Abstract
Background 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.
Methods 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.
Results 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).
Conclusions 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.
Footnotes
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Conflict of interest: None of the authors have any conflicts of interest to report.
Conflict of interest: V. Scaravilli reports Fondazione Ricerca Fibrosi Cistica grant number FFC 27/2019 (project adopted by: Delegazione FFC di Napoli San Giuseppe Vesuviano and Delegazione FFC di Como Dongo), and support for congress participation and payment for article writing from Biomerieux S.p.a. Italy, in the past 36 months.
Conflict of interest: L. Bos reports the Dirkje Postma Award from Longfonds, a grant from the Innovative Medicines Initiative COVID-19 call, a fellowship from Amsterdam University Medical Center, a PPP grant from Health Holland via Longfonds, VIDI and COVID-19 urgency grants from ZonMW, consulting fees from Scailyte paid to his institution, and advisory board fees from Sobi NL, Impentri, Novartis, AstraZeneca and CSL Behring paid to his institution, in the past 36 months.
Conflict of interest: G. Grasselli reports honoraria from Thermo Fisher and Pfizer Pharmaceuticals outside the present work, in the past 36 months.
Conflict of interest: The remaining authors have nothing to disclose.
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- Received November 10, 2023.
- Accepted March 12, 2024.
- Copyright ©The authors 2024
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