Wound fluid proteomics reveal elevated alpha-1 antitrypsin levels are associated with healing of medical device related pressure injury

The Medical Device Related Pressure Injuries (MDRPIs) are a wound type that has been extensively tracked and recorded within observational studies, with a global patient prevalence of 19.3% [Zhang N et al. in Eur J Med Res 1:425, 2024] and 28.1% in acute care patients [Brophy S et al. in J Tissue Viability 4:489-498, 2021]. Yet, despite being an injury caused directly by medical intervention, to the author’s knowledge, no in-depth proteomic analysis in this wound type has been published previously. This study represents a novel proteomic analysis of clinical MDRPI samples providing initial characterization of a protein pathway significant to wound healing in the context of MDRPIs developed in an ICU setting (Fig. 1). To investigate the proteomic changes associated with the healing outcomes of medical device related pressure injuries through comprehensive proteome characterisation. Clinical wound fluid samples were collected from Intensive Care Unit (ICU) patients with MDRPIs. These samples underwent analysis using Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS) mass spectrometry. The severity and healing trajectories of the injuries were assessed using the Pressure Ulcer Scale for Healing (PUSH) scores, facilitating the comparison of protein abundances to identify key pathways involved in healing and non-healing MDRPIs. The study identified a significant inverse correlation between the severity of non-healing MDRPIs and the levels of alpha-1 antitrypsin (A1AT) (R = -0.43; P = 0.035). A1AT functions as an inhibitor of neutrophil elastase (NE), which targets kininogen-1 (KNG-1). This relationship was further substantiated by a strong positive correlation between A1AT and KNG-1 levels (R = 0.76; Q < 6.8 × 10− 10), indicating a protective function of A1AT over KNG-1 from NE. Given that KNG-1 contributes to early wound healing through its derivative, bradykinin, the misregulation of A1AT may disrupt the healing process of MDRPIs. The findings suggest that decreased levels of A1AT are associated with increased severity in non-healing MDRPIs, potentially due to the disruption of KNG-1 activity. These insights offer a foundation for further research into targeted therapeutic strategies aimed at enhancing the healing of MDRPIs.