Alveolitis and Fibrosis in Scleroderma Lung Disease

描述（由申请人提供）： 目前，肺泡炎的支气管肺泡灌洗（Bal）证据用于诊断硬皮病肺病（SLD）患者的活动性肺泡炎。 因此，肺泡炎的检测在这些病例的评估中几乎没有预后或致病相关性。 初步的新型定量图像分析（QIA）已被证明与BAL细胞结构相关，并且单独使用BAL无法评估整个肺的区域异质性。 CT Q！A还可以识别纤维化的表现，这是BAL或HRCT的目视检查所不可能的，因此，有可能使用该技术来研究肺泡炎和纤维化在SLD发病机制中的关系。 具体地，如果可以确定纤维化或肺泡炎中的QIA检测的区域变化的进展彼此独立，则可以暗示纤维化是由于除肺泡炎之外的途径引起的假设。 本研究的假设是，在SLD进展过程中，肺泡炎的程度和分布与纤维化的关系可以通过QIA技术在全面和区域基础上独立评估肺泡炎和纤维化的额外能力进一步阐明，这是传统技术无法实现的。 本研究的具体目的是：（1）通过对无症状的轻、中度SLD患者进行全面的肺泡炎和纤维化评估，（全肺）和局部（肺段部分）基础;（2）确定肺泡炎和纤维化之间的相互关系（通过QIA测量）在SLD的进展中;以及（3）确定随访CT上纤维化和肺泡炎的整体和局部QIA特征的间隔变化是否可预测由症状评估的结果（呼吸困难指数）和FVC。 提出了两个实验：实验一：肺泡炎和纤维化的全面区域检测和定量（具体目标1）;实验2：评估SLD进展中肺泡炎和纤维化之间的关系（具体目标2和3）。 这些发现将潜在地提高我们对肺泡炎和纤维化之间的关系以及对SLD中纤维化的发病机制的理解。

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.