title: Blood eosinophils as a marker of response to inhaled corticosteroids in COPD.
abstract: Identification of a biomarker that predicts response to inhaled corticosteroids (ICS) would help evaluate the risk/benefit profile of ICS in chronic obstructive pulmonary disease (COPD) and guide treatment.The ISOLDE study randomised 751 patients (mean post-bronchodilator forced expiratory volume in 1 s (FEV1) 1.4 L: 50% predicted normal) to fluticasone propionate 500 μg twice daily or placebo for 3 years, finding no difference in FEV1 rate of decline between treatments (p=0.16) and a significant reduction in median exacerbation rate with fluticasone propionate versus placebo (p=0.026). We re-analysed ISOLDE results by baseline blood eosinophil count to investigate whether eosinophil level predicts ICS benefit.Patients with eosinophils <2% (n=456) had a similar rate of post-bronchodilator FEV1 decline with fluticasone propionate as placebo (-2.9 mL·year(-1); p=0.688). With eosinophils ≥2% (n=214), the rate of decline decreased by 33.9 mL·year(-1) with fluticasone propionate versus placebo (p=0.003). Exacerbation rate reduction on ICS for fluticasone propionate versus placebo was higher in the eosinophil <2% group compared with the ≥2% group; time-to-first moderate/severe exacerbation was not different between treatments in either group.A baseline blood eosinophil count of ≥2% identifies a group of COPD patients with slower rates of decline in FEV1 when treated with ICS: prospective testing of this hypothesis is now warranted.
authors.affiliation: Respiratory Medical Franchise, GSK, Brentford, UK William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK neil.c.barnes@gsk.com.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Barnes
authors.affiliation: Respiratory Medical Franchise, GSK, Brentford, UK.
authors.forename: Raj
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Clinical Statistics and Programming, GSK, Uxbridge, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Lettis
authors.affiliation: Respiratory Research Dept, University of Liverpool, Liverpool, UK.
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage; D004804:Eosinophils / Q000166:cytology*; D005260:Female; D000068298:Fluticasone / Q000008:administration & dosage; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000188:drug therapy*; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D012907:Smoking
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D000068298:Fluticasone