Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma
Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma
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COPD与哮喘患者血嗜酸性粒细胞计数和气道上皮细胞转录组的关系
DOI：
10.1111/all.14016
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发表时间：
2020-02-01
期刊：
影响因子：
12.4
通讯作者：
Brightling, Christopher E.
中科院分区：
文献类型：
--
作者：
George, Leena;Taylor, Adam R.;Brightling, Christopher E.
背景资料：COPD患者的“可治疗特征”高血嗜酸性粒细胞计数的临床或病理生理学意义是否与哮喘相同仍存在争议。我们试图确定血液嗜酸性粒细胞计数，临床特征和基因表达之间的关系，从支气管刷在COPD和asthene.Methods：受试者被招募到COPD（肺气肿与气道疾病[伊娃]）或哮喘队列（无偏生物标志物预测呼吸系统疾病的结果，U-BIOPRED）。我们使用伊娃中的RNAseq（n = 283）和U-BIOPRED中的Affyseq微阵列（n = 85）确定基因表达。我们使用血液嗜酸性粒细胞> 200个细胞/μ L作为截止值，对支气管刷毛转录信号与血液嗜酸性粒细胞计数以及差异表达进行线性回归分析。结果：嗜酸性粒细胞与非嗜酸性粒细胞COPD患者在年龄、性别、肺功能、运动能力和定量CT方面无差异。嗜酸性粒细胞性哮喘和COPD患者血清总IgE升高。在伊娃中，有12个基因与线性血液嗜酸性粒细胞计数具有统计学显著的正相关性，而在U-BIOPRED中，1197个基因显示出显著的相关性（266个阳性和931个阴性）。转录组显示与哮喘和COPD患者血嗜酸性粒细胞计数相关的基因和途径之间几乎没有重叠。只有CST 1是常见的嗜酸性粒细胞性哮喘和COPD，并复制在独立的cohols.Conclusion：尽管共享的“可治疗的性状”之间的哮喘和COPD，这些临床实体的分子机制主要是不同的。
Background: Whether the clinical or pathophysiologic significance of the "treatable trait" high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma.Methods: Subjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U-BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U-BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil > 200 cells/mu L as a cut-off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values).Results: There were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U-BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts.Conclusion: Despite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.