Sarcoidosis is a systemic granulomatous disease of unknown etiology. It may develop in response to an exposure or inflammatory trigger in the background of a genetically primed abnormal immune response. Thus, genetic studies are potentially important to our understanding of the pathogenesis of sarcoidosis. We developed a case-control study which explored the genetic variations between firefighters in the Fire Department of the City of New York (FDNY) with World Trade Center (WTC)-related sarcoidosis and those with WTC exposure, but without sarcoidosis. The loci of fifty-one candidate genes related to granuloma formation, inflammation, immune response, and/or sarcoidosis were sequenced at high density in enhancer/promoter, exonic, and 5’ untranslated regions. Seventeen allele variants of human leukocyte antigen (HLA) and non-HLA genes were found to be associated with sarcoidosis, and all were within chromosomes 1 and 6. Our results also suggest an association between extrathoracic involvement and allele variants of HLA and non-HLA genes found not only on chromosomes 1 and 6, but also on chromosomes 16 and 17. We found similarities between genetic variants with WTC-related sarcoidosis and those reported previously in sporadic sarcoidosis cases within the general population. In addition, we identified several allele variants never previously reported in association with sarcoidosis. If confirmed in larger studies with known environmental exposures, these novel findings may provide insight into the gene-environment interactions key to the development of sarcoidosis.

The World Trade Center (WTC) attacks on 9/11/2001 have consistently been associated with elevated rates of physical and mental health morbidities, while evidence about mortality has been limited. We examined mortality between 9/12/2001 and 12/31/2017 among 15,431 WTC-exposed Fire Department of the City of New York (FDNY) firefighters and emergency medical service providers (EMS), specifically assessing associations between intensity of WTC-exposure and mortality risk. Standardized mortality ratios (SMR) and 95% confidence intervals (CI) compared FDNY cohort mortality with the US general population using life table analysis. Deaths were identified via linkage to the National Death Index. Cox proportional hazards regression models were used to identify associations between intensity of WTC-exposure and mortality, accounting for age, sex, race/ethnicity, smoking history, and other relevant confounders. We identified 546 deaths and a lower than expected all-cause mortality rate (SMR = 0.34; 95% CI, 0.31–0.37). No cause-specific SMRs were meaningfully elevated. Mortality hazard ratios showed no association or linear trend with level of WTC-exposure. Our results provide evidence of the healthy worker effect, despite exposure to the World Trade Center. More follow-up time may be needed to assess the full impact of WTC-exposure on mortality in this occupational population.

Peripheral neuropathy can result from numerous conditions including metabolic disorders, inflammatory disease, or exposure to environmental or biological toxins. We analyzed questionnaire data from 9239 Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters and emergency medical service workers (EMS) to evaluate the association between work at the WTC site and subsequent peripheral neuropathy symptoms using the validated Diabetic Neuropathy Symptom (DNS) score. We grouped the population into an “Indicated” group with conditions known to be associated with paresthesia (N = 2059) and a “Non-Indicated” group without conditions known to be associated (N = 7180). The level of WTC exposure was categorized by time of arrival to the WTC. Overall, 25% of workers aged 40 and older reported peripheral neuropathy symptoms: 30.6% in the Indicated and 23.8% in the Non-Indicated groups, respectively. Multivariable logistic models performed on the Non-Indicated group, and on the Non-Indicated in comparison with non-WTC exposed National Health and Nutrition Examination Survey (NHANES), found that the highest level of WTC-exposure was significantly associated with DNS positive outcomes, after controlling for potential confounders. In conclusion, this study suggests that symptoms of peripheral neuropathy and paresthesias are common and are associated with WTC-exposure intensity.

Fire Department of New York (FDNY) rescue and recovery workers exposed to World Trade Center (WTC) particulates suffered loss of forced expiratory volume in 1 s (FEV₁). Metabolic Syndrome increased the risk of developing WTC-lung injury (WTC-LI)_. We aim to attenuate the deleterious effects of WTC exposure through a dietary intervention targeting these clinically relevant disease modifiers. We hypothesize that a calorie-restricted Mediterranean dietary intervention will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI. To assess our hypothesis, we developed the Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE), a randomized controlled clinical trial (RCT). Male firefighters with WTC-LI and a BMI > 27 kg/m² will be included. We will randomize subjects (1:1) to either: (1) Low Calorie Mediterranean (LoCalMed)—an integrative multifactorial, technology-supported approach focused on behavioral modification, nutritional education that will include a self-monitored diet with feedback, physical activity recommendations, and social cognitive theory-based group counseling sessions; or (2) Usual Care. Outcomes include reduction in body mass index (BMI) (primary), improvement in FEV₁, fractional exhaled nitric oxide, pulse wave velocity, lipid profiles, targeted metabolic/clinical biomarkers, and quality of life measures (secondary). By implementing a technology-supported LoCalMed diet our FIREHOUSE RCT may help further the treatment of WTC associated pulmonary disease.