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Multicenter Study
. 2010 Nov;29(11):1231-9.
doi: 10.1016/j.healun.2010.05.013. Epub 2010 Jul 22.

Construct validity of the definition of primary graft dysfunction after lung transplantation

Jason D Christie  1 , Scarlett Bellamy, Lorraine B Ware, David Lederer, Denis Hadjiliadis, James Lee, Nancy Robinson, A Russell Localio, Keith Wille, Vibha Lama, Scott Palmer, Jonathan Orens, Ann Weinacker, Maria Crespo, Ejigaehu Demissie, Stephen E Kimmel, Steven M Kawut
Affiliations
Multicenter Study

Construct validity of the definition of primary graft dysfunction after lung transplantation

Jason D Christie et al. J Heart Lung Transplant. 2010 Nov.

Abstract

Background: This study tested the discriminant validity of International Society for Heart and Lung Transplantation (ISHLT) primary graft dysfunction (PGD) grades with lung injury biomarker profiles and survival.

Methods: The study samples consisted of a multicenter prospective cohort study for the biomarker analysis and a cohort study of 450 patients for the mortality analyses. PGD was defined according to ISHLT consensus at 24, 48, and 72 hours after transplantation. We compared the changes in plasma markers of acute lung injury between PGD grades using longitudinal data models. To test predictive validity, we compared differences in the 30-day mortality and long-term survival according to PGD grade.

Results: PGD Grade 3 demonstrated greater differences between plasma intercellular adhesion molecule 1 (ICAM-1), protein C, and plasminogen activator inhibitor type 1 (PAI-1) levels than did PGD Grades 0 to 2 at 24, 48, and 72 hours after lung transplantation (p < 0.05 for each). Grade 3 had the highest 30-day (test for trend p < 0.001) and overall mortality (log rank p < 0.001), with PGD Grades 1 and 2 demonstrating intermediate risks of mortality. The ability to discriminate both 30-day and overall mortality improved as the time of grading moved away from the time of transplantation (test for trend p < 0.001).

Conclusions: The ISHLT grading system has good discriminant validity, based on plasma markers of lung injury and mortality. Grade 3 PGD was associated with the most severely altered plasma biomarker profile and the worst outcomes, regardless of the time point of grading. PGD grade at 48 and 72 hours discriminated mortality better than PGD grade at 24 hours.

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Conflict of interest statement

The authors have no relationships with commercial entities that have an interest in the subject matter of this manuscript.

Figures

Figure 1
Figure 1
Biomarkers of acute lung injury by different PGD grades at T72: a) protein C, b) PAI-1, c) ICAM-1. The different grades appear as numbers in the lines at the different time points. Solid lines indicate grade 0; dotted lines indicate grade1; dashed lines indicate grade 2; and dash-dot lines indicate grade 3 PGD. *p<0.05; **p<0.01 for grade 3 versus the rest.
Figure 1
Figure 1
Biomarkers of acute lung injury by different PGD grades at T72: a) protein C, b) PAI-1, c) ICAM-1. The different grades appear as numbers in the lines at the different time points. Solid lines indicate grade 0; dotted lines indicate grade1; dashed lines indicate grade 2; and dash-dot lines indicate grade 3 PGD. *p<0.05; **p<0.01 for grade 3 versus the rest.
Figure 1
Figure 1
Biomarkers of acute lung injury by different PGD grades at T72: a) protein C, b) PAI-1, c) ICAM-1. The different grades appear as numbers in the lines at the different time points. Solid lines indicate grade 0; dotted lines indicate grade1; dashed lines indicate grade 2; and dash-dot lines indicate grade 3 PGD. *p<0.05; **p<0.01 for grade 3 versus the rest.
Figure 2
Figure 2
Impact of PGD grades at different time points on 30-day mortality rates.
Figure 3
Figure 3
Kaplan Meier survival curves of PGD grades at different time points: a) T24, b) T48, c) T72.
Figure 3
Figure 3
Kaplan Meier survival curves of PGD grades at different time points: a) T24, b) T48, c) T72.
Figure 3
Figure 3
Kaplan Meier survival curves of PGD grades at different time points: a) T24, b) T48, c) T72.
See this image and copyright information in PMC

References

    1. Arcasoy SM, Fisher A, Hachem RR, et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part V: predictors and outcomes. J Heart Lung Transplant. 2005;24:1483–1488. - PubMed
    1. Christie JD, Bavaria JE, Palevsky HI, et al. Primary Graft Failure following lung transplantation. Chest. 1998;114:51–60. - PubMed
    1. Christie JD, Kotloff RM, Ahya VN, et al. The effect of primary graft dysfunction on survival after lung transplantation. American Journal of Respiratory & Critical Care Medicine. 2005;171:1312–1316. - PMC - PubMed
    1. Christie JD, Kotloff RM, Pochettino A, et al. Clinical risk factors for primary graft failure following lung transplantation. Chest. 2003;124:1232–1241. - PubMed
    1. King RC, Binns OA, Rodriguez F, et al. Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation. Annals of Thoracic Surgery. 2000;69:1681–1685. - PubMed

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