Update on the Features and Measurements of Experimental Acute Lung Injury in Animals: An Official American Thoracic Society Workshop Report

Abstract

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.

Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury

“…ALI was assessed using multiple domains ( 64 ). To assess alveolar-capillary barrier disruption, we used the lung wet-dry ratio and/or BAL protein levels.…”

Differential Protein Expression among Two Different Ovine ARDS Phenotypes—A Preclinical Randomized Study

“…ARDS was induced according to the definition and guidance of Acute Lung Injury in experimental animal models as provided by the American Thoracic Society (ATS) [ 48 , 49 ].…”

“…ARDS was induced according to the definition and guidance of Acute Lung Injury in experimental animal models as provided by the American Thoracic Society (ATS) [48,49] This study is a secondary analysis of control animals of Ph1 and Ph2 ARDS from a blinded, randomized, controlled preclinical trial in an ovine model. A total of 9 female non-pregnant Merino-Dorset crossbreed ewes, aged 1-3 years, mean weight 50 ± 5 kg, were included in this analysis and randomly assigned to one of the two groups: Ph1 (n = 5) and Ph2 (n = 4).…”

Experimental Acute Lung Injury in Animals: With Age Comes Knowledge

“…With great interest, we read the recent American Thoracic Society (ATS) workshop update on features and measurements of experimental acute lung injury (ALI) in animals ( 1 ). The workshop committee needs to be commended for their ongoing effort to develop a much needed, transparent, and unequivocal framework for animal research studying the complex patho-biological and patho-physiological aspects of ALI.…”

“…Findings from the current literature involving animal models seem to mirror the situation in humans: increasing age is associated with higher susceptibility to, and severity of ALI in response to an identical trigger ( 4 ). More importantly, studies of ALI in animals show the existence of highly differential, age-related pulmonary responses in all of the four key pathophysiological domains (histological injury, alteration of the alveolar-capillary barrier, inflammatory response, and physiologic dysfunction), as identified by the ATS workshop committee ( 1 , 4 ). For example, in a study with rats treated with intratracheal lipopolysaccharide and mechanical ventilation, adult rats (3–4 months old) showed marked increases in alveolar permeability and inflammation as compared with infant rats (2–3 wk), but these findings were not accompanied by more histopathological lung injury ( 5 ).…”