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Excess mucus viscosity and airway dehydration impact COPD airway clearance
European Respiratory Journal ( IF 16.6 ) Pub Date : 2019-10-31 , DOI: 10.1183/13993003.00419-2019
Vivian Y. Lin , Niroop Kaza , Susan E. Birket , Harrison Kim , Lloyd J. Edwards , Jennifer LaFontaine , Linbo Liu , Marina Mazur , Stephen A. Byzek , Justin Hanes , Guillermo J. Tearney , S. Vamsee Raju , Steven M. Rowe

The mechanisms by which cigarette smoking impairs airway mucus clearance are not well understood. We recently established a ferret model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) exhibiting chronic bronchitis. We investigated the effects of cigarette smoke on mucociliary transport (MCT). Adult ferrets were exposed to cigarette smoke for 6 months, with in vivo mucociliary clearance measured by technetium-labelled DTPA retention. Excised tracheae were imaged with micro-optical coherence tomography. Mucus changes in primary human airway epithelial cells and ex vivo ferret airways were assessed by histology and particle tracking microrheology. Linear mixed models for repeated measures identified key determinants of MCT. Compared to air controls, cigarette smoke-exposed ferrets exhibited mucus hypersecretion, delayed mucociliary clearance (−89.0%, p<0.01) and impaired tracheal MCT (−29.4%, p<0.05). Cholinergic stimulus augmented airway surface liquid (ASL) depth (5.8±0.3 to 7.3±0.6 µm, p<0.0001) and restored MCT (6.8±0.8 to 12.9±1.2 mm·min−1, p<0.0001). Mixed model analysis controlling for covariates indicated smoking exposure, mucus hydration (ASL) and ciliary beat frequency were important predictors of MCT. Ferret mucus was hyperviscous following smoke exposure in vivo or in vitro, and contributed to diminished MCT. Primary cells from smokers with and without COPD recapitulated these findings, which persisted despite the absence of continued smoke exposure. Cigarette smoke impairs MCT by inducing airway dehydration and increased mucus viscosity, and can be partially abrogated by cholinergic secretion of fluid secretion. These data elucidate the detrimental effects of cigarette smoke exposure on mucus clearance and suggest additional avenues for therapeutic intervention. Mucus abnormalities impact COPD airway clearance http://bit.ly/2VEhFjd

中文翻译:

粘液粘度过高和气道脱水会影响 COPD 气道清除率

吸烟损害气道粘液清除的机制尚不清楚。我们最近建立了香烟烟雾诱发的慢性阻塞性肺疾病 (COPD) 表现出慢性支气管炎的雪貂模型。我们研究了香烟烟雾对黏液纤毛运输 (MCT) 的影响。成年雪貂暴露于香烟烟雾中 6 个月,通过锝标记的 DTPA 保留测量体内黏液纤毛清除率。切除的气管用微光学相干断层扫描成像。通过组织学和粒子追踪微流变学评估原代人类气道上皮细胞和离体雪貂气道的粘液变化。重复测量的线性混合模型确定了 MCT 的关键决定因素。与空气对照相比,暴露在香烟烟雾中的雪貂表现出粘液分泌过多,黏液纤毛清除延迟 (-89.0%, p<0.01) 和气管 MCT 受损 (-29.4%, p<0.05)。胆碱能刺激增强气道表面液体 (ASL) 深度(5.8±0.3 至 7.3±0.6 µm,p<0.0001)并恢复 MCT(6.8±0.8 至 12.9±1.2 mm·min-1,p<0.0001)。控制协变量的混合模型分析表明吸烟暴露、粘液水化 (ASL) 和纤毛搏动频率是 MCT 的重要预测因素。在体内或体外暴露于烟雾后,雪貂粘液变得粘稠,并导致 MCT 降低。患有和不患有 COPD 的吸烟者的原代细胞概括了这些发现,尽管没有持续接触烟雾,但这些发现仍然存在。香烟烟雾通过诱导气道脱水和粘液粘度增加来损害 MCT,并且可以通过液体分泌的胆碱能分泌部分消除。这些数据阐明了香烟烟雾暴露对粘液清除的不利影响,并提出了治疗干预的其他途径。粘液异常影响 COPD 气道清除 http://bit.ly/2VEhFjd
更新日期:2019-10-31
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