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，不受目前已知的肺纤维化的影响。 可用的医学疗法。虽然传统上被认为是一种慢性进行性疾病， 最近认识到，患者的病程可能不同，虽然有些患者有慢性缓慢下降， 在他们的肺功能中，其他人具有以“急性加重”为特征的更加速的过程。 疾病的可变病程和最近的观察结果，即患者生存率的改善并不意味着 必须与传统肺功能检查的改善相关，这表明传统 跟踪IPF进展的方法最多可作为放弃结论的记录者， 提供任何有关疾病进展的有用信息。我们假设宿主的防御因素， 可能但不一定与疾病的主要原因有关，确定 疾病进展。表征这些因素将使我们能够确定一套综合的替代 外周血中与IPF进展相关并可能先于IPF进展的生物标志物。该提案 具体目标如下： 1.使用西蒙斯中心ILD数据库和转诊基础以及短期IPF 一项结局研究，一组经过仔细描述的IPF患者，将在临床上进行前瞻性研究 根据现行临床实践指南进行随访。 2.使用多分析物微珠分析靶分子血清中的蛋白质表达水平 基于蛋白质谱分析的测定。 3.鉴定PBMC中诊断性和与疾病相关的基因表达特征 进展和治疗效果。 4.确定适应性免疫在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.