Lung Transplant Failure and Rejection

This study is for people who have had a lung transplant and developed a condition called chronic lung allograft dysfunction (CLAD), which is a type of chronic rejection. Doctors often treat CLAD with a procedure called extracorporeal photopheresis (ECP), but it can take up to six months to know if the treatment is working. The goal of the study is to find early signs (biomarkers) that show whether ECP is helping, so patients can get the right care sooner. For participants in the study, small blood samples will be collected at three points during ECP treatment and, for some participants, two MRI scans of the lungs will be performed-one before starting ECP and one after finishing treatment. The MRI uses a safe contrast dye to help us see changes in lung blood flow and tissue. Investigators will also look at certain immune cells in the blood. This is not a study of a new drug or treatment-participants will receive the same ECP therapy their doctor already recommended. The study will help researchers understand how ECP works and identify markers that predict who benefits most. There is no direct benefit to participants, but participation may help improve care for future lung transplant patients.

LTx has the shortest survival of all solid organ transplants. The complex and time-demanding diagnostics of allograft dysfunction are a significant reason for this. The current study aims overarchingly to improve survival after lung transplantation (LTx) through precise and fast diagnostics. The specific aim is to develop direct-to-clinical implementation biomarkers for the most important aspects of long-term survival after LTx. An in-house-developed PCR-based cell-free-DNA methodology (cf-DNA) will be used for allograft damage and combined with specific other biomarkers to identify damage type. The current clinical golden standard for damage identification will be performed at every sampling instance. The research will be a single-centre prospective observational cohort study. The control samples at all time points will consist of the samples without allograft damage. Blood will be drawn at fixed time points and clinical events. All analyses will be performed at a separate lab, blinded to the patient's status. .

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.