Activation of MMP-9 in BAL is increased in COPD exacerbation independently of smoking, lung function, microbiology and treatment

BACKGROUND : Acute exacerbations of COPD (AE-COPD) are associated with accelerated deterioration of respiratory symptoms and pulmonary function. Matrix metalloproteinases (MMPs) are involved in cleavage of extracellular matrix and COPD pathogenesis. AIM: To investigate whether AE-COPD are associated with differential expression and activity of MMPs in BAL. METHODS: 94 COPD patients diagnosed with either stable disease (S-COPD) (n=53) or AE-COPD (n=44), undergoing diagnostic bronchoscopy with BAL were included in this study. Enzymatic activity of MMP-2 and -9 was assessed by gelatin zymography in BAL and protein levels of MMP-2, -9, -12 and of their tissue inhibitors were measured by ELISA. Immunocytochemistry using specific antibodies for MMP-2, -9 and -12 was also performed in cytospins of BAL cells. RESULTS: Activation of MMP-9 in BAL samples was significantly increased in AE-COPD, as compared to S-COPD (p=0.017). This association remained significant after adjustment for age, gender, PY, FEV 1 % pred, DLCO% pred, RV% pred, bacterial and viral infection and oral steroid treatment in a multivariable logistic model. Furthermore, there was a significant negative correlation of MMP-9 with FEV1%pred but not with RV%pred in AE-COPD. CONCLUSION: Activation of MMP-9 is a persistent aggravating factor in AE-COPD associated rather to airway obstruction than to emphysema. This observation indicates a putative therapeutic role of MMP-9 inhibitors in preventing AE-COPD.