Pneumonia Requiring Respiratory Support in the PICU: Single-Center Study of Admission Plasma Nucleosome, Histone, and Citrullinated Histone H3 Levels in Relation to Complications

OBJECTIVES: To investigate plasma nucleosome, histone H3 (H3), and citrullinated histone H3 (CitH3) levels in PICU patients with viral or bacterial pneumonia, and the associations with pediatric acute respiratory distress syndrome (PARDS) and sepsis. DESIGN: Single-center observational study of plasma nucleosome, H3, and CitH3 levels collected within 24 hours of PICU admission in patients with pneumonia requiring respiratory support. SETTING: A children's hospital PICU in Yunnan, China. PATIENTS: Pneumonia patients and healthy controls seen during 2022-2024. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 152 children (0.3-12 years old) with severe pneumonia were enrolled and, post hoc, 47 met the 2024 Phoenix criteria for sepsis, and 45 met the 2023 criteria for PARDS. Pneumonia in comparison with 22 controls was associated with higher levels of all three markers (nucleosome, p = 0.0006; H3, p = 0.003; and CitH3, p = 0.029). In comparison with non-sepsis and non-PARDS cases, the sepsis and PARDS categories were associated with higher levels of all three markers (sepsis, p < 0.0001, p = 0.015, p < 0.0001; PARDS, p = 0.003, p < 0.0001, p = 0.0002). The area under the receiver operating characteristic curve (AUROC) analysis with nucleosome level using the sepsis endpoint was 0.79 (95% CI, 0.71-0.87), p < 0.0001. The relationship between H3 and PARDS vs. non-ARDS patients was AUROC 0.83 (95% CI, 0.75-0.91), p < 0.0001; and there was a negative correlation with Pa o2 to F io2 of r -0.63 ( p < 0.0001). Regarding, the association between bacterial vs. viral etiology of pneumonia, the combination of plasma CitH3 and C-reactive protein showed AUROC of 0.84 (95% CI, 0.76-0.92), p < 0.0001. CONCLUSIONS: In PICU patients with pneumonia requiring respiratory support, we detected significant plasma of nucleosome, H3, and CitH3 within the first 24 hours of admission. Furthermore, categorization as PARDS or sepsis was associated with higher levels of these biomarkers.