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

AbstractBACKGROUND:
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 mug/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.
AuthorsT Hirano, T Yamagata, M Gohda, Y Yamagata, T Ichikawa, S Yanagisawa, K Ueshima, K Akamatsu, M Nakanishi, K Matsunaga, Y Minakata, M Ichinose
JournalThorax (Thorax) Vol. 61 Issue 9 Pg. 761-6 (Sep 2006) ISSN: 0040-6376 [Print] England
PMID16936236 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
Chemical References
  • Adrenal Cortex Hormones
  • Androstadienes
  • Bronchodilator Agents
  • Reactive Nitrogen Species
  • Theophylline
  • Fluticasone
Topics
  • Administration, Inhalation
  • Administration, Oral
  • Adrenal Cortex Hormones (administration & dosage)
  • Aged
  • Androstadienes (administration & dosage)
  • Bronchodilator Agents (administration & dosage)
  • Cross-Over Studies
  • Female
  • Fluticasone
  • Forced Expiratory Volume (drug effects)
  • Humans
  • Male
  • Oxidative Stress
  • Pulmonary Disease, Chronic Obstructive (drug therapy, metabolism, physiopathology)
  • Reactive Nitrogen Species (biosynthesis)
  • Theophylline (administration & dosage)
  • Vital Capacity (drug effects)

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