title: Defining a new diagnostic assessment parameter for wound care: Elevated protease activity, an indicator of nonhealing, for targeted protease-modulating treatment.
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-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.
authors.affiliation: SerenaGroup, Cambridge, Massachusetts.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Serena
authors.affiliation: Systagenix, Gargrave, United Kingdom.
authors.forename: Breda M
authors.initials: BM
authors.lastname: Cullen
authors.affiliation: Woundchek Laboratories, Gargrave, United Kingdom.
authors.forename: Simon W
authors.initials: SW
authors.lastname: Bayliff
authors.affiliation: Systagenix, Gargrave, United Kingdom.
authors.forename: Molly C
authors.initials: MC
authors.lastname: Gibson
authors.affiliation: Strategic Solutions, Cody, Wyoming.
authors.forename: Marissa J
authors.initials: MJ
authors.lastname: Carter
authors.affiliation: Alere, Scarborough, Maine.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Chen
authors.affiliation: SerenaGroup, Cambridge, Massachusetts.
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Yaakov
authors.affiliation: Regional Medical Center, Orangeburg, South Carolina.
authors.forename: John
authors.initials: J
authors.lastname: Samies
authors.affiliation: Snyder Institute for Vascular Health and Research, Kittanning, Pennsylvania.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sabo
authors.affiliation: St. Vincent Health Center, Erie, Pennsylvania.
authors.forename: Daniel
authors.initials: D
authors.lastname: DeMarco
authors.affiliation: Miami Valley Hospital, Dayton, Ohio.
authors.forename: Namchi
authors.initials: N
authors.lastname: Le
authors.affiliation: Miami Valley Hospital, Dayton, Ohio.
authors.forename: James
authors.initials: J
authors.lastname: Galbraith
mesh_terms: D019540:Area Under Curve; D017719:Diabetic Foot / Q000175:diagnosis / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D003668:Pressure Ulcer / Q000175:diagnosis / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D012372:ROC Curve; D016896:Treatment Outcome; D014647:Varicose Ulcer / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy; D014945:Wound Healing / Q000187:drug effects; D014947:Wounds and Injuries / Q000175:diagnosis* / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*
chemical_list: D004791:Enzyme Inhibitors; D010447:Peptide Hydrolases; D020782:Matrix Metalloproteinases