title: Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study.
abstract: 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 aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Robert
authors: R
authors: Linder
authors: Eva
authors: E
authors: Rönmark
authors: Jamshid
authors: J
authors: Pourazar
authors: Annelie
authors: A
authors: Behndig
authors: Anders
authors: A
authors: Blomberg
authors: Anne
authors: A
authors: Lindberg
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003371:Cough / Q000209:etiology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000503:physiopathology; D012307:Risk Factors; D012720:Severity of Illness Index; D013548:Sweden; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9