Effects of theophylline and ipratropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease.
BACKGROUND
The effects of theophylline or anticholinergic agents on exercise capacity in patients with chronic obstructive pulmonary disease (COPD) remain controversial. The aim of the present study was to compare the effect of an oral theophylline with an inhaled anticholinergic agent and to examine the effects of combined therapy on exercise performance using progressive cycle ergometry.


METHODS
Twenty one men with stable COPD and a mean (SD) forced expiratory volume in one second (FEV1) of 1.00 (0.40) 1 were studied. Theophylline (600 or 800 mg daily), ipratropium bromide (160 micrograms), a combination of both drugs, and placebo were given in a randomised, double blind, four period crossover design study. Spirometric data, pulse rate, and blood pressure were assessed before and at 90 and 120 minutes after inhalation. Symptom limited progressive cycle ergometer exercise tests (20 watts/min) were performed 90 minutes after each inhalation, and dyspnoea was measured during exercise using the Borg scale.


RESULTS
The mean (SD) serum theophylline concentration was 18.3 (6.3) micrograms/ml, and seven patients had side effects during treatment with theophylline. Theophylline and ipratropium bromide produced greater increases in FEV1, maximal oxygen consumption, maximal minute ventilation, and several dyspnoea ratios than placebo. There were no differences between theophylline and ipratropium bromide except in maximal heart rate. A combination of both drugs produced greater improvements in pulmonary function and exercise capacity than either drug alone.


CONCLUSIONS
Both high dose theophylline and high dose ipratropium bromide improved exercise capacity in patients with stable COPD. Although data based on short term effects cannot be directly applied to long term therapy, theophylline added to an inhaled anticholinergic agent may have beneficial effects on exercise capacity in patients with COPD.
Tsukino
M
M
Chest Disease Research Institute, Kyoto University, Japan.
Nishimura
K
K
Ikeda
A
A
Hajiro
T
T
Koyama
H
H
Izumi
T
T
D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D015444:Exercise; D005080:Exercise Test; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D009241:Ipratropium / Q000627:therapeutic use*; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013806:Theophylline / Q000627:therapeutic use*
D001993:Bronchodilator Agents; D004338:Drug Combinations; D013806:Theophylline; D009241:Ipratropium