Article Text

This article has a correction. Please see:

Download PDFPDF
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}


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

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published Online First 31 May 2006

  • Competing interests: none declared

Linked Articles

  • Correction
    BMJ Publishing Group Ltd and British Thoracic Society