Predictive Value of H3K18 Lactylation for Early Detection and Prognosis of Sepsis-Related ARDS: 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 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 datawere collected within 24 hours 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), APACHE II scores, and SOFA 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 SOFA 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