title: Revisiting the pathologic finding of diffuse alveolar damage after lung transplantation.
abstract: BACKGROUND
  Diffuse alveolar damage (DAD) is a non-specific pathologic diagnosis frequently encountered after lung transplantation. We examined the relationship between DAD and different forms of chronic lung allograft dysfunction (CLAD).
  
  
  METHODS
  We reviewed the results of 4,085 transbronchial biopsies obtained from 720 lung transplant recipients. DAD detected in biopsies within 3 months and newly detected DAD after 3 months were defined as early DAD and late new-onset DAD, respectively. Among patients with CLAD (FEV(1) <80% baseline), restrictive allograft syndrome (RAS) was defined by a decline in total lung capacity to <90% baseline and bronchiolitis obliterans syndrome (BOS) as CLAD without restrictive allograft syndrome (RAS). Kaplan-Meier analyses and multivariate proportional hazard models were used.
  
  
  RESULTS
  DAD was observed in 320 of 720 (44.4%) patients at least once; early and late new-onset DAD were observed in 264 of 707 (37.3%) and 87 of 655 (13.3%) patients, respectively. Early DAD was associated with significantly higher 90-day mortality (20 of 264 [7.6%] vs 11 of 443 [2.5%]; p = 0.001). Moreover, among 502 bilateral lung transplant recipients who had sufficient pulmonary function tests to distinguish BOS and RAS, early DAD was associated with earlier BOS onset (hazard ratio [HR] 1.24; confidence interval [CI] 1.04 to 1.47; p = 0.017; median time of BOS onset: 2,902 vs 4,005 days). Conversely, treated as a time-varying covariate, late new-onset DAD was a significant risk factor for RAS in a Cox model (HR 36.8; CI 18.3 to 74.1; p < 0.0001).
  
  
  CONCLUSIONS
  Early DAD is associated with early mortality and BOS, and late new-onset DAD increases the risk of RAS.
authors.affiliation: Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: David M
authors.initials: DM
authors.lastname: Hwang
authors.forename: Kaori
authors.initials: K
authors.lastname: Ohmori-Matsuda
authors.forename: Cecilia
authors.initials: C
authors.lastname: Chaparro
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.forename: Lianne G
authors.initials: LG
authors.lastname: Singer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hutcheon
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D000328:Adult; D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000453:epidemiology* / Q000503:physiopathology; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D016040:Lung Transplantation / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000453:epidemiology* / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000473:pathology* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors