Serum CitH3 and PTX3 Levels for Early Prediction of Acute Respiratory Distress Syndrome Following Severe Traumatic Brain Injury

OBJECTIVE: To evaluate the predictive value of serum citrullinated histone H3 (CitH3) and pentraxin 3 (PTX3) for acute respiratory distress syndrome (ARDS) after severe traumatic brain injury (sTBI). METHODS: This prospective observational study enrolled 395 consecutive sTBI patients admitted between April 2025 and February 2026. Patients were categorized into ARDS (n = 111) and non-ARDS (n = 284) groups. Serum CitH3 and PTX3 were measured by ELISA. Candidate predictors were selected by LASSO regression. Spearman correlation, multivariable logistic regression, and receiver operating characteristic (ROC) analyses were performed. The DeLong test, category-free net reclassification improvement (NRI), and integrated discrimination improvement (IDI) assessed incremental predictive value over the conventional model. RESULTS: Serum CitH3 and PTX3 were significantly higher in the ARDS group (both P < 0.001) and were positively correlated with each other but negatively with oxygenation indices and albumin. Multivariable analysis identified pulmonary contusion, shock, fluid balance within 12 h of admission, APACHE II and SOFA scores, and elevated CitH3 and PTX3 as independent risk factors (all P < 0.05), whereas a higher GCS score and elevated albumin were protective. Their combination yielded an AUC of 0.841, superior to either alone. When added to the conventional model, biomarkers increased the AUC from 0.926 to 0.943 (P = 0.025), with category-free NRI of 0.554 (95% CI: 0.320-0.778, P < 0.001) and IDI of 0.072 (95% CI: 0.040-0.105, P < 0.001). CONCLUSION: Combined serum CitH3 and PTX3 demonstrate early predictive potential for ARDS after sTBI but require external validation.