title: Increased levels of osteopontin in sputum supernatant in severe refractory asthma.
abstract: BACKGROUND
  Osteopontin (OPN) is a glycoprotein that has been associated with inflammation and fibrosis. Severe refractory asthma (SRA) is characterised by an intense inflammatory and remodelling process. The aim of this study was to investigate the levels of OPN in sputum supernatants of patients with SRA, to compare them with milder forms of the disease and to investigate their possible association with mediators and cells involved in the inflammatory and remodelling process.
  
  
  METHODS
  33 patients with SRA, 29 with moderate asthma, 21 with steroid-naïve asthma and 20 healthy subjects were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of OPN, vascular endothelial growth factor, transforming growth factor beta1 (TGF-beta1), cysteinyl leukotrienes, interleukin 13 (IL-13), eosinophilic cationic protein (ECP) and IL-8 in sputum supernatants.
  
  
  RESULTS
  Median (IQR) OPN levels (pg/ml) were significantly higher in patients with SRA than in those with moderate asthma, steroid-naive asthma and healthy control subjects (1840 (1125-11000) vs 130 (100-210) vs 100 (67-130) vs 50 (42-70), respectively, p<0.001). Regression analysis showed a significant association between log OPN and sputum eosinophils, cysteinyl leukotrienes, IL-13, TGF-beta1 and ECP. TGF-beta1 represented the strongest association with OPN. The above associations were not observed in milder forms of the disease or in healthy subjects.
  
  
  CONCLUSIONS
  The results indicate that OPN levels are higher in SRA than in less severe forms of the disease. Moreover, OPN is associated with mediators involved in both the inflammatory and remodelling process such as TGF-beta1, IL-13 and cysteinyl leukotrienes only in SRA.
authors.affiliation: 2nd Respiratory Medicine Department, University of Athens Medical School, Attikon Hospital, Smolika 2 16673, Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Delimpoura
authors.forename: Petros
authors.initials: P
authors.lastname: Bakakos
authors.forename: Eleni
authors.initials: E
authors.lastname: Tseliou
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Bessa
authors.forename: Georgios
authors.initials: G
authors.lastname: Hillas
authors.forename: Davina C M
authors.initials: DC
authors.lastname: Simoes
authors.forename: Spyros
authors.initials: S
authors.lastname: Papiris
authors.forename: Stelios
authors.initials: S
authors.lastname: Loukides
mesh_terms: D000328:Adult; D000368:Aged; D056151:Airway Remodeling / Q000502:physiology; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000032:analysis*; D013183:Sputum / Q000737:chemistry*; D014797:Vital Capacity / Q000502:physiology
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D018836:Inflammation Mediators; D053495:Osteopontin