• Simone Redaelli, Dario von Wedel, Maxime Fosset, Aiman Suleiman, Guanqing Chen, Julie Alingrin, Michelle N Gong, Ognjen Gajic, Valerie Goodspeed, Daniel Talmor, Maximilian S Schaefer, and Boris Jung.
• Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA.
• Intensive Care Med. 2023 Dec 1; 49 (12): 149915071499-1507.

PurposeLatent class analysis (LCA) has identified hyper- and non-hyper-inflammatory subphenotypes in patients with acute respiratory distress syndrome (ARDS). It is unknown how early inflammatory subphenotypes can be identified in patients at risk of ARDS. We aimed to test for inflammatory subphenotypes upon presentation to the emergency department.MethodsLIPS-A was a trial of aspirin to prevent ARDS in at-risk patients presenting to the emergency department. In this secondary analysis, we performed LCA using clinical, blood test, and biomarker variables.ResultsAmong 376 (96.4%) patients from the LIPS-A trial, two classes were identified upon presentation to the emergency department (day 0): 72 (19.1%) patients demonstrated characteristics of a hyper-inflammatory and 304 (80.9%) of a non-hyper-inflammatory subphenotype. 15.3% of patients in the hyper- and 8.2% in the non-hyper-inflammatory class developed ARDS (p = 0.07). Patients in the hyper-inflammatory class had fewer ventilator-free days (median [interquartile range, IQR] 28[23-28] versus 28[27-28]; p = 0.010), longer intensive care unit (3[2-6] versus 0[0-3] days; p < 0.001) and hospital (9[6-18] versus 5[3-9] days; p < 0.001) length of stay, and higher 1-year mortality (34.7% versus 20%; p = 0.008). Subphenotypes were identified on day 1 and 4 in a subgroup with available data (n = 244). 77.9% of patients remained in their baseline class throughout day 4. Patients with a hyper-inflammatory subphenotype throughout the study period (n = 22) were at higher risk of ARDS (36.4% versus 10.4%; p = 0.003).ConclusionHyper- and non-hyper-inflammatory subphenotypes may precede ARDS development, remain identifiable over time, and can be identified upon presentation to the emergency department. A hyper-inflammatory subphenotype predicts worse outcomes.© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.

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