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George, L.* ; Taylor, A.R.* ; Esteve-Codina, A.* ; Soler Artigas, M.* ; Thun, G.A.* ; Bates, S.* ; Pavlidis, S.* ; Wagers, S.* ; Boland, A.* ; Prasse, A.* ; Boschetto, P.* ; Parr, D.G.* ; Nowinski, A.* ; Barta, I.* ; Hohlfeld, J.* ; Greulich, T.* ; van den Berge, M.* ; Hiemstra, P.S.* ; Timens, W.* ; Hinks, T.* ; Wenzel, S.* ; Siddiqui, S.* ; Richardson, M.* ; Venge, P.* ; Heath, S.* ; Gut, I.* ; Tobin, M.D.* ; Edwards, L.* ; Riley, J.H.* ; Djukanovic, R.* ; Auffray, C.* ; De-Meulder, B.* ; Erik-Dahlen, S.* ; Adcock, I.M.* ; Chung, K.F.* ; Ziegler-Heitbrock, L. ; Sterk, P.J.* ; Singh, D.* ; Brightling, C.E.*

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

Allergy 75, 370-380 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Asthma ; Chronic Obstructive Pulmonary Disease ; Eosinophil ; Gene Expression ; T2-immunity; Obstructive Pulmonary-disease; Post-hoc Analysis; Secondary Analysis; Exacerbations; Lung; Mepolizumab; Sputum; Phase
ISSN (print) / ISBN 0105-4538
e-ISSN 1398-9995
Journal Allergy
Quellenangaben Volume: 75, Issue: 2, Pages: 370-380 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status Peer reviewed