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Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant.
Am J Respir Crit Care Med. 2018 01 15; 197(2):235-243.AJ

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+Show Affiliations

1 Division of Cardiovascular Surgery and.2 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.1 Division of Cardiovascular Surgery and.1 Division of Cardiovascular Surgery and.1 Division of Cardiovascular Surgery and.1 Division of Cardiovascular Surgery and.2 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.2 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.3 Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, New York.2 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 4 Center for Clinical Epidemiology and Biostatistics and. 5 Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.6 Division of Pulmonary, Allergy, and Critical Care Medicine and.6 Division of Pulmonary, Allergy, and Critical Care Medicine and.7 Division of Cardiothoracic Surgery, Duke University, Durham, North Carolina.8 Division of Pulmonary, Allergy, and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan.9 Division of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois.1 Division of Cardiovascular Surgery and.2 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.10 Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh, Pittsburgh, Pennsylvania.11 Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.12 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Johns Hopkins University Hospital, Baltimore, Maryland.12 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Johns Hopkins University Hospital, Baltimore, Maryland.13 Division of Pulmonary and Critical Care Medicine, Stanford University, Palo Alto, California.14 Institute for Advanced Organ Disease and Transplantation, University of South Florida, Tampa, Florida.15 Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana.15 Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana.15 Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana.16 Department of Medicine and. 17 Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee; and.18 Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania.2 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 4 Center for Clinical Epidemiology and Biostatistics and.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28872353

Citation

Cantu, Edward, et al. "Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction After Lung Transplant." American Journal of Respiratory and Critical Care Medicine, vol. 197, no. 2, 2018, pp. 235-243.
Cantu E, Diamond JM, Suzuki Y, et al. Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant. Am J Respir Crit Care Med. 2018;197(2):235-243.
Cantu, E., Diamond, J. M., Suzuki, Y., Lasky, J., Schaufler, C., Lim, B., Shah, R., Porteous, M., Lederer, D. J., Kawut, S. M., Palmer, S. M., Snyder, L. D., Hartwig, M. G., Lama, V. N., Bhorade, S., Bermudez, C., Crespo, M., McDyer, J., Wille, K., ... Christie, J. D. (2018). Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant. American Journal of Respiratory and Critical Care Medicine, 197(2), 235-243. https://doi.org/10.1164/rccm.201706-1140OC
Cantu E, et al. Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction After Lung Transplant. Am J Respir Crit Care Med. 2018 01 15;197(2):235-243. PubMed PMID: 28872353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant. AU - Cantu,Edward, AU - Diamond,Joshua M, AU - Suzuki,Yoshikazu, AU - Lasky,Jared, AU - Schaufler,Christian, AU - Lim,Brian, AU - Shah,Rupal, AU - Porteous,Mary, AU - Lederer,David J, AU - Kawut,Steven M, AU - Palmer,Scott M, AU - Snyder,Laurie D, AU - Hartwig,Matthew G, AU - Lama,Vibha N, AU - Bhorade,Sangeeta, AU - Bermudez,Christian, AU - Crespo,Maria, AU - McDyer,John, AU - Wille,Keith, AU - Orens,Jonathan, AU - Shah,Pali D, AU - Weinacker,Ann, AU - Weill,David, AU - Wilkes,David, AU - Roe,David, AU - Hage,Chadi, AU - Ware,Lorraine B, AU - Bellamy,Scarlett L, AU - Christie,Jason D, AU - ,, PY - 2017/9/6/pubmed PY - 2019/4/10/medline PY - 2017/9/6/entrez KW - lung transplant KW - lung transplant outcomes KW - primary graft dysfunction SP - 235 EP - 243 JF - American journal of respiratory and critical care medicine JO - Am. J. Respir. Crit. Care Med. VL - 197 IS - 2 N2 - 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. SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/28872353/Quantitative_Evidence_for_Revising_the_Definition_of_Primary_Graft_Dysfunction_after_Lung_Transplant_ L2 - http://www.atsjournals.org/doi/full/10.1164/rccm.201706-1140OC?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -