Risk factors for chronic lung allograft dysfunction (CLAD) in the SysCLAD cohort

Introduction: CLAD and its phenotypes, Bronchiolitis Obliterans Syndrome (BOS) and Restrictive Allograft Syndrome (RAS) are major causes of mortality after lung transplantation (LT). Aims: To identify clinical factors associated with stable allograft function, BOS or RAS in the French and Swiss LT cohorts (SysCLAD cohort). Methods: Patients who completed a 3-year follow-up, died or had a 2^nd LT within 3 years were included in the study. An audit group of LT specialists assessed pulmonary function tests, chest CT scans and confounding factors to identify stable patients, RAS and BOS. Recipient and donor baseline characteristics, data on surgery, immunosuppressive treatment, follow-up events and outcomes were collected. Logistic regression analysis (LRA) was used for predictors of CLAD and multivariate multinomial analysis (MMA) for predictors of BOS, RAS and stability. Results: The SysCLAD cohort included 422 patients, 19% of whom had CLAD (BOS n=51, RAS n=31), 35% were stable, 10% had an inconclusive CLAD phenotype due to the presence of confounding factors and 36% died or underwent a 2^nd LT not due to CLAD. Factors positively associated with CLAD in the LRA were thymoglobulin use and the number of treated infections during year 1. In MMA, thymoglobulin induction was associated with BOS, the number of treated infections by year 1 was associated with RAS, the presence of de novo donor-specific antibodies was associated with BOS and RAS while stability was associated with the diagnosis of cystic fibrosis. Conclusion: Clinical factors such as thymoglobulin use or infections early after LT may assist to predict stability, BOS or RAS. Their identification may allow intervention or guide risk stratification.