Thomas J. Luben

Particulate Matter―Induced Health Effects: Who Is Susceptible?

Background Epidemiological, controlled human exposure, and toxicological studies have demonstrated a variety of health effects in response to particulate matter (PM) exposure with some of these studies indicating that populations with certain characteristics may be disproportionately affected. Objective To identify populations potentially at greatest risk for PM-related health effects, we evaluated epidemiological studies that examined various characteristics that may influence susceptibility, while using results from controlled human exposure and toxicological studies as supporting evidence. Additionally, we formulated a definition of susceptibility, building from the varied and inconsistent definitions of susceptibility and vulnerability used throughout the literature. Data synthesis We evaluated recent epidemiological studies to identify characteristics of populations potentially susceptible to PM-related health effects. Additionally, we evaluated controlled human exposure and toxicological studies to provide supporting evidence. We conducted a comprehensive review of epidemiological studies that presented stratified results (e.g., < 65 vs. ≥ 65 years of age), controlled human exposure studies that examined individuals with underlying disease, and toxicological studies that used animal models of disease. We evaluated results for consistency across studies, coherence across disciplines, and biological plausibility to assess the potential for increased susceptibility to PM-related health effects in a specific population or life stage. Conclusions We identified a diverse group of characteristics that can lead to increased risk of PM-related health effects, including life stage (i.e., children and older adults), preexisting cardiovascular or respiratory diseases, genetic polymorphisms, and low-socioeconomic status. In addition, we crafted a comprehensive definition of susceptibility that can be used to encompass all populations potentially at increased risk of adverse health effects as a consequence of exposure to an air pollutant.

The Effect of Ambient Air Pollution on Sperm Quality

Background Research has suggested an association with ambient air pollution and sperm quality. Objectives We investigated the effect of exposure to ozone (O3) and particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) on sperm quality. Methods We reexamined a previous cohort study of water disinfection by-products to evaluate sperm quality in 228 presumed fertile men with different air pollution profiles. Outcomes included sperm concentration, total sperm per ejaculate (count), and morphology, as well as DNA integrity and chromatin maturity. Exposures to O3 and PM2.5 were evaluated for the 90–day period before sampling. We used multivariable linear regression, which included different levels of adjustment (i.e., without and with season and temperature) to assess the relationship between exposure to air pollutants during key periods of sperm development and adverse sperm outcomes. Results Sperm concentration and count were not associated with exposure to PM2.5, but there was evidence of an association (but not statistically significant) with O3 concentration and decreased sperm concentration and count. Additionally, a significant increase in the percentage of sperm cells with cytoplasmic drop [β = 2.64; 95% confidence interval (CI), 0.21–5.06] and abnormal head (β = 0.47; 95% CI, 0.03–0.92) was associated with PM2.5 concentration in the base model. However, these associations, along with all other sperm outcomes, were not significantly associated with either pollutant after controlling for season and temperature. Overall, although we found both protective and adverse effects, there was generally no consistent pattern of increased abnormal sperm quality with elevated exposure to O3 or PM2.5. Conclusions Exposures to O3 or PM2.5 at levels below the current National Ambient Air Quality Standards were not associated with statistically significant decrements in sperm outcomes in this cohort of fertile men. However, some results suggested effects on sperm concentration, count, and morphology.

Agricultural pesticide use and hypospadias in eastern Arkansas

Introduction We assessed the relationship between hypospadias and proximity to agricultural pesticide applications using a GIS-based exposure method. Methods We obtained information for 354 cases of hypospadias born between 1998 and 2002 in eastern Arkansas; 727 controls were selected from birth certificates. We classified exposure on pounds of pesticides (estimated by crop type) applied or persisting within 500 m of each subject’s home during gestational weeks 6 to 16. We restricted our analyses to 38 pesticides with some evidence of reproductive, developmental, estrogenic, and/or antiandrogenic effects. We estimated timing of pesticide applications using crop phenology and published records. Results Gestational age at birth [odds ratio (OR) = 0.91; 95% confidence interval (CI), 0.83–0.99], parity (OR = 0.79; 95% CI, 0.65–0.95), and delaying prenatal care until the third trimester (OR = 4.04; 95% CI, 1.46–11.23) were significantly associated with hypospadias. Risk of hypospadias increased by 8% for every 0.05-pound increase in estimated exposure to diclofop-methyl use (OR = 1.08; 95% CI, 1.01–1.15). Pesticide applications in aggregate (OR = 0.82; 95% CI, 0.70–0.96) and applications of alachlor (OR = 0.56; 95% CI, 0.35–0.89) and permethrin (OR = 0.37; 95% CI, 0.16–0.86) were negatively associated with hypospadias. Conclusions Except for diclofop-methyl, we did not find evidence that estimated exposure to pesticides known to have reproductive, developmental, or endocrine-disrupting effects increases risk of hypospadias. Further research on the potential effects of exposure to diclofop-methyl is recommended.

The healthy men study: An evaluation of exposure to disinfection by-products in tap water and sperm quality

Background Chlorination of drinking water generates disinfection by-products (DBPs), which have been shown to disrupt spermatogenesis in rodents at high doses, suggesting that DBPs could pose a reproductive risk to men. In this study we assessed DBP exposure and testicular toxicity, as evidenced by altered semen quality. Methods We conducted a cohort study to evaluate semen quality in men with well-characterized exposures to DBPs. Participants were 228 presumed fertile men with different DBP profiles. They completed a telephone interview about demographics, health history, water consumption, and other exposures and provided a semen sample. Semen outcomes included sperm concentration and morphology, as well as DNA integrity and chromatin maturity. Exposures to DBPs were evaluated by incorporating data on water consumption and bathing and showering with concentrations measured in tap water. We used multivariable linear regression to assess the relationship between exposure to DBPs and adverse sperm outcomes. Results The mean (median) sperm concentration and sperm count were 114.2 (90.5) million/mL and 362 (265) million, respectively. The mean (median) of the four trihalomethane species (THM4) exposure was 45.7 (65.3) μg/L, and the mean (median) of the nine haloacetic acid species (HAA9) exposure was 30.7 (44.2) μg/L. These sperm parameters were not associated with exposure to these classes of DBPs. For other sperm outcomes, we found no consistent pattern of increased abnormal semen quality with elevated exposure to trihalomethanes (THMs) or haloacetic acids (HAAs). The use of alternate methods for assessing exposure to DBPs and site-specific analyses did not change these results. Conclusions The results of this study do not support an association between exposure to levels of DBPs near or below regulatory limits and adverse sperm outcomes in humans.

Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the national birth defects prevention study.

Background: Epidemiologic literature suggests that exposure to air pollutants is associated with fetal development. Objectives: We investigated maternal exposures to air pollutants during weeks 2–8 of pregnancy and their associations with congenital heart defects. Methods: Mothers from the National Birth Defects Prevention Study, a nine-state case–control study, were assigned 1-week and 7-week averages of daily maximum concentrations of carbon monoxide, nitrogen dioxide, ozone, and sulfur dioxide and 24-hr measurements of fine and coarse particulate matter using the closest air monitor within 50 km to their residence during early pregnancy. Depending on the pollutant, a maximum of 4,632 live-birth controls and 3,328 live-birth, fetal-death, or electively terminated cases had exposure data. Hierarchical regression models, adjusted for maternal demographics and tobacco and alcohol use, were constructed. Principal component analysis was used to assess these relationships in a multipollutant context. Results: Positive associations were observed between exposure to nitrogen dioxide and coarctation of the aorta and pulmonary valve stenosis. Exposure to fine particulate matter was positively associated with hypoplastic left heart syndrome but inversely associated with atrial septal defects. Examining individual exposure-weeks suggested associations between pollutants and defects that were not observed using the 7-week average. Associations between left ventricular outflow tract obstructions and nitrogen dioxide and between hypoplastic left heart syndrome and particulate matter were supported by findings from the multipollutant analyses, although estimates were attenuated at the highest exposure levels. Conclusions: Using daily maximum pollutant levels and exploring individual exposure-weeks revealed some positive associations between certain pollutants and defects and suggested potential windows of susceptibility during pregnancy. Citation: Stingone JA, Luben TJ, Daniels JL, Fuentes M, Richardson DB, Aylsworth AS, Herring AH, Anderka M, Botto L, Correa A, Gilboa SM, Langlois PH, Mosley B, Shaw GM, Siffel C, Olshan AF, National Birth Defects Prevention Study. 2014. Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the National Birth Defects Prevention Study. Environ Health Perspect 122:863–872; http://dx.doi.org/10.1289/ehp.1307289

Spatial distribution of acid-volatile sulfur in the sediments of Canadohta Lake, PA

Lake sediments are an important source of dissolvedsubstances and can be the site of processes importantto the biogeochemical cycling of nutrients and metals. Most studies which examine these processes, however,are based on the analysis of a single or a very fewsediment cores taken at or near the deepest area ofthe lake. The implicit assumption is that lakesediments are spatially homogeneous and thatextrapolations from such limited samples arerepresentative of the lake sediments throughout thelake basin. We examined this assumption with respectto concentrations of acid volatile sulfides (S2-vol) – sulfur species which have beenimplicated in eutrophication, acid-neutralization, andheavy-metal toxicity. S2-volconcentrations measured in the surficial sediments ofCanadohta Lake, PA, a lake of very simple morphometry,ranged from 0.07 to 30.32 μg g-1 sediment dryweight. Concentrations were directly correlated withdepth and inversely correlated with organic matter. These results suggest that results extrapolated froma few deep-water cores can lead to a seriousoverestimation of S2-vol in the lakesediments.

Influence of urbanicity and county characteristics on the association between ozone and asthma emergency department visits in North Carolina.

Background: Air pollution epidemiologic studies, often conducted in large metropolitan areas because of proximity to regulatory monitors, are limited in their ability to examine potential associations between air pollution exposures and health effects in rural locations. Methods: Using a time-stratified case-crossover framework, we examined associations between asthma emergency department (ED) visits in North Carolina (2006–2008), collected by a surveillance system, and short-term ozone (O3) exposures using predicted concentrations from the Community Multiscale Air Quality (CMAQ) model. We estimated associations by county groupings based on four urbanicity classifications (representative of county size and urban proximity) and county health. Results: O3 was associated with asthma ED visits in all-year and warm season (April–October) analyses [odds ratio (OR) = 1.019; 95% CI: 0.998, 1.040; OR = 1.020; 95% CI: 0.997, 1.044, respectively, for a 20-ppb increase in lag 0–2 days O3]. The association was strongest in Less Urbanized counties, with no evidence of a positive association in Rural counties. Associations were similar when adjusted for fine particulate matter in copollutant models. Associations were stronger for children (5–17 years of age) compared with other age groups, and for individuals living in counties identified with poorer health status compared with counties that had the highest health rankings, although estimated associations for these subgroups had larger uncertainty. Conclusions: Associations between short-term O3 exposures and asthma ED visits differed by overall county health and urbanicity, with stronger associations in Less Urbanized counties, and no positive association in Rural counties. Results also suggest that children are at increased risk of O3-related respiratory effects. Citation: Sacks JD, Rappold AG, Davis JA Jr, Richardson DB, Waller AE, Luben TJ. 2014. Influence of urbanicity and county characteristics on the association between ozone and asthma emergency department visits in North Carolina. Environ Health Perspect 122:506–512; http://dx.doi.org/10.1289/ehp.1306940

Associations Between Prenatal Exposure to Air Pollution, Small for Gestational Age, and Term Low Birthweight in a State-Wide Birth Cohort

A range of health effects, including adverse pregnancy outcomes, have been associated with exposure to ambient concentrations of particulate matter (PM) and ozone (O3). The objective of this study was to determine whether maternal exposure to fine particulate matter (PM2.5) and O3 during pregnancy is associated with the risk of term low birthweight and small for gestational age infants in both single and co-pollutant models. Term low birthweight and small for gestational age were determined using all birth certificates from North Carolina from 2003 to 2005. Ambient air concentrations of PM2.5 and O3 were predicted using a hierarchical Bayesian model of air pollution that combined modeled air pollution estimates from the EPA׳s Community Multi-Scale Air Quality (CMAQ) model with air monitor data measured by the EPA׳s Air Quality System. Binomial regression, adjusted for multiple potential confounders, was performed. In adjusted single-pollutant models for the third trimester, O3 concentration was positively associated with small for gestational age and term low birthweight births [risk ratios for an interquartile range increase in O3: 1.16 (95% CI 1.11, 1.22) for small for gestational age and 2.03 (95% CI 1.80, 2.30) for term low birthweight]; however, inverse or null associations were observed for PM2.5 [risk ratios for an interquartile range increase in PM2.5: 0.97 (95% CI 0.95, 0.99) for small for gestational age and 1.01 (95% CI 0.97, 1.06) for term low birthweight]. Findings were similar in co-pollutant models and linear models of birthweight. These results suggest that O3 concentrations in both urban and rural areas may be associated with an increased risk of term low birthweight and small for gestational age births.

Early prenatal exposure to air pollution and its associations with birth defects in a state-wide birth cohort from North Carolina

BACKGROUND Few studies have examined the potential relationship between air pollution and birth defects. The objective of this study was to investigate whether maternal exposure to particulate matter (PM2.5 ) and ozone (O3 ) during pregnancy is associated with birth defects among women living throughout North Carolina. METHODS Information on maternal and infant characteristics was obtained from North Carolina birth certificates and health service data (2003-2005) and linked with information on birth defects from the North Carolina Birth Defects Monitoring Program. The 24-hr PM2.5 and O3 concentrations were estimated using a hierarchical Bayesian model of air pollution generated by combining modeled air pollution predictions from the U.S. Environmental Protection Agencys Community Multi-Scale Air Quality model with air monitor data from the Environmental Protection Agencys Air Quality System. Maternal residence was geocoded and assigned pollutant concentrations averaged over weeks 3 to 8 of gestation. Binomial regression was performed and adjusted for potential confounders. RESULTS No association was observed between either PM2.5 or O3 concentrations and most birth defects. Positive effect estimates were observed between air pollution and microtia/anotia and lower limb deficiency defects, but the 95% confidence intervals were wide and included the null. CONCLUSION Overall, this study suggested a possible relationship between air pollution concentration during early pregnancy and certain birth defects (e.g., microtia/anotia, lower limb deficiency defects), although this study did not have the power to detect such an association. The risk for most birth defects does not appear to be affected by ambient air pollution.

An Ecologic Analysis of County-Level PM2.5 Concentrations and Lung Cancer Incidence and Mortality

Few studies have explored the relationship between PM2.5 and lung cancer incidence. Although results are mixed, some studies have demonstrated a positive relationship between PM2.5 and lung cancer mortality. Using an ecologic study design, we examined the county-level associations between PM2.5 concentrations (2002–2005) and lung cancer incidence and mortality in North Carolina (2002–2006). Positive trends were observed between PM2.5 concentrations and lung cancer incidence and mortality; however, the R2 for both were <0.10. The slopes for the relationship between PM2.5 and lung cancer incidence and mortality were 1.26 (95% CI 0.31, 2.21, p-value 0.01) and 0.73 (95% CI 0.09, 1.36, p-value 0.03) per 1 μg/m3 PM2.5, respectively. These associations were slightly strengthened with the inclusion of variables representing socioeconomic status and smoking. Although variability is high, thus reflecting the importance of tobacco smoking and other etiologic agents that influence lung cancer incidence and mortality besides PM2.5, a positive trend is observed between PM2.5 and lung cancer incidence and mortality. This suggests the possibility of an association between PM2.5 concentrations and lung cancer incidence and mortality.