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Wound care and the value of protease testing

Could the world’s first point-of-care diagnostic test for chronic wounds help to ease the burden of chronic wounds, both clinically and economically?
West Sussex, UK
It is estimated that there are over 34.5 million chronic wounds worldwide.(1) These are wounds that fail to progress through a normal, orderly, timely sequence of repair and where comorbidities interfere with the normal healing process.(2) Chronic wounds globally are mostly made up of approximately 13.5 million diabetic foot ulcers, 12.5 million venous leg ulcers and over 8.5 million pressure ulcers. These wounds are causing a significant burden to healthcare systems around the world and it is estimated that chronic wounds make up 2–4% of all health care expense globally.(3) Despite such large numbers, wound care has largely lacked easy-to-use and easy-to-access diagnostic devices that can identify biochemical factors known to hinder the healing process. 
Traditional and contemporary wound care dressings, such as gauze, foams, or hydrocolloids, are mostly aimed at absorbing exudate and exudate management, to create an optimal moist wound healing environment by dealing with the symptoms of stalled wound healing. By contrast, most advanced wound care therapies have been developed to address specific underlying causes of non-healing, such as infection, excess proteases, lack of growth factors, or tissue hypoxia, however it remains challenging to identify the specific underlying biochemical problem affecting each wound with the very few diagnostic tools available today to help assess the wound biochemistry itself.
This means that the efficacy of advanced therapies can be unpredictable depending on how effectively treatment is targeted based on clinical assessment alone. The result is often purely experience-based treatment decisions at each patient visit, where dressing choices are made based primarily on clinical assessment and past experience in a ‘trial and error’ fashion where advanced wound care therapies are often used as a last resort, largely due to higher dressing costs.
Apart from the clinical burden this poses to both healthcare professional and patient, the resulting economic burden of chronic wound care is therefore not surprising given that over 50% of chronic wounds stay open for over one year,(4,5)  mostly requiring regular dressing changes assisted by community based healthcare professionals.
The need for improved diagnostics
The need for improved wound diagnosis at a localised level was widely recognised and clearly outlined in the publication of ‘Diagnostics and Wounds: A consensus document’ by The World Union of Wound Healing Societies in 2008. The consensus document written by leading wound care experts from around the world outlined the need for diagnostics in wound care and stated that the development of specific diagnostic tests for use in wounds had the potential to revolutionise their treatment.(6)
The document went on to recommend a test for enzymes and their substrates, in particular matrix metalloproteinases, among other markers of impaired healing. More recently ‘International Consensus: The role of proteases in wound diagnostics’, published in 2011, pinpointed protease activity as the best understood marker of impaired healing, based on numerous scientific publications, and stated that accurate detection of elevated protease activity would aid in the appropriate use of treatments aimed at modulating protease activity and would help to avoid inappropriate use of advanced wound care products.(7) 
The value of protease testing in wound care
In 2012, Systagenix launched WOUNDCHEK™ Protease Status, the world’s first point of care test for chronic wounds, designed specifically to detect elevated protease activity (EPA), which previously had gone undetected in chronic wounds.  EPA in chronic wounds is associated with a 90% probability of the wound not healing without appropriate intervention.(8) By identifying EPA in chronic wounds, WOUNDCHEK™ Protease Status allows clinicians to target advanced protease modulating therapies to the most appropriate wounds, removing the trial-and-error approach used previously, as there are no visual cues to detect EPA in a wound.(9)
Around a third of non-healing chronic wounds may have EPA.(8) To date the majority of these wounds have been treated with standard care with a high probability of not responding to the treatment. Dressings are available that are specifically designed to modulate EPA, such as PROMOGRAN® and PROMOGRAN PRISMA® (Systagenix). These dressings have been shown to increase response rates to as high as 77% when used specifically on wounds that have EPA.(10) 
Clinicians who have used the test since its introduction have recognised both its clinical and economic value. Dr Paul Chadwick, Principal Podiatrist, Salford Royal Foundation (NHS) Trust, recently stated: “Diabetic foot ulcers have significant impacts in terms of adverse outcomes, quality of life, mortality and financial. In England there are around 6000 lower extremity amputations a year in people with diabetes, people with diabetic foot ulcers have significantly poorer quality of life scores than many other long term conditions and astonishingly have poorer five-year survival rates than many cancers including breast and prostate. […] It became apparent that in order to help reduce the adverse outcomes described above the addition of a test to check for EPA could become an important component in our treatment algorithm for diabetic foot ulcers.” He concluded: “Detection of EPA should be seen as a new but integral diagnostic indicator that sits alongside established tests such as X-ray, magnetic resonance imaging, bacterial wound swabs and blood tests to improve the potential for healing in these complex wounds.”(11)
On the subject of the economic value of testing for EPA in venous leg ulcers, Dr Caroline Dowsett, Nurse Consultant, Tissue Viability, East London NHS Foundation Trust, added: “Identifying problems at the wound bed through the use of wound diagnostic tools such as a point-of-care test for EPA allows for targeted interventions that can improve healing rates, increase patient satisfaction and make health economic savings.” She estimated cost savings of 41% per chronic wound with EPA identified and treated with a protease-modulating therapy compared with current standard care and concluded: “The suggested tariff for complex venous leg ulcers is £1920 under AQP, so if EPA is not identified and treated and costs escalate then the service provider is unlikely to be able to sustain their service.”(12)
Both the clinicians quoted above and numerous wound care experts across Europe, in several consensus publications since 2011, have recommended a revised algorithm for care for chronic wounds, incorporating testing for EPA as a routine aspect of wound assessment, once infection has been excluded or treated, but stalled healing is apparent.(7,13–17) Could this be the beginning of a more evidence-based approach to wound care facilitated by new diagnostic tools and targeted treatment decisions at the point of care? This would mean an end to years of ‘trial and error’ and purely experience-based practice.
  1. Worldwide Wound Management 2008–2017: Established and emerging products, technologies and markets in the US, Europe, Japan, and Rest of the World. Medmarket Diligence Report #S247; September 2009.
  2. Lazarus GS et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 1994;130(4):489–93.
  3. Acute and Chronic Wounds: Current Management Concepts, Third Edition. Bryant RA, Nix DP (eds).
  4. Prompers L et al. Resource utilisation and costs associated with the treatment of diabetic foot ulcers. Prospective data from the Eurodiale Study.  Diabetologia 2008;51(10):1826–34.
  5. Operational Guidance to the NHS: Extending patient choice of the provider. Department of Health, July 2011;Crown Copyright.
  6. World Union of Wound Healing Societies. Principles of best practice: Diagnostics and wounds. A consensus document. London: MEP Ltd;2008.
  7. International consensus. The role of proteases in wound diagnostics. An expert working group review. London: Wounds International, 2011.
  8. Serena T et al. Protease activity levels associated with healing status of chronic wounds. Poster presentation, Wounds UK 2011.
  9. Snyder RJ, Cullen B, Nisbet LT. An audit to assess the perspectives of US wound care specialists regarding the importance of proteases in wound healing and wound assessment. Int Wound J 2012;29 July [Epub ahead of print].
  10. Cullen B et al. Targeted use of collagen/ORC improves clinical outcome. EWMA 2012 poster presentation.
  11. Chadwick P. Symposia. Wound diagnostics: Elevated Protease Activity (EPA) when and where, can you afford to ignore it? Wounds UK conference: Harrogate, November 2012.
  12. Dowsett C, The economic benefits of identifying and treating elevated protease activity. Symposia. Wound diagnostics: Elevated Protease Activity (EPA) when and where, can you afford to ignore it? Wounds UK conference: Harrogate November 2012.
  13. Protease diagnostics in wound care: round-table meeting (October 2011). Wounds UK 7(4):supplement.
  14. Snyder RJ et al. Using a diagnostic tool to identify elevated protease activity levels in chronic and stalled Wounds: A consensus panel discussion. Ostomy Wound Manag 2011;57(12):36–46.
  15. Italian Consensus Document: Meaning and assessment of proteases in the tissue repair process. AIUC 2011.
  16. The role of a point-of-care protease activity diagnostic test in Canadian clinical practice. BCS Communications Ltd (supplement to Wound Care Canada).
  17. The role of a point-of-care protease test in wound diagnostics. Wound Management 2012