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a A.
Cardarelli Hospital, Division of Pneumology and Allergology, Naples,
Italy, b University of Milan,
Medical School, San Paolo Hospital, Respiratory Diseases Unit, Milan,
Italy, c S Maugeri Foundation,
Institute of Care and Research, Medical Centre of Rehabilitation,
Division of Pneumology, Veruno, Italy
Correspondence to: Dr M Cazzola, Via del Parco Margherita 24, 80121 Napoli, Italy
Received 16 April 1999; Returned to authors 14 July 1999; Revised version received 29 July 1999; Accepted for publication 17 August 1999
BACKGROUND
An earlier
study documented that, in patients with chronic obstructive pulmonary
disease (COPD), addition of ipratropium bromide at the clinically
recommended dose (40 µg) does not produce any further
bronchodilation than that achieved with salmeterol 50 µg alone.
However, the dose of ipratropium bromide needed to produce near maximal
bronchodilation is several times higher than the customary dosage. The
full therapeutic potential of combined salmeterol plus an
anticholinergic drug can therefore only be established using doses
higher than those currently recommended in the marketing of these
agents. A study was undertaken to examine the possible acute effects of
higher than conventional doses of an anticholinergic agent on the
single dose salmeterol induced bronchodilation in patients with stable
and partially reversible COPD.
METHODSThirty
two outpatients received 50 µg salmeterol or placebo. Two hours
after inhalation a dose-response curve to inhaled oxitropium bromide
(100 µg/puff) or placebo was constructed using one puff, one puff,
two puffs, and two puffsthat is, a total cumulative dose of 600 µg
oxitropium bromide. Dose increments were given at 20 minute
intervals with measurements being made 15 minutes after each dose. On
four separate days all patients received one of the following: (1)
50 µg salmeterol + 600 µg oxitropium bromide; (2) 50 µg
salmeterol + placebo; (3) placebo + 600 µg oxitropium bromide; (4)
placebo + placebo.
RESULTSSalmeterol
induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium bromide elicited
an evident dose-dependent increase in forced expiratory volume in one
second (FEV1) and this occurred also after pretreatment
with salmeterol with a further mean maximum increase of 0.152 l (95%
CI of differences 0.124 to 0.180).
CONCLUSIONSThis study
shows that acute pretreatment with 50 µg salmeterol does not block
the possibility of inducing more bronchodilation with an
anticholinergic agent when a higher than normal dosage of the
muscarinic antagonist is used.
This article has been cited by other articles:
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  J. F. Donohue Combination Therapy for Chronic Obstructive Pulmonary Disease: Clinical Aspects Proceedings of the ATS, November 1, 2005; 2(4): 272 - 281. [Abstract] [Full Text] [PDF]
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 M. Cazzola and M. G. Matera Long-Acting Bronchodilators Are the First-Choice Option for the Treatment of Stable COPD Chest, January 1, 2004; 125(1): 9 - 11. [Full Text] [PDF]
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