背景:慢性肺移植功能障碍(CLAD)包括三种主要表型:闭塞性细支气管炎综合征(BOS),限制性同种异体移植综合征(RAS)和结合两种病理的混合表型。在这些表型中气道结构整体如何受到影响仍然知之甚少。
方法:对气道形态计量学进行了详细分析,以深入了解气道重塑对终末期CLAD中肺泡通气分布的影响。六个对照的离体全肺μCT和组织核心μCT扫描,六个BOS,三个RAS和三个混合外植体肺移植物(9个男性,9女,2014-2021年,鲁汶,比利时)用于数字气道重建和计算与管腔阻塞有关的气道尺寸。
结果:BOS和混合外植体显示近端细支气管气道阻塞(从第5代开始),而RAS外植体特别是在最远端的细支气管(第>12代)有气道阻塞。在BOS和混合外植体中,76%和84%的细支气管被阻塞,分别,而在RAS中这是22%。支气管阻塞主要由气道壁淋巴细胞炎症或纤维化重塑引起,即缩窄性细支气管炎。在所有CLAD表型中都存在近端支气管扩张和远端肺通气失衡,这解释了肺功能不良和特定肺功能参数的恶化。
结论:传导细支气管结构的改变显示,CLAD以区域性方式影响肺泡通气分布。各种障碍物的意义,特别是那些与粘液有关的,突出显示。
背景:这项研究由国家研究基金佛兰德斯(G060322N)资助,由R.V.收到
BACKGROUND: Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood.
METHODS: A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung μCT and tissue-core μCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions.
RESULTS: BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters.
CONCLUSIONS: Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted.
BACKGROUND: This research was funded with the National research fund Flanders (G060322N), received by R.V.