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Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

Leeming, DJ; Byrjalsen, I; Sand, JMB; Bihlet, AR; Lange, P; Evaluation of COPD Longitudinally to Identify Surrogate Endpoint; Thal-Singer, R; ... Vestbo, J; + view all (2017) Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study. BMC Pulmonary Medicine , 17 , Article 164. 10.1186/s12890-017-0505-4. Green open access

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Abstract

BACKGROUND: Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. 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.

Type: Article
Title: Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12890-017-0505-4
Publisher version: http://doi.org/10.1186/s12890-017-0505-4
Language: English
Additional information: Copyright © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: COPD, Extracellular matrix, Lung function change, Prognosis, Serological marker, Aged, Biomarkers, C-Reactive Protein, Collagen Type I, Collagen Type VI, Female, Forced Expiratory Volume, Humans, Male, Matrix Metalloproteinases, Middle Aged, Peptide Fragments, Pulmonary Disease, Chronic Obstructive
UCL classification: UCL
UCL > Provost and Vice Provost Offices > VP: Health
URI: https://discovery.ucl.ac.uk/id/eprint/10064951
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