Acid stress in the pathology of asthma
Acid stress in the pathology of asthma
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DOI：
10.1016/j.jaci.2003.12.034
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发表时间：
2004-04-01
影响因子：
14.2
通讯作者：
Hunt, J
中科院分区：
文献类型：
--
作者：
Ricciardolo, FLM;Gaston, B;Hunt, J
虽然气道pH值的改变可能有助于宿主的先天防御能力，但它也涉及阻塞性气道疾病的病理生理学。酸诱导的哮喘似乎与意外吸入酸（雾、污染和工作场所暴露）后的胃食管反流有关，并且存在气道pH稳态改变。内源性和外源性暴露于酸引起咳嗽、支气管收缩、气道高反应性、微血管渗漏以及粘液、液体和一氧化氮的产生增加。呼吸道的异常酸度反映在呼出气测定中。酸诱导的气道阻塞的内在机制依赖于辣椒素敏感的感觉神经的激活。质子激活这些神经，随后释放速激肽（该途径的主要介质），速激肽与激肽、一氧化氮、氧自由基和蛋白酶一起调节气道功能障碍和炎症的各个方面。酸应激可能引发或加重气道阻塞性肺病的认识促使人们考虑针对pH稳态的新疗法。
Although alteration of airway pH may serve an innate host defense capacity, it also is implicated in the pathophysiology of obstructive airway diseases. Acid-induced asthma appears in association with gastroesophageal reflux after accidental inhalation of acid (fog, pollution, and workplace exposure) and in the presence of altered airway pH homeostasis. Endogenous and exogenous exposures to acids evoke cough, bronchoconstriction, airway hyperreactivity, microvascular leakage, and heightened production of mucous, fluid, and nitric oxide. Abnormal acidity of the airways is reflected in exhaled breath assays. The intimate mechanisms of acid-induced airway obstruction are dependent on activation of capsaicin-sensitive sensory nerves. Protons activate these nerves with the subsequent release of tachykinins (major mediators of this pathway) that, in conjunction with kinins, nitric oxide, oxygen radicals, and proteases, modulate diverse aspects of airway dysfunction and inflammation. The recognition that acid stress might initiate or exacerbate airway obstructive symptomatology has prompted the consideration of new therapies targeting pH homeostasis.