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. POD 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 POD grade. RESULTS: POD Grade 3 demonstrated greater differences between plasma intercellular adhesion molecule 1 (ICAM-1), protein C, and plasminogen activator inhibitor type I (PAI-1) levels than did POD 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 POD Grades I 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 POD was associated with the most severely altered plasma biomarker profile and the worst outcomes, regardless of the time point of grading. POD grade at 48 and 72 hours discriminated mortality better than PGD grade at 24 hours. J Heart Lung Transplant 2010;29:1231-9 (C) 2010 International Society for Heart and Lung Transplantation. All rights reserved.