Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.
Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 microg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction.
Culpitt
S V
SV
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London.
Maziak
W
W
Loukidis
S
S
Nightingale
J A
JA
Matthews
J L
JL
Barnes
P J
PJ
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000336:Aerosols; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D016207:Cytokines / Q000032:analysis*; D004311:Double-Blind Method; D010450:Endopeptidases / Q000032:analysis*; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000032:analysis; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000032:analysis; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000032:analysis; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000032:analysis; D013183:Sputum / Q000737:chemistry* / Q000166:cytology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
D000336:Aerosols; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D016209:Interleukin-8; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D000068298:Fluticasone; D010450:Endopeptidases; D010196:Pancreatic Elastase; D020782:Matrix Metalloproteinases