A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation

Rupal J. Shah, Scarlett L. Bellamy, A. Russell Localio, Nancy Wickersham, Joshua M. Diamond, Ann Weinacker, Vibha N. Lama, Sangeeta Bhorade, John A. Belperio, Maria Crespo, Ejigayehu Demissie, Steven M. Kawut, Keith M. Wille, David J. Lederer, James C. Lee, Scott M. Palmer, Jonathan B Orens, John Reynolds, Ashish Shah, David S. WilkesLorraine B. Ware, Jason D. Christie

Research output: Contribution to journalArticle

Abstract

Background: We aimed to identify combinations of biomarkers to enhance the definition of primary graft dysfunction (PGD) for translational research. Methods: Biomarkers reflecting lung epithelial injury (soluble receptor for advance glycation end products [sRAGE] and surfactant protein-D [SP-D]), coagulation cascade (plasminogen activator inhibitor-1 [PAI-1] and protein C), and cell adhesion (intracellular adhesion molecule-1 [ICAM-1]) were measured in the plasma of 315 individuals derived from the Lung Transplant Outcomes Group cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in 2 ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality. Results: PGD developed in 86 of 315 individuals (27%). Twenty-patients (8%) died within 90 days of transplantation, of which 16 (70%) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (area under the curve [AUC], 0.71) and PAI-1 (AUC, 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC, 0.75), PAI-1 with ICAM-1 (AUC, 0.75), and PAI-1 with SP-D (AUC, 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC, 0.72) and ICAM-1 with sRAGE (AUC, 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved the prediction of 90-day mortality (p <0.001 each). Conclusions: Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early death and may provide an alternative outcome useful in future research.

Original languageEnglish (US)
Pages (from-to)942-949
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume31
Issue number9
DOIs
StatePublished - Sep 2012

Fingerprint

Primary Graft Dysfunction
Lung Transplantation
Lung Injury
Plasminogen Activator Inhibitor 1
Area Under Curve
Biomarkers
Pulmonary Surfactant-Associated Protein D
Cell Adhesion
Mortality
Replication Protein C
Transplantation
Translational Medical Research
Fibrinolysis
Protein C
Transplants

Keywords

  • acute lung injury
  • biomarkers
  • lung transplantation
  • primary graft dysfunction

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Shah, R. J., Bellamy, S. L., Localio, A. R., Wickersham, N., Diamond, J. M., Weinacker, A., ... Christie, J. D. (2012). A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation. Journal of Heart and Lung Transplantation, 31(9), 942-949. https://doi.org/10.1016/j.healun.2012.05.001

A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation. / Shah, Rupal J.; Bellamy, Scarlett L.; Localio, A. Russell; Wickersham, Nancy; Diamond, Joshua M.; Weinacker, Ann; Lama, Vibha N.; Bhorade, Sangeeta; Belperio, John A.; Crespo, Maria; Demissie, Ejigayehu; Kawut, Steven M.; Wille, Keith M.; Lederer, David J.; Lee, James C.; Palmer, Scott M.; Orens, Jonathan B; Reynolds, John; Shah, Ashish; Wilkes, David S.; Ware, Lorraine B.; Christie, Jason D.

In: Journal of Heart and Lung Transplantation, Vol. 31, No. 9, 09.2012, p. 942-949.

Research output: Contribution to journalArticle

Shah, RJ, Bellamy, SL, Localio, AR, Wickersham, N, Diamond, JM, Weinacker, A, Lama, VN, Bhorade, S, Belperio, JA, Crespo, M, Demissie, E, Kawut, SM, Wille, KM, Lederer, DJ, Lee, JC, Palmer, SM, Orens, JB, Reynolds, J, Shah, A, Wilkes, DS, Ware, LB & Christie, JD 2012, 'A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation', Journal of Heart and Lung Transplantation, vol. 31, no. 9, pp. 942-949. https://doi.org/10.1016/j.healun.2012.05.001
Shah, Rupal J. ; Bellamy, Scarlett L. ; Localio, A. Russell ; Wickersham, Nancy ; Diamond, Joshua M. ; Weinacker, Ann ; Lama, Vibha N. ; Bhorade, Sangeeta ; Belperio, John A. ; Crespo, Maria ; Demissie, Ejigayehu ; Kawut, Steven M. ; Wille, Keith M. ; Lederer, David J. ; Lee, James C. ; Palmer, Scott M. ; Orens, Jonathan B ; Reynolds, John ; Shah, Ashish ; Wilkes, David S. ; Ware, Lorraine B. ; Christie, Jason D. / A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation. In: Journal of Heart and Lung Transplantation. 2012 ; Vol. 31, No. 9. pp. 942-949.
@article{115de61ab18e4050a436a4805a748b89,
title = "A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation",
abstract = "Background: We aimed to identify combinations of biomarkers to enhance the definition of primary graft dysfunction (PGD) for translational research. Methods: Biomarkers reflecting lung epithelial injury (soluble receptor for advance glycation end products [sRAGE] and surfactant protein-D [SP-D]), coagulation cascade (plasminogen activator inhibitor-1 [PAI-1] and protein C), and cell adhesion (intracellular adhesion molecule-1 [ICAM-1]) were measured in the plasma of 315 individuals derived from the Lung Transplant Outcomes Group cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in 2 ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality. Results: PGD developed in 86 of 315 individuals (27{\%}). Twenty-patients (8{\%}) died within 90 days of transplantation, of which 16 (70{\%}) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (area under the curve [AUC], 0.71) and PAI-1 (AUC, 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC, 0.75), PAI-1 with ICAM-1 (AUC, 0.75), and PAI-1 with SP-D (AUC, 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC, 0.72) and ICAM-1 with sRAGE (AUC, 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved the prediction of 90-day mortality (p <0.001 each). Conclusions: Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early death and may provide an alternative outcome useful in future research.",
keywords = "acute lung injury, biomarkers, lung transplantation, primary graft dysfunction",
author = "Shah, {Rupal J.} and Bellamy, {Scarlett L.} and Localio, {A. Russell} and Nancy Wickersham and Diamond, {Joshua M.} and Ann Weinacker and Lama, {Vibha N.} and Sangeeta Bhorade and Belperio, {John A.} and Maria Crespo and Ejigayehu Demissie and Kawut, {Steven M.} and Wille, {Keith M.} and Lederer, {David J.} and Lee, {James C.} and Palmer, {Scott M.} and Orens, {Jonathan B} and John Reynolds and Ashish Shah and Wilkes, {David S.} and Ware, {Lorraine B.} and Christie, {Jason D.}",
year = "2012",
month = "9",
doi = "10.1016/j.healun.2012.05.001",
language = "English (US)",
volume = "31",
pages = "942--949",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "Elsevier USA",
number = "9",

}

TY - JOUR

T1 - A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation

AU - Shah, Rupal J.

AU - Bellamy, Scarlett L.

AU - Localio, A. Russell

AU - Wickersham, Nancy

AU - Diamond, Joshua M.

AU - Weinacker, Ann

AU - Lama, Vibha N.

AU - Bhorade, Sangeeta

AU - Belperio, John A.

AU - Crespo, Maria

AU - Demissie, Ejigayehu

AU - Kawut, Steven M.

AU - Wille, Keith M.

AU - Lederer, David J.

AU - Lee, James C.

AU - Palmer, Scott M.

AU - Orens, Jonathan B

AU - Reynolds, John

AU - Shah, Ashish

AU - Wilkes, David S.

AU - Ware, Lorraine B.

AU - Christie, Jason D.

PY - 2012/9

Y1 - 2012/9

N2 - Background: We aimed to identify combinations of biomarkers to enhance the definition of primary graft dysfunction (PGD) for translational research. Methods: Biomarkers reflecting lung epithelial injury (soluble receptor for advance glycation end products [sRAGE] and surfactant protein-D [SP-D]), coagulation cascade (plasminogen activator inhibitor-1 [PAI-1] and protein C), and cell adhesion (intracellular adhesion molecule-1 [ICAM-1]) were measured in the plasma of 315 individuals derived from the Lung Transplant Outcomes Group cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in 2 ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality. Results: PGD developed in 86 of 315 individuals (27%). Twenty-patients (8%) died within 90 days of transplantation, of which 16 (70%) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (area under the curve [AUC], 0.71) and PAI-1 (AUC, 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC, 0.75), PAI-1 with ICAM-1 (AUC, 0.75), and PAI-1 with SP-D (AUC, 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC, 0.72) and ICAM-1 with sRAGE (AUC, 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved the prediction of 90-day mortality (p <0.001 each). Conclusions: Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early death and may provide an alternative outcome useful in future research.

AB - Background: We aimed to identify combinations of biomarkers to enhance the definition of primary graft dysfunction (PGD) for translational research. Methods: Biomarkers reflecting lung epithelial injury (soluble receptor for advance glycation end products [sRAGE] and surfactant protein-D [SP-D]), coagulation cascade (plasminogen activator inhibitor-1 [PAI-1] and protein C), and cell adhesion (intracellular adhesion molecule-1 [ICAM-1]) were measured in the plasma of 315 individuals derived from the Lung Transplant Outcomes Group cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in 2 ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality. Results: PGD developed in 86 of 315 individuals (27%). Twenty-patients (8%) died within 90 days of transplantation, of which 16 (70%) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (area under the curve [AUC], 0.71) and PAI-1 (AUC, 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC, 0.75), PAI-1 with ICAM-1 (AUC, 0.75), and PAI-1 with SP-D (AUC, 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC, 0.72) and ICAM-1 with sRAGE (AUC, 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved the prediction of 90-day mortality (p <0.001 each). Conclusions: Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early death and may provide an alternative outcome useful in future research.

KW - acute lung injury

KW - biomarkers

KW - lung transplantation

KW - primary graft dysfunction

UR - http://www.scopus.com/inward/record.url?scp=84864929093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864929093&partnerID=8YFLogxK

U2 - 10.1016/j.healun.2012.05.001

DO - 10.1016/j.healun.2012.05.001

M3 - Article

C2 - 22694851

AN - SCOPUS:84864929093

VL - 31

SP - 942

EP - 949

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

SN - 1053-2498

IS - 9

ER -