The purpose of this K23 proposal is to allow for my continued development as a clinical researcher with the goal of becoming an independent leader in the investigation of interstitial lung disease. Under the mentorship of Dr. Talmadge E. King, Jr. and Dr. Michael A. Matthay, and with guidance from a network of experienced clinical and basic researchers, I will obtain the experience and skills necessary to achieve this goal. The research proposal I have designed involves defining acute exacerbations of Idiopathic Pulmonary Fibrosis (IPF) at a clinical and biological level. IPF is a common and highly morbid form of interstitial lung disease, of which acute exacerbations are an important component. The incidence, causes, and clinical significance of acute exacerbations remain poorly understood. Recently, the NHLBI has created the IPF Clinical Research Network (IPFNet) to allow for large-scale, well-designed interventional studies of IPF. By positioning my research proposal to take advantage of IPFNet subjects and infrastructure, I plan to achieve the following four specific aims:
Aim 1 : To determine the incidence of and risk factors for acute exacerbations ofIPF.
Aim 2 : To define the etiologic role of occult viral infection in acute exacerbations ofIPF.
Aim 3 : To determine the role of disordered coagulation in acute exacerbations ofIPF.
Aim 4 : To demonstrate the prognostic significance of acute exacerbations ofIPF. To achieve these aims, clinical data, respiratory secretions, and blood samples will be collected from an estimated 150 subjects with acute exacerbations of IPF and appropriate controls. This research proposal may provide insight into the frequency and causes of acute exacerbations,providing evidence upon which to design interventional trials of prevention and treatment. Importantly, this research proposal will also serve to foster my career development goals of gaining experience and expertise in conducting prospective clinical research trials, mastering sophisticated biostatistical techniques, and developing multidisciplinary collaborations among clinical and basic scientists. These skills will allow me to fully realize the power of clinical research to inform basic biology and advance medical knowledge.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL086516-05
Application #
8010629
Study Section
Special Emphasis Panel (ZHL1-CSR-R (O1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2007-01-01
Project End
2012-12-31
Budget Start
2011-01-01
Budget End
2012-12-31
Support Year
5
Fiscal Year
2011
Total Cost
$152,692
Indirect Cost
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
Ley, Brett; Elicker, Brett M; Hartman, Thomas E et al. (2014) Idiopathic pulmonary fibrosis: CT and risk of death. Radiology 273:570-9
Johannson, Kerri A; Vittinghoff, Eric; Lee, Kiyoung et al. (2014) Acute exacerbation of idiopathic pulmonary fibrosis associated with air pollution exposure. Eur Respir J 43:1124-31
Johannson, Kerri; Collard, Harold R (2013) Acute Exacerbation of Idiopathic Pulmonary Fibrosis: A Proposal. Curr Respir Care Rep 2:
Lee, Joyce S; Kim, Eunice J; Lynch, Kara L et al. (2013) Prevalence and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis. Respir Med 107:249-55
Cha, Seung-Ick; Ryerson, Christopher J; Lee, Joyce S et al. (2012) Cleaved cytokeratin-18 is a mechanistically informative biomarker in idiopathic pulmonary fibrosis. Respir Res 13:105
Ley, Brett; Ryerson, Christopher J; Vittinghoff, Eric et al. (2012) A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med 156:684-91
Lee, J S; Song, J W; Wolters, P J et al. (2012) Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J 39:352-8
Richeldi, Luca; Ryerson, Christopher J; Lee, Joyce S et al. (2012) Relative versus absolute change in forced vital capacity in idiopathic pulmonary fibrosis. Thorax 67:407-11
Lee, Joyce S; Ryu, Jay H; Elicker, Brett M et al. (2011) Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 184:1390-4
Wootton, Sharon Chao; Kim, Dong Soon; Kondoh, Yasuhiro et al. (2011) Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 183:1698-702

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