Predicting survival and planning for lung transplantation in severe cystic fibrosis

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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.