Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction.
AuthorDunican, Eleanor M
Elicker, Brett M
Gierada, David S
Nagle, Scott K
Schiebler, Mark L
Newell, John D
Raymond, Wilfred W
Lachowicz-Scroggins, Marrah E
Di Maio, Selena
Hoffman, Eric A
Fain, Sean B
Jarjour, Nizar N
Levy, Bruce D
Erzurum, Serpil C
Wenzel, Sally E
Meyers, Deborah A
Bleecker, Eugene R
Phillips, Brenda R
Mauger, David T
Gordon, Erin D
Woodruff, Prescott G
Peters, Michael C
Fahy, John V
AffiliationUniv Arizona, Dept Med, Div Genet Genom & Precis Med
MetadataShow full item record
PublisherAMER SOC CLINICAL INVESTIGATION INC
CitationJ Clin Invest. 2018;128(3):997-1009. https://doi.org/10.1172/JCI95693.
RightsCopyright © 2018, American Society for Clinical Investigation
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractThe 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. 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. 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. 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.
VersionFinal published version
SponsorsNational Institutes of Health
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- Issue date: 2018 Nov
- Correlation of nasal inflammation and nasal airflow with forced expiratory volume in 1 second in patients with perennial allergic rhinitis and asthma.
- Authors: Ciprandi G, Cirillo I, Vizzaccaro A, Milanese M, Tosca MA
- Issue date: 2004 Dec
- Childhood-onset asthma in smokers. association between CT measures of airway size, lung function, and chronic airflow obstruction.
- Authors: Diaz AA, Hardin ME, Come CE, San José Estépar R, Ross JC, Kurugol S, Okajima Y, Han MK, Kim V, Ramsdell J, Silverman EK, Crapo JD, Lynch DA, Make B, Barr RG, Hersh CP, Washko GR, COPDGene Investigators.
- Issue date: 2014 Nov
- Parameters associated with persistent airflow obstruction in chronic severe asthma.
- Authors: Bumbacea D, Campbell D, Nguyen L, Carr D, Barnes PJ, Robinson D, Chung KF
- Issue date: 2004 Jul
- Plugs of the Air Passages: A Clinicopathologic Review.
- Authors: Panchabhai TS, Mukhopadhyay S, Sehgal S, Bandyopadhyay D, Erzurum SC, Mehta AC
- Issue date: 2016 Nov