title: Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks. At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured.
  
  
  RESULTS
  Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo. Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo). However, inclusion of contaminated samples did not affect the overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils. Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder analyses showed 42% of patients had ≥20% decrease in neutrophils from baseline; and 47% of patients had a ≥200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant.
  
  
  CONCLUSIONS
  This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population. In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo. Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Asai
authors.affiliation: Biomedical Data Sciences, GlaxoSmithKline, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Medical Affairs Respiratory Department, GlaxoSmithKline, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Makihara
authors.affiliation: Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006304:Health Status; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007564:Japan; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000276:immunology / Q000503:physiopathology; D013183:Sputum / Q000166:cytology / Q000276:immunology; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D001993:Bronchodilator Agents; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; D018836:Inflammation Mediators
keywords: IL-8; biomarkers; neutrophils; serum; sputum