Diffuse alveolar damage, acute respiratory distress syndrome (ARDS), and non-cardiogenic pulmonary edema (NCPE). Part 2: NCPE apart from ARDS, molecular and cellular consequences of primary injury to the lung interstitium, with comparative immunology

Diffuse alveolar damage (DAD) and the related clinical syndrome-acute respiratory distress syndrome (ARDS)-result in non-cardiogenic pulmonary edema (NCPE) through acute endothelial and/or alveolar epithelial injury. ARDS endotypes that have been suggested for human medicine may be applicable to veterinary contexts, and the molecular signatures of those endotypes require classification. Both the primary injury and the subsequent amplification by secondary inflammatory processes contribute to the molecular signature; raising awareness of these primary and secondary input processes increases the resolution of data analysis. Furthermore, species-specific differences in inflammatory pathways should be considered when interpreting data or applying new precision immunomodulatory therapeutics. We review other causes of NCPE in dogs and cats and explore the challenges in diagnosing pathologic pulmonary edema with histology. We explore the subsequent immune and cell-death processes that amplify the primary insult to the lung interstitium, ultimately leading to ARDS or DAD, along with the comparative immunology. For cases of acute lung damage-which result in non-cardiogenic edema that lack the classical histologic features of DAD-the histologic changes in dogs and cats can be subtle and nonspecific. Combining these subtle findings with a multidisciplinary approach to reviewing case evidence can yield greater diagnostic accuracy. Therefore, we summarize the histologic features that support a diagnosis of pathologic pulmonary edema and differentiate this condition from peracute agonal pulmonary edema or artefact.