Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study

Respiratory Research

Anne Lindberg²  Anders Blomberg²  Annelie Behndig²  Jamshid Pourazar²  Eva Rönmark¹  Robert Linder² 

[1] Department of Public Health and Clinical Medicine, the OLIN unit, Division of Occupational and Environmental Medicine, Umeå, University,, SE-90187, Umeå, Sweden;Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, SE-90187, Sweden

关键词: Proteases;    MMP-9/TIMP-1 ratio;    TIMP-1;    Productive cough;    Lung function;   

Others  :  1133334
DOI  :  10.1186/s12931-015-0188-4

 received in 2014-11-22, accepted in 2015-02-04,  发布年份 2015

【 摘 要 】

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).

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.

【 授权许可】

   
2015 Linder et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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