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Author Notes:

Correspondence to: Anne M. Fitzpatrick, 2015 Uppergate Drive #340, Atlanta, Georgia 30322, anne.fitzpatrick@emory.edu, Telephone: 404-727-9112, Facsimile: 404-712-0920

The authors would like to acknowledge the Children’s Healthcare of Atlanta and Emory University Pediatric Flow Cytometry Core for the provision of flow cytometry equipment utilized for this study.

Disclosures: All authors have nothing to disclose.

Subjects:

Research Funding:

None declared

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Allergy
  • Immunology
  • Severe asthma
  • Asthma phenotype
  • Asthma endotype
  • Neutrophil activation
  • Neutrophil extracellular trap
  • Respiratory burst
  • Airway macrophage
  • Phagocytosis
  • Non-type 2 inflammation
  • Pediatric patients with asthma
  • Healthy adults
  • Differential gene-expression
  • Pediatric severe asthma
  • Inflammation
  • Sputum
  • Identification
  • Heterogeneity
  • Eosinophils
  • Phenotype
  • Relevant
  • Reveals

Children with Neutrophil-Predominant Severe Asthma Have Proinflammatory Neutrophils With Enhanced Survival and Impaired Clearance

Journal Title:

Journal of Allergy and Clinical Immunology: In Practice

Volume:

Volume 7, Number 2

Publisher:

, Pages 516-+

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background: Airway neutrophils are abundant in some children with severe asthma, but their functions are poorly understood. Objective: To characterize that the inflammatory airway environment of children with neutrophil-predominant severe asthma promotes neutrophil survival and disrupts neutrophil-associated innate immune defenses. Methods: Sixty-seven children with severe asthma refractory to high-dose inhaled corticosteroid treatment undergoing bronchoscopy with bronchoalveolar lavage (BAL) for clinical indications were stratified into neutrophil “high” versus “low” groups on the basis of BAL differential counts. Neutrophil activation markers, functional assays, and phenotyping studies were performed, as well as airway macrophage functional assays. Results were compared with those from children with moderate asthma treated with inhaled corticosteroids. Results: Children with neutrophil-predominant severe asthma had increased markers of neutrophil activation/degranulation and a greater magnitude of airway proinflammatory cytokine and chemokine release. Primary neutrophils exposed to BAL of these children exhibited greater phagocytic capability and greater neutrophil extracellular trap formation, but a more impaired respiratory burst. Despite greater abundance of airway TGF-β1, the neutrophils were not more apoptotic. Instead, neutrophils had a highly proinflammatory phenotype associated with a number of surface markers that regulate neutrophil activation, recruitment/migration, and granule release. Airway macrophages from children with neutrophil-predominant severe asthma were also more proinflammatory with impaired phagocytosis and increased apoptosis. Conclusions: Children with neutrophil-predominant severe asthma have proinflammatory neutrophils with enhanced survival. Airway macrophages are also proinflammatory and dysfunctional and may contribute to global innate immune impairment. Therapies that target neutrophils and related inflammation may be warranted in this subset of children.

Copyright information:

© 2018 American Academy of Allergy, Asthma & Immunology

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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