The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas liquid pumping and cough-dependent mechanisms, and mucus transport rates are heavily dependent on mucus concentration. Importantly, mucus transport rates are accurately predicted by the gel-on-brush model of the mucociliary apparatus from the relative osmotic moduli of the mucus and periciliary-glycocalyceal (PCL-G) layers. The fluid available to hydrate mucus is generated by transepithelial fluid transport. Feedback interactions between mucus concentrations and cilia beating, via purinergic signaling, coordinate Na⁺ absorptive vs Cl^- secretory rates to maintain mucus hydration in health. In disease, mucus becomes hyperconcentrated (dehydrated). Multiple mechanisms derange the ion transport pathways that normally hydrate mucus in muco-obstructive lung diseases, e.g., CF, COPD, NCFB, and PCD. A key step in muco-obstructive disease pathogenesis is the osmotic compression of the mucus layer onto the airway surface with the formation of adherent mucus plaques and plugs, particularly in distal airways. Mucus plaques create locally hypoxic conditions and produce airflow obstruction, inflammation, infection, and, ultimately, airway wall damage. Therapies to clear adherent mucus with hydrating and mucolytic agents are rational, and strategies to develop these agents are reviewed.

中文翻译：

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人类气道粘液的生理学和病理生理学

粘液清除系统是人肺的主要机械宿主防御系统。粘液通过纤毛和气流从肺部清除，包括两相气液泵送和咳嗽依赖性机制，并且粘液转运速率很大程度上取决于粘液浓度。重要的是，粘液转运速率可以通过粘液纤毛器的凝胶刷模型根据粘液和纤毛周围糖萼（PCL-G）层的相对渗透模量准确预测。可用于水合粘液的液体是通过跨上皮液体运输产生的。粘液浓度和纤毛跳动之间的反馈相互作用，通过嘌呤能信号传导，协调 Na ⁺吸收率与 Cl ^-分泌率，以维持健康的粘液水合作用。在疾病中，粘液变得高度浓缩（脱水）。多种机制扰乱了粘液阻塞性肺病（例如 CF、COPD、NCFB 和 PCD）中通常水合粘液的离子转运途径。粘液阻塞性疾病发病机制的一个关键步骤是粘液层渗透压到气道表面，形成粘附的粘液斑和栓塞，特别是在远端气道中。粘液斑块会造成局部缺氧，并产生气流阻塞、炎症、感染，并最终导致气道壁损伤。使用保湿剂和粘液溶解剂清除粘附粘液的疗法是合理的，并且对开发这些药物的策略进行了回顾。