Predicting survival and planning for lung transplantation in severe cystic fibrosis

Kathleen拉莫斯，医学博士计划作为囊性纤维化（CF）领域的临床结果研究员的职业生涯 和肺移植。拟议的职业发展奖的目的是提供必要的 培训研究方法，以促进拉莫斯博士过渡到独立研究。营商友导 在华盛顿大学肺部和重症监护医学部提供的 非常出色。拉莫斯博士的导师是生物统计学、临床流行病学和定性研究方面的专家 方法-她希望在拟议的奖项中发展和完善的技能。她将追求先进的 全国知名的华盛顿大学公共卫生学院的课程， 来自导师的个性化指导拉莫斯博士在过去的3年里开发了一种多管齐下的 研究计划使用现有的数据和问卷调查，开始解决CF社区的问题， 她一直在强调严重CF患者肺移植的有限转诊。 随着CF患者年龄的增长，肺功能下降，最终达到与增加的肺功能相关的阈值。 肺部症状和死亡率增加，这可能促使对肺移植的评估;通常， 一秒用力呼气量（FEV 1）的参考阈值<预测正常值的30%。 博士拉莫斯表明，在国家CF患者登记处，35%的CF患者明确符合肺 基于功能的转诊标准，未转诊进行肺移植评估。然后她证明， 尽管转诊率很低，但CF医生认为FEV 1 < 30%是最重要的临床变量 这应该会推动推荐。随后，她对一个全国性CF患者队列进行了生存分析， 与历史估计相比，<30%表明无移植生存率有所提高。拉莫斯医生描述了 临床医生面临的临床难题：尽管FEV 1达到 <30%，10%的人口在达到这个阈值的第一年内仍然没有移植而死亡。 计划研究的目标包括：1）识别CF和晚期肺部疾病患者 使用预测模型，短期死亡风险最高的人; 2）临床 参数（即6分钟步行测试距离），以了解识别临床相关 短时间间隔内的变化; 3）评估患者报告的及时肺移植障碍 评价总体研究目标是提高我们预测生存率和计划肺移植的能力。 严重CF患者的移植。本申请中计划的工作利用了拉莫斯博士独特的 获得大量CF成人患者和大型临床肺移植计划。数据 该项目产生的影响可能会影响医生和患者如何处理肺移植的时机 评估，并将为拉莫斯博士未来的独立资助申请提供初步数据。

Kathleen Ramos, MD plans for a career as a clinical outcomes researcher in the fields of cystic fibrosis (CF) and lung transplantation. The objective of the proposed career development award is to provide necessary training in research methods to facilitate Dr. Ramos' transition to independent research. The mentorship available at the University of Washington in the Division of Pulmonary and Critical Care Medicine is outstanding. Dr. Ramos' mentors are experts in biostatistics, clinical epidemiology, and qualitative research methods – skills that she hopes to develop and refine during the proposed award. She will pursue advanced coursework at the nationally-renowned University of Washington School of Public Health and will have personalized instruction from her mentors. Dr. Ramos has developed, over the last 3 years, a multi-pronged research program using existing data and questionnaires to start to address a problem in the CF community that she has been central in highlighting – the limited referral of patients with severe CF for lung transplantation. As patients with CF age, lung function declines and eventually reaches a threshold associated with increased pulmonary symptoms and increased mortality, which may prompt evaluation for lung transplantation; typically, the referral threshold for forced expiratory volume in one second (FEV1) is <30% of the predicted normal value. Dr. Ramos showed that 35% of patients with CF in the national CF patient registry, who clearly met lung function-based referral criteria, were not referred for lung transplant evaluation. She then demonstrated that despite this low rate of referral, CF physicians felt that an FEV1 < 30% was the most important clinical variable that should drive referral. Subsequently, her survival analysis of a national cohort of CF patients with FEV1 <30% revealed improved transplant-free survival when compared to historical estimates. Dr. Ramos delineated the clinical conundrum facing clinicians: despite the improved transplant free survival after reaching an FEV1 of < 30%, 10% of the population still dies without transplant within the first year of reaching this threshold. The objectives of the planned research include: 1) identification of patients with CF and advanced lung disease who are at the highest risk of short-term death using predictive modeling; 2) serial measurement of clinical parameters (i.e. six-minute walk test distance) to understand the feasibility of identifying clinically-relevant changes over short time intervals; and 3) assessment of patient-reported barriers to timely lung transplant evaluation. The overall study objective is to improve our ability to predict survival and plan for lung transplantation in patients with severe CF. The work planned in this application leverages Dr. Ramos' unique access to a large population of adult patients with CF and a large clinical lung transplant program. Data generated from this project could affect how physicians and patients approach the timing of lung transplant evaluation and will provide preliminary data for Dr. Ramos' future independent funding applications.