BACKGROUND Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype. OBJECTIVE Within the U-BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions. METHODS Bronchial biopsies were collected from two severe asthma groups, one non-smoker (SAns, n=28) and one current/ex-smoker (SAs/ex, n=13), and a mild-moderate asthma group (MMA, n=28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n=33). A Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) were counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa were also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry. RESULTS The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAns, 18.9% SAs/ex) compared to the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n= 18-20, rho=0.544, p=0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans it was not feasible to compare airway morphometry between the asthma groups. CONCLUSION These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma.

中文翻译：

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气道弹性蛋白在严重哮喘中增加并与近端壁面积有关：U-BIOPRED 严重哮喘研究的组织学和计算机断层扫描结果

背景技术气道重塑，其可能包括杯状细胞增生/肥大、上皮完整性的改变、细胞外基质成分的积累、平滑肌肥大和网状层增厚，是严重哮喘的一个特征并且有助于临床表型。目标 在 U-BIOPRED 重症哮喘研究中，我们评估了气道重塑的组织学要素及其与近端气道尺寸的计算机断层扫描 (CT) 测量的关系。方法 从两个重度哮喘组，一个不吸烟者（SAs，n=28）和一个当前/前吸烟者（SAs/ex，n=13）和一个轻度中度哮喘组（MMA，n =28) 根据 GINA 指南进行分类和治疗，加上一个健康对照组 (HC, n=33)。A Movat 的五色技术用于鉴定粘蛋白，这些活组织检查中的弹性蛋白和总胶原蛋白。杯状细胞（粘蛋白+）的数量被计数为上皮细胞总数的百分比和测量的粘蛋白上皮面积百分比。还测量了黏膜下层中弹性纤维的百分比面积和总胶原蛋白，并对弹性纤维的形态进行了分类。哮喘组的参与者还进行了 CT 扫描以评估大气道形态测量。结果 与 HC (9.7%) 相比，两个严重哮喘组的黏膜下组织弹性蛋白百分比 (16.1% SAs, 18.9% SAs/ex) 较高，但哮喘组之间没有差异。弹性蛋白与 CT 测量的气道壁面积呈正相关（n = 18-20，rho = 0.544，p = 0.024），这也与弹性纤维的增加和增厚的层状形态外观有关。四组间粘蛋白上皮面积和总胶原蛋白无差异。由于少量合适的 CT 扫描，比较哮喘组之间的气道形态测量是不可行的。结论 这些发现确定了重度哮喘中弹性蛋白沉积程度与气道壁增厚之间的联系。