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Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort

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
Medicine, Research & Experimental
Research & Experimental Medicine
asthma exacerbations
severe asthma
frequent exacerbators
persistent frequent exacerbators
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

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