Alveolitis and Fibrosis in Scleroderma Lung Disease

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DESCRIPTION (provided by applicant): Currently bronchoalveolar lavage (Bal) evidence of alveolitis is used to diagnose active alveolitis in patients with Scleroderma Lung Disease (SLD). Detection of alveolitis may therefore have little prognostic or pathogenic relevance in the assessment of these cases. Preliminary novel quantitative image analysis (QIA) of HRCT data has been shown to correlate with BAL cellularity with the added ability of assessing regional heterogeneity of the entire lung not possible with BAL alone. CT Q!A can also identify manifestation of fibrosis, which is not possible with BAL or visual inspection of HRCT, thus, there is the potential for using this technique to investigate the relationship between alveolitis and fibrosis in the pathogenesis os SLD. Specifically if the progression of QIA-detected regional variation in fibrosis or alveolitis can be determined to be independent of each other the postulate that the fibrosis is due to pathways other than alveolitis can be implied. The hypothesis of this study is that the relationship of the extent and distribution of alveolitis to fibrosis in the progression of SLD can be further elucidated by the added ability of QIA techniques to assess alveolitis and fibrosis independently on a comprehensive and regional basis which is not possible with conventional techniques. The specific aims of this project are: (1) To assess the presence and severity of alveolitis and fibrosis in asymptomatic patients with mild or moderate SLD on a comprehensive (whole lung) and regional (portion of lung segment) basis; (2) to determine the interrelationship between alveolitis and fibrosis (as measured by QIA) in the progression of SLD; and (3) to determine whether interval changes of global and regional QIA features of fibrosis and alveolitis on follow up CT are predictive of outcome as assessed by symptoms (dyspnea index) and FVC in treated and untreated patients. Two experiments are proposed: Experiment 1: Comprehensive regional detection and quantitation of alveolitis and fibrosis (specific aim1); Experiment 2: Assessment of the relationship between alveolitis and fibrosis in the progression of SLD (specific aims 2 and 3). These findings will potentially improve our understanding of the relationship between alveolitis and fibrosis and to the pathogenesis of fibrosis in SLD.