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

Summary

Using a near-patient 1-hour immunoassay for IL-6 and sTNFR1 plus bicarbonate, clinicians prospectively classified ARDS/AHRF patients into hyper- and hypoinflammatory subphenotypes. The hyperinflammatory group (18%) had markedly higher 60-day mortality (51% vs 28%; adjusted OR 2.7), validating bedside precision phenotyping.

Key Findings

• Near-patient benchtop assay (≈1 h) measuring IL-6 and sTNFR1 plus bicarbonate enabled real-time ARDS subphenotyping in 490 of 512 enrolled patients.
• Hyperinflammatory phenotype prevalence was 18% and was associated with higher 60-day mortality (51% vs 28%; RR 1.8; adjusted OR 2.7, p=0.0002).
• Clinical characteristics (e.g., sepsis prevalence, metabolic acidosis) aligned with prior retrospective subphenotype descriptions.

Clinical Implications

Hospitals can implement near-patient biomarker panels to stratify ARDS patients by inflammatory phenotype for prognostication and trial enrollment. Until phenotype-specific therapies are validated, results should inform risk communication and targeted monitoring rather than dictate therapy changes.

Limitations

• Observational design precludes causal inference and does not test phenotype-specific therapies.
• Generalizability beyond UK/Ireland health systems and missing biomarker data in a subset (22 not phenotyped) may limit applicability.

Future Directions

Conduct subphenotype-stratified RCTs, validate assay thresholds in diverse settings, and integrate rapid phenotyping into adaptive platform trials.