Bedside identification of subphenotypes in acute respiratory failure (PHIND): a multicentre, observational cohort study.

Summary

In a prospective, multicentre ICU cohort, a near-patient assay measuring IL-6 and sTNFR1, combined with plasma bicarbonate, classified ARDS/AHRF patients into hyperinflammatory (18%) and hypoinflammatory (82%) subphenotypes at the bedside. Hyperinflammatory patients had markedly higher 60-day mortality (51% vs 28%; adjusted OR 2.7), demonstrating the feasibility and prognostic utility of real-time subphenotyping.

Key Findings

• A rapid near-patient immunoassay (∼1 h) quantified IL-6 and sTNFR1; combined with plasma bicarbonate and a parsimonious logistic model to assign ARDS subphenotypes.
• Among 490 subphenotyped patients, 18% were hyperinflammatory and 82% hypoinflammatory.
• 60-day mortality was higher in the hyperinflammatory group (51% vs 28%; risk ratio 1.8; adjusted OR 2.7; p<0.0001).
• Subphenotypes aligned with clinical features (eg, sepsis prevalence, metabolic acidosis) consistent with prior retrospective work.

Clinical Implications

Real-time identification of hyperinflammatory ARDS could guide risk stratification, enrollment into subphenotype-targeted trials, and potentially inform differential supportive or anti-inflammatory strategies.

Limitations

• Observational design precludes causal inference and therapeutic guidance
• Generalizability may be limited (predominantly White UK/Ireland cohort); not all enrolled patients were subphenotyped
• Biomarker panel restricted to two inflammatory markers plus bicarbonate

Future Directions

Prospective, subphenotype-stratified interventional RCTs; validation across diverse populations; expansion of near-patient panels to include additional mechanistic biomarkers.