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

身体成分对肺移植围手术期和以患者为中心的结果的影响。

• 批准号: 10429878
• 负责人: Jonathan Paul Singer
• 金额: $ 45.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10429878
• 关键词: Accounting; Address; Adoption; Anxiety; Area; Biolectric Impedance; Biological Assay; Body Composition; Body measure procedure; Cessation of life; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Cognitive; Collaborations; Data; Development; Dual-Energy X-Ray Absorptiometry; Enrollment; Evaluation; Event; Foundations; Future; Habilitation; Health; Hospitalization; Individual; Intervention; Intervention Studies; Intuition; Investigation; Knowledge; Length of Stay; Lung Transplantation; Mental Depression; Methods; Modality; Modeling; Multicenter Studies; Multicenter Trials; National Heart, Lung, and Blood Institute; Obesity; Observational Study; Outcome; Outcome Measure; Patient Outcomes Assessments; Patient Selection; Patient-Focused Outcomes; Patients; Perioperative; Perioperative complication; Phenotype; Physical Function; Postoperative Period; Quality of life; Reporting; Risk; Risk Factors; Scanning; Sum; Surveys; Survivors; Technology; Time; Transplant Recipients; Transplantation; Waiting Lists; Work; clinical care; clinical practice; cost; disability; experience; frailty; graft dysfunction; graft failure; graft function; health related quality of life; improved; innovation; mortality; novel; nutrition; patient response; physical conditioning; post-transplant; predictive modeling; prognostic; pulmonary function; response; sarcopenia; sarcopenic obesity; transplant centers

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.

项目摘要 肺移植旨在延长生存期、缓解残疾并改善与健康相关的生活质量（HRQL）。 尽管许多人做得很好，但围手术期并发症有所增加，三分之一的患者在前三年内死亡 移植后数年，20-40% 的幸存者没有报告患者报告结果 (PRO) 的改善 例如功能和 HRQL。缺乏改进的原因通常未知。结果，RFA- 022-002 强调身体成分和 PRO 作为进一步调查和干预的关键优先领域。 在早期使用 BMI、CT 扫描和 DXA 的研究中，我们的小组表明肥胖和肌肉减少症在肺部普遍存在 移植候选者，是虚弱、原发性移植物功能障碍（PGD）和死亡的危险因素。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，可以克服这些挑战。我们 通过 BIA 证明肥胖和肌肉减少症是 PGD 和候补死亡的危险因素。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，围手术期风险较高 并发症。移植后，PGD 和其他围手术期并发症会导致残疾、HRQL 较差、 以及移植后死亡。尽管 PRO 具有临床首要地位，但关于 PRO 影响的唯一经验数据 PRO 的围手术期并发症来自我们的单中心工作。 PRO 响应的数据 缺乏围手术期并发症，阻碍了在未来研究中明智地选择 PROs。最后， 定义从移植前到移植后早期影响 PRO 的因素和事件可以识别和 优先考虑干预目标，并通过丰富预后来提高临床试验效率。致地址 针对这些问题，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，即使对于正常体重的患者也是如此。 体重指数。在目标 2 中，我们将定义 PRO 措施对 PGD 和其他围手术期的反应 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、围术期和术后早期因素，以确定术后 6 个月和时间段 PRO 较差的群体 移植后 3 年内移植失败。开发围手术期和术后早期结果的新模型 预测哪些人面临不良结果的风险将为所需的预后丰富策略提供信息 提高肺移植临床试验效率。总之，我们通过以下方式解决 RFA HL-22-022 中的关键优先事项： 以创新且可扩展的方式检查身体成分；为未来的研究确定高产 PRO 并生成基础知识，为未来的肺移植研究和试验提供信息。