Scientific Value of the Sub-Cohort of Children in the World Trade Center Health Registry.

The World Trade Center Health Registry (WTCHR) was established in 2002 as a public health resource to monitor the health effects from the World Trade Center (WTC) disaster. We evaluated the representativeness of the WTC youth population (<18 years on 11 September 2001) by comparing the distributions of age, gender, race/ethnic groups, and income to 2000 census data for the matched geographic area, including distance from disaster. There were 2379 WTCHR enrolled children living in Lower Manhattan south of Canal Street on 11 September 2001, along with 752 enrolled students who attended school in Lower Manhattan but were not area residents. The WTCHR sub-group of children who were residents was similar to the geographically corresponding census population on age and sex. Black and Hispanic children are moderately overrepresented at 0.9% and 2.4% in the WTCHR compared to 0.8% and 1.7% in census population, respectively, while lower-income households are slightly under-represented, 28.8% in the WTCHR and 30.8% for the corresponding census information. Asian children appear underrepresented at 3.0% participation compared to 6.3% in the census. While the demographics of WTCHR youth are somewhat skewed, the gaps are within expected patterns of under-representation observed in other longitudinal cohorts and can be effectively addressed analytically or through targeted study design.

End-stage renal disease incidence in a cohort of US firefighters from San Francisco, Chicago, and Philadelphia.

BACKGROUND: Firefighters perform strenuous work in hot environments, which may increase their risk of chronic kidney disease. The purpose of this study was to evaluate the risk of end-stage renal disease (ESRD) and types of ESRD among a cohort of US firefighters compared to the US general population, and to examine exposure-response relationships. METHODS: ESRD from 1977 through 2014 was identified through linkage with Medicare data. ESRD incidence in the cohort compared to the US population was evaluated using life table analyses. Associations of all ESRD, systemic ESRD, hypertensive ESRD, and diabetic ESRD with exposure surrogates (exposed days, fire runs, and fire hours) were examined in Cox proportional hazards models adjusted for attained age (the time scale), race, birth date, fire department, and employment duration. RESULTS: The incidence of all ESRD was less than expected (standardized incidence ratio (SIR) = 0.79; 95% confidence interval = 0.69-0.89, observed = 247). SIRs for ESRD types were not significantly increased. Positive associations of all ESRD, systemic ESRD, and hypertensive ESRD with exposed days were observed: however, 95% confidence intervals included one. CONCLUSIONS: We found little evidence of increased risk of ESRD among this cohort of firefighters. Limitations included the inability to evaluate exposure-response relationships for some ESRD types due to small observed numbers, the limitations of the surrogates of exposure, and the lack of information on more sensitive outcome measures for potential kidney effects.

The World Trade Center Health Program: Twenty years of health effects research.

It has been 20 years since the devastating terrorist attacks on September 11, 2001. Thousands were injured or killed during the attacks and many more are at risk of adverse health stemming from physical, psychological, and emotional stressors born out of the attacks. Private, federal, state, and local resources were gathered soon after the attacks to address impacts to the community, including the health and well-being of both responders and survivors. Many of these efforts are now largely consolidated under the federally mandated World Trade Center (WTC) Health Program. This program provides medical monitoring and treatment of qualifying conditions among the 9/11-exposed population and supports related physical and mental health research. In this commentary, we describe the WTC Health Program, with emphasis on the health-effects research it has funded since inception in 2011. We describe sentinel research publications, and how science has impacted the program. We provide examples relating studies in this special issue to important roles in the WTC Health Program research agenda. Finally, we provide a perspective on future research needs.

A Workshop on Cognitive Aging and Impairment in the 9/11-Exposed Population.

The terrorist attacks on 11 September 2001 potentially exposed more than 400,000 responders, workers, and residents to psychological and physical stressors, and numerous hazardous pollutants. In 2011, the World Trade Center Health Program (WTCHP) was mandated to monitor and treat persons with 9/11-related adverse health conditions and conduct research on physical and mental health conditions related to the attacks. Emerging evidence suggests that persons exposed to 9/11 may be at increased risk of developing mild cognitive impairment. To investigate further, the WTCHP convened a scientific workshop that examined the natural history of cognitive aging and impairment, biomarkers in the pathway of neurodegenerative diseases, the neuropathological changes associated with hazardous exposures, and the evidence of cognitive decline and impairment in the 9/11-exposed population. Invited participants included scientists actively involved in health-effects research of 9/11-exposed persons and other at-risk populations. Attendees shared relevant research results from their respective programs and discussed several options for enhancements to research and surveillance activities, including the development of a multi-institutional collaborative research network. The goal of this report is to outline the meeting's agenda and provide an overview of the presentation materials and group discussion.

World Trade Center Health Program: First Decade of Research.

The terrorist attacks on 11 September 2001 placed nearly a half million people at increased risk of adverse health. Health effects research began shortly after and continues today, now mostly as a coordinated effort under the federally mandated World Trade Center (WTC) Health Program (WTCHP). Established in 2011, the WTCHP provides medical monitoring and treatment of covered health conditions for responders and survivors and maintains a research program aimed to improve the care and well-being of the affected population. By 2020, funds in excess of USD 127 M had been awarded for health effects research. This review describes research findings and provides an overview of the WTCHP and its future directions. The literature was systematically searched for relevant articles published from 11 September 2001 through 30 June 2020. Synthesis was limited to broad categories of mental health, cancer, respiratory disease, vulnerable populations, and emerging conditions. In total, 944 WTC articles were published, including peer-reviewed articles funded by the WTCHP (n = 291) and other sources. Research has focused on characterizing the burden and etiology of WTC-related health conditions. As the program moves forward, translational research that directly enhances the care of individuals with chronic mental and physical health conditions is needed.

Mortality in a cohort of US firefighters from San Francisco, Chicago and Philadelphia: an update.

OBJECTIVES: To update the mortality experience of a previously studied cohort of 29 992 US urban career firefighters compared with the US general population and examine exposure-response relationships within the cohort. METHODS: Vital status was updated through 2016 adding 7 years of follow-up. Cohort mortality compared with the US population was evaluated via life table analyses. Full risk-sets, matched on attained age, race, birthdate and fire department were created and analysed using the Cox proportional hazards regression to examine exposure-response associations between select mortality outcomes and exposure surrogates (exposed-days, fire-runs and fire-hours). Models were adjusted for a potential bias from healthy worker survivor effects by including a categorical variable for employment duration. RESULTS: Compared with the US population, mortality from all cancers, mesothelioma, non-Hodgkin's lymphoma (NHL) and cancers of the oesophagus, intestine, rectum, lung and kidney were modestly elevated. Positive exposure-response relationships were observed for deaths from lung cancer, leukaemia and chronic obstructive pulmonary disease (COPD). CONCLUSIONS: This update confirms previous findings of excess mortality from all cancers and several site-specific cancers as well as positive exposure-response relations for lung cancer and leukaemia. New findings include excess NHL mortality compared with the general population and a positive exposure-response relationship for COPD. However, there was no evidence of an association between any quantitative exposure measure and NHL.

A study update of mortality in workers at a phosphate fertilizer production facility.

OBJECTIVE: To evaluate the mortality experience among 3,199 workers employed 1951-1976 at a phosphate fertilizer production plant in central Florida with follow-up through 2011. METHODS: Cause-specific standardized mortality ratios (SMRs) for the full cohort were calculated with the U.S. population as referent. Lung cancer and leukemia risks were further analyzed using conditional logistic regression. RESULTS: The mortality due to all-causes (SMR = 1.07, 95% confidence interval [CI] 1.02-1.13, observed deaths [n] = 1,473), all-cancers (SMR = 1.16, 95%CI 1.06-1.28, n = 431), and a priori outcomes of interests including lung cancer (SMR = 1.32, 95%CI = 1.13-1.53, n = 168) and leukemia (SMR = 1.74, 95%CI = 1.11-2.62, n = 23) were statistically significantly elevated. Regression modeling on employment duration or estimated radiation scores did not show exposure-response relation with lung cancer or leukemia mortality. CONCLUSION: SMR results showed increased lung cancer and leukemia mortality in a full cohort of the phosphate fertilizer production facility. There was, however, no exposure-response relation observed among cases and matched controls.

Exposure-response relationships for select cancer and non-cancer health outcomes in a cohort of U.S. firefighters from San Francisco, Chicago and Philadelphia (1950-2009).

OBJECTIVES: To examine exposure-response relationships between surrogates of firefighting exposure and select outcomes among previously studied US career firefighters. METHODS: Eight cancer and four non-cancer outcomes were examined using conditional logistic regression. Incidence density sampling was used to match each case to 200 controls on attained age. Days accrued in firefighting assignments (exposed-days), run totals (fire-runs) and run times (fire-hours) were used as exposure surrogates. HRs comparing 75th and 25th centiles of lagged cumulative exposures were calculated using loglinear, linear, log-quadratic, power and restricted cubic spline general relative risk models. Piecewise constant models were used to examine risk differences by time since exposure, age at exposure and calendar period. RESULTS: Among 19,309 male firefighters eligible for the study, there were 1333 cancer deaths and 2609 cancer incidence cases. Significant positive associations between fire-hours and lung cancer mortality and incidence were evident. A similar relation between leukaemia mortality and fire-runs was also found. The lung cancer associations were nearly linear in cumulative exposure, while the association with leukaemia mortality was attenuated at higher exposure levels and greater for recent exposures. Significant negative associations were evident for the exposure surrogates and colorectal and prostate cancers, suggesting a healthy worker survivor effect possibly enhanced by medical screening. CONCLUSIONS: Lung cancer and leukaemia mortality risks were modestly increasing with firefighter exposures. These findings add to evidence of a causal association between firefighting and cancer. Nevertheless, small effects merit cautious interpretation. We plan to continue to follow the occurrence of disease and injury in this cohort.

Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950-2009).

OBJECTIVES: To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009. METHODS: Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias. RESULTS: Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques. CONCLUSIONS: Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.

A cohort mortality study of chemical laboratory workers at Department of Energy Nuclear Plants.

OBJECTIVE: This study evaluates the mortality experience of 6,157 chemical laboratory workers employed at United States Department of Energy facilities. METHODS: All cause, all cancer and cause-specific standardized mortality ratios were calculated. Cox regression analyses were conducted to further evaluate the relation between chemical exposure and mortality risk due to selected cancers. RESULTS: The mortality due to all causes combined and all cancers combined were below expectation for the cohort. There were no statistically significant elevations reported among males for any specific cancer or non-cancer outcome. There no statistically significant elevations among females for any specific non-cancer and most specific cancers; however, multiple myeloma deaths were significantly elevated (SMR = 3.56; 95% CI = 1.43-7.33; number of observed deaths, n = 7). Statistically significant elevations were seen among workers employed 20+ years for leukemia using both 2- and 5-year lag periods. Also, a statistically significant positive trend of elevated lung cancer mortality with increasing employment duration was seen using both 5- and 10-year lags. A similar trend was seen for smoking related cancers among men. CONCLUSION: While lymphatic and hematopoietic cancer mortality was below expectation, a significant elevation of multiple myeloma deaths among females and an elevation of leukemia among workers employed 20+ years (possibly due to radiation and benzene exposure) were observed. A NIOSH case-control study is underway to examine more closely the relation between multiple myeloma and a variety of chemical exposures among workers employed at the Oak Ridge K-25 facility.

A nested case-control study of lung cancer risk and ionizing radiation exposure at the portsmouth naval shipyard.

Results have been inconsistent between studies of lung cancer risk and ionizing radiation exposures among workers at the Portsmouth Naval Shipyard (PNS). The purpose of this nested case-control study was to evaluate the relationship between lung cancer risk and external ionizing radiation exposure while adjusting for potential confounders that included gender, radiation monitoring status, smoking habit surrogates (socioeconomic status and birth cohort), welding fumes and asbestos. By incidence density sampling, we age-matched 3,291 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992 with 1,097 lung cancer deaths from among the same cohort. Analyses using conditional logistic regression were conducted in various model forms: log-linear (main), linear excess relative risk (ERR), and categorical. Lung cancer risk was positively associated with occupational dose (OR = 1.02 at 10 mSv; 95% CI 0.99- 1.04) but flattened after the inclusion of work-related medical X-ray doses (OR = 1.00; 95% CI 0.98-1.03) in multivariate analyses. Similar risk estimates were observed in the linear ERR model at 10 mSv of cumulative exposure with a 15-year lag.

A nested case-control study of leukemia mortality and ionizing radiation at the Portsmouth Naval Shipyard.

A nested case-control study using conditional logistic regression was conducted to evaluate the exposure-response relationship between external ionizing radiation exposure and leukemia mortality among civilian workers at the Portsmouth Naval Shipyard (PNS), Kittery, Maine. The PNS civilian workers received occupational radiation exposure while performing construction, overhaul, repair and refueling activities on nuclear-powered submarines. The study age-matched 115 leukemia deaths with 460 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992. In addition to radiation doses received in the workplace, a secondary analysis incorporating doses from work-related medical X rays and other occupational radiation exposures was conducted. A significant positive association was found between leukemia mortality and external radiation exposure, adjusting for gender, radiation worker status, and solvent exposure duration (OR = 1.08 at 10 mSv of exposure; 95% CI = 1.01, 1.16). Solvent exposure (including benzene and carbon tetrachloride) was also significantly associated with leukemia mortality adjusting for radiation dose, radiation worker status, and gender. Incorporating doses from work-related medical X rays did not change the estimated leukemia risk per unit of dose.

Risk of lung cancer and leukemia from exposure to ionizing radiation and potential confounders among workers at the Portsmouth Naval Shipyard.

Significantly elevated lung cancer deaths and statistically significantly positive linear trends between leukemia mortality and radiation exposure were reported in a previous analysis of Portsmouth Naval Shipyard workers. The purpose of this study was to conduct a modeling-based analysis that incorporates previously unanalyzed confounders in exploring the exposure-response relationship between cumulative external ionizing radiation exposure and mortality from these cancers among radiation-monitored workers in this cohort. The main analyses were carried out with Poisson regression fitted with maximum likelihood in linear excess relative risk models. Sensitivity analyses varying model components and using other regression models were conducted. The positive association between lung cancer risk and ionizing radiation observed previously was no longer present after adjusting for socioeconomic status (smoking surrogate) and welding fume and asbestos exposures. Excesses of leukemia were found to be positively, though not significantly, associated with external ionizing radiation, with or without including potential confounders. The estimated excess relative risk was 10.88% (95% CI -0.90%, 38.77%) per 10 mSv of radiation exposure, which was within the ranges of risk estimates in previous epidemiological studies (-4.1 to 19.0%). These results are limited by many factors and are subject to uncertainties of the exposure and confounder estimates.

Radiation exposure from work-related medical X-rays at the Portsmouth Naval Shipyard.

BACKGROUND: Previous analyses suggest that worker radiation dose may be significantly increased by routine occupational X-ray examinations. Medical exposures are investigated for 570 civilian workers employed at the Portsmouth Naval Shipyard (PNS) at Kittery, Maine. The research objective was to determine the radiation exposure contribution of work-related chest X-rays (WRX) relative to conventional workplace radiation sources. METHODS: Methods were developed to estimate absorbed doses to the active (hematopoietic) bone marrow from X-ray examinations and workplace exposures using data extracted from worker dosimetry records (8,468) and health records (2,453). Dose distributions were examined for radiation and non-radiation workers. RESULTS: Photofluorographic chest examinations resulted in 82% of the dose from medical sources. Radiation workers received 26% of their collective dose from WRX and received 66% more WRX exposure than non-radiation workers. CONCLUSIONS: WRX can result in a significant fraction of the total dose, especially for radiation workers who were more likely to be subjected to routine medical monitoring. Omission of WRX from the total dose is a likely source of bias that can lead to dose category misclassification and may skew the epidemiologic dose-response assessment for cancers induced by the workplace.

Differences in mortality by radiation monitoring status in an expanded cohort of Portsmouth Naval Shipyard workers.

Studies of leukemia and lung cancer mortality at the Portsmouth Naval Shipyard (PNS) have yielded conflicting results. In an expanded cohort of PNS workers employed between 1952 and 1992 and followed through 1996, the all-cause standardized mortality ratio (SMR) was 0.95 (95% confidence interval, 0.93-0.96). Employment duration SMRs were elevated with confidence intervals excluding 1.00 for lung cancer, esophageal cancer, and all cancers combined. Leukemia mortality was as expected overall, but standardized rate ratio analyses showed a significant positive linear trend with increasing external radiation dose. The role of solvent exposures could not be evaluated. Findings differed by radiation monitoring subcohort, with excess asbestosis deaths limited to radiation workers and several smoking-related causes of death higher among nonmonitored workers. At PNS, asbestos exposure and possibly smoking could be nonrandomly distributed with respect to radiation exposure, suggesting potential for confounding in internal analyses of an occupational cohort.