Plasma Levels of Soluble ST2 Reflect Extrapulmonary Organ Dysfunction and Predict Outcomes in Acute Respiratory...

Area of Science:

• Biomarkers in critical care medicine
• Immunology of acute respiratory failure
• Interleukin-33 (IL-33) signaling pathway

Background:

• Soluble ST2 (sST2) is a decoy receptor for IL-33, a key alarmin.
• sST2 has been associated with adverse outcomes in acute respiratory failure (ARF).
• Understanding sST2 distribution and associations in ARF is crucial for clinical management.

Purpose of the Study:

• To evaluate sST2 distribution in diverse ARF patient cohorts.
• To compare plasma and lower respiratory tract (LRT) sST2 concentrations.
• To examine associations of sST2 with organ dysfunction, subphenotypes, and outcomes in ARF.

Main Methods:

• Observational study utilizing multicenter cohorts of ARF patients.
• Inclusion of 1432 ARF patients (863 non-COVID, 569 COVID-19).
• Measurement of sST2 in plasma and LRT specimens, with statistical analysis of associations.

Main Results:

• Plasma sST2 levels were higher in non-COVID ARF patients than COVID-19 patients and markedly elevated compared to LRT levels.
• Elevated plasma sST2 correlated with extrapulmonary organ dysfunction and hyperinflammatory ARF subphenotypes.
• Plasma sST2 independently predicted 30-day mortality in ARF patients, with persistently higher levels in non-survivors.

Conclusions:

• Plasma sST2 is an independent predictor of outcomes in ARF, strongly linked to extrapulmonary organ dysfunction.
• The weak correlation between plasma and LRT sST2 suggests a primarily systemic origin.
• The IL-33/ST2 axis represents a potential therapeutic target for ARF and multiple organ dysfunction.