Effect of low-dose theophylline on airway inflammation in COPD

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.