Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report.
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.
Kulkarni, HS; Lee, JS; Bastarache, JA; Kuebler, WM; Downey, GP; Albaiceta, GM; Altemeier, WA; Artigas, A; Bates, JHT; Calfee, CS; Dela Cruz, CS; Dickson, RP; Englert, JA; Everitt, JI; Fessler, MB; Gelman, AE; Gowdy, KM; Groshong, SD; Herold, S; Homer, RJ; Horowitz, JC; Hsia, CCW; Kurahashi, K; Laubach, VE; Looney, MR; Lucas, R; Mangalmurti, NS; Manicone, AM; Martin, TR; Matalon, S; Matthay, MA; McAuley, DF; McGrath-Morrow, SA; Mizgerd, JP; Montgomery, SA; Moore, BB; Noël, A; Perlman, CE; Reilly, JP; Schmidt, EP; Skerrett, SJ; Suber, TL; Summers, C; Suratt, BT; Takata, M; Tuder, R; Uhlig, S; Witzenrath, M; Zemans, RL; Matute-Bello, G
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