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The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS

BACKGROUND: Pulmonary and systemic inflammation are central features of chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated relationships between biologically active extracellular matrix components, or matrikines, and COPD pathogenesis. We studied the relationships betwe...

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Autores principales: Wells, J. Michael, Xing, Dongqi, Viera, Liliana, Burkes, Robert M., Wu, Yixin, Bhatt, Surya P., Dransfield, Mark T., Couper, David J., O’Neal, Wanda, Hoffman, Eric A., Gaggar, Amit, Barjaktarevic, Igor, Curtis, Jeffrey L., Labaki, Wassim W., Han, Mei Lan K., Freeman, Christine M., Putcha, Nirupama, Schlange, Thomas, Blalock, J. Edwin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852714/
https://www.ncbi.nlm.nih.gov/pubmed/31718676
http://dx.doi.org/10.1186/s12931-019-1230-8
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author Wells, J. Michael
Xing, Dongqi
Viera, Liliana
Burkes, Robert M.
Wu, Yixin
Bhatt, Surya P.
Dransfield, Mark T.
Couper, David J.
O’Neal, Wanda
Hoffman, Eric A.
Gaggar, Amit
Barjaktarevic, Igor
Curtis, Jeffrey L.
Labaki, Wassim W.
Han, Mei Lan K.
Freeman, Christine M.
Putcha, Nirupama
Schlange, Thomas
Blalock, J. Edwin
author_facet Wells, J. Michael
Xing, Dongqi
Viera, Liliana
Burkes, Robert M.
Wu, Yixin
Bhatt, Surya P.
Dransfield, Mark T.
Couper, David J.
O’Neal, Wanda
Hoffman, Eric A.
Gaggar, Amit
Barjaktarevic, Igor
Curtis, Jeffrey L.
Labaki, Wassim W.
Han, Mei Lan K.
Freeman, Christine M.
Putcha, Nirupama
Schlange, Thomas
Blalock, J. Edwin
author_sort Wells, J. Michael
collection PubMed
description BACKGROUND: Pulmonary and systemic inflammation are central features of chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated relationships between biologically active extracellular matrix components, or matrikines, and COPD pathogenesis. We studied the relationships between the matrikine acetyl-proline-glycine-proline (AcPGP) in sputum and plasma and clinical features of COPD. METHODS: Sputum and plasma samples were obtained from COPD participants in the SPIROMICS cohort at enrollment. AcPGP was isolated using solid phase extraction and measured by mass spectrometry. Demographics, spirometry, quality of life questionnaires, and quantitative computed tomography (CT) imaging with parametric response mapping (PRM) were obtained at baseline. Severe COPD exacerbations were recorded at 1-year of prospective follow-up. We used linear and logistic regression models to measure associations between AcPGP and features of COPD, and Kaplan-Meier analyses to measure time-to-first severe exacerbation. RESULTS: The 182 COPD participants in the analysis were 66 ± 8 years old, 62% male, 84% White race, and 39% were current smokers. AcPGP concentrations were 0.61 ± 1.89 ng/mL (mean ± SD) in sputum and 0.60 ± 1.13 ng/mL in plasma. In adjusted linear regression models, sputum AcPGP was associated with FEV(1)/FVC, spirometric GOLD stage, PRM-small airways disease, and PRM-emphysema. Sputum AcPGP also correlated with severe AECOPD, and elevated sputum AcPGP was associated with shorter time-to-first severe COPD exacerbation. In contrast, plasma AcPGP was not associated with symptoms, pulmonary function, or severe exacerbation risk. CONCLUSIONS: In COPD, sputum but not plasma AcPGP concentrations are associated with the severity of airflow limitation, small airways disease, emphysema, and risk for severe AECOPD at 1-year of follow-up. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01969344 (SPIROMICS).
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spelling pubmed-68527142019-11-20 The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS Wells, J. Michael Xing, Dongqi Viera, Liliana Burkes, Robert M. Wu, Yixin Bhatt, Surya P. Dransfield, Mark T. Couper, David J. O’Neal, Wanda Hoffman, Eric A. Gaggar, Amit Barjaktarevic, Igor Curtis, Jeffrey L. Labaki, Wassim W. Han, Mei Lan K. Freeman, Christine M. Putcha, Nirupama Schlange, Thomas Blalock, J. Edwin Respir Res Research BACKGROUND: Pulmonary and systemic inflammation are central features of chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated relationships between biologically active extracellular matrix components, or matrikines, and COPD pathogenesis. We studied the relationships between the matrikine acetyl-proline-glycine-proline (AcPGP) in sputum and plasma and clinical features of COPD. METHODS: Sputum and plasma samples were obtained from COPD participants in the SPIROMICS cohort at enrollment. AcPGP was isolated using solid phase extraction and measured by mass spectrometry. Demographics, spirometry, quality of life questionnaires, and quantitative computed tomography (CT) imaging with parametric response mapping (PRM) were obtained at baseline. Severe COPD exacerbations were recorded at 1-year of prospective follow-up. We used linear and logistic regression models to measure associations between AcPGP and features of COPD, and Kaplan-Meier analyses to measure time-to-first severe exacerbation. RESULTS: The 182 COPD participants in the analysis were 66 ± 8 years old, 62% male, 84% White race, and 39% were current smokers. AcPGP concentrations were 0.61 ± 1.89 ng/mL (mean ± SD) in sputum and 0.60 ± 1.13 ng/mL in plasma. In adjusted linear regression models, sputum AcPGP was associated with FEV(1)/FVC, spirometric GOLD stage, PRM-small airways disease, and PRM-emphysema. Sputum AcPGP also correlated with severe AECOPD, and elevated sputum AcPGP was associated with shorter time-to-first severe COPD exacerbation. In contrast, plasma AcPGP was not associated with symptoms, pulmonary function, or severe exacerbation risk. CONCLUSIONS: In COPD, sputum but not plasma AcPGP concentrations are associated with the severity of airflow limitation, small airways disease, emphysema, and risk for severe AECOPD at 1-year of follow-up. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01969344 (SPIROMICS). BioMed Central 2019-11-12 2019 /pmc/articles/PMC6852714/ /pubmed/31718676 http://dx.doi.org/10.1186/s12931-019-1230-8 Text en © 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.
spellingShingle Research
Wells, J. Michael
Xing, Dongqi
Viera, Liliana
Burkes, Robert M.
Wu, Yixin
Bhatt, Surya P.
Dransfield, Mark T.
Couper, David J.
O’Neal, Wanda
Hoffman, Eric A.
Gaggar, Amit
Barjaktarevic, Igor
Curtis, Jeffrey L.
Labaki, Wassim W.
Han, Mei Lan K.
Freeman, Christine M.
Putcha, Nirupama
Schlange, Thomas
Blalock, J. Edwin
The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS
title The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS
title_full The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS
title_fullStr The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS
title_full_unstemmed The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS
title_short The matrikine acetyl-proline-glycine-proline and clinical features of COPD: findings from SPIROMICS
title_sort matrikine acetyl-proline-glycine-proline and clinical features of copd: findings from spiromics
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852714/
https://www.ncbi.nlm.nih.gov/pubmed/31718676
http://dx.doi.org/10.1186/s12931-019-1230-8
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