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

Autor: Hoda U; National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK., Pavlidis S; Department of Computing & Data Science Institute, Imperial College London., Bansal AT; Acclarogen, Cambridge, UK., Takahashi K; National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK.; Research Centre for Allergy and Clinical Immunology, Asahi General Hospital, Asahi, Japan., Hu S; Acclarogen, Cambridge, UK., Ng Kee Kwong F; National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK., Rossios C; National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK., Sun K; Acclarogen, Cambridge, UK., Bhavsar P; National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK., Loza M; Janssen Research and Development, High Wycombe, Buckinghamshire, UK., Baribaud F; Janssen Research and Development, High Wycombe, Buckinghamshire, UK., Chanez P; Assistance Publique des Hôpitaux de Marseille, Clinique des Bronches, Allergies et Sommeil, Aix Marseille Université, Marseille, France., Fowler SJ; Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, School of Biological Sciences, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, and NIHR Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK., Horvath I; Department of Pulmonology, Semmelweis University, Budapest, Hungary., Montuschi P; Catholic University of Sacred Heart, Rome, Italy., Singer F; Department of Respiratory Medicine, University Children's Hospital Zurich and Childhood Research Center, Zurich, and Department of Paediatrics, Inselspital, University of Bern, Switzerland., Musial J; Department of Medicine, Jagiellonian University Medical College, Krakow, Poland., Dahlen B; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden., Krug N; Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany., Sandstrom T; Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden., Shaw DE; Respiratory Research Unit, University of Nottingham, UK., Lutter R; Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Fleming LJ; National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK., Howarth PH; NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK., Caruso M; Department of Biochemical and Biotechnological Medicine, University of Catania, Catania, Italy., Sousa AR; Respiratory Therapeutic Unit, GSK, Stockley Park, UK., Corfield J; AstraZeneca R&D, Molndal, Sweden, and Areteva R&D, Nottingham, UK., Auffray C; European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Lyon, France., De Meulder B; European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Lyon, France., Lefaudeux D; European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Lyon, France., Dahlen SE; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden., Djukanovic R; NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK., Sterk PJ; Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Guo Y; Acclarogen, Cambridge, UK., Adcock IM; National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK., Chung KF; National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK.
Jazyk: angličtina
Zdroj: Clinical and translational medicine [Clin Transl Med] 2022 Apr; Vol. 12 (4), pp. e816.
DOI: 10.1002/ctm2.816
Abstrakt: Background: Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.
Objectives: To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the 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% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated 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 four 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 there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.
Conclusion: The 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.
(© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)
Databáze: MEDLINE
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