Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function
(2017) In Journal of Allergy and Clinical Immunology 139(6). p.11-1829- 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 pediatric asthma is unknown.
OBJECTIVES: We sought to investigate the role of neutrophils and the IL-17A pathway in mediating pediatric severe therapy-resistant asthma (STRA).
METHODS: Children with STRA (n = 51; age, 12.6 years; range, 6-16.3 years) and controls without asthma (n = 15; age, 4.75 years; range, 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... (More)
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 pediatric asthma is unknown.
OBJECTIVES: We sought to investigate the role of neutrophils and the IL-17A pathway in mediating pediatric severe therapy-resistant asthma (STRA).
METHODS: Children with STRA (n = 51; age, 12.6 years; range, 6-16.3 years) and controls without asthma (n = 15; age, 4.75 years; range, 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 were stimulated with IL-17A and/or IL-22, with and without budesonide.
RESULTS: Children with STRA had increased intraepithelial neutrophils, which positively correlated with FEV1 %predicted (r = 0.43; P = .008). Neutrophilhigh patients also had better symptom control, despite lower dose maintenance inhaled steroids. Submucosal neutrophils were not increased in children with STRA. Submucosal and epithelial IL-17A-positive cells and BAL IL-17A and IL-22 levels were similar in children with STRA and controls. However, there were significantly more IL-17RA-positive cells in the submucosa and epithelium in children with STRA compared with controls (P = .001). Stimulation of primary bronchial epithelial cells 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 intraepithelial airway neutrophilia that correlated with better lung function. STRA was also characterized by increased airway IL-17RA expression. These data suggest a potential beneficial rather than adverse role for neutrophils in pediatric severe asthma pathophysiology.
(Less)
- author
- Andersson, Cecilia K. LU ; Adams, Alexandra ; Nagakumar, Prasad ; Bossley, Cara ; Gupta, Atul ; De Vries, Daphne ; Adnan, Afiqah ; Bush, Andrew ; Saglani, Sejal and Lloyd, Clare M
- publishing date
- 2017-06
- type
- Contribution to journal
- publication status
- published
- keywords
- Adolescent, Asthma, Biopsy, Bronchoalveolar Lavage Fluid, Bronchoscopy, Child, Child, Preschool, Female, Humans, Infant, Interleukin-17, Interleukins, Lung, Male, Neutrophils, Receptors, Interleukin-17, Respiratory Mucosa, Journal Article
- in
- Journal of Allergy and Clinical Immunology
- volume
- 139
- issue
- 6
- pages
- 11 - 1829
- publisher
- Elsevier
- external identifiers
-
- pmid:27746241
- scopus:85006932870
- ISSN
- 1097-6825
- DOI
- 10.1016/j.jaci.2016.09.022
- language
- English
- LU publication?
- no
- id
- 3a111f39-4a34-45bf-befa-c9196f7391a1
- date added to LUP
- 2018-01-08 13:30:59
- date last changed
- 2024-12-11 00:47:54
@article{3a111f39-4a34-45bf-befa-c9196f7391a1,
abstract = {{<p>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 pediatric asthma is unknown.</p><p>OBJECTIVES: We sought to investigate the role of neutrophils and the IL-17A pathway in mediating pediatric severe therapy-resistant asthma (STRA).</p><p>METHODS: Children with STRA (n = 51; age, 12.6 years; range, 6-16.3 years) and controls without asthma (n = 15; age, 4.75 years; range, 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 were stimulated with IL-17A and/or IL-22, with and without budesonide.</p><p>RESULTS: Children with STRA had increased intraepithelial neutrophils, which positively correlated with FEV1 %predicted (r = 0.43; P = .008). Neutrophilhigh patients also had better symptom control, despite lower dose maintenance inhaled steroids. Submucosal neutrophils were not increased in children with STRA. Submucosal and epithelial IL-17A-positive cells and BAL IL-17A and IL-22 levels were similar in children with STRA and controls. However, there were significantly more IL-17RA-positive cells in the submucosa and epithelium in children with STRA compared with controls (P = .001). Stimulation of primary bronchial epithelial cells with IL-17A enhanced mRNA expression of IL-17RA and increased release of IL-8, even in the presence of budesonide.</p><p>CONCLUSIONS: A proportion of children with STRA exhibit increased intraepithelial airway neutrophilia that correlated with better lung function. STRA was also characterized by increased airway IL-17RA expression. These data suggest a potential beneficial rather than adverse role for neutrophils in pediatric severe asthma pathophysiology.</p>}},
author = {{Andersson, Cecilia K. and Adams, Alexandra and Nagakumar, Prasad and Bossley, Cara and Gupta, Atul and De Vries, Daphne and Adnan, Afiqah and Bush, Andrew and Saglani, Sejal and Lloyd, Clare M}},
issn = {{1097-6825}},
keywords = {{Adolescent; Asthma; Biopsy; Bronchoalveolar Lavage Fluid; Bronchoscopy; Child; Child, Preschool; Female; Humans; Infant; Interleukin-17; Interleukins; Lung; Male; Neutrophils; Receptors, Interleukin-17; Respiratory Mucosa; Journal Article}},
language = {{eng}},
number = {{6}},
pages = {{11--1829}},
publisher = {{Elsevier}},
series = {{Journal of Allergy and Clinical Immunology}},
title = {{Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function}},
url = {{http://dx.doi.org/10.1016/j.jaci.2016.09.022}},
doi = {{10.1016/j.jaci.2016.09.022}},
volume = {{139}},
year = {{2017}},
}