Journal article
Structural and cellular mechanisms of airway mucus plugging in the larger airways
Chinese medical journal pulmonary and critical care medicine, Vol.4(2)
06/10/2026
DOI: 10.1016/j.pccm.2026.05.001
PMID: 42396192
Abstract
Intractable mucus plugging drives mortality in cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD). While surface metaplasia narrows small airways, the massive volumetric reservoir capacity of hypertrophied submucosal glands (SMGs) dictates catastrophic mucus plugging in the larger airways. This review proposes a flush-load model to explain this structural failure: a biophysical imbalance in which SMG serous fluid secretion (the flush) is insufficient to hydrate and clear the burden of high-molecular-weight mucins (the load), leading to osmotic compression, ciliary collapse, and intractable luminal occlusion. The review delineates the disease-specific etiologies of this imbalance. In CF, dysfunction of ion channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channels (ENaC), causes mechanical uncoupling and mucin 5B (MUC5B) tethering to glandular ducts. In asthma, Type 2 inflammation disrupts the glandular stem cells, driving an explosive release of mucin. In COPD, epidermal growth factor receptor (EGFR)-driven remodeling and senescent inflammaging perpetuate chronic hypersecretion. Ultimately, anchored MUC5B strands from hypertrophic SMGs structurally integrate with surface-derived mucin 5AC (MUC5AC), forming an intractable adhesive mesh. Synthesizing these insights, we advocate shifting the therapeutic paradigm from symptomatic downstream clearance to upstream, disease-modifying interventions that target the glandular stem cell niche, restore ion channel homeostasis, and correct coordinated airway surface dysfunction.
Details
- Title: Subtitle
- Structural and cellular mechanisms of airway mucus plugging in the larger airways
- Creators
- Zheqing Hu - Ningxia UniversityLiyuan Yang - University of Alabama at BirminghamYabo Ma - Ningxia UniversityJuan Chen - Ningxia Medical UniversityXiaoming Liu - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Chinese medical journal pulmonary and critical care medicine, Vol.4(2)
- DOI
- 10.1016/j.pccm.2026.05.001
- PMID
- 42396192
- ISSN
- 2097-1982
- eISSN
- 2772-5588
- Publisher
- Elsevier
- Grant note
- National Natural Science Foundation of China: 82460200 Special Project of Central Government Guiding Local Science and Technology Development of Ningxia: 2024FRD05046 Key Research and Development Project of Ningxia: 2023BEG02021, 2025BEG02002 National Science and Technology Major Project of China: 2024ZD0528905 Ningxia Science and Technology Benefits for the People Project: 2025CMG03002 Ningxia Hui Autonomous Region Scientific and Technological Infrastructure Construction Project: 2025DPC05027
This work was funded by National Natural Science Foundation of China (No. 82460200) , Special Project of Central Government Guiding Local Science and Technology Development of Ningxia (No. 2024FRD05046) , Key Research and Development Project of Ningxia (No. 2023BEG02021 and No. 2025BEG02002) , National Science and Technology Major Project of China (No. 2024ZD0528905) , Ningxia Science and Technology Benefits for the People Project (No. 2025CMG03002) , and Ningxia Hui Autonomous Region Scientific and Technological Infrastructure Construction Project (No. 2025DPC05027) .
- Language
- English
- Electronic publication date
- 06/10/2026
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9985175377202771
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