Physiology and pathophysiology of human airway mucus.
Journal Article (Review;Journal Article)
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., cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis (NCFB), and primary ciliary dyskinesia (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.
Full Text
Duke Authors
Cited Authors
- Hill, DB; Button, B; Rubinstein, M; Boucher, RC
Published Date
- October 2022
Published In
Volume / Issue
- 102 / 4
Start / End Page
- 1757 - 1836
PubMed ID
- 35001665
Pubmed Central ID
- PMC9665957
Electronic International Standard Serial Number (EISSN)
- 1522-1210
International Standard Serial Number (ISSN)
- 0031-9333
Digital Object Identifier (DOI)
- 10.1152/physrev.00004.2021
Language
- eng