Wound Repair Regen · 2016
Defining a New Diagnostic Assessment Parameter for Wound Care: Elevated Protease Activity (EPA), an Indicator of Non-healing, for Targeted Protease-modulating Treatment
Serena, T.E., Cullen, B.M., Bayliff, S.W., Gibson, M.C., Carter, M.J., Chen, L., Yaakov, R.A., Samies, J., Sabo, M., DeMarco, D., Le, N., & Galbraith, J.
Wound Repair and Regeneration, 2016 (accepted article)
In brief
This study measured the activity of two groups of wound enzymes, human neutrophil elastase and matrix metalloproteases, in 290 chronic wound swab samples from 4 US wound centers and compared them with whether each wound had been healing over the previous 2 to 4 weeks (known for 211 wounds). In ROC analysis, the area under the curve for identifying non-healing wounds was 0.69 for elastase and 0.70 for metalloproteases across all wounds, and 0.78 and 0.82 in a small subset with the most reliable healing data (n=40). The authors propose that wounds with elastase above 5 and/or metalloprotease activity of 13 or more be considered healing impaired, while noting that there is no gold standard for predicting healing, so these cut-offs carry uncertainty.
Co-authored by SerenaGroup researchers.
Plain-language summary by SerenaGroup. See the full text for complete methods and results.
Abstract
It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil elastase (HNE) and matrix metalloproteases (MMP) activities correlate with non-healing wounds. Chronic wound swab samples (n=290) were collected from 4 wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2-4 weeks; this was available for 211 wounds. Association between protease activity and non-healing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0·69 for all wounds and 0·78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0·70 and 0·82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of non-healing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are non-healing, thus enabling targeted treatment with protease modulating therapies. Wound Repair and Regeneration This article is protected by copyright. All rights reserved. Page 3 of 26 Manuscript under review - CONFIDENTIAL 3
Keywords
Wound diagnosticchronic woundhuman neutrophil elastasematrix metalloproteases
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