The effects of the combination of inhaled ipratropium and oral theophylline in asthma.
BACKGROUND
In comparison to beta-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 beta-agonist bronchodilator drugs in asthmatics, to our knowledge, the effects of combined treatment with ipratropium and theophylline have not been assessed.


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


METHODS
Double-blind, placebo-controlled, crossover study.


METHODS
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 microg/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 microg) 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.
Burki
N K
NK
Division of Pulmonary and Critical Care Medicine, University of Kentucky Medical Center, Lexington 40536, USA.
D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013147:Spirometry / Q000706:statistics & numerical data; D013806:Theophylline / Q000008:administration & dosage*
D001993:Bronchodilator Agents; D013806:Theophylline; D009241:Ipratropium