Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant.

Abstract

RATIONALE:

Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted.

OBJECTIVES:

We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity.

METHODS:

Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination.

MEASUREMENTS AND MAIN RESULTS:

A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination.

CONCLUSIONS:

The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.

• Authors: Edward Cantu, Joshua M Diamond, Yoshikazu Suzuki, Jared Lasky, Christian Schaufler, Brian Lim, Rupal Shah, Mary Porteous, David J Lederer, Steven M Kawut, Scott M Palmer, Laurie D Snyder, Matthew G Hartwig, Vibha N Lama, Sangeeta Bhorade, Christian Bermudez, Maria Crespo, John McDyer, Keith Wille, Jonathan Orens, Pali D Shah, Ann Weinacker, David Weill, David Wilkes, David Roe, Chadi Hage, Lorraine B Ware, Scarlett L Bellamy, Jason D Christie, Lung Transplant Outcomes Group
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 197 Issue 2 Pg. 235-243 (01 15 2018) ISSN: 1535-4970 [Electronic] United States
• PMID: 28872353 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers

Topics

• Adult
• Biomarkers (analysis)
• Cause of Death
• Cohort Studies
• Consensus
• Female
• Graft Rejection
• Graft Survival
• Humans
• Kaplan-Meier Estimate
• Logistic Models
• Lung Transplantation (adverse effects, methods, mortality)
• Male
• Middle Aged
• Primary Graft Dysfunction (mortality, pathology)
• Proportional Hazards Models
• Reproducibility of Results
• Retrospective Studies
• Risk Assessment
• Severity of Illness Index
• Survival Rate
• Time Factors
• United States
• Young Adult