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Author Notes:

Corresponding author: Anne M. Fitzpatrick, PhD, Department of Pediatrics, Emory University, 2015 Uppergate Dr, Atlanta, GA 30322. anne.fitzpatrick@emory.edu

A. M. Fitzpatrick has received money for consultancy from Genentech and Boehringer Ingelheim.

A. M. Fitzpatrick’s institution, S. T. Stephenson’s institution, M. R. Brown’s institution, K. Nguyen’s institution, S. Douglas’ institution, and L. A. S. Brown’s institution have received a grant from the National Institutes of Health (NIH)/National Institute of Nursing Research (grant no. R01NR012021).

Subject:

Research Funding:

This study was funded by grant number R01 NR012021 and was supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health (award no. UL1 TR000454).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Allergy
  • Immunology
  • Childhood asthma
  • Phenotype
  • Refractory asthma
  • Severe asthma
  • Gene expression
  • Corticosteroid
  • EXHALED NITRIC-OXIDE
  • INTRAMUSCULAR TRIAMCINOLONE ACETONIDE
  • QUALITY-OF-LIFE
  • DIFFICULT ASTHMA
  • CONTROL QUESTIONNAIRE
  • PEDIATRIC-PATIENTS
  • RESISTANT ASTHMA
  • THERAPY
  • RESPONSIVENESS
  • INFLAMMATION

Systemic Corticosteroid Responses in Children with Severe Asthma: Phenotypic and Endotypic Features

Tools:

Journal Title:

Journal of Allergy and Clinical Immunology: In Practice

Volume:

Volume 5, Number 2

Publisher:

, Pages 410-+

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background: Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking. Objective: This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response. Methods: Asthma-related quality of life, exhaled nitric oxide, blood eosinophils, lung function, and inflammatory cytokine and chemokine mRNA gene expression in peripheral blood mononuclear cells were assessed in 56 children with severe asthma at baseline and 14 days after intramuscular triamcinolone injection. The Asthma Control Questionnaire was used to classify children with severe asthma into corticosteroid response groups. Results: Three groups of children with severe asthma were identified: controlled severe asthma, children who achieved control after triamcinolone, and children who did not achieve control. At baseline, these groups were phenotypically similar. After triamcinolone, discordance between symptoms, lung function, exhaled nitric oxide, and blood eosinophils was noted. Clinical phenotypic predictors were of limited utility in predicting the triamcinolone response, whereas systemic mRNA expression of inflammatory cytokines and chemokines related to IL-2, IL-10, and TNF signaling pathways, namely, . AIMP1, . CCR2, . IL10RB, and . IL5, strongly differentiated children who failed to achieve control with triamcinolone administration. Conclusions: Systemic corticosteroid responsiveness in children with severe asthma is heterogeneous. Alternative prediction models that include molecular endotypic as well as clinical phenotypic features are needed to identify which children derive the most clinical benefit from systemic corticosteroid step-up therapy given the potential side effects.

Copyright information:

© 2016 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 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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