Defining a new diagnostic assessment parameter for wound care: Elevated protease activity, an indicator of nonhealing, for targeted protease-modulating treatment
Defining a new diagnostic assessment parameter for wound care: Elevated protease activity, an indicator of nonhealing, for targeted protease-modulating treatment
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DOI：
10.1111/wrr.12431
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发表时间：
2016-05-01
影响因子：
2.9
通讯作者：
Galbraith, James
中科院分区：
文献类型：
--
作者：
Serena, Thomas E.;Cullen, Breda M.;Galbraith, James
人们普遍认为，慢性伤口中蛋白酶活性（EPA）升高会阻碍愈合。然而，在量化不利于愈合的蛋白酶活性水平方面进展甚微。本研究的目的是确定炎症蛋白酶活性与伤口愈合状态之间的关系，并确定 EPA 水平，高于该水平，人中性粒细胞源性弹性蛋白酶 (HNE) 和基质金属蛋白酶 (MMP) 活性与不愈合伤口相关。从美国四个伤口中心收集慢性伤口拭子样本 (n=290)，以测量 HNE 和 MMP 活性。根据过去 2-4 周伤口面积减少的百分比来确定愈合状态；这可用于治疗 211 处伤口。蛋白酶活性与不愈合伤口之间的关联通过接受者操作特征分析（ROC）来确定，ROC是一种用于可视化和分析诊断测试性能的统计技术。 ROC 分析显示，HNE 的所有伤口的曲线下面积 (AUC) 为 0.69，对于具有最可靠伤口轨迹信息的伤口，曲线下面积 (AUC) 分别为 0.78。对于MMP，相应的AUC值为0.70和0.82。分析表明，HNE > 5 和/或 MMP 13 值的慢性伤口应被视为伤口愈合受损。 EPA 表示未愈合的伤口。在临床实践中使用诊断测试来检测 EPA 可以使临床医生识别无法愈合的伤口，从而能够使用蛋白酶调节疗法进行有针对性的治疗。
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-derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples (n=290) were collected from four 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 nonhealing 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 nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies.