Objective lung assessment tools for improved organ use in lung transplantation

项目总结/摘要 原发性移植物功能障碍（PGD）是肺移植后发病和死亡的最常见原因。 移植对生活质量和成本产生显著的负面影响。PGD有一个 与供体器官使用的复杂关系，因为器官质量和关注的不确定性 差的供体质量导致对PGD的易感性，这导致潜在的高丢弃率。 可移植器官近五分之一的候选人在等待肺移植时死亡， 新的方法来确定供体质量和PGD风险已成为一个主要的公共卫生 挑战. 我们研究的长期目标是防止受体死亡， 通过更好的捐赠者选择来建立捐赠者库。最近的证据表明先天免疫激活 在基于来自供体肺组织、支气管冲洗物 还有血利用这些转录本，我们已经开发了两个基于 风险评估工具，对PGD风险进行分层，并确定可能适合 从未使用的器官池中移植利用这些工具，我们将进行一个前瞻性的 多中心队列研究，以外部验证我们的预测工具，供者库扩大。 成功完成我们的目标将导致一个客观的指标，供体器官的质量， 应用程序将简化捐赠者选择和新的识别的主观决策 扩大捐赠者库。

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.