title: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Institute of Virology, Medizinische Hochschule Hannover, Hannover, Germany. i.engelmann@googlemail.com
authors.forename: Ilka
authors.initials: I
authors.lastname: Engelmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Thomas
authors.initials: T
authors.lastname: Fühner
authors.forename: Andre R
authors.initials: AR
authors.lastname: Simon
authors.forename: Frauke
authors.initials: F
authors.lastname: Mattner
authors.forename: Ludwig
authors.initials: L
authors.lastname: Hoy
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schulz
authors.forename: Jens
authors.initials: J
authors.lastname: Gottlieb
mesh_terms: D000258:Adenovirus Infections, Human / Q000150:complications / Q000821:virology; D000260:Adenoviruses, Human / Q000302:isolation & purification; D000293:Adolescent; D000328:Adult; D000368:Aged; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000150:complications / Q000821:virology; D004279:DNA, Viral / Q000097:blood*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000821:virology*; D005260:Female; D006084:Graft Rejection; D016041:Heart-Lung Transplantation / Q000009:adverse effects; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D014763:Viral Matrix Proteins / Q000097:blood
chemical_list: D004279:DNA, Viral; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa