Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort.

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Title: Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort.
Authors: Organ, L
Duggan, A-M
Oballa, E
Taggart, S
Simpson, J
Kang’ombe, A
Braybrooke, R
Molyneaux, P
North, B
Karkera, Y
Leeming, D
Karsdal, M
Nanthakumar, C
Fahy, W
Marshall, R
Jenkins, G
Maher, T
Item Type: Journal Article
Abstract: Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was assessed in 145 newly-diagnosed individuals with IPF. Serum levels of collagen synthesis neoepitopes, PRO-C3 and PRO-C6 (collagen type 3 and 6), were elevated in IPF compared with controls at baseline, and progressive disease versus stable disease during follow up, (PRO-C3 p < 0.001; PRO-C6 p = 0.029). Assessment of rate of change in neoepitope levels from baseline to 3 months (defined as ‘slope to month 3’: HIGH slope, slope > 0 vs. LOW slope, slope < =0) demonstrated no relationship with mortality for these markers (PRO-C3 (HR 1.62, p = 0.080); PINP (HR 0.76, p = 0.309); PRO-C6 (HR 1.14, p = 0.628)). As previously reported, rising concentrations of collagen degradation markers C1M, C3M, C6M and CRPM were associated with an increased risk of overall mortality (HR = 1.84, CI 1.03–3.27, p = 0.038, HR = 2.44, CI 1.39–4.31, p = 0.002; HR = 2.19, CI 1.25–3.82, p = 0.006; HR = 2.13 CI 1.21–3.75, p = 0.009 respectively). Elevated levels of PRO-C3 and PRO-C6 associate with IPF disease progression. Collagen synthesis and degradation biomarkers have the potential to enhance clinical trials in IPF and may inform prognostic assessment and therapeutic decision making in the clinic.
Issue Date: 12-Jul-2019
Date of Acceptance: 1-Jul-2019
URI: http://hdl.handle.net/10044/1/71764
DOI: https://doi.org/10.1186/s12931-019-1118-7
ISSN: 1465-9921
Publisher: BioMed Central
Start Page: 1
End Page: 10
Journal / Book Title: Respiratory Research
Volume: 20
Copyright Statement: © The Author(s). 2019 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
Sponsor/Funder: National Institute for Health Research
British Lung Foundation
Funder's Grant Number: CS-2013-13-017
C17-3
Keywords: 1102 Cardiorespiratory Medicine and Haematology
1103 Clinical Sciences
Respiratory System
Publication Status: Published
Article Number: 148
Online Publication Date: 2019-07-12
Appears in Collections:National Heart and Lung Institute



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