TY - JOUR
T1 - Update on the Features and Measurements of Experimental Acute Lung Injury in Animals An Official American Thoracic Society Workshop Report
AU - on behalf of the American Thoracic Society Assembly on Allergy, Immunology, and Inflammation
AU - Kulkarni, Hrishikesh S.
AU - Lee, Janet S.
AU - Bastarache, Julie A.
AU - Kuebler, Wolfgang M.
AU - Downey, Gregory P.
AU - Albaiceta, Guillermo M.
AU - Altemeier, William A.
AU - Artigas, Antonio
AU - Bates, Jason H.T.
AU - Calfee, Carolyn S.
AU - Dela Cruz, Charles S.
AU - Dickson, Robert P.
AU - Englert, Joshua A.
AU - Everitt, Jeffrey I.
AU - Fessler, Michael B.
AU - Gelman, Andrew E.
AU - Gowdy, Kymberly M.
AU - Groshong, Steve D.
AU - Herold, Susanne
AU - Homer, Robert J.
AU - Horowitz, Jeffrey C.
AU - Hsia, Connie C.W.
AU - Kurahashi, Kiyoyasu
AU - Laubach, Victor E.
AU - Looney, Mark R.
AU - Lucas, Rudolf
AU - Mangalmurti, Nilam S.
AU - Manicone, Anne M.
AU - Martin, Thomas R.
AU - Matalon, Sadis
AU - Matthay, Michael A.
AU - McAuley, Daniel F.
AU - McGrath-Morrow, Sharon A.
AU - Mizgerd, Joseph P.
AU - Montgomery, Stephanie A.
AU - Moore, Bethany B.
AU - Noel, Alexandra
AU - Perlman, Carrie E.
AU - Reilly, John P.
AU - Schmidt, Eric P.
AU - Skerrett, Shawn J.
AU - Suber, Tomeka L.
AU - Summers, Charlotte
AU - Suratt, Benjamin T.
AU - Takata, Masao
AU - Tuder, Rubin
AU - Uhlig, Stefan
AU - Witzenrath, Martin
AU - Zemans, Rachel L.
AU - Matute-Bello, Gutavo
N1 - Funding Information:
Author Disclosures: J.S.L. served as a consultant for Janssen; and received research support from the National Institutes of Health. G.P.D. served as a consultant for Angion Biomedica, Altimmune, LAM Foundation, and Lovelace Respiratory Institute; and received research support from the National Institutes of Health. G.M.-B. served as a consultant for Jensen. G.M.A. received research support from Instituto de Salud Carlos III; and has intellectual property/patent unsold for Pcsk9 inhibitors for specific uses with the Instituto de Investigación Sanitaria del Principado de Asturias. A.A. served on an advisory committee for Aerogen and Grifols; and received research support from Fisher & Paykel, Grifols, and Instituto de Salud Carlos III. J.H.T.B. served on an advisory committee for the Parker B. Francis Foundation; served as a consultant for Healthy Design LLC, Johnson & Johnson, and Oscillavent LLC; had ownership or investment interest in Oscillavent LLC; and received research support from the National Heart, Lung, and Blood Institute. C.S.C. served on an advisory committee for Quark Pharmaceuticals; served as a consultant for Bayer, Gen1e Life Sciences, Roche/Genentech, and Vasomune; and received research support from Bayer, National Institutes of Health, Roche/Genentech, and Quantum Leap Healthcare Collaborative. S.D.G. served as a consultant for Veracyte. J.C.H. served on an advisory committee for United Therapeutics. C.C.W.H. served as a consultant for Allena, Allynum, Applied Therapeutics, Dicerna, Oscillavent LLC, and Tricida; received research support from ATyr Pharmaceutical, Mallinckrodt, and the National Heart, Lung, and Blood Institute; had ownership or investment interest in Oscillavent LLC; and has a patent pending for device and method for lung measurement (US 20160007882 A1), variable ventilation as a diagnostic tool for assessing lung mechanical function (WO2015127377 A1), and ventilator and ventilator valve (PCT/US21/24537). R.L. received research support from the National Institutes of Health; and has intellectual property/patent unsold with Apeptico. T.R.M. served as a consultant for Bill & Melinda Gates Foundation, Boehringer Ingelheim, Novartis, and Vespina. S.M. served as editor in chief for American Physiological Society’s Physiological Reviews; and received research support from IMSA. M.A.M. served as a consultant for Citius, Gilead, Johnson & Johnson, and Novartis; and received research support from Roche/ Genentech. D.F.M. served as a consultant for Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Novartis, and SOBI; and received research support from Faron Pharmaceuticals, Innovate UK, Medical Research Council, National Institute for Health Research, Northern Ireland HSC R&D Division, Randox, Vir Biotechnology, and Wellcome Trust. C.S. received research support from AstraZeneca/Medimmune and GlaxoSmithKline; and had ownership or investment interest in Exvastat Limited. B.T.S. is an employee of Sanofi-Genzyme; and received research support from the National Institutes of Health. M.T. received research support from NeRRe Therapeutics Ltd. R.L.Z. received research support from the National Institutes of Health. H.S.K., W.A.A., J.A.B., C.S.D.C., R.P.D., J.A.E., J.I.E., M.B.F., A.E.G., K.M.G., S.H., R.J.H., W.M.K., K.K., V.E.L., M.R.L., N.S.M., A.M.M., S.A.M.-M., J.P.M., S.A.M., B.B.M., A.N., C.E.P., J.P.R., E.P.S., S.J.S., T.L.S., R.T., S.U., and M.W. reported no commercial or relevant noncommercial interests.
Publisher Copyright:
© 2022 by the American Thoracic Society
PY - 2022/2
Y1 - 2022/2
N2 - Advancements in methods, technology, and our understanding of the pathobiology of lung injury have created the need to update the definition of experimental acute lung injury (ALI). We queried 50 participants with expertise in ALI and acute respiratory distress syndrome using a Delphi method composed of a series of electronic surveys and a virtual workshop. We propose that ALI presents as a “multidimensional entity” characterized by four “domains” that reflect the key pathophysiologic features and underlying biology of human acute respiratory distress syndrome. These domains are 1) histological evidence of tissue injury, 2) alteration of the alveolar–capillary barrier, 3) presence of an inflammatory response, and 4) physiologic dysfunction. For each domain, we present “relevant measurements,” defined as those proposed by at least 30% of respondents. We propose that experimental ALI encompasses a continuum of models ranging from those focusing on gaining specific mechanistic insights to those primarily concerned with preclinical testing of novel therapeutics or interventions. We suggest that mechanistic studies may justifiably focus on a single domain of lung injury, but models must document alterations of at least three of the four domains to qualify as “experimental ALI.” Finally, we propose that a time criterion defining “acute” in ALI remains relevant, but the actual time may vary based on the specific model and the aspect of injury being modeled. The continuum concept of ALI increases the flexibility and applicability of the definition to multiple models while increasing the likelihood of translating preclinical findings to critically ill patients.
AB - Advancements in methods, technology, and our understanding of the pathobiology of lung injury have created the need to update the definition of experimental acute lung injury (ALI). We queried 50 participants with expertise in ALI and acute respiratory distress syndrome using a Delphi method composed of a series of electronic surveys and a virtual workshop. We propose that ALI presents as a “multidimensional entity” characterized by four “domains” that reflect the key pathophysiologic features and underlying biology of human acute respiratory distress syndrome. These domains are 1) histological evidence of tissue injury, 2) alteration of the alveolar–capillary barrier, 3) presence of an inflammatory response, and 4) physiologic dysfunction. For each domain, we present “relevant measurements,” defined as those proposed by at least 30% of respondents. We propose that experimental ALI encompasses a continuum of models ranging from those focusing on gaining specific mechanistic insights to those primarily concerned with preclinical testing of novel therapeutics or interventions. We suggest that mechanistic studies may justifiably focus on a single domain of lung injury, but models must document alterations of at least three of the four domains to qualify as “experimental ALI.” Finally, we propose that a time criterion defining “acute” in ALI remains relevant, but the actual time may vary based on the specific model and the aspect of injury being modeled. The continuum concept of ALI increases the flexibility and applicability of the definition to multiple models while increasing the likelihood of translating preclinical findings to critically ill patients.
KW - Extravascular lung water
KW - Hypoxia
KW - Lung injury
KW - Pneumonia
KW - Respiratory distress syndrome
UR - http://www.scopus.com/inward/record.url?scp=85123967739&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2021-0531ST
DO - 10.1165/rcmb.2021-0531ST
M3 - Article
C2 - 35103557
AN - SCOPUS:85123967739
SN - 1044-1549
VL - 66
SP - E1-E14
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 2
ER -