Clinical Phenotypes from Fatal Cases of Acute Respiratory Distress Syndrome Caused by Pneumonia

Abstract Background: The COVID-19 pandemic has renewed interest and discussion about clinical phenotypes of acute respiratory distress syndrome (ARDS). Since the Berlin definition, various clinical disease courses with fatal outcome have been described but early objective indicators predicting distinct clinical courses have remained elusive. Objectives: Identify clinically available predictors that distinguish between two phenotypes of fatal ARDS due to pneumonia.Methods: 104 Japanese patients with pneumonia induced ARDS were extracted from our prospectively collected database. Fatal cases were divided into early (< 7 days after diagnosis) and late death (≥ 7 days) groups and their clinical variables and prognostic factors were statistically evaluated.Results: Of 50 cases, fatal within 180 days, 18 (36%) comprised the early death group (median 2 days, IQR [1, 5]) and 32 (64%), the late death group (median 16 days, IQR [13, 29]). Multivariate regression analyses showed APACHE II score (HR 1.14, 95%CI 1.01-1.28, p 0.047) was the only independent prognostic factor for early death. Late deaths were associated with disseminated intravascular coagulation score (HR 1.30, 95%CI 1.07-1.58, p 0.007), culture sensitivity to initial antimicrobials (HR 3.42, 95%CI 1.86-6.29, p <0.0001), and high-resolution computed tomography (HRCT) score indicating early fibroproliferation. ROC analyses estimated a late death propensity score for HRCT score ≥ 211, of 5.42 (95%CI 1.54–19.12; p 0.008).Conclusions: The extent of fibroproliferation on HRCT, along with coagulation abnormalities and APACHE II scores, should be considered for use in predictive trial enrichment and personalized medicine for patients with ARDS due to pneumonia.