Anti-inflammatory effects and clinical efficacy of theophylline and tulobuterol in mild-to-moderate chronic obstructive pulmonary disease.

The airway inflammation of chronic obstructive pulmonary disease (COPD) demonstrates a poor response to the anti-inflammatory actions of corticosteroids. However, long-acting beta(2)-agonists and low-dose theophylline are reported to have a possible anti-inflammatory effect in COPD. The aim of this study was to compare the effects of treatment between theophylline and the tulobuterol patch (transdermal patch preparation designed to yield sustained beta(2)-agonistic effects for 24h) on airway inflammation in addition to quality of life (QOL) and pulmonary function in mild-to-moderate COPD. The study subjects consisted of 26 patients with COPD who were treated with theophylline or tulobuterol for 8 weeks with a wash-out period of 4 weeks in a randomized open-label crossover study. We prospectively investigated the differential cell counts and levels of inflammatory markers in induced sputum before and after treatment with theophylline and tulobuterol. We also examined pulmonary function and quality of life (QOL) as assessed by St. George's Respiratory Questionnaire. In the induced sputum, the total inflammatory cell count and number of neutrophils were significantly reduced by treatment with low-dose theophylline. Neither of these parameters was significantly changed by treatment with tulobuterol. Pulmonary function measurements such as FEV(1), FEV(1) % pred, FVC, PEF, MEF(50), and MEF(25) were significantly improved by the treatment with low-dose theophylline but not tulobuterol. The total QOL scores, levels of interleukin 8 and myeloperoxidase in the supernatants of induced sputum, and serum levels of hypersensitive C-reactive protein were not significantly changed by either of the treatments. These results suggest that treatment with low-dose theophylline but not the tulobuterol patch may have anti-inflammatory effects and improve pulmonary function in mild-to-moderate COPD.