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Hekking, PP; Loza, MJ; Pavlidis, S; de, Meulder, B; Lefaudeux, D; Baribaud, F; Auffray, C; Wagener, AH; Brinkman, P; Lutter, R; Bansal, AT; Sousa, AR; Bates, SA; Pandis, Y; Fleming, LJ; Shaw, DE; Fowler, SJ; Guo, Y; Meiser, A; Sun, K; Corfield, J; Howarth, PH; Bel, EH; Adcock, IM; Chung, KF; Djukanovic, R; Sterk, PJ, , U-BIOPRED, Study, Group, , U-BIOPRED, Study, Group.
Pathway discovery using transcriptomic profiles in adult-onset severe asthma.
J Allergy Clin Immunol. 2018; 141(4):1280-1290
Doi: 10.1016/j.jaci.2017.06.037
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PubMed
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Singer Florian
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- Abstract:
- BACKGROUND: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. OBJECTIVE: We sought to identify gene profiles associated with adult-onset severe asthma. METHODS: This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways. RESULTS: Significant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma. CONCLUSIONS: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.
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Adult - administration & dosage
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Age of Onset - administration & dosage
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Asthma - genetics, immunology
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Cross-Sectional Studies - administration & dosage
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Female - administration & dosage
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Gene Expression Profiling - administration & dosage
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Genetic Markers - administration & dosage
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Humans - administration & dosage
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Male - administration & dosage
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Middle Aged - administration & dosage
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Oligonucleotide Array Sequence Analysis - administration & dosage
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Phenotype - administration & dosage
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Severity of Illness Index - administration & dosage
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Transcriptome - immunology
- Find related publications in this database (Keywords)
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Adult-onset asthma
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severe asthma
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gene set variation analysis
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phenotyping
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transcriptomics
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mechanisms
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eosinophils
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mast cells
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ILC3