Airways mucus pathogenesis in patients with non-cystic fibrosis bronchiectasis

粘蛋白 医学 粘液 囊性纤维化 支气管扩张 胃肠病学 内科学 气道 发病机制 病理 微生物学 外科 生物 生态学 肺结核
作者
Kathryn Ramsey,Giorgia Radicioni,David B. Hill,Camille Ehré,Brian Button,Neil E. Alexis,Michael R. Knowles,Scott H. Donaldson,Mehmet Kesimer,Michael A. McGuckin,Richard C. Boucher
标识
DOI:10.1183/13993003.congress-2018.pa5049
摘要

Background: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic airway condition characterized by the production of purulent sputum, prolonged inflammation, and repeated episodes of airway infection. We assessed the biochemical and biophysical properties of airway mucous in patients with NCB and healthy adults. Methods: Induced sputum was collected in 99 patients with NCFB and 15 healthy adults. We assessed the sputum samples for mucus percent solids (% solids), total mucin (refractometry), extracellular DNA (ELISA), osmotic pressure (custom-made oncometer), complex viscosity (cone and plate rheology), and sputum proteomics (mass spectrometry). Data are presented as mean (standard deviation). Results: Patients with NCFB were older (62.3 years (10.3)) and had lower FEV1 (66.3% (18.1)) compared with controls (42.2 years (19.3); 99.9% (9.0)). Sputum from patients with NCFB had higher mucus percent solids (3.3% (1.9) vs. 1.2% (0.5)), mucin concentration (5, 612µg/ml (3, 327) vs. 1, 637µg/ml (1030)), and DNA concentration (435µg/ml (487) vs. 22µg/ml (26)) compared with controls (p<0.05). In addition, NCFB sputum had higher osmotic pressure (543 Pa (393) vs. 136 Pa (41)) and higher complex viscosity (3.62 Pa/s (4.21) vs. 1.43 Pa/s (1.71) (p<0.05). Mucin proteins (MUC5B, MUC5AC, MUC4 and MUC16), trefoil factor 3, IgGFC-binding protein, and pulmonary-surfactant-associated protein B concentrations were higher in NCFB sputum compared with controls (p<0.05). Conclusion: Airway mucous in patients with NCFB is biochemically and biophysically abnormal compared with healthy airways. Mucus hyper-concentration likely contributes to infection, inflammation, and impaired mucociliary clearance in NCFB lung disease.

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