The goal of this K23 award is to provide the candidate resources needed to develop an independent research career in the clinical investigation of end stage lung disease including the following: (1) focused additional didactic training in the analysis of longitudinal data, nonparametric statistics, the handling of missing data, and patient centered outcomes;(2) protected time to gain further practical experience in clinical trial conduct as an investigative trainee of the IPF CRN;and, (3) close mentoring under both Drs. Fernando J. Martinez and Kevin Flaherty, individuals with extensive experience in IPF clinical research and successful mentoring. To maximize these goals the research plan will not only seek to prospectively describe gender differences in physiologic progression, survival, and symptoms in idiopathic pulmonary fibrosis (IPF) but also investigate why these differences might exist using clinical and biologic data from the IPF CRN and Lung Tissue Research Consortium. Retrospective data suggests that men with IPF progress more rapidly and experience worse survival. Preliminary data suggest that measurable biologic (peptide hormone relaxin) and physiologic (pulmonary artery systolic pressure) differences contribute to gender differences in disease phenotype.
Specific aims i nclude: (1a) characterize male and female IPF phenotypes through baseline comparison of biologic and physiologic parameters (1 b) determine the relationship between biologic and physiologic parameters to better understand mechanisms behind gender differences in IPF phenotype;(2a) determine if gender influences longitudinal change in pulmonary function and explore the contribution of other factors improves known to be associated with gender (2b) compare the rate of acute exacerbations between men and women (2c) determine prospectively whether female gender is associated with improved survival in IPF independent of other biologic and physiologic parameters associated with gender;(3a) determine whether baseline health status and symptom measures, particularly anxiety and depression, are more abnormal in women with IPF than men (3b) determine whether gender differences exist in the longitudinal behavior of health status and symptom measures.

Public Health Relevance

This research has the potential for significant public health impact. The results could lead not only to better prognostication of IPF and improved insights into the role of gender in the design of future studies of chronic lung disease but will also provide key data that could lead to the both the development of a biomarker for IPF and a therapeutic clinical trial.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL093351-04
Application #
8261366
Study Section
Special Emphasis Panel (ZHL1-CSR-R (F1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2009-05-01
Project End
2013-09-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$126,157
Indirect Cost
$9,345
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Schmidt, Shelley L; Tayob, Nabihah; Han, Meilan K et al. (2014) Predicting pulmonary fibrosis disease course from past trends in pulmonary function. Chest 145:579-85
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Freeman, Christine M; Stolberg, Valerie R; Crudgington, Sean et al. (2014) Human CD56+ cytotoxic lung lymphocytes kill autologous lung cells in chronic obstructive pulmonary disease. PLoS One 9:e103840
Freeman, Christine M; McCubbrey, Alexandra L; Crudgington, Sean et al. (2014) Basal gene expression by lung CD4+ T cells in chronic obstructive pulmonary disease identifies independent molecular correlates of airflow obstruction and emphysema extent. PLoS One 9:e96421
Martinez, Carlos H; Okajima, Yuka; Murray, Susan et al. (2014) Impact of self-reported gastroesophageal reflux disease in subjects from COPDGene cohort. Respir Res 15:62
Martinez, Carlos H; Kim, Victor; Chen, Yahong et al. (2014) The clinical impact of non-obstructive chronic bronchitis in current and former smokers. Respir Med 108:491-9
Han, Meilan K; Bach, David S; Hagan, Peter et al. (2013) Sildenafil Preserves Exercise Capacity in IPF Patients with Right Ventricular Dysfunction. Chest :
Han, MeiLan K; Bach, David S; Hagan, Peter G et al. (2013) Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction. Chest 143:1699-708
Estepar, Raul San Jose; Kinney, Gregory L; Black-Shinn, Jennifer L et al. (2013) Computed tomographic measures of pulmonary vascular morphology in smokers and their clinical implications. Am J Respir Crit Care Med 188:231-9

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