Introduction and objectives Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extra-cellular matrix (ECM) and drive tissue remodelling, key processes in the pathogenesis of COPD. The development of small airway disease and emphysema have been identified as critical mechanisms in the development of airflow obstruction but the contribution of MMPs in human disease is poorly characterised.
We investigated the role of MMPs in the lung by quantifying levels and determining relationships with the key pathological components of COPD, measured by CT, in patients and healthy controls.
Methods 24 mild and moderate COPD and 8 control subjects were enrolled onto the study and underwent bronchoalveolar lavage (BAL) and high resolution CT. We analysed levels of MMPs in BAL using a Luminex immunoassay. Image analysis, performed using VIDA Apollo software, quantitatively assessed emphysema, bronchial wall thickening and small airways disease.
Results Multiple MMPs (MMP-1, -2, -3, -8, -9 and -10) were significantly elevated in the lungs of COPD subjects. MMP -3, -7, -8, -9, -10, and -12 concentrations were closely associated with CT markers of small airways disease (Table 1). Emphysema severity was also associated with MMP-3, -7, -8 and -10. However there were no strong relationships between MMPs and bronchial wall thickness of the larger airways.
Stepwise linear regression analysis identified MMP-10 to be the only significant predictor of emphysema (R2 0.34, p 0.001) that was independent of each of the other MMPs while MMP-8 was the only significant predictor of small airways disease (R2 0.56, p < 0.001) independent of each of the other MMPs.
Conclusion Pulmonary MMP concentrations are directly associated with the extent of gas trapping and small airways disease identified on CT scan. This suggests that MMPs may play a significant role in the pathogenesis of COPD by causing breakdown of the pulmonary ECM leading to abnormal remodelling in both the small airways and lung parenchyma. Whilst most previous work has focused on MMPs and emphysema, this study shows the strongest associations were with small airways disease.