CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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

T Hirano, T Yamagata, M Gohda, Y Yamagata, T Ichikawa, S Yanagisawa, K Ueshima, K Akamatsu, M Nakanishi, K Matsunaga, Y Minakata, M Ichinose

Third Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan

Correspondence to:
Professor M Ichinose
Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-8509, Japan; masakazu{at}wakayama-med.ac.jp

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 µg/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.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FP, fluticasone propionate; FVC, forced vital capacity; HDAC, histone deacetylase; HPLC/ECD, high performance liquid chromatography with electrochemical detection; IL, interleukin; 3-NT, 3-nitrotyrosine; RNS, reactive nitrogen species

Keywords: chronic obstructive pulmonary disease; nitrative stress; 3-nitrotyrosine; inhaled corticosteroid; theophylline; histone deacetylase; peroxynitrite

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