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Author Notes:

Correspondence: Anne M. Fitzpatrick, PhD, 2015 Uppergate Drive, Atlanta, GA 30322; Email: anne.fitzpatrick@emory.edu

Acknowledgments: The Severe Asthma Research Program is a multicenter asthma research group consisting of multiple contributors (Steering Committee members); See publication for full list of contributors

We acknowledge Brian Fitzpatrick for his assistance with database formation and data analysis, Leandrea Burwell for her assistance with glutathione measurement, and Eric Hunter for his assistance with subject characterization.

Disclosures: The authors have declared that they have no conflict of interest.

Subjects:

Research Funding:

Supported by the National Institutes of Health (NIH)/National Institute for Nursing Research (NINR) KO1 NR010584, NIH/National Center for Research Resources (NCRR) K12 RR017643, NIH/National Heart, Lung, and Blood Institute (NHLBI) Severe Asthma Research Program RO1 HL69170, and the American Nurses Foundation.

The Severe Asthma Research Program is a multicenter asthma research group funded by the National Heart, Lung, and Blood Institute

Keywords:

  • Asthma
  • children
  • glutathione
  • 8-isoprostanes
  • hydrogen peroxide
  • malondialdehyde
  • oxidative stress
  • redox potential

Airway glutathione homeostasis is altered in children with severe asthma: Evidence for oxidant stress

Tools:

Journal Title:

Journal of Allergy and Clinical Immunology: In Practice

Volume:

Volume 123, Number 1

Publisher:

, Pages 146-152.e8

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background Severe asthma is characterized by persistent airway inflammation and increased formation of reactive oxygen species. Objectives Glutathione (GSH) is an important antioxidant in the epithelial lining fluid (ELF). We hypothesized that airway GSH homeostasis was altered in children with severe asthma and was characterized by decreased GSH and increased glutathione disulfide (GSSG) concentrations. Methods Bronchoalveolar lavage was obtained from 65 children with severe asthma, including 35 children with baseline airway obstruction evidenced by FEV1 <80%. Control data were obtained from 6 children with psychogenic (habit) cough or vocal cord dysfunction undergoing diagnostic bronchoscopy and 35 healthy adult controls. GSH, GSSG, and other determinants of airway oxidative stress including glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde, 8-isoprostane, and H2O2 were measured in the ELF. The ELF redox potential was calculated from GSH and GSSG by using the Nernst equation. Results: Compared with controls, subjects with severe asthma had lower airway GSH with increased GSSG despite no differences in GST, GR, and GPx activities between groups. This was accompanied by increased malondialdehyde, 8-isoprostane, and H2O2 concentrations in the ELF. GSH oxidation was most apparent in subjects with severe asthma with airway obstruction and was supported by an upward shift in the ELF GSH redox potential. Conclusion Children with severe asthma have increased biomarkers of oxidant stress in the ELF that are associated with increased formation of GSSG and a shift in the GSH redox potential toward the more oxidized state.

Copyright information:

© 2009 Elsevier

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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