CHRONIC OBSTRUCTIVE PULMONARY DISEASE Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline

Received 26 December 2005 Accepted 1 May 2006 Published Online First 31 May 2006 . . . . . . . . . . . . . . . . . . . . . . . Background: Reactive nitrogen species (RNS) are thought to be one of the important factors in the pathogenesis of chronic obstructive pulmonary disease (COPD). A study was undertaken to examine the effects of theophylline and fluticasone propionate (FP) on RNS production in subjects with COPD. Methods: Sixteen COPD subjects participated in the study. Theophylline (400 mg/day orally) or FP (400 mg/day inhalation) were administered for 4 weeks in a randomised crossover manner with a washout period of 4 weeks. Induced sputum was collected at the beginning and end of each treatment period. 3-nitrotyrosine (3-NT), which is a footprint of RNS, was quantified by high performance liquid chromatography with an electrochemical detection method as well as by immunohistochemical staining. Results: Theophylline significantly reduced the level of 3-NT in the sputum supernatant as well as the number of 3-NT positive cells (both p,0.01). FP also reduced 3-NT formation, but the effect was smaller than that of theophylline. Theophylline also significantly reduced the neutrophil cell counts in the sputum (p,0.01), while FP treatment had no effect on the number of inflammatory cells in the sputum, except eosinophils. Conclusions: Theophylline reduces nitrative stress and neutrophil infiltration in COPD airways to a larger extent than inhaled corticosteroid.