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Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma

机译：血嗜酸性粒细胞计数和气道上皮转录组在COPD与哮喘中的关系

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摘要

Abstract 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/μL 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.
机译：摘要背景是“可治疗性状”高血嗜酸性粒细胞计数的临床或病理生理学意义，与哮喘相同仍然存在争议。我们试图确定来自COPD和哮喘的支气管胶囊的血液嗜酸性粒细胞计数，临床特征和基因表达的关系。方法将受试者招募到COPD（肺气肿与呼吸道疾病[EVA]）或哮喘队列（在预测呼吸道疾病结果，U-BIOPRED的预测）。在U-Biopred中使用RNASEQ（n？=Δ283）和ydymetrix微阵列的基因表达（n？=Δ85）。我们用血液嗜酸血粒细胞对支气管胶带转录信号以及血液粒细胞计数的线性回归分析与血液嗜酸性粒细胞计数相比，β200？Δ200≤α，作为截止值。错误的发现率以1％（连续值）控制，5％（具有二分度值）。结果嗜酸性粒细胞与非聚环粒细胞COPD病例之间的年龄，性别，肺功能，运动能力和定量计算断层没有差异。在嗜酸性嗜型哮喘和COPD中增加了总血清IgE。在EVA中，有12个基因具有统计学上显着的正相关性与线性血液粒细胞计数，而在U-BioPred中，1197个基因显示出显着的关联（266℃和931个阴性）。转录组在哮喘与COPD中的血液嗜酸性粒细胞相关的基因和途径之间表现出几乎没有重叠。仅CST1对嗜酸性哮喘和COPD常见，并在独立的队列中被复制。结论尽管哮喘和COPD之间的“可治疗性质”，但这些临床实体的分子机制主要是不同的。

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  • 来源
    《Allergy》 |2020年第2期|共11页
  • 作者

    George Leena; Taylor Adam R.; Esteve‐Codina Anna; Soler Artigas María; Thun Gian Andri; Bates Stewart; Pavlidis Stelios; Wagers Scott; Boland Anne; Prasse Antje; Boschetto Piera; Parr David G.; Nowinski Adam; Barta Imre; Hohlfeld Jens; Greulich Timm; den Berge Maarten; Hiemstra Pieter S.; Timens Wim; Hinks Timothy; Wenzel Sally; Siddiqui Salman; Richardson Matthew; Venge Per; Heath Simon; Gut Ivo; Tobin Martin D.; Edwards Lindsay; Riley John H.; Djukanovic Ratko; Auffray Charles; De‐Meulder Bertrand; Erik‐Dahlen Sven; Adcock Ian M.; Chung Kian Fan; Ziegler‐Heitbrock Loems; Sterk Peter J.; Singh Dave; Brightling Christopher E.; the U‐BIOPRED and the EvA study teams;

  • 作者单位

    Institute for Lung Health Leicester NIHR Biomedical Research CentreUniversity of;

    GSK Respiratory Therapeutic Area UnitStevenage UK;

    Centre for Genomic RegulationCNAG‐CRG Centre Nacional d'Anàlisi Genòmica Barcelona Institute for;

    Institute for Lung Health Leicester NIHR Biomedical Research CentreUniversity of;

    Centre for Genomic RegulationCNAG‐CRG Centre Nacional d'Anàlisi Genòmica Barcelona Institute for;

    GSK Respiratory Therapeutic Area UnitStevenage UK;

    Airway Disease SectionNational Heart &

    Lung Institute Imperial College LondonLondon UK;

    Biosci ConsultingMaasmechelen Belgium;

    Institut de Génomique CEACNG Centre National de GénotypageEvry France;

    Department of PneumologyUniversity Medical CenterFreiburg Germany;

    Department of Medical SciencesUniversity of Ferrara and Ferrara City HospitalFerrara Italy;

    Department of Respiratory MedicineUniversity Hospitals Coventry and Warwickshire NHS TrustCoventry;

    Department of Respiratory MedicineNational Institute of Tuberculosis and Lung DiseasesWarsaw Poland;

    Department of PathophysiologyNational Koranyi Institute for TB and PulmonologyBudapest Hungary;

    Fraunhofer Institute for Toxicology and Experimental MedicineHannover Germany;

    Department of Medicine Pulmonary and Critical Care MedicineUniversity Medical Center Giessen and;

    Department of Pulmonary DiseasesUniversity Medical Center Groningen University of;

    Department of Pulmonary DiseasesLeiden University Medical Center University of LeidenLeiden The;

    Department of Pathology and Medical BiologyUniversity Medical Center Groningen University of;

    University of OxfordOxford UK;

    Department of MedicineUniversity of PittsburghPittsburgh PA USA;

    Institute for Lung Health Leicester NIHR Biomedical Research CentreUniversity of;

    Institute for Lung Health Leicester NIHR Biomedical Research CentreUniversity of;

    Department of Medical Sciences Clinical ChemistryUppsala UniversityUppsala Sweden;

    Centre for Genomic RegulationCNAG‐CRG Centre Nacional d'Anàlisi Genòmica Barcelona Institute for;

    Centre for Genomic RegulationCNAG‐CRG Centre Nacional d'Anàlisi Genòmica Barcelona Institute for;

    Institute for Lung Health Leicester NIHR Biomedical Research CentreUniversity of;

    GSK Respiratory Therapeutic Area UnitStevenage UK;

    GSK Respiratory Therapeutic Area UnitStevenage UK;

    NIHR Southampton Respiratory Biomedical Research Unit and Clinical and Experimental;

    European Institute for Systems Biology and Medicine (EISBM)CNRS‐ENS‐UCBL Université de LyonLyon;

    European Institute for Systems Biology and Medicine (EISBM)CNRS‐ENS‐UCBL Université de LyonLyon;

    Karolinska InstituteStockholm Sweden;

    Instituto de Salud Carlos IIIBiomedical Network Research Centre on Mental Health (CIBERSAM;

    Instituto de Salud Carlos IIIBiomedical Network Research Centre on Mental Health (CIBERSAM;

    EvA Study CenterHelmholtz Zentrum Muenchen and Asklepios‐KlinikGauting Germany;

    Department Respiratory MedicineAmsterdam University Medical Centres University of;

    Centre for Respiratory Medicine and AllergyThe University of ManchesterManchester UK;

    Institute for Lung Health Leicester NIHR Biomedical Research CentreUniversity of;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

    asthma; chronic obstructive pulmonary disease; eosinophil; gene expression; T2‐immunity;

    机译：哮喘;慢性阻塞性肺疾病;嗜酸性粒细胞;基因表达;T2-acfuny;

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