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

粘液过度分泌是哮喘和支气管扩张症的一个问题。粘液由粘膜下腺和杯状细胞分泌，是呼吸道炎症的结果。过多的粘液不容易被呼吸道中的纤毛(毛发状结构)运输，积聚会导致生产性咳嗽和反复感染。当粘液纤毛系统衰竭时，咳嗽是清除粘液的第二种机制。咳嗽会产生较高的气流速度，可以移动粘液。然而，中度到重度阻塞的患者不能产生高气流速度。此外，如果咳嗽粘稠，那么它在移动粘液方面就会变得非常低效。由于纤毛不能运输大量的粘液，最好的方法是改变粘液的性质，以促进咳嗽的清除。粘液水化程度的增加会改变其表面性质和流变性。吸入盐或糖的气雾剂后，水通过渗透运动进入气道腔，从而增加水合作用。我们有证据表明，使用放射性气雾剂的甘露醇，一种糖，可以显著增加过度分泌物患者对粘液的清除。我们也有新的证据表明，在两周内每天服用甘露醇可以增加支扩患者的健康状况。此外，我们现在有初步数据表明，甘露醇改变了粘液的表面性质。我们的目标是研究粘液的性质与其在人体内的清除有关。这是以前从未做过的。如果我们能够证明甘露醇引起的清除变化与粘液的变化有关，那么我们将能够很容易地评估目前对过度分泌物患者的治疗方法和剂量，并找到新的治疗方法。甘露醇是一种潜在的治疗分泌物过多的疾病的方法，对其作用机制的了解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.