1448

Background: Exposure to ionizing radiation, even at low-to-moderate doses, increases the risk of circulatory disease (CD) incidence and mortality. The risk of CD is also influenced by an individual’s social environment, and this may modify the effect of occupational exposures like ionizing radiation. Aim: We examined the effect of neighborhood socioeconomic status (nSES) on incidence and mortality from overall CD, ischemic heart disease (IHD) and cerebrovascular disease (CeVD) in the US Radiologic Technologists Study (USRT) between 1994 and 2012. Additionally, we assessed whether nSES confounds and/or modifies the association between occupational radiation exposure and CD outcomes. Methods: Cumulative radiation dose (mGy) was estimated for each participant. We created tertiles of nSES combining six items from the 1990 Census (household income, housing value, % households with interest/income, % adults who completed high school, % adults who completed college, % of persons in managerial occupations). Using discrete time hazard models, we estimated HR and 95%CI for the association between radiation, nSES and CD outcomes. Results: Compared to residents from the top nSES tertile, technologists from low-nSES areas had an elevated risk of overall CD mortality, IHD mortality and incidence, and CeVD incidence (HRs ranging from 1.18 to 1.25, 95%CIs:1.07-1.42), but not for CeVD mortality (HR: 0.92, 95%CI: 0.75-1.15) adjusting for radiation and individual education. We found no evidence of confounding by nSES on the association between radiation and any CD outcomes. There was evidence of a multiplicative interaction between nSES tertiles and radiation exposure for all mortality outcomes (p-value for interaction: <0.001 for overall CD, 0.003 for IHD and 0.004 for CeVD), but not for incidence. Conclusion: nSES is independently associated with CD mortality and incidence in a group of US radiologic technologists occupationally exposed to radiation. Additionally, nSES modifies (but does not confound) the association between radiation and CD mortality outcomes.

1355

Aim: The Pooled Uranium Miners Analysis (PUMA) is the largest pooled study of uranium miners to date. Here we report initial observations on temporal patterns of variation in the association between cumulative exposure to radon decay products and lung cancer mortality in this large multinational pooled study. Methods: PUMA combines cohorts of uranium miners from Canada, the Czech Republic, France, Germany, and the United States. PUMA includes approximately 120,000 males followed for lung cancer deaths between 1946 and 2014. Associations between occupational radon progeny exposure and lung cancer mortality were estimated using internal Poisson regression with background stratification by cohort, attained age, calendar period, and race. This analysis focuses on windows of age at exposure and time since exposure modeled simultaneously and separately as modifiers. Results: In this study with 7,774 lung cancer deaths and 4.4 million person-years, there was statistically significant evidence of a positive association between cumulative exposure to radon decay products, under a 5-year lag assumption, and lung cancer mortality. There was statistically significant evidence of variation by age at exposure in the association between cumulative exposure to radon decay products, under a 5-year lag assumption, and lung cancer mortality. There also was statistically significant evidence of variation in the association between cumulative exposure to radon decay products and lung cancer mortality with time since exposure; the estimated excess relative rate (ERR) per working level month (WLM) tended to diminish across windows defined by increasing time since exposure; however, estimated ERR per WLM remained above the null even 35+ years after exposure. Conclusion: Preliminary analyses yield estimates with substantial statistical precision of the radon-lung cancer association and its variation with age at exposure and time since exposure. Further analyses will investigate additional effect modification by exposure rate and heterogeneity between individual studies.

2222

Inorganic arsenic (iAs) is a ubiquitous metalloid, carcinogen, and reproductive toxicant commonly found in drinking water at levels exceeding the World Health Organization’s (WHO) recommended limit of 10 ppb. Upon ingestion, iAs is biotransformed to monomethylated (MMA) and dimethylated (DMA) arsenic through the addition of methyl groups. As a methyl-donor nutrient, folate contributes to the methylation process, and folic acid supplementation among adults exposed to iAs has been shown to improve methylation efficiency. Since maternal iAs exposure has been linked to adverse birth outcomes, we sought to evaluate whether serum folate concentrations modified the relationship between maternal iAs exposure and various birth outcomes in a cross-sectional cohort of 193 women residing in Gómez Palacio, State of Durango, Mexico between 2011 and 2012. Folate intake was measured in maternal serum, and indicators of arsenic exposure were evaluated in drinking water and maternal urine samples. In evaluating effect modification by folate, likelihood ratio tests were implemented to evaluate the goodness-of-fit of interaction models as compared to main effects models. The prevalence of folate deficiency, defined as < 9 nM, was minimal, still effect modification by folate was significant (p < 0.1) on the additive scale for associations between several indicators of maternal iAs exposures and birth outcomes, namely birth weight and head circumference. In many cases, increased serum folate concentrations attenuated or changed the direction of associations. This cross-sectional study suggests that higher serum folate concentrations attenuate the negative association between maternal iAs exposure and anthropometric measures at birth.

3206

Background/Aim: Cadmium exposure is widespread, accumulates in the body, triggers pulmonary inflammation, is associated with decrements in respiratory function, and has been shown to enhance lung injury by respiratory syncytial virus. Our aim was to examine the association of cadmium burden with influenza-related mortality in U.S. adults. Methods: This prospective cohort study of the National Health and Nutrition Examination Survey (NHANES) included 7179 and 8682 participants aged 45 years and older enrolled from NHANES-3 and NHANES 1999-2006, respectively. Associations were evaluated between urinary and blood concentrations of cadmium and mortality from influenza and pneumonia during a median follow-up of 17.3 years (NHANES-3) and 11.4 years (NHANES 1999-2006). Survey-weighted Cox proportional hazard models were used to compute hazard ratios (HRs) comparing the mortality experience of individuals at the 80^th v. the 20^th percentile of the distribution of cadmium biomarker levels. Results: In NHANES-3 (141 deaths from influenza/pneumonia, incidence rate=1.24 per 1000 person-years), creatinine-corrected cadmium was associated with a hazard ratio (HR) of 1.16 (95% CI, 1.07-1.26; P=0.0004) after adjustment for age, sex, race/ethnicity, education, body mass index, serum cholesterol, and hypertension. The HR was 1.23 (95% CI, 1.07-1.43; P=0.005) when the analysis was restricted to never smokers. In NHANES 1999-2006 (56 deaths from influenza/pneumonia, incidence rate=0.59 per 1000 person-years), blood cadmium was associated with an adjusted HR of 1.16 (95% CI, 0.98-1.37; P=0.08); and 1.69 (95% CI, 0.97-2.97; P=0.07) in never smokers. The pooled HRs combining both datasets were 1.16 (95% CI, 1.08-1.25); and 1.26 (95% CI, 1.09-1.45) in never smokers. Conclusions and Relevance: Higher cadmium burden is associated with higher mortality from influenza/ pneumonia among middle-aged and older adults in the US general population. Higher cadmium burdens may also worsen outcomes from COVID-19 infections.

1707

Background. Cities around the world are taking action to limit greenhouse gas emissions through ambitious climate targets and climate action plans. These strategies are likely to simultaneously improve local air quality, leading to public health and monetary co-benefits. We quantify and value the health impacts of eliminating emissions from the City of Boston, and in doing so, highlight the importance of considering health impacts alongside environmental impacts of local climate action.
Methods. We simulated at a 4km resolution how the elimination of anthropogenic emissions from the City of Boston would impact air quality within a 120km by 120km study domain. We then estimate how this change in air quality would impact a number of annual health outcomes and the associated monetary savings.
Results. We found that eliminating anthropogenic emissions from Boston would result in a decline in PM2.5 concentration across the entire study region ranging from 8.5 ug/m3 in Boston to less than 1 ug/m3 elsewhere in the domain. In addition, we estimate that summer ozone would increase for the Greater Boston Area and areas west, and decrease elsewhere. The monetary impact of the change in air quality on health is estimated to be a $2.4 billion per year savings across the full domain and $1.7 billion within Suffolk County only, about 1.4% of the gross domestic product of the county. These monetary impacts are driven primarily by reduced incidence of mortality. We estimate that 288 deaths would be avoided per year across the study domain, about six deaths avoided, annually, per 100,000 people. Within Suffolk County, we estimate that 47 deaths would be avoided per 100,000 people, around 16% of all-cause premature mortality. We also find a net decrease in cardiovascular and respiratory illness. Across the study domain, these health benefits would be disproportionately conferred upon people of color.

2487

BackgroundThe association between air pollution and mortality requires further investigation in areas with low air pollution levels for evaluation of current air quality limits. Within the Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) study we examined associations between long-term exposure to air pollution and cause-specific mortality in a Danish national administrative cohort.
MethodsWe linked 3,334,143 Danish adults aged ≥30 years in 2000 to the Danish Cause of Death Registry until 2015. Annual mean concentrations of fine particulate matter (PM_2.5), nitrogen dioxide (NO₂) and black carbon (BC) were centrally modelled with European-wide hybrid ELAPSE land-use regression model in 2010 at 100m² resolution. We applied Cox proportional hazard models for natural and cause-specific mortality in association with annual mean air pollution with age as underlying time, and adjusting for sex, education, employment status, birth country, area-level income and unemployment, and area-level lung cancer and COPD mortality rates.
ResultsDuring 45,932,793 person-years of follow-up, we observed 817,029 deaths from natural causes in total, of which 245,489, 89,909, and 67,389 deaths were due to cardiovascular disease (CVD), respiratory disease (RD), and cerebrovascular disease (CeVD), respectively. Mean levels of PM_2.5, NO₂ and BC were 12.4 µg/m³, 20.2 µg/m³ and 1,0 10^-5m^-1, respectively. Hazard ratios and 95% confidence intervals for associations of PM_2.5, NO₂ and BC with natural mortality were 1.13 (1.11-1.16) per 5 µg/m³, 1.09 (1.08-1.10) per 10 µg/m³, and 1.08 (1.07-1.10) per 0.5 10^-5m^-1, respectively. Corresponding estimates for CVD mortality were 1.11 (1.08-1.15), 1.07 (1.06-1.09) and 1.07 (1.05-1.08); for RD mortality were 1.13 (1.09-1.18), 1.12 (1.10-1.15) and 1.10 (1.08-1.13); and for CeVD mortality were 1.07 (1.02-1.11), 1.04 (1.02-1.07) and 1.04 (1.02-1.06). Associations persisted below PM_2.5 and NO₂ EU limit values for all outcomes.
ConclusionsLong-term exposures to PM_2.5, NO₂ and BC were associated with mortality even below EU limit values.

2037

Background: Childhood exposure to particulate matter < 2.5 micrometer (PM_2.5) or nitrogen oxides (NOx) is an established risk factor for the development of asthma. However, associations of these exposures with other atopic diseases and factors that modify these associations are less clear. We aim to study associations between exposure to PM and NOx and the prevalence of asthma and atopic manifestations at age 17 in Israel.
Methods: The study population comprised of all Israeli born adolescents aged 17 at medical evaluation for mandatory army service between 1967 and 2017 (N = 2,523,745, of whom 5.9% had prevalent asthma). Average birth to age 17 exposure assessments were based on a land use regression model for NOx at 500 m resolution, and a hybrid satellite-based model for PM at 1 km resolution. Associations were calculated from logistic regression models adjusted for year of birth and census socio-economic status (SES).
Results: Exposure to either PM_2.5 or NOx from birth to age 17 was associated with prevalent asthma in a dose-response manner, with an odds ratio for 5^th quintile of each exposure of 1.49 (95% CI: 1.45-1.54) and 1.61 (1.56-1.67), respectively, in comparison to the lowest exposure quintile. Associations for both pollutants were stronger in males and much stronger in lower socio-economic strata. Associations of PM_2.5 and NOx were also found with prevalent rhinitis, conjunctivitis and dermatitis. Strongest associations were seen for asthma with comorbid rhinitis, with an almost two-fold increased odds of upper versus lower quintile of exposure for either PM_2.5 (OR = 1.9, 1.81-2.0) or NOx (OR = 1.96, 1.82-2.11).
Conclusions: Early life exposure to air pollution is associated with asthma and atopic disease in a dose-dependent manner. The association is stronger in lower SES, providing important evidence for improving health disparities.

2808

Background: Although inorganic arsenic in drinking water at high levels (100s–1000s ug/L [ppb]) increases cancer risk (skin, bladder, lung, and possibly prostate), the evidence at lower levels is limited.
Methods: We conducted an ecologic analysis of the dose-response relationship between prostate cancer incidence and low arsenic levels in drinking water in a large study of U.S. counties (N = 710). County arsenic levels were < 200 ug/L with median < 100 ug/L and dependency greater than 10%. Groundwater well usage, water arsenic levels, prostate cancer incidence rates (2009–2013), and co-variate data were obtained from various U.S. governmental agencies. Poisson and negative-binomial regression analyses and stratified analysis were performed.
Results: The best fitting polynomial analysis yielded a J-shaped linear-quadratic model. Linear and quadratic terms were significant (p < 0.001) in the Poisson model, and the quadratic term was significant (p < 0.05) in the negative binomial model. This model indicated a decreasing risk of prostate cancer with increasing arsenic level in the low range and increasing risk above.
Conclusions: This study of prostate cancer incidence in US counties with low levels of arsenic in their well-water arsenic levels finds a j-shaped model with decreasing risk at very low levels and increasing risk at higher levels.

2005

Objective: To investigate potential effects of short- and medium-term exposure to low levels of ozone (O3) on glucose-homeostasis in non-diabetic older adults. Methods: 166 non-diabetic, older participants in Beijing were deemed eligible to partake in this longitudinal population-based study. Observations were recorded on three separate occasions from November 2016 up until January 2018. Concentrations of outdoor O3 were monitored throughout the study period. Biomarkers indicative of glucose-homeostasis, including fasting blood glucose, insulin, hemoglobin A1c (HbAlc), glycated albumin percentage, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Homeostatic Model Assessment of Beta cell function (HOMA-B) were measured at 3 sessions. A linear mixed effects model with random effects was adopted to quantify the effect of O3 across a comprehensive set of glucose-homeostasis markers. Results: short-term O3 exposure positively associated with increased fasting blood glucose, insulin, HOMA-IR and HOMA-B. The effect on glucose occurred at 3-, 5-, 6- and 7-days, although the largest effect manifested on 6-days (5.6%, 95%CI: 1.4, 9.9). Significant associations with both insulin and HOMA-IR were observed on the 3- and 4-days, although the largest effect consistently occured on 4-days with estimations of 90.0% (95%CI: 19.0, 203.4) and 96.5% (95%CI: 14.9, 235.9), respectively. For HOMA-B, positive associations were identified from 3- to 7-days with estimates ranging from 40.0% (95%CI: 2.3, 91.5) to 83.1% (95%CI: 25.3, 167.5). Stratification suggests that women may be more susceptible to short-term O3 exposure with positive associations observed at 1-, 2-, 5-, 6-, and 7-days in both insulin and HOMA-IR. Conclusions: In this study, we found that O3 exposure is at least partially related to the onset of type II diabetes in older adults with no prior history of this condition. O3 therefore acts as a kind of catalyst for metabolic disorders, which is a particular concern when we consider the rise in global concentrations.

1545

Background Carbon monoxide (CO) is a colorless, odorless, nonirritating gas that is produced through the incomplete combustion of carbon-containing substances. CO poisoning is a leading cause of unintentional poisoning deaths in the United States. The Centers for Disease Control and Prevention (CDC) routinely collects surveillance data from different sources to better understand unintentional CO exposures and identify potential environmental risk factors. Methods We used four different data sources to track unintentional CO-related exposures and CO poisoning: exposures called to poison control centers (PCCs), emergency department (ED) visits, hospitalizations, and mortality for 2005-2016. We conducted descriptive analyses by cause (fire, non-fire, unknown), month, age, region, and medical outcome (no effect, minor effect, moderate effect, major effect, and death). Results Over the 12-year study period, we observed 141,762 PCCS calls (national), 92,390 ED visits (16 states), 14,816 hospitalizations (25 states), and 12,478 deaths (national) due to unintentional CO poisoning. Non-fire unintentional cases comprised more than 70% of all hospitalizations and ED visits and 48% of all deaths compared to other unintentional cases. Across all data sources, CO exposures and poisonings were most commonly reported in January and December. Adults aged 50-59 years were the highest proportions for hospitalizations (19.7%) and deaths (17.0%). For PCC data, CO exposures were most frequently reported among children aged 0-9 years (21.1%) and in Northeastern states (>70 per 100,000 population). Medical outcomes were most often reported as none or minor effect (n=146,067, 72.2%) in PCC data. Conclusions This surveillance report provides the most comprehensive review of unintentional CO poisonings in the US. Unintentional CO poisoning remains a public health concern. More standardized and continued public health surveillance of unintentional CO poisoning will be necessary to monitor the public health burden, identify novel exposure pathways, and assess the effectiveness of targeted prevention strategies.

2315

Background: Exposure to ionizing radiation has been associated with hypertension outside pregnancy, but the association between residential radon and pregnancy-induced hypertensive (PIH) disorders has not been evaluated. Methods: We used the Massachusetts Birth Registry of Vital Records from 2001-2015 to study women with a singleton pregnancy without prior hypertension. The PIH disorders status was obtained from the birth certificates as a binary variable. Median zip code level measurements were used to estimate radon exposure at the lowest livable level of each place under closed-house conditions. We used a mixed-effects model adjusted for sociodemographic covariates, maternal comorbidities, PM_2.5, temperature, and relative humidity. We examined effect modification by maternal age in two categories at the cutoff of 35 years. Results: Of 990,364 women, 3.7% (37,027) of them developed gestational hypertension. Median zip code level ranged from 0.1 to 19.9 pCi/L. An interquartile range (IQR) increase in median zip code radon level throughout pregnancy was associated with a 3% increase in the odds of PIH disorders (95% CI 2% to 5%) in the full cohort. In women less than 35 years old, an IQR increase in medial residential zip code level, radon was associated with a 4.1% increase in the odds of PIH disorders (95% CI 3% to 6%), while in women more than 35 years old, the association was null. Conclusions: In this cohort, higher levels of residential radon are associated with increased odds of PIH disorders. After stratifying by age, this effect remained significant only in women less than 35 years old. Since the burden of pregnancy-induced hypertensive disorders is high and affects women’s future cardiovascular health, the identification of modifiable risk factors is of great importance.

3314

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection recently became an issue of national relevance in Italy, especially in healthcare workers (HCWs) who have been exposed to the virus in times when preventive measures were not yet fully established. Methods: We collected occupational and clinical characteristics of all HCWs who had performed a nasopharyngeal swab for the detection of SARS-CoV-2 at the Policlinico Hospital in Milan, the capital city of Lombardy (the most affected Italian region), from February 24^th to March 31^st 2020. Laboratory data were collected as of April 9^th. We compared frequencies of positive tests according to selected variables using chi-squared test and applied multivariable logistic regression models including gender, age class, occupation, and reported symptoms. Results: We found 138 test-positive HCWs out of a total of 1,573 (8.8%, 95% confidence interval [CI]: 7.4-10.3). Symptomatic subjects showed a much higher proportion of positive tests (20.2%, 95%CI: 16.7-24.1) when compared to asymptomatic ones (3.7%, 95%CI: 2.7-5.1, p<0.001). The strongest predictors of a positive test were fever (Odds ratio [OR] = 7.21, 95%CI: 4.45-11.7) and taste and smell alterations (OR = 29.7, 95%CI: 10.1-87.5). Fifty percent of subjects took up to 23 days (95%CI: 19-24) to become negative from first positive test. When considering occupation, the highest frequency of positive tests was detected among physicians (10.6%, 95%CI: 8.3-13.4). Conclusions: In a sample of HCWs exposed to confirmed cases of COVID-19, we found fever and taste and smell alterations to be strongly associated with SARS-CoV-2 infection, together with a median time to clear the virus of 23 days. The investigation in the Hospital is currently continuing by performing serological tests for identification of SARS-CoV-2 S1/S2 IgG antibodies including also the present study subjects. This will allow to assess the presence of specific antibodies to be compared with nasal swab tests.