title: Long-term survival after lung transplantation depends on development and severity of bronchiolitis obliterans syndrome.
abstract: BACKGROUND
  The objectives of this study were to describe the natural history of bronchiolitis obliterans syndrome (BOS) in a large consecutive series of patients from a national center in accordance with the most recent grading criteria, and to examine the prognosis with respect to onset and severity of BOS.
  
  
  METHODS
  All patients receiving a cadaveric lung transplant between 1992 and 2004 were included in the study (n = 389). Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and lack of available lung function measurements (n = 4).
  
  
  RESULTS
  The 1-, 3-, 5- and 10-year actuarial survival rates for the entire series were 81%, 67%, 60% and 36%, respectively. The 1-, 3-, 5- and 10-year actuarial freedom from BOS Grade > or = 1 was 81%, 53%, 38% and 15%, respectively. A Cox regression model with BOS grade as a time-dependent covariate was performed in a sub-group of patients surviving at least 3 years (n = 237). Both progression from BOS Grade 1 to 2 and from BOS Grade 2 to 3 were associated with a significant increase in mortality: hazard ratio (HR) = 3.1 (confidence interval [CI] 1.2 to 7.9) and HR = 2.9 (CI 1.6 to 5.3), respectively. The addition of a non-time-dependent covariate to signify early (within 18 months of transplantation) or late (after 18 months) development of BOS was not significant (p = 0.5).
  
  
  CONCLUSIONS
  The development and progression of chronic allograft rejection after lung transplantation (BOS Grades 2 and 3) is associated with a 3-fold increase in the risk of death at each stage, irrespective of whether BOS developed early or late.
authors.affiliation: Department of Cardiology, Division of Lung Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. cmburton@doctors.net.uk
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Burton
authors.forename: Jørn
authors.initials: J
authors.lastname: Carlsen
authors.forename: Jann
authors.initials: J
authors.lastname: Mortensen
authors.forename: Claus B
authors.initials: CB
authors.lastname: Andersen
authors.forename: Nils
authors.initials: N
authors.lastname: Milman
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
mesh_terms: D000328:Adult; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation / Q000009:adverse effects / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D017741:Survivors