Non-immune acute graft injury after lung transplantation and the risk of subsequent bronchiolitis obliterans syndrome (BOS)

Abstract

Background: Primary graft dysfunction remains a major cause of early morbidity and mortality after lung transplantation. Evidence from animal models shows acute non-immune lung injury increases organ immunogenicity by enhancing MHC Class II expression. We hypothesized that acute non-immune injury in the lung allograft may impact, not only on early survival, but also on longer term survival by increasing the incidence of bronchiolitis obliterans syndrome (BOS).

Methods: A single-center, retrospective, observational study in a population of over 320 lung transplant recipients was undertaken. The histologic diagnosis of diffuse alveolar damage (DAD) in an early graft biopsy was used to define those recipients at risk. Serial measurements of forced expiratory volume in 1 second (FEV(1)) in long-term follow-up defined the incidence of BOS.

Results: Early graft biopsy was available in 291 of the recipients following transplantation. DAD was confirmed in 55 (19%); their 30-day survival (62.5%) was significantly worse than in recipients without DAD (87.5%; p < 0.0001, chi-square test). When 30-day deaths were excluded, however, there was no difference in survival between recipients with and without DAD (hazards ratio 0.69 [0.37 to 1.3]; p = 0.25, Wilcoxon's survival analysis). The incidence of subsequent BOS over the follow-up period was not significantly different in those with and without DAD on early biopsy at 46% and 59%, respectively (hazards ratio 0.88 [0.48 to 1.62]; p = 0.22, chi-square test). BOS did not occur any earlier in the DAD group (median 953 days, range 152 to 1,393) days compared with the non-DAD group (median 665 days, range 52 to 4,299) (p = 0.48, Fisher's exact test).

Conclusions: The development of severe non-immune acute graft injury after lung transplantation has a poor early prognosis. However, recipients with non-immune acute graft injury who survive >30 days show no significant difference in long-term survival or BOS-free time compared with recipients without early injury.