Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, USA.
Pulm Pharmacol Ther. 2013 Oct;26(5):510-3. doi: 10.1016/j.pupt.2013.02.003. Epub 2013 Feb 19.
A variety of foreign "invaders" such as viruses, bacteria and other particulates e.g., cigarette smoke, are inhaled, deposit on the airway surface and invade the "host." Mucins produced by the surface airway epithelium and by the submucosal glands are secreted into the airway lumen. Deposited particulates adhere to the mucus and are cleared via mucociliary transport and via cough. Mucins are major constituents of mucus, which is important in the clearance of inhaled materials. Normally, secreted mucus is cleared without symptoms or interference with lung function. However, in obstructive airway diseases such as COPD, asthma, and cystic fibrosis, excessive mucus is produced. Because of the prominence of mucous hypersecretion as a cause of cough, this discussion focuses on mechanisms regulating normal production of mucins and the mechanisms underlying exaggerated mucin secretion in chronic obstructive airway diseases. Mucins are produced by airway epithelial cells via a cascade of signals (the Epidermal Growth Factor Cascade) and secreted on the luminal epithelial surface, often in response to the deposition of inhaled irritants. Normally, only minimal amounts of mucins are secreted, which assist in clearance of the inhaled particulates. However, in disease, additional pathways are induced via positive feedback systems, which lead to mucous hypersecretion. In the large conducting airways, where cough receptors are concentrated, mucous hypersecretion causes stimulation of neural receptors that result in cough. However, in small airways (e.g., bronchioles), because of their small diameters, mucous hypersecretion leads to plugging of the airways. Because there are so many small airways, their plugging is difficult to detect early, and this locus is known as a "silent zone." In chronic obstructive airway diseases, plugging of small airways may persist and increase over time, finally resulting in severe airway obstruction. Different obstructive airway diseases induce inflammatory signaling (including mucous hypersecretion) via different stimuli, but often via similar signaling pathways. Application of present knowledge of signaling that occurs with mucous hypersecretion can lead to novel therapies for hypersecretion and cough induced in conducting airways and could prevent plugging in small airways that can lead to clinical deterioration and death.
各种外来“侵略者”，如病毒、细菌和其他颗粒物（如香烟烟雾）被吸入，沉积在气道表面并侵入“宿主”。表面气道上皮和黏膜下腺产生的黏蛋白分泌到气道腔中。沉积的颗粒物附着在黏液上，并通过黏液纤毛运输和咳嗽清除。黏蛋白是黏液的主要成分，对吸入物质的清除很重要。通常，分泌的黏液在没有症状或不干扰肺功能的情况下被清除。然而，在阻塞性气道疾病（如 COPD、哮喘和囊性纤维化）中，会产生过多的黏液。由于黏液过度分泌是咳嗽的主要原因，因此本文重点讨论了调节正常黏蛋白产生的机制以及慢性阻塞性气道疾病中黏液过度分泌的机制。黏蛋白由气道上皮细胞通过一系列信号（表皮生长因子级联）产生，并在腔上皮表面分泌，通常是对吸入刺激物的沉积做出反应。正常情况下，只有少量的黏蛋白被分泌，这些黏蛋白有助于清除吸入的颗粒物。然而，在疾病中，通过正反馈系统诱导了额外的途径，导致黏液过度分泌。在大的传导气道中，咳嗽感受器集中，黏液过度分泌会刺激神经受体，导致咳嗽。然而，在小气道（如细支气管）中，由于其直径较小，黏液过度分泌会导致气道堵塞。由于有如此多的小气道，它们的堵塞很难早期发现，这个部位被称为“沉默区”。在慢性阻塞性气道疾病中，小气道的堵塞可能会随着时间的推移而持续增加，最终导致严重的气道阻塞。不同的阻塞性气道疾病通过不同的刺激物诱导炎症信号（包括黏液过度分泌），但通常通过相似的信号通路。应用目前对黏液过度分泌发生的信号的认识，可以为传导气道中的过度分泌和咳嗽提供新的治疗方法，并可以防止导致临床恶化和死亡的小气道堵塞。
