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N Engl J Med. 2020 Feb 20;382(8):697-705. doi: 10.1056/NEJMoa1916433. Epub 2019 Dec 20.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

Collaborators (158)

Attfield K, Blount RJ, Brasky TM, Brewer BN, Carlson EM, Chatham-Stephens K, Ellington S, Evans ME, Fowles J, Freed J, Fruedenheim JL, Galindo T, Garcia M, Grant A, Hayes D, Heinzerling A, Jatlaoui TC, Johnson R, Lisko JG, Lozier MJ, Lynfield R, McElroy JP, Melstrom P, Mikosz C, Onyenwe W, Pray I, Reagan-Steiner S, Reisinger SA, Ritchey MD, Rollins M, Sapp C, Soroka SD, Stanton N, Weng DY, Williams I, Wiltz J, Adams A, Ahamed R, Ally K, Arnstein S, Ash D, Blake T, Bragg W, Bravo R, Carter M, Chambers C, Doyle A, Favors R, Gonzalez-Jimenez N, Gray N, Guillot T, Hamelin B, Hearn B, Holder A, Isenberg S, Jarchow L, Jones A, Krajewski L, Kendall-Kyle C, Lewis E, Liverance H, McGahee E, McGuigan M, Mendez M, Mojica M, Negrete S, Rivera Nieves K, Pahno N, Pappas RS, Perez J, Pittman C, Puetz A, De Leon Salazar S, Shaner R, Shields K, Smith M, Tuberville T, Vesper H, Wade E, Warton R, Watson A, Wilmore A, Wooten J, Kerr S, Santana A, Woodward S, Elliott N, O'Hegarty M, Petty J, O'Sullivan M, Kabbani S, Erskine S, Hocevar Adkins S, Hunter K, Khan I, Kang J, Koumans EH, Montandon M, Weissman D, Balamurugan A, Sutphin B, Allison J, Wheeler G, Becker S, Blank E, Nassif J, Thomas K, Volner A, Perez J, Noel D, Jones S, Kelley KA, Charles M, Morales C, Nasir MS, Clark C, Pope B, Epie N, Hawkins E, Chowdhary S, Harris D, Green N, Blythe D, Feder K, Mitchell C, Bashore M, Seith R, Wells E, Cole C, D'Heilly P, Hanson K, Holzbauer S, Lunda M, Peterson J, Saravia S, Wiens T, Wogen M, Turabelidze G, Howard V, Michie K, Bowler R, Koehler K, Vanzandt L, Hall E, Shetty V, Ainsworth B, Green J, Goller R, Patel J, Satzger D, Schmidt R, Comellas A, Spink D, McBee S, Barr L, Reed C, Lange M, Meiman J.

Author information

From the Division of Laboratory Sciences, National Center for Environmental Health (B.C.B., M.P.K., M.M.-E., L.V.-B., M.G., M.B., C.R.B., K.T.C., D.C., J.C., E.C., V.R.D.J., P.E., C.F., C.H., Z.K., J.D.K., C.N., G.B.R., J.R., C.R., L.S., T.S., C.S., D.T., L.W., C.W., B.X., J.R.B., J.T., J.L.P.), Epidemic Intelligence Service, Center for Surveillance, Epidemiology, and Laboratory Sciences (I.G.), the Office of the Director (P.B.) and the Office on Smoking and Health (B.A.K.), National Center for Chronic Disease Prevention and Health Promotion, the Office of the Director, National Institute for Occupational Safety and Health (L.J.D.), the Office of Strategy and Innovation (C.M.J.) and the Division of Overdose Prevention (G.T.B.), National Center for Injury Prevention and Control, the Office of the Director, National Center for Immunization and Respiratory Diseases (A.P.), the Division of Birth Defects and Infant Disorders, National Center on Birth Defects and Developmental Disabilities (D.M.D.), the Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases (D.R.), and the Office of the Director, National Center for Injury Prevention and Control (V.K.) - all at the Centers for Disease Control and Prevention, Atlanta; the Comprehensive Cancer Center, Ohio State University and James Cancer Hospital (P.G.S.), and the Division of Environmental Health Science, College of Public Health (M.-A.S.), and Pulmonary and Critical Care Medicine, Department of Internal Medicine (C.R.S., M.D.W.), Ohio State University, Columbus; the Food and Drug Administration, Silver Spring, MD (D.T.H.); and the Illinois Department of Public Health, Chicago (I.G., J.L.).



The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung.


BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.


State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%).


Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

[Available on 2021-02-20]
[Indexed for MEDLINE]

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