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

Rekha Chaudhuri, Charles Mcsharry, Mark Spears, Jeffrey Brady, Christal Grierson, C Messow, Gino Miele, Karl Nocka, William Macnee, Martin Connell, John T Murchison, Michael Sproule, Omar Hilmi, Douglas K Miller, Neil C Thomson

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)11
JournalTranslational Respiratory Medicine
Volume1
Issue number1
DOIs
Publication statusPublished - 6 Jun 2013

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