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Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development

BACKGROUND: We conducted an exploratory study of genome-wide gene expression in whole blood and found that the expression of neutrophil elastase inhibitor (PI3, elafin) was down-regulated during the early phase of ARDS. Further analyses of plasma PI3 levels revealed a rapid decrease during early ARD...

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Autores principales: Wang, Zhaoxi, Chen, Feng, Zhai, Rihong, Zhang, Lingsong, Su, Li, Lin, Xihong, Thompson, Taylor, Christiani, David C.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633615/
https://www.ncbi.nlm.nih.gov/pubmed/19197381
http://dx.doi.org/10.1371/journal.pone.0004380
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author Wang, Zhaoxi
Chen, Feng
Zhai, Rihong
Zhang, Lingsong
Su, Li
Lin, Xihong
Thompson, Taylor
Christiani, David C.
author_facet Wang, Zhaoxi
Chen, Feng
Zhai, Rihong
Zhang, Lingsong
Su, Li
Lin, Xihong
Thompson, Taylor
Christiani, David C.
author_sort Wang, Zhaoxi
collection PubMed
description BACKGROUND: We conducted an exploratory study of genome-wide gene expression in whole blood and found that the expression of neutrophil elastase inhibitor (PI3, elafin) was down-regulated during the early phase of ARDS. Further analyses of plasma PI3 levels revealed a rapid decrease during early ARDS development. PI3 and secretory leukocyte proteinase inhibitor (SLPI) are important low-molecular-weight proteinase inhibitors produced locally at neutrophil infiltration site in the lung. In this study, we tested the hypothesis that an imbalance between neutrophil elastase (HNE) and its inhibitors in blood is related to the development of ARDS. METHODOLOGY/PRINCIPAL FINDINGS: PI3, SLPI, and HNE were measured in plasma samples collected from 148 ARDS patients and 63 critical ill patients at risk for ARDS (controls). Compared with the controls, the ARDS patients had higher HNE, but lower PI3, at the onset of ARDS, resulting in increased HNE/PI3 ratio (mean = 14.5; 95% CI, 10.9–19.4, P<0.0001), whereas plasma SLPI was not associated with the risk of ARDS development. Although the controls had elevated plasma PI3 and HNE, their HNE/PI3 ratio (mean = 6.5; 95% CI, 4.9–8.8) was not significantly different from the healthy individuals (mean = 3.9; 95% CI, 2.7–5.9). Before the onset (7-days period prior to ARDS diagnosis), we only observed significantly elevated HNE, but the HNE-PI3 balance remained normal. With the progress from prior to the onset of ARDS, the plasma level of PI3 declined, whereas HNE was maintained at a higher level, tilting the balance toward more HNE in the circulation as characterized by an increased HNE/PI3 ratio. In contrast, three days after ICU admission, there was a significant drop of HNE/PI3 ratio in the at-risk controls. CONCLUSIONS/SIGNIFICANCE: Plasma profiles of PI3, HNE, and HNE/PI3 may be useful clinical biomarkers in monitoring the development of ARDS.
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spelling pubmed-26336152009-02-06 Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development Wang, Zhaoxi Chen, Feng Zhai, Rihong Zhang, Lingsong Su, Li Lin, Xihong Thompson, Taylor Christiani, David C. PLoS One Research Article BACKGROUND: We conducted an exploratory study of genome-wide gene expression in whole blood and found that the expression of neutrophil elastase inhibitor (PI3, elafin) was down-regulated during the early phase of ARDS. Further analyses of plasma PI3 levels revealed a rapid decrease during early ARDS development. PI3 and secretory leukocyte proteinase inhibitor (SLPI) are important low-molecular-weight proteinase inhibitors produced locally at neutrophil infiltration site in the lung. In this study, we tested the hypothesis that an imbalance between neutrophil elastase (HNE) and its inhibitors in blood is related to the development of ARDS. METHODOLOGY/PRINCIPAL FINDINGS: PI3, SLPI, and HNE were measured in plasma samples collected from 148 ARDS patients and 63 critical ill patients at risk for ARDS (controls). Compared with the controls, the ARDS patients had higher HNE, but lower PI3, at the onset of ARDS, resulting in increased HNE/PI3 ratio (mean = 14.5; 95% CI, 10.9–19.4, P<0.0001), whereas plasma SLPI was not associated with the risk of ARDS development. Although the controls had elevated plasma PI3 and HNE, their HNE/PI3 ratio (mean = 6.5; 95% CI, 4.9–8.8) was not significantly different from the healthy individuals (mean = 3.9; 95% CI, 2.7–5.9). Before the onset (7-days period prior to ARDS diagnosis), we only observed significantly elevated HNE, but the HNE-PI3 balance remained normal. With the progress from prior to the onset of ARDS, the plasma level of PI3 declined, whereas HNE was maintained at a higher level, tilting the balance toward more HNE in the circulation as characterized by an increased HNE/PI3 ratio. In contrast, three days after ICU admission, there was a significant drop of HNE/PI3 ratio in the at-risk controls. CONCLUSIONS/SIGNIFICANCE: Plasma profiles of PI3, HNE, and HNE/PI3 may be useful clinical biomarkers in monitoring the development of ARDS. Public Library of Science 2009-02-06 /pmc/articles/PMC2633615/ /pubmed/19197381 http://dx.doi.org/10.1371/journal.pone.0004380 Text en Wang 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
Wang, Zhaoxi
Chen, Feng
Zhai, Rihong
Zhang, Lingsong
Su, Li
Lin, Xihong
Thompson, Taylor
Christiani, David C.
Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development
title Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development
title_full Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development
title_fullStr Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development
title_full_unstemmed Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development
title_short Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development
title_sort plasma neutrophil elastase and elafin imbalance is associated with acute respiratory distress syndrome (ards) development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633615/
https://www.ncbi.nlm.nih.gov/pubmed/19197381
http://dx.doi.org/10.1371/journal.pone.0004380
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