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Intraepithelial neutrophils in pediatric severe asthma are associated with better lung function

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 (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.

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author
publishing date
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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
  • 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
2018-10-28 04:50:13
@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},
  keyword      = {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},
  volume       = {139},
  year         = {2017},
}