Objective lung assessment tools for improved organ use in lung transplantation

项目摘要/摘要 原发性移植物功能障碍(Pgd)是继肺部之后最常见的发病率和死亡率的原因。 移植会对患者的生活质量和成本产生明显的负面影响。PGD有一个 与捐赠者器官使用的复杂关系，因为器官质量的不确定性和担忧 供体质量差导致对PGD的易感性导致潜在的高丢弃率 可移植的器官。由于近五分之一的候选人在等待肺移植时死亡，电话 因为定义捐献者质量和PGD风险的新方法已经成为一个主要的公共卫生问题 挑战。 我们研究的长期目标是防止受者死亡并扩大 通过更好地选择捐赠者来汇集捐赠者。最近的证据表明先天免疫激活 在PGD发病机制中很重要，基于来自供体肺组织的转录本，支气管冲洗 还有鲜血。利用这些转录本，我们开发了两个基于 风险评估工具，用于对PGD风险进行分层，并确定可能适合 从未使用的器官池中进行移植。利用这些工具，我们将进行前瞻性的 多中心队列研究，以外部验证我们的预测工具，以扩大捐赠者池。 成功完成我们的目标将导致捐赠器官质量的客观标志，其 应用将简化捐赠者选择和新的识别的主观决策 用于扩大捐赠库的器官。

Project Summary/Abstract Primary graft dysfunction (PGD) is the most common cause of morbidity and mortality after lung transplantation resulting in significant negative effects on quality of life and cost. PGD has a complex relationship with donor organ use because uncertainty in organ quality and concern that poor donor quality causes susceptibility to PGD results in high discard rates for potentially transplantable organs. With almost 1 in 5 candidates dying awaiting lungs for transplant, calls for new methods to define donor quality and PGD risk have become a major public health challenge. The long-term objective of our line of research is to prevent recipient death and expand the donor pool through better donor selection. Recent evidence suggests innate immune activation is important in PGD pathogenesis based on transcripts from donor lung tissue, bronchial wash and blood. Using these transcripts, we have developed two objective gene expression based risk assessment tools to stratify PGD risk and identify organs which may be suitable for transplant from the pool of unused organs. Utilizing these tools, we will conduct a prospective multicenter cohort study to externally validate our prediction tools for donor pool expansion. Successful completion of our aims will lead to an objective marker of donor organ quality whose application will simplify subjective decision making in donor selection and identification of new organs for donor pool expansion.