Effects of theophylline and ipratropium bromide on exerciseperformance in patients with stable chronic obstructive pulmonarydisease

BACKGROUND—The effects of theophylline oranticholinergic agents on exercise capacity in patients with chronicobstructive pulmonary disease (COPD) remain controversial. The aim ofthe present study was to compare the effect of an oral theophyllinewith an inhaled anticholinergic agent and to examine the effects ofcombined therapy on exercise performance using progressive cycle ergometry.
METHODS—Twenty one men with stable COPD anda mean (SD) forced expiratory volume in one second (FEV₁)of 1.00 (0.40) l were studied. Theophylline (600 or 800 mg daily),ipratropium bromide (160 µg), a combination of both drugs, andplacebo were given in a randomised, double blind, four period crossoverdesign study. Spirometric data, pulse rate, and blood pressure wereassessed before and at 90 and 120 minutes after inhalation. Symptomlimited progressive cycle ergometer exercise tests (20 watts/min) wereperformed 90minutes after each inhalation, and dyspnoea was measuredduring exercise using the Borg scale.
RESULTS—The mean (SD) serum theophyllineconcentration was 18.3 (6.3) µg/ml, and seven patients had sideeffects during treatment with theophylline. Theophylline andipratropium bromide produced greater increases in FEV₁,maximal oxygen consumption, maximal minute ventilation, and severaldyspnoea ratios than placebo. There were no differences betweentheophylline and ipratropium bromide except in maximal heart rate. Acombination of both drugs produced greater improvements in pulmonaryfunction and exercise capacity than either drug alone.
CONCLUSIONS—Both high dose theophylline and highdose ipratropium bromide improved exercise capacity in patients withstable COPD. Although data based on short term effects cannot bedirectly applied to long term therapy, theophylline added to an inhaledanticholinergic agent may have beneficial effects on exercise capacityin patients with COPD.