Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI
Authors: Cory Cole
Bryan Hearn
Susan Hocevar Adkins
Michele Montandon
Joe Wooten
Tonya Guillot
Kayla Thomas
Dana Meaney-Delman
Stephanie Negrete
Jennifer Freed
Christy Reed
Shannon McBee
Lindsay Barr
Matt Bashore
Kristy Michie
Baoyun Xia
Elizabeth Cowan
Michelle O&#x27;Hegarty
Connie Sosnoff
Noel Stanton
Stephen D Soroka
Robert J Blount
Beth Hamelin
Julianne Nassif
Jennifer Wiltz
Rodney Goller
Sam Isenberg
Jose Perez
David Chambers
Stephen Arnstein
Sarah Reagan-Steiner
Dixie Harris
Magaly Mendez
Michael Gardner
Stefan Saravia
Kathleen Attfield
David Weissman
Lisa J Delaney
Mary E Evans
Meshel Lange
Maria Morel-Espinosa
Richard Steve Pappas
Mateusz P Karwowski
Mike Rollins
Jo L Fruedenheim
Emily Hall
Stefanie Erskine
Hubert Vesper
James L Pirkle
Grant T Baldwin
George Turabelidze
Peter Briss
Erica Lewis
David Blythe
Ashley Jones
Amy Heinzerling
Kenneth Feder
Denise Tevis
Chariety Sapp
Emily M Carlson
Martha Braselton
Howard Liverance
Theodore M Brasky
Lalith Silva
Kate Koehler
Carlos Morales
Sascha Ellington
Lanqing Wang
Joseph Corstvet
Douglas T Heitkemper
Paige D&#x27;Heilly
Brian Pope
Rayaj Ahamed
Matt Wogen
Nathalie Gonzalez-Jimenez
Abbey Doyle
Min-Ae Song
Charles Chambers
Sydney Jones
Tiffany Seyler
Alejandro Comellas
Brandy Sutphin
Eric Blank
Chris Pittman
Paul Melstrom
Gregory B Reis
Carolina Fernandez
Bobby N Brewer
Mohammad S Nasir
Varun Shetty
Tonya Tuberville
Appathurai Balamurugan
David Spink
Donald Hayes
Kaila Hanson
Ibad Khan
Rebecca Shaner
Mitchell Smith
Peter G Shields
Nick Pahno
Jennifer Layden
Aaron Adams
Tiana Galindo
Jon Meiman
Sandeep Chowdhary
Cody Newman
Megan O&#x27;Sullivan
Melissa Carter
Kelly Ally
Jackie Patel
Naudia Gray
Jerry Thomas
Carleen R Spitzer
Kevin T Caron
Alan Holder
Joseph G Lisko
Julian Perez
Ian Williams
Shannon Woodward
Joann Kang
Jason Peterson
William Bragg
Jeff Fowles
Cory Holder
Scott Becker
Víctor R De Jesús
Liza Valentin-Blasini
Karen Shields
Mark D Wewers
Rachael Schmidt
Joseph P McElroy
Christina R Brosius
Duane Satzger
Zsuzsanna Kuklenyik
Lung Injury Response Laboratory Working Group
Emily H Koumans
Terra Wiens
Vikram Krishnasamy
Christopher M Jones
Rudolph Johnson
Eric Hawkins
Alberto Santana
Andrew Puetz
Leslie Jarchow
Chris Reese
Benjamin C Blount
Amy Watson
John R Barr
Ryan Favors
James Allison
Branden Ainsworth
Thomas Blake
Paul Espinosa
Doris Ash
Macarena Garcia
Russ Bowler
Gary Wheeler
Nicolas Epie
Rebekah Warton
Sarah A Reisinger
Andrew Wilmore
Lorene Vanzandt
Charles Clark
Brian A King
Valerie Howard
Logan Krajewski
Daniel Y Weng
Josh Petty
Jordan Green
Sarah Kabbani
Nicole Green
Stacy Holzbauer
Cassandra Kendall-Kyle
Stephanie Kerr
Ian Pray
Cliff Mitchell
Karen Rivera Nieves
Mike Mojica
Roberto Bravo
Anita Patel
Dale Rose
Matthew J Lozier
Alon Volner
Jon Rees
Matt Charles
Diane Noel
Eden Wells
Christina Mikosz
Kevin Chatham-Stephens
Tara C Jatlaoui
Katherine A Kelley
Rita Seith
Wellington Onyenwe
Sina De Leon Salazar
Matthew D Ritchey
Ernest McGahee
Mark Lunda
Cliff Watson
Nicole Elliott
Althea Grant
Karen Hunter
Erin Wade
Jennifer D Kusovschi
Ruth Lynfield
Isaac Ghinai
Megan McGuigan
Journal: New England Journal of Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: EVALI; electronic-cigarette; vaping; lung injury; toxicants
Affiliations: 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.).

Abstract:  Background: 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. Methods: 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. Results: 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%). Conclusions: 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.). 

Retracted: No

PubPeer comments:
 The abstract notes,  Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients . This statement is somewhat misleading: u2b24 25 25u00a0confirmedu00a0EVALI subjects had vitamin E acetate in BAL fluid. u2b24 23 26u00a0probableu00a0EVALI subjects had vitamin E acetate in BAL fluid. Moreover, the three  probable patients negative for vitamin E acetate had (1) multi-drug overdose, (2) coccidioidomycosis infection and (3) heavy alcohol use bacterial pneumonia -- all which are independently associated with Acute Respiratory Distress Syndrome (ARDS). It is therefore misleading to categorize these  probable cases. Furthermore, while the CDC reports refuse to stratify THC-related findings by confirmed and  probable EVALI cases, an [MMWR report] on Illinois  EVALI cases indicates that 48 48 of confirmed cases had an indication of THC use (extracted from [table 1] ). Also, the authors write:  9 of 11 patients who reported no use of THC-containing e-cigarette products in the 90 days before the onset of illness had detectable THC or its metabolites in their BAL fluid . Can the authors please stratify these results by probable and confirmed cases? Also, how do these overlap with the three probable subjects testing negative for vitamin E acetate? In a final note, the authors write:  FDA detected no vitamin E acetate in 197 case-associated nicotine products analyzed to date . It is thus quite surprising the CDC continues to implicate e-cigarettes in relation to this disease. E-cigarettes are not used to vape THC. THC vaping products have a different nomenclature than e-cigarettes, and implicating e-cigarettes in the term EVALI is highly misleading. ,