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The Effects of the Combination of Inhaled Ipratropium and Oral Theophylline in Asthma FREE TO VIEW

Nausherwan K. Burki
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From the Division of Pulmonary and Critical Care Medicine, University of Kentucky Medical Center, Lexington

1997 by the American College of Chest Physicians

Chest. 1997;111(6):1509-1513. doi:10.1378/chest.111.6.1509
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Background: In comparison to β-agonist drugs, which are the primary bronchodilator drugs in current use in asthma, both oral theophylline and inhaled ipratropium have a weaker bronchodilating action in asthma. Although a number of studies have shown an additive effect of ipratropium in combination with β-agonist bronchodilator drugs in asthmatics, to our knowledge, the effects of combined treatment with ipratropium and theophylline have not been assessed.

Study objective: To assess whether the combination of oral theophylline and inhaled ipratropium has an additive bronchodilator effect in asthmatics.

Design: Double-blind, placebo-controlled, crossover study.

Subjects: Nineteen patients (8 male, 11 female) with mild-to-moderate stable asthma.

Methods: Initially the optimal single oral dose of theophylline required to achieve therapeutic blood levels (10 to 20 µg/mL) was established in each patient. They then returned at varying intervals on 4 subsequent days. On each day, they received, in a random, placebo-controlled, double-blind, crossover design, one of four different therapies: oral and inhaled placebo; oral theophylline at the established optimal dose (range, 300 to 700 mg) plus inhaled placebo; oral placebo plus inhaled (40 µg) ipratropium; and the combination of theophylline and ipratropium. Spirometry was performed at baseline and at 15 min, 30 min, and hourly intervals for 6 h after therapy.

Results: Each drug regimen resulted in a significant (p<0.05) increase in FEV1, but the combined regimen resulted in a significantly greater bronchodilation (p<0.05) over either ipratropium or theophylline alone (FEV1=3.00±0.75 L vs 2.48±0.77 L vs 2.61±0.72 L, respectively, at 3 h postdrug).

Conclusions: There was a significant, early, sustained additive bronchodilator effect of the combination therapy; there were no untoward side effects. These findings indicate that the addition of inhaled ipratropium to oral theophylline provides greater bronchodilation than either drug alone and may be a useful therapeutic modality in asthma.




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