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.

Public Health Relevance

Although poor health-related quality of life (HRQL) is a primary indication for lung transplantation, how lung transplant reduces disability and improves HRQL in patients with end-stage lung disease has not been well studied. Characterizing how lung transplant reduces disability and improves HRQL should provide valuable information to patients, their families, and clinicians coping with this complex surgical intervention. Moreover, elucidating the causes of incident disability and worsening HRQL after transplant may identify new areas for intervention strategies aiming to improve HRQL in lung transplant recipients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL111115-02
Application #
8534269
Study Section
Special Emphasis Panel (ZHL1-CSR-X (M1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2012-09-01
Project End
2017-07-31
Budget Start
2013-09-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$158,432
Indirect Cost
$11,682
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Singer, Jonathan Paul; Chen, Joan; Katz, Patricia P et al. (2015) Defining novel health-related quality of life domains in lung transplantation: a qualitative analysis. Qual Life Res 24:1521-33
Singer, Jonathan Paul; Blanc, Paul David; Dean, Y Monica et al. (2014) Development and validation of a lung transplant-specific disability questionnaire. Thorax 69:437-42
Singer, Jonathan P; Peterson, Eric R; Snyder, Mark E et al. (2014) Body composition and mortality after adult lung transplantation in the United States. Am J Respir Crit Care Med 190:1012-21
Kern, Ryan M; Seethamraju, Harish; Blanc, Paul D et al. (2014) The feasibility of lung transplantation in HIV-seropositive patients. Ann Am Thorac Soc 11:882-9
Singer, J P; Chen, J; Blanc, P D et al. (2013) A thematic analysis of quality of life in lung transplant: the existing evidence and implications for future directions. Am J Transplant 13:839-50
Sottile, Peter D; Iturbe, David; Katsumoto, Tamiko R et al. (2013) Outcomes in systemic sclerosis-related lung disease after lung transplantation. Transplantation 95:975-80