Circulating nucleosomes are associated with mortality in pediatric acute respiratory distress syndrome

Nadir Yehya, Neal J. Thomas, Susan S. Margulies

Research output: Contribution to journalArticle

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Abstract

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 h 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) h] after PARDS onset. Nucleosome levels were higher in nonsurvivors [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 nonpulmonary organ failures (P = 0.009 for trend), and were higher in patients whose PaO2/FiO2 worsened (P = 0.012) over the first 72 h of PARDS. In regression analysis, nucleosome levels were independently associated with mortality after adjusting for either age, severity of illness score, number of nonpulmonary 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 nonpulmonary organ failures, and preceded worsening oxygenation. The potential utility of this biomarker for prognostication, risk stratification, and mechanistic insight should be investigated further.

Original languageEnglish (US)
Pages (from-to)L1177-L1184
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume310
Issue number11
DOIs
StatePublished - Jun 1 2016

Fingerprint

Nucleosomes
Adult Respiratory Distress Syndrome
Pediatrics
Mortality
Organ Dysfunction Scores
Berlin
Observational Studies
Survivors
Sepsis
Biomarkers
Enzyme-Linked Immunosorbent Assay
Regression Analysis
Prospective Studies
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

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title = "Circulating nucleosomes are associated with mortality in pediatric acute respiratory distress syndrome",
abstract = "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 h 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) h] after PARDS onset. Nucleosome levels were higher in nonsurvivors [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 nonpulmonary organ failures (P = 0.009 for trend), and were higher in patients whose PaO2/FiO2 worsened (P = 0.012) over the first 72 h of PARDS. In regression analysis, nucleosome levels were independently associated with mortality after adjusting for either age, severity of illness score, number of nonpulmonary 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 nonpulmonary organ failures, and preceded worsening oxygenation. The potential utility of this biomarker for prognostication, risk stratification, and mechanistic insight should be investigated further.",
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Circulating nucleosomes are associated with mortality in pediatric acute respiratory distress syndrome. / Yehya, Nadir; Thomas, Neal J.; Margulies, Susan S.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 310, No. 11, 01.06.2016, p. L1177-L1184.

Research output: Contribution to journalArticle

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