Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with Acute Respiratory Distress Syndrome (ARDS) Development
Open Access
- 6 February 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (2), e4380
- https://doi.org/10.1371/journal.pone.0004380
Abstract
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. 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. Plasma profiles of PI3, HNE, and HNE/PI3 may be useful clinical biomarkers in monitoring the development of ARDS.Keywords
This publication has 40 references indexed in Scilit:
- A Genome-Wide Expression Analysis in Blood Identifies Pre-Elafin as a Biomarker in ARDSAmerican Journal of Respiratory Cell and Molecular Biology, 2008
- Inhibitor κB-α haplotype GTC is associated with susceptibility to acute respiratory distress syndrome in Caucasians*Critical Care Medicine, 2007
- Higher Urine Nitric Oxide Is Associated with Improved Outcomes in Patients with Acute Lung InjuryAmerican Journal of Respiratory and Critical Care Medicine, 2007
- Elafin and Its Precursor Trappin-2 Still Inhibit Neutrophil Serine Proteinases when They Are Covalently Bound to Extracellular Matrix Proteins by Tissue TransglutaminaseBiochemistry, 2005
- −308GAandTNFBpolymorphisms in acute respiratory distress syndromeEuropean Respiratory Journal, 2005
- Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injuryAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Neutrophils and acute lung injuryCritical Care Medicine, 2003
- Secretory leukocyte proteinase inhibitor is preferentially increased in patients with acute respiratory distress syndromeEuropean Respiratory Journal, 1999
- DIAGNOSTIC CRITERIA FOR ADULT RESPIRATORY DISTRESS SYNDROME: TIME FOR REAPPRAISALThe Lancet, 1989
- Elastolytic Activity in Pulmonary Lavage Fluid from Patients with Adult Respiratory-Distress SyndromeNew England Journal of Medicine, 1981