Novel biomarkers for rapid aspiration identification in donor lung grafts, enabling improved triaging prior to lung transplantation.

• Applicant: Dr. Mohamed Elbayomi
• Subject Area: Pneumology, Thoracic Surgery ; Clinical Immunology and Allergology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570627661

While lung transplantation is a lifesaving procedure for people with end-stage lung diseases, it has the worst survival rate of all solid organ transplants. The quality of the donor organ, among other factors, can impact outcomes. Aspiration of stomach contents into the tracheobronchial tree can harm the donor’s lungs. Currently, bronchoscopy primarily uses visual inspection to assess aspiration in donor lungs. However, this approach is subjective and insensitive. Thus, there is a clear need for objective and easy-to-measure biomarkers of clinically significant aspiration in donor lungs. A large airway bronchial wash (LABW) sample is commonly collected during donor bronchoscopy. Our group previously showed that levels of bile acids in the donor LABW correlate with aspiration and non-acceptance for transplantation. Importantly, pre-transplant ex vivo treatment of porcine lungs reversed the effects of aspiration and improved outcomes, making aspiration a high-yield modifiable donor lung diagnosis. Our recent large-scale study of 605 human donor lungs identified a link between high levels of total bile acids (TBA) in the donor LABW and non-acceptance for transplantation, worse donor lung function pre-transplant, and negative recipient outcomes. In this study, we measured TBA using a colorimetric assay, which is time-consuming and not suitable for point-of-care testing. Additionally, the specific biological effects of bile acids and aspiration on the lung graft remain unclear. Our goal is to develop a rapid point-of-care assay that will measure aspiration biomarkers in donor LABW for effective assessment and treatment determination. We hypothesize that donor aspiration causes inflammation and epithelial injury by enhancing pathogen-associated molecular patterns (PAMPs). Aim 1: Translate the LABW aspiration signature for rapid clinical adoption. In a pilot study (Figure 1B-D), we demonstrated that TBA can be measured using an enzyme-linked immunosorbent assay (ELISA) (MyBioSource MBS723419), which can be easily translated into a point-of-care test. We will optimize and validate the TBA ELISA in the donor LABW samples (n=605), comparing results to our previous data. Aim 2: Determine whether LABW biomarkers of aspiration correlate with PAMPs, inflammation, and epithelial damage. We will use ELISA or multiplex assays to measure lipopolysaccharide and beta-glucan PAMPS, IL-6, and IL-8 cytokines, and markers of epithelial injury (cytokeratin-18 breakdown products, club cell secretory protein, and surfactant protein-D). Significance: We anticipate that implementation of our LABW aspiration biomarker signature will enable early detection of aspiration in donor lungs, resulting in improved triage for further assessment and treatment of the lungs on the ex-vivo lung perfusion platform.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professorin Tereza Martinu