1. Plasma Biomarker Analysis in Pediatric ARDS: Generating Future Framework from a Pilot Randomized Control Trial of Methylprednisolone: A Framework for Identifying Plasma Biomarkers Related to Clinical Outcomes in Pediatric ARDS
- Author
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Kimura, Dai, Saravia, Jordy, Rovnaghi, Cynthia R, Meduri, Gianfranco Umberto, Schwingshackl, Andreas, Cormier, Stephania A, and Anand, Kanwaljeet J
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Pediatric ,Clinical Research ,Clinical Trials and Supportive Activities ,Acute Respiratory Distress Syndrome ,Lung ,Rare Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Respiratory ,Good Health and Well Being ,ARDS ,biomarker ,pediatric ,methylprednisolone ,MMP-8 ,Ang-2 ,ICAM-1 ,sRAGE ,Paediatrics and Reproductive Medicine ,Other Medical and Health Sciences ,Paediatrics - Abstract
ObjectiveLung injury activates multiple pro-inflammatory pathways, including neutrophils, epithelial, and endothelial injury, and coagulation factors leading to acute respiratory distress syndrome (ARDS). Low-dose methylprednisolone therapy (MPT) improved oxygenation and ventilation in early pediatric ARDS without altering duration of mechanical ventilation or mortality. We evaluated the effects of MPT on biomarkers of endothelial [Ang-2 and soluble intercellular adhesion molecule-1 (sICAM-1)] or epithelial [soluble receptor for activated glycation end products (sRAGE)] injury, neutrophil activation [matrix metalloproteinase-8 (MMP-8)], and coagulation (plasminogen activator inhibitor-1).DesignDouble-blind, placebo-controlled randomized trial.SettingTertiary-care pediatric intensive care unit (ICU).PatientsMechanically ventilated children (0-18 years) with early ARDS.InterventionsBlood samples were collected on days 0 (before MPT), 7, and 14 during low-dose MPT (n = 17) vs. placebo (n = 18) therapy. The MPT group received a 2-mg/kg loading dose followed by 1 mg/kg/day continuous infusions from days 1 to 7, tapered off over 7 days; placebo group received equivalent amounts of 0.9% saline. We analyzed plasma samples using a multiplex assay for five biomarkers of ARDS. Multiple regression models were constructed to predict associations between changes in biomarkers and the clinical outcomes reported earlier, including P/F ratio on days 8 and 9, plateau pressure on days 1 and 2, PaCO2 on days 2 and 3, racemic epinephrine following extubation, and supplemental oxygen at ICU discharge.ResultsNo differences occurred in biomarker concentrations between the groups on day 0. On day 7, reduction in MMP-8 levels (p = 0.0016) occurred in the MPT group, whereas increases in sICAM-1 levels (p = 0.0005) occurred in the placebo group (no increases in sICAM-1 in the MPT group). sRAGE levels decreased in both MPT and placebo groups (p
- Published
- 2016