC, Hole R, Westphal CV, Vij N. Airway exposure to e-cigarette vapors impairs autophagy and induces aggresome formation. Antioxid Redox Signal ars.2015.6367, 2015. doi:10.1089/ars.2015.6367.
    1. Singh T, Arrazola RA, Corey CG, Husten CG, Neff LJ, Homa DM, King BA. Tobacco use among middle and high school students—United States, 2011–2015. MMWR Morb Mortal Wkly Rep 65: 361–367, 2016. doi:10.15585/mmwr.mm6514a1.
    1. Sleiman M, Logue JM, Montesinos VN, Russell ML, Litter MI, Gundel LA, Destaillats H. Emissions from electronic cigarettes: key parameters affecting the release of harmful chemicals. Environ Sci Technol 50: 9644–9651, 2016. doi:10.1021/acs.est.6b01741.
    1. Spindel ER, McEvoy CT. The role of nicotine in the effects of maternal smoking during pregnancy on lung development and childhood respiratory disease. implications for dangers of e-cigarettes. Am J Respir Crit Care Med 193: 486–494, 2016. doi:10.1164/rccm.201510-2013PP.
    1. Spindle TR, Hiler MM, Cooke ME, Eissenberg T, Kendler KS, Dick DM. Electronic cigarette use and uptake of cigarette smoking: A longitudinal examination of U.S. college students. Addict Behav 67: 66–72, 2017. doi:10.1016/j.addbeh.2016.12.009.
    1. Suber RL, Deskin R, Nikiforov I, Fouillet X, Coggins CR. Subchronic nose-only inhalation study of propylene glycol in Sprague-Dawley rats. Food Chem Toxicol 27: 573–583, 1989. doi:10.1016/0278-6915(89)90016-1.
    1. Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim J-H, Sudini K, Consolini N, Cormier SA, Lomnicki S, Hasan F, Pekosz A, Biswal S. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS One 10: e0116861, 2015. doi:10.1371/journal.pone.0116861.
    1. Tan ASL, Bigman CA, Sanders-Jackson A. Sociodemographic correlates of self-reported exposure to e-cigarette communications and its association with public support for smoke-free and vape-free policies: results from a national survey of US adults. Tob Control 24: 574–581, 2015. doi:10.1136/tobaccocontrol-2014-051685.
    1. Tavolacci M-P, Vasiliu A, Romo L, Kotbagi G, Kern L, Ladner J. Patterns of electronic cigarette use in current and ever users among college students in France: a cross-sectional study. BMJ Open 6: e011344, 2016. doi:10.1136/bmjopen-2016-011344.
    1. Tran I, Ji C, Ni I, Min T, Tang D, Vij N. Role of cigarette smoke-induced aggresome formation in chronic obstructive pulmonary disease-emphysema pathogenesis. Am J Respir Cell Mol Biol 53: 159–173, 2015. doi:10.1165/rcmb.2014-0107OC.
    1. 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 E-Cigarette Use Among Youth and Young Adults. A Report From the Surgeon General. Rockville, MD: U.S. Dept of Health and Human Services, 2016.
    1. US Fire Administration Electronic Cigarette Fires and Explosions [Online]. FEMA; 2014. .
    1. van Eijl S, van Oorschot R, Olivier B, Nijkamp FP, Bloksma N. Stress and hypothermia in mice in a nose-only cigarette smoke exposure system. Inhal Toxicol 18: 911–918, 2006. doi:10.1080/08958370600822672.
    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 141: 1400–1406, 2012. doi:10.1378/chest.11-2443.
    1. Varughese S, Teschke K, Brauer M, Chow Y, van Netten C, Kennedy SM. Effects of theatrical smokes and fogs on respiratory health in the entertainment industry. Am J Ind Med 47: 411–418, 2005. doi:10.1002/ajim.20151.
    1. Wagener TL, Floyd EL, Stepanov I, Driskill LM, Frank SG, Meier E, Leavens EL, Tackett AP, Molina N, Queimado L. Have combustible cigarettes met their match? The nicotine delivery profiles and harmful constituent exposures of second-generation and third-generation electronic cigarette users. Tob Control 26, e1: e23–e28, 2017. doi:10.1136/tobaccocontrol-2016-053041.
    1. Wang MP, Ho SY, Leung LT, Lam TH. Electronic cigarette use and respiratory symptoms in chinese adolescents in hong kong. JAMA Pediatr 170: 89–91, 2016. doi:10.1001/jamapediatrics.2015.3024.
    1. Werley MS, Kirkpatrick DJ, Oldham MJ, Jerome AM, Langston TB, Lilly PD, Smith DC, Mckinney WJ Jr. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: a 90-day inhalation study in rats. Inhal Toxicol 28: 22–38, 2016. doi:10.3109/08958378.2015.1130758.
    1. Werley MS, McDonald P, Lilly P, Kirkpatrick D, Wallery J, Byron P, Venitz J. Non-clinical safety and pharmacokinetic evaluations of propylene glycol aerosol in Sprague-Dawley rats and beagle dogs. Toxicology 287: 76–90, 2011. doi:10.1016/j.tox.2011.05.015.
    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 58: 649–655, 2001. doi:10.1136/oem.58.10.649.
    1. Williams M, To A, Bozhilov K, Talbot P. Strategies to reduce tin and other metals in electronic cigarette aerosol. PLoS One 10: e0138933, 2015. doi:10.1371/journal.pone.0138933.
    1. Williams M, Villarreal A, Bozhilov K, Lin S, Talbot P. Metal and silicate particles including nanoparticles are present in electronic cigarette cartomizer fluid and aerosol. PLoS One 8: e57987, 2013. doi:10.1371/journal.pone.0057987.
    1. Wilson FA, Wang Y. Recent findings on the prevalence of e-cigarette use among adults in the U.S. Am J Prev Med 52: 385–390, 2017. doi:10.1016/j.amepre.2016.10.029.
    1. Wu Q, Jiang D, Minor M, Chu HW. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells. PLoS One 9: e108342, 2014. doi:10.1371/journal.pone.0108342.
    1. You G, Rhee J, Park Y, Park S. Determination of nicotine, cotinine and trans-3′-hydroxycotinine using LC/MS/MS in forensic samples of a nicotine fatal case by oral ingestion of e-cigarette liquid. J Forensic Sci 61: 1149–1154, 2016. doi:10.1111/1556-4029.13083.
    1. Zhu S-H, Sun JY, Bonnevie E, Cummins SE, Gamst A, Yin L, Lee M. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control 23, Suppl 3: iii3–iii9, 2014. doi:10.1136/tobaccocontrol-2014-051670.

Source: PubMed

3
Subscribe