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.

Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Summary Bias Assessment and Meta-Analysis.

BACKGROUND: Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases. METHODS: Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006-2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia. RESULTS: Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers. CONCLUSIONS: Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.

Occupational asthma risk from exposures to toluene diisocyanate: A review and risk assessment.

BACKGROUND: Toluene Diisocyanate (TDI) is a known respiratory sensitizer linked to occupational asthma (OA). To better manage worker risks, an appropriate characterization of the TDI-OA dose-risk relationship is needed. METHODS: The literature was reviewed for data suitable for dose-response modeling. Previous study data were fit to models to derive prospective occupational exposure limits (OELs), using benchmark dose (BMD) and low-dose extrapolation approaches. RESULTS: Data on eight TDI-exposed populations were suitable for analysis. There were 118 OA cases in a population contributing 13 590 person-years. The BMD-based OEL was 0.4 ppb. The OEL based on low-dose extrapolation to working lifetime extra risk of 1/1000 was 0.3 ppb. CONCLUSIONS: This study synthesized epidemiologic data to characterize the TDI-OA dose-risk relationship. This approach yielded prospective OEL estimates below recent recommendations by the American Conference of Governmental Industrial Hygienists, but given significant study limitations, this should be interpreted with caution. Confirmatory research is needed.

Site-specific Solid Cancer Mortality After Exposure to Ionizing Radiation: A Cohort Study of Workers (INWORKS).

BACKGROUND: There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS: Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation-mortality associations were estimated using a maximum-likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS: The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS: The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

Exposure assessment for a cohort of workers at a former uranium processing facility.

Exposure was assessed for a cohort of 6409 workers at a former uranium processing facility as part of a mortality study. Workers at the facility had potential for exposure to a wide variety of radiological and chemical agents including uranium, thorium, radon, external ionizing radiation, acid mists, asbestos, and various solvents. Organ dose from internal exposure to uranium was assessed, along with dose from external ionizing radiation and exposure to radon. Qualitative assessment of exposure to thorium, acid mists, asbestos, coal dust, welding fumes, and other chemicals was also performed. Mean cumulative organ dose from internal uranium exposure ranged from 1.1 mGy (lung) to 6.7 µGy (pancreas). Mean cumulative external ionizing radiation dose was 13.4 mGy. Mean cumulative radon exposure was 26 working level months (WLMs). The chemical agents to which the largest numbers of study subjects were exposed were acid mists, machining fluids, and a tributyl phosphate/kerosene mixture used in the refining process.

Population monitoring for acute exposure to 210Po.

OBJECTIVE: To investigate the feasibility of using single void urine samples to monitor internal radiation exposure of first responders and large populations int he event of a radiological incident involving the intentional dispersal of 210Po. METHODS: Urinary excretion of 210Po was evaluated and organ absorbed and effective doses were calculated subsequent to an acute unit intake of 210Po. RESULTS: 210Po can be detected in single void urine samples at levels sufficient to detect effective dose below recommended limits. Minimum intakes of 210Po that would result in clinically significant effects were estimated. CONCLUSIONS: Collection and analysis of single void urine samples is adequate to identify persons who may be exposed in the event of a radiological emergency involving 210Po. Also, the first responder limit appears to be sufficiently protective to prevent clinically significant deterministic effects.