title: Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction.
abstract: BACKGROUND
  Bronchiolitis obliterans syndrome (BOS) with small-airway pathology and obstructive pulmonary physiology may not be the only form of chronic lung allograft dysfunction (CLAD) after lung transplantation. Characteristics of a form of CLAD consisting of restrictive functional changes involving peripheral lung pathology were investigated.
  
  
  METHODS
  Patients who received bilateral lung transplantation from 1996 to 2009 were retrospectively analyzed. Baseline pulmonary function was taken as the time of peak forced expiratory volume in 1 second (FEV(1)). CLAD was defined as irreversible decline in FEV(1) < 80% baseline. The most accurate threshold to predict irreversible decline in total lung capacity and thus restrictive functional change was at 90% baseline. Restrictive allograft syndrome (RAS) was defined as CLAD meeting this threshold. BOS was defined as CLAD without RAS. To estimate the effect on survival, Cox proportional hazards models and Kaplan-Meier analyses were used.
  
  
  RESULTS
  Among 468 patients, CLAD developed in 156; of those, 47 (30%) showed the RAS phenotype. Compared with the 109 BOS patients, RAS patients showed significant computed tomography findings of interstitial lung disease (p < 0.0001). Prevalence of RAS was approximately 25% to 35% of all CLAD over time. Patient survival of RAS was significantly worse than BOS after CLAD onset (median survival, 541 vs 1,421 days; p = 0.0003). The RAS phenotype was the most significant risk factor of death among other variables after CLAD onset (hazard ratio, 1.60; confidential interval, 1.23-2.07).
  
  
  CONCLUSIONS
  RAS is a novel form of CLAD that exhibits characteristics of peripheral lung fibrosis and significantly affects survival of lung transplant patients.
authors.affiliation: University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sato
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.forename: Ute
authors.initials: U
authors.lastname: Wagnetz
authors.forename: Heidi C
authors.initials: HC
authors.lastname: Roberts
authors.forename: David M
authors.initials: DM
authors.lastname: Hwang
authors.forename: Ayesha
authors.initials: A
authors.lastname: Haroon
authors.forename: Dirk
authors.initials: D
authors.lastname: Wagnetz
authors.forename: Cecilia
authors.initials: C
authors.lastname: Chaparro
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; D000704:Analysis of Variance; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D016041:Heart-Lung Transplantation / Q000009:adverse effects / Q000401:mortality / Q000502:physiology; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D055031:Primary Graft Dysfunction / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013577:Syndrome; D014109:Total Lung Capacity / Q000502:physiology; D014184:Transplantation, Homologous; D016896:Treatment Outcome