The utility of angiopoietin-2 and blood cell-derived biomarker indices in differentiating rapidly improving acute respiratory distress syndrome (RIARDS) phenotype from persistent-ARDS: a prospective observational study

Background: Rapidly improving acute respiratory distress syndrome (RIARDS) is defined as normalization of oxygenation (PaO₂/FiO₂ >300 mmHg) within 24 h of invasive mechanical ventilation. Angiopoietin-2 (Ang-2), a marker of endothelial dysfunction, may predict acute respiratory distress syndrome (ARDS) outcomes, but its role in RIARDS is unclear. This study evaluated Ang-2 and other biomarkers for predicting RIARDS and their association with survival. Research design and methods: In this prospective observational study (June 2023–January 2025) at a 2032-bedded tertiary centre, 193 consecutively enrolled mechanically ventilated ARDS patients were assessed. Demographic, clinical, and laboratory data were recorded on Day 1. Plasma Ang-2 was measured using a high-sensitivity ELISA. Primary outcome was RIARDS; secondary outcome was ICU survival. Results: RIARDS occurred in 18.6% of patients, highest in mild ARDS (52.9%) versus moderate (19.2%) and severe (10.4%). Multivariable regression identified Ang-2 as an independent predictor. A cut-off of 5896 pg/mL yielded an AUC of 0.731 (sensitivity 57.3%, specificity 88.9%). Patients with Ang-2 < 5896 pg/mL were more likely to develop RIARDS (86.1% vs. 13.9%, p-value < 0.001). Kaplan–Meier analysis showed significantly better ICU survival in RIARDS. Conclusions: Early Ang-2 measurement may help differentiate RIARDS from persistent ARDS, enabling prognostic enrichment and personalized management.