Background: Markers of extracellular matrix turnover were evaluated in the ECLIPSE study, an observational, multicentre, three-year study ([NCT00292552][1]). Methods: 1000 COPD subjects from ECLIPSE (GOLD stage II-IV) selected based on the most or the least rapid lung function decline were included. Tissue turnover was assessed in serum samples from the year 1 visit by ELISAs measuring MMP-generated fragments of collagen type I, and VI. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV1 (FEV1-PD) and FEV1% predicted (FEV1%-PD) loss over two years including the co-variates gender, age, BMI, smoking, bronchodilator reversibility, #prior AECOPDs, emphysema and chronic bronchitis status at baseline. Results: Annual loss of lung function by FEV1-PD and FEV1%-PD was estimated from a linear model for the year 1 to 3 study period. Serum C1M and C6M were independent predictors of lung function decline ( p=0.007/0.005 (FEV1-PD) and p=0.02/0.03 (FEV1%-PD), respectively). Smoking status, bronchodilator reversibility, and emphysema were also confirmed as predictors. The effect on annual change in FEV1-PD (mL/yr) per 1 standard deviation (1SD) of C1M and C6M was 10.4mL and 8.6mL, respectively; for FEV1%-PD (%/yr) the effect of 1SD change in C1M and C6M was 0.37% and 0.29%, respectively. Conclusion: We demonstrated that markers of tissue turnover were prognostic for progression of lung function decline and may used as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials. Funding statement: ECLIPSE (SCO104960, [NCT00292552][1]) was sponsored by GSK. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00292552&atom=%2Ferj%2F46%2Fsuppl_59%2FPA3988.atom