Recently, imbalance in angiogenesis, dysregulation of the extra cellular matrix and fibroproliferation rather than inflammation has been postulated to perpetuate lung fibrosis in IPF. Detection of alveolitis may therefore have little prognostic or pathogenic relevance in the assessment of these cases. The heterogeneous pathology of UIP results in BAL and trans-bronchial biopsy (TBBx) to be subject to sampling errors compounding attempts to elucidate pathogenic pathways. A noninvasive mechanism to provide a """"""""morphometric"""""""" assessment of the whole lung on a global and regional basis would be ideal. Quantitative Image Analysis (QIA) of HRCT data has shown a correlation with inflammation, angiogenesis and fibrosis and can identify these independent manifestations of IPF on a global and regional basis not possible with bronchoscopy or visual inspection of HRCT. The hypothesis is: CT-QIA can better detect the presence, extent and progression of inflammation, angiogenesis and fibrosis in patients with ILD and so can be used to distinguish patients with UIP, DIP, NSIP or NSIP with fibrosis not possible with conventional clinical, radiographic and physiologic assessment or with sampling limited BAL and TBBx.
The specific aims are to 1) develop a CT-QIA model of pulmonary fibrosis in a murine model capable of assessing the development and progression of pulmonary fibrosis 2) develop a CT-QIA model of IPF capable of distinguishing inflammation, angiogenesis and fibrosis to better characterize patients with clinically diagnosed ILD with respect to pathologically defined UIP, DIP, NSIP and NSIP with fibrosis and 3) to determine the relative progression of inflammation, angiogenesis and fibrosis in patients with clinically assessed IPF treated with Prednisone alone, or IFN-gamma and low-dose prednisone or azathioprine plus prednisone. The main objective of this project is to distinguish between angiogenesis, inflammation and fibrosis in the pathogenesis of IPF in order to better characterize their relationship to the pathogenesis of IPF and to distinguish patients with UIP, DIP, NSIP or NSIP with fibrosis not possible with conventional techniques.
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