Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress.
BACKGROUND
Severe asthma is characterized by persistent airway inflammation and increased formation of reactive oxygen species.


OBJECTIVE
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 FEV(1) <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 H(2)O(2) 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 H(2)O(2) 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.


CONCLUSIONS
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.
Fitzpatrick
Anne M
AM
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA. anne.fitzpatrick@emory.edu
Teague
W Gerald
WG
Holguin
Fernando
F
Yeh
Mary
M
Brown
Lou Ann S
LA
D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D002648:Child; D002675:Child, Preschool; D003371:Cough / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics; D005982:Glutathione Transferase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014832:Voice Disorders / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; C075750:8-epi-prostaglandin F2alpha; D008315:Malondialdehyde; D015237:Dinoprost; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione