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dc.contributor.authorDunican, Eleanor M
dc.contributor.authorElicker, Brett M
dc.contributor.authorGierada, David S
dc.contributor.authorNagle, Scott K
dc.contributor.authorSchiebler, Mark L
dc.contributor.authorNewell, John D
dc.contributor.authorRaymond, Wilfred W
dc.contributor.authorLachowicz-Scroggins, Marrah E
dc.contributor.authorDi Maio, Selena
dc.contributor.authorHoffman, Eric A
dc.contributor.authorCastro, Mario
dc.contributor.authorFain, Sean B
dc.contributor.authorJarjour, Nizar N
dc.contributor.authorIsrael, Elliot
dc.contributor.authorLevy, Bruce D
dc.contributor.authorErzurum, Serpil C
dc.contributor.authorWenzel, Sally E
dc.contributor.authorMeyers, Deborah A
dc.contributor.authorBleecker, Eugene R
dc.contributor.authorPhillips, Brenda R
dc.contributor.authorMauger, David T
dc.contributor.authorGordon, Erin D
dc.contributor.authorWoodruff, Prescott G
dc.contributor.authorPeters, Michael C
dc.contributor.authorFahy, John V
dc.date.accessioned2018-06-12T23:57:14Z
dc.date.available2018-06-12T23:57:14Z
dc.date.issued2018-03-01
dc.identifier.citationJ Clin Invest. 2018;128(3):997-1009. https://doi.org/10.1172/JCI95693.en_US
dc.identifier.issn1558-8238
dc.identifier.pmid29400693
dc.identifier.doi10.1172/JCI95693
dc.identifier.urihttp://hdl.handle.net/10150/627957
dc.description.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.en_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.language.isoenen_US
dc.publisherAMER SOC CLINICAL INVESTIGATION INCen_US
dc.relation.urlhttps://www.jci.org/articles/view/95693en_US
dc.rightsCopyright © 2018, American Society for Clinical Investigationen_US
dc.subjectAsthmaen_US
dc.subjectCytokinesen_US
dc.subjectPulmonologyen_US
dc.subjectTh2 responseen_US
dc.titleMucus plugs in patients with asthma linked to eosinophilia and airflow obstruction.en_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Med, Div Genet Genom & Precis Meden_US
dc.identifier.journalJOURNAL OF CLINICAL INVESTIGATIONen_US
dc.description.collectioninformationThis 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 repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleThe Journal of clinical investigation
refterms.dateFOA2018-06-12T23:57:14Z


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