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.

Three cohorts including the Fire Department of the City of New York (FDNY), the World Trade Center Health Registry (WTCHR), and the General Responder Cohort (GRC), each funded by the World Trade Center Health Program have reported associations between WTC-exposures and cancer. Results have generally been consistent with effect estimates for excess incidence for all cancers ranging from 6 to 14% above background rates. Pooling would increase sample size and de-duplicate cases between the cohorts. However, pooling required time consuming steps: obtaining Institutional Review Board (IRB) approvals and legal agreements from entities involved; establishing an honest broker for managing the data; de-duplicating the pooled cohort files; applying to State Cancer Registries (SCRs) for matched cancer cases; and finalizing analysis data files. Obtaining SCR data use agreements ranged from 6.5 to 114.5 weeks with six states requiring >20 weeks. Records from FDNY (n = 16,221), WTCHR (n = 29,372), and GRC (n = 33,427) were combined de-duplicated resulting in 69,102 unique individuals. Overall, 7894 cancer tumors were matched to the pooled cohort, increasing the number cancers by as much as 58% compared to previous analyses. Pooling resulted in a coherent resource for future research for studies on rare cancers and mortality, with more representative of occupations and WTC- exposure.

Objective: In occupational hearing conservation programmes, age adjustments may be used to subtract expected age effects. Adjustments used in the U.S. came from a small dataset and overlooked important demographic factors, ages, and stimulus frequencies. The present study derived a set of population-based age adjustment tables and validated them using a database of exposed workers. Design: Cross-sectional population-based study and retrospective longitudinal cohort study for validation. Study sample: Data from the U.S. National Health and Nutrition Examination Survey (unweighted n = 9937) were used to produce these tables. Male firefighters and emergency medical service workers (76,195 audiograms) were used for validation. Results: Cross-sectional trends implied less change with age than assumed in current U.S. regulations. Different trends were observed among people identifying with non-Hispanic Black race/ethnicity. Four age adjustment tables (age range: 18–85) were developed (women or men; non-Hispanic Black or other race/ethnicity). Validation outcomes showed that the population-based tables matched median longitudinal changes in hearing sensitivity well. Conclusions: These population-based tables provide a suitable replacement for those implemented in current U.S. regulations. These tables address a broader range of worker ages, account for differences in hearing sensitivity across race/ethnicity categories, and have been validated for men using longitudinal data.

Rationale: Low FEV1 is a biomarker of increased mortality. The association of normal lung function and mortality is not well described. Objectives: To evaluate the FEV1–mortality association among participants with normal lung function. Methods: A total of 10,999 Fire Department of the City of New York (FDNY) responders and 10,901 Third National Health and Nutrition Examination Survey (NHANES III) participants, aged 18–65 years with FEV1 ≥80% predicted, were analyzed, with FEV1 percent predicted calculated using Global Lung Function Initiative Global race-neutral reference equations. Mortality data were obtained from linkages to the National Death Index. Cox proportional hazards models estimated the association between FEV1 and all-cause mortality, controlling for age, sex, race/ethnicity, smoking history, and, for FDNY, work assignment. Cohorts were followed for a maximum of 20.3 years. Measurements and Main Results: We observed 504 deaths (4.6%) of 10,999 for FDNY and 1,237 deaths (9.4% [weighted]) of 10,901 for NHANES III. Relative to FEV1 ≥120% predicted, mortality was significantly higher for FEV1 100–109%, 90–99%, and 80–89% predicted in the FDNY cohort. In the NHANES III cohort, mortality was significantly higher for FEV1 90–99% and 80–89% predicted. Each 10% higher predicted FEV1 was associated with 15% (hazard ratio, 0.85; 95% confidence interval, 0.80–0.91) and 23% (hazard ratio, 0.77; 95% confidence interval, 0.71–0.84) lower mortality for FDNY and NHANES III, respectively. Conclusions: In both cohorts, higher FEV1 is associated with lower mortality, suggesting higher FEV1 is a biomarker of better health. These findings demonstrate that a single cross-sectional measurement of FEV1 is predictive of mortality over two decades, even when FEV1 is in the normal range.

Background: World Trade Center (WTC)‐exposed responders may be eligible to receive no‐cost medical monitoring and treatment for certified conditions, including cancer. The survival of responders with cancer has not previously been investigated.Methods: This study compared the estimated relative survival of WTC‐exposed responders who developed cancer while enrolled in two WTC medical monitoring and treatment programs in New York City (WTC‐MMTP responders) and WTC‐exposed responders not enrolled (WTC‐non‐MMTP responders) to non‐responders from New York State (NYS‐non‐responders), all restricted to the 11‐southernmost NYS counties, where most responders resided. Parametric survival models estimated cancer‐specific and all‐cause mortality. Follow‐up ended at death or on December 31, 2016.Results: From January 1, 2005 to December 31, 2016, there were 2,037 cancer cases and 303 deaths (248 cancer‐related deaths) among WTC‐MMTP responders, 564 cancer cases, and 143 deaths (106 cancer‐related deaths) among WTC‐non‐MMTP responders, and 574,075 cancer cases and 224,040 deaths (158,645 cancer‐related deaths) among the NYS‐non‐responder population. Comparing WTC‐MMTP responders with NYS‐non‐responders, the cancer‐specific mortality hazard ratio (HR) was 0.72 (95% confidence interval [CI] = 0.64–0.82), and all‐cause mortality HR was 0.64 (95% CI = 0.58–0.72). The cancer‐specific HR was 0.94 (95% CI = 0.78–1.14), and all‐cause mortality HR was 0.93 (95% CI = 0.79–1.10) comparing WTC‐non‐MMTP responders to the NYS‐non‐responder population.Conclusions: WTC‐MMTP responders had lower mortality compared with NYS‐non‐responders, after controlling for demographic factors and temporal trends. There may be survival benefits from no‐out‐of‐pocket‐cost medical care which could have important implications for healthcare policy, however, other occupational and socioeconomic factors could have contributed to some of the observed survival advantage.

Objective To compare mortality rates in World Trade Center (WTC)-exposed Fire Department of the City of New York (FDNY) firefighters with rates in similarly healthy, non-WTC-exposed/non-FDNY firefighters, and compare mortality in each firefighter cohort with the general population. Methods 10 786 male WTC-exposed FDNY firefighters and 8813 male non-WTC-exposed firefighters from other urban fire departments who were employed on 11 September 2001 were included in the analyses. Only WTC-exposed firefighters received health monitoring via the WTC Health Programme (WTCHP). Follow-up began 11 September 2001 and ended at the earlier of death date or 31 December 2016. Death data were obtained from the National Death Index and demographics from the fire departments. We estimated standardised mortality ratios (SMRs) in each firefighter cohort versus US males using demographic-specific US mortality rates. Poisson regression models estimated relative rates (RRs) of all-cause and cause-specific mortality in WTC-exposed versus non-WTC-exposed firefighters, controlling for age and race. Results Between 11 September 2001 and 31 December 2016, there were 261 deaths among WTC-exposed firefighters and 605 among non-WTC-exposed. Both cohorts had reduced all-cause mortality compared with US males (SMR (95% CI)=0.30 (0.26 to 0.34) and 0.60 (0.55 to 0.65) in WTC-exposed and non-WTC-exposed, respectively). WTC-exposed firefighters also had lower rates of all-cause mortality (RR=0.54, 95% CI=0.49 to 0.59) and cancer-specific, cardiovascular-specific and respiratory disease-specific mortality compared with non-WTC-exposed firefighters. Conclusion Both firefighter cohorts had lower than expected all-cause mortality. Fifteen years post 11 September 2001, mortality was lower in WTC-exposed versus non-WTC-exposed firefighters. Lower mortality in the WTC-exposed suggests not just a healthy worker effect, but additional factors such as greater access to free health monitoring and treatment that they receive via the WTCHP.