Marsico Lung Institute.
Department of Pediatrics, Pediatric Respiratory Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
Am J Respir Crit Care Med. 2020 Mar 15;201(6):661-670. doi: 10.1164/rccm.201906-1219OC.
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. This study was designed to: ) measure mucus concentration and biophysical properties of bronchiectasis mucus; ) identify the secreted mucins contained in bronchiectasis mucus; ) relate mucus properties to airway epithelial mucin RNA/protein expression; and ) explore relationships between mucus hyperconcentration and disease severity. 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. 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 and positively with bronchiectasis extent, as measured by high-resolution computed tomography, and inflammatory mediators. No difference was detected in rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced non-cystic fibrosis bronchiectasis mucus concentration by 5%. Hyperconcentrated airway mucus is characteristic of subjects with bronchiectasis, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy.
非囊性纤维化性支气管扩张症的特征是气道黏液积聚和痰液生成，但黏液浓度在这些异常发病机制中的作用尚未确定。本研究旨在：）测量支气管扩张症黏液的黏液浓度和生物物理特性；）鉴定支气管扩张症黏液中所含的分泌型黏蛋白；）将黏液特性与气道上皮黏蛋白 RNA/蛋白表达相关联；）探索黏液高浓度与疾病严重程度之间的关系。收集了支气管扩张症患者（包括接受慢性红霉素治疗和未接受慢性红霉素治疗的患者）和健康对照者的痰液样本。测量了痰液的固体百分比浓度、总黏液和各单个黏蛋白浓度、渗透压、流变学特性和炎症介质。通过免疫组织化学和基因表达在支气管活检中测量细胞内黏蛋白。通过定量 PCR 鉴定 MUC5B（黏蛋白 5B）多态性。在复制的支气管扩张症队列中，收集了自发性咳痰和高渗盐水诱导的痰液，并测量了黏液/黏蛋白浓度。与健康痰液相比，支气管扩张症痰液的固体百分比、总黏液和各单个黏蛋白（MUC5B 和 MUC5AC）浓度、渗透压以及弹性和粘性模量均增加。在支气管扩张症患者中，痰固体百分比与 FEV 呈负相关，与高分辨率计算机断层扫描测量的支气管扩张症程度以及炎症介质呈正相关。在支气管扩张症和健康个体之间，rs35705950 SNP 等位基因频率没有差异。高渗盐水吸入可使非囊性纤维化性支气管扩张症的气道黏液浓度急性降低 5%。富含黏液的气道黏液是支气管扩张症患者的特征，可能有助于疾病发病机制，并可能成为药物治疗的靶点。
