title: Regulation of inflammatory biomarkers by intravenous methylprednisolone in pediatric ARDS patients: Results from a double-blind, placebo-controlled randomized pilot trial.
abstract: OBJECTIVE
  A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients.
  
  
  METHODS
  Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7.
  
  
  METHODS
  Tertiary care children's hospital.
  
  
  METHODS
  Children (0-18years) with ARDS undergoing mechanical ventilation.
  
  
  METHODS
  35 children were randomized within 72h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2mg/kg loading dose followed by 1mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7.
  
  
  RESULTS
  At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson's correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity.
  
  
  CONCLUSIONS
  This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.
authors.affiliation: Department of Pediatrics, Mattel Children's Hospital at UCLA, Los Angeles, CA, United States. Electronic address: aschwingshackl@gmail.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schwingshackl
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Dai
authors.initials: D
authors.lastname: Kimura
authors.affiliation: Pain Neurobiology Laboratory, University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Rovnaghi
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Jordy S
authors.initials: JS
authors.lastname: Saravia
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Stephania A
authors.initials: SA
authors.lastname: Cormier
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Teng
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Alina N
authors.initials: AN
authors.lastname: West
authors.affiliation: Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Umberto G
authors.initials: UG
authors.lastname: Meduri
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, CA, United States.
authors.forename: Kanwaljeet J S
authors.initials: KJ
authors.lastname: Anand
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood*; D007262:Infusions, Intravenous; D008171:Lung Diseases / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D010865:Pilot Projects; D011379:Prognosis; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D002097:C-Reactive Protein; D008775:Methylprednisolone
keywords: ARDS; Chemokines; Cytokines; Glucocorticoids; Inflammation; Lung injury; Mediators; Pediatrics; Steroids