The Natural History of Chronic Lung Allograft Dysfunction in Single and Bilateral Orthotopic Lung Transplant Recipients

BACKGROUND: A better understanding of chronic lung allograft dysfunction (CLAD) natural history could be useful in targeting interventions to those most likely to progress. We hypothesized that pre-CLAD lung function trajectory would predict post-CLAD lung function and survival. METHODS: We identified first lung transplant recipients between January 1, 2000, and January 1, 2020, diagnosed with probable or definite CLAD. We examined the trajectory of forced expiratory volume in 1 s (FEV1) in the 3 mo before CLAD onset and divided patients into 3 groups based on slow, intermediate, or rapid decline in FEV1. We compared clinical characteristics, post-CLAD pulmonary function changes, and survival between these groups. RESULTS: There were 293 subjects with CLAD meeting eligibility criteria, including 162 bilateral orthotopic lung transplant (BOLT) and 131 single orthotopic lung transplant (SOLT) recipients. In BOLT recipients, intermediate and rapid progressors had significantly lower FEV1 and forced vital capacity at 3 and 6 mo post-CLAD as compared with slow progressors. Among SOLT, rapid progressors also had significantly lower FEV1 and forced vital capacity at 3 and 6 mo post-CLAD. Mortality was also increased in intermediate and rapid progressors compared with slow progressors. In an adjusted Cox proportional hazards regression model, rapid pre-CLAD progression and higher CLAD stage were associated with increased hazard of CLAD progression in entire cohort. CONCLUSIONS: Rates of FEV1 decline in the 3 mo before CLAD onset predict CLAD progression and mortality after CLAD onset in BOLT and SOLT recipients. The ability to predict CLAD progression at CLAD onset could help enrich future interventional trials.