Long Term Follow up of the Lung Transplant Outcomes Group Cohort

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Lung transplantation is a potentially life extending treatment for patients with end stage lung diseases; however, lung transplant is a relatively new field, and long-term outcomes are disappointing with a median survival of ~6 years.2 Furthermore, among those who survive, half suffer from impaired lung function - chronic lung allograft dysfunction (CLAD) – which causes distressing symptoms and disability.3 Yet, fundamental knowledge gaps persist in the understanding of the clinical and biological processes that occur after lung transplantation; advancing such knowledge is critical to improve long-term outcomes. The Lung Transplant Outcomes Group (LTOG) is the first and largest multicentered epidemiologic study in lung transplantation designed to address issues surrounding early post-transplant complications. LTOG began as an 11-center prospective cohort study formed in 2007. Initially, LTOG focused on the clinical mechanisms and biomarkers for the early post-transplant complication of primary graft dysfunction (PGD), a serious condition that often leads to early graft failure and death. Over 3000 subjects have been enrolled in the LTOG during the past ten years. In this application, we aim to extend follow up of the LTOG and capitalize on this rich resource of clinical data, biosamples, and infrastructure to address fundamental but previously unanswerable questions about the long term outcomes of lung transplantation. We will have two aims focused on major long- term issues key to lung transplant patient outcomes: in Aim 1 we will perform long-term CLAD phenotyping of all subjects enrolled in the LTOG until death or study end using current state-of-the-art definitions; and in Aim 2 we will determine the long term functional status of the recipient including targeted measures of frailty domains and functioning, disability, and health-related quality of life. Our proposal is significant in that it will create a unique resource capable of generating tremendous new knowledge in a growing field, both directly as a result of data in hand and by facilitating new research on NHLBI-relevant lung diseases. It is innovative in generation of a novel data source at a low cost by leveraging a unique established cohort, and in efficient data practices. It is impactful in developing new knowledge that may change transplant practices worldwide by merging long-term graft and patient phenotype data with a rich early-transplant data and biosample resource, by defining new mechanisms of relevant lung transplant syndromes, and by providing a platform for ancillary research applications for a generation of investigators.