title: Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD.
abstract: BACKGROUND
  Matrix-metalloproteinase (MMP)-9 has been implicated in the pathogenesis of COPD, although its link to disease severity is unclear. The purpose of the study was to examine the relationship between disease severity assessed by lung function and computed tomography (CT) and sputum MMP-9 expression, concentration and activity in patients with COPD.
  
  
  RESULTS
  In 53 COPD subjects, smokers and ex-smokers; 46 healthy controls, smokers and never smokers, we measured sputum MMP-9 concentrations (ELISA) and enzyme activity (FRET), sputum MMP-9 mRNA expression, spirometry, diffusing capacity for carbon monoxide (DLco) and CT assessment of emphysema (% low attenuation areas below-950 Hounsfield units). Sputum MMP-9 concentrations and mRNA expression in COPD subjects were significantly greater than in healthy never-smokers (p = 0.007 and p = 0.001 respectively) and similar to those in healthy smokers. Disease severity when assessed by the extent of emphysema measured by CT, but not by spirometry or DLco values, was directly associated with sputum MMP-9 concentrations [r = 0.442 (0.171, 0.634), p = 0.020], and MMP-9 activity [r = 0.447 (0.219, 0.643), p = 0.010]. In moderate to severe COPD, increased MMP-9 mRNA expression levels were associated with reduced post-bronchodilator FEV1 [r = -0.530 (-0.686, -0.327), p < 0.001], FEV1/FVC ratio [r = -0.551 (-0.701, -0.354), p < 0.001] and reduced DLco [r = -0.399 (-539, -0.102), p = 0.048].
  
  
  CONCLUSIONS
  Sputum MMP-9 concentrations in COPD are directly associated with the extent of emphysema measured by CT and MMP-9 expression levels are inversely associated with DLco. These findings support a role for MMP-9 in the pathogenesis of COPD.
authors.affiliation: Immunology, Institute of Infection, Immunity & Inflammation, University of Glasgow and Gartnavel General Hospital, Glasgow, Scotland, G12 OYN, UK.
authors.forename: Rekha
authors.initials: R
authors.lastname: Chaudhuri
authors.affiliation: Immunology, Institute of Infection, Immunity & Inflammation, University of Glasgow and Gartnavel General Hospital, Glasgow, Scotland, G12 OYN, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: McSharry
authors.affiliation: Immunology, Institute of Infection, Immunity & Inflammation, University of Glasgow and Gartnavel General Hospital, Glasgow, Scotland, G12 OYN, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Spears
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK.|Pfizer Research/Translational Medicine Research Collaboration, Cambridge, MA, USA.|Pfizer Research/Translational Medicine Research Collaboration, Collegeville, PA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Brady
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK.|Pfizer Research/Translational Medicine Research Collaboration, Cambridge, MA, USA.|Pfizer Research/Translational Medicine Research Collaboration, Collegeville, PA, USA.
authors.forename: Christal
authors.initials: C
authors.lastname: Grierson
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: C Martina
authors.initials: CM
authors.lastname: Messow
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK.|Pfizer Research/Translational Medicine Research Collaboration, Cambridge, MA, USA.|Pfizer Research/Translational Medicine Research Collaboration, Collegeville, PA, USA.
authors.forename: Gino
authors.initials: G
authors.lastname: Miele
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK.|Pfizer Research/Translational Medicine Research Collaboration, Cambridge, MA, USA.|Pfizer Research/Translational Medicine Research Collaboration, Collegeville, PA, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Nocka
authors.affiliation: MRC Centre for Inflammation Research, Medical Physics and Clinical Radiology, University of Edinburgh, Edinburgh, UK.
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.affiliation: MRC Centre for Inflammation Research, Medical Physics and Clinical Radiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Connell
authors.affiliation: MRC Centre for Inflammation Research, Medical Physics and Clinical Radiology, University of Edinburgh, Edinburgh, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: Murchison
authors.affiliation: Radiology Department, Gartnavel General Hospital, Glasgow, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Sproule
authors.affiliation: Ear Nose and Throat Department, Gartnavel General Hospital, Glasgow, UK.
authors.forename: Omar
authors.initials: O
authors.lastname: Hilmi
authors.affiliation: Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK.|Pfizer Research/Translational Medicine Research Collaboration, Cambridge, MA, USA.|Pfizer Research/Translational Medicine Research Collaboration, Collegeville, PA, USA.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Miller
authors.affiliation: Immunology, Institute of Infection, Immunity & Inflammation, University of Glasgow and Gartnavel General Hospital, Glasgow, Scotland, G12 OYN, UK. neil.thomson@glasgow.ac.uk.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Thomson
keywords: COPD; Computed tomography; MMP-9; MMP-9 expression