Idiopathic pulmonary fibrosis (IPF) is a uniformly fatal diffuse lung disease with no effective treatment. Emerging data suggest that microaspiration may play a role in the pathogenesis and natural history of IPF. Defining the relationship between microaspiration and IPF could have major pathobiological and therapeutic implications. Objectives and Aims: The long-term objective of this proposal is to define the role of microaspiration in IPF.
Aim 1 : To determine the prevalence of microaspiration in patients with IPF.
Aim 2 : To elucidate biomarkers of microaspiration in patients with IPF.
Aim 3 : To define the impact of microaspiration on disease progression in IPF. Research Design and Methods: This proposal involves a prospectively identified cohort of 30 subjects with IPF. The prevalence of microaspiration in IPF (Aim 1) will be determined by measuring pepsin levels in bronchoaveolar lavage fluid. Biomarkers for microaspiration in IPF (Aim 2) will be identified using esophageal function studies (24h pH monitoring and manometry), laboratory tests, radiological imaging, and survey. The impact of microaspiration on disease progression (Aim 3) will be defined by measuring changes in pulmonary function over 12 months and assessing rates of urgent medical care use (unscheduled clinic visit, emergency room visit, and hospitalization). This proposal is directly relevant to the mission of the NHLBI: """"""""supporting research training and career development of new researchers to enable conduct of clinical research related to diagnosis of lung disease."""""""" This proposal includes advanced training in clinical research skills that will provide the necessary skills for future success as an independent clinical researcher. Relevance of Research to Public Health: Idiopathic pulmonary fibrosis (IPF) is a fatal disease without any known treatment or cure. Defining the role of microaspiration in IPF is important because it could lead to effective treatment options. Effective treatment will substantially improve the quality of life and survival of those patients suffering with IPF.
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| 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 |
| Lee, Joyce S; Su, Xiao; Rackley, Craig et al. (2011) Priming with endotoxin increases acute lung injury in mice by enhancing the severity of lung endothelial injury. Anat Rec (Hoboken) 294:165-72 |
| Lee, Joyce S; Collard, Harold R; Raghu, Ganesh et al. (2010) Does chronic microaspiration cause idiopathic pulmonary fibrosis? Am J Med 123:304-11 |
