title: Lymphocytic airway infiltration as a precursor to fibrous obliteration in a rat model of bronchiolitis obliterans.
abstract: BACKGROUND
  Bronchiolitis obliterans is the most significant complication adversely affecting prolonged survival of lung allograft recipients. The evolution from the initial insult to the final pathologic entity is largely unknown. The aim of this study was to characterize the evolution of transplant-induced fibrous airway obliteration in a rat tracheal transplant model of bronchiolitis obliterans.
  
  
  METHODS
  Tracheal segments were transplanted from Brown Norway rats to Brown Norway rats (isografts) or to Lewis rats (allografts). Grafts were implanted into a subcutaneous pouch and an abdominal omental wrap. They were harvested at 14 different time points (from 1 day to 1 year after transplantation) and assessed histologically.
  
  
  RESULTS
  The fibrous airway obliteration developed only in allografts showing a triphasic time course: an initial ischemic phase (observed in both isografts and allografts) was followed by a marked lymphocytic infiltrative phase with complete epithelial loss (observed only in allografts, P<0.01), and finally by an obliterative phase with fibrous obliteration of the allograft airway lumen (P<0.01).
  
  
  CONCLUSIONS
  This animal model shows a distinct and reproducible triphasic time course in the development of obliterative airway lesions in allografts. It confirms that the mechanism leading to airway obliteration is immune mediated as only allografts showed this lesion and that lymphocytic infiltration is a precursor of the lesion in this model. The insights into the different phases demonstrated may lead to novel approaches regarding the type and timing of therapeutic interventions.
authors.affiliation: Division of Thoracic Surgery, The Toronto Hospital, University of Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Boehler
authors.forename: D
authors.initials: D
authors.lastname: Chamberlain
authors.forename: S
authors.initials: S
authors.lastname: Kesten
authors.forename: A S
authors.initials: AS
authors.lastname: Slutsky
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000473:pathology*; D004195:Disease Models, Animal; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology; D013997:Time Factors; D014132:Trachea / Q000637:transplantation; D014184:Transplantation, Homologous / Q000473:pathology; D014185:Transplantation, Isogeneic / Q000473:pathology