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

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.

Allergy (Copenhagen), 2020-02, Vol.75 (2), p.370-380 [Periódico revisado por pares]

Denmark: Wiley

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Título:
Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma
Autor: 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.
Assuntos: Aged ; Allergology ; asthma ; Asthma - blood ; Asthma - genetics ; Asthma - immunology ; Biochemistry, Molecular Biology ; Biomarkers - blood ; chronic obstructive pulmonary disease ; eosinophil ; Eosinophils - immunology ; Female ; gene expression ; Genomics ; Humans ; Immunoglobulin E - blood ; Immunology ; Leukocyte Count ; Life Sciences ; Male ; Medicin och hälsovetenskap ; Middle Aged ; Original ; ORIGINAL ARTICLES ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive - blood ; Pulmonary Disease, Chronic Obstructive - genetics ; Pulmonary Disease, Chronic Obstructive - immunology ; Respiratory Mucosa - immunology ; RNA-Seq ; T2-immunity ; Th2 Cells - immunology ; Transcriptome
É parte de: Allergy (Copenhagen), 2020-02, Vol.75 (2), p.370-380
Notas: Funding information
This work was funded in part by Airway Disease Predicting Outcomes through Patient Specific Computational Modelling (AirPROM) project (funded through FP7 EU grant), U‐BIOPRED (IMI) (No. 115010), eTRIKS (IMI) (No. 115446), Emphysema versus Airways Disease (EvA FP7; 200506), Wellcome Trust and National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Centre. This paper presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
See Appendix S1 for inverstigators of U‐BIOPRED and the EvA study teams.
George, Taylor, and Esteve‐Codina denotes first authors with equal contribution.
Descrição: 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. 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.
Editor: Denmark: Wiley
Idioma: Inglês

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

Denmark: Wiley

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