Antiinflammatory effects of salmeterol/fluticasone propionate in chronic obstructive lung disease.
BACKGROUND
No currently available treatment is reported to reduce the exaggerated airway wall inflammation of chronic obstructive pulmonary disease.


OBJECTIVE
We tested the hypothesis that inhaled combined long-acting beta2-agonist (salmeterol) and corticosteroid (fluticasone propionate) will reduce inflammation.


METHODS
Bronchial biopsies and induced sputum were taken from 140 current and former smokers (mean age, 64 yr) with moderate to severe disease, randomized in a 13-wk double-blind study to placebo (n = 73) or salmeterol/fluticasone propionate 50/500 microg (n = 67) twice daily. Biopsies were repeated at 12 wk and sputa at 8 and 13 wk. After adjustment for multiplicity, comparisons between active and placebo were made for median change from baseline in the numbers of biopsy CD8+ and CD68+ cells/mm2 and sputum neutrophils.


RESULTS
Combination therapy was associated with a reduction in biopsy CD8+ cells of -118 cells/mm2 (95% confidence interval [CI], -209 to -42; p = 0.02), a reduction of 36% over placebo (p = 0.001). CD68+ cells were unaffected by combination treatment. Sputum differential (but not total) neutrophils reduced progressively and, at Week 13, significantly with combination treatment (median treatment difference, 8.5%; 95% CI, 1.75%-15.25%; p = 0.04). The combination also significantly reduced biopsy CD45+ and CD4+ cells and cells expressing genes for tumor necrosis factor-alpha and IFN-gamma and sputum total eosinophils (all p < or = 0.03). These antiinflammatory effects were accompanied by a 173-ml (95% CI, 104-242; p < 0.001) improvement in prebronchodilator FEV1.


CONCLUSIONS
The combination of salmeterol and fluticasone propionate has a broad spectrum of antiinflammatory effects in both current and former smokers with chronic obstructive pulmonary disease, which may contribute to clinical efficacy.
Barnes
Neil C
NC
Department of Respiratory Medicine, London Chest Hospital, London, UK.
Qiu
Yu-Sheng
YS
Pavord
Ian D
ID
Parker
Debbie
D
Davis
Peter A
PA
Zhu
Jie
J
Johnson
Malcolm
M
Thomson
Neil C
NC
Jeffery
Peter K
PK
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001706:Biopsy; D001999:Bronchoscopy; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000068299:Salmeterol Xinafoate; D013183:Sputum / Q000166:cytology; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol