View clinical trials related to Lung Transplant Rejection.
Filter by:The aim of this study is to generate evidence regarding organizing pneumonia in lung transplant recipients.
Lung transplantation is a consolidated treatment in selected patients with end-stage respiratory diseases; however, acute rejection remains an important cause of lung allograft loss and a risk factor for chronic allograft dysfunction. Histopathological examination of lung tissue is the gold standard for the diagnosis of acute rejection, therefore recipients undergo surveillance transbronchial biopsy and bronchoalveolar lavage after transplantation. However, the obtained tissue is sometimes inadequate for histopathology, and the endoscopic procedure can lead to complications (bleeding, pneumothorax). The quantification of donor-derived cell-free DNA (ddcfDNA) in the recipient plasma has shown to be increased in case of acute rejection, and could represent an early and non-invasive diagnostic marker to detect acute rejection. We planned to enroll all patients aged 18 to 65 years old enlisted for lung transplantation at our centre. Patients undergoing retransplantation and patients with a history of prior solid organ transplantation were excluded. The quantification of donor-derived cell-free DNA was performed 15 days and 3, 6, and 12 months after transplantation, concurrently with the routine surveillance bronchoscopies as per our protocol; the same analysis was also conducted in case of suspected clinical rejection.
The LAMBDA 002 registry study is an observational, longitudinal, multi-center study observing patients undergoing lung transplant.
Lung transplantation is an established therapy for end-stage lung disease such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and pulmonary hypertension. However, Chronic Lung Allograft Dysfunction (CLAD) is a major cause of morbidity and mortality in long-term survivors. The 5-year survival rate is reported to be 50%, which is considerably inferior compared to other solid organ transplantation. In addition, the financial burden of CLAD (around 80.000 euro/year for a patient with CLAD) is considerable. No curative therapy is available yet. To date, the two most effective treatment are azithromycin and extracorporeal photopheresis. Azithromycin is used as first-line treatment and it is effective in stopping FEV1 decline, however its effects are only limited to a set of patients. ECP can be used as second-line treatment in patients unresponsive to azithromycin. ECP has been firstly developed for treatment of cutaneous T cell lymphomas and later used in a variety of other indications including solid organ transplantation. The process starts with leukapheresis, followed by incubation of the isolated cells with 8-methoxypsoralen (8-MOP) and subsequent activation of 8-MOP with ultraviolet A radiation. At the end, the cells are reinfused into the patient. 8-MOP is a biologically inert substance, but in the presence of UVA light it cross-links DNA by forming covalent bonds with pyrimidine bases and causes apoptosis. ECP is effective in the palliative treatment of cutaneous T-cell lymphoma but its effectiveness was also shown in several other T-cell-mediated diseases, particularly in the treatment and prevention of acute and chronic graft-versus-host disease. In depth knowledge on the mechanisms whereby ECP manipulates the immune system are still unclear. Most of the experimental studies have been performed in murine models of GvHD. Apoptotic cells isolated during ECP treatment have the potential to induce IL-10 secretion, reduce dendritic cells activation and increase percentage of Tregs. In addition, ECP reduces the production of IL-6 and TNF-α and increases TGF-β production. In lung transplantation, ECP treatment is used as second-line treatment of CLAD and it has the potential to stabilize lung function decline and to improve long-term graft. According to the published literature, however, approximately 30 to 40% of treated recipients did not profit from ECP. Greer and colleagues found that RAS patients as well as rapid lung function decliners showed lower rate of response and worse long-term outcomes. On the contrary in a more recent analysis only BOS diagnosis was associated with better outcomes. A single prospective interventional study was published by our group and it confirmed results from other previous retrospective analysis. Up to now, no clear predictors for response have been identified yet.
Chronic lung allograft dysfunction (CLAD) is the leading cause of long-term mortality after lung transplantation. Several risk factors for CLAD have been identified, but the exact pathophysiology and triggering molecular factors remain largely unknown. Moreover, in clinical practice, no integration of the different risk factors is achieved. CLAD is therefore diagnosed most often late with the persistent decline in respiratory function, revealing a profound and irreversible alteration of the pulmonary graft. Several blood biomarkers that can predict the occurrence of CLAD more than 6 months before clinical diagnosis have been identified and validated. From these preliminary results, a composite score is being developed from independent samples from the COLT (COhort in Lung Transplantation) cohort. The main objective of this project is to validate this robust and predictive composite score (biological and clinical) of CLAD.
The objective of the trial is to assess efficacy and safety of add-on aerosolized liposomal cyclosporine A (L-CsA) to Standard of Care (SoC) therapy as compared to SoC therapy alone in the treatment of Bronchiolitis obliterans syndrome (BOS) in single lung transplant recipients.
The objective of the trial is to assess efficacy and safety of add-on aerosolized liposomal cyclosporine A (L-CsA) to Standard of Care (SoC) therapy as compared to SoC therapy alone in the treatment of Bronchiolitis obliterans syndrome (BOS) in double lung transplant recipients.