title: Survival determinants in lung transplant patients with chronic allograft dysfunction.
abstract: BACKGROUND
  Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality after lung transplantation.
  
  
  METHODS
  In this retrospective single-center study, we aimed to identify different phenotypes of and risk factors for mortality after CLAD diagnosis using univariate and multivariate Cox proportional hazard survival regression analysis.
  
  
  RESULTS
  CLAD was diagnosed in 71 of 294 patients (24.2%) at 30.9±22.8 months after transplantation. Pulmonary function was obstructive in 51 (71.8%) of the CLAD patients, restrictive in 20 (28.2%) patients, of whom 17 had persistent parenchymal infiltrates on pulmonary computer tomography (CAT) scan. In univariate analysis, previous development of neutrophilic reversible allograft dysfunction (NRAD, P=0.012) and a restrictive pulmonary function (P=0.0024) were associated with a worse survival, whereas there was a strong trend for early development of CLAD and persistent parenchymal infiltrates on CAT scan (P=0.067 and 0.056, respectively). In multivariate analysis, early development of CLAD (P=0.0067), previous development of NRAD (P=0.0016), and a restrictive pulmonary function pattern (P=0.0005) or persistent parenchymal infiltrates on CAT scan (P=0.0043) remained significant.
  
  
  CONCLUSIONS
  Although most CLAD patients develop an obstructive pulmonary function, 28% develop a restrictive pulmonary function, compatible with the recently defined restrictive allograft syndrome phenotype. Early-onset CLAD, previous development of NRAD, and the development of restrictive allograft syndrome are associated with worse survival after CLAD has been diagnosed.
authors.affiliation: Lung Transplantation Unit, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. geert.verleden@uzleuven.be
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
authors.forename: Robin
authors.initials: R
authors.lastname: Vos
authors.forename: Stijn E
authors.initials: SE
authors.lastname: Verleden
authors.forename: Walter
authors.initials: W
authors.lastname: De Wever
authors.forename: Stéphanie I
authors.initials: SI
authors.lastname: De Vleeschauwer
authors.forename: Anna
authors.initials: A
authors.lastname: Willems-Widyastuti
authors.forename: Hans
authors.initials: H
authors.lastname: Scheers
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Van Raemdonck
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000401:mortality* / Q000628:therapy*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D014057:Tomography, X-Ray Computed / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome