Clinical characteristics and outcomes of WTC-associated Sarcoidosis

 描述（由申请人提供）：结节病，一种特发性肉芽肿性炎症，在大量暴露于世界贸易中心（WTC）的人员中发现，包括82名纽约消防局人员，其中70名为白色男性消防员。该建议是对该组进行重新检查，以确定其临床模式和遗传标志物，并将其与先前报告的非WTC暴露的结节病患者进行比较，并评估与未发生结节病的类似WTC暴露的消防员的遗传差异。具体目标是：（1）表征在暴露于WTC后发展结节病的FDNY消防员中结节病的当前和过去的临床概况，关于15个器官或系统中的每一个的受累，以便（1a）确定WTC相关的结节病中的肉芽肿性炎症是否限于胸腔内受累以及在多大程度上限于胸腔内受累，和（1b）表征诊断后5至13年内疾病进展或消退的时间过程;和（2）比较已知的与结节病相关的遗传标记的频率与对照组--暴露于WTC的消防员的频率，种族、年龄、吸烟史、WTC暴露史匹配，未发生结节病。我们将尽可能多地对70名9/11后新出现结节病的消防员进行一系列测试，根据过去的经验，我们估计至少可以招募60名。每个人都将有关于WTC暴露的详细问卷;结节病，吸烟和职业/环境史;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;钆增强心脏MRI;非造影胸部CT;关节X射线; 24小时尿钙;和血液检查，包括离子钙、25-羟基和1，25-二羟基维生素D、铍反应性CD 4 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的相关性而选择的。将检测对照品的相同遗传标记和铍应答性CD 4 T细胞。结果应使我们能够确定，在这个暴露于WTC的结节病队列中，其他暴露，遗传和共病因素的相互作用，以前与结节病在其他环境中，并定义结节病的程度，严重程度，活动，临床过程和影响，在每个器官和系统中指定的标准评估工具。

 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.