1 Division of Cardiovascular Surgery and.
2 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Am J Respir Crit Care Med. 2018 Jan 15;197(2):235-243. doi: 10.1164/rccm.201706-1140OC.
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.
We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity.
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.
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.
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.
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形式。PGD 的定义于 2005 年标准化。自那时以来，临床实践不断发展，该定义越来越多地被用作临床试验的主要终点；因此，有必要进行验证。
我们旨在确定 2005 年共识定义的改进是否可以进一步提高结构效度。
使用肺移植结果组多中心队列的数据，比较 PGD 定义的变化，包括替代氧合阈值、纳入其他严重程度组，以及手术类型和机械通气的影响。比较死亡率预测和同时的肺损伤生物标志物鉴别力的收敛和发散有效性。
共纳入来自 10 个中心的 1179 名患者，入组时间为 2007 年至 2012 年。中位随访时间为 4 年（四分位间距=2.4-5.9）。无 PGD（0 级）和轻度 PGD（1 级）之间的死亡率无差异。所有定义的死亡率差异在较晚的时间点（48、72 或 48-72 小时；P<0.001）都有明显改善。合并 0 级和 1 级后，生物标志物发散鉴别力更好。增加严重程度等级、使用机械通气和移植手术类型对死亡率或生物标志物鉴别力影响很小或没有影响。
可以通过合并较低的 PGD 等级来简化 PGD 共识定义。无论移植手术类型或使用机械通气，分级的结构效度均存在。增加严重程度类别对死亡率或生物标志物鉴别力影响很小。
