Thorax 1998;53:269-273 ( April )

Effects of theophylline and ipratropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease

Mitsuhiro Tsukino, Koichi Nishimura, Akihiko Ikeda, Takashi Hajiro, Hiroshi Koyama, Takateru Izumi

Chest Disease Research Institute, Kyoto University, 53 Shogoin, Kawaramachi, Sakyo-ku, Kyoto 606-01, Japan

Correspondence to: Dr M Tsukino.

Received 12 May 1997; Returned to authors 17 July 1997; Revised version received 19 December 1997; Accepted for publication 22 December 1997

BACKGROUNDThe 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.
METHODSTwenty one men with stable COPD and a 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, 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.
RESULTSThe mean (SD) serum theophylline concentration was 18.3 (6.3) µg/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.
CONCLUSIONSBoth 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.

Keywords: chronic obstructive pulmonary disease; exercise capacity; ipratropium bromide; theophylline

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© 1998 by Thorax
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