Journal article
Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction
The Journal of clinical investigation, Vol.128(3), pp.997-1009
03/01/2018
DOI: 10.1172/JCI95693
PMCID: PMC5824874
PMID: 29400693
Abstract
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.
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.
Clinicaltrials.gov NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01759186, NCT01716494, and NCT01760915.
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.
Details
- Title: Subtitle
- Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction
- Creators
- Eleanor M Dunican - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, andBrett M Elicker - Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USADavid S Gierada - Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USAScott K Nagle - Department of Medical Physics and Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USAMark L Schiebler - Department of Medical Physics and Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USAJohn D Newell - Division of Cardiovascular and Pulmonary Imaging, Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAWilfred W Raymond - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, andMarrah E Lachowicz-Scroggins - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, andSelena Di Maio - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, andEric A Hoffman - Division of Cardiovascular and Pulmonary Imaging, Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAMario Castro - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University, St. Louis, Missouri, USASean B Fain - Department of Medical Physics and Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USANizar N Jarjour - Allergy, Pulmonary and Critical Care Medicine Division, University of Wisconsin School of Medicine, Madison, Wisconsin, USAElliot Israel - Pulmonary and Critical Care Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts, USABruce D Levy - Pulmonary and Critical Care Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts, USASerpil C Erzurum - Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OhioSally E Wenzel - Pulmonary, Allergy and Critical Care Medicine Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USADeborah A Meyers - Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USAEugene R Bleecker - Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USABrenda R Phillips - Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State University, Hershey, Pennsylvania, USADavid T Mauger - Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State University, Hershey, Pennsylvania, USAErin D Gordon - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, andPrescott G Woodruff - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, andMichael C Peters - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, andJohn V Fahy - Division of Pulmonary and Critical Care Medicine, Department of Medicine and Cardiovascular Research Institute, and
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.128(3), pp.997-1009
- Publisher
- United States
- DOI
- 10.1172/JCI95693
- PMID
- 29400693
- PMCID
- PMC5824874
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- P01 HL128191 / NHLBI NIH HHS P30 ES005605 / NIEHS NIH HHS U10 HL109146 / NHLBI NIH HHS U19 AI077439 / NIAID NIH HHS U10 HL109250 / NHLBI NIH HHS R01 HL122531 / NHLBI NIH HHS K23 HL138303 / NHLBI NIH HHS R01 HL080414 / NHLBI NIH HHS UL1 TR002345 / NCATS NIH HHS UL1 TR000448 / NCATS NIH HHS K24 HL137013 / NHLBI NIH HHS UL1 TR002373 / NCATS NIH HHS U10 HL109086 / NHLBI NIH HHS KL2 TR000428 / NCATS NIH HHS U10 HL064313 / NHLBI NIH HHS KL2 TR002374 / NCATS NIH HHS U10 HL109168 / NHLBI NIH HHS U10 HL109257 / NHLBI NIH HHS U10 HL109164 / NHLBI NIH HHS P01 HL107202 / NHLBI NIH HHS UL1 TR000427 / NCATS NIH HHS U10 HL109152 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS U10 HL109172 / NHLBI NIH HHS
- Language
- English
- Date published
- 03/01/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Iowa Neuroscience Institute; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984051519402771
Metrics
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