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.