EPITHELIAL ION TRANSPORT DEFECTS IN CYSTIC FIBROSIS: PATHOPHYSIOLOGY AND TREATMENT

覆盖空气通道表面的流体薄层用于保护气道表面免于干燥。这种液体还允许气道细胞顶部的毛发状突起或纤毛更有效地跳动。这种液体的体积和成分由盐和水穿过气道粘膜的运动决定。这种液体的重要性表现在囊性纤维化（CF）中发生的问题，这是影响澳大利亚人的最常见的致命遗传性疾病。在CF中，改变的盐运输导致气道表面干燥，这损害了纤毛的工作。这会导致粘液滞留在气道中，反复的细菌感染会损害肺部。设计了简单的测试，使用细软橡胶管直接测量盐在鼻通道表面的移动。鼻内粘液的移动是使用目前诊断中使用的其他简单技术来测量的。总之，这些鼻子测试提供了有关正常人体气道表面如何移动盐，水和粘液的重要信息。CF患者中发现的任何差异都将使我们对CF肺中发现的问题有一个很好的了解。我们将研究钙，钠和氯化物之间的相互作用，在流体衬里的气道，测量盐和粘液运动的变化。一系列测试程序将用于人类志愿者、麻醉小鼠和羊的分离组织。我们已经证明了气道内衬液体和盐运动之间的重要联系，我们希望这可能会导致囊性纤维化新疗法的发展。这种疗法将侧重于治疗CF患者的肺部问题，这是残疾的主要原因。我们预计这种预防性治疗可能会在治疗CF的斗争中提供真实的益处。

The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, altered salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airway with repeated bacterial infections damaging the lungs. Simple tests have been designed to directly measure the movement of salt across the surface of the nasal passage using a fine soft rubber tube. Movement of mucous in the nose is measured using other simple techniques that are currently used diagnostically. Together, these tests in the nose provide vital information about how the surface of normal human airway moves salt, water and mucous. Any differences found in CF patients will then give us a good idea of the problems found in the CF lung. We will study the interactions between calcium, sodium and chloride in the fluid lining the airways, measuring changes in salt and mucous movement. A range of testing procedures will be used in human volunteers, anaesthetised mice and isolated tissues from sheep. We have already demonstrated important links between the fluid lining the airways and salt movement, and we expect that this may lead to the development of new treatments for Cystic Fibrosis. This therapy will focus on treating the lung problems of CF patients, the major cause of disability. We anticipate that this preventative therapy may offer real benefits in the fight to cure CF.