title: Validation and Refinement of Chronic Lung Allograft Dysfunction Phenotypes in Bilateral and Single Lung Recipients.
abstract: The clinical course of chronic lung allograft dysfunction (CLAD) is heterogeneous. Forced vital capacity (FVC) loss at onset, which may suggest a restrictive phenotype, was associated with worse survival for bilateral lung transplant recipients in one previously published single-center study.
  
  
  
  We sought to replicate the significance of FVC loss in an independent, retrospectively identified cohort of bilateral lung transplant recipients and to investigate extended application of this approach to single lung recipients.
  
  
  
  FVC loss and other potential predictors of survival after the onset of CLAD were assessed using Kaplan-Meier and Cox proportional hazards models.
  
  
  
  FVC loss at the onset of CLAD was associated with higher mortality in an independent cohort of bilateral lung transplant recipients (hazard ratio [HR], 2.75; 95% confidence interval [CI], 2.02-3.73; P < 0.0001) and in a multicenter cohort of single lung recipients (HR, 1.80; 95% CI, 1.09-2.98; P = 0.02). Including all subjects, the deleterious impact of FVC loss on survival persisted after adjustment for other relevant clinical variables (HR, 2.36; 95% CI, 1.77-3.15; P < 0.0001). In patients who develop CLAD without FVC loss, chest computed tomography features suggestive of pleural or parenchymal fibrosis also predicted worse survival in both bilateral (HR, 2.01; 95% CI, 1.16-5.20; P = 0.02) and single recipients (HR, 2.47; 95% CI, 1.24-10.57; P = 0.02).
  
  
  
  We independently validated the prognostic significance of FVC loss for bilateral lung recipients and demonstrated that this approach to CLAD classification also confers prognostic information for single lung transplant recipients. Improved understanding of these discrete phenotypes is critical to the development of effective therapies.
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: Ariss
authors.initials: A
authors.lastname: DerHovanessian
authors.affiliation: 2 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Todd
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: Alice
authors.initials: A
authors.lastname: Zhang
authors.affiliation: 3 Department of Biomathematics, and.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: Aradhna
authors.initials: A
authors.lastname: Mayalall
authors.affiliation: 2 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and.
authors.forename: C Ashley
authors.initials: CA
authors.lastname: Finlen Copeland
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: Michael
authors.initials: M
authors.lastname: Shino
authors.affiliation: 4 Department of Pathology, Duke University, Durham, North Carolina.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Pavlisko
authors.affiliation: 5 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California; and.
authors.forename: W Dean
authors.initials: WD
authors.lastname: Wallace
authors.affiliation: 6 Division of Infectious Diseases, Department of Medicine.
authors.forename: Aric
authors.initials: A
authors.lastname: Gregson
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: David J
authors.initials: DJ
authors.lastname: Ross
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: Rajan
authors.initials: R
authors.lastname: Saggar
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Lynch
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: John
authors.initials: J
authors.lastname: Belperio
authors.affiliation: 2 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and.
authors.forename: Laurie D
authors.initials: LD
authors.lastname: Snyder
authors.affiliation: 2 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.affiliation: 1 Division of Pulmonary and Critical Care Medicine.
authors.forename: S Sam
authors.identifier: 0000-0001-5351-8936
authors.initials: SS
authors.lastname: Weigt
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D001989:Bronchiolitis Obliterans / Q000503:physiopathology; D005260:Female; D006801:Humans; D008168:Lung / Q000503:physiopathology / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D055031:Primary Graft Dysfunction / Q000503:physiopathology*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D014481:United States; D014797:Vital Capacity
keywords: bronchiolitis obliterans; graft rejection; lung transplantation; spirometry