UCLA

Background: Primary graft dysfunction (PGD) is an early complication of lung transplantation associated with poor early outcomes, however less is known about its prolonged effects on morbidity and mortality. We hypothesized that PGD is associated with long-term mortality and chronic rejection in the form of bronchiolitis obliterans syndrome.

Methods: A retrospective study of 279 adult lung transplant recipients between 2000 and 2007 was performed. PGD grade was determined both immediately after transplantation (T0) and at 72 hours post-transplant (T72). Chronic rejection defined as stage 1 bronchiolitis obliterans syndrome (BOS), long-term mortality in 90-day survivors were modeled using competing risk and extended Cox models with time-dependent covariates with internal validation performed via bootstrapping. Cumulative incidence plots for the outcome of BOS were created for each PGD grade and at both time points.

Results: We found that there was a significant stepwise increase in the hazard ratio for both BOS and mortality with increasing PGD grade. This association was most severe among patients with grade 3 PGD at T72, and the association with BOS persisted in adjusted multivariable models with a hazard ratio of 3.75 (95% CI 1.11-21.4, p < 0.001). Stratified analyses in recipients with either single or bilateral transplants were also consistent with this finding. The association between PGD and long-term mortality also persisted after adjustment for baseline covariates, but in multivariable models of mortality that also incorporated BOS as a time-dependent variable, PGD was no longer significantly associated with mortality.

Conclusions: These results suggest that severe PGD in the early perioperative period may play a causal role in the subsequent development of BOS after lung transplantation in some patients, and that the development of BOS in patients with PGD may account for increased rates of death even among recipients with severe PGD who survive the early perioperative period.