Pulmonary type2 innate lymphoid cells in paediatric severe asthma: phenotype and response to steroids
File(s)1801809.full.pdf (862.61 KB)
Published version
Author(s)
Type
Journal Article
Abstract
Children with severe therapy resistant asthma (STRA) have poor control despite maximal treatment, while those with difficult asthma (DA) have poor control from failure to implement basic management including adherence to therapy. Although recognised as clinically distinct, the airway molecular phenotype, including the role of ILCs and their response to steroids in DA and STRA is unknown.Immunophenotyping of sputum and blood ILCs and T cells from STRA, DA and non-asthmatic controls was undertaken. Leukocytes were analysed longitudinally pre and post intramuscular triamcinolone in children with STRA. Cultured ILCs were also evaluated to assess steroid responsiveness in vitroAirway eosinophils, Th2 cells and ILC2s were significantly higher in STRA patients compared to DA and disease controls, while IL-17+ lymphoid cells were similar. ILC2s and Th2 cells were significantly reduced in vivo following intramuscular triamcinolone and in vitro with steroids. Asthma attacks and symptoms also reduced after systemic steroids despite persistence of steroid resistant IL-17+ cells and eosinophils.Paediatric STRA and DA have distinct airway molecular phenotypes with STRA characterised by elevated type2 cells. Systemic corticosteroids but not maintenance inhaled steroids resulted in improved symptom control and exacerbations concomitant with a reduction in functional ILC2s despite persistently elevated IL-17+ lymphoid cells.
Date Issued
2019-06-04
Date Acceptance
2019-05-26
Citation
European Respiratory Journal, 2019, 54 (2), pp.1-14
ISSN
0903-1936
Publisher
European Respiratory Society
Start Page
1
End Page
14
Journal / Book Title
European Respiratory Journal
Volume
54
Issue
2
Copyright Statement
©ERS 2019. This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
Sponsor
Wellcome Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31164437
PII: 13993003.01809-2018
Grant Number
087618/Z/08/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Respiratory System
AIRWAY INFLAMMATION
IL-17
EXPRESSION
IL-33
LUNG
EXACERBATION
EOSINOPHILIA
NEUTROPHILS
CHILDREN
THERAPY
Respiratory System
11 Medical and Health Sciences
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2019-08-29