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

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• dc.contributor.author George, Leena
• dc.contributor.author Esteve-Codina, Anna
• dc.contributor.author Soler Artigas, María
• dc.contributor.author Thun, Gian Andri
• dc.contributor.author Heath, Simon
• dc.contributor.author Gut, Ivo Glynne
• dc.contributor.author Brightling, Christopher E.
• dc.date.accessioned 2020-03-17T07:33:28Z
• dc.date.available 2020-03-17T07:33:28Z
• dc.date.issued 2020
• dc.description.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.
• dc.description.sponsorship 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)
• dc.format.mimetype application/pdf
• dc.identifier.citation George L, Taylor AR, Esteve-Codina A, Soler Artigas M, Thun GA, Bates S et al. Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma. Allergy. 2020 Feb; 75(2): 370-380. DOI: 10.1111/all.14016
• dc.identifier.doi http://dx.doi.org/10.1111/all.14016
• dc.identifier.issn 0105-4538
• dc.identifier.uri http://hdl.handle.net/10230/43906
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Allergy. 2020 Feb; 75(2): 370-80
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/270194
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115010
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115446
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/200506
• dc.rights © 2019 Leena George et al. Allergy published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Immunitat
• dc.subject.other Asma
• dc.subject.other Pulmons -- Malalties
• dc.subject.other Eosinòfils
• dc.subject.other Expressió gènica
• dc.title Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion