A COMPARISON OF THE EFFECTS OF ANTICHOLINERGIC AND BETA-2-AGONIST AND COMBINATION THERAPY ON RESPIRATORY IMPEDANCE IN COPD

The effects of three different regimens of inhaled bronchodilators on spirometry and respiratory impedance as measured with the technique of forced oscillations were compared in a double-blind crossover study in 22 patients with stable chronic obstructive pulmonary disease (FEV1 < 70 percent predicted). On three trial days, patients inhaled, in random order, 40-mu-g ipratropium bromide, 200-mu-g fenoterol hydrobromide, or a combination of 40-mu-g ipratropium and 100-mu-g fenoterol from a powder inhaler, followed by a second dose of the same drug after 60 min. The effects were measured at baseline and 20, 40, 60, and 120 min after the first inhalation. No significant decrease in total respiratory resistance at 8 Hz (Rrs [8]) was observed after ipratropium, whereas Rrs (8) decreased significantly 20 min after fenoterol and 40 min after the combination regimen (p < 0.05). All three studied drugs resulted in a significant increase in the reactance (p < 0.01) and decrease in resonant frequency. Both fenoterol (DELTA-FEV1 34 percent, p < 0.001) and the combination regimen (DELTA-FEV1 38 percent, p < 0.0001) resulted in a significantly larger increase in FEV1 than ipratropium alone (DELTA-FEV1 17 percent, p < 0.0001). A second dose of fenoterol and of the combination regimen resulted in a further significant increase in FEV1 after 120 min (p < 0.05). A second dose of ipratropium did not result in a further significant increase in FEV1. The changes in respiratory impedance were qualitatively similar for all three drug regimens, but larger in absolute terms after fenoterol and the combination regimen than after ipratropium. The similar effect of these drugs on the reactance can be explained by an increase in the capacitance of the respiratory system, and in combination with a decrease in frequency dependence of resistance, by assuming a decrease in peripheral airway resistance.