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Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study
INTRODUCTION: 30 day mortality in patients with Acute Respiratory Failure (ARF) is approximately 30%, defined as patients requiring ventilator support for more than 6 hours. Novel biomarkers are needed to predict patient outcomes and to guide potential future therapies. The activins A and B, members...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057391/ https://www.ncbi.nlm.nih.gov/pubmed/24172607 http://dx.doi.org/10.1186/cc13093 |
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author | de Kretser, David Morritz Bensley, Jonathan Guy Pettilä, Ville Linko, Rita Hedger, Mark Peter Hayward, Susan Allan, Carolyn Anne McLachlan, Robert Ian Ludlow, Helen Phillips, David James |
author_facet | de Kretser, David Morritz Bensley, Jonathan Guy Pettilä, Ville Linko, Rita Hedger, Mark Peter Hayward, Susan Allan, Carolyn Anne McLachlan, Robert Ian Ludlow, Helen Phillips, David James |
author_sort | de Kretser, David Morritz |
collection | PubMed |
description | INTRODUCTION: 30 day mortality in patients with Acute Respiratory Failure (ARF) is approximately 30%, defined as patients requiring ventilator support for more than 6 hours. Novel biomarkers are needed to predict patient outcomes and to guide potential future therapies. The activins A and B, members of the Transforming Growth Factor β family of proteins, and their binding protein, follistatin, have recently been shown to be important regulators of inflammation and fibrosis but no substantial data are available concerning their roles in ARF. Our objectives were to evaluate whether the serum levels of activin A, B and follistatin are elevated in 518 patients with ARF from the FINNALI study compared the concentrations in 138 normal subjects that form a reference range. METHODS: Specific assays for activin A, B and follistatin were used and the results analyzed according to diagnostic groups as well as according to standard measures in intensive care. Multivariable logistic regression was used to create a model to predict death at 90 days and 12 months from the onset of the ARF. RESULTS: Serum activin A and B were significantly elevated in most patients and in most of the diagnostic groups. Patients who had activin A and/or B concentrations above the reference maximum were significantly more likely to die in the 12 months following admission [either activin A or B above reference maximum: Positive Likelihood Ratio [LR+] 1.65 [95% CI 1.28-2.12, P = 0.00013]; both activin A and B above reference maximum: LR + 2.78 [95% CI 1.96-3.95, P < 0.00001]. The predictive model at 12 months had an overall accuracy of 80.2% [95% CI 76.6-83.3%]. CONCLUSIONS: The measurement of activin A and B levels in these patients with ARF would have assisted in predicting those at greatest risk of death. Given the existing data from animal studies linking high activin A levels to significant inflammatory challenges, the results from this study suggest that approaches to modulate activin A and B bioactivity should be explored as potential therapeutic agents. |
format | Online Article Text |
id | pubmed-4057391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40573912014-06-16 Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study de Kretser, David Morritz Bensley, Jonathan Guy Pettilä, Ville Linko, Rita Hedger, Mark Peter Hayward, Susan Allan, Carolyn Anne McLachlan, Robert Ian Ludlow, Helen Phillips, David James Crit Care Research INTRODUCTION: 30 day mortality in patients with Acute Respiratory Failure (ARF) is approximately 30%, defined as patients requiring ventilator support for more than 6 hours. Novel biomarkers are needed to predict patient outcomes and to guide potential future therapies. The activins A and B, members of the Transforming Growth Factor β family of proteins, and their binding protein, follistatin, have recently been shown to be important regulators of inflammation and fibrosis but no substantial data are available concerning their roles in ARF. Our objectives were to evaluate whether the serum levels of activin A, B and follistatin are elevated in 518 patients with ARF from the FINNALI study compared the concentrations in 138 normal subjects that form a reference range. METHODS: Specific assays for activin A, B and follistatin were used and the results analyzed according to diagnostic groups as well as according to standard measures in intensive care. Multivariable logistic regression was used to create a model to predict death at 90 days and 12 months from the onset of the ARF. RESULTS: Serum activin A and B were significantly elevated in most patients and in most of the diagnostic groups. Patients who had activin A and/or B concentrations above the reference maximum were significantly more likely to die in the 12 months following admission [either activin A or B above reference maximum: Positive Likelihood Ratio [LR+] 1.65 [95% CI 1.28-2.12, P = 0.00013]; both activin A and B above reference maximum: LR + 2.78 [95% CI 1.96-3.95, P < 0.00001]. The predictive model at 12 months had an overall accuracy of 80.2% [95% CI 76.6-83.3%]. CONCLUSIONS: The measurement of activin A and B levels in these patients with ARF would have assisted in predicting those at greatest risk of death. Given the existing data from animal studies linking high activin A levels to significant inflammatory challenges, the results from this study suggest that approaches to modulate activin A and B bioactivity should be explored as potential therapeutic agents. BioMed Central 2013 2013-10-31 /pmc/articles/PMC4057391/ /pubmed/24172607 http://dx.doi.org/10.1186/cc13093 Text en Copyright © 2013 de Kretser et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research de Kretser, David Morritz Bensley, Jonathan Guy Pettilä, Ville Linko, Rita Hedger, Mark Peter Hayward, Susan Allan, Carolyn Anne McLachlan, Robert Ian Ludlow, Helen Phillips, David James Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study |
title | Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study |
title_full | Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study |
title_fullStr | Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study |
title_full_unstemmed | Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study |
title_short | Serum activin A and B levels predict outcome in patients with acute respiratory failure: a prospective cohort study |
title_sort | serum activin a and b levels predict outcome in patients with acute respiratory failure: a prospective cohort study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057391/ https://www.ncbi.nlm.nih.gov/pubmed/24172607 http://dx.doi.org/10.1186/cc13093 |
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