Prognostic significance of early pulmonary function changes after onset of chronic lung allograft dysfunction

BACKGROUND: Chronic lung allograft dysfunction (CLAD), including the phenotypes of bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (R-CLAD), represents the leading cause of late death after lung transplantation. Little is known, however, regarding the natural history or prognostic significance of pulmonary function changes after the onset of these conditions. We examined changes in forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) over the first 18 months after CLAD. We also sought to determine whether lung function changes occurring early after CLAD impact longer term outcomes. METHODS: We performed a retrospective analysis of 216 bilateral lung recipients with CLAD, which included those with R-CLAD ( n  = 65) or BOS ( n  = 151). The course of FEV 1 and FVC after CLAD was described. Cox proportional hazards models were used to evaluate the impact of a ≥10% decline in FEV 1 or FVC within the first 6 months of CLAD on graft loss after that time. RESULTS: Lung recipients with CLAD, whether BOS or R-CLAD, had the largest decreases in FEV 1 and FVC within the first 6 months after onset. Moreover, a decline in FEV 1 or FVC of ≥10% within the first 6 months after CLAD was associated with a significantly increased hazard for graft loss after that time (hazard ratio [HR] = 3.17, 95% confidence interval [CI] 1.56 to 6.42, p  = 0.001, and HR = 2.80, 95% CI 1.66 to 4.70, p ≤ 0.001, respectively), an effect observed in both BOS and R-CLAD patients. CONCLUSIONS: Early physiologic changes after CLAD were independently associated with graft loss. This suggests lung function changes after CLAD, specifically a ≥10% decline in FEV 1 or FVC, could be a surrogate measure of graft survival.