Inhaled mannitol for the treatment of mucociliary dysfunction- Its effect and mechanisms on the clearance of mucus

粘液分泌过多是哮喘和支气管扩张的一个问题。粘液是由粘膜下腺和杯状细胞分泌的，是气道炎症的结果。过多的粘液不容易通过气道中的纤毛（毛发状结构）运输，积聚导致咳嗽和反复感染。当黏液纤毛系统失效时，咳嗽是清除黏液的次要机制。咳嗽产生高气流速率，可以移动粘液。然而，中度至重度气道阻塞的患者不能产生高气流速率。此外，如果粘液粘稠，咳嗽在移动粘液方面变得非常低效。由于纤毛不能运输大量粘液，最好的方法是改变粘液的性质，以促进咳嗽的清除。黏液水化程度的增加可改变其表面和流变特性。增加水合作用可以通过水的渗透运动进入气道管腔，以响应吸入盐或糖的气溶胶。我们有证据表明，使用放射性气雾剂，甘露醇，一种糖，可以在分泌物过多的病人中急剧增加粘液的清除。我们也有新的证据表明，每天服用甘露醇超过两周会增加支气管扩张患者的健康状况。此外，我们现在有初步的数据表明甘露醇改变了黏液的表面性质。我们的目的是研究黏液的性质及其在人体内的清除。这是前所未有的。如果我们能证明甘露醇对清除率的影响与黏液的变化有关，那么我们就能很容易地评估目前对分泌物过多患者的治疗方法和剂量，并确定新的治疗方法。甘露醇是一种治疗分泌过多疾病的潜在药物，了解它的工作原理有望为患者带来更好的结果。

Excessive secretion of mucus is a problem in asthma and bronchiectasis. Mucus is secreted from submucosal glands and goblet cells as a result of inflammation present in the airways. Excessive mucus is not easily transported by the cilia (hair like structures) in the airways and accumulation leads to productive cough and to recurrent infections. Cough is a secondary mechanism to clear mucus when the mucociliary system fails. Cough generates high airflow rates that can move mucus. However, patients with moderately to severely obstructed airways cannot generate high airflow rates. In addition, cough becomes very inefficient in moving mucus if it is sticky and viscous. As the cilia cannot transport large quantities of mucus the best approach is to alter the properties of mucus that would facilitate cough clearance. Increased hydration of mucus could change its surface and rheological properties. Increased hydration can be achieved by the osmotic movement of water into the airway lumen in response to inhaling an aerosol of salt or sugar. We have evidence using radioactive aerosols, that mannitol, a sugar, increases clearance of mucus acutely in patients with excessive secretions. We also have new evidence that mannitol taken daily over two weeks increases the health status in patients with bronchiectasis. Further we now have preliminary data demonstrating that mannitol changes the surface properties of mucus. We aim to study the properties of mucus in relation to its clearance in vivo in humans. This has not been done before. If we can demonstrate that changes in clearance in response to mannitol relate to the changes in mucus then we will be able to easily evaluate current treatments and doses for patients with excessive secretions and to identify new treatments. Mannitol is a potential treatment for diseases with excessive secretions and understanding of how it works will hopefully lead to better outcomes for patients.