Clinical characteristics and outcomes of WTC-associated Sarcoidosis

 描述(申请人提供)：结节病是一种特发性肉芽肿性炎症，出人意料地在大量暴露于世界贸易中心(WTC)的人中发现，其中包括82名纽约消防局人员，其中70人是白人男性消防员。这项建议是为了重新检查这一群体，定义他们的临床模式和遗传标记，并将它们与先前报道的非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暴露的消防员的基因差异。具体目的是：(1)根据15个器官或系统的受累情况，描述暴露于WTC后发生结节病的FDNY消防员目前和过去的临床特征，以(1a)确定WTC相关结节病的肉芽肿性炎症是否以及在多大程度上仅限于胸腔内受累，以及(1b)描述诊断后5至13年内疾病进展或消退的时间进程；以及(2)比较已知的与结节病相关的遗传标记的频率与对照组-接触WTC的消防员的频率，他们的种族、年龄、吸烟史、WTC接触史相匹配，后者没有发生结节病。我们将尽可能多地对70名患有9·11后新结节病的消防员进行一系列测试--根据可靠的过去经验，我们估计我们可以招募至少60名消防员。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；用药回顾；系统回顾；全身和眼科检查；肺功能测试；24小时EKG；超声心动图；增强的心脏MRI；胸部平扫CT；关节X光；24小时尿钙；以及血液测试，包括电离钙、25-羟基和1，25-二羟基维生素D、铍反应的CD4T细胞，以及一组24个HLA等位基因和其他被选择的基因，因为它们与非WTC暴露人群的结节病有关。对照组将接受相同的遗传标记和对铍有反应的CD4T细胞的测试。结果应该使我们能够确定，在这个WTC暴露的结节病队列中，先前在其他环境中与结节病相关的额外暴露、遗传和共病因素的相互作用，并确定标准评估工具中指定的每个器官和系统的结节病受累程度、严重性、活动性、临床病程和影响。

 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.