Detection of Epstein–Barr virus DNA in peripheral blood is associated with the development of bronchiolitis obliterans syndrome after lung transplantation

Abstract Background The long-term success of lung transplantation is limited by the development of bronchiolitis obliterans syndrome (BOS). Virus infections may be involved in the development of BOS. Objectives The study intended to investigate whether there is an association of Epstein–Barr virus (EBV), cytomegalovirus (CMV) and human adenovirus (HAdV) with the development of BOS and to identify risk factors for EBV detection in blood. Study design A prospective cohort study was conducted in lung and heart–lung transplant recipients (LTR) who are followed in our outpatient clinic. 385 LTR were monitored for CMV pp65 antigen, EBV and HAdV DNA in blood at follow-up visits for 6 months. The development of BOS was recorded for a median of 21 months. Results EBV DNA, HAdV DNA and CMV pp65 antigen were detected at least once in, respectively, 202/385 LTR (52.5%), 10/382 LTR (2.6%) and 19/385 LTR (4.9%). Repeated EBV DNA detection and acute rejection were associated with the development of BOS. Variables associated with EBV DNA detection in blood were the diagnosis of BOS before study entry, retransplantation and immunosuppressive therapy with sirolimus or everolimus. Conclusions EBV reactivation is frequent in LTR. The variables found associated with EBV reactivation probably reflect increased immunosuppression. Repeated EBV DNA detection in blood, possibly reflecting chronic EBV replication, is associated with the development of BOS. The elucidation of whether and how EBV DNAemia triggers the development of BOS could improve long-term survival of LTR.