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 c hronic obstructive pulmonary disease (COPD), despite lack of proven efficac y. Because COPD involves airway inflammation and probable protease-antiprot ease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients w ith COPD were treated with fluticasone propionate (500 mu g twice a day) fo r 4 wk, delivered via MDI and spacer, in a double-blind crossover study. Th ere was no clinical benefit in terms of lung function or symptom scores, an d induced sputum inflammatory cells, percentage neutrophils, and IL-8 level s were unchanged. Sputum supernatant elastase activity, matrix metalloprote inase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibit or (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhal ed steroids have no anti-inflammatory action in stable COPD. Furthermore, i nhaled steroids do not appear to redress the protease-antiprotease imbalanc e that is thought to be important in the pathogenesis of airway obstruction .