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Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia

RATIONALE: Ventilator-associated pneumonia (VAP) is a common complication in patients with acute lung injury (ALI) and can lead to increased morbidity and mortality. Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms...

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Autores principales: Nguyen, Elizabeth V., Gharib, Sina A., Palazzo, Steven J., Chow, Yu-hua, Goodlett, David R., Schnapp, Lynn M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591362/
https://www.ncbi.nlm.nih.gov/pubmed/23505561
http://dx.doi.org/10.1371/journal.pone.0058782
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author Nguyen, Elizabeth V.
Gharib, Sina A.
Palazzo, Steven J.
Chow, Yu-hua
Goodlett, David R.
Schnapp, Lynn M.
author_facet Nguyen, Elizabeth V.
Gharib, Sina A.
Palazzo, Steven J.
Chow, Yu-hua
Goodlett, David R.
Schnapp, Lynn M.
author_sort Nguyen, Elizabeth V.
collection PubMed
description RATIONALE: Ventilator-associated pneumonia (VAP) is a common complication in patients with acute lung injury (ALI) and can lead to increased morbidity and mortality. Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms of disease, and identify putative targets for therapeutic intervention. METHODS: BALF was obtained from 5 normal subjects and 30 ALI patients: 14 with VAP (VAP(+)) and 16 without VAP (VAP(–)). Each sample underwent shotgun proteomic analysis based on tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation and protein interaction network analysis. Supervised classification algorithms were implemented to discover a proteomic classifier for identifying critically ill patients with VAP. RESULTS: ALI patients had distinct BALF proteomic profiles compared to normal controls. Within the ALI group, we identified 76 differentially expressed proteins between VAP(+) and VAP(–). Functional analysis of these proteins suggested activation of pro-inflammatory pathways during VAP. We identified and validated a limited proteomic signature that discriminated VAP(+) from VAP(–) patients comprised of three proteins: S100A8, lactotransferrin (LTF), and actinin 1 (ACTN1). CONCLUSIONS: Combining proteomic with computational analyses is a powerful approach to study the BALF proteome during lung injury and development of VAP. This integrative methodology is a promising strategy to differentiate clinically relevant subsets of ALI patients, including those suffering from VAP.
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spelling pubmed-35913622013-03-15 Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia Nguyen, Elizabeth V. Gharib, Sina A. Palazzo, Steven J. Chow, Yu-hua Goodlett, David R. Schnapp, Lynn M. PLoS One Research Article RATIONALE: Ventilator-associated pneumonia (VAP) is a common complication in patients with acute lung injury (ALI) and can lead to increased morbidity and mortality. Identifying protein profiles specific to VAP in bronchoalveolar lavage fluid (BALF) may aid in earlier diagnosis, elucidate mechanisms of disease, and identify putative targets for therapeutic intervention. METHODS: BALF was obtained from 5 normal subjects and 30 ALI patients: 14 with VAP (VAP(+)) and 16 without VAP (VAP(–)). Each sample underwent shotgun proteomic analysis based on tandem mass spectrometry. Differentially expressed proteins between the groups were identified using statistical methods based on spectral counting. Mechanisms of disease were explored using functional annotation and protein interaction network analysis. Supervised classification algorithms were implemented to discover a proteomic classifier for identifying critically ill patients with VAP. RESULTS: ALI patients had distinct BALF proteomic profiles compared to normal controls. Within the ALI group, we identified 76 differentially expressed proteins between VAP(+) and VAP(–). Functional analysis of these proteins suggested activation of pro-inflammatory pathways during VAP. We identified and validated a limited proteomic signature that discriminated VAP(+) from VAP(–) patients comprised of three proteins: S100A8, lactotransferrin (LTF), and actinin 1 (ACTN1). CONCLUSIONS: Combining proteomic with computational analyses is a powerful approach to study the BALF proteome during lung injury and development of VAP. This integrative methodology is a promising strategy to differentiate clinically relevant subsets of ALI patients, including those suffering from VAP. Public Library of Science 2013-03-07 /pmc/articles/PMC3591362/ /pubmed/23505561 http://dx.doi.org/10.1371/journal.pone.0058782 Text en © 2013 Nguyen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nguyen, Elizabeth V.
Gharib, Sina A.
Palazzo, Steven J.
Chow, Yu-hua
Goodlett, David R.
Schnapp, Lynn M.
Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia
title Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia
title_full Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia
title_fullStr Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia
title_full_unstemmed Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia
title_short Proteomic Profiling of Bronchoalveolar Lavage Fluid in Critically Ill Patients with Ventilator-Associated Pneumonia
title_sort proteomic profiling of bronchoalveolar lavage fluid in critically ill patients with ventilator-associated pneumonia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591362/
https://www.ncbi.nlm.nih.gov/pubmed/23505561
http://dx.doi.org/10.1371/journal.pone.0058782
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