title: Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial.
abstract: BACKGROUND
  Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous.
  
  
  OBJECTIVE
  Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations.
  
  
  METHODS
  Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and ≤ 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms.
  
  
  RESULTS
  There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0-0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01-0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04).
  
  
  CONCLUSIONS
  The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.
authors.affiliation: Institute for Lung Health, Clinical Sciences Wing, University Hospitals of Leicester, Leicester, UK. mb353@le.ac.uk
authors.forename: Mona
authors.initials: M
authors.lastname: Bafadhel
authors.forename: Susan
authors.initials: S
authors.lastname: McKenna
authors.forename: Sarah
authors.initials: S
authors.lastname: Terry
authors.forename: Vijay
authors.initials: V
authors.lastname: Mistry
authors.forename: Mitesh
authors.initials: M
authors.lastname: Pancholi
authors.forename: Per
authors.initials: P
authors.lastname: Venge
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barer
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.forename: Ian D
authors.initials: ID
authors.lastname: Pavord
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Brightling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D018450:Disease Progression; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D012129:Respiratory Function Tests
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D011239:Prednisolone