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Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elast...

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Autores principales: Bihlet, Asger Reinstrup, Karsdal, Morten Asser, Sand, Jannie Marie Bülow, Leeming, Diana Julie, Roberts, Mustimbo, White, Wendy, Bowler, Russell
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5248528/
https://www.ncbi.nlm.nih.gov/pubmed/28103932
http://dx.doi.org/10.1186/s12931-017-0509-x
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author Bihlet, Asger Reinstrup
Karsdal, Morten Asser
Sand, Jannie Marie Bülow
Leeming, Diana Julie
Roberts, Mustimbo
White, Wendy
Bowler, Russell
author_facet Bihlet, Asger Reinstrup
Karsdal, Morten Asser
Sand, Jannie Marie Bülow
Leeming, Diana Julie
Roberts, Mustimbo
White, Wendy
Bowler, Russell
author_sort Bihlet, Asger Reinstrup
collection PubMed
description BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs. During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes. The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study. METHODS: The COPDGene study recruited 10,300 COPD patients in 21 centers. A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE). Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed. RESULTS: The circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05). EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%. C1M was inversely associated with forced expiratory volume in 1 s (FEV(1)) (r = −0.344, p = 0.001), as was EL-NE (r = −0.302, p = 0.004) and Pro-C6 (r = −0.259, p = 0.015). In the patients with COPD, Pro-C6 was correlated with percent predicted Forced Vital Capacity (FVC) (r = 0.281, p = 0.046) and quality of life using SF-36. C6M and Pro-C6, were positively correlated with blood eosinophil numbers in COPD patients (r = 0.382, p = 0.006 and r = 0.351, p = 0.012, respectively). CONCLUSIONS: These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema. Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials.
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spelling pubmed-52485282017-01-25 Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD Bihlet, Asger Reinstrup Karsdal, Morten Asser Sand, Jannie Marie Bülow Leeming, Diana Julie Roberts, Mustimbo White, Wendy Bowler, Russell Respir Res Research BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs. During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes. The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study. METHODS: The COPDGene study recruited 10,300 COPD patients in 21 centers. A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE). Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed. RESULTS: The circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05). EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%. C1M was inversely associated with forced expiratory volume in 1 s (FEV(1)) (r = −0.344, p = 0.001), as was EL-NE (r = −0.302, p = 0.004) and Pro-C6 (r = −0.259, p = 0.015). In the patients with COPD, Pro-C6 was correlated with percent predicted Forced Vital Capacity (FVC) (r = 0.281, p = 0.046) and quality of life using SF-36. C6M and Pro-C6, were positively correlated with blood eosinophil numbers in COPD patients (r = 0.382, p = 0.006 and r = 0.351, p = 0.012, respectively). CONCLUSIONS: These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema. Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials. BioMed Central 2017-01-19 2017 /pmc/articles/PMC5248528/ /pubmed/28103932 http://dx.doi.org/10.1186/s12931-017-0509-x Text en © The Author(s). 2017 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
Bihlet, Asger Reinstrup
Karsdal, Morten Asser
Sand, Jannie Marie Bülow
Leeming, Diana Julie
Roberts, Mustimbo
White, Wendy
Bowler, Russell
Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
title Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
title_full Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
title_fullStr Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
title_full_unstemmed Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
title_short Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
title_sort biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in copd
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5248528/
https://www.ncbi.nlm.nih.gov/pubmed/28103932
http://dx.doi.org/10.1186/s12931-017-0509-x
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