Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation

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

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: There is signifi cant 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 fi rst 72 h after transplantation. LCA identifi ed 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.

Original languageEnglish (US)
Pages (from-to)616-622
Number of pages7
JournalCHEST
Volume144
Issue number2
DOIs
StatePublished - Jan 1 2013

Fingerprint

Primary Graft Dysfunction
Lung Transplantation
Phenotype
Lung
Transplantation
Transplants
Pulmonary Edema
Cardiopulmonary Bypass
Pulmonary Artery
Cohort Studies

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Shah, R. J., Diamond, J. M., Cantu, E., Lee, J. C., Lederer, D. J., Lama, V. N., ... Christie, J. D. (2013). Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation. CHEST, 144(2), 616-622. https://doi.org/10.1378/chest.12-1480
Shah, Rupal J. ; Diamond, Joshua M. ; Cantu, Edward ; Lee, James C. ; Lederer, David J. ; Lama, Vibha N. ; Orens, Jonathan ; Weinacker, Ann ; Wilkes, David S. ; Bhorade, Sangeeta ; Wille, Keith M. ; Ware, Lorraine B. ; Palmer, Scott M. ; Crespo, Maria ; Localio, A. Russell ; Demissie, Ejigayehu ; Kawut, Steven M. ; Bellamy, Scarlett L. ; Christie, Jason D. / Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation. In: CHEST. 2013 ; Vol. 144, No. 2. pp. 616-622.
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abstract = "Background: There is signifi cant 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 fi rst 72 h after transplantation. LCA identifi ed 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.",
author = "Shah, {Rupal J.} and Diamond, {Joshua M.} and Edward Cantu and Lee, {James C.} and Lederer, {David J.} and Lama, {Vibha N.} and Jonathan Orens and Ann Weinacker and Wilkes, {David S.} and Sangeeta Bhorade and Wille, {Keith M.} and Ware, {Lorraine B.} and Palmer, {Scott M.} and Maria Crespo and Localio, {A. Russell} and Ejigayehu Demissie and Kawut, {Steven M.} and Bellamy, {Scarlett L.} and Christie, {Jason D.}",
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Shah, RJ, Diamond, JM, Cantu, E, Lee, JC, Lederer, DJ, Lama, VN, Orens, J, Weinacker, A, Wilkes, DS, Bhorade, S, Wille, KM, Ware, LB, Palmer, SM, Crespo, M, Localio, AR, Demissie, E, Kawut, SM, Bellamy, SL & Christie, JD 2013, 'Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation', CHEST, vol. 144, no. 2, pp. 616-622. https://doi.org/10.1378/chest.12-1480

Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation. / Shah, Rupal J.; Diamond, Joshua M.; Cantu, Edward; Lee, James C.; Lederer, David J.; Lama, Vibha N.; Orens, Jonathan; Weinacker, Ann; Wilkes, David S.; Bhorade, Sangeeta; Wille, Keith M.; Ware, Lorraine B.; Palmer, Scott M.; Crespo, Maria; Localio, A. Russell; Demissie, Ejigayehu; Kawut, Steven M.; Bellamy, Scarlett L.; Christie, Jason D.

In: CHEST, Vol. 144, No. 2, 01.01.2013, p. 616-622.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation

AU - Shah, Rupal J.

AU - Diamond, Joshua M.

AU - Cantu, Edward

AU - Lee, James C.

AU - Lederer, David J.

AU - Lama, Vibha N.

AU - Orens, Jonathan

AU - Weinacker, Ann

AU - Wilkes, David S.

AU - Bhorade, Sangeeta

AU - Wille, Keith M.

AU - Ware, Lorraine B.

AU - Palmer, Scott M.

AU - Crespo, Maria

AU - Localio, A. Russell

AU - Demissie, Ejigayehu

AU - Kawut, Steven M.

AU - Bellamy, Scarlett L.

AU - Christie, Jason D.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Background: There is signifi cant 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 fi rst 72 h after transplantation. LCA identifi ed 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.

AB - Background: There is signifi cant 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 fi rst 72 h after transplantation. LCA identifi ed 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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U2 - 10.1378/chest.12-1480

DO - 10.1378/chest.12-1480

M3 - Article

VL - 144

SP - 616

EP - 622

JO - Chest

JF - Chest

SN - 0012-3692

IS - 2

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