LUTIN

The overall goal of The European LUng Transplantation and INovation (LUTIN) proposal is to prepare an application in response to the H2020 call SC1-BHC-30-2019: Towards risk-based screening strategies. Specifically, we propose to use lung transplantation as a model for developing new risk-based screening strategies to improve allograft allocation, prevention of chronic lung allograft dysfunction and overall survival of patients suffering from end-stage pulmonary diseases by bringing to the bedside personalized decision-support tools based on contextualised individual bioclinical data. Lung transplantation (LT) is the ultimate treatment for patients suffering from end-stage pulmonary diseases. It is the fastest growing segment of solid organ transplantation because of increasing incidence of advanced lung diseases such as COPD and lung donor utilization rates. The demand for lung transplants is however far greater than the available supply of donated lungs. Effective risk-based screening strategies to improve both the indications and timing of lung transplantation are therefore urgently needed. Post-transplantation, the development of chronic lung allograft dysfunction (CLAD), with an occurrence of 50% within 5 years is the major factor limiting the positive long-term outcome of LT [1,2].CLAD is a diagnosis of exclusion, once confounding factors related to allograft (persistent acute rejection, infection, anastomotic stricture, disease recurrence), or extra-allograft complications (pleural disease, diaphragm dysfunction or native lung hyperinflation) are ruled out[3]. The late diagnosis of CLAD, based upon persistent decline in lung function, reveals an advanced degradation of the allograft. Prognosis is poor, with respectively 4 and 2 years median survival for bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) after onset. Robust early decision support tools are therefore needed to set up active preventive immuno-interventions, improve the management of transplant recipients and transform lung transplantation into a sustained and long-term treatment of lung disease. To address these challenges the project aims to i) reframe paradigms for lung transplantation indications, ii) improve the timing of lung transplantation, and iii) after transplantation transform current management practices with real-time computations leveraging the wealth of data from existing cohorts; ultimately, we will deliver an integrated risk stratification and prognosis platform for lung transplant candidates and transplant recipients. - The specific aim 1 focuses on pre-transplant care: To enhance the risk stratification, personalization and timing for lung transplantation referral, according to geographic, demographic, functional and molecular data. - The specific aim 2 focuses on precision management of transplant recipients: To deliver data-driven diagnostic interpretation, prognosis, and a comprehensive disease management strategy a clinical decision support system (CDSS). - The specific aim 3 focuses on the patient perspective and evaluation of innovative tools in LT: To account for and integrate the patient’s perspective facing the emerging role of massive data visualization and probabilistic representations untangling multiple therapeutic scenarios. Our project considers a wide view of lung transplantation: from the patient with end stage respiratory disease and his pre-transplant process to the long term follow-up of LT recipients. This systematic study aims to deliver an integrated approach of lung transplantation.