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SHR Neuro Krebs Kardio Lipid Stoffw Microb

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, SE; Djukanovic, R; Sterk, PJ; Guo, Y; Adcock, IM; Chung, KF, , U-BIOPRED, study, group.
Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort.
Clin Transl Med. 2022; 12(4):e816 Doi: 10.1002/ctm2.816 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Singer Florian
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Abstract:
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.
Find related publications in this database (using NLM MeSH Indexing)
Asthma - genetics, metabolism, pathology
Bronchi - pathology
Cohort Studies - administration & dosage
Humans - administration & dosage
Sputum - metabolism
Transcriptome - genetics

Find related publications in this database (Keywords)
asthma exacerbations
severe asthma
CEACAM5
frequent exacerbators
persistent frequent exacerbators
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