title: The significance of a single episode of minimal acute rejection after lung transplantation.
abstract: BACKGROUND
  Bronchiolitis obliterans syndrome (BOS) remains the leading obstacle to better long-term outcomes after lung transplantation. Acute rejection has been identified as the primary risk factor for BOS, but the impact of minimal acute rejection, especially a solitary episode, has usually been discounted as clinically insignificant.
  
  
  METHODS
  We performed a retrospective cohort study of 259 adult lung transplant recipients to determine the risk of BOS associated with a single episode of A1 rejection, without recurrence or subsequent progression to a higher grade. The cohort was divided into 3 groups based on the severity of acute rejection (none, single episode of A1, and single episode of A2). We determined the risks of BOS stages 1, 2, 3, and death for each group using univariate and multivariate Cox regression analyses.
  
  
  RESULTS
  A solitary episode of A1 rejection was a significant risk factor for BOS stages 1 and 2, but not stage 3 or death, in the univariate analysis. Multivariate Cox regression models confirmed that the risk of BOS attributable to a single episode of A1 rejection was independent of other potential risk factors, such as community acquired respiratory viral infections, number of HLA mismatches, and cytomegalovirus pneumonitis. Likewise, univariate and multivariate analyses demonstrated that a single episode of A2 rejection was a significant risk factor for all stages of BOS but not death.
  
  
  CONCLUSIONS
  A single episode of minimal acute rejection without recurrence or subsequent progression to a higher grade is a significant predictor of BOS independent of other risk factors.
authors.affiliation: Division of Pulmonary and Critical Care, Washington University School of Medicine, St. Louis, MO 63110, USA. Rhachem@im.wustl.edu
authors.forename: Ramsey R
authors.initials: RR
authors.lastname: Hachem
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Khalifah
authors.forename: Murali M
authors.initials: MM
authors.lastname: Chakinala
authors.forename: Roger D
authors.initials: RD
authors.lastname: Yusen
authors.forename: Aviva A
authors.initials: AA
authors.lastname: Aloush
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.forename: G Alexander
authors.initials: GA
authors.lastname: Patterson
authors.forename: Elbert P
authors.initials: EP
authors.lastname: Trulock
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walter
mesh_terms: D000328:Adult; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000473:pathology*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis