不同哮喘表型痰柱状上皮细胞及其产物的失调
2019/07/11
摘要
背景：支气管上皮功能障碍在哮喘中起着重要作用，但其测量具有挑战性。在诱导性痰研究中，柱状上皮细胞通常被定量，但很少被分析。
目的：探讨哮喘患者痰柱状上皮细胞比例和计数是否发生变化，是否与临床和炎症变化有关。我们的目的是测试基于痰的检查是否能够提供一种相对无创的手段，通过它来监测气道上皮细胞的激活状态。
方法：在一个大型回顾性横断面队列（901名哮喘患者和138名健康对照者）中，我们研究了痰柱状上皮细胞与哮喘临床和炎症变化的关系。在进一步的研究中，我们使用流式细胞仪、微阵列、qPCR和ELISA来表征痰柱状上皮细胞及其产物。
结果：多变量分析和第90个百分位值（≥11%或≥18.1x104/ml）的产生，发现痰柱细胞升高与男性、重度哮喘和非中性粒细胞性气道炎症有显著关系。流式细胞仪显示所有被测痰样本中均存在活柱状上皮细胞。在多柱状上皮细胞痰中检测到上皮基因标记（SCGB3A1, LDLRAD1, FOXJ1, DNALI1, CFAP157, CFAP53）。在多柱状上皮细胞痰样本中，CLCA1的mRNA和periostin蛋白（既往确定的IL-13介导的上皮细胞活化的生物标志物）升高，但仅在伴有嗜酸性粒细胞增多时升高。
结论与临床相关性：痰柱状上皮细胞与哮喘的重要临床和炎症变化有关。痰标本中上皮生物标志物的测量可以无创评估哮喘患者支气管上皮状态的改变。
Dysregulation of sputum columnar epithelial cells and products in distinct asthma phenotypes
Qin L, Gibson PG, Simpson JL, Baines KJ, McDonald VM, Wood LG, Powell H, Fricker M
Abstract
BACKGROUND: 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.
OBJECTIVE: We aimed to test if sputum columnar epithelial cell proportion and count are altered in asthma, and if 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.
METHODS: 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 characterise sputum columnar epithelial cells and their products.
RESULTS: Multivariate analysis and generation of 90th centile cut-offs (≥11% or ≥18.1x104 /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.
背景：支气管上皮功能障碍在哮喘中起着重要作用，但其测量具有挑战性。在诱导性痰研究中，柱状上皮细胞通常被定量，但很少被分析。
目的：探讨哮喘患者痰柱状上皮细胞比例和计数是否发生变化，是否与临床和炎症变化有关。我们的目的是测试基于痰的检查是否能够提供一种相对无创的手段，通过它来监测气道上皮细胞的激活状态。
方法：在一个大型回顾性横断面队列（901名哮喘患者和138名健康对照者）中，我们研究了痰柱状上皮细胞与哮喘临床和炎症变化的关系。在进一步的研究中，我们使用流式细胞仪、微阵列、qPCR和ELISA来表征痰柱状上皮细胞及其产物。
结果：多变量分析和第90个百分位值（≥11%或≥18.1x104/ml）的产生，发现痰柱细胞升高与男性、重度哮喘和非中性粒细胞性气道炎症有显著关系。流式细胞仪显示所有被测痰样本中均存在活柱状上皮细胞。在多柱状上皮细胞痰中检测到上皮基因标记（SCGB3A1, LDLRAD1, FOXJ1, DNALI1, CFAP157, CFAP53）。在多柱状上皮细胞痰样本中，CLCA1的mRNA和periostin蛋白（既往确定的IL-13介导的上皮细胞活化的生物标志物）升高，但仅在伴有嗜酸性粒细胞增多时升高。
结论与临床相关性：痰柱状上皮细胞与哮喘的重要临床和炎症变化有关。痰标本中上皮生物标志物的测量可以无创评估哮喘患者支气管上皮状态的改变。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Clin Exp Allergy. 2019 Jul 1. doi: 10.1111/cea.13452)
(Clin Exp Allergy. 2019 Jul 1. doi: 10.1111/cea.13452)
Dysregulation of sputum columnar epithelial cells and products in distinct asthma phenotypes
Qin L, Gibson PG, Simpson JL, Baines KJ, McDonald VM, Wood LG, Powell H, Fricker M
Abstract
BACKGROUND: 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.
OBJECTIVE: We aimed to test if sputum columnar epithelial cell proportion and count are altered in asthma, and if 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.
METHODS: 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 characterise sputum columnar epithelial cells and their products.
RESULTS: Multivariate analysis and generation of 90th centile cut-offs (≥11% or ≥18.1x104 /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.
