NEW STRATEGY BASED ON REGULATION OF OXTPATIVE STRESS IN TREATMENT OF BRONCHIAL ASTHMA

我们先前发现，哮喘患者呼出的空气和诱导痰中的氮氧化物含量高于正常对照组，并且在实验动物模型中，氮氧化物改变了β_2 -肾上腺素能受体（β_-AR）的功能。因此，本研究旨在确定氮氧化物是否影响哮喘患者β_2-AR激动剂的支气管扩张活性。我们同时测量了20名哮喘患者呼出空气和诱导痰中的氮氧化物水平。β_2-AR激动剂的支气管扩张活性表现为自发恢复（乙酰胆碱前）和从乙酰胆碱激发引起的FEV1最低值恢复（乙酰胆碱后）。在第一次研究后的1周内，所有患者均给予400 μg二丙酸倍氯米松（BDP），每日2次，并重复上述方案。β_2-AR激动剂后FEV1（前甲胆碱）的恢复与任何基线FEV1和PC20甲胆碱均无显著相关。此外，β_2-AR激动剂后FEV1的恢复与乙酰胆碱刺激后FEV1的最大下降和乙酰胆碱PC20的最大下降也没有显著相关。然而，β_2-AR激动剂后FEV1的恢复与呼出空气中NO水平以及诱导痰中亚硝酸盐和硝酸盐浓度呈负相关。吸入BDP治疗1周后，基线FEV1无显著变化。诱导痰中亚硝酸盐和硝酸盐浓度明显降低。我们发现，BDP治疗1周后诱导痰中亚硝酸盐和硝酸盐水平的变化与BDP治疗前后β_2-AR激动剂支气管扩张活性的变化显著相关。我们确定气道中的氮氧化物降低了哮喘患者β_2-AR激动剂诱导的心肌舒张。

We have previously found that higher levels of nitrogen oxides in exhaled air and in induced sputum were found in asthmatics compared to normal control subjects, and that nitrogen oxides altered β_2 -adrenoceptor (β_-AR) function in an experimental animal model. Therefore, this study was designed to determine whether nitrogen oxides influence the bronchodilating activity of β_2-AR agonists in asthmatic patients. We simultaneously measured the levels of nitrogen oxides in exhaled air and in induced sputum in 20 asthmatic patients. The bronchodilating activity of β_2-AR agonists was expressed as a spontaneous recovery (pre- raethacholine) and recovery from the lowest value in FEV1 evoked by methacholine challenge (post-methacholine). For 1-week after the first study, 400 μg of beclomethasone dipropionate (BDP) twice daily was administered for all patients, and the above mentioned protocols were repeated. Recovery in FEV1 (pre-methacholine) after β_2-AR agonists was not significantly correlated with any baseline FEV1 and PC20 methacholine. Moreover, recovery in FEV1 (post-methacholine) after β_2-AR agonists was not also significantly correlated with maximal fall in FEV1 after methacholine challenge and PC20 methacholine. However, recovery in FEV1 after β_2-AR agonists was inversely correlated with NO levels in exhaled air, and concentration of nitrite and nitrate in induced sputum. After treatment with inhaled BDP for 1-week, there was no significant change in baseline FEV1. However, there was a significant decrease in the concentration of nitrite and nitrate in induced sputum. We found that change of nitrite and nitrate levels in induced sputum after 1-week BDP therapy was significantly correlated with change in bronchodilating activity of β_2-AR agonists between pre- and post-BDP therapy. We determined that nitrogen oxides in the airways reduced β_2-AR agonists-induced brochodilation in asthmatics.