Mechanisms underlying pediatric acute respiratory distress syndrome (PARDS) are poorly understood. The recent implication of circulating nucleosomes as pathogenic in sepsis and trauma-associated ARDS in adults led us to investigate the significance of nucleosomes in PARDS. We conducted a prospective, observational study on children with PARDS at the Children's Hospital of Philadelphia between July 2014 and September 2015. Plasma was collected within 48 hours of PARDS onset and nucleosomes quantified by enzyme-linked immunosorbent assay. Samples from 76 children with PARDS (11 deaths, 14%) were collected early (median 15 [IQR 7, 21] hours) after PARDS onset. Nucleosome levels were higher in non-survivors (0.59 AU [IQR 0.46, 0.84]) relative to survivors (0.21 AU [IQR 0.08, 0.33], rank-sum p < 0.001). Nucleosome levels were not associated with either Berlin (p = 0.845) or PALICC (p = 0.886) oxygenation categories, nor with etiology of PARDS (p = 0.527). Nucleosomes were correlated with increasing numbers of non-pulmonary organ failures (p = 0.009 for trend), and were higher in patients whose PaO2/FIO2 worsened (p = 0.012) over the first 72 hours of PARDS. In regression analysis, nucleosome levels were independently associated with mortality after adjusting for either age, severity of illness score, number of non-pulmonary organ failures, vasopressor score, or PaO2/FIO2 (all p < 0.05). In conclusion, plasma nucleosome levels in early PARDS were associated with increased mortality, correlated with number of non-pulmonary organ failures, and preceded worsening oxygenation. The potential utility of this biomarker for prognostication, risk stratification, and mechanistic insight should be investigated further.
- acute respiratory distress syndrome
- pediatric acute respiratory distress syndrome
- Copyright © 2016, American Journal of Physiology - Lung Cellular and Molecular Physiology