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

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 ass...

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Autores principales: Organ, Louise A., Duggan, Anne-Marie R., Oballa, Eunice, Taggart, Sarah C., Simpson, Juliet K., Kang’ombe, Arthur R., Braybrooke, Rebecca, Molyneaux, Philip L., North, Bernard, Karkera, Yakshitha, Leeming, Diana J., Karsdal, Morten A., Nanthakumar, Carmel B., Fahy, William A., Marshall, Richard P., Jenkins, R. Gisli, Maher, Toby M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624898/
https://www.ncbi.nlm.nih.gov/pubmed/31299951
http://dx.doi.org/10.1186/s12931-019-1118-7
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author Organ, Louise A.
Duggan, Anne-Marie R.
Oballa, Eunice
Taggart, Sarah C.
Simpson, Juliet K.
Kang’ombe, Arthur R.
Braybrooke, Rebecca
Molyneaux, Philip L.
North, Bernard
Karkera, Yakshitha
Leeming, Diana J.
Karsdal, Morten A.
Nanthakumar, Carmel B.
Fahy, William A.
Marshall, Richard P.
Jenkins, R. Gisli
Maher, Toby M.
author_facet Organ, Louise A.
Duggan, Anne-Marie R.
Oballa, Eunice
Taggart, Sarah C.
Simpson, Juliet K.
Kang’ombe, Arthur R.
Braybrooke, Rebecca
Molyneaux, Philip L.
North, Bernard
Karkera, Yakshitha
Leeming, Diana J.
Karsdal, Morten A.
Nanthakumar, Carmel B.
Fahy, William A.
Marshall, Richard P.
Jenkins, R. Gisli
Maher, Toby M.
author_sort Organ, Louise A.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1118-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-66248982019-07-23 Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort Organ, Louise A. Duggan, Anne-Marie R. Oballa, Eunice Taggart, Sarah C. Simpson, Juliet K. Kang’ombe, Arthur R. Braybrooke, Rebecca Molyneaux, Philip L. North, Bernard Karkera, Yakshitha Leeming, Diana J. Karsdal, Morten A. Nanthakumar, Carmel B. Fahy, William A. Marshall, Richard P. Jenkins, R. Gisli Maher, Toby M. Respir Res Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1118-7) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-12 2019 /pmc/articles/PMC6624898/ /pubmed/31299951 http://dx.doi.org/10.1186/s12931-019-1118-7 Text en © The Author(s). 2019 Open AccessThis 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.
spellingShingle Research
Organ, Louise A.
Duggan, Anne-Marie R.
Oballa, Eunice
Taggart, Sarah C.
Simpson, Juliet K.
Kang’ombe, Arthur R.
Braybrooke, Rebecca
Molyneaux, Philip L.
North, Bernard
Karkera, Yakshitha
Leeming, Diana J.
Karsdal, Morten A.
Nanthakumar, Carmel B.
Fahy, William A.
Marshall, Richard P.
Jenkins, R. Gisli
Maher, Toby M.
Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort
title Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort
title_full Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort
title_fullStr Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort
title_full_unstemmed Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort
title_short Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort
title_sort biomarkers of collagen synthesis predict progression in the profile idiopathic pulmonary fibrosis cohort
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624898/
https://www.ncbi.nlm.nih.gov/pubmed/31299951
http://dx.doi.org/10.1186/s12931-019-1118-7
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