Abstract
BACKGROUND:
Exacerbations of COPD are associated with accelerated deterioration of respiratory symptoms and pulmonary function. Matrix metalloproteinases (MMP) are a family of endopeptidases involved in extracellular matrix cleavage. We hypothesize that there is a difference in the expression and the enzymatic activity of MMP in bronchoalveolar lavage fluid (BALF) of COPD patients with and without exacerbation.
METHODS:
Seventy patients with COPD diagnosed according to the GOLD guidelines with either stable disease or exacerbation and undergoing diagnostic bronchoscopy were included in this prospective cohort study. BAL was performed by installation of 3 x 50 ml of pyrogen-free sterile NaCL 0.9% solution over the working channel of the bronchoscope according to standard guidelines. Enzymatic activity of MMP was assessed by gelatin zymography and protein levels of MMP-2, MMP-9 and of tissue inhibitors of MMP (TIMP) were measured by ELISA.
RESULTS:
Data of 40 patients with COPD (stable COPD n=20, exacerbation n=20) have been analyzed so far. Mean age was 68.9 years (±9.5), mean FEV1 %pred 49.9% (±16.9), mean DLCO %pred 43.1% (±18.8). As compared to patients with COPD at stable state, the MMP-9 enzymatic activity and protein expression were increased by 73% and 62%, respectively (p<0.001) in the BALF of patients with COPD at exacerbation. In contrast, there was no significant alteration in TIMP expression, indicating a net increase of collagenase activity associated with exacerbation.
CONCLUSION:
Increased activity of MMP-9 during acute exacerbation might contribute to tissue destruction and development of emphysema in patients with recurrent exacerbations of COPD.
- © 2012 ERS