PREDICTIVE VALUE OF H3K18 LACTYLATION FOR EARLY DETECTION AND PROGNOSIS OF SEPSIS-RELATED ACUTE RESPIRATORY DISTRESS SYNDROME: A PROSPECTIVE OBSERVATIONAL CLINICAL STUDY.

Summary

In a prospective ICU cohort of 91 septic patients, BALF histone H3K18 lactylation was higher in those who developed ARDS, independently predicted ARDS risk, and correlated with systemic inflammation and severity scores. Diagnostic performance was strong (AUC 0.804) and improved when combined with SOFA (AUC 0.830); day-3 rises associated with mortality.

Key Findings

• BALF H3K18la levels were significantly higher in sepsis-related ARDS versus non-ARDS and controls (P < 0.05).
• H3K18la correlated positively with lactate, IL-6, TNF-α, APACHE II, and SOFA scores (P < 0.01).
• H3K18la independently predicted ARDS development with AUC 0.804; combined with SOFA, AUC improved to 0.830 (sensitivity 88.9%, specificity 67.3%).
• Day-3 BALF H3K18la increased significantly in the mortality group, indicating prognostic value.

Clinical Implications

H3K18la measurement in BALF could support early ARDS identification and risk stratification in septic ICU patients, guiding monitoring intensity and enrollment into trials of targeted therapies.

Limitations

• Single-center, moderate sample size (N=91) limits generalizability.
• BALF sampling may not be feasible in all patients and lacks external validation.

Future Directions

External validation across centers, development of blood-based surrogates, and integration into multimodal risk models to guide early interventions.