Background
Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis. Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways. Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD. The
Conclusion
Productive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort. The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes.
Methods
Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.
Results
Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).