| Summary: | The aim of this retrospective and international study is to identify those clinical variables associated with diffuse alveolar damage (DAD), and to explore the impact of DAD on hospital mortality risk. Inclusion criteria were: adult patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy (OLB) during their intensive care unit (ICU) management. The main end-points were: DAD and hospital mortality. In the training (<i>n</i> = 193) and validation cohorts (<i>n</i> = 65), the respiratory rate (odd ratio (OR) 0.956; confidence interval (CI) 95% 0.918; 0.995) and coronary ischemia (OR 5.974; CI95% 1.668; 21.399) on the day of ARDS had an average area under the receiver operating characteristic curve (AUROC) of 0.660 (CI95% 0.585; 0.736) and 0.562 (0.417; 0.706), respectively. PEEP (OR 1.131; CI95% 1.051; 1.218) and coronary ischemia (OR 6.820; CI95% 1.856; 25.061) on the day of OLB had an average AUROC of 0.696 (CI95% 0.621; 0.769) and 0.534 (CI95% 0.391; 0.678), respectively, to predict DAD. DAD (OR 2.296; CI95% 1.228; 4.294), diabetes mellitus requiring insulin (OR 0.081; CI95% 0.009; 0.710) and the respiratory rate (OR 1.045; CI95% 1.001; 1.091) on the day of ARDS had an average AUROC of 0.659 (CI95% 0.583; 0.737) and 0.513 (CI95% 0.361; 0.664) to predict hospital mortality and DAD (OR 2.081; CI95% 1.053; 4.114), diabetes mellitus requiring insulin (OR 0.093; CI95% 0.009; 0.956), PaCO<sub>2</sub> (OR 1.051; CI95% 1.019; 1.084), and platelets count (OR 0.999; CI95% 0.999; 0.999) the day of OLB had an average AUROC of 0.778 (CI95% 0.710; 0.843) and 0.634 (CI95%0.481; 0.787) to predict hospital mortalty in the training and validation cohorts, respectively. In conclusion, DAD could not to be predicted clinically and was significantly associated with hospital mortality.
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