The impact of body composition on peri-operative and patient-centered outcomes in lung transplantation.

项目摘要 肺移植旨在延长生存期，减轻残疾，改善健康相关的生活质量（HRQL）。 虽然许多人做得很好，但围手术期并发症增加，三分之一的患者在前三年内死亡 20-40%的存活者没有报告患者报告结局（PRO）的改善 例如功能和HRQL。这种缺乏改善的原因通常是未知的。因此，RFA- 022-002强调身体成分和PRO是进一步调查和干预的关键优先领域。 在使用BMI，CT扫描和DXA的早期工作中，我们的研究小组表明肥胖和肌肉减少症在肺部普遍存在， 移植候选人，是虚弱，原发性移植功能障碍（PGD）和死亡率的危险因素。我们也 强调了更广泛地实施这些模式和引入生物电阻抗的挑战 (BIA)作为一种先进的身体成分量化方法，克服了这些挑战。我们 BIA显示肥胖和肌肉减少症是PGD和等待名单死亡的危险因素。我们的初步 数据表明，肌肉减少性肥胖可能是一种新的表型， 并发症移植后，PGD和其他围手术期并发症导致残疾，HRQL差， 移植后死亡。尽管PRO在临床上占首位，但关于 PRO的围手术期并发症来自我们的单中心工作。专业人员响应的数据 缺乏围手术期并发症，阻碍了在未来研究中使用的PRO的知情选择。最后， 定义从移植前到移植后早期影响PRO识别的因素和事件， 优先考虑干预目标，并通过预后富集提高临床试验效率。解决 为了解决这些问题，我们将招募803名肺移植候选人，并在目标1中定义肌肉减少症的影响。 围手术期和6个月时PRO的肥胖、肌肉减少症和肥胖。我们假设肌肉减少症 肥胖会增加围手术期并发症的风险，包括PGD，即使在正常的患者中， 体重指数。在目标2中，我们将定义PRO指标对PGD和其他围手术期指标的反应性。 并发症目标2将提供所需的基础经验数据，为适当的PRO选择提供信息， 未来的观察和干预研究。目标3，将开发具有里程碑意义的预测模型， 术前、术中和术后早期因素，以确定术后6个月时PRO较差的组 移植后3年内移植失败。开发围手术期和早期术后结果的新模型 预测哪些个体有不良结局的风险将为所需的预后富集策略提供信息， 提高肺移植临床试验效率。总而言之，我们通过以下方式解决了RFA HL-22-022中的关键优先事项 以创新和可扩展的方式检查身体组成;为未来的研究确定高产PRO 并产生基础知识，为肺移植的未来研究和试验提供信息。

PROJECT ABSTRACT Lung transplantation aims to extend survival, relieve disability, and improve health-related quality of life (HRQL). Although many do well, perioperative complications have increased, one third of patients die within the first three post-transplant years and 20-40% of survivors do not report improvements in patient-reported outcomes (PROs) such as functioning and HRQL. Reasons for this lack of improvement are generally unknown. As a result, RFA- 022-002 highlights body composition and PROs as key priority areas for further investigation and intervention. In earlier work using BMI, CT scans, and DXA, our group showed that obesity and sarcopenia are prevalent in lung transplant candidates and are risk factors for frailty, primary graft dysfunction (PGD), and mortality. We also highlighted, the challenges to more widely implementing these modalities and introduced bioelectrical impedance (BIA) as a method of advanced body composition quantification that overcomes these challenges. We demonstrated that obesity and sarcopenia by BIA are risk factors for PGD, and wait-list death. Our preliminary data suggests that sarcopenic obesity may be a novel phenotype at heightened risk for perioperative complications. After transplant, PGD and other perioperative complications contribute to disability, poor HRQL, and death after transplant. Despite the clinical primacy of PROs, the only empirical data on the impact of perioperative complications on PROs comes from our single-center work. Data on which PROs are responsive to perioperative complications is lacking, hindering informed selection of PROs for use in future research. Finally, defining the factors and events from before through early after transplant that impact PROs can identify and prioritize targets for intervention and improve clinical trial efficiency through prognostic enrichment. To address these problems, we will enroll 803 lung transplant candidates and, in Aim 1, will define the impact of sarcopenic obesity, sarcopenia, and adiposity on peri-operative and PROs at 6-months. We hypothesize that sarcopenic obesity will confer heightened risk for perioperative complications, including PGD, even in patients with normal BMI. In Aim 2, we will define the responsiveness of PRO measures to PGD and other perioperative complications. Aim 2 will provide the foundational empirical data needed to inform appropriate PRO selection for future observational and interventional studies. Aim 3, will develop landmark prediction models accounting for pre-, peri- and early post-operative factors to identify groups with worse post-operative PROs at 6-months and time to graft failure up to 3-years after transplant. Developing new modeling of peri- and early post-operative outcomes to predict which individuals are at risk for poor outcomes will inform the prognostic enrichment strategies needed to improve clinical trial efficiency in lung transplant. In sum, we address key priorities in RFA HL-22-022 by examining body composition in an innovative and scalable manner; identifying high yield PROs for future studies and generating foundational knowledge to inform future studies and trials in lung transplantation.