View clinical trials related to Lung Transplant Rejection.
Filter by:This is an open label, multicenter, safety and PK study comparing safety, efficacy, and pharmacokinetic (PK) levels of Tacrolimus Inhalation Powder in lung transplant patients that require reduced tacrolimus blood levels due to kidney toxicity. Part A of the study will consist of a 12 week safety, efficacy, and PK study. Part B of the study will be an optional safety extension following successful completion of the 12 week safety, efficacy, and PK study. Patients would have the option to continue Tacrolimus Inhalation Powder for up to 1 year, with a possibility to extend to 2 years depending on the results from Part A.
Lung transplantation (LTx) is the only effective treatment for patients with end stage lung disease. Of the major organs transplanted, survival following LTx is the lowest with a mean of 5 years. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and contributes to the development of chronic lung allograft dysfunction (CLAD) that remains the leading cause of late mortality. Earlier detection of rejection after LTx is of substantial importance as it would improve the possibilities of treatment and could increase survival. The investigators have shown in previous work that exhaled breath particles (EBP) reflect the composition of respiratory tract lining fluid (RTLF). EBP and particle flow rate (PFR) can be used as non-invasive methods for early detection and monitoring of airway diseases such as acute respiratory distress syndrome (ARDS). It has also been shown that the particle flow prolife after lung transplantation differs between patients who develop PGD and those who do not and that the composition of EBP differs between patients with and without bronchiolitis obliterans syndrome (BOS), an obstructive form of CLAD. Samples of EBP and measurements of PFR will be collected from lung transplanted patients. Membranes with EBP will be saved for molecular analysis. The investigators aim to identify potential particle flow patterns and biomarkers for earlier detection of rejection after lung transplantation.
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.
CLAD is defined as loss of lung function after other factors, particularly infections have been excluded. Readily accessible diagnostic procedures to detect acute cellular rejection at the earliest possible occasion is crucial for posttransplant survival. Serial lung function tests, laboratory testing and pulmonary imaging are only clinical indicators of chronic allograft dysfunction in lung transplant recipients. Since forceps biopsy to detect acute cellular rejection in lung transplant recipients has several shortcomings, the purpose of this study is to investigate a new biopsy technique using the transbronchial cryoprobe.
Chronic complications such as chronic lung allograft dysfunction (CLAD) remain the leading cause of death and the primary limitation to long-term survival for lung transplant recipients. CT is currently use for longitudinal assessment in the pediatric population with lung transplant. However, it uses radiation that has been related to increase cancer risk. MRI has played a limited role in the evaluation of lung pathologies. To overcome these limitations, the use of inhaled, hyperpolarized (HP) noble gases such as helium-3 (3He) and xenon-129 (129Xe) has come into play. Filling the air spaces within the lungs with either of these HP gases provides enough signal and contrast to obtain quality images on MRI. The primary objective of this study is to evaluate the diagnostic performance of hyperpolarized xenon MRI for the assessment of CLAD in pediatric patients with lung transplant.
Transplant results vary considerably from one organ to another. Lung transplantation has poorer long-term outcomes than other solid organ transplants, with a current median post-transplant survival of 6.0 years. Allograft rejection remains the leading cause of morbidity and mortality in all organ groups and is the leading cause of death, accounting for more than 40% of deaths beyond the first year after lung transplantation. Each dysfunctions impacts the fate of the graft and therefore the survival of the recipient. Their early and precise diagnosis is therefore a major issue. The identification of the pathophysiological mechanisms underlying these different subtypes of dysfunction (transcriptomics, polymorphism of target genes of the immune system or tissue repair, cell phenotyping) is an essential step. It can only be done on the basis of a collection of samples linked to a clinical database allowing to contextualize each sample.
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.
To investigate safety of treatment with allogeneic adipose tissue-derived mesenchymal stromal cells (ASCs) in patients undergoing lung transplantation, to evaluate whether the treatment can reduce host immunological reaction towards the graft, and to reduce the ischemic reperfusion-injury after transplantation.
The purpose of this investigation is to determine the association of the fraction of donor-derived cell-free DNA in plasma and lung fluid samples with acute rejection as proven by biopsy in lung transplant recipients.