Airway Mucus Hyperconcentration in Non-Cystic Fibrosis Bronchiectasis.

Ramsey, Kathryn A; Chen, Alice C H; Radicioni, Giorgia; Lourie, Rohan; Martin, Megan; Broomfield, Amy; Sheng, Yong H; Hasnain, Sumaira Z; Radford-Smith, Graham; Simms, Lisa A; Burr, Lucy; Thornton, David J; Bowler, Simon D; Livengood, Stephanie; Ceppe, Agathe; Knowles, Michael R; Noone, Peadar G; Donaldson, Scott H; Hill, David B; Ehre, Camille; ... (2020). Airway Mucus Hyperconcentration in Non-Cystic Fibrosis Bronchiectasis. American journal of respiratory and critical care medicine, 201(6), pp. 661-670. American Thoracic Society 10.1164/rccm.201906-1219OC

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Rationale: Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these abnormalities has not been characterized.Objectives: This study was designed to: 1) measure mucus concentration and biophysical properties of bronchiectasis mucus; 2) identify the secreted mucins contained in bronchiectasis mucus; 3) relate mucus properties to airway epithelial mucin RNA/protein expression; and 4) explore relationships between mucus hyperconcentration and disease severity.Methods: Sputum samples were collected from subjects with bronchiectasis, with and without chronic erythromycin administration, and healthy control subjects. Sputum percent solid concentrations, total and individual mucin concentrations, osmotic pressures, rheological properties, and inflammatory mediators were measured. Intracellular mucins were measured in endobronchial biopsies by immunohistochemistry and gene expression. MUC5B (mucin 5B) polymorphisms were identified by quantitative PCR. In a replication bronchiectasis cohort, spontaneously expectorated and hypertonic saline-induced sputa were collected, and mucus/mucin concentrations were measured.Measurements and Main Results: Bronchiectasis sputum exhibited increased percent solids, total and individual (MUC5B and MUC5AC) mucin concentrations, osmotic pressure, and elastic and viscous moduli compared with healthy sputum. Within subjects with bronchiectasis, sputum percent solids correlated inversely with FEV1 and positively with bronchiectasis extent, as measured by high-resolution computed tomography, and inflammatory mediators. No difference was detected in MUC5B rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced non-cystic fibrosis bronchiectasis mucus concentration by 5%.Conclusions: Hyperconcentrated airway mucus is characteristic of subjects with bronchiectasis, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pneumologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Pneumology

UniBE Contributor:

Ramsey, Kathryn Angela

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1535-4970

Publisher:

American Thoracic Society

Language:

English

Submitter:

Anette van Dorland

Date Deposited:

02 Dec 2020 10:45

Last Modified:

05 Dec 2022 15:41

Publisher DOI:

10.1164/rccm.201906-1219OC

PubMed ID:

31765597

Uncontrolled Keywords:

gene expression induced sputum mucin

BORIS DOI:

10.7892/boris.147755

URI:

https://boris.unibe.ch/id/eprint/147755

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