Chronic Venous Leg Ulcers - Current and Future Therapies to Target Neutrophil Activity

Monday, 18 November 2013: 2:25 PM

Jodi McDaniel, PhD, MS, RN
College of Nursing, The Ohio State University, Columbus, OH

Learning Objective 1: The learner will be able to describe the primary physiological factors contributing to the escalating global health problem of chronic venous leg ulcers.

Learning Objective 2: The learner will be able to describe the function of neutrophils in wound healing and identify current and future therapies that target excessive neutrophil activity.

Chronic venous leg ulcers (CVLUs) pose significant global healthcare burdens because of high prevalence and recurrence rates.  In the United States alone, CVLUs affect approximately 600,000 people annually and accrue yearly treatment costs of $2.5-5 billion.  Furthermore, it is predicted that as the population ages, demands on healthcare resources for CVLU treatments will drastically increase. Thus, it is critical that factors associated with CVLUs be discerned and adjuvant, evidence-based therapies be identified.  Previous studies have suggested that the pathogenesis of CVLUs involves the prolonged presence of high numbers of activated neutrophils secreting excessive proteases in wound beds that prolong inflammation, and destroy growth factors, receptors and the extracellular matrix that are essential for healing.  However, further evidence is needed before innovative treatments targeting neutrophils are recommended for CVLU care.  Therefore, the primary purpose of this project was to review observational or intervention studies from the past 15 years that characterized neutrophil activity in the microenvironment of human CVLUs for new evidence explicating the relationship between excessive, sustained neutrophil activity and CVLUs. Other principal goals were to review 1) the function of neutrophils in wound healing, and 2) appraise the strength of evidence for current and potential therapeutics that target excessive neutrophil activity.  A literature search was conducted with PubMed, Medline and Cochrane databases. The collective evidence suggests that upregulated neutrophil activity impedes CVLU healing. The evidence also supports using novel wound dressings that sequester proteases or deliver inhibitors of neutrophil-derived proteases directly in the biochemical environment of CVLUs.  In addition to specialized dressings, studies show that two systemic agents, pentoxifylline and micronized purified flavonoid fraction, are effective in modulating neutrophil activity. Therefore, adjunctive therapies that target excessive neutrophil activity may assist with resolving the persistent inflammation associated with CVLUs and improve healing outcomes for patients with these tenacious wounds.