Blood Eosinophils to Direct Corticosteroid Treatment of Exacerbations of COPD: a Randomized Placebo Controlled Trial.
Am J Respir Crit Care Med. 2012 Mar 23;
Authors: Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE
Abstract
RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. OBJECTIVES: Investigate the utility 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, whilst 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 non-inferiority 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 arm. MEASUREMENTS AND MAIN RESULTS: There were 86 and 80 exacerbations in the biomarker-directed and standard treatment group. In the biomarker-directed group 49% of the exacerbations were not treated with prednisolone. CRQ improvement following treatment in the standard and biomarker-directed therapy group was similar (0.8 vs. 1.1, mean difference 0.3, 95% CI 0.0 to 0.6, p=0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared to those given prednisolone (mean difference 0.45; 95% CI 0.01 to 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). CONCLUSION: The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.Clinical trial registration available at www.controlled-trials.com/ISRCTN92422949.
PMID: 22447964 [PubMed - as supplied by publisher]