哮喘联盟

   摘要
   气道平滑肌（ASM）是支气管收缩通路的效应细胞。据认为，哮喘患者的支气管收缩与气道内环境的变化有关，会影响ASM兴奋 - 收缩偶联和Ca2 +摄取。哮喘患者对机械通气张力也有不同的反应。健康人深吸气（DI）会产生支气管扩张，而对哮喘患者效果较差，甚至会增加中、重度哮喘患者的支气管收缩。我们的实验室先前研究了气道拉伸激活收缩（Rstretch）导致DI-诱发支气管收缩的机械应力转换途径。我们还证实了激动剂通过作用于血栓素A2（TXA2）受体来放大呼吸道Rstretch反应的能力。尽管支气管收缩中有兴奋性前列腺素的参与，以TXA2合成酶抑制剂和TP受体拮抗剂为靶点的临床实验产生了不同的结果。针对西方人群的研究大多产生阴性结果，而在亚洲人群中进行的研究大多显示为阳性结果。在此篇综述中，我们将探讨TXA2合成酶抑制剂和TP-受体拮抗剂在哮喘治疗中的作用。我们列出了关于研究设计的变化和TP-受体基因多态性在以前显示差异信息的研究中可能发挥的作用。也许，未来的研究应尤其注重对DI-诱发支气管收缩哮喘患者的研究，为哮喘患者的个体化治疗奠定基础。

 

  （杨冬 审校）
Can J Physiol Pharmacol. 2014 Dec 9:1-7. [Epub ahead of print]


 

Revisiting the usefulness of thromboxane-A2 modulation in the treatment of bronchoconstriction in asthma.
 

Hernandez JM1, Janssen LJ.
 

Abstract
Airway smooth muscle (ASM) is the effector cell in the bronchoconstrictory pathway. It is believed that the bronchoconstriction present in asthma is associated with changes in the airway milieu that affect ASM excitation-contraction coupling and Ca2+-handling. Asthmatics also react differently to ventilatory mechanical strain. Deep inspiration (DI), which produces bronchodilation in healthy individuals, is less effective in asthmatics, and even enhances bronchoconstriction in moderate to severely affected patients. Our laboratory has previously studied the mechanotransductory pathway of airway stretch-activated contractions (Rstretch) leading to DI-induced bronchoconstriction. We demonstrated the ability of agonists acting through thromboxane A2 (TxA2) receptors to amplify airway Rstretch responses. Despite the involvement of excitatory prostanoids in bronchoconstriction, clinical trials on treatments targeting TxA2-synthase inhibition and TP-receptor antagonism have produced mixed results. Studies in Western populations produced mostly negative results, whereas studies performed in Asian populations showed mostly positive outcomes. In this review, we discuss the role of TxA2-synthase inhibition and TP-receptor antagonism in the treatment of asthmatics. We present information regarding variations in study designs and the possible role of TP-receptor gene polymorphisms in previous study outcome discrepancies. Perhaps future studies should focus on asthmatic patients with DI-induced bronchoconstriction in particular, planting the seed for the individualized treatments for asthmatics.
 

Can J Physiol Pharmacol. 2014 Dec 9:1-7. [Epub ahead of print]