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Original Research: Transplantation |

Latent Class Analysis Identifies Distinct Phenotypes of Primary Graft Dysfunction After Lung TransplantationIdentifying Primary Graft Dysfunction Phenotypes

Rupal J. Shah, MD; Joshua M. Diamond, MD; Edward Cantu, MD; James C. Lee, MD; David J. Lederer, MD; Vibha N. Lama, MD; Jonathan Orens, MD, FCCP; Ann Weinacker, MD, FCCP; David S. Wilkes, MD; Sangeeta Bhorade, MD, FCCP; Keith M. Wille, MD; Lorraine B. Ware, MD; Scott M. Palmer, MD, FCCP; Maria Crespo, MD; A. Russell Localio, PhD; Ejigayehu Demissie, MSN; Steven M. Kawut, MD, FCCP; Scarlett L. Bellamy, ScD; Jason D. Christie, MD, FCCP
Author and Funding Information

From the Pulmonary, Allergy, and Critical Care Division (Drs Shah, Diamond, Lee, Kawut, and Christie), Center for Clinical Epidemiology and Biostatistics (Drs Shah, Diamond, Localio, Kawut, Bellamy, and Christie and Ms Demissie), Division of Cardiovascular Surgery (Dr Cantu), University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Pulmonary, Allergy, and Critical Care Medicine (Dr Lederer), Columbia University College of Physicians and Surgeons, New York, NY; Division of Pulmonary, Allergy, and Critical Care Medicine (Dr Lama), University of Michigan, Ann Arbor, MI; Division of Pulmonary, Allergy, and Critical Care Medicine (Dr Orens), Department of Medicine, Johns Hopkins University Hospital, Baltimore, MD; Department of Pulmonary and Critical Care (Dr Weinacker), Stanford University, Palo Alto, CA; Division of Pulmonary, Allergy, and Critical Care Medicine (Dr Wilkes), Indiana University School of Medicine, Indianapolis, IN; Division of Pulmonary and Critical Care Medicine (Dr Bhorade), University of Chicago, Chicago, IL; Division of Pulmonary and Critical Care Medicine (Dr Wille), University of Alabama at Birmingham, Birmingham, AL; Division of Allergy, Pulmonary, and Critical Care Medicine (Dr Ware), Vanderbilt University Medical Center, Nashville, TN; Division of Pulmonary, Allergy, and Critical Care Medicine (Dr Palmer), Duke University, Raleigh-Durham, NC; and Division of Pulmonary, Allergy, and Critical Care (Dr Crespo), University of Pittsburgh, Pittsburgh, PA.

Correspondence to: Rupal J. Shah, MD, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pennsylvania School of Medicine, 3400 Spruce St, 8 W Gates, Philadelphia, PA 19104; e-mail: rupal.shah@uphs.upenn.edu


Funding/Support: This work was supported by the National Institutes of Health [Grants R01-HL087115 to J. D. C. and HL088263 to L. B. W.].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(2):616-622. doi:10.1378/chest.12-1480
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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 < .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.

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