Is oral theophylline effective in combination with both inhaled anticholinergic agent and inhaled beta 2-agonist in the treatment of stable COPD?

To investigate the additive effect of oral theophylline on combined inhaled anticholinergic agent and beta 2-agonist therapy, 12 patients with stable COPD (64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial of oral theophylline for a 4-week period (400 mg for 2 weeks, followed by 600 mg for 2 weeks). All of the patients continued to inhale both salbutamol, 200 micrograms, and ipratropium bromide, 40 micrograms, using a metered-dose inhaler four times a day. Spirometry was assessed before, and 15 and 60 min after the inhalation of bronchodilators at 2-week intervals. Even after the inhalation of salbutamol and ipratropium, theophylline significantly improved FEV1 and daily peak expiratory flow rate compared with the placebo. No significant improvement in the daily symptom scores for cough, sputum, wheezing, or shortness of breath was observed throughout the different phases of treatment. This study shows that the additive bronchodilating effect of theophylline, when used in combination with salbutamol, 200 micrograms, and ipratropium, 40 micrograms, is significant but small in stable COPD. The addition of theophylline did not significantly improve the patient's symptoms. Oral theophylline, when used in combination with an inhaled anticholinergic agent and an inhaled beta 2-agonist, may be of limited value in the treatment of stable COPD.