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.
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ABSTRACT: OBJECTIVE:Lung 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). DESIGN:Double-blind, placebo-controlled randomized trial. SETTING:Tertiary-care pediatric intensive care unit (ICU). PATIENTS:Mechanically ventilated children (0-18?years) with early ARDS. INTERVENTIONS:Blood 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. RESULTS:No 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?
SUBMITTER: Kimura D
PROVIDER: S-EPMC4815896 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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