Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Pathogenesis of E‐Cigarette Vaping Product Use‐Associated Lung Injury (EVALI)

Irina Petrache, Arnav Gupta, Patrick S. Hume, Tanner Rivera, Kelly S. Schweitzer, Hong Wei Chu

10.1002/cphy.c220022

Source: Volume 13, Issue 2, April 2023

Published online: March 2023

Full Article on Wiley Online Library



Abstract

EVALI is an acute inflammatory disease in response to lung cell injury induced by electronic cigarettes and vaping devices (EV) frequently containing Vitamin E Acetate or tetrahydrocannabinol additives, in the context of risk factors such as microbial exposure. EVALI resembles a respiratory viral illness that may progress to acute respiratory failure and acute respiratory distress syndrome (ARDS) but can also affect extra pulmonary organs. Manifestations may be severe, leading to death or long‐term morbidity and current treatments are largely supportive. While COVID‐19 has demanded public and research attention, EVALI continues to affect young individuals and its better understanding via research remains a priority. Although clinical research led to improved recognition of triggers, clinical and pathological manifestations, and natural course of EVALI, important questions remain that require a better understanding of disease pathogenesis. Preclinical models utilizing laboratory animals and cell or tissue culture platforms provide insight into the physiologic and mechanistic consequences of acute and chronic EV exposure, including the characteristics of the respiratory dysfunction and inflammatory response. However, a key limitation in the field is the absence of an established animal model of EVALI. Important areas of research emphasis include identifying triggers and risk factors to understand why only certain vapers develop EVALI, the role of specific lung immune and structural cells in the pathogenesis of EVALI, and the most important molecular mediators and therapeutic targets in EVALI. © 2023 American Physiological Society. Compr Physiol 13:4617‐4630, 2023.

Figure 1. Figure 1. Schematic of triggers and pathways involved in EVALI pathogenesis. Made in © BioRender ‐ biorender.com.
Figure 2. Figure 2. Effect of EV on lung cell barriers. (A) Measurement system for barrier measurement using Electric Cell‐Substrate Impedance Sensing (ECIS) using the 8WFilter and TEER24 units. (B) Effect of EV Juul brand juice, containing 10% nicotine on barrier function in small airway epithelial cells (SAEC) grown on air‐liquid interface; shown for comparison is TER of SAEC exposed to cigarette smoke (CS) extract (10%) and TER of human bronchial epithelial cell line Beas2B exposed to vitamin E acetate. Effect of Juul juice containing 5% (low) or 10% nicotine on primary human lung microvascular cells (HLMVEC). Trans‐cellular electrical resistance (TER) was measured in real time using ECIS and normalized by baseline resistance. A decrease in TER signifies loss of barrier function. Note that EV weakens the barrier of lung microvascular barrier in a nicotine‐dose‐dependent manner, but not that of lung epithelial barrier, which in turn is weakened by vitamin E acetate. Each tracing reflects one experiment that is representative of n = 3–10.


Figure 1. Schematic of triggers and pathways involved in EVALI pathogenesis. Made in © BioRender ‐ biorender.com.


Figure 2. Effect of EV on lung cell barriers. (A) Measurement system for barrier measurement using Electric Cell‐Substrate Impedance Sensing (ECIS) using the 8WFilter and TEER24 units. (B) Effect of EV Juul brand juice, containing 10% nicotine on barrier function in small airway epithelial cells (SAEC) grown on air‐liquid interface; shown for comparison is TER of SAEC exposed to cigarette smoke (CS) extract (10%) and TER of human bronchial epithelial cell line Beas2B exposed to vitamin E acetate. Effect of Juul juice containing 5% (low) or 10% nicotine on primary human lung microvascular cells (HLMVEC). Trans‐cellular electrical resistance (TER) was measured in real time using ECIS and normalized by baseline resistance. A decrease in TER signifies loss of barrier function. Note that EV weakens the barrier of lung microvascular barrier in a nicotine‐dose‐dependent manner, but not that of lung epithelial barrier, which in turn is weakened by vitamin E acetate. Each tracing reflects one experiment that is representative of n = 3–10.
References
 1.Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342: 1301‐1308, 2000.
 2.Agrawal A, Lynskey MT, Pergadia ML, Bucholz KK, Heath AC, Martin NG, Madden PA. Early cannabis use and DSM‐IV nicotine dependence: A twin study. Addiction 103: 1896‐1904, 2008.
 3.Akkanti BH, Hussain R, Patel MK, Patel JA, Dinh K, Zhao B, Elzamly S, Pelicon K, Petek K, Salas de Armas IA, Akay M, Kar B, Gregoric ID, Buja LM. Deadly combination of vaping‐lnduced lung injury and Influenza: Case report. Diagn Pathol 15: 83, 2020.
 4.Al‐Abdouh A, Phillips E, Allison MG. E‐cigarette or vaping product use‐associated lung injury: A severe case that responded to corticosteroid treatment. Cureus 12: e11544, 2020.
 5.Aloufi N, Namkung Y, Traboulsi H, Wilson ET, Laporte SA, Kaplan BLF, Ross MK, Nair P, Eidelman DH, Baglole CJ. Standardized cannabis smoke extract induces inflammation in human lung fibroblasts. Front Pharmacol 13: 852029, 2022.
 6.Amirahmadi R, Childress J, Patel S, Wagner LA. Electric cigarette‐related lung injury and cardiovascular insult. BMJ Case Rep 14: e238352, 2021.
 7.Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J, Sullivan K, Matakidou A, Wang Y, Mills G, Doheny K, Tsai YY, Chen WV, Shete S, Spitz MR, Houlston RS. Genome‐wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40: 616‐622, 2008.
 8.Bagale K, Paudel S, Cagle H, Sigel E, Kulkarni R. Electronic cigarette (e‐cigarette) vapor exposure alters the Streptococcus pneumoniae transcriptome in a nicotine‐dependent manner without affecting pneumococcal virulence. Appl Environ Microbiol 86: e02125‐19, 2020.
 9.Baldan A, Gomes AV, Ping P, Edwards PA. Loss of ABCG1 results in chronic pulmonary inflammation. J Immunol 180: 3560‐3568, 2008.
 10.Barletta JF, Bruno JJ, Buckley MS, Cook DJ. Stress ulcer prophylaxis. Crit Care Med 44: 1395‐1405, 2016.
 11.Bhat TA, Kalathil SG, Bogner PN, Blount BC, Goniewicz ML, Thanavala YM. An animal model of inhaled vitamin E acetate and EVALI‐like lung injury. N Engl J Med 382: 1175‐1177, 2020.
 12.Bizon M, Maciejewski D, Kolonko J. E‐cigarette or vaping product use‐associated acute lung injury (EVALI) as a therapeutic problem in anaesthesiology and intensive care departments. Anaesthesiol Intensive Ther 52: 219‐225, 2020.
 13.Blount BC, Karwowski MP, Morel‐Espinosa M, Rees J, Sosnoff C, Cowan E, Gardner M, Wang L, Valentin‐Blasini L, Silva L, De Jesus VR, Kuklenyik Z, Watson C, Seyler T, Xia B, Chambers D, Briss P, King BA, Delaney L, Jones CM, Baldwin GT, Barr JR, Thomas J, Pirkle JL. Evaluation of Bronchoalveolar Lavage Fluid from Patients in an Outbreak of E‐cigarette, or Vaping, Product Use‐Associated Lung Injury ‐ 10 States, August‐October 2019. MMWR Morb Mortal Wkly Rep 68: 1040‐1041, 2019.
 14.Bonner E, Chang Y, Christie E, Colvin V, Cunningham B, Elson D, Ghetu C, Huizenga J, Hutton SJ, Kolluri SK, Maggio S, Moran I, Parker B, Rericha Y, Rivera BN, Samon S, Schwichtenberg T, Shankar P, Simonich MT, Wilson LB, Tanguay RL. The chemistry and toxicology of vaping. Pharmacol Ther 225: 107837, 2021.
 15.Butt YM, Smith ML, Tazelaar HD, Vaszar LT, Swanson KL, Cecchini MJ, Boland JM, Bois MC, Boyum JH, Froemming AT, Khoor A, Mira‐Avendano I, Patel A, Larsen BT. Pathology of vaping‐associated lung injury. N Engl J Med 381: 1780‐1781, 2019.
 16.Callahan SJ, Harris D, Collingridge DS, Guidry DW, Dean NC, Lanspa MJ, Blagev DP. Diagnosing EVALI in the time of COVID‐19. Chest 158: 2034‐2037, 2020.
 17.Chang SW, Wellmerling J, Zhang X, Rayner RE, Osman W, Mertz S, Amer AO, Peeples ME, Boyaka PN, Cormet‐Boyaka E. The psychoactive substance of cannabis Delta9‐tetrahydrocannabinol (THC) negatively regulates CFTR in airway cells. Biochim Biophys Acta Gen Subj 1862: 1988‐1994, 2018.
 18.Chatterjee S, Tao JQ, Johncola A, Guo W, Caporale A, Langham MC, Wehrli FW. Acute exposure to e‐cigarettes causes inflammation and pulmonary endothelial oxidative stress in nonsmoking, healthy young subjects. Am J Physiol Lung Cell Mol Physiol 317: L155‐L166, 2019.
 19.Chaumont M, Bernard A, Pochet S, Melot C, El Khattabi C, Reye F, Boudjeltia KZ, Van Antwerpen P, Delporte C, van de Borne P. High‐wattage e‐cigarettes induce tissue hypoxia and lower airway injury: A randomized clinical trial. Am J Respir Crit Care Med 198: 123‐126, 2018.
 20.Chaumont M, de Becker B, Zaher W, Culie A, Deprez G, Melot C, Reye F, Van Antwerpen P, Delporte C, Debbas N, Boudjeltia KZ, van de Borne P. Differential effects of E‐cigarette on microvascular endothelial function, arterial stiffness and oxidative stress: A randomized crossover trial. Sci Rep 8: 10378, 2018.
 21.Chen L, Arens R, Chidambaram AG, Capponi S, Alshawa L, Claeys TA, Hayes D Jr, Robinson RT. Vaping associated pulmonary nontuberculous mycobacteria. Lung 199: 21‐27, 2021.
 22.Christiani DC. Vaping‐induced acute lung injury. N Engl J Med 382: 960‐962, 2020.
 23.Chung S, Baumlin N, Dennis JS, Moore R, Salathe SF, Whitney PL, Sabater J, Abraham WM, Kim MD, Salathe M. Electronic cigarette vapor with nicotine causes airway mucociliary dysfunction preferentially via TRPA1 receptors. Am J Respir Crit Care Med 200: 1134‐1145, 2019.
 24.Cirillo S, Urena JF, Lambert JD, Vivarelli F, Canistro D, Paolini M, Cardenia V, Rodriguez‐Estrada MT, Richie JP Jr, Elias RJ. Impact of electronic cigarette heating coil resistance on the production of reactive carbonyls, reactive oxygen species and induction of cytotoxicity in human lung cancer cells in vitro. Regul Toxicol Pharmacol 109: 104500, 2019.
 25.Corriden R, Moshensky A, Bojanowski CM, Meier A, Chien J, Nelson RK, Crotty Alexander LE. E‐cigarette use increases susceptibility to bacterial infection by impairment of human neutrophil chemotaxis, phagocytosis, and NET formation. Am J Physiol Cell Physiol 318: C205‐C214, 2020.
 26.Crotty Alexander LE, Drummond CA, Hepokoski M, Mathew D, Moshensky A, Willeford A, Das S, Singh P, Yong Z, Lee JH, Vega K, Du A, Shin J, Javier C, Tian J, Brown JH, Breen EC. 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 314: R834‐R847, 2018.
 27.Cruz‐Vidal DA, Mull ES, Taveras J, Shell R, Hunt GW, Fowler B, Wallihan R, Erdem G. EVALI versus MIS‐C, one more overlapping diagnosis to consider. Pediatr Pulmonol 56: 2918‐2924, 2021.
 28.Davidson K, Brancato A, Heetderks P, Mansour W, Matheis E, Nario M, Rajagopalan S, Underhill B, Wininger J, Fox D. Outbreak of electronic‐cigarette‐associated acute lipoid pneumonia ‐ North Carolina, July‐August 2019. MMWR Morb Mortal Wkly Rep 68: 784‐786, 2019.
 29.Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H. Effects of cigarette smoking on reproduction. Hum Reprod Update 17: 76‐95, 2011.
 30.DiPasquale M, Gbadamosi O, Nguyen MHL, Castillo SR, Rickeard BW, Kelley EG, Nagao M, Marquardt D. A mechanical mechanism for vitamin E acetate in e‐cigarette/vaping‐associated lung injury. Chem Res Toxicol 33: 2432‐2440, 2020.
 31.Dransfield MT, Wilhelm AM, Flanagan B, Courville C, Tidwell SL, Raju SV, Gaggar A, Steele C, Tang LP, Liu B, Rowe SM. Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the lower airways in COPD. Chest 144: 498‐506, 2013.
 32.Eaton DL, Kwan LY, Stratton K, editors. Public Health Consequences of E‐Cigarettes. Washington, DC: National Academies Press, 2018.
 33.Eenjes E, van Riet S, Kroon AA, Slats AM, Khedoe P, Boerema‐de Munck A, Buscop‐van Kempen M, Ninaber DK, Reiss IKM, Clevers H, Rottier RJ, Hiemstra PS. Disease modeling following organoid‐based expansion of airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 321: L775‐L786, 2021.
 34.Ejaz A, Ahmed MM, Tasleem A, Rafay Khan Niazi M, Ahsraf MF, Ahmad I, Zakir A, Raza A. Thromboprophylaxis in intensive care unit patients: A literature review. Cureus 10: e3341, 2018.
 35.El‐Mahdy MA, Ewees MG, Eid MS, Mahgoup EM, Khaleel SA, Zweier JL. Electronic cigarette exposure causes vascular endothelial dysfunction due to NADPH oxidase activation and eNOS uncoupling. Am J Physiol Heart Circ Physiol 322: H549‐H567, 2022.
 36.Escobar YH, Nipp G, Cui T, Petters SS, Surratt JD, Jaspers I. In vitro toxicity and chemical characterization of aerosol derived from electronic cigarette humectants using a newly developed exposure system. Chem Res Toxicol 33: 1677‐1688, 2020.
 37.Fan T, DuBose L, Wayne C, Sisniega C. E‐cigarette, or vaping, associated lung and hepatic injury. J Pediatr Gastroenterol Nutr 71: e98‐e100, 2020.
 38.Farooq U, Anwar M, Alcantar D, Amine M, Colon HD. Gastroenteritis and miliary lung opacities: An interesting combination of findings. Cureus 12: e8848, 2020.
 39.Farsalinos KE, Voudris V, Poulas K. Are metals emitted from electronic cigarettes a reason for health concern? A risk‐assessment analysis of currently available literature. Int J Environ Res Public Health 12: 5215‐5232, 2015.
 40.Filbey FM, Gohel S, Prashad S, Biswal BB. Differential associations of combined vs. isolated cannabis and nicotine on brain resting state networks. Brain Struct Funct 223: 3317‐3326, 2018.
 41.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 5: e00230, 2017.
 42.Forrester SJ, Kikuchi DS, Hernandes MS, Xu Q, Griendling KK. Reactive oxygen species in metabolic and inflammatory signaling. Circ Res 122: 877‐902, 2018.
 43.Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Beduneau G, Deletage‐Metreau C, Richard JC, Brochard L, Robert R, Group FS, Network R. High‐flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 372: 2185‐2196, 2015.
 44.Gaiha SM, Cheng J, Halpern‐Felsher B. Association between youth smoking, electronic cigarette use, and COVID‐19. J Adolesc Health 67: 519‐523, 2020.
 45.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.
 46.Ghosh A, Coakley RC, Mascenik T, Rowell TR, Davis ES, Rogers K, Webster MJ, Dang H, Herring LE, Sassano MF, Livraghi‐Butrico A, Van Buren SK, Graves LM, Herman MA, Randell SH, Alexis NE, Tarran R. Chronic e‐cigarette exposure alters the human bronchial epithelial proteome. Am J Respir Crit Care Med 198: 67‐76, 2018.
 47.Ghosh A, Coakley RD, Ghio AJ, Muhlebach MS, Esther CR Jr, Alexis NE, Tarran R. Chronic e‐cigarette use increases neutrophil elastase and matrix metalloprotease levels in the lung. Am J Respir Crit Care Med 200: 1392‐1401, 2019.
 48.Ghosh B, Reyes‐Caballero H, Akgun‐Olmez SG, Nishida K, Chandrala L, Smirnova L, Biswal S, Sidhaye VK. Effect of sub‐chronic exposure to cigarette smoke, electronic cigarette and waterpipe on human lung epithelial barrier function. BMC Pulm Med 20: 216, 2020.
 49.Gilpin DF, McGown KA, Gallagher K, Bengoechea J, Dumigan A, Einarsson G, Elborn JS, Tunney MM. Electronic cigarette vapour increases virulence and inflammatory potential of respiratory pathogens. Respir Res 20: 267, 2019.
 50.Glynos C, Bibli SI, Katsaounou P, Pavlidou A, Magkou C, Karavana V, Topouzis S, Kalomenidis I, Zakynthinos S, Papapetropoulos A. 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 315: L662‐L672, 2018.
 51.Goniewicz ML, Knysak J, Gawron M, Kosmider L, Sobczak A, Kurek J, Prokopowicz A, Jablonska‐Czapla M, Rosik‐Dulewska C, Havel C, Jacob P 3rd, Benowitz N. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control 23: 133‐139, 2014.
 52.Gupta VS, Hayes D Jr, Hsu SC, Tonna JE, Rycus PT, Bridges BC, Diaban F, Bosma KJ, Bhatt JM, Sakla NM, Han JJ, Bermudez CA, Manetta F, Garcia EI, Harting MT. Extracorporeal life support for respiratory failure in patients with electronic cigarette or vaping product use‐associated lung injury. Crit Care Med 50: e173‐e182, 2022.
 53.Harada HA, Liu J, Shortell JD, Beesley SJ. A 20‐year‐old man with e‐cigarette or vaping product use‐associated lung injury (EVALI) and thrombotic coagulopathy. Am J Case Rep 22: e929915‐1, 2021.
 54.Hasan KM, Friedman TC, Shao X, Parveen M, Sims C, Lee DL, Espinoza‐Derout J, Sinha‐Hikim I, Sinha‐Hikim AP. E‐cigarettes and western diet: Important metabolic risk factors for hepatic diseases. Hepatology 69: 2442‐2454, 2019.
 55.Herr C, Tsitouras K, Niederstrasser J, Backes C, Beisswenger C, Dong L, Guillot L, Keller A, Bals R. Cigarette smoke and electronic cigarettes differentially activate bronchial epithelial cells. Respir Res 21: 67, 2020.
 56.Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz‐Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM, Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 364: 1293‐1304, 2011.
 57.Higham A, Rattray NJ, Dewhurst JA, Trivedi DK, Fowler SJ, Goodacre R, Singh D. Electronic cigarette exposure triggers neutrophil inflammatory responses. Respir Res 17: 56, 2016.
 58.Ho J, Sciuscio D, Kogel U, Titz B, Leroy P, Vuillaume G, Talikka M, Martin E, Pospisil P, Lebrun S, Xia W, Lee T, Chng YX, Phillips BW, Veljkovic E, Guedj E, Xiang Y, Ivanov NV, Peitsch MC, Hoeng J, Vanscheeuwijck P. Evaluation of toxicity of aerosols from flavored e‐liquids in Sprague–Dawley rats in a 90‐day OECD inhalation study, complemented by transcriptomics analysis. Arch Toxicol 94: 2179‐2206, 2020.
 59.Holbrook BD. The effects of nicotine on human fetal development. Birth Defects Res C Embryo Today 108: 181‐192, 2016.
 60.Hom S, Chen L, Wang T, Ghebrehiwet B, Yin W, Rubenstein DA. Platelet activation, adhesion, inflammation, and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentrations. Platelets 27: 694‐702, 2016.
 61.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.
 62.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 6: e00282, 2018.
 63.Jasper AE, Sapey E, Thickett DR, Scott A. Understanding potential mechanisms of harm: The drivers of electronic cigarette‐induced changes in alveolar macrophages, neutrophils, and lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 321: L336‐L348, 2021.
 64.Jessri M, Sultan AS, Magdy E, Hynes N, Sultan S. Nicotine e‐vaping and cardiovascular consequences: A case series and literature review. Eur Heart J Case Rep 4: 1‐7, 2020.
 65.Jimenez‐Valdes RJ, Can UI, Niemeyer BF, Benam KH. Where we stand: Lung organotypic living systems that emulate human‐relevant host‐environment/pathogen interactions. Front Bioeng Biotechnol 8: 989, 2020.
 66.Jonas AM, Raj R. Vaping‐related acute parenchymal lung injury: A systematic review. Chest 158: 1555‐1565, 2020.
 67.Kalantary A, Abdelazeem B, Shams N, Pratiti R, Al‐Sanouri I. Coagulopathy and acute respiratory distress syndrome: Dual complications of e‐cigarette‐associated lung injury. Cureus 13: e13531, 2021.
 68.Kaslow JA, Rosas‐Salazar C, Moore PE. E‐cigarette and vaping product use‐associated lung injury in the pediatric population: A critical review of the current literature. Pediatr Pulmonol 56: 1857‐1867, 2021.
 69.Kaur G, Lungarella G, Rahman I. SARS‐CoV‐2 COVID‐19 susceptibility and lung inflammatory storm by smoking and vaping. J Inflamm (Lond) 17: 21, 2020.
 70.Khanijo S, Lou BX, Makaryus M, Weber A, Fryman C, Iakovou A. Coagulopathy and inflammatory dysregulation with e‐cigarette use. Am J Med 133: 530‐531, 2020.
 71.Kivrak T, Sunbul M, Durmus E, Dervisova R, Sari I, Yesildag O. Acute myocardial infarction due to liquid nicotine in a young man. Ther Adv Cardiovasc Dis 8: 32‐34, 2014.
 72.Kleinman MT, Arechavala RJ, Herman D, Shi J, Hasen I, Ting A, Dai W, Carreno J, Chavez J, Zhao L, Kloner RA. E‐cigarette or vaping product use‐associated lung injury produced in an animal model from electronic cigarette vapor exposure without tetrahydrocannabinol or vitamin E oil. J Am Heart Assoc 9: e017368, 2020.
 73.Kligerman S, Raptis C, Larsen B, Henry TS, Caporale A, Tazelaar H, Schiebler ML, Wehrli FW, Klein JS, Kanne J. Radiologic, pathologic, clinical, and physiologic findings of electronic cigarette or vaping product use‐associated lung injury (EVALI): Evolving knowledge and remaining questions. Radiology 294: 491‐505, 2020.
 74.Kligerman SJ, Kay FU, Raptis CA, Henry TS, Sechrist JW, Walker CM, Vargas D, Filev PD, Chung MS, Digumarthy SR, Ropp AM, Mohammed TL, Pope KW, Marquis KM, Chung JH, Kanne JP. CT findings and patterns of e‐cigarette or vaping product use‐associated lung injury: A multicenter cohort of 160 cases. Chest 160: 1492‐1511, 2021.
 75.Kopsombut G, Ajjegowda A, Livingston F, Epelman M, Brown B, Werk L, Brogan R. Clinical findings in adolescents hospitalized with EVALI; Novel report on coagulopathy. Hosp Pediatr 12: 229‐240, 2022.
 76.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 313: L67‐L79, 2017.
 77.Layden JE, Ghinai I, Pray I, Kimball A, Layer M, Tenforde MW, Navon L, Hoots B, Salvatore PP, Elderbrook M, Haupt T, Kanne J, Patel MT, Saathoff‐Huber L, King BA, Schier JG, Mikosz CA, Meiman J. Pulmonary illness related to e‐cigarette use in illinois and wisconsin ‐ final report. N Engl J Med 382: 903‐916, 2020.
 78.Le VL, Courtney CL, Steel J, Compans RW. Closely related influenza viruses induce contrasting respiratory tract immunopathology. PLoS One 8: e76708, 2013.
 79.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.
 80.Leung JM, Yang CX, Sin DD. COVID‐19 and nicotine as a mediator of ACE‐2. Eur Respir J 55: 2001261, 2020.
 81.Li G, Saad S, Oliver BG, Chen H. Heat or burn? Impacts of intrauterine tobacco smoke and e‐cigarette vapor exposure on the offspring's health outcome. Toxics 6: 43, 2018.
 82.Lin VY, Fain MD, Jackson PL, Berryhill TF, Wilson LS, Mazur M, Barnes SJ, Blalock JE, Raju SV, Rowe SM. Vaporized e‐cigarette liquids induce ion transport dysfunction in airway epithelia. Am J Respir Cell Mol Biol 61: 162‐173, 2019.
 83.Liu B, Xu G, Rong S, Santillan DA, Santillan MK, Snetselaar LG, Bao W. National estimates of e‐cigarette use among pregnant and nonpregnant women of reproductive age in the United States, 2014–2017. JAMA Pediatr 173: 600‐602, 2019.
 84.Maddock SD, Cirulis MM, Callahan SJ, Keenan LM, Pirozzi CS, Raman SM, Aberegg SK. Pulmonary lipid‐laden macrophages and vaping. N Engl J Med 381: 1488‐1489, 2019.
 85.Madison MC, Landers CT, Gu BH, Chang CY, Tung HY, You R, Hong MJ, Baghaei N, Song LZ, Porter P, Putluri N, Salas R, Gilbert BE, Levental I, Campen MJ, Corry DB, Kheradmand F. Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine. J Clin Invest 129: 4290‐4304, 2019.
 86.Madrigal JM, Persky V, Pappalardo A, Argos M. Association of heavy metals with measures of pulmonary function in children and youth: Results from the National Health and Nutrition Examination Survey (NHANES). Environ Int 121: 871‐878, 2018.
 87.Mart MF, Ware LB. The long‐lasting effects of the acute respiratory distress syndrome. Expert Rev Respir Med 14: 577‐586, 2020.
 88.Martin SL, Reihill JA. Promotion of a protease‐antiprotease imbalance in the airways through chronic vaping. Am J Respir Crit Care Med 200: 1337‐1339, 2019.
 89.Martinez JD, Easwaran M, Ramirez D, Erickson‐DiRenzo E. Effects of electronic (E)‐cigarette vapor and cigarette smoke in cultured vocal fold fibroblasts. Laryngoscope 133: 139‐146, 2023.
 90.Matsumoto S, Traber MG, Leonard SW, Choi J, Fang X, Maishan M, Wick KD, Jones KD, Calfee CS, Gotts JE, Matthay MA. Aerosolized vitamin E acetate causes oxidative injury in mice and in alveolar macrophages. Am J Physiol Lung Cell Mol Physiol 322: L771‐L783, 2022.
 91.Matta P, Hamati JN, Unno HL, Fox MD. E‐cigarette or vaping product use‐associated lung injury (EVALI) without respiratory symptoms. Pediatrics 145: e20193408, 2020.
 92.Middlekauff HR, Park J, Moheimani RS. Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: Mechanisms and implications for cardiovascular risk. J Am Coll Cardiol 64: 1740‐1750, 2014.
 93.Miyashita L, Suri R, Dearing E, Mudway I, Dove RE, Neill DR, Van Zyl‐Smit R, Kadioglu A, Grigg J. E‐cigarette vapour enhances pneumococcal adherence to airway epithelial cells. Eur Respir J 51, 2018.
 94.Morjaria JB, Mondati E, Polosa R. E‐cigarettes in patients with COPD: Current perspectives. Int J Chron Obstruct Pulmon Dis 12: 3203‐3210, 2017.
 95.Mukhopadhyay S, Mehrad M, Dammert P, Arrossi AV, Sarda R, Brenner DS, Maldonado F, Choi H, Ghobrial M. Lung biopsy findings in severe pulmonary illness associated with e‐cigarette use (vaping). Am J Clin Pathol 153: 30‐39, 2020.
 96.Muthumalage T, Lamb T, Friedman MR, Rahman I. E‐cigarette flavored pods induce inflammation, epithelial barrier dysfunction, and DNA damage in lung epithelial cells and monocytes. Sci Rep 9: 19035, 2019.
 97.Nacca N, McGraw MD, Croft DP, Kalininskiy A. Weight loss in adolescents presenting with EVALI. Pediatr Pulmonol 56: 2785‐2786, 2021.
 98.Navon L, Jones CM, Ghinai I, King BA, Briss PA, Hacker KA, Layden JE. Risk factors for e‐cigarette, or vaping, product use‐associated lung injury (EVALI) among adults who use e‐cigarette, or vaping, products ‐ Illinois, July–October 2019. MMWR Morb Mortal Wkly Rep 68: 1034‐1039, 2019.
 99.Nemeh H, Coba V, Chulkov M, Gupta A, Yeldo N, Chamogeorgakis T, Tanaka D, Allenspach L, Simanovski J, Shanti C. Lung transplantation for the treatment of vaping‐induced, irreversible, end‐stage lung injury. Ann Thorac Surg 111: e353‐e355, 2021.
 100.Neuhaus V, Schaudien D, Golovina T, Temann UA, Thompson C, Lippmann T, Bersch C, Pfennig O, Jonigk D, Braubach P, Fieguth HG, Warnecke G, Yusibov V, Sewald K, Braun A. Assessment of long‐term cultivated human precision‐cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality. J Occup Med Toxicol 12: 13, 2017.
 101.Nguyen T, Li GE, Chen H, Cranfield CG, McGrath KC, Gorrie CA. Maternal e‐cigarette exposure results in cognitive and epigenetic alterations in offspring in a mouse model. Chem Res Toxicol 31: 601‐611, 2018.
 102.Nieuwenhuizen L, de Groot PG, Grutters JC, Biesma DH. A review of pulmonary coagulopathy in acute lung injury, acute respiratory distress syndrome and pneumonia. Eur J Haematol 82: 413‐425, 2009.
 103.Noel A, Hossain E, Perveen Z, Zaman H, Penn AL. Sub‐ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air‐liquid interface. Respir Res 21: 305, 2020.
 104.Odish MF, Bellinghausen A, Golts E, Owens RL. E‐cigarette, or vaping, product use‐associated lung injury (EVALI) treated with veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) and ultra‐protective ventilator settings. BMJ Case Rep 13: 1‐4, 2020.
 105.Orzabal MR, Lunde‐Young ER, Ramirez JI, Howe SYF, Naik VD, Lee J, Heaps CL, Threadgill DW, Ramadoss J. Chronic exposure to e‐cig aerosols during early development causes vascular dysfunction and offspring growth deficits. Transl Res 207: 70‐82, 2019.
 106.Pasquin S, Laplante V, Kouadri S, Milasan A, Mayer G, Tormo AJ, Savin V, Sharma M, Martel C, Gauchat JF. Cardiotrophin‐like cytokine increases macrophage‐foam cell transition. J Immunol 201: 2462‐2471, 2018.
 107.Patton GC, Coffey C, Carlin JB, Sawyer SM, Lynskey M. Reverse gateways? Frequent cannabis use as a predictor of tobacco initiation and nicotine dependence. Addiction 100: 1518‐1525, 2005.
 108.Peruzzi M, Biondi‐Zoccai G, Carnevale R, Cavarretta E, Frati G, Versaci F. Vaping cardiovascular health risks: An updated umbrella review. Curr Emerg Hosp Med Rep 8: 103‐109, 2020.
 109.Phillips B, Titz B, Kogel U, Sharma D, Leroy P, Xiang Y, Vuillaume G, Lebrun S, Sciuscio D, Ho J, Nury C, Guedj E, Elamin A, Esposito M, Krishnan S, Schlage WK, Veljkovic E, Ivanov NV, Martin F, Peitsch MC, Hoeng J, Vanscheeuwijck P. 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 109: 315‐332, 2017.
 110.Prasad KN, Bondy SC. Electronic cigarette aerosol increases the risk of organ dysfunction by enhancing oxidative stress and inflammation. Drug Chem Toxicol 45: 2561‐2567, 2022.
 111.Ramji DP, Davies TS. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets. Cytokine Growth Factor Rev 26: 673‐685, 2015.
 112.Reade MC, Finfer S. Sedation and delirium in the intensive care unit. N Engl J Med 370: 444‐454, 2014.
 113.Rouabhia M, Semlali A. Electronic cigarette vapor increases Streptococcus mutans growth, adhesion, biofilm formation, and expression of the biofilm‐associated genes. Oral Dis 27: 639‐647, 2021.
 114.Rowell TR, Keating JE, Zorn BT, Glish GL, Shears SB, Tarran R. Flavored e‐liquids increase cytoplasmic Ca(2+) levels in airway epithelia. Am J Physiol Lung Cell Mol Physiol 318: L226‐L241, 2020.
 115.Russell DG, Cardona PJ, Kim MJ, Allain S, Altare F. Foamy macrophages and the progression of the human tuberculosis granuloma. Nat Immunol 10: 943‐948, 2009.
 116.Saeed S, Tadic M, Larsen TH, Grassi G, Mancia G. Coronavirus disease 2019 and cardiovascular complications: Focused clinical review. J Hypertens 39: 1282‐1292, 2021.
 117.Schaunaman N, Crue T, Cervantes D, Schweitzer K, Robbins H, Day BJ, Numata M, Petrache I, Chu HW. Electronic cigarette vapor exposure exaggerates the pro‐inflammatory response during influenza A viral infection in human distal airway epithelium. Arch Toxicol 96: 2319‐2328, 2022.
 118.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 Cell Physiol 309: L175‐L187, 2015.
 119.Schweitzer KS, Johnstone BH, Garrison J, Rush NI, Cooper S, Traktuev DO, Feng D, Adamowicz JJ, Van Demark M, Fisher AJ, Kamocki K, Brown MB, Presson RG Jr, Broxmeyer HE, March KL, Petrache I. Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking. Am J Respir Crit Care Med 183: 215‐225, 2011.
 120.Scott A, Lugg ST, Aldridge K, Lewis KE, Bowden A, Mahida RY, Grudzinska FS, Dosanjh D, Parekh D, Foronjy R, Sapey E, Naidu B, Thickett DR. Pro‐inflammatory effects of e‐cigarette vapour condensate on human alveolar macrophages. Thorax 73: 1161‐1169, 2018.
 121.Shi H, Fan X, Horton A, Haller ST, Kennedy DJ, Schiefer IT, Dworkin L, Cooper CJ, Tian J. The effect of electronic‐cigarette vaping on cardiac function and angiogenesis in mice. Sci Rep 9: 4085, 2019.
 122.Siegel DA, Jatlaoui TC, Koumans EH, Kiernan EA, Layer M, Cates JE, Kimball A, Weissman DN, Petersen EE, Reagan‐Steiner S, Godfred‐Cato S, Moulia D, Moritz E, Lehnert JD, Mitchko J, London J, Zaki SR, King BA, Jones CM, Patel A, Meaney Delman D, Koppaka R. Update: Interim guidance for health care providers evaluating and caring for patients with suspected e‐cigarette, or vaping, product use associated lung injury—United States, October 2019. Am J Transplant 19: 3420‐3428, 2019.
 123.Singh KP, Lawyer G, Muthumalage T, Maremanda KP, Khan NA, McDonough SR, Ye D, McIntosh S, Rahman I. Systemic biomarkers in electronic cigarette users: Implications for noninvasive assessment of vaping‐associated pulmonary injuries. ERJ Open Res 5: 00182‐2019, 2019.
 124.Stevens VL, Bierut LJ, Talbot JT, Wang JC, Sun J, Hinrichs AL, Thun MJ, Goate A, Calle EE. Nicotinic receptor gene variants influence susceptibility to heavy smoking. Cancer Epidemiol Biomark Prev 17: 3517‐3525, 2008.
 125.Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim JH, 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.
 126.Sussman MA. Vaping into ARDS: Acute respiratory distress syndrome and cardiopulmonary failure. Pharmacol Ther 232: 108006, 2022.
 127.Szumilas K, Szumilas P, Grzywacz A, Wilk A. The effects of e‐cigarette vapor components on the morphology and function of the male and female reproductive systems: A systematic review. Int J Environ Res Public Health 17: 1‐13, 2020.
 128.Tarran R, Barr RG, Benowitz NL, Bhatnagar A, Chu HW, Dalton P, Doerschuk CM, Drummond MB, Gold DR, Goniewicz ML, Gross ER, Hansel NN, Hopke PK, Kloner RA, Mikheev VB, Neczypor EW, Pinkerton KE, Postow L, Rahman I, Samet JM, Salathe M, Stoney CM, Tsao PS, Widome R, Xia T, Xiao D, Wold LE. E‐cigarettes and cardiopulmonary health. Function (Oxf) 2: zqab004, 2021.
 129.The Lancet Respiratory Medicine. The EVALI outbreak and vaping in the COVID‐19 era. Lancet Respir Med 8: 831, 2020.
 130.Vajdi B, Tuktamyshov R. Electronic cigarettes ‐ myocardial infarction, hemodynamic compromise during pregnancy, and systolic and diastolic dysfunction: Minireview. World J Cardiol 12: 475‐483, 2020.
 131.Verweij KJH, Treur JL, Vink JM. Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: A two‐sample bidirectional Mendelian randomization study. Addiction 113: 1333‐1338, 2018.
 132.Wang JB, Olgin JE, Nah G, Vittinghoff E, Cataldo JK, Pletcher MJ, Marcus GM. Cigarette and e‐cigarette dual use and risk of cardiopulmonary symptoms in the Health eHeart Study. PLoS One 13: e0198681, 2018.
 133.Werner AK, Koumans EH, Chatham‐Stephens K, Salvatore PP, Armatas C, Byers P, Clark CR, Ghinai I, Holzbauer SM, Navarette KA, Danielson ML, Ellington S, Moritz ED, Petersen EE, Kiernan EA, Baldwin GT, Briss P, Jones CM, King BA, Krishnasamy V, Rose DA, Reagan‐Steiner S. Hospitalizations and deaths associated with EVALI. N Engl J Med 382: 1589‐1598, 2020.
 134.Wickstrom R. Effects of nicotine during pregnancy: Human and experimental evidence. Curr Neuropharmacol 5: 213‐222, 2007.
 135.Wu CH, Liao TY, Chen YH, Kuo PH. Treatment of electronic cigarette or vaping product use‐associated lung injury (EVALI) by corticosteroid and low‐dose pirfenidone: Report of a case. Respirol Case Rep 9: 5‐9, 2021.
 136.Xian H, Scherrer JF, Grant JD, Eisen SA, True WR, Jacob T, Bucholz KK. Genetic and environmental contributions to nicotine, alcohol and cannabis dependence in male twins. Addiction 103: 1391‐1398, 2008.
 137.Xu J, Zhang P, Sun H, Liu Y. LINC01094/miR‐577 axis regulates the progression of ovarian cancer. J Ovarian Res 13: 122, 2020.
 138.Xu X, Balsiger R, Tyrrell J, Boyaka PN, Tarran R, Cormet‐Boyaka E. Cigarette smoke exposure reveals a novel role for the MEK/ERK1/2 MAPK pathway in regulation of CFTR. Biochim Biophys Acta 1850: 1224‐1232, 2015.
 139.Young‐Wolff KC, Adams SR, Sterling SA, Tan ASL, Salloum RG, Torre K, Carter‐Harris L, Prochaska JJ. Nicotine and cannabis vaping among adolescents in treatment for substance use disorders. J Subst Abus Treat 125: 108304, 2021.
 140.Yu XH, Fu YC, Zhang DW, Yin K, Tang CK. Foam cells in atherosclerosis. Clin Chim Acta 424: 245‐252, 2013.
 141.Zakarya R, Adcock I, Oliver BG. Epigenetic impacts of maternal tobacco and e‐vapour exposure on the offspring lung. Clin Epigenetics 11: 32, 2019.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Pathogenesis of E‐Cigarette Vaping Product Use‐Associated Lung Injury (EVALI)
 

How to Cite

Irina Petrache, Arnav Gupta, Patrick S. Hume, Tanner Rivera, Kelly S. Schweitzer, Hong Wei Chu. Pathogenesis of E‐Cigarette Vaping Product Use‐Associated Lung Injury (EVALI). Compr Physiol 2023, 13: 4617-4630. doi: 10.1002/cphy.c220022