Construct validity of the definition of primary graft dysfunction after lung transplantation.
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.
Christie
Jason D
JD
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, 423 Guardian Drive, Philadelphia, PA 19104, USA. jchristi@mail.med.upenn.edu
Bellamy
Scarlett
S
Ware
Lorraine B
LB
Lederer
David
D
Hadjiliadis
Denis
D
Lee
James
J
Robinson
Nancy
N
Localio
A Russell
AR
Wille
Keith
K
Lama
Vibha
V
Palmer
Scott
S
Orens
Jonathan
J
Weinacker
Ann
A
Crespo
Maria
M
Demissie
Ejigaehu
E
Kimmel
Stephen E
SE
Kawut
Steven M
SM
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000097:blood* / Q000401:mortality; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011237:Predictive Value of Tests; D055031:Primary Graft Dysfunction / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D015203:Reproducibility of Results; D012189:Retrospective Studies; D015996:Survival Rate
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D018799:Intercellular Adhesion Molecule-1