Blood Eosinophils to Direct Corticosteroid Treatment of Exacerbations of Chronic Obstructive Pulmonary Disease A Randomized Placebo-Controlled Trial

• Published in: American journal of respiratory and critical care medicine Vol. 186; no. 1; pp. 48 - 55
• Main Authors: Bafadhel, Mona, McKenna, Susan, Terry, Sarah, Mistry, Vijay, Pancholi, Mitesh, Venge, Per, Lomas, David A., Barer, Michael R., Johnston, Sebastian L., Pavord, Ian D., Brightling, Christopher E.
• Format: Journal Article
• Language: English
• Published: New York, NY American Thoracic Society 01.07.2012
• Subjects: Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Biomarkers; Biomarkers - analysis; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Chronic obstructive pulmonary disease; Confidence intervals; Disease Progression; eosinophils; Eosinophils - metabolism; exacerbations; Failure; Female; Glucocorticoids - administration & dosage; Humans; infection; Inflammation; Intensive care medicine; Male; Medical sciences; Middle Aged; Mortality; prednisolone; Prednisolone - administration & dosage; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Questionnaires; Respiratory Function Tests; Statistical analysis; Steroids; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Antineoplastic agent; Lung disease; Corticosteroid; Intensive care; Respiratory disease; Antiinflammatory agent; eosinophils; Eosinophil; Infection; Treatment; exacerbations; Adrenal hormone; Bronchus disease; Chronic obstructive pulmonary disease; Immunosuppressive agent; Prednisolone; Resuscitation
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.201108-1553OC

Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations. 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. 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). The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.