Pathway discovery using transcriptomic profiles in adult-onset severe asthma.
Publisher DOI
PubMed ID
28756296
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.
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.
Date Issued
2018-04
Publication Type
Article
Subject(s)
Subjects
Adult-onset asthma ILC3 eosinophils gene set variation analysis mast cells mechanisms phenotyping severe asthma transcriptomics
Language(s)
en
Author(s)
Hekking, Pieter-Paul | |
Loza, Matt J | |
Pavlidis, Stelios | |
de Meulder, Bertrand | |
Lefaudeux, Diane | |
Baribaud, Fred | |
Auffray, Charles | |
Wagener, Ariane H | |
Brinkman, Paul | |
Lutter, Rene | |
Bansal, Aruna T | |
Sousa, Ana R | |
Bates, Steve A | |
Pandis, Yannis | |
Fleming, Louise J | |
Shaw, Dominique E | |
Fowler, Stephen J | |
Guo, Y | |
Meiser, Andrea | |
Sun, Kai | |
Corfield, Julie | |
Howarth, Peter H | |
Bel, Elisabeth H | |
Adcock, Ian M | |
Chung, Kian Fan | |
Djukanovic, Ratko | |
Sterk, Peter J | |
U-BIOPRED, Study Group |
Journal
The Journal of allergy and clinical immunology
Publisher
Elsevier
ISSN
1097-6825
Access(Rights)
metadata.only