Browsing by Author "Weill, David"

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    Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation
    (Public Library of Science, 2012) Diamond, Joshua M.; Porteous, Mary K.; Cantu, Edward; Meyer, Nuala J.; Shah, Rupal J.; Lederer, David J.; Kawut, Steven M.; Lee, James; Bellamy, Scarlett L.; Palmer, Scott M.; Lama, Vibha N.; Bhorade, Sangeeta M.; Crespo, Maria; Demissie, Ejigayehu; Wille, Keith; Orens, Jonathan; Shah, Pali D.; Weinacker, Ann; Weill, David; Arcasoy, Selim; Wilkes, David S.; Ware, Lorraine B.; Christie, Jason D.; Lung Transplant Outcomes Group; Medicine, School of Medicine
    Introduction: Primary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD. Methods: We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE). Results: There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40%) and 47 non-PGD subjects (59%) received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF). Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03). The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02); there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD) (p = 0.9). Conclusions: Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.
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    Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant
    (American Thoracic Society, 2018-01-15) Cantu, Edward; Diamond, Joshua M.; Suzuki, Yoshikazu; Lasky, Jared; Schaufler, Christian; Lim, Brian; Shah, Rupal; Porteous, Mary; Lederer, David J.; Kawut, Steven M.; Palmer, Scott M.; Snyder, Laurie D.; Hartwig, Matthew G.; Lama, Vibha N.; Bhorade, Sangeeta; Bermudez, Christian; Crespo, Maria; McDyer, John; Wille, Keith; Orens, Jonathan; Shah, Pali D.; Weinacker, Ann; Weill, David; Wilkes, David; Roe, David; Hage, Chadi; Ware, Lorraine B.; Bellamy, Scarlett L.; Christie, Jason D.; Medicine, School of Medicine
    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.