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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
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.
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.
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