Airway Mucus Hyperconcentration in Non–Cystic Fibrosis Bronchiectasis
| Autor: | Amy Broomfield, Agathe Ceppe, Scott H. Donaldson, Yong H. Sheng, Megan L. Martin, Sumaira Z. Hasnain, Peadar G. Noone, Stephanie Livengood, Michael A. McGuckin, Lucy D. Burr, Camille Ehre, Alice C.-H. Chen, Graham L. Radford-Smith, Kathryn A. Ramsey, Richard C. Boucher, Michael R. Knowles, Brian Button, David J. Thornton, Giorgia Radicioni, Simon D. Bowler, Neil E. Alexis, David B. Hill, Lisa A. Simms, Mehmet Kesimer, Rohan Lourie |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Respiratory System Critical Care and Intensive Care Medicine Cystic fibrosis 03 medical and health sciences 0302 clinical medicine fluids and secretions Medicine Humans 030212 general & internal medicine Respiratory system Lung Bronchiectasis business.industry Mucin Original Articles respiratory system medicine.disease Mucus Fibrosis Hypertonic saline medicine.anatomical_structure 030228 respiratory system Sputum medicine.symptom business |
| Zdroj: | Am J Respir Crit Care Med |
| Popis: | 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 FEV(1) 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. |
| Databáze: | OpenAIRE |
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