Priority Research Centre for Healthy Lungs, The University of Newcastle, New Lambton Heights, NSW, Australia.
Department of Respiratory Medicine (Department of Pulmonary and Critical Care Medicine), Xiangya Hospital, Central South University, Changsha, China.
Clin Exp Allergy. 2019 Nov;49(11):1418-1428. doi: 10.1111/cea.13452. Epub 2019 Aug 6.
Dysfunction of the bronchial epithelium plays an important role in asthma; however, its measurement is challenging. Columnar epithelial cells are often quantified, yet rarely analysed, in induced sputum studies.
We aimed to test whether sputum columnar epithelial cell proportion and count are altered in asthma, and whether they are associated with clinical and inflammatory variables. We aimed to test whether sputum-based measures could provide a relatively non-invasive means through which to monitor airway epithelial activation status.
We examined the relationship of sputum columnar epithelial cells with clinical and inflammatory variables of asthma in a large retrospective cross-sectional cohort (901 participants with asthma and 138 healthy controls). In further studies, we used flow cytometry, microarray, qPCR and ELISA to characterize sputum columnar epithelial cells and their products.
Multivariate analysis and generation of 90th centile cut-offs (≥11% or ≥18.1 × 10 /mL) to identify columnar epithelial cell "high" asthma revealed a significant relationship between elevated sputum columnar cells and male gender, severe asthma and non-neutrophilic airway inflammation. Flow cytometry showed viable columnar epithelial cells were present in all sputum samples tested. An epithelial gene signature (SCGB3A1, LDLRAD1, FOXJ1, DNALI1, CFAP157, CFAP53) was detected in columnar epithelial cell-high sputum. CLCA1 mRNA and periostin protein, previously identified biomarkers of IL-13-mediated epithelial activation, were elevated in columnar epithelial cell-high sputum samples, but only when accompanied by eosinophilia.
CONCLUSIONS & CLINICAL RELEVANCE: Sputum columnar epithelial cells are related to important clinical and inflammatory variables in asthma. Measurement of epithelial biomarkers in sputum samples could allow non-invasive assessment of altered bronchial epithelium status in asthma.
支气管上皮功能障碍在哮喘中起着重要作用；然而，其测量具有挑战性。在诱导痰研究中，柱状上皮细胞通常被定量，但很少被分析。
我们旨在测试哮喘患者的痰柱状上皮细胞比例和计数是否改变，以及它们是否与临床和炎症变量相关。我们旨在测试基于痰液的测量是否可以提供一种相对非侵入性的方法，通过这种方法可以监测气道上皮细胞的激活状态。
我们在一个大型回顾性横断面队列（901 例哮喘患者和 138 例健康对照者）中检查了痰柱状上皮细胞与哮喘的临床和炎症变量的关系。在进一步的研究中，我们使用流式细胞术、微阵列、qPCR 和 ELISA 来表征痰柱状上皮细胞及其产物。
多变量分析和生成第 90 百分位截值（≥11%或≥18.1×10 6 /mL）以识别柱状上皮细胞“高”哮喘，表明升高的痰柱状细胞与男性、严重哮喘和非中性粒细胞性气道炎症之间存在显著关系。流式细胞术显示所有测试的痰样本中都存在有活力的柱状上皮细胞。在柱状上皮细胞高的痰样本中检测到上皮基因特征（SCGB3A1、LDLRAD1、FOXJ1、DNALI1、CFAP157、CFAP53）。以前鉴定为 IL-13 介导的上皮激活的生物标志物 CLCA1 mRNA 和periostin 蛋白在柱状上皮细胞高的痰样本中升高，但仅在伴有嗜酸性粒细胞增多时升高。
痰柱状上皮细胞与哮喘中的重要临床和炎症变量相关。在痰样本中测量上皮生物标志物可以允许非侵入性评估哮喘中改变的支气管上皮状态。
