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. Objective: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. Methods: Data from the Lung Transplant Outcomes Group multi-centered cohort was used to compare variations to 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. Main Results: 1,179 subjects from 10 centers were enrolled from 2007-2012. Median length of follow-up was 4 years (IQR [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.

中文翻译：

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修订肺移植后原发性移植物功能障碍定义的定量证据

基本原理：原发性移植物功能障碍 (PGD) 是肺移植后发生的一种急性肺损伤。PGD​​ 的定义于 2005 年标准化。从那时起，临床实践不断发展，这一定义越来越多地用作临床试验的主要终点；因此，验证是必要的。目的：我们试图确定对 2005 年共识定义的改进是否可以进一步提高结构效度。方法：来自肺移植结果组多中心队列的数据用于比较 PGD 定义的变化，包括替代氧合阈值、包含其他严重程度组以及手术类型和机械通气的影响。比较了死亡率预测和并发肺损伤生物标志物鉴别的收敛和发散有效性。主要结果：2007-2012 年间，来自 10 个中心的 1,179 名受试者入组。中位随访时间为 4 年（IQR [2.4; 5.9]）。无 PGD（0 级）和轻度 PGD（1 级）之间没有发现死亡率差异。使用较晚时间点（48、72 或 48-72 小时 - p<0.001）的所有定义都明显更好地区分死亡率。在 0 级和 1 级崩溃时，生物标志物的差异识别效果更好。其他严重程度等级、机械通气的使用和移植手术类型对死亡率或生物标志物识别的影响很小或没有影响。结论：PGD 共识定义可以通过结合较低的 PGD 等级来简化。无论移植程序类型或机械通气的使用如何，分级的结构有效性都存在。