Nucleosomes and Nuclear DNA, but Not Mitochondrial DNA, Are Associated With Pediatric ARDS Mortality
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Pulmonary, Quality and Patient Safety, Pediatrics, 2022
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INTRODUCTION: Plasma cell-free DNA (cfDNA) has been proposed as a prognostic, and potentially causative, biomarker in acute respiratory distress syndrome (ARDS). However, this has not been investigated in children. We therefore determined the kinetics of plasma mitochondrial (mtDNA) and nuclear (nDNA) over the first 7 days of pediatric ARDS and assessed the association with pediatric intensive care unit (PICU) mortality. Given that nDNA can circulate alone or complexed with histones as nucleosomes, we determined the kinetics and prognostic utility of nucleosomes. METHODS: This was a prospective cohort study of intubated children with ARDS (Berlin), with blood collection on day 0, 3, and 7 after ARDS onset. We measured mtDNA, nDNA, and nucleosomes using RT-PCRs and ELISA. Day 0 biomarkers were correlated with ARDS severity and number of organ failures, and mortality discrimination assessed by computing areas under the receiver operating characteristic (AUROC) curve. Log-transformed biomarkers were tested for association with mortality using mixed models adjusting for age, ARDS etiology, immunocompromised status, and ARDS severity. We tested for overall differences in biomarker levels between survivors and non-survivors over the first 7 days, as well as differences in trajectories between survivors and non-survivors over the first 7 days. RESULTS: There were 279 ARDS subjects (64 [23%] non-survivors). Nucleosomes and nDNA levels were correlated (pearson r = 0.65). Day 0 nucleosomes, but not nDNA or mtDNA, were associated with ARDS severity (trend p = 0.022). Higher levels of day 0 nucleosomes and nDNA, but not mtDNA, were associated with more organ failures (both p < 0.001) and modestly discriminated mortality (both AUROC 0.76). Nucleosomes and nDNA, but not mtDNA, were persistently elevated in non-survivors over the first 7 days of ARDS (both p < 0.001), without differences in trajectory. Levels of all cfDNAs, but not nucleosomes, increased over the first 7 days. CONCLUSIONS: Nucleosomes and nDNA, but not mtDNA, were associated with mortality in pediatric ARDS. These findings differ from the established utility of mtDNA in adult ARDS, highlighting the importance of pediatric-specific investigations. Whether nucleosomes or nDNA themselves induce damage or are markers of organ failure requires further investigation.
Meta Tag
Content Type Presentation
Knowledge Area Pulmonary
Knowledge Area Quality and Patient Safety
Knowledge Area Pediatrics
Knowledge Level Advanced
Membership Level Select
Tag Acute Respiratory Distress Syndrome ARDS
Tag Mortality
Tag Pediatrics
Year 2022
nuclear DNA
pediatric ARDS
cell-free DNA
mitochondrial DNA


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