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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (F1))
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Colombini-Hatch, Sandra
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University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
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Martinez, Carlos H; Mannino, David M; Curtis, Jeffrey L et al. (2015) Socioeconomic Characteristics Are Major Contributors to Ethnic Differences in Health Status in Obstructive Lung Disease: An Analysis of the National Health and Nutrition Examination Survey 2007-2010. Chest 148:151-158
Martinez, Carlos H; Richardson, Caroline R; Han, MeiLan K et al. (2014) Chronic obstructive pulmonary disease, cognitive impairment, and development of disability: the health and retirement study. Ann Am Thorac Soc 11:1362-70
Han, MeiLan K; Zhou, Yueren; Murray, Susan et al. (2014) Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study. Lancet Respir Med 2:548-56
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
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
Schmidt, Shelley L; Tayob, Nabihah; Han, Meilan K et al. (2014) Predicting pulmonary fibrosis disease course from past trends in pulmonary function. Chest 145:579-585
Washko, G R; Diaz, A A; Kim, V et al. (2014) Computed tomographic measures of airway morphology in smokers and never-smoking normals. J Appl Physiol (1985) 116:668-73
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
Freeman, Christine M; Martinez, Fernando J; Han, Meilan K et al. (2013) Lung CD8+ T cells in COPD have increased expression of bacterial TLRs. Respir Res 14:13

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