Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating, and ultimately fatal disease for which no effective therapy exists. During the development of IPF, extracellular matrix (ECM) proteins are deposited in the walls of the airspaces, resulting in obliteration of the underlying lung structure and disrupting normal lung function. ECM remodeling, the turnover of numerous matrix and matrix-related proteins, during IPF is accompanied by the release of proteins and their fragments into the peripheral blood circulation. Some of these proteins have been proposed to be possible biomarkers in IPF. However, little is known about whether peripheral blood protein levels accurately reflect the pathophysiologic state of the lung microenvironment. Moreover, few studies have evaluated the accuracy of these putative biomarkers in a well-characterized cohort of patients with IPF to determine whether a biomarker panel can be used to provide accurate prognostic information in IPF patients. Thus, this proposal will address the hypotheses: a) that plasma biomarkers in IPF correlate with matrix turnover in the lung microenvironment, b) that a biomarker 'signature'can be identified that will distinguish patients with IPF from patients with non-IPF interstitial lung disease, COPD, or controls, and c) that a biomarker profile can be identified that will provide enhanced prognostic information in IPF patients. Among the questions to be addressed are: 1) Do plasma biomarker profiles accurately correspond to pathophysiologic ECM turnover in the lung parenchyma? 2) Can plasma biomarkers be used as an accurate surrogate for lung biopsy in patients with IPF? 3) Can plasma biomarkers distinguish among patients with IPF, other diffuse parenchymal lung diseases, COPD, and normal subjects? 4) In IPF patients, do plasma biomarker profiles predict clinical course with respect to decline in lung function, development of acute exacerbations, or time to death? Successful completion of these studies will shed significant insight into the pathophysiology of IPF, and may provide novel clinical tools necessary to help in the treatment or prognostication (or both) of patients with this disease.
The relevance of this research is to determine whether blood levels of various proteins accurately reflect the scarring process in the lung in patients with inappropriate lung scar tissue formation (pulmonary fibrosis). The research will also test whether blood levels of various proteins can be used to diagnose and predict outcomes of patients with pulmonary fibrosis.
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