Differences in responses upon corticosteroid therapy between smoking and non-smoking patients with COPD.

Inhaled corticosteroids have a high level of topical anti-inflammatory activity. However, in patients with COPD these drugs have been reported to exert limited effects. A reduction in histone deacetylase (HDAC) activity is suggested to prevent the anti-inflammatory action of corticosteroids. Cigarette smoke is known to reduce HDAC expression. The aim of this study is to compare the outcome of corticosteroid therapy in both smoking and non-smoking COPD patients. Twenty-three smoking patients and 18 ex-smoking patients with COPD were treated with inhaled corticosteroids for a period of 2 months. Blood and induced sputum samples were collected before and after treatment. Values of FEV1 %-predicted did not change upon the therapy, but there was a trend to improve in the ex-smokers (63.1 -> 64.8%-pred.), compared with a decrease in the smokers (63.3 -> 61.6%-pred.). The levels of the pro-inflammatory cytokine IL-8 increased in the group of smokers from 379 +/- 78 to 526 +/- 118 ng/ml. Although not significant, a slight decrease from 382 +/- 70 to 342 +/- 62 ng/ml was observed in the group of ex-smokers. The neutrophil related elastase activity showed similar effects after steroid treatment, it went up from 36.4 +/- 12.0 to 113.5 +/- 9.7 nmol/l in smokers, and decreased from 346.2 +/- 72.1 to 131.1 +/- 6.5 nmol/l in ex-smokers with COPD. These results support the evidence that inhaled corticosteroids have no anti-inflammatory effects in COPD patients, but only when these patients are still smoking. Smoking cessation seems the best therapy for COPD patients.