Nitrogen oxides reduce albuterol-induced bronchodilation in patients with bronchial asthma

Background: We have previously found that asthmatics exhibit higher levels of nitrogen oxides (NOs) in exhaled air and in induced sputum than normal controls, and that NOs altered beta(2)-adrenoceptor (beta(2)-AR) function in an experimental animal model.

Objectives: To determine whether NOs influence the bronchodilator activity of albuterol in asthmatic patients.

Methods: We simultaneously measured the levels of NOs in exhaled air and in induced sputum in 20 asthmatic patients. The bronchodilator activity of albuterol was expressed as spontaneous recovery (before methacholine) and recovery from the lowest value in FEV(1) evoked by the methacholine challenge (after methacholine). After the first study, 400 microg of beclomethasone dipropionate (BDP) was administered twice daily for 1 week to all patients, and the above-mentioned protocols were repeated.

Results: The recovery of FEV(1) (before methacholine) after albuterol was not significantly correlated with either baseline FEV(1) or PC(20) methacholine. Nor was the recovery of FEV(1) (after methacholine) after albuterol significantly correlated with the maximal fall in FEV(1) after the methacholine challenge and PC(20) methacholine. However, the recovery of FEV(1) after albuterol was inversely correlated with the nitric oxide levels in exhaled air (before methacholine: r = -0.556, p = 0.0151; after methacholine: r = -0.684, p = 0.0028), and the concentration of nitrite and nitrate in induced sputum (before methacholine: r = -0.459, p = 0.0448; after methacholine: r = -0.830, p = 0.0003). After treatment with inhaled BDP for 1 week, there was no significant change in baseline FEV(1). However, there was a significant decrease in the concentration of nitrite and nitrate in induced sputum (p < 0.0001). The changes in nitrite and nitrate levels in induced sputum after 1 week of BDP therapy were significantly correlated with the changes in bronchodilator activity of albuterol before and after BDP therapy (before methacholine: r = 0.704, p = 0.0022; after methacholine: r = 0.727, p = 0.0015).

Conclusions: We demonstrated that NOs in the airways reduced albuterol-induced bronchodilation in asthmatics.