Endogenous airway acidification - Implications for asthma pathophysiology
Endogenous airway acidification - Implications for asthma pathophysiology
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DOI：
10.1164/ajrccm.161.3.9911005
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发表时间：
2000-03-01
影响因子：
24.7
通讯作者：
Gaston, B
中科院分区：
文献类型：
--
作者：
Hunt, JF;Fang, KZ;Gaston, B
哮喘患者气道中许多活性氮和氧的浓度很高。这些物种的稳定性和生物活性是ph依赖性的；然而，急性哮喘期间气道的pH值以前没有研究过。与胃和尿酸化一样，哮喘气道酸化可能会显著改变内源性氮氧化物的浓度和生物活性/细胞毒性。在这里，我们证明急性哮喘患者（5.23 +/- 0.21,n = 22）比对照组（7.65 +/- 0.20,n = 19, p < 0.001）低两个log数量级以上，并在皮质类固醇治疗后恢复正常。数值具有高度可重复性，不受唾液或治疗伪影的影响，并且与直接从下气道采集的样本相同。此外，在这些低pH值下，内源性气道化合物亚硝酸盐被转化为一氧化氮（NO），其数量足以在很大程度上解释哮喘呼气中NO的浓度，并且嗜酸性粒细胞加速坏死。我们推测气道pH值可能是一氧化氮浓度和气道炎症的重要决定因素，并提示气道pH值的调节在哮喘病理生理中具有先前未被发现的作用。
Airway concentrations of many reactive nitrogen and oxygen species are high In asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivites/cytotoxicities of endogenous nitrogen oxides. Here, we demonstrate that the pH of deaerated exhaled airway vapor condensate is over two log orders lower in patients with acute asthma (5.23 +/- 0.21, n = 22) than in control subjects (7.65 +/- 0.20, n = 19, p < 0.001) and normalizes with corticosteroid therapy. Values are highly reproducible, unaffected by salivary or therapeutic artifact, and identical to samples taken directly from the lower airway. Further, at these low pH values the endogenous airway compound, nitrite, is converted to nitric oxide (NO) in quantities sufficient largely to account for the concentrations of NO in asthmatic expired air, and eosinophils undergo accelerated necrosis. We speculate that airway pH may be an important determinant of expired NO concentration and airway inflammation, and suggest that regulation of airway pH has a previously unsuspected role in asthma pathophysiology.