Purpose of Review
Vaping is gaining popularity in the USA, particularly among teens and young adults. While e-cigs are commonly represented as safer alternatives to tobacco cigarettes, little is known regarding the health effects of their short- or long-term use, especially in individuals with pre-existing respiratory diseases such as asthma. Flavored e-cig liquids (e-liquids) and e-cig aerosols contain airway irritants and toxicants that have been implicated in the pathogenesis and worsening of lung diseases. In this review, we will summarize existing data on potential health effects of components present in e-cig aerosols, such as propylene glycol, vegetable glycerin, nicotine, and flavorings, and discuss their relevance in the context of asthma.
Recent survey data indicate that adolescents with asthma had a higher prevalence of current e-cig use (12.4%) compared to their non-asthmatics peers (10.2%) and conveyed positive beliefs about tobacco products, especially e-cigs. Similarly, a study conducted among high school students from Ontario, Canada, indicated a greater likelihood of e-cig use in asthmatics as compared to their non-asthmatic peers. Availability of different flavorings is often cited as the main reason among youth/adolescents for trying e-cigs or switching from cigarettes to e-cigs. Occupational inhalation of some common food-safe flavoring agents is reported to cause occupational asthma and worsen asthmatic symptoms. Moreover, workplace inhalation exposures to the flavoring agent diacetyl have caused irreversible obstructive airway disease in healthy workers. Additionally, recent studies report that thermal decomposition of propylene glycol (PG) and vegetable glycerin (VG), the base constituents of e-liquids, produces reactive carbonyls, including acrolein, formaldehyde, and acetaldehyde, which have known respiratory toxicities. Furthermore, recent nicotine studies in rodents reveal that prenatal nicotine exposures lead to epigenetic reprogramming in the offspring, abnormal lung development, and multigenerational transmission of asthmatic-like symptoms.
Comparisons of the toxicity and health effects of e-cigs and conventional cigarettes often focus on toxicants known to be present in cigarette smoke (CS) (i.e., formaldehyde, nitrosamines, etc.), as well as smoking-associated clinical endpoints, such as cancer, bronchitis, and chronic obstructive pulmonary disease (COPD). However, this approach disregards potential toxicity of components unique to flavored e-cigs, such as PG, VG, and the many different flavoring chemicals, which likely induce respiratory effects not usually observed in cigarette smokers.
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Organization WH. WHO global report on mortality attributable to tobacco. 2012.
Courtney R. The health consequences of smoking—50 years of progress: a report of the surgeon general, 2014 US Department of Health and Human Services Atlanta, GA: 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, 20141081 pp. Online (grey literature): http://www/. surgeongeneral. gov/library/reports/50-years-of-progress. Drug Alcohol Rev. 2015;34(6):694–5.
Garrett BE, Dube S, Trosclair A, Caraballo R, Pechacek T. Cigarette smoking-United States, 1965–2008. MMWR Surveill Summ. 2011;60:109–13.
Eaton DK, Kann L, Kinchen S, Shanklin S, Flint KH, Hawkins J, et al. Youth risk behavior surveillance—United States, 2011. Morb Mortal Wkly Rep Surveill Summ. 2012;61(4):1–162.
Hopkins DP, Razi S, Leeks KD, Priya Kalra G, Chattopadhyay SK, Soler RE, et al. Smokefree policies to reduce tobacco use: a systematic review. Am J Prev Med. 2010;38(2 Suppl):S275–89. https://doi.org/10.1016/j.amepre.2009.10.029.
Siegel M, Albers AB, Cheng DM, Hamilton WL, Biener L. Local restaurant smoking regulations and the adolescent smoking initiation process: results of a multilevel contextual analysis among Massachusetts youth. Arch Pediatr Adolesc Med. 2008;162(5):477–83. https://doi.org/10.1001/archpedi.162.5.477.
Elders MJ, Perry CL, Eriksen MP, Giovino GA. The report of the Surgeon General: preventing tobacco use among young people. Am J Public Health. 1994;84(4):543–7.
Besaratinia A, Tommasi S. Electronic cigarettes: the road ahead. Prev Med. 2014;66:65–7. https://doi.org/10.1016/j.ypmed.2014.06.014.
Anand V, McGinty KL, O’Brien K, Guenthner G, Hahn E, Martin CA. E-cigarette use and beliefs among urban public high school students in North Carolina. J Adolesc Health. 2015;57(1):46–51. https://doi.org/10.1016/j.jadohealth.2015.03.018.
Amrock SM, Zakhar J, Zhou S, Weitzman M. Perception of e-cigarette harm and its correlation with use among US adolescents. Nicotine Tob Res. 2015;17(3):330–6. https://doi.org/10.1093/ntr/ntu156.
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. 2016;219(3):268–77. https://doi.org/10.1016/j.ijheh.2016.01.004.
Kosmider L, Sobczak A, Fik M, Knysak J, Zaciera M, Kurek J, et al. Carbonyl compounds in electronic cigarette vapors: effects of nicotine solvent and battery output voltage. Nicotine Tob Res. 2014;16(10):1319–26. https://doi.org/10.1093/ntr/ntu078.
• Sleiman M, Logue JM, Montesinos VN, Russell ML, Litter MI, Gundel LA, et al. Emissions from electronic cigarettes: key parameters affecting the release of harmful chemicals. Environ Sci Technol. 2016;50(17):9644–51. https://doi.org/10.1021/acs.est.6b01741. This study quantified potentially toxic compounds in e-cig aerosol emissions and identified key parameters affecting toxic compound generation, including heating coil configuration and applied voltage.
Zezima K. Cigarettes without smoke or regulation. New York Times. 2009;1.
•• McNeill A, Brose L, Calder R, Hitchman S, Hajek P, McRobbie H. E-cigarettes: an evidence update. Public Health England. 2015;3. A government report by Public Health England (PHE), an agency of England’s Department of Health, which estimates that e-cigs are 95% less harmful to your health than normal cigarettes and supports the use of e-cigs as effective tobacco cessation and reduction aids.
• Zhu SH, Zhuang YL, Wong S, Cummins SE, Tedeschi GJ. E-cigarette use and associated changes in population smoking cessation: evidence from US current population surveys. BMJ. 2017;358:j3262. https://doi.org/10.1136/bmj.j3262. This study used survey data from the largest representative sample of e-cig users among the US population to show that that e-cig use is not only associated with a higher smoking cessation rate at the individual user level but also at the population level.
• Polosa R, Morjaria J, Caponnetto P, Caruso M, Strano S, Battaglia E, et al. Effect of smoking abstinence and reduction in asthmatic smokers switching to electronic cigarettes: evidence for harm reversal. Int J Environ Res Public Health. 2014;11(5):4965–77. https://doi.org/10.3390/ijerph110504965. A retrospective study which identifies improvements in asthma control, airway hyper-responsiveness, and pulmonary function in asthmatic smokers who quit or dramatically reduced their tobacco consumption by switching to e-cigs.
Polosa R, Morjaria JB, Caponnetto P, Caruso M, Campagna D, Amaradio MD, et al. Persisting long term benefits of smoking abstinence and reduction in asthmatic smokers who have switched to electronic cigarettes. Discov Med. 2016;21(114):99–108.
Polosa R, Campagna D, Sands MF. Counseling patients with asthma and allergy about electronic cigarettes: an evidence-based approach. Ann Allergy Asthma Immunol. 2016;116(2):106–11. https://doi.org/10.1016/j.anai.2015.10.012.
•• Fedele DA, Barnett TE, Dekevich D, Gibson-Young LM, Martinasek M, Jagger MA. Prevalence of and beliefs about electronic cigarettes and hookah among high school students with asthma. Ann Epidemiol. 2016;26(12):865–9. https://doi.org/10.1016/j.annepidem.2016.10.004. This study used 2014 Florida Youth Tobacco Survey data ( n = 32,921) to assess current cigarette, hookah, and e-cig use among high school students with and without asthma. Adolescents with asthma had a higher prevalence of current hookah and e-cig use, reported positive beliefs about tobacco products, and were more likely to live with individuals who used cigarettes, hookah, and e-cig compared with their peers.
•• Choi K, Bernat D. E-cigarette use among Florida youth with and without asthma. Am J Prev Med. 2016;51(4):446–53. https://doi.org/10.1016/j.amepre.2016.03.010. A study which used the 2012 Florida Youth Tobacco Survey data ( n = 36,085) to assess the prevalence of e-cig use among asthmatic youth and examine the associations between e-cig use, susceptibility to cigarette smoking, and asthma attack. The authors conclude that e-cig use is more common among asthmatic youth and is associated with increased susceptibility to cigarette smoking.
•• Larsen K, GEJ F, Boak A, Hamilton HA, Mann RE, Irving HM, et al. Looking beyond cigarettes: are Ontario adolescents with asthma less likely to smoke e-cigarettes, marijuana, waterpipes or tobacco cigarettes? Respir Med. 2016;120:10–5. https://doi.org/10.1016/j.rmed.2016.09.013. This study used the 2013 Ontario Student Drug Use and Health Survey data ( n = 6,159 high school students) to determine whether asthmatic students in Ontario smoke cigarettes, waterpipes, marijuana, or e-cig more or less than those without asthma. Students with asthma have higher odds of using e-cigs but not cigarettes, waterpipes, or marijuana, when compared to their non-asthmatic peers.
•• Cho JH, Paik SY. Association between electronic cigarette use and asthma among high school students in South Korea. PLoS One. 2016;11(3):e0151022. https://doi.org/10.1371/journal.pone.0151022. This cross-sectional study investigated the association between e-cig use and asthma in 35,904 high school students. The authors report that e-cig users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms.
•• Boulay ME, Henry C, Bosse 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(1):33. https://doi.org/10.1186/s12931-017-0518-9. A crossover, placebo-controlled study investigating the effects of a 1-h acute vaping session of nicotine- and flavor-free e-liquid on the pulmonary functions and respiratory mechanics of healthy and asthmatic individuals. Acute exposure to propylene glycol and glycerin aerosol in a controlled environment does not significantly impact pulmonary function or symptoms in both healthy and asthmatic subjects.
Ferrari M, Zanasi A, Nardi E, Morselli Labate AM, Ceriana P, Balestrino A, 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. https://doi.org/10.1186/s12890-015-0106-z.
Flouris AD, Chorti MS, Poulianiti KP, Jamurtas AZ, Kostikas K, Tzatzarakis MN, et al. Acute impact of active and passive electronic cigarette smoking on serum cotinine and lung function. Inhal Toxicol. 2013;25(2):91–101. https://doi.org/10.3109/08958378.2012.758197.
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. 2005;47(5):411–8. https://doi.org/10.1002/ajim.20151.
• Wang P, Chen W, Liao J, Matsuo T, Ito K, Fowles J, et al. A device-independent evaluation of carbonyl emissions from heated electronic cigarette solvents. PLoS One. 2017;12(1):e0169811. https://doi.org/10.1371/journal.pone.0169811. Quantitation of toxic volatile carbonyl compounds produced when vaping propylene glycol and glycerin under precisely controlled temperatures in the absence of nicotine and flavor additives.
Yao Y, Liang W, Zhu L, Duan Y, Jin Y, He L. Relationship between the concentration of formaldehyde in the air and asthma in children: a meta-analysis. Int J Clin Exp Med. 2015;8(6):8358–62.
Tillett T. Formaldehyde exposure among children: a potential building block of asthma. Environ Health Perspect. 2010;118(3):A 131. https://doi.org/10.1289/ehp.118-a131b.
Golden R, Holm S. Indoor air quality and asthma: has unrecognized exposure to acrolein confounded results of previous studies? Dose Response. 2017;15(1):1559325817691159. https://doi.org/10.1177/1559325817691159.
Prieto L, Gutierrez V, Cervera A, Linana J. Airway obstruction induced by inhaled acetaldehyde in asthma: repeatability relationship to adenosine 5′-monophosphate responsiveness. J Investig Allergol Clin Immunol. 2002;12(2):91–8.
Yildiz D. Nicotine, its metabolism and an overview of its biological effects. Toxicon. 2004;43(6):619–32. https://doi.org/10.1016/j.toxicon.2004.01.017.
Benowitz NL, Hukkanen J, Jacob III P. Nicotine chemistry, metabolism, kinetics and biomarkers. Nicotine psychopharmacology. Springer; 2009. p. 29–60.
D’alessandro A, Boeckelmann I, Hammwhöner M, Goette A. Nicotine, cigarette smoking and cardiac arrhythmia: an overview. Eur J Prev Cardiol. 2012;19(3):297–305.
Kershbaum A, Bellet S, Dickstein ER, Feinbergl J. Effect of cigarette smoking and nicotine on serum free fatty acids based on a study in the human subject and the experimental animal. Circ Res. 1961;9:631–8.
Kershbaum A, Osada H, Pappajohn DJ, Bellet S. Effect of nicotine on the mobilization of free fatty acids from adipose tissue in vitro. Experientia. 1969;25(2):128.
Carlson LA, Orö L. The effect of nicotinic acid on the plasma free fatty acids demonstration of a metabolic type of sympathicolysis. J Intern Med. 1962;172(6):641–5.
Omvik P. How smoking affects blood pressure. Blood Press. 1996;5(2):71–7.
Wright S, Zhong J, Zheng H, Larrick J. Nicotine inhibition of apoptosis suggests a role in tumor promotion. FASEB J. 1993;7(11):1045–51.
Walker LM, Preston MR, Magnay JL, Thomas PB, El Haj AJ. Nicotinic regulation of c-fos and osteopontin expression in human-derived osteoblast-like cells and human trabecular bone organ culture. Bone. 2001;28(6):603–8.
Nisell M, Nomikos GG, Chergui K, Grillner P, Svensson TH. Chronic nicotine enhances basal and nicotine-induced Fos immunoreactivity preferentially in the medial prefrontal cortex of the rat. Neuropsychopharmacology. 1997;17(3):151–61. https://doi.org/10.1016/S0893-133X(97)00040-7.
Whitley D, Goldberg SP, Jordan WD. Heat shock proteins: a review of the molecular chaperones. J Vasc Surg. 1999;29(4):748–51.
Doolittle DJ, Winegar R, Lee CK, Caldwell WS, Hayes AW, Donald deBethizy J. The genotoxic potential of nicotine and its major metabolites. Mutat Res Genet Toxicol. 1995;344(3–4):95–102.
Rehan VK, Liu J, Naeem E, Tian J, Sakurai R, Kwong K, et al. Perinatal nicotine exposure induces asthma in second generation offspring. BMC Med. 2012;10:129. https://doi.org/10.1186/1741-7015-10-129.
Liu J, Sakurai R, Rehan VK. PPAR-gamma agonist rosiglitazone reverses perinatal nicotine exposure-induced asthma in rat offspring. Am J Physiol Lung Cell Mol Physiol. 2015;308(8):L788–96. https://doi.org/10.1152/ajplung.00234.2014.
Rehan VK, Liu J, Sakurai R, Torday JS. Perinatal nicotine-induced transgenerational asthma. Am J Physiol Lung Cell Mol Physiol. 2013;305(7):L501–7. https://doi.org/10.1152/ajplung.00078.2013.
Benowitz NL, Henningfield JE. Reducing the nicotine content to make cigarettes less addictive. Tob Control. 2013;22(suppl 1):i14–i7.
Galle-Treger L, Suzuki Y, Patel N, Sankaranarayanan I, Aron JL, Maazi H, et al. Nicotinic acetylcholine receptor agonist attenuates ILC2-dependent airway hyperreactivity. Nat Commun. 2016;7:13202. https://doi.org/10.1038/ncomms13202.
Mabley J, Gordon S, Pacher P. Nicotine exerts an anti-inflammatory effect in a murine model of acute lung injury. Inflammation. 2011;34(4):231–7. https://doi.org/10.1007/s10753-010-9228-x.
Kalra R, Singh SP, Pena-Philippides JC, Langley RJ, Razani-Boroujerdi S, Sopori ML. Immunosuppressive and anti-inflammatory effects of nicotine administered by patch in an animal model. Clin Diagn Lab Immunol. 2004;11(3):563–8. https://doi.org/10.1128/CDLI.11.3.563-568.2004.
Kalra R, Singh SP, Kracko D, Matta SG, Sharp BM, Sopori ML. Chronic self-administration of nicotine in rats impairs T cell responsiveness. J Pharmacol Exp Ther. 2002;302(3):935–9.
Sopori ML, Kozak W, Savage SM, Geng Y, Soszynski D, Kluger MJ, et al. Effect of nicotine on the immune system: possible regulation of immune responses by central and peripheral mechanisms. Psychoneuroendocrinology. 1998;23(2):189–204.
Sopori ML, Kozak W, Savage SM, Geng Y, Kluger MJ. Nicotine-induced modulation of T cell function. Implications for inflammation and infection. Adv Exp Med Biol. 1998;437:279–89.
Sopori ML, Kozak W. Immunomodulatory effects of cigarette smoke. J Neuroimmunol. 1998;83(1–2):148–56.
Bencherif M, Lippiello PM, Lucas R, Marrero MB. Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases. Cell Mol Life Sci. 2011;68(6):931–49. https://doi.org/10.1007/s00018-010-0525-1.
Mishra NC, Rir-Sima-Ah J, Langley RJ, Singh SP, Pena-Philippides JC, Koga T, et al. Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. J Immunol. 2008;180(11):7655–63.
Chen EY, Sun A, Chen CS, Mintz AJ, Chin WC. Nicotine alters mucin rheological properties. Am J Physiol Lung Cell Mol Physiol. 2014;307(2):L149–57. https://doi.org/10.1152/ajplung.00396.2012.
Gundavarapu S, Wilder JA, Mishra NC, Rir-Sima-Ah J, Langley RJ, Singh SP, et al. Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia, and airway mucus formation in vitro and in vivo. J Allergy Clin Immunol. 2012;130(3):770–780 e11. https://doi.org/10.1016/j.jaci.2012.04.002.
Razani-Boroujerdi S, Singh SP, Knall C, Hahn FF, Pena-Philippides JC, Kalra R, et al. Chronic nicotine inhibits inflammation and promotes influenza infection. Cell Immunol. 2004;230(1):1–9. https://doi.org/10.1016/j.cellimm.2004.07.007.
Zhu SH, Sun JY, Bonnevie E, Cummins SE, Gamst A, Yin L, et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control. 2014;23(Suppl 3):iii3–9. https://doi.org/10.1136/tobaccocontrol-2014-051670.
Harrell MB, Weaver SR, Loukas A, Creamer M, Marti CN, Jackson CD, et al. Flavored e-cigarette use: characterizing youth, young adult, and adult users. Prev Med Rep. 2017;5:33–40. https://doi.org/10.1016/j.pmedr.2016.11.001.
Pepper JK, Ribisl KM, Brewer NT. Adolescents’ interest in trying flavoured e-cigarettes. Tob Control. 2016;25(Suppl 2):ii62–i6. https://doi.org/10.1136/tobaccocontrol-2016-053174.
Cobb CO, Hendricks PS, Eissenberg T. Electronic cigarettes and nicotine dependence: evolving products, evolving problems. BMC Med. 2015;13:119. https://doi.org/10.1186/s12916-015-0355-y.
Dai H, Hao J. Flavored electronic cigarette use and smoking among youth. Pediatrics. 2016;138:e20162513.
Zhong J, Cao S, Gong W, Fei F, Wang M. Electronic cigarettes use and intention to cigarette smoking among never-smoking adolescents and young adults: a meta-analysis. Int J Environ Res Public Health. 2016;13(5):pii: E465. https://doi.org/10.3390/ijerph13050465.
Padon AA, Maloney EK, Cappella JN. Youth-targeted e-cigarette marketing in the US. Tob Regul Sci. 2017;3(1):95–101.
Behar RZ, Luo W, Lin SC, Wang Y, Valle J, Pankow JF, et al. Distribution, quantification and toxicity of cinnamaldehyde in electronic cigarette refill fluids and aerosols. Tob Control. 2016;25(Suppl 2):ii94–ii102. https://doi.org/10.1136/tobaccocontrol-2016-053224.
Clapp PW, Pawlak EA, Lackey JT, Keating JE, Reeber SL, Glish GL, et al. Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune cell function. Am J Physiol Lung Cell Mol Physiol. 2017; https://doi.org/10.1152/ajplung.00452.2016.
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. 2002;347(5):330–8. https://doi.org/10.1056/NEJMoa020300.
van Rooy FG, Rooyackers JM, Prokop M, Houba R, Smit LA, Heederik DJ. Bronchiolitis obliterans syndrome in chemical workers producing diacetyl for food flavorings. Am J Respir Crit Care Med. 2007;176(5):498–504. https://doi.org/10.1164/rccm.200611-1620OC.
Barrington-Trimis JL, Samet JM, McConnell R. Flavorings in electronic cigarettes: an unrecognized respiratory health hazard? JAMA. 2014;312(23):2493–4. https://doi.org/10.1001/jama.2014.14830.
•• 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. 2015;17(2):168–74. https://doi.org/10.1093/ntr/ntu176. This study found that diacetyl and acetyl propionyl, known respiratory toxicants, were present in a large proportion of sweet-flavored e-cig liquids. The authors conclude that the use of many of the products evaluated would result in exposures that exceed NIOSH-defined safety levels.
Alert N. Preventing Lung Disease in Workers Who Use or Make Flavorings. NIOSH Publication No. 2004-110. 2003.
Lopez-Saez MP, Carrillo P, Huertas AJ, Fernandez-Nieto M, Lopez JD. Occupational asthma and dermatitis induced by eugenol in a cleaner. J Investig Allergol Clin Immunol. 2015;25(1):64–5.
Quirce S, Fernandez-Nieto M, del Pozo V, Sastre B, Sastre J. Occupational asthma and rhinitis caused by eugenol in a hairdresser. Allergy. 2008;63(1):137–8. https://doi.org/10.1111/j.1398-9995.2007.01525.x.
Kern AB. Contact dermatitis from cinnamon. Arch Dermatol. 1960;81:599–600.
Vandersall A, Katta R. Eyelid dermatitis as a manifestation of systemic contact dermatitis to cinnamon. Dermatitis. 2015;26(4):189. https://doi.org/10.1097/DER.0000000000000126.
Lauriola MM, De Bitonto A, Sena P. Allergic contact dermatitis due to cinnamon oil in galenic vaginal suppositories. Acta Derm Venereol. 2010;90(2):187–8. https://doi.org/10.2340/00015555-0782.
Ackermann L, Aalto-Korte K, Jolanki R, Alanko K. Occupational allergic contact dermatitis from cinnamon including one case from airborne exposure. Contact Dermatitis. 2009;60(2):96–9. https://doi.org/10.1111/j.1600-0536.2008.01486.x.
Hartmann K, Hunzelmann N. Allergic contact dermatitis from cinnamon as an odour-neutralizing agent in shoe insoles. Contact Dermatitis. 2004;50(4):253–4. https://doi.org/10.1111/j.0105-1873.2004.00301.x.
Sanchez-Perez J, Garcia-Diez A. Occupational allergic contact dermatitis from eugenol, oil of cinnamon and oil of cloves in a physiotherapist. Contact Dermatitis. 1999;41(6):346–7.
De Benito V, Alzaga R. Occupational allergic contact dermatitis from cassia (Chinese cinnamon) as a flavouring agent in coffee. Contact Dermatitis. 1999;40(3):165.
Uragoda CG. Asthma and other symptoms in cinnamon workers. Br J Ind Med. 1984;41(2):224–7.
•• Kosmider L, Sobczak A, Prokopowicz A, Kurek J, Zaciera M, Knysak J, et al. Cherry-flavoured electronic cigarettes expose users to the inhalation irritant, benzaldehyde. Thorax. 2016;71(4):376–7. https://doi.org/10.1136/thoraxjnl-2015-207895. This study measured benzaldehyde, a known respiratory irritant, in aerosol generated from flavored e-cigs purchased online. Benzaldehyde was detected in 108 out of 145 products.
Laham S, Broxup B, Robinet M, Potvin M, Schrader K. Subacute inhalation toxicity of benzaldehyde in the Sprague-Dawley rat. Am Ind Hyg Assoc J. 1991;52(12):503–10. https://doi.org/10.1080/15298669191365126.
Andersen A. Final report on the safety assessment of benzaldehyde. Int J Toxicol. 2006;25(Suppl 1):11–27. https://doi.org/10.1080/10915810600716612.
Leikauf GD. 12 formaldehyde and other aldehydes. Environmental toxicants: human exposures and their health effects. 2000:409.
Leikauf GD. Mechanisms of aldehyde-induced bronchial reactivity: role of airway epithelium. Res Rep Health Eff Inst. 1992;49:1–35.
Leikauf GD. Hazardous air pollutants and asthma. Environ Health Perspect. 2002;110(Suppl 4):505–26.
Annesi-Maesano I, Hulin M, Lavaud F, Raherison C, Kopferschmitt C, de Blay F, et al. Poor air quality in classrooms related to asthma and rhinitis in primary schoolchildren of the French 6 Cities Study. Thorax. 2012;67(8):682–8. https://doi.org/10.1136/thoraxjnl-2011-200391.
Jang TY, Park CS, Kim KS, Heo MJ, Kim YH. Benzaldehyde suppresses murine allergic asthma and rhinitis. Int Immunopharmacol. 2014;22(2):444–50. https://doi.org/10.1016/j.intimp.2014.07.029.
Spurlock BW, Dailey TM. Shortness of (fresh) breath--toothpaste-induced bronchospasm. N Engl J Med. 1990;323(26):1845–6.
Subiza J, Subiza JL, Valdivieso R, Escribano PM, Garcia R, Jerez M, et al. Toothpaste flavor-induced asthma. J Allergy Clin Immunol. 1992;90(6 Pt 1):1004–6.
Paiva M, Piedade S, Gaspar A. Toothpaste-induced anaphylaxis caused by mint (Mentha) allergy. Allergy. 2010;65(9):1201–2. https://doi.org/10.1111/j.1398-9995.2010.02329.x.
Plevkova J, Kollarik M, Poliacek I, Brozmanova M, Surdenikova L, Tatar M, et al. The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol. J Appl Physiol (1985). 2013;115(2):268–74. https://doi.org/10.1152/japplphysiol.01144.2012.
Willis DN, Liu B, Ha MA, Jordt SE, Morris JB. Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. FASEB J. 2011;25(12):4434–44. https://doi.org/10.1096/fj.11-188383.
•• Tierney PA, Karpinski CD, Brown JE, Luo W, Pankow JF. Flavour chemicals in electronic cigarette fluids. Tob Control. 2016;25(e1):e10–5. https://doi.org/10.1136/tobaccocontrol-2014-052175. This study quantified flavoring chemicals in 30 popular e-cig liquids. Many of the e-liquids contained aldehyde flavoring agents that made up 1 to 4% of the total e-liquid volume. The authors conclude that concentrations of some flavor chemicals in e-cigs are sufficiently high for inhalation exposure by vaping to be of toxicological concern.
Berridge MJ, Lipp P, Bootman MD. Signal transduction. The calcium entry pas de deux. Science. 2000;287(5458):1604–5.
Montell C. The TRP superfamily of cation channels. Sci STKE. 2005;2005(272):re3. https://doi.org/10.1126/stke.2722005re3.
Geppetti P, Materazzi S, Nicoletti P. The transient receptor potential vanilloid 1: role in airway inflammation and disease. Eur J Pharmacol. 2006;533(1–3):207–14. https://doi.org/10.1016/j.ejphar.2005.12.063.
Jia Y, Lee LY. Role of TRPV receptors in respiratory diseases. Biochim Biophys Acta. 2007;1772(8):915–27. https://doi.org/10.1016/j.bbadis.2007.01.013.
Takemura M, Quarcoo D, Niimi A, Dinh QT, Geppetti P, Fischer A, et al. Is TRPV1 a useful target in respiratory diseases? Pulm Pharmacol Ther. 2008;21(6):833–9. https://doi.org/10.1016/j.pupt.2008.09.005.
Lee LY, Gu Q. Role of TRPV1 in inflammation-induced airway hypersensitivity. Curr Opin Pharmacol. 2009;9(3):243–9. https://doi.org/10.1016/j.coph.2009.02.002.
Lee LY, Ni D, Hayes D Jr, Lin RL. TRPV1 as a cough sensor and its temperature-sensitive properties. Pulm Pharmacol Ther. 2011;24(3):280–5. https://doi.org/10.1016/j.pupt.2010.12.003.
Cantero-Recasens G, Gonzalez JR, Fandos C, Duran-Tauleria E, Smit LA, Kauffmann F, et al. Loss of function of transient receptor potential vanilloid 1 (TRPV1) genetic variant is associated with lower risk of active childhood asthma. J Biol Chem. 2010;285(36):27532–5. https://doi.org/10.1074/jbc.C110.159491.
Chen CL, Li H, Xing XH, Guan HS, Zhang JH, Zhao JW. Effect of TRPV1 gene mutation on bronchial asthma in children before and after treatment. Allergy Asthma Proc. 2015;36(2):e29–36. https://doi.org/10.2500/aap.2015.36.3828.
Rehman R, Bhat YA, Panda L, Mabalirajan U. TRPV1 inhibition attenuates IL-13 mediated asthma features in mice by reducing airway epithelial injury. Int Immunopharmacol. 2013;15(3):597–605. https://doi.org/10.1016/j.intimp.2013.02.010.
Rogerio AP, Andrade EL, Calixto JB. C-fibers, but not the transient potential receptor vanilloid 1 (TRPV1), play a role in experimental allergic airway inflammation. Eur J Pharmacol. 2011;662(1–3):55–62. https://doi.org/10.1016/j.ejphar.2011.04.027.
Yocum GT, Chen J, Choi CH, Townsend EA, Zhang Y, Xu D, et al. Role of transient receptor potential vanilloid 1 in the modulation of airway smooth muscle tone and calcium handling. Am J Physiol Lung Cell Mol Physiol. 2017;312(6):L812–L21. https://doi.org/10.1152/ajplung.00064.2017.
Brooks SM. Irritant-induced chronic cough: irritant-induced TRPpathy. Lung. 2008;186(Suppl 1):S88–93. https://doi.org/10.1007/s00408-007-9068-0.
Facchinetti F, Patacchini R. The rising role of TRPA1 in asthma. Open Drug Discov J. 2010;2(1):71–80.
• Yang H, Li S. Transient receptor potential ankyrin 1 (TRPA1) channel and neurogenic inflammation in pathogenesis of asthma. Med Sci Monit. 2016;22:2917–23. This review discusses how activation of TRPA1 expressed in C-fiber nociceptors promotes neurogenic inflammation in asthma.
Bessac BF, Jordt SE. Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology (Bethesda). 2008;23:360–70. https://doi.org/10.1152/physiol.00026.2008.
Symanowicz PT, Gianutsos G, Morris JB. Lack of role for the vanilloid receptor in response to several inspired irritant air pollutants in the C57Bl/6J mouse. Neurosci Lett. 2004;362(2):150–3. https://doi.org/10.1016/j.neulet.2004.03.016.
Hinman A, Chuang HH, Bautista DM, Julius D. TRP channel activation by reversible covalent modification. Proc Natl Acad Sci U S A. 2006;103(51):19564–8. https://doi.org/10.1073/pnas.0609598103.
Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, et al. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature. 2007;445(7127):541–5. https://doi.org/10.1038/nature05544.
Andersson DA, Gentry C, Moss S, Bevan S. Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008;28(10):2485–94. https://doi.org/10.1523/JNEUROSCI.5369-07.2008.
Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006;124(6):1269–82. https://doi.org/10.1016/j.cell.2006.02.023.
Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 2008;118(5):1899–910. https://doi.org/10.1172/JCI34192.
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–84. https://doi.org/10.1016/j.cell.2009.09.028.
Caceres AI, Brackmann M, Elia MD, Bessac BF, del Camino D, D’Amours M, et al. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc Natl Acad Sci U S A. 2009;106(22):9099–104. https://doi.org/10.1073/pnas.0900591106.
Premkumar LS. Transient receptor potential channels as targets for phytochemicals. ACS Chem Neurosci. 2014;5(11):1117–30.
• Wu SW, Fowler DK, Shaffer FJ, Lindberg JEM, Peters JH. Ethyl vanillin activates TRPA1. J Pharmacol Exp Ther. 2017;362(3):368–77. https://doi.org/10.1124/jpet.116.239384. This study provides evidence that ethyl vanillin, a common e-cig flavoring agent, is a potent activator of TRPA1.
Xu H, Delling M, Jun JC, Clapham DE. Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci. 2006;9(5):628–35. https://doi.org/10.1038/nn1692.
Inoue M, Fujita T, Goto M, Kumamoto E. Presynaptic enhancement by eugenol of spontaneous excitatory transmission in rat spinal substantia gelatinosa neurons is mediated by transient receptor potential A1 channels. Neuroscience. 2012;210:403–15. https://doi.org/10.1016/j.neuroscience.2012.02.040.
Chung G, Im ST, Kim YH, Jung SJ, Rhyu MR, Oh SB. Activation of transient receptor potential ankyrin 1 by eugenol. Neuroscience. 2014;261:153–60. https://doi.org/10.1016/j.neuroscience.2013.12.047.
Kaimoto T, Hatakeyama Y, Takahashi K, Imagawa T, Tominaga M, Ohta T. Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene. Eur J Pain. 2016;20(7):1155–65. https://doi.org/10.1002/ejp.840.
Silverman RA, Hasegawa K, Egan DJ, Stiffler KA, Sullivan AF, Camargo CA. Multicenter study of cigarette smoking among adults with asthma exacerbations in the emergency department, 2011–2012. Respir Med. 2017;125:89–91.
Thomson NC, Chaudhuri R, Livingston E. Asthma and cigarette smoking. Eur Respir J. 2004;24(5):822–33. https://doi.org/10.1183/09031936.04.00039004.
This work was supported by the National Institutes of Health (NIH) grants T32-ES-007126 and P50-HL-120100. Research reported in this publication was in part supported by the NIH and the Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.
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The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Allergies and the Environment
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Clapp, P.W., Jaspers, I. Electronic Cigarettes: Their Constituents and Potential Links to Asthma. Curr Allergy Asthma Rep 17, 79 (2017). https://doi.org/10.1007/s11882-017-0747-5
- E-cigarette and asthma
- E-liquid and asthma
- E-cigarette flavorings
- E-cigarette and inflammation