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Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort
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Title: | Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort |
Authors: | Hoda, U Pavlidis, S Bansal, AT Takahashi, K Hu, S Ng Kee Kwong, F Rossios, C Sun, K Bhavsar, P Loza, M Baribaud, F Chanez, P Fowler, SJ Horvath, I Montuschi, P Singer, F Musial, J Dahlen, B Krug, N Sandstrom, T Shaw, DE Lutter, R Fleming, LJ Howarth, PH Caruso, M Sousa, AR Corfield, J Auffray, C De Meulder, B Lefaudeux, D Dahlen, S-E Djukanovic, R Sterk, PJ Guo, Y Adcock, IM Chung, KF |
Item Type: | Journal Article |
Abstract: | Background: Exacerbation-prone asthma is a feature of severe disease. Yet, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of the frequent-exacerbator (FE) and of persistent FEs (PFE) in U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures. Results: Of 317 patients, 62.4 % were FE of whom 63.6% were PFE, while 37.6% were IE of whom 61.3% were PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE with eczema, short-acting beta-agonist use and asthma control index. CEA Cell Adhesion Molecule 5 (CEACAM5) was the only differentially-expressed transcript in bronchial biopsies between PE and IE. There were no differentially-expressed genes in the other 4 compartments. There were higher expression scores for Type 2 , T-helper type-17 and Type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while higher expression scores of Type 2, Type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE. Conclusion: FE group and its PFE subgroup are associated with poor asthma control while expressing higher Type 1 and Type 2 activation pathways compared to IE and PIE, respectively. |
Issue Date: | 26-Apr-2022 |
Date of Acceptance: | 29-Mar-2022 |
URI: | http://hdl.handle.net/10044/1/96689 |
DOI: | 10.1002/ctm2.816 |
ISSN: | 2001-1326 |
Publisher: | Wiley |
Journal / Book Title: | Clinical and Translational Medicine |
Volume: | 12 |
Issue: | 4 |
Copyright Statement: | © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics 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. |
Sponsor/Funder: | Commission of the European Communities |
Funder's Grant Number: | 115010 |
Keywords: | Science & Technology Life Sciences & Biomedicine Oncology Medicine, Research & Experimental Research & Experimental Medicine asthma exacerbations severe asthma CEACAM5 frequent exacerbators persistent frequent exacerbators PHENOTYPES STATEMENT LUNG CEACAM5 asthma exacerbations frequent exacerbators persistent frequent exacerbators severe asthma U-BIOPRED study group 1110 Nursing |
Publication Status: | Published |
Article Number: | ARTN e816 |
Appears in Collections: | National Heart and Lung Institute |
This item is licensed under a Creative Commons License