The Journal of Heart and Lung Transplantation
Volume 29, Issue 11 , Pages 1231-1239, November 2010

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

  • Jason D. Christie, MD, MS

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • Corresponding Author InformationReprint requests: Jason D. Christie, MD, MS, Associate Professor of Medicine and Epidemiology, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pennsylvania School of Medicine, Center for Clinical Epidemiology and Biostatistics, 423 Guardian Dr, 719 Blockley Hall, Philadelphia, PA 19104. Telephone: 215 573-3209. Fax: 215 573-0198
    • ,
  • Scarlett Bellamy, PhD

      Affiliations

    • Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • ,
  • Lorraine B. Ware, MD

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, Vanderbilt University, Nashville, Tennessee
    • ,
  • David Lederer, MD

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, New York
    • ,
  • Denis Hadjiliadis, MD, MHS

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • ,
  • James Lee, MD

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • ,
  • Nancy Robinson, PhD

      Affiliations

    • Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • ,
  • A. Russell Localio, PhD

      Affiliations

    • Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • ,
  • Keith Wille, MD

      Affiliations

    • Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama
    • ,
  • Vibha Lama, MD

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan
    • ,
  • Scott Palmer, MD

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Durham, North Carolina
    • ,
  • Jonathan Orens, MD

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Johns Hopkins University Hospital, Baltimore, Maryland
    • ,
  • Ann Weinacker, MD

      Affiliations

    • Division of Pulmonary and Critical Care Medicine, Stanford University, Palo Alto, California
    • ,
  • Maria Crespo, MD

      Affiliations

    • Division of Pulmonary and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
    • ,
  • Ejigaehu Demissie, MSN

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • ,
  • Stephen E. Kimmel, MD, MS

      Affiliations

    • Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • Cardiovascular Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • ,
  • Steven M. Kawut, MD, MS

      Affiliations

    • Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

published online 23 July 2010.

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.

Keywords: lung transplantation, complications, acute lung injury, primary graft dysfunction, reperfusion injury

 

PII: S1053-2498(10)00294-9

doi:10.1016/j.healun.2010.05.013

The Journal of Heart and Lung Transplantation
Volume 29, Issue 11 , Pages 1231-1239, November 2010

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