Intra-epithelial neutrophils in paediatric severe asthma are associated with better lung function

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Title: Intra-epithelial neutrophils in paediatric severe asthma are associated with better lung function
Author(s): Andersson, CK
Adams, A
Nagakumar, P
Bossley, C
Gupta, A
De Vries, D
Adnan, A
Bush, A
Saglani, S
Lloyd, CM
Item Type: Journal Article
Abstract: BACKGROUND: Neutrophils and IL-17A have been linked mechanistically in models of allergic airways disease and have been associated with asthma severity. However, their role in paediatric asthma is unknown. OBJECTIVES: To investigate the role of neutrophils and the IL-17A pathway in mediating paediatric severe therapy resistant asthma (STRA). METHODS: Children with STRA (n=51, age 12.6 (6 -16.3) years) and non-asthmatic controls (n=15, age 4.75 (1.6-16) years) underwent clinically indicated fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial brushings and biopsy. Neutrophils, IL-17A and IL-17RA expressing cells and levels of IL-17A and IL-22 were quantified in BAL and biopsies and related to clinical features. Primary bronchial epithelial cells (PBECs) were stimulated with IL-17A and/or IL-22, with and without Budesonide. RESULTS: Children with STRA had increased intra-epithelial neutrophils, which positively correlated with FEV1 %predicted (r=0.43, p=0.008). Neutrophil-high patients also had better symptom control, despite lower dose maintenance inhaled steroids. Submucosal neutrophils were not increased in STRA. Submucosal and epithelial IL-17A positive cells and BAL IL-17A and IL-22 levels were similar in STRA and controls. However, there were significantly more IL-17RA positive cells in the submucosa and epithelium in children with STRA compared to controls (p=0.001). Stimulation of PBECs with IL-17A enhanced mRNA expression of IL-17RA and increased release of IL-8, even in the presence of Budesonide. CONCLUSIONS: A proportion of children with STRA exhibit increased intra-epithelial airway neutrophilia that correlated with better lung function. STRA was additionally characterised by increased airway IL-17RA expression. These data suggest a potential beneficial rather than adverse role for neutrophils in paediatric severe asthma pathophysiology.
Publication Date: 13-Oct-2016
Date of Acceptance: 6-Sep-2016
URI: http://hdl.handle.net/10044/1/42237
DOI: https://dx.doi.org/10.1016/j.jaci.2016.09.022
ISSN: 1097-6825
Publisher: Elsevier
Start Page: 1819
End Page: 1829.e11
Journal / Book Title: Journal of Allergy and Clinical Immunology
Volume: 139
Issue: 6
Copyright Statement: © 2016 The Authors, published by Elsevier. This paper is available under a CC-BY licence (https://creativecommons.org/licenses/by/4.0/)
Keywords: Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
Pediatric asthma
severe therapy-resistant asthma
IL-17A
IL-17A receptor
neutrophils
BRONCHIAL EPITHELIAL-CELLS
COLONY-STIMULATING FACTOR
AIRWAY INFLAMMATION
T-CELLS
CLINICAL CHARACTERISTICS
MESSENGER-RNA
RECEPTOR
HYPERRESPONSIVENESS
INTERLEUKIN-17
IL-17A
IL-17A receptor
Pediatric asthma
neutrophils
severe therapy-resistant asthma
IL-17A
IL-17A receptor
Paediatric asthma
neutrophils
severe therapy resistant asthma
Allergy
1107 Immunology
Publication Status: Published
Conference Place: United States
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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