Effect of low-dose theophylline on airway inflammation in COPD

Motoko Kobayashi, Yasuyuki Nasuhara, Tomoko Betsuyaku, Eiji Shibuya, Yoshinori Tanino, Mishie Tanino, Kei Takamura, Katsura Nagai, Takeshi Hosokawa, Masaharu Nishimura

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


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), α1-antitrypsin (αs1-AT), leukotriene B 4 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.

Original languageEnglish
Pages (from-to)249-254
Number of pages6
Issue number2
Publication statusPublished - 2004 Jun
Externally publishedYes


  • Airway inflammation
  • COPD
  • Induced sputum
  • Neutrophils
  • Theophylline

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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