Kharitonov S A, Yates D H, Barnes P J
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Am J Respir Crit Care Med. 1996 Jan;153(1):454-7. doi: 10.1164/ajrccm.153.1.8542158.
Exhaled nitric oxide (NO) is elevated in untreated patients with asthma but not in patients treated with inhaled glucocorticoids. This may reflect an inhibitory effect of glucocorticoids on the induction of the enzyme NO synthase in the respiratory tract. We have now studied the effect of an inhaled glucocorticoid (budesonide 800 micrograms twice daily via a dry powder delivery system for 3 wk) on exhaled NO in 11 patients with mild asthma in a double-blind crossover randomized-order placebo-controlled study. Exhaled NO was reduced from a baseline value of 203 +/- 29 parts per billion (ppb) to 120 +/- 26 ppb after 3 wk of treatment (p < 0.01), whereas there was no change after a matched placebo (169 +/- 20 at baseline compared with 184 +/- 16 ppb after 3 wk). A significant and progressive fall in exhaled NO was found from 1 to 3 wk. There was no significant change in FEV1 after inhaled steroids (although mean FEV1 was 92% predicted normal at baseline), although there was a reduction in airway responsiveness to methacholine (approximately 2.5 doubling dilutions). These results add further support to the view that the elevated levels of exhaled NO in asthma may derive from induction of an inducible isoform of NO synthase and indicate that exhaled NO may be a useful way of monitoring the anti-inflammatory effects of glucocorticoids and other anti-inflammatory treatments in asthma.
哮喘未治疗患者呼出的一氧化氮（NO）水平升高，但吸入糖皮质激素治疗的患者则不然。这可能反映了糖皮质激素对呼吸道中一氧化氮合酶诱导的抑制作用。我们现在在一项双盲交叉随机顺序安慰剂对照研究中，研究了吸入糖皮质激素（布地奈德800微克，通过干粉给药系统，每日两次，共3周）对11例轻度哮喘患者呼出NO的影响。治疗3周后，呼出NO从基线值203±29十亿分之一（ppb）降至120±26 ppb（p<0.01），而匹配的安慰剂治疗后无变化（基线时为169±20，3周后为184±16 ppb）。从第1周到第3周，呼出NO显著且逐渐下降。吸入类固醇后FEV1无显著变化（尽管基线时平均FEV1为预测正常值的92%），尽管气道对乙酰甲胆碱的反应性有所降低（约2.5倍稀释）。这些结果进一步支持了以下观点：哮喘患者呼出NO水平升高可能源于诱导型一氧化氮合酶同工型的诱导，并表明呼出NO可能是监测糖皮质激素和其他抗炎治疗在哮喘中抗炎作用的有用方法。
