Repetitive viral infection accentuates airway wall remodelling

哮喘肺发生结构改变或重塑，这被认为是气道功能异常的原因。哮喘气道发生的这些重塑事件包括形成气道支架的蛋白质沉积增加（细胞外基质ECM蛋白）和支气管平滑肌细胞质量增加。目前的哮喘治疗无法逆转或预防这些关键的结构变化。重塑是哮喘发生和发展的重要过程。哮喘患者肺部发生重塑的原因尚不清楚。据认为，持续的炎症驱动了重塑过程；然而，重塑可以使炎症长期存在，从而产生一系列循环事件。此外，我们已经证明，来自非哮喘志愿者的细胞在哮喘的ECM上生长，变得更像来自哮喘受试者的细胞。感染肺部的病毒可能在哮喘的发展中发挥作用，并在观察到的增加的重塑中发挥作用。许多常见的呼吸道病毒能够感染肺细胞，如上皮细胞，从而引起炎症反应。我将研究病毒感染是否可以改变重塑过程，使用从哮喘和非哮喘志愿者身上分离的肺细胞。此外，我将评估当前和新的治疗方法是否有效地减少重塑过程。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ECM的数量。我推测，与非哮喘志愿者相比，哮喘志愿者的细胞中这个过程会增加。由于目前的治疗方法不太可能逆转这些重塑事件，这些实验将使开发新的治疗方法能够针对气道疾病的这一重要方面。

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.