title: Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects.
abstract: BACKGROUND
  Matrix-metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in the turnover of extracellular matrix. Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are inflammatory diseases characterized by excessive matrix degradation and tissue fibrosis. We have compared sputum concentrations of MMP-9, TIMP-1 and the controlling cytokine tumor necrosis factor (TNF)-alpha in patients with COPD, IPF and healthy subjects.
  
  
  METHODS
  In a cross-sectional analysis, 12 patients with stable COPD, 15 patients with IPF and 14 healthy subjects underwent sputum induction. Induced sputum cells were counted and concentrations of MMP-9, TIMP-1 and TNF were measured by enzyme immunoassays.
  
  
  RESULTS
  Sputum neutrophils were markedly elevated in COPD and IPF patients compared with controls (P<0.001, both comparisons). Concentrations of MMP-9 and the MMP-9:TIMP-1 ratio were increased in COPD (P<0.001 vs. IPF and controls), whereas sputum TIMP-1 levels were both elevated in COPD and IPF (P<0.01 vs. controls, both comparisons). TNF levels were similar in all three groups (P>0.2, all comparisons). MMP-9 concentrations were negatively correlated with airway obstruction (FEV1 FVC) in COPD (rho=-0.62, P=0.03), but not with diffusion capacity or vital capacity (% predicted) in IPF (rho=-0.06, P=0.85, and rho=-0.3, P=0.29, respectively). MMP-9 was positively correlated with sputum neutrophils in all patients (rho=0.68, P<0.0001), and with TNF in COPD patients (rho=0.76, P=0.004).
  
  
  CONCLUSIONS
  These data underline the significance of protease/antiprotease imbalance for the pathogenesis of inflammatory lung diseases. Despite similar cellular inflammatory patterns both in COPD and IPF sputa, marked differences were observed with regard to MMP-9:TIMP-1 balance.
authors.affiliation: Pulmonary Department, Internal Medicine University Hospital Mainz, Lagen beckstr. 1, Main 2 55131, Germany. k.beech@3-med.klnik
authors.forename: K M
authors.initials: KM
authors.lastname: Beeh
authors.forename: J
authors.initials: J
authors.lastname: Beier
authors.forename: O
authors.initials: O
authors.lastname: Kornmann
authors.forename: R
authors.initials: R
authors.lastname: Buhl
mesh_terms: D000368:Aged; D002452:Cell Count; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013183:Sputum / Q000166:cytology / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014797:Vital Capacity / Q000502:physiology
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9