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.

Summary

In a prospective ARDS cohort (n=193), lower plasma angiopoietin-2 independently predicted the rapidly improving ARDS phenotype and was associated with better ICU survival. A cut-off of 5896 pg/mL yielded AUC 0.731 with high specificity (88.9%), supporting early biomarker-based prognostic enrichment.

Key Findings

• RIARDS occurred in 18.6% overall, most frequent in mild ARDS (52.9%) versus moderate (19.2%) and severe (10.4%).
• Angiopoietin-2 independently predicted RIARDS; a 5896 pg/mL cut-off achieved AUC 0.731 with 88.9% specificity and 57.3% sensitivity.
• Patients with Ang-2 <5896 pg/mL were more likely to experience RIARDS (86.1% vs 13.9%, p<0.001).
• RIARDS phenotype showed significantly better ICU survival on Kaplan–Meier analysis.

Clinical Implications

Early Ang-2 measurement could guide expectations for rapid improvement, inform ventilator weaning trials, and prioritize resources, while supporting stratification in interventional studies.

Limitations

• Single-center study without external validation; moderate AUC and modest sensitivity
• Observational design precludes causal inference; potential confounding remains

Future Directions

External validation, integration into multimarker panels and clinical scores, and use for prognostic enrichment in ARDS interventional trials.