Related Experiment Video
Updated: Feb 15, 2026
The WinCF Model - An Inexpensive and Tractable Microcosm of a Mucus Plugged Bronchiole to Study the Microbiology of Lung Infections
Published on: May 8, 2017
Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction
Eleanor M Dunican1, Brett M Elicker2, David S Gierada3
1Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, and.
Background:
The link between mucus plugs and airflow obstruction has not been established in chronic severe asthma, and the role of eosinophils and their products in mucus plug formation is unknown.
Methods:
In clinical studies, we developed and applied a bronchopulmonary segment-based scoring system to quantify mucus plugs on multidetector computed tomography (MDCT) lung scans from 146 subjects with asthma and 22 controls, and analyzed relationships among mucus plug scores, forced expiratory volume in 1 second (FEV1), and airway eosinophils. Additionally, we used airway mucus gel models to explore whether oxidants generated by eosinophil peroxidase (EPO) oxidize cysteine thiol groups to promote mucus plug formation.
Results:
Mucus plugs occurred in at least 1 of 20 lung segments in 58% of subjects with asthma and in only 4.5% of controls, and the plugs in subjects with asthma persisted in the same segment for years. A high mucus score (plugs in ≥ 4 segments) occurred in 67% of subjects with asthma with FEV1 of less than 60% of predicted volume, 19% with FEV1 of 60%-80%, and 6% with FEV1 greater than 80% (P < 0.001) and was associated with marked increases in sputum eosinophils and EPO. EPO catalyzed oxidation of thiocyanate and bromide by H2O2 to generate oxidants that crosslink cysteine thiol groups and stiffen thiolated hydrogels.
Conclusion:
Mucus plugs are a plausible mechanism of chronic airflow obstruction in severe asthma, and EPO-generated oxidants may mediate mucus plug formation. We propose an approach for quantifying airway mucus plugging using MDCT lung scans and suggest that treating mucus plugs may improve airflow in chronic severe asthma.
Trial Registration:
Clinicaltrials.gov NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01759186, NCT01716494, and NCT01760915.
Funding:
NIH grants P01 HL107201, R01 HL080414, U10 HL109146, U10 HL109164, U10 HL109172, U10 HL109086, U10 HL109250, U10 HL109168, U10 HL109257, U10 HL109152, and P01 HL107202 and National Center for Advancing Translational Sciences grants UL1TR0000427, UL1TR000448, and KL2TR000428.
Insights
Mucus plugs are common in severe asthma and linked to airflow obstruction. Eosinophil peroxidase may cause these plugs by oxidizing cysteine, suggesting a new treatment target.
Area of Science:
- Pulmonary Medicine
- Respiratory Research
- Asthma Pathophysiology
Background:
- The relationship between mucus plugs and airflow obstruction in chronic severe asthma remains unclear.
- The specific role of eosinophils and their byproducts in mucus plug formation is unknown.
Purpose of the Study:
- To establish the link between mucus plugs and airflow obstruction in severe asthma.
- To investigate the role of eosinophils and eosinophil peroxidase (EPO) in mucus plug formation.
- To develop and validate a method for quantifying mucus plugs using computed tomography (CT) scans.
Main Methods:
- Developed a bronchopulmonary segment-based scoring system to quantify mucus plugs on multidetector computed tomography (MDCT) lung scans.
- Analyzed the association between mucus plug scores, forced expiratory volume in 1 second (FEV1), and airway eosinophil counts in 146 asthma patients and 22 controls.
- Utilized airway mucus gel models to investigate the role of eosinophil peroxidase (EPO) in oxidizing cysteine thiol groups and promoting mucus plug formation.
Main Results:
- Mucus plugs were present in 58% of asthma patients versus 4.5% of controls, persisting in the same lung segments for years.
- A high mucus plug score (≥ 4 segments) was significantly associated with lower FEV1 (P < 0.001) and higher sputum eosinophils and EPO levels.
- In vitro, EPO catalyzed oxidant generation, leading to cysteine thiol group oxidation and stiffening of mucus hydrogels.
Conclusions:
- Mucus plugs are a likely contributor to chronic airflow obstruction in severe asthma.
- Oxidants generated by EPO may play a key role in the formation of mucus plugs.
- Quantification of airway mucus plugging via MDCT is feasible, and targeting mucus plugs could improve airflow in severe asthma.
Related Concept Videos
01:22Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
01:29Asthma-I: Introduction
02:04Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
01:24Asthma-III: Symptoms and Complications
Classification of Asthma
01:30Asthma-IV: Diagnostic and Management
Clinical Assessment for Asthma:
This is the first step in diagnosing and managing asthma. It includes:
01:20Asthma: Pathogenesis and Management
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.