Surrogate Biomarkers for Disease Progression in IPF

特发性肺纤维化(IPF)是一种进行性肺纤维化疾病，目前不受 可用的医疗方法。尽管传统上被认为是一种慢性进行性疾病，但它一直被 最近认识到，患者的病程可能不同，虽然一些患者有慢性缓慢的下降 在他们的肺功能方面，另一些人的病程更快，特征是“急性加重”。 疾病的不同病程和最近的观察结果，即患者生存的改善并不 必须与传统肺功能测试的改善有关，这表明传统的 追踪IPF进展的方法充其量只能作为前述结论的编年史，而不是 提供有关疾病进展的任何有用信息。我们假设宿主防御因素， 可能但不一定与疾病的主要原因相关，确定 疾病的发展。表征这些因素将使我们能够识别出一套完整的替代者 外周血液中与IPF进展相关的生物标志物，并可能早于IPF进展。这项提案已经 以下是具体目标： 1.使用西蒙斯中心ILD数据库和推荐库以及短期IPF创建 结果研究：一组经过仔细描述的IPF患者，将在预期的临床上接受治疗 按现行临床实践指南进行随访。 2.使用多分析珠分析靶分子血清中的蛋白质表达水平 基于蛋白质组分的分析方法。 3.确定PBMC中可诊断并与疾病相关的基因表达特征 进展和治疗效果。 4.探讨获得性免疫在IPF疾病进展中的作用。

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of the lung unaffected by currently available medical therapies. Although traditionally considered a chronic progressive disease it has been recently recognized that patient's course may differ and that while some patients have a chronic slow decline in their pulmonary functions others have a more accelerated course characterized by "acute exacerbations". The variable course of the disease and the recent observation that improvement in patient survival does not have to be associated with an improvement in traditional pulmonary function tests, suggest that traditional methods for tracking IPF progression may at best serve as chroniclers of a forgone conclusion and not provide any useful information about disease progression. We hypothesize that host defense factors, potentially but not necessarily associated with the primary cause of the disease, determine the rate of disease progression. Characterizing these factors will allow us to identify an integrated set of surrogate biomarkers in the peripheral blood that correlate and potentially predate IPF progression. The proposal has the following specific aims: 1. To create, using the Simmons Center ILD Database and referral base, and the Short term IPF outcome study, a cohort of carefully characterized IPF patients that will be prospectively clinically followed up according to current clinical practice guidelines. 2. To analyze protein expression levels in the serum of target molecules using a multianalyte bead based protein profiling assays assay. 3. To identify a gene expression signature in PBMC that is diagnostic and relevant to disease progression and treatment effect. 4. To determine the role of adaptive immunity in IPF disease progression.