Clinical characteristics and outcomes of WTC-associated Sarcoidosis

WTC 相关结节病的临床特征和结果

• 批准号: 9275649
• 负责人: SIMON D SPIVACK
• 金额: $ 49.23万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-10 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9275649
• 关键词: Clinical; characteristics; outcomes; WTC; associated

 DESCRIPTION (provided by applicant): Sarcoidosis, an idiopathic granulomatous inflammation, has been noted in unexpectedly large numbers of World Trade Center (WTC)-exposed persons, including 82 FDNY personnel, 70 of them White male firefighters. This proposal is for a re-examination of this group, to define their clinical patterns and genetic markers and compare them with those of previously reported non-WTC-exposed sarcoidosis patients, and to assess genetic differences with similarly WTC-exposed firefighters who did not develop sarcoidosis. Specific aims are: (1) to characterize the current and past clinical profiles of sarcoidosis among FDNY firefighters who developed sarcoidosis after WTC-exposure, with regard to involvement of each of 15 organs or systems, in order to (1a) determine whether and to what extent granulomatous inflammation in WTC- associated sarcoidosis is limited to intrathoracic involvement, and (1b) characterize the time course of disease progression or resolution over the 5 to 13 years after diagnosis; and (2) to compare the frequency of known genetic markers associated with sarcoidosis with the frequencies in a control group---WTC-exposed firefighters, matched for race, age, smoking history, WTC-exposure history, who did not develop sarcoidosis. We will perform a battery of tests on as many of the 70 firefighters with new post-9/11 sarcoidosis as possible-we estimate, based on solid past experience, that we can recruit at least 60 of them. Each will have detailed questionnaires regarding WTC-exposure; sarcoid, smoking, and occupational/environmental history; medication review; review of systems; general and ophthalmologic examinations; pulmonary function testing; 24 hour EKG; echocardiogram; gadolinium-enhanced cardiac MRI; noncontrast chest CT; joint Xrays; 24 hour urine calcium; and blood tests, including ionized calcium, 25-hydroxy and 1,25-di-hydroxy-vitamin D, beryllium- responsive CD4 T cells, and a battery of 24 HLA alleles and other genes selected for their previously reported association with sarcoidosis in non-WTC-exposed populations. The controls will be tested for the same genetic markers and beryllium-responsive CD4 T cells. The results should allow us to determine, in this WTC-exposed sarcoidosis cohort the interplay of additional exposure, genetic, and comorbid factors previously associated with sarcoidosis in other settings, and to define the extent, severity, activity, clinical course and impact of sarcoidosis involvement in each of the organs and systems specified in a standard assessment instrument.

 描述（由申请人提供）：结节病是一种特发性肉芽肿性炎症，在世贸中心 (WTC) 暴露人群中出人意料地大量被发现，其中包括 82 名 FDNY 工作人员，其中 70 名是白人男性消防员。该提案旨在重新检查该群体，以确定他们的临床模式和遗传标记，并将其与之前报告的未暴露于世贸中心的结节病患者进行比较，并评估与类似暴露于世贸中心但未患结节病的消防员的遗传差异。具体目标是：(1) 描述在 WTC 暴露后发生结节病的 FDNY 消防员当前和过去的结节病临床特征，涉及 15 个器官或系统的受累情况，以便 (1a) 确定 WTC 相关结节病中的肉芽肿性炎症是否仅限于胸腔内受累以及在何种程度上仅限于胸腔内受累，以及 (1b) 描述疾病的时间进程 诊断后 5 至 13 年内疾病进展或缓解； (2) 将与结节病相关的已知遗传标记的频率与对照组（接触过世贸中心的消防员）的频率进行比较，这些对照组的种族、年龄、吸烟史、未患结节病的世贸中心接触史相匹配。我们将对 70 名患有 9/11 后新发结节病的消防员中的尽可能多的人进行一系列测试——根据过去的丰富经验，我们估计我们可以招募至少 60 名消防员。每个人都会有关于世贸中心暴露的详细调查问卷；结节病、吸烟和职业/环境史；药物审查；系统审查；一般检查和眼科检查；肺功能测试； 24小时心电图；超声心动图；钆增强心脏 MRI；胸部平扫 CT；关节X光检查； 24小时尿钙；和血液测试，包括离子钙、25-羟基和 1,25-二羟基维生素 D、铍反应性 CD4 T 细胞，以及一组 24 个 HLA 等位基因和其他基因，这些基因是根据先前报道的与非 WTC 暴露人群中的结节病相关而选择的。将测试对照的相同遗传标记和铍反应性 CD4 T 细胞。结果应使我们能够确定，在这个暴露于世贸中心的结节病队列中，其他环境中与结节病相关的额外暴露、遗传和共病因素之间的相互作用，并确定结节病累及标准评估工具中指定的每个器官和系统的范围、严重性、活动性、临床过程和影响。