Advanced body composition imaging to improve outcomes in lung transplantation - PROJECT SUMMARY Median survival after lung transplantation (Tx) is only 6.7 years, compared to >11 years after other solid organ Tx. Obesity increases risk of death on the Tx waitlist, early severe lung injury (primary graft dysfunction, PGD), and death after lung Tx. We have repeatedly shown that measures of adipose distribution on computed tomography (CT) scan identify candidates at risk for pre-Tx, peri-operative, and post-Tx morbidity and mortality beyond body mass index (BMI). Measures of adipose distribution are routinely used to quantify risk in the general population. In fact after screening with BMI, obesity guidelines recommend further risk stratification by adipose distribution. How to similarly integrate adipose distribution measures into lung Tx risk assessments is a knowledge gap. Better quantification of obesity-related risk is critical to ensuring that candidates at risk for these outcomes are (i) waitlisted before they are too sick to undergo Tx, and (ii) receive operative management that minimizes the risk of post-Tx morbidity and mortality. Optimal waitlist timing balances pre-Tx and post-Tx survival: sick enough to benefit from Tx but not so sick that the patient develops complications and dies soon after Tx. Guidelines recommend waitlisting candidates at >50% risk of death within 2 years without Tx and >80% likelihood of living 5-years post-Tx. CT-measured adipose distribution is associated with survival in both periods: risk of death without Tx (Aim 1) and risk of death after Tx (Aim 3) beyond BMI. Inclusion of adipose distribution measures in these risk assessments will improve timely waitlisting leading to decreased waitlist mortality and increased post-Tx survival. Measures of adipose distribution will also inform operative management. Once a candidate is added to the waitlist, estimates of PGD risk are critical to selecting the operative approach that minimizes post-Tx morbidity and mortality (e.g. extracorporeal support, bilateral vs single lung Tx). We have shown that CT-measured adipose distribution identifies recipients at risk for severe PGD beyond BMI (Aim 2). It is now feasible to obtain these CT measures in clinical practice: we validated an automated tool in radiology software already in use at our center. The logical next step is to establish metrics of adipose distribution that inform Tx risk assessments. The Lung Transplant Outcomes Group multi-center cohort study (LTOG, U01 HL145435) prospectively enrolled lung Tx candidates to identify risk factors for PGD and death. Since chest CT scans are universally performed in lung Tx to evaluate the lungs, we will retrospectively collect these clinical CTs to measure adipose distribution. We will leverage LTOG's data on Tx recipients while expanding the database to include all subjects evaluated for Tx. We will establish metrics of adipose distribution that predict 2-year survival without Tx (Aim 1), identify recipients at high risk of PGD (Aim 2), and improve discrimination of post-Tx survival (Aim 3). We will externally validate our findings in a cohort at WashU previously used to validate our LTOG PGD risk score. Accomplishing these aims will improve lung Tx outcomes by optimizing waitlist timing and informing operative management.
