The development of subsensitivity to atropine methylnitrate. A double-blind, placebo-controlled crossover study

This is a double-blind, placebo-controlled crossover study designed to assess the effectiveness of nebulized atropine methylnitrate (AMN) with chronic use. We studied 22 patients with asthma, 10 receiving theophylline and inhaled beta-agonists and 12 who were receiving corticosteroids as well. All had demonstrated at least a 15% change in FEV1 either spontaneously or after bronchodilator. Bronchodilator effect was measured serially for 4 h after inhalation of the initial dose and again after 2 wk of four-times-daily use. Significant bronchodilator effect was seen initially with AMN when compared to placebo (p less than 0.01). After 2 wk of use, the bronchodilator effect of AMN was significantly diminished as compared to the initial effect (p less than 0.01) but was still better than placebo (p less than 0.05). Subsensitivity did develop to varying degrees in the patients, but we were unable to identify any clinical parameters that would allow prediction of subsequent subsensitivity. We conclude that the development of subsensitivity to AMN occurs in certain patients with chronic administration but does not reflect a total loss of bronchodilator effect.