Early serum biomarkers to characterise different phenotypes of primary graft dysfunction after lung transplantation: a systematic scoping review

Lung transplantation (LUTX) often is complicated by primary graft dysfunction (PGD). Plasma biomarkers hold potential for PGD phenotyping and targeted therapy. This scoping review aims to collect the available literature in search of serum biomarkers for PGD phenotyping.Following JBI and PRISMA guidelines, we conducted a systematic review searching MEDLINE, Web of Science, EMBASE, and The Cochrane Library for papers reporting the association between serum biomarkers measured within 72 h of reperfusion and PGD, following ISHLT guidelines. We extracted study details, patient demographics, PGD definition and timing, biomarker concentration, and their performance in identifying PGD cases.Among the 1050 papers screened, 25 prospective observational studies were included, with only 9 conducted in the last decade. These papers included 1793 unique adult patients (1195 double LUTX, median study size 100 (IQR 44–119). Most (n=21) compared PGD grade 3 to less severe PGD, but only 4 adhered to 2016 PGD definitions. Enzyme-linked immunosorbent assays and the multiplex bead array technique were utilised in 23 and 2 papers, respectively. In total, 26 candidate biomarkers were identified, comprising 13 inflammatory, 3 endothelial activation, 3 epithelial injury, 3 cellular damage, 2 coagulation dysregulation markers. Only 5 biomarkers (sRAGE, ICAM-1, PAI-1, SP-D, FSTL-1) underwent AUROCC analysis, yielding a median value of 0.58 (0.51, 0.78) in 406 patients (276 double LUTX).Several biomarkers exhibit promise for future studies aimed at PGD phenotyping after LUTX. To uncover the significant existing knowledge gaps, further international prospective studies incorporating updated diagnostic criteria, modern platforms, and advanced statistical approaches are essential.