title: Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma.
abstract: BACKGROUND
  Increased oxidative stress and decreased superoxide dismutase (SOD) activity in the asthmatic airway are correlated to airflow limitation and hyperreactivity. We hypothesized that asthmatic individuals with higher levels of oxidative stress may have greater loss of SOD activity, which would be reflected systemically in loss of circulating SOD activity and clinically by development of severe asthma and/or worsening airflow limitation.
  
  
  METHODS
  To investigate this, serum SOD activity and proteins, the glutathione peroxidase/glutathione antioxidant system, and oxidatively modified amino acids were measured in subjects with asthma and healthy control subjects.
  
  
  RESULTS
  SOD activity, but not Mn-SOD or Cu,Zn-SOD protein, was lower in asthmatic serum as compared with control, and activity loss was significantly related to airflow limitation. Further, serum SOD activity demonstrated an inverse correlation with circulating levels of 3-bromotyrosine, a posttranslational modification of proteins produced by the eosinophil peroxidase system of eosinophils. Exposure of purified Cu,Zn-SOD to physiologically relevant levels of eosinophil peroxidase-generated reactive brominating species, reactive nitrogen species, or tyrosyl radicals in vitro confirmed that eosinophil-derived oxidative pathways promote enzyme inactivation.
  
  
  CONCLUSIONS
  These findings are consistent with greater oxidant stress in asthma leading to greater inactivation of SOD, which likely amplifies inflammation and progressive airflow obstruction.
authors.affiliation: Department of Pathology, Cleveland Clinic Foundation, OH 44195, USA. comhais@ccf.org
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Ricci
authors.forename: Mercedes
authors.initials: M
authors.lastname: Arroliga
authors.forename: Abigail R
authors.initials: AR
authors.lastname: Lara
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Annette
authors.initials: A
authors.lastname: Hastie
authors.forename: Mark
authors.initials: M
authors.lastname: Hew
authors.forename: Nizar
authors.initials: N
authors.lastname: Jarjour
authors.forename: Wendy
authors.initials: W
authors.lastname: Moore
authors.forename: Stephen
authors.initials: S
authors.lastname: Peters
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
mesh_terms: D000328:Adult; D000402:Airway Obstruction / Q000201:enzymology; D000596:Amino Acids / Q000097:blood; D001249:Asthma / Q000201:enzymology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D012129:Respiratory Function Tests; D013147:Spirometry; D013482:Superoxide Dismutase / Q000097:blood / Q000172:deficiency*
chemical_list: D000596:Amino Acids; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione