Biomarkers of collagen turnover are related to annual change in FEV<sub>1</sub> in patients with chronic obstructive pulmonary disease within the ECLIPSE study.



Leeming, Diana J, Byrjalsen, Inger, Sand, Jannie MB ORCID: 0000-0002-3239-0934, Bihlet, Asger R, Lange, Peter, Evaluation of COPD Longitudinally to Identify Surrogate Endpoint, , Thal-Singer, Ruth, Miller, Bruce E, Karsdal, Morten A ORCID: 0000-0001-5026-8740 and Vestbo, Jørgen
(2017) Biomarkers of collagen turnover are related to annual change in FEV<sub>1</sub> in patients with chronic obstructive pulmonary disease within the ECLIPSE study. BMC pulmonary medicine, 17 (1). 164 - ?.

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Abstract

<h4>Background</h4>Change in forced expiratory volume in one second (FEV<sub>1</sub>) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV<sub>1</sub>.<h4>Methods</h4>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 FEV<sub>1</sub> (PD-FEV<sub>1</sub>) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline.<h4>Results</h4>Annual change of PD-FEV<sub>1</sub> 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-FEV<sub>1</sub> 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 FEV<sub>1</sub>.<h4>Conclusion</h4>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.<h4>Trial registration</h4>NCT00292552 , Retrospectively registered, trial registration in February 2006.

Item Type: Article
Uncontrolled Keywords: Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators, Humans, Pulmonary Disease, Chronic Obstructive, Collagen Type I, Matrix Metalloproteinases, Peptide Fragments, C-Reactive Protein, Collagen Type VI, Forced Expiratory Volume, Aged, Middle Aged, Female, Male, Biomarkers
Depositing User: Symplectic Admin
Date Deposited: 08 Aug 2019 14:04
Last Modified: 11 May 2022 15:13
DOI: 10.1186/s12890-017-0505-4
URI: https://livrepository.liverpool.ac.uk/id/eprint/3051294