The Effects of Lung Transplant on Disability and Health-Related Quality of Life

描述（由申请人提供）：作为加州大学旧金山分校弗朗西斯科的肺移植肺病学家和初级教师，我的长期职业目标是成为一名成功的独立研究者，研究肺移植受者以患者为导向的结局，特别是残疾和健康相关的生活质量（HRQL）。重要的是，虽然差的HRQL是肺移植的主要适应症，尽管HRQL是许多其他慢性疾病中以患者为中心的中心结局指标，但HRQL仍然是肺移植领域研究的一个相对不足的领域。因此，为了追求我的长期职业目标并解决这一知识差距，我建议1）前瞻性评估肺移植如何影响患有终末期肺病的受试者的残疾和HRQL变化，2）确定肺移植受者残疾和HRQL变化的关键预测因素，包括肺和肺外因素。三个具体目标使这些目标可操作：目标1：确定肺移植受者中残疾和HRQL随时间的变化;目标2：确定肺移植受者中残疾和HRQL变化的肺和肺外生理和心理预测因素;以及目标3。评估其他心理社会因素对肺移植受者HRQL的影响。为了实现这些目标，我提出了一种混合方法的分析方法，利用我正在进行的试点研究，目前由我的F32奖和诺华的校外资助。将确定105例肺移植受试者，并在移植后前瞻性随访3年。 移植前，将通过病历审查、家庭访视和结构化电话调查评估肺和肺外生理功能、合并症、残疾和HRQL的基线指标。移植后，将在移植后3、6、12、18、24、30和36个月重复这些测量。15名受试者的子集将完成半结构化的定性访谈，研究社会心理因素对HRQL的影响。统计分析将采用混合效应模型来分析数据集的重复测量性质。为了确定残疾和HRQL随时间的变化，将残疾和HRQL评分的纵向变化与基线移植前评分进行比较。接下来，将使用混合效应建模的分层方法来确定移植后残疾和HRQL变化的生理预测因素。描述肺移植对残疾和HRQL的影响具有直接的临床和研究意义。这一贡献将允许临床医生提供数据驱动的术前咨询，以了解肺移植可预期的残疾减少和HRQL改善的轨迹、程度和持久性。此外，强调肺外损伤作为移植后残疾和HRQL受损的风险因素的重要性可能会影响护理并改善结果。此外，识别移植后功能状态中的残留或新限制赋予残疾/HRQL结果差的特定风险，允许开发新的干预策略。虽然我有一个富有成效的开始，我的研究生涯，实现这个项目的目标和独立作为一个调查员，我需要进一步的培训。加州大学旧金山分校弗朗西斯科的肺科医学部提供了一个丰富的环境，具有培养成功的学术肺科医生的悠久历史，其中包括一个令人印象深刻的基础设施和致力于我的职业发展的研究人员网络。在这种环境下，我确定了5个短期职业目标。这些目标包括：（1）设计和实施多波数据的前瞻性研究;（2）先进的定量方法，包括重复测量分析，以最好地处理多波数据集;（3）使用现有工具测量残疾和HRQL的额外培训;（4）与HRQL工具开发相关的定性研究方法;和（5）通过UCSF临床和翻译K学者（CTSK）计划重点和结构化的职业发展。为了帮助我实现这5个目标，在我导师的指导下，我设计了一个5年的职业发展计划，其中包括高级生物统计学的教学课程，包括混合效应模型，使用问卷测量自我报告的健康（包括HRQL），以及定性研究方法。该计划还包括设计和实施前瞻性队列研究的一对一学徒培训;高级生物统计学;如何概念化和解释残疾，功能和HRQL的措施;以及定性研究方法，包括半结构化访谈的设计，访谈响应的编码和数据解释。最后，我的计划包括“动手”的实践经验，在实施前瞻性研究，解释残疾和HRQL数据的背景下，肺移植，分析结果，从我的研究在一个混合效应建模框架，并执行本研究项目的定性组成部分的各个方面。这个量身定制的5年职业发展计划，加上为这个奖项提出的前瞻性队列研究，将帮助我实现作为一个独立的研究者与明确界定的研究利基，我自己是独一无二的在加州大学旧金山分校弗朗西斯科，也解决了一个重要的，但在该领域的研究相对不足的领域 肺移植医学的一部分

DESCRIPTION (provided by applicant): As a lung transplant pulmonologist and junior faculty at UC San Francisco, my long term career goal is to become a successful independent investigator of patient-oriented outcomes in recipients of lung transplantation, specifically disability and health related quality of life (HRQL). Importantly, while poor HRQL is a primary indication for lung transplant and, although HRQL is a central, patient-centered outcome measure in many other chronic diseases, HRQL remains a relatively understudied area of research in the field of lung transplantation. Thus, to pursue my long term career goal and address this knowledge gap, I propose to 1) prospectively evaluate how lung transplant effects change in disability and HRQL in subjects suffering from end-stage lung disease and 2) identify key predictors, both pulmonary and extra-pulmonary, of change in disability and HRQL in lung transplant recipients. Three Specific Aims make operational these objectives: Aim 1: Determine changes in disability and HRQL over time among lung transplant recipients; AIM 2: Identify pulmonary and extra-pulmonary physiological and psychosocial predictors of change in disability and HRQL among lung transplant recipients; and AIM 3. Estimate the effect of additional psychosocial factors on HRQL among lung transplant recipients. To accomplish these Aims, I propose a mixed-methods analytic approach that leverages my ongoing pilot study currently supported by my F32 award and an extramural grant from Novartis. 105 subjects listed for lung transplant will be identified and prospectively followed for three years after transplant. Before transplant, baseline measures of pulmonary and extra-pulmonary physiological functioning, co-morbidities, disability and HRQL will be assessed through medical record review, a home visit, and a structured telephone survey. After transplant these measures will be repeated at 3, 6, 12, 18, 24, 30, and 36 months post-transplant. A subset of 15 subjects will complete semi-structured qualitative interviews examining the impact of psychosocial factors on HRQL. Statistical analyses will employ mixed-effects models to analyze the repeated measures nature of the dataset. To determine the change in disability and HRQL over time, longitudinal changes in disability and HRQL scores will be compared to baseline pre-transplant scores. Next, a hierarchical approach to mixed-effects modeling will be used to identify physiological predictors of change in disability and HRQL following transplant. Delineating the effects of lung transplant on disability and HRQL has immediate clinical and research implications. This contribution will permit clinicians to provide data- driven preoperative counseling on the trajectory, magnitude, and durability of reduced disability and improved HRQL that can be anticipated from lung transplant. Also, highlighting the importance of extra-pulmonary impairments as risk factors for disability and impaired HRQL post-transplant could impact care and improve outcomes. Further, identifying residual or new limitations in post-transplant functional status impart particular risk for poor disability/HRQL outcomes permits the development of novel intervention strategies. Though I have had a productive start to my research career, to achieve objectives of this project and independence as an investigator I need further training. The Division of Pulmonary Medicine at UC San Francisco offers a rich environment with a long history of training successful academic pulmonologists that includes an impressive infrastructure and network of researchers dedicated to my career development. Within this environment, I have identified 5 short-term career goals. These goals include (1) the design and implementation of prospective studies with multiple waves of data; (2) advanced quantitative methods including repeated measures analysis to best handle multi-wave data sets; (3) additional training in measuring disability and HRQL with existing instruments; 4) qualitative research methodology relevant to HRQL instrument development; and (5) focused and structured career development through the UCSF Clinical and Translational K Scholars (CTSK) program. To help me achieve these 5 goals, under the guidance of my mentor, I have designed a 5-year career development plan that includes didactic coursework in advanced biostatistics including mixed effects models, measurement of self-reported health (including HRQL) using questionnaires, and qualitative research methodology. This plan also includes one-on-one apprenticeship training in the design and implementation of prospective cohort studies; advanced biostatistics; how to conceptualize and interpret measures of disability, functioning, and HRQL; and qualitative research methods including the design of semi- structured interviews, the coding of interview responses, and data interpretation. Finally, my plan includes "hands-on" practical experiences in implementing prospective studies, interpreting disability and HRQL data within the context of lung transplantation, analyzing results from my study within a mixed-effects modeling framework, and executing all aspects of the qualitative component of this research project. This tailored 5- year career development plan coupled with the prospective cohort study proposed for this award will help me to achieve independence as an investigator with a clearly defined research niche of my own that is unique at UC San Francisco and that also addresses an important but relatively understudied area of investigation in the field of lung transplant medicine.