Acute effects of aerosolized S-nitrosoglutathione in cystic fibrosis
Acute effects of aerosolized S-nitrosoglutathione in cystic fibrosis
复制标题
DOI：
10.1164/ajrccm.165.7.2105032
复制
发表时间：
2002-04-01
影响因子：
24.7
通讯作者：
Gaston, B
中科院分区：
文献类型：
--
作者：
Snyder, AH;McPherson, ME;Gaston, B
S-亚硝基谷胱甘肽（GSNO）是气道衬里液的天然成分，可增强纤毛运动，松弛气道平滑肌，抑制气道上皮阿米洛利敏感性钠转运，并防止病原体复制。值得注意的是，囊性纤维化（CF）患者的气道GSNO水平较低。我们假设气道GSNO的替代会改善CF的气体交换。在一项双盲、安慰剂对照研究中，我们通过气雾剂向CF患者施用0.05 ml/kg的10 mM GSNO或磷酸盐缓冲盐水，并随后进行氧饱和度、肺量计、呼吸率、血压、心率和呼出的一氧化氮（NO）。9名患者接受GSNO，11名患者接受安慰剂。在所有时间点，GSNO吸入与氧饱和度适度但持续的增加相关。在GSNO治疗的情况下，呼出的NO在低ppb范围内增加，在5分钟时达到峰值，但在30分钟时保持高于基线。无不良反应。我们的结论是，GSNO在CF患者的耐受性良好，并通过一种机制，可能是独立的游离NO改善氧合。此外，GSNO的击穿增加过期NO。我们建议，旨在恢复内源性GSNO水平的治疗CF气道可能值得研究。
S-Nitrosoglutathione (GSNO), a naturally occurring constituent of airway lining fluid, enhances ciliary motility, relaxes airway smooth muscle, inhibits airway epithelial amiloride-sensitive sodium transport, and prevents pathogen replication. Remarkably, airway levels of GSNO are low in patients with cystic fibrosis (CF). We hypothesized that replacement of airway GSNO would improve gas exchange in CF. In a double-blind, placebo controlled study, we administered 0.05 ml/kg of 10 mM GSNO or phosphate buffered saline by aerosol to patients with CF and followed oxygen saturation, spirometry, respiratory rate, blood pressure, heart rate, and expired nitric oxide (NO). Nine patients received GSNO and 11 placebo. GSNO inhalation was associated with a modest but sustained increase in oxygen saturation at all time points. Expired NO increased in the low ppb range with GSNO treatment, peaking at 5 minutes but remaining above baseline at 30 minutes. There were no adverse effects. We conclude that GSNO is well tolerated in patients with CF and improves oxygenation through a mechanism that may be independent of free NO. Further, GSNO breakdown increases expired NO. We suggest that therapy aimed at restoring endogenous GSNO levels in the CF airway may merit study.