Clinical characteristics and outcomes of WTC-associated Sarcoidosis

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 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.