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（由适用提供）：结节病是一种特发性肉芽肿性炎症，已在大量的世界贸易中心（WTC）暴露的人中注意到，包括82名FDNY人员，其中70名白人男性男性消防员。该提议是为了重新检查该组，定义其临床模式和遗传标记，并将其与先前报道的非WTC暴露的结节症患者进行比较，并评估与未发展性疾病的WTC暴露的消防员的遗传差异。具体目的是：（1）表征在暴露后发生结节病的FDNY消防员中结节病的当前和过去临床特征，以涉及15个器官或系统中的每一个，以（1a）的参与，以确定粒子症在何种程度上以及在何种程度上涉及wtc-相关的疾病，并在何种程度上涉及疾病的疾病。或诊断后5至13年的分辨率； （2）将与结节病相关的已知遗传标志物的频率与对照组的频率相关的频率 - 与WTC暴露的消防员相匹配，与种族，年龄，吸烟史，WTC暴露史相匹配，后者没有发展为结节病。我们将根据稳定的过去经验，对70名带有新的后9/11后结节病后的消防员中的许多测试进行了一系列测试，我们可以招募其中至少60个。每个人都会有有关WTC暴露的详细问卷；结节，吸烟和职业/环境历史；药物审查；系统审查；一般和眼科检查；肺功能测试； 24小时EKG;超声心动图； Gadolinium增强心脏MRI；非对比度胸部CT；关节Xrays; 24小时尿钙；和血液测试，包括离子化钙，25-羟基和1,25-Di-羟基抗原蛋白D，铍反应性CD4 T细胞以及24 HLA等位基因的电池和其他基因，用于在非WTC暴露的人群中与先前报道的与之相关的基因。对照将对相同的遗传标记和铍反应性CD4 T细胞进行测试。结果应该使我们能够确定在这种暴露于WTC的结节病中，在其他情况下，其他与结节症相关的额外暴露，遗传和合并症的相互作用，并确定在每个器官和标准评估工具中指定的每个人的严重性，活性，活动，临床过程和结节症的程度，活动，临床过程和影响。