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Inhibition of reactive nitrogen species production in COPD airways: comparison of inhaled corticosteroid and oral theophylline
  1. T Hirano,
  2. T Yamagata,
  3. M Gohda,
  4. Y Yamagata,
  5. T Ichikawa,
  6. S Yanagisawa,
  7. K Ueshima,
  8. K Akamatsu,
  9. M Nakanishi,
  10. K Matsunaga,
  11. Y Minakata,
  12. M Ichinose
  1. Third Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan
  1. 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

Abstract

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.

  • 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
  • chronic obstructive pulmonary disease
  • nitrative stress
  • 3-nitrotyrosine
  • inhaled corticosteroid
  • theophylline
  • histone deacetylase
  • peroxynitrite

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Footnotes

  • Published Online First 31 May 2006

  • Competing interests: none declared

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  • Correction
    BMJ Publishing Group Ltd and British Thoracic Society