Biomolecular Phenotyping Primary Graft Dysfunction after Lung Transplantation: a scoping review

Primary graft dysfunction (PGD) is the most common complication and leading cause of early mortality and long-term disability after lung transplantation (LUTX). PGD is an acute form of acute lung injury resulting from ischemia-reperfusion injury, with an incidence around 30%, defined and graded upon alteration of oxygenation and radiographic criteria occurring within 72 hours after graft reperfusion. Predictive enrichment by measurement of plasma biomarkers may allow for the detection of different treatable traits in patients who have undergone lung transplant (e.g., hypoinflammatory vs. hyperinflammatory) and thus apply further targeted treatments to these sub-cohorts. With this scoping review, we want to collate the literature regarding early plasmatic biomarkers of PGD in adult patients who have undergone double-lung transplantation

Biomolecular Phenotyping Primary Graft Dysfunction after Lung Transplantation: a scoping review

Primary graft dysfunction (PGD) is the most common complication and leading cause of early mortality and long-term disability after lung transplantation (LUTX). PGD is an acute form of acute lung injury resulting from ischemia-reperfusion injury, with an incidence around 30%, defined and graded upon alteration of oxygenation and radiographic criteria occurring within 72 hours after graft reperfusion. Predictive enrichment by measurement of plasma biomarkers may allow for the detection of different treatable traits in patients who have undergone lung transplant (e.g., hypoinflammatory vs. hyperinflammatory) and thus apply further targeted treatments to these sub-cohorts. With this scoping review, we want to collate the literature regarding early plasmatic biomarkers of PGD in adult patients who have undergone double-lung transplantation

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

Background Lung transplantation (LUTX) is often 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 International Society for Heart and Lung Transplantation (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 nine 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 four adhered to 2016 PGD definitions. Enzyme-linked immunosorbent assays and the multiplex bead array technique were utilised in 23 and two papers, respectively. In total, 26 candidate biomarkers were identified, comprising 13 inflammatory, three endothelial activation, three epithelial injury, three cellular damage and two coagulation dysregulation markers. Only five biomarkers (sRAGE, ICAM-1, PAI-1, SP-D, FSTL-1) underwent area under the receiver operating characteristic curve 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

Right ventricle free wall longitudinal strain screening of lung transplant candidates

Background Lung transplant (LUTX) candidates have subclinical right ventricular (RV) dysfunction, which has not yet been assessed by speckle-tracking echocardiography (STE)-derived RV free-wall longitudinal strain (RVFWLS). To evaluate the prevalence of RV dysfunction by RVFWLS and its relationship with conventional RV echocardiographic indexes in LUTX candidates. Methods In a single-center prospective observational cohort study, from January 2021 to March 2023 consecutive LUTX candidates underwent cardiac catheterization, radionuclide ventriculography, standard and STE. The diagnostic accuracy of RV ejection fraction by ventriculography (RVEF), tricuspid annular plane excursion (TAPSE), fractional area change (FAC), tricuspid peak annulus systolic velocity (S') versus RVFWS were computed. Results Thirty-four patients (female, 41%) with a mean age of 48 [36-59] years old enlisted for pulmonary fibrosis (35%) and cystic fibrosis (30%) were included. At cardiac catheterization, only 7 (23%) had pulmonary hypertension. Around 15-25% presented right heart enlargement. Tricuspid regurgitation was present in 20 (60%) of the patients. Median RVFWLS was -20.1% [-22.5%--17%], being impaired (> -20%) in 16 (47%) of the patients. RVFWLS identified the highest percentage (47%) of RV dysfunction, compared to TAPSE (32%), S' (27%), FAC (26%), and ventriculography (15%), which had very low sensitivity for detecting RV dysfunction compared to RVFWLS. Conclusions In patients enlisted for LUTX, RV dysfunction assessed by STE-derived RVFWLS is highly prevalent. STE can detect RV dysfunction better than standard two-dimensional echocardiography and ventriculography. Further studies are urgently needed to define the clinical implications and the prognostic value of RV dysfunction measured with RVFWLS