Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study
Research output: Contribution to journal › Journal article › Research › peer-review
- Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study
Final published version, 640 KB, PDF document
Diana J. Leeming, Inger Byrjalsen, Jannie M. B. Sand, Asger R. Bihlet, Peter Lange, Ruth Thal-Singer, Bruce E. Miller, Morten A. Karsdal, Jørgen Vestbo
Methods: One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. 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 (PD-FEV1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline.
Results: Annual change of PD-FEV1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV1.
Conclusion: We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD.
Trial registration: NCT00292552, Retrospectively registered, trial registration in February 2006.
|Journal||B M C Pulmonary Medicine|
|Number of pages||10|
|Publication status||Published - 4 Dec 2017|
- COPD, Lung function change, Prognosis, Serological marker, Extracellular matrix
Number of downloads are based on statistics from Google Scholar and www.ku.dk