Identifying early changes in skin integrity using biomarkers

Abstract

Skin damage, in particular, those involving chronic wounds such as pressure ulcer (PU) and incontinence associated dermatitis (IAD) represent a major challenge for both vulnerable patients and health care providers. Current skin evaluation involves subjective tools, such as risk assessment scales and visual skin assessment. However, these are known to have limited reliability and diagnostic accuracy. Therefore, there is a pressing need for early detection of skin damage using novel techniques to provide timely interventions to prevent chronic wounds. Accordingly, this project is designed to identify, develop and evaluate the performance of a range of biomarkers to detect local changes in skin health. Protocols were developed to investigate changes in skin health following different insult models, ranging from lab-based insult models to clinical cohort studies. Changes in skin parameters were investigated using a combination of prospective and secondary analysis studies. Secondary analysis involved technical evaluation of biophysical parameters measured at different anatomical regions and following different insult models. Prospective studies involved development of an efficient extraction methodology to analyse low-abundant inflammatory markers from sebum and the corresponding use of the methodology in evaluating skin’s inflammatory status. Results from the studies suggest a high level of variability in the basal values of biophysical parameters, skin surface sebum volumes and corresponding inflammatory biomarker concentrations. The secondary analysis revealed that thresholds derived from single biophysical parameters were limited in detecting skin damage following insults. Moreover, a high level of variability was observed in the basal values of sub-epidermal moisture (SEM), both at different body locations and between subjects. The prospective studies involving healthy volunteers revealed an optimum time point for sebum collection. An optimised extraction protocol was developed resulting in an 1.5-2.0-fold increase in recovery of high and low abundant cytokines. Skin cytokine response following the use of respirators, incontinence pads and shavers revealed a selective upregulation of inflammatory biomarkers. Indeed, the findings revealed that the use of shavers and masks led to a pronounced increase in inflammatory response compared to exposure to incontinence pads. There were distinct clusters of responses within a cohort of healthy volunteers which could possibly suggest an intrinsic risk of skin damage. Skin inflammation assessed on sites presenting with Stage-I PU revealed a localized upregulation of pro-inflammatory cytokines and a downregulation of anti-inflammatory cytokine IL-1RA. Selected cytokines, namely IL-1α, IL-1RA, IL-8, G-CSF and the ratio of IL-1α/ IL-1RA offered clear delineation in the classification of healthy and Stage-I PU, with good receiver operating characteristic curves. The findings from the studies clearly indicate that changes in inflammatory status of skin serve as promising biomarkers for detecting early and established signs of skin damage. The new extraction methodology and the identified markers have also been critical in evaluating the skin status following the use of various products, such as shavers, incontinence pads and respirators. Although further studies are required to investigate the biochemical changes occurring prior to skin damage, the current studies provide an indication for their use as a point of care diagnostic tool.

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Identifiers

ORCID for Hemalatha Jayabal: orcid.org/0000-0003-4192-4464

ORCID for Pete Worsley: orcid.org/0000-0003-0145-5042

ORCID for Daniel L Bader: orcid.org/0000-0002-1208-3507

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