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Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD

Rekha Chaudhuri1, Charles McSharry1, Mark Spears1, Jeffrey Brady234, Christal Grierson234, C Martina Messow5, Gino Miele234, Karl Nocka234, William MacNee6, Martin Connell6, John T Murchison6, Michael Sproule7, Omar Hilmi8, Douglas K Miller234 and Neil C Thomson1*

Author Affiliations

1 Immunology, Institute of Infection, Immunity & Inflammation, University of Glasgow and Gartnavel General Hospital, Glasgow, Scotland G12 OYN, UK

2 Pfizer Research/Translational Medicine Research Collaboration, Dundee, UK

3 Pfizer Research/Translational Medicine Research Collaboration, Cambridge, MA, USA

4 Pfizer Research/Translational Medicine Research Collaboration, Collegeville, PA, USA

5 Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK

6 MRC Centre for Inflammation Research, Medical Physics and Clinical Radiology, University of Edinburgh, Edinburgh, UK

7 Radiology Department, Gartnavel General Hospital, Glasgow, UK

8 Ear Nose and Throat Department, Gartnavel General Hospital, Glasgow, UK

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Translational Respiratory Medicine 2013, 1:11  doi:10.1186/2213-0802-1-11

Published: 6 June 2013

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.

Findings

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.

Keywords:
MMP-9; MMP-9 expression; COPD; Computed tomography