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)证据被用来诊断硬皮病(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可能几乎没有预后或致病相关性。HRCT数据的初步定量图像分析(QIA)已被证明与BAL细胞密度相关，并增加了单独使用BAL无法评估整个肺的区域异质性的能力。CT Q！A还可以确定纤维化的表现，这是BAL或HRCT肉眼检查所不能做到的，因此，有可能利用这一技术来研究SLD发病机制中肺泡炎和纤维化之间的关系。具体地说，如果QIA检测到的纤维化或肺泡炎的局部变异的进展可以被确定为彼此独立，则可以暗示纤维化是由肺泡炎以外的途径引起的。这项研究的假设是，在SLD的进展过程中，肺泡炎的程度和分布与纤维化的关系可以通过QIA技术的增加而进一步阐明，该技术能够在全面和区域性的基础上独立评估肺泡炎和纤维化，这是传统技术所不可能的。该项目的具体目标是：(1)全面(全肺)和区域性(部分肺段)评估无症状的轻、中度SLD患者肺泡炎和纤维化的存在和严重程度；(2)确定SLD进展过程中肺泡炎和纤维化(以QIA衡量)之间的相互关系；(3)确定治疗和未治疗患者的症状(呼吸困难指数)和FVC评估的纤维化和肺泡炎的整体和局部QIA特征的间隔变化是否可以预测预后。建议进行两个实验：实验1：对肺泡炎和纤维化进行全面的区域检测和量化(特定目标1)；实验2：评估SLD进展过程中肺泡炎和纤维化之间的关系(特定目标2和3)。这些发现可能会提高我们对肺泡炎和纤维化之间的关系以及SLD纤维化发病机制的理解。

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.