Repetitive viral infection accentuates airway wall remodelling

在哮喘患者中，会发生结构改变或重塑，这被认为是导致呼吸道功能异常的原因。这些发生在哮喘呼吸道的重塑事件包括形成呼吸道支架的蛋白质(细胞外基质ECM蛋白质)沉积增加，以及支气管平滑肌细胞数量增加。这些关键的结构变化中的许多都不能通过目前的哮喘治疗来逆转或预防。重塑是哮喘发生发展过程中的一个重要过程。哮喘患者肺部发生重塑的原因尚不清楚。人们认为，持续的炎症推动了重塑过程；然而，重塑可以使炎症永久化，从而产生一系列循环事件。此外，我们还发现，在哮喘患者的ECM上生长的非哮喘志愿者的细胞会变得更像哮喘患者的细胞。感染肺部的病毒可能在哮喘的发展中发挥作用，并在观察到的重塑增加中发挥作用。许多常见的呼吸道病毒能够感染肺部细胞，例如上皮细胞，这会引起炎症反应。我将使用从哮喘和非哮喘志愿者身上分离的肺细胞来研究病毒感染是否会改变重塑过程。此外，我将评估目前和新的治疗方法是否在减少重塑过程方面有效。我们有初步证据表明，鼻病毒(普通感冒病毒)感染肺上皮细胞会改变这些细胞沉积的细胞外基质的数量。我假设，与非哮喘患者相比，患有哮喘的志愿者的细胞中这一过程会增加。由于目前的疗法不太可能逆转这些重塑事件，这些实验将使能够针对呼吸道疾病这一重要方面的新疗法的开发成为可能。

In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an important process in both the development and progression of asthma. The reason why remodelling occurs in the lungs of people with asthma is not known. It is thought that persistent inflammation drives the remodelling process; however remodelling can perpetuate inflammation, thereby creating a cyclic series of events. Furthermore we have shown that cells from non-asthmatic volunteers which are grown on asthmatic ECM change to become more like cells from asthmatic subjects. Viruses which infect the lungs may play a role in the development of asthma, and in the increased remodelling which is observed. Many common respiratory viruses are capable of infecting lung cells, eg epithelial cells, which evokes an inflammatory response. I will investigate if viral infection can alter the remodelling process, using lung cells isolated from asthmatic and non-asthmatic volunteers. Furthermore, I will assess if current and novel treatments are effective in reducing the remodelling process. We have preliminary evidence that infection of lung epithelial cells with rhinovirus (the common cold virus) alters the amount of ECM deposited by these cells. I hypothesise that this process will be increased in cells from volunteers with asthma compared to non-asthma. As current therapeutics are unlikely to be able to reverse these remodelling events these experiments will enable the development of new therapeutics which can target this important aspect of airway disease.