Inflammatory subphenotypes in patients at risk of ARDS: evidence from the LIPS-A trial

• Published in: Intensive care medicine Vol. 49; no. 12; pp. 1499 - 1507
• Main Authors: Redaelli, Simone, von Wedel, Dario, Fosset, Maxime, Suleiman, Aiman, Chen, Guanqing, Alingrin, Julie, Gong, Michelle N., Gajic, Ognjen, Goodspeed, Valerie, Talmor, Daniel, Schaefer, Maximilian S., Jung, Boris
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2023; Springer; Springer Nature B.V; Springer Verlag
• Subjects: Acute respiratory distress syndrome; Anesthesiology; Aspirin; Biomarkers; Blood; Clinical trials; Critical Care Medicine; Emergency medical care; Emergency medical services; Emergency Medicine; Evaluation; Genotype & phenotype; Health aspects; Health risks; Human health and pathology; Humans; Inflammation; Intensive; Life Sciences; Medical colleges; Medical examination; Medicine; Medicine & Public Health; Original; Pain Medicine; Patients; Pediatrics; Pneumology/Respiratory System; Respiratory Distress Syndrome; Respiratory failure; Risk; Subgroups; France; United Kingdom; Aspirin; Inflammation; Respiratory distress syndrome; Latent class analysis
• ISSN: 0342-4642; 1432-1238; 1432-1238
• DOI: 10.1007/s00134-023-07244-z

Purpose Latent 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. Methods LIPS-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. Results Among 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). Conclusion Hyper- 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.