Hsieh Aileen, Vasilescu Dragoş M, Barker-Mulleder Jenna, Fouadi May, Ledoux Stacey, Erle David J, Liegeois Maude A, Fahy John V, Hackett Tillie-Louise
The University of British Columbia, Anesthesiology, Pharmacology and Therapeutics, Center for Heart Lung Innovation, Vancouver, British Columbia, Canada.
University of British Columbia, The James C Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Vancouver, British Columbia, Canada.
Am J Respir Crit Care Med. 2025 Aug 22. doi: 10.1164/rccm.202501-0310OC.
The observation that mucus plugs in proximal airways on computed tomography (CT) correlate with disease severity and airflow obstruction has highlighted their role in asthma. Due to the resolution of CT, it is unknown if mucus plugs within the distal small airways (<2mm in diameter) also contribute to asthma severity.
To assess the prevalence of distal mucus plugs and their association with small airway remodelling in asthma.
12 control, 5 non-fatal, and 11 fatal asthma lungs underwent systematic uniform random sampling to obtain 239 lung tissue samples that were imaged using micro-CT and matched histology to assess mucus plugs, airway wall remodelling and mucus composition.
Within the distal lung of non-fatal and fatal asthmatics, 30% and 38% of pre-terminal bronchioles, 29% and 34% of terminal bronchioles, and 33% and 21% of transitional bronchioles contained mucus plugs, with a high coefficient of variation in their spatial location. Mucus plugs were comprised of 84% and 82% MUC5AC and 16% and 18% MUC5B in non-fatal and fatal asthma, and 67% extended over 80% of the bronchiole pathlength. In asthmatic lungs, mucus-plugged airways had thickened airway walls, narrowed airway lumens, and luminal folding compared to unplugged airways, due to increased epithelial, basement membrane, and smooth muscle thickening.
In asthma, mucus plugs are a prominent and spatially heterogeneous feature within the distal small airways, and are associated with airway wall remodelling and lumen narrowing, making them a key target for improving lung ventilation and patient outcomes.
计算机断层扫描（CT）显示近端气道中的黏液栓与疾病严重程度和气流阻塞相关，这突出了它们在哮喘中的作用。由于CT的分辨率，尚不清楚直径小于2mm的远端小气道内的黏液栓是否也会导致哮喘严重程度增加。
评估哮喘患者远端黏液栓的患病率及其与小气道重塑的关系。
对12例对照者、5例非致死性哮喘患者和11例致死性哮喘患者的肺进行系统均匀随机抽样，获取239个肺组织样本，使用微型CT成像并进行匹配的组织学检查，以评估黏液栓、气道壁重塑和黏液成分。
在非致死性和致死性哮喘患者的远端肺中，30%和38%的终末前细支气管、29%和34%的终末细支气管以及33%和21%的过渡性细支气管含有黏液栓，其空间位置的变异系数较高。在非致死性和致死性哮喘中，黏液栓分别由84%和82%的MUC5AC以及16%和18%的MUC5B组成，67%的黏液栓延伸超过细支气管路径长度的80%。与未阻塞的气道相比，哮喘患者的肺中，有黏液栓的气道壁增厚、管腔变窄且有管腔折叠，这是由于上皮、基底膜和平滑肌增厚增加所致。
在哮喘中，黏液栓是远端小气道内一个突出且空间异质性的特征，与气道壁重塑和管腔狭窄相关，使其成为改善肺通气和患者预后的关键靶点。
