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Author Notes:

Correspondence: Anne M. Fitzpatrick, 2015 Uppergate Drive, Atlanta, GA, 30322; Email: anne.fitzpatrick@emory.edu; Phone: 404-727-9112; Fax: 404-712-0920

Subjects:

Research Funding:

Funded by NIH RO1 NR012021 and supported in part by PHS Grant UL1RR025008 from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources.

Keywords:

  • Airway remodeling
  • Asthma
  • Children
  • Lung function
  • Oxidant stress
  • Transforming growth factor beta-1

Airway TGF-β1 and oxidant stress in children with severe asthma: association with airflow limitation

Tools:

Journal Title:

Journal of Allergy and Clinical Immunology: In Practice

Volume:

Volume 129, Number 2

Publisher:

, Pages 388-396.e8

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background Transforming growth factor beta-1 (TGFβ1) is thought to play a role in airway remodeling in asthma. TGFβ1 expression may be mediated by an excessive burden of reactive oxygen species and oxidant stress. Objective Given the profound airway oxidant stress we have previously observed in children with severe asthma, we sought to: 1) quantify TGFβ1 protein and mRNA gene expression in the airways of children with mild-to-moderate and severe atopic asthma; and to 2) determine the relationship of airway TGFβ1 concentrations to oxidant burden (i.e., lipid peroxidation), Th2-mediated eosinophilic inflammation, and airflow limitation. Methods Bronchoalveolar lavage fluid was collected from 68 atopic children with asthma (severe asthma, n = 28) and 12 atopic adult controls. Airway TGFβ1 expression and activation were assessed in relation to airway IL-13, 8-isoprostane, and malondialdehyde concentrations. The relationship of airway TGFβ1 expression to airflow limitation in children with asthma was also assessed. Results Children with severe asthma had higher total airway concentrations of TGFβ1 that were associated with increased protein and mRNA expression of TGFβ1 in airway macrophages and an increase in the lipid peroxidation biomarkers 8-isoprostanes and malondialdehyde. TGFβ1 activation was also greater in children with severe asthma and was associated with higher airway 8-isoprostane, malondialdehyde and IL-13 concentrations. Total airway TGFβ1 concentrations were further associated with airflow limitation. Conclusions Children with severe asthma have increased airway TGFβ1 expression and activation associated with an increased airway oxidant burden. Oxidant stress may mediate the effects of TGFβ1 and promote airway remodeling in children with severe asthma.

Copyright information:

© 2011 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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