Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma
George, Leena (University of Leicester)
Taylor, Adam R. (GSK Respiratory Therapeutic Area Unit)
Esteve-Codina, Anna (Centre Nacional d'Anàlisi Genòmica)
Soler Artigas, María (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Thun, Gian Andri (Centre Nacional d'Anàlisi Genòmica)
Bates, Stewart (GSK Respiratory Therapeutic Area Unit)
Pavlidis, Stelios (Imperial College London)
Wagers, Scott (Biosci Consulting)
Boland, Anne (CNG Centre National de Génotypage)
Prasse, Antje (University Medical Center)
Boschetto, Piera (University of Ferrara and Ferrara City Hospital)
Parr, David G. (University Hospitals Coventry and Warwickshire NHS Trust)
Nowinski, Adam (National Institute of Tuberculosis and Lung Diseases)
Barta, Imre (National Koranyi Institute for TB and Pulmonology)
Hohlfeld, Jens (Fraunhofer Institute for Toxicology and Experimental Medicine)
Greulich, Timm (Member of the German Center for Lung Research (DZL))
van den Berge, Maarten (University of Groningen)
Hiemstra, Pieter S. (University of Leiden)
Timens, Wim (University of Groningen)
Hinks, Timothy (University of Oxford)
Wenzel, Sally (University of Pittsburgh)
Siddiqui, Salman (University of Leicester)
Richardson, Matthew (University of Leicester)
Venge, Per (Uppsala University)
Heath, Simon (Centre Nacional d'Anàlisi Genòmica)
Gut, Ivo (Universitat Pompeu Fabra)
Tobin, Martin D. (University of Leicester)
Edwards, Lindsay (GSK Respiratory Therapeutic Area Unit)
Riley, John H. (GSK Respiratory Therapeutic Area Unit)
Djukanovic, Ratko (NIHR Southampton Respiratory Biomedical Research Unit and Clinical and Experimental Sciences)
Auffray, Charles (Université de Lyon)
De-Meulder, Bertrand (Université de Lyon)
Erik-Dahlen, Sven (Karolinska Institutet (Estocolm, Suècia))
Adcock, Ian M. (Centro de Investigación Biomédica en Red de Salud Mental)
Chung, Kian Fan (Centro de Investigación Biomédica en Red de Salud Mental)
Ziegler-Heitbrock, Loems (Helmholtz Zentrum Muenchen and Asklepios-Klinik)
Sterk, Peter J. (Amsterdam Universitair Medische Centra (Amsterdam, Països Baixos))
Singh, Dave (University Hospital of South Manchester NHS Foundation Trust)
Brightling, Chris (University of Leicester)
Universitat Autònoma de Barcelona

Fecha:	2019
Resumen:	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. 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). 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. Despite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different. In a chronic obstructive pulmonary disease (COPD) cohort (EvA, n = 283), 12 genes, whereas in asthma cohort (UBIOPRED, n = 85), 1197 genes in bronchial epithelial brushes were correlated with a blood eosinophil count. The gene CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts. Despite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Asthma ; Chronic obstructive pulmonary disease ; Eosinophil ; Gene expression ; T2-immunity
Publicado en:	Allergy, Vol. 75 (september 2019) , p. 370-380, ISSN 1398-9995

DOI: 10.1111/all.14016
PMID: 31506971

11 p, 839.0 KB

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