title: Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation.
abstract: BACKGROUND
  There is significant heterogeneity within the primary graft dysfunction (PGD) syndrome. We aimed to identify distinct grade 3 PGD phenotypes based on severity of lung dysfunction and patterns of resolution.
  
  
  METHODS
  Subjects from the Lung Transplant Outcomes Group (LTOG) cohort study with grade 3 PGD within 72 h after transplantation were included. Latent class analysis (LCA) was used to statistically identify classes based on changes in PGD International Society for Heart & Lung Transplantation grade over time. Construct validity of the classes was assessed by testing for divergence of recipient, donor, and operative characteristics between classes. Predictive validity was assessed using time to death.
  
  
  RESULTS
  Of 1,255 subjects, 361 had grade 3 PGD within the first 72 h after transplantation. LCA identified three distinct phenotypes: (1) severe persistent dysfunction (class 1), (2) complete resolution of dysfunction within 72 h (class 2), and (3) attenuation, without complete resolution within 72 h (class 3). Increased use of cardiopulmonary bypass, greater RBC transfusion, and higher mean pulmonary artery pressure were associated with persistent PGD (class 1). Subjects in class 1 also had the greatest risk of death (hazard ratio, 2.39; 95% CI, 1.57-3.63; P &lt; .001).
  
  
  CONCLUSIONS
  There are distinct phenotypes of resolution of dysfunction within the severe PGD syndrome. Subjects with early resolution may represent a different mechanism of lung pathology, such as resolving pulmonary edema, whereas those with persistent PGD may represent a more severe phenotype. Future studies aimed at PGD mechanism or treatment may focus on phenotypes based on resolution of graft dysfunction.
authors: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA. Electronic address: rupal.shah@uphs.upenn.edu.
authors: Rupal J
authors: RJ
authors: Shah
authors: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: Joshua M
authors: JM
authors: Diamond
authors: Division of Cardiovascular Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: Edward
authors: E
authors: Cantu
authors: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: James C
authors: JC
authors: Lee
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
authors: David J
authors: DJ
authors: Lederer
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Michigan, Ann Arbor, MI.
authors: Vibha N
authors: VN
authors: Lama
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Johns Hopkins University Hospital, Baltimore, MD.
authors: Jonathan
authors: J
authors: Orens
authors: Department of Pulmonary and Critical Care, Stanford University, Palo Alto, CA.
authors: Ann
authors: A
authors: Weinacker
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Indiana University School of Medicine, Indianapolis, IN.
authors: David S
authors: DS
authors: Wilkes
authors: Division of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL.
authors: Sangeeta
authors: S
authors: Bhorade
authors: Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL.
authors: Keith M
authors: KM
authors: Wille
authors: Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors: Lorraine B
authors: LB
authors: Ware
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Raleigh-Durham, NC.
authors: Scott M
authors: SM
authors: Palmer
authors: Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh, Pittsburgh, PA.
authors: Maria
authors: M
authors: Crespo
authors: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: A Russell
authors: AR
authors: Localio
authors: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: Ejigayehu
authors: E
authors: Demissie
authors: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: Steven M
authors: SM
authors: Kawut
authors: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: Scarlett L
authors: SL
authors: Bellamy
authors: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors: Jason D
authors: JD
authors: Christie
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D055031:Primary Graft Dysfunction; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index