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

Abstract: Background: This study aimed to investigate the predictive value of histone H3 lysine 18 lactylation (H3K18la) for the early identification and prognosis of sepsis-related acute respiratory distress syndrome (ARDS). Methods: This prospective observational study included patients with sepsis admitted to the intensive care unit (ICU) between March 2023 and September 2024. The patients were divided into two groups: the sepsis with ARDS group and the sepsis without ARDS group. Clinical data were collected within 24 h of ICU admission. Bronchoalveolar lavage fluid (BALF) samples were obtained on day 1 for all participants, and a second BALF sample was collected on day 3 from patients requiring continued mechanical ventilation. Results: In total, 91 sepsis patients were enrolled in the study: 36 with ARDS and 55 without ARDS. H3K18la levels in BALF were significantly higher in the sepsis-related ARDS group than in the non-ARDS group and the control group ( P < 0.05). Elevated H3K18la levels were positively correlated with inflammatory markers (lactate, IL-6, and TNF-α), Acute Physiology and Chronic Health Evaluation II scores, and Sequential Organ Failure Assessment scores ( P < 0.01). Logistic regression analysis revealed that H3K18la was an independent predictor of ARDS development ( P < 0.05), and ROC curve analysis revealed that H3K18la had high diagnostic accuracy (AUC = 0.804). Combining H3K18la with the Sequential Organ Failure Assessment score further improved diagnostic performance (AUC = 0.830, sensitivity = 88.9%, specificity = 67.3%). Furthermore, H3K18la levels significantly increased on day 3 in the mortality group. Conclusion: H3K18la is a promising biomarker for the early identification and prognostic prediction of sepsis-related ARDS.