Background: The association between organizing pneumonia (OP) after lung transplantation with the development of acute rejection (AR) remains undefined. In addition, molecular allograft injury, as measured by donor-derived cell-free DNA (dd-cfDNA), during episodes of OP and its relationship to episodes of AR, chronic lung allograft dysfunction (CLAD), or death is unknown.
Methods: This multicenter, prospective cohort study collected serial plasma samples from 188 lung transplant recipients for dd-cfDNA at the time of bronchoscopy with biopsy. Multivariable Cox regression was used to analyze the association between OP with the development of AR (antibody-mediated rejection (AMR) and acute cellular rejection (ACR)), CLAD, and death. Multivariable models were performed to test the association of dd-cfDNA at OP with the risk of AR, CLAD, or death.
Results: In multivariable analysis, OP was associated with increased risk of AMR (hazard ratio (HR) = 2.26, 95% confidence interval (CI) 1.04-4.92, p = 0.040) but not ACR (HR = 1.29, 95% CI: 0.66-2.5, p = 0.45) or the composite outcome of CLAD or death (HR = 0.88, 95% CI, 0.47-1.65, p = 0.69). Median levels of dd-cfDNA were higher in OP compared to stable controls (1.33% vs 0.43%, p = 0.0006). Multivariable analysis demonstrated that levels of dd-cfDNA at diagnosis of OP were associated with increased risk of both AMR (HR = 1.29, 95% CI 1.03-1.62, p = 0.030) and death (HR = 1.16, 95% CI, 1.02-1.31, p = 0.026).
Conclusions: OP is independently associated with an increased risk of AMR but not CLAD or death. The degree of molecular allograft injury at the diagnosis of OP may further predict the risk of AMR and death.
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http://dx.doi.org/10.1016/j.healun.2023.11.008 | DOI Listing |
Transpl Int
January 2025
Department of Chronic Diseases, Metabolism and Ageing, Laboratory for Respiratory Diseases and Thoracic Surgery, Faculty of Medicine, KU Leuven, Leuven, Belgium.
Lung transplantation is a life-saving therapeutic option for many chronic end-stage pulmonary diseases, but long-term survival may be limited by rejection of the transplanted organ. Since HLA disparity between donor and recipient plays a major role in rejection, we performed a single center, retrospective observational cohort analysis in our lung transplant cohort (n = 128) in which we calculated HLA compatibility scores for B-cell epitopes (HLAMatchmaker, HLA-EMMA), T-cell epitopes (PIRCHE-II) and missing self-induced NK cell activation (KIR Ligand Calculator). Adjusted Cox proportional hazards model was used to investigate the association between mismatched scores and time to development of donor-specific antibodies (DSA) post-transplant, time to first biopsy-proven acute rejection episode, freedom from CLAD, graft survival and overall survival.
View Article and Find Full Text PDFJ Clin Pathol
January 2025
Department of Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.
Aims: In cystic fibrosis lung transplant recipients (LTRs), graft dysfunction due to acute infections, rejection or chronic lung allograft dysfunction (CLAD) is difficult to distinguish. Characterisation of the airway inflammatory milieu could help detect and prevent graft dysfunction. We speculated that an eosinophil or neutrophil-rich milieu is associated with higher risk of CLAD.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Surgery, University of Florida, Gainesville, FL, United States.
Lung ischemia-reperfusion injury (IRI), a common complication after lung transplantation (LTx), plays a crucial role in both primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) thereby adversely impacting the clinical outcomes in these patient cohorts. Lung IRI is characterized by several molecular events including immune cell infiltration, reactive oxygen species (ROS) generation, calcium overload, inflammation and various forms of cell death pathways. Currently, no therapeutic agents are available to clinically prevent lung IRI.
View Article and Find Full Text PDFJ Heart Lung Transplant
December 2024
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington; Hospital and Specialty Service, Veterans Affairs Puget Sound Health Care System, Seattle, Washington. Electronic address:
There is a paucity of data reporting the positive and negative predictive values (PPV, NPV) of acute declines in lung function on chronic lung allograft dysfunction (CLAD). We sought to define the predictive ability of single or repeated forced expiratory volume in the first second (FEV) declines for at least 3 weeks on the development of CLAD or death by 1-year. We analyzed 340 subjects with at least 3 years of follow-up data from two lung transplant centers.
View Article and Find Full Text PDFJ Heart Lung Transplant
November 2024
Toronto Lung Transplant Program, Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Netwrok, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada. Electronic address:
Background: Surveillance bronchoscopies with bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) are primarily used to detect acute cellular rejection (ACR) or infection in lung transplant (LTx) recipients. We previously identified a BAL protein signature associated with chronic lung allograft dysfunction (CLAD) or death/retransplant in patients with stable minimal (grade A1) ACR. This present study aimed to determine whether similar BAL biomarkers predict outcomes in stable patients when ACR grade is undetermined.
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