Effect of low-dose theophylline on airway inflammation in COPD

Respirology. 2004 Jun;9(2):249-54. doi: 10.1111/j.1440-1843.2004.00573.x.

Abstract

Objective: Recent studies have shown that theophylline may exert anti-inflammatory effects on neutrophils. We undertook to assess the effect of theophylline on airway inflammation in COPD.

Methodology: We performed a 4-week randomized double-blind, placebo-controlled study in 11 theophylline-naive patients with mild to moderate COPD. After a 1-week run-in period, six subjects were administered 400 mg/day theophylline (Theodur; Nikken Chemicals Co. Ltd, Tokyo, Japan) for 4 weeks, while five subjects were administered a placebo. Induced sputum was obtained before and after the run-in period and then after 2 and 4 weeks of treatment. Cell differential count and levels of interleukin-8, matrix metalloproteinase-9, neutrophil elastase (NE), myeloperoxidase (MPO), alpha1-antitrypsin (alpha1-AT), leukotriene B4 and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assessed.

Results: No variable was significantly different during the run-in period or with placebo treatment. In contrast, theophylline treatment significantly decreased NE and MPO levels at 4 weeks, although the cell differential count did not change appreciably as a result of treatment.

Conclusion: These results suggest that 4 weeks of theophylline treatment attenuates neutrophil-associated inflammation in the airways of mild to moderate COPD patients. However, the clinical benefits remain to be determined.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bronchodilator Agents / administration & dosage*
  • Double-Blind Method
  • Female
  • Humans
  • Leukocyte Elastase / analysis
  • Male
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Respiratory Function Tests
  • Sputum / cytology
  • Sputum / drug effects*
  • Theophylline / administration & dosage*

Substances

  • Bronchodilator Agents
  • Theophylline
  • Leukocyte Elastase