title: Biomarkers define the clinical response to dexamethasone in community-acquired pneumonia.
abstract: OBJECTIVE
  Adjuvant dexamethasone treatment in patients with community-acquired pneumonia (CAP) can reduce length of hospital stay. Whether there are subgroups of patients that especially might benefit from corticosteroids is unknown. We hypothesized that a discrepancy between systemic inflammation and cortisol level can define a subgroup that lacks a sufficient cortisol response during CAP, and therefore particularly might benefit from corticosteroids.
  
  
  METHODS
  A secondary analysis was performed on data from hospitalized patients with CAP, randomized to a four-day course of dexamethasone (5 mg daily) or placebo. Subgroups were made based on plasma cytokine levels (interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1)) and total plasma cortisol on presentation. Intensive care unit (ICU) admission and mortality were assessed.
  
  
  RESULTS
  275 Patients (131 dexamethasone, 144 placebo) were analyzed. In the subgroup of patients (n = 23) with a high cytokine response (IL-6 ≥ 92.5 pg/mL, IL-8 ≥ 14.8 pg/mL and MCP-1 ≥ 1154.5 pg/mL) and a discrepantly low cortisol (lowest 50%), dexamethasone treatment was associated with a significant decrease on a combined endpoint of mortality/ICU admission, as compared with placebo (0% vs. 43%, p < 0.01). In the subgroup of patients with a high cytokine response and high cortisol (n = 23), this favorable effect of dexamethasone was absent (30% vs. 39%, p: 0.67).
  
  
  CONCLUSIONS
  In CAP patients presenting with a high pro-inflammatory cytokine response but a discrepantly low cortisol, adjuvant dexamethasone treatment was associated with a significant decrease in mortality/ICU admission.
authors.affiliation: Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Heidelberglaan 100, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. H.H.F.Remmelts-2@umcutrecht.nl
authors.forename: Hilde H F
authors.initials: HH
authors.lastname: Remmelts
authors.forename: Sabine C A
authors.initials: SC
authors.lastname: Meijvis
authors.forename: Rik
authors.initials: R
authors.lastname: Heijligenberg
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: Jan Jelrik
authors.initials: JJ
authors.lastname: Oosterheert
authors.forename: Willem Jan W
authors.initials: WJ
authors.lastname: Bos
authors.forename: Henrik
authors.initials: H
authors.lastname: Endeman
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Douwe H
authors.initials: DH
authors.lastname: Biesma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003422:Critical Care / Q000706:statistics & numerical data; D016207:Cytokines / Q000097:blood; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011014:Pneumonia / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D044967:Serum / Q000737:chemistry; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D010919:Placebos; D003907:Dexamethasone