Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population.

BACKGROUND: The 'exposome' represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics) defines an individual's metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium. METHODS: High-resolution ¹H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress. RESULTS: Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4-deoxy-erythronic acid) or one-carbon metabolism (dimethylglycine, creatinine, creatine), were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels) was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction. CONCLUSIONS: This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental concentrations, paving the way for exposome research.

Creating a national register of childhood type 1 diabetes using routinely collected hospital data.

INTRODUCTION: There is no national register of childhood type 1 diabetes mellitus for England. Our aim was to assess the feasibility of using routine hospital admissions data as a surrogate for a childhood diabetes register across England, and to create a geographically referenced childhood diabetes dataset for use in epidemiologic studies and health service research. METHODS: Hospital Episodes Statistics data for England from April 1992 to March 2006 referring to a type 1 diabetes diagnosis in 0-14 yr olds were cleaned to approximate an incident dataset. The cleaned data were validated against regional population-based register data, available for Yorkshire and the area of the former Oxford Regional Health Authority. RESULTS: There were 32 665 unique cases of type 1 and type unknown diabetes over the study period. The hospital-derived data improved in quality over time (91% concordance with regional register data over the period 2000-2006 vs. 52% concordance over the period 1992-1999), and data quality was better for younger (0-9 yr) (86.5% concordance with regional register data) than older cases (10-14 yr). Overall incidence was 24.99 (95% confidence interval 24.71-25.26) per 100 000. Basic trends in age distribution, seasonality of onset, and incidence matched well with previously reported findings. CONCLUSION: We were able to create a surrogate register of childhood diabetes based on national hospital admissions data, containing approximately 2300 cases/yr, and geo-coded to a high resolution. For younger cases (0-9 yr) and more recent years (from 2000) these data will be a useful resource for epidemiological studies exploring the determinants of childhood diabetes.

Outdoor and indoor cadmium distributions near an abandoned smelting works and their relations to human exposure.

The relationship of measured or modelled Cd concentrations in soil, house dust and available to plants with human urinary Cd concentrations were assessed in a population living around a Cd/Pb/Zn smelter in the UK. Modelled air concentrations explained 35% of soil Cd variation indicating the smelter contributed to soil Cd loads. Multi-variate analysis confirmed a significant role of biological and life-style factors in determining urinary Cd levels. Significant correlations of urinary Cd with soil, house dust and modelled plant available Cd concentrations were not, however, found. Potential reasons for the absence of clear relationships include limited environmental contact in urban populations; the role of undefined factors in determining exposure; and the limited spatial scope of the survey which did not sample from the full pollution gradient. Further, the absence of any significant relationship indicates that environmental measures provide limited advantage over atmospheric model outputs for first stage human exposure assessment.

Can exposure to noise affect the 24 h blood pressure profile? Results from the HYENA study.

UNLABELLED: OBJECTIVE; To study the association between exposure to transportation noise and blood pressure (BP) reduction during nighttime sleep. METHODS: 24-h ambulatory BP measurements at 15-min intervals were carried out on 149 persons living near four major European airports. Noise indicators included total and source-specific equivalent indoor noise, total number of noise events, annoyance scores for aircraft and road traffic nighttime noise. Long-term noise exposure was also determined. Multivariate linear regression analysis was applied. RESULTS: The pooled estimates show that the only noise indicator associated consistently with a decrease in BP dipping is road traffic noise. The effect shows that a 5 dB increase in measured road traffic noise during the study night is associated with 0.8% (-1.55, -0.05) less dipping in diastolic BP. Noise from aircraft was not associated with a decrease in dipping, except for a non-significant decrease noted in Athens, where the aircraft noise was higher. Noise from indoor sources did not affect BP dipping. CONCLUSIONS: Road traffic noise exposure may be associated with a decrease in dipping. Noise from aircraft was not found to affect dipping in a consistent way across centres and indoor noise was not associated with dipping.

Medication use in relation to noise from aircraft and road traffic in six European countries: results of the HYENA study.

OBJECTIVES: Studies on the health effects of aircraft and road traffic noise exposure suggest excess risks of hypertension, cardiovascular disease and the use of sedatives and hypnotics. Our aim was to assess the use of medication in relation to noise from aircraft and road traffic. METHODS: This cross-sectional study measured the use of prescribed antihypertensives, antacids, anxiolytics, hypnotics, antidepressants and antasthmatics in 4,861 persons living near seven airports in six European countries (UK, Germany, the Netherlands, Sweden, Italy, and Greece). Exposure was assessed using models with 1 dB resolution (5 dB for UK road traffic noise) and spatial resolution of 250×250 m for aircraft and 10×10 m for road traffic noise. Data were analysed using multilevel logistic regression, adjusting for potential confounders. RESULTS: We found marked differences between countries in the effect of aircraft noise on antihypertensive use; for night-time aircraft noise, a 10 dB increase in exposure was associated with ORs of 1.34 (95% CI 1.14 to 1.57) for the UK and 1.19 (1.02 to 1.38) for the Netherlands but no significant associations were found for other countries. For day-time aircraft noise, excess risks were found for the UK (OR 1.35; CI: 1.13 to 1.60) but a risk deficit for Italy (OR 0.82; CI: 0.71 to 0.96). There was an excess risk of taking anxiolytic medication in relation to aircraft noise (OR 1.28; CI: 1.04 to 1.57 for daytime and OR 1.27; CI: 1.01 to 1.59 for night-time) which held across countries. We also found an association between exposure to 24hr road traffic noise and the use of antacids by men (OR 1.39; CI 1.11 to 1.74). CONCLUSION: Our results suggest an effect of aircraft noise on the use of antihypertensive medication, but this effect did not hold for all countries. Results were more consistent across countries for the increased use of anxiolytics in relation to aircraft noise.

Evaluation of spatial relationships between health and the environment: the rapid inquiry facility.

BACKGROUND: The initiation of environmental public health tracking systems in the United States and the United Kingdom provided an opportunity to advance techniques and tools available for spatial epidemiological analysis integrating both health and environmental data. OBJECTIVE: The Rapid Inquiry Facility (RIF) allows users to calculate adjusted and unadjusted standardized rates and risks. The RIF is embedded in ArcGIS so that further geographical information system (GIS) spatial functionality can be exploited or results can be exported to statistical packages for further tailored analyses where required. The RIF also links directly to several statistical packages and displays the results in the GIS. METHODS: The value of the RIF is illustrated here with two case studies: risk of leukemia in areas surrounding oil refineries in the State of Utah (USA) and an analysis of the geographical variation of risk of esophageal cancer in relation to zinc cadmium sulfide exposure in Norwich (United Kingdom). RESULTS: The risk analysis study in Utah did not suggest any evidence of increased relative risk of leukemia, multiple myeloma, or Hodgkin's lymphoma in the populations around the five oil-refining facilities but did reveal an excess risk of non-Hodgkin's lymphoma that might warrant further investigation. The disease-mapping study in Norwich did not reveal any areas with higher relative risks of esophageal cancer common to both males and females, suggesting that a common geographically determined exposure was unlikely to be influencing cancer risk in the area. CONCLUSION: The RIF offers a tool that allows epidemiologists to quickly carry out ecological environmental epidemiological analysis such as risk assessment or disease mapping.

An approach for estimating the health effects of changes over time in air pollution: an illustration using cardio-respiratory hospital admissions in London.

OBJECTIVES: First, we present a general analytical approach to estimating the association between medium-term changes in air pollution and health across small areas. As a specific illustration, we then applied the approach to data on London residents from a 4-year period to test whether reductions in traffic-related air pollution were associated with reductions in cardio-respiratory hospital admissions. METHODS: A binomial distribution was used to model change in admissions over time in each small area, which was measured as the proportion of admissions in 2003-2004 out of admissions over all study years (2001-2004). Annual average concentrations of nitrogen oxides (NO(x)) were modelled using an emissions-dispersion model. The association between change in NO(x) and change in hospital admissions was estimated using logistic regression and an instrumental variable approach. RESULTS: For some diagnostic groups, suggestive associations between reductions in NO(x) and reductions in admissions were observed, for example, OR=0.97 (95% CI 0.96 to 0.99) for an IQR decrease in NO(x) (3 microg/m(3)) and all respiratory admissions. Accounting for spatial dependence attenuated several of the associations; for respiratory admissions, the OR was 1.00 (95% CI 0.98 to 1.02), leaving only that for bronchiolitis significant (OR=0.91; 95% CI 0.84 to 0.99). In this particular illustration, the instrumental variable approach did not appear to add information. CONCLUSIONS: In this illustration, there was relatively limited power to detect an association between changes in air pollution and hospital admissions over time. However, the analytical approach could deliver more robust estimates of the health effects of changes in air pollution in settings with greater spatial contrast in changes in air pollution over time.

Annoyance due to aircraft noise has increased over the years--results of the HYENA study.

In the HYENA study (HYpertension and Exposure to Noise near Airports) noise annoyances due to aircraft and road traffic noise were assessed in subjects that lived in the vicinity of 6 major European airports using the 11-point ICBEN scale (International Commission on Biological Effects of Noise). A distinction was made between the annoyance during the day and during the night. L(den) and L(night) were considered as indicators of noise exposure. Pooled data analyses showed clear exposure-response relationships between the noise level and the noise annoyance for both exposures. The exposure-response curves for road noise were congruent with the EU standard curves used for predicting the number of highly noise annoyed subjects in European communities. Annoyance ratings due to aircraft noise, however, were higher than predicted by the EU standard curves. The data supports other findings suggesting that the people's attitude towards aircraft noise has changed over the years, and that the EU standard curve for aircraft noise should be modified.

Current status of cadmium as an environmental health problem.

Cadmium is a toxic metal occurring in the environment naturally and as a pollutant emanating from industrial and agricultural sources. Food is the main source of cadmium intake in the non-smoking population. The bioavailability, retention and toxicity are affected by several factors including nutritional status such as low iron status. Cadmium is efficiently retained in the kidney (half-time 10-30 years) and the concentration is proportional to that in urine (U-Cd). Cadmium is nephrotoxic, initially causing kidney tubular damage. Cadmium can also cause bone damage, either via a direct effect on bone tissue or indirectly as a result of renal dysfunction. After prolonged and/or high exposure the tubular injury may progress to glomerular damage with decreased glomerular filtration rate, and eventually to renal failure. Furthermore, recent data also suggest increased cancer risks and increased mortality in environmentally exposed populations. Dose-response assessment using a variety of early markers of kidney damage has identified U-Cd points of departure for early kidney effects between 0.5 and 3 microg Cd/g creatinine, similar to the points of departure for effects on bone. It can be anticipated that a considerable proportion of the non-smoking adult population has urinary cadmium concentrations of 0.5 microg/g creatinine or higher in non-exposed areas. For smokers this proportion is considerably higher. This implies no margin of safety between the point of departure and the exposure levels in the general population. Therefore, measures should be put in place to reduce exposure to a minimum, and the tolerably daily intake should be set in accordance with recent findings.

Health effects of real-world exposure to diesel exhaust in persons with asthma.

Many people, including people with asthma, experience short-term exposure to diesel exhaust (DE*) during daily activities. The health effects of such exposures, however, remain poorly understood. The present study utilized a real-world setting to examine whether short-term DE exposure would (1) worsen asthma symptoms, (2) augment airway inflammation, or (3) increase oxidative stress burdens. The study also examined exposure-response relations for several DE components and the contribution of background asthma severity to individuals' respiratory responses to DE exposure. Sixty people participated in the study; 31 had mild asthma and 29 had moderate asthma. Each participant completed an exposure and a control session. During the exposure session, participants walked for 2 hours along a heavily trafficked city street where motor vehicle access was restricted to buses and official taxicabs. These vehicles were powered by diesel engines. During the control session, participants walked for the same duration and at the same speed in a public park where motor vehicle traffic was prohibited. The concentrations of elemental carbon (EC), NO2, ultrafine particles (UFP), and particulate matter less than or equal to 2.5 microm in aerodynamic diameter (PM2.5) during exposure sessions were, on average, 4.8, 4.0, 3.4, and 2.0 times higher, respectively, than during control sessions. Increases in asthma symptom score and in the daily use of asthma reliever medication within the 7-day measurement period after exposure were not significant. Some effects on lung function were statistically significant. Compared with control sessions, forced expiratory volume in the first second (FEV1) was reduced 3.0% to 4.1%, and forced vital capacity (FVC) was reduced 2.8% to 3.7% in the 5 hours immediately after the exposure sessions. Analyses of biomarkers showed that the exposure sessions led to a significant reduction in exhaled breath condensate (EBC) pH and to significant increases in induced sputum neutrophils and myeloperoxidase (MPO). The changes in lung function indices (FEV1, FVC, and forced expiratory flow during the middle half of the FVC [FEF25-75]) were most consistently associated with UFP and EC exposures, whereas the changes in EBC pH were most consistently associated with NO2 exposure. In addition, NO2 had a significant effect on bronchial reactivity and on the amount of interleukin-8 (IL-8) in induced sputum; it also modified the UFP effect on EBC pH and the EC effect on exhaled nitric oxide (eNO). However, our findings cannot be taken as demonstrating a causal association with any measured pollutant, because the measured pollutant concentrations may simply represent the entire roadside diesel-traffic exposure that comprises not only the pollutants measured in this study but also other pollutants in the complex DE mixture and resuspended coarse particles from road dust, engine debris, and tire debris. The effects of exposure appeared to be larger in the more severe asthmatic group for most outcomes measured. In conclusion, short-term exposure to urban roadside diesel traffic led to consistent and significant reductions in lung function, accompanied by airway acidification and neutrophilic inflammation. Our findings help to explain the epidemiologic evidence on diesel traffic health effects in persons with asthma.

Early kidney damage in a population exposed to cadmium and other heavy metals.

BACKGROUND: Exposure to heavy metals may cause kidney damage. The population living near the Avonmouth zinc smelter has been exposed to cadmium and other heavy metals for many decades. OBJECTIVES: We aimed to assess Cd body burden and early signs of kidney damage in the Avonmouth population. METHODS: We used dispersion modeling to assess exposure to Cd. We analyzed urine samples from the local population (n = 180) for Cd (U-Cd) to assess dose (body burden) and for three biomarkers of early kidney damage [N-acetyl-beta-d-glucosaminidase (U-NAG), retinol-binding protein, and alpha-1-microglobulin]. We collected information on occupation, intake of homegrown vegetables, smoking, and medical history by questionnaire. RESULTS: Median U-Cd concentrations were 0.22 nmol/mmol creatinine (nonsmoking 0.18/smoking 0.40) and 0.34 nmol/mmol creatinine (nonsmoking 0.31/smoking 0.46) in non-occupationally exposed men and women, respectively. There was a significant dose-response relationship between U-Cd and the prevalence of early renal damage-defined as U-NAG > 0.22 IU/mmol-with odds ratios of 2.64 [95% confidence interval (95% CI), 0.70-9.97] and 3.64 (95% CI, 0.98-13.5) for U-Cd levels of 0.3 to < 0.5 and levels >or= 0.5 nmol/mmol creatinine, respectively (p for trend = 0.045). CONCLUSION: U-Cd concentrations were close to levels where kidney and bone effects have been found in other populations. The dose-response relationship between U-Cd levels and prevalence of U-NAG above the reference value support the need for measures to reduce environmental Cd exposure.

Saliva cortisol and exposure to aircraft noise in six European countries.

BACKGROUND: Several studies show an association between exposure to aircraft or road traffic noise and cardiovascular effects, which may be mediated by a noise-induced release of stress hormones. OBJECTIVE: Our objective was to assess saliva cortisol concentration in relation to exposure to aircraft noise. METHOD: A multicenter cross-sectional study, HYENA (Hypertension and Exposure to Noise near Airports), comprising 4,861 persons was carried out in six European countries. In a subgroup of 439 study participants, selected to enhance the contrast in exposure to aircraft noise, saliva cortisol was assessed three times (morning, lunch, and evening) during 1 day. RESULTS: We observed an elevation of 6.07 nmol/L [95% confidence interval (CI), 2.32-9.81 nmol/L] in morning saliva cortisol level in women exposed to aircraft noise at an average 24-hr sound level (L(Aeq,24h)) > 60 dB, compared with women exposed to L(Aeq,24h) < or = 50 dB, corresponding to an increase of 34%. Employment status appeared to modify the response. We found no association between noise exposure and saliva cortisol levels in men. CONCLUSIONS: Our results suggest that exposure to aircraft noise increases morning saliva cortisol levels in women, which could be of relevance for noise-related cardiovascular effects.

Bone mineral density changes in relation to environmental PCB exposure.

BACKGROUND: Bone toxicity has been linked to organochlorine exposure following a few notable poisoning incidents, but epidemiologic studies in populations with environmental organochlorine exposure have yielded inconsistent results. OBJECTIVES: The aim of this study was to investigate whether organochlorine exposure was associated with bone mineral density (BMD) in a population 60-81 years of age (154 males, 167 females) living near the Baltic coast, close to a river contaminated by polychlorinated biphenyls (PCBs). METHODS: We measured forearm BMD in participants using dual energy X-ray absorptiometry; and we assessed low BMD using age- and sex-standardized Z-scores. We analyzed blood samples for five dioxin-like PCBs, the three most abundant non-dioxin-like PCBs, and p,p'-dichloro-phenyldichloroethylene (p,p'-DDE). RESULTS: In males, dioxin-like chlorobiphenyl (CB)-118 was negatively associated with BMD; the odds ratio for low BMD (Z-score less than -1) was 1.06 (95% confidence interval, 1.01-1.12) per 10 pg/mL CB-118. The sum of the three most abundant non-dioxin-like PCBs was positively associated with BMD, but not with a decreased risk of low BMD. In females, CB-118 was positively associated with BMD, but this congener did not influence the risk of low BMD in women. CONCLUSIONS: Environmental organochlorine exposures experienced by this population sample since the 1930s in Sweden may have been sufficient to result in sex-specific changes in BMD.

Methodologic issues and approaches to spatial epidemiology.

Spatial epidemiology is increasingly being used to assess health risks associated with environmental hazards. Risk patterns tend to have both a temporal and a spatial component; thus, spatial epidemiology must combine methods from epidemiology, statistics, and geographic information science. Recent statistical advances in spatial epidemiology include the use of smoothing in risk maps to create an interpretable risk surface, the extension of spatial models to incorporate the time dimension, and the combination of individual- and area-level information. Advances in geographic information systems and the growing availability of modeling packages have led to an improvement in exposure assessment. Techniques drawn from geographic information science are being developed to enable the visualization of uncertainty and ensure more meaningful inferences are made from data. When public health concerns related to the environment arise, it is essential to address such anxieties appropriately and in a timely manner. Tools designed to facilitate the investigation process are being developed, although the availability of complete and clean health data, and appropriate exposure data often remain limiting factors.

Comparison of different methods for spatial analysis of cancer data in Utah.

BACKGROUND: The standardized incidence ratio (SIR) and SaTScan software are used by the Environmental Epidemiology Program (EEP), Utah Department of Health, to investigate health concerns and exposures in Utah (USA). Recently, the EEP acquired the Rapid Inquiry Facility (RIF). The RIF enables access of additional dimensions of data, identifies potentially exposed populations, and computes disease rates and relative risk statistics for that potentially exposed population. OBJECTIVE: In this article we present a comparison of the SIR, SaTScan, and RIF methodologies in an investigation of cancer rates in residents living over contaminated groundwater plumes near Hill Air Force Base (HAFB) in Utah. METHODS: For this study, we used cancer data from the Utah Cancer Registry for cancers of the lung, kidney, and non-Hodgkin lymphoma. We used SIR and the RIF to investigate the cancer rate in a defined population within the study area during six consecutive 5-year time intervals (1975-2004). We used SaTScan and the RIF to explore the study area for clusters. RESULTS: The RIF risk analysis and SIR are mathematically identical. SIR is set up and computed by programming SAS; the RIF risk analysis, on the other hand, is set up through four menu-driven steps. The RIF disease-mapping feature enhanced the interpretation of SaTScan results. We found kidney and lung cancer to be statistically elevated for the potentially exposed population for one and two periods, respectively. SaTScan found two clusters, one outside the potentially exposed population and one that included a portion of that population. CONCLUSION: The RIF is an easy-to-use and useful tool that extends the ability of the investigator to conduct analysis of disease rates and interpret the findings.

Hypertension and exposure to noise near airports: the HYENA study.

BACKGROUND: An increasing number of people are exposed to aircraft and road traffic noise. Hypertension is an important risk factor for cardiovascular disease, and even a small contribution in risk from environmental factors may have a major impact on public health. OBJECTIVES: The HYENA (Hypertension and Exposure to Noise near Airports) study aimed to assess the relations between noise from aircraft or road traffic near airports and the risk of hypertension. METHODS: We measured blood pressure and collected data on health, socioeconomic, and lifestyle factors, including diet and physical activity, via questionnaire at home visits for 4,861 persons 45-70 years of age, who had lived at least 5 years near any of six major European airports. We assessed noise exposure using detailed models with a resolution of 1 dB (5 dB for United Kingdom road traffic noise), and a spatial resolution of 250 x 250 m for aircraft and 10 x 10 m for road traffic noise. RESULTS: We found significant exposure-response relationships between night-time aircraft as well as average daily road traffic noise exposure and risk of hypertension after adjustment for major confounders. For night-time aircraft noise, a 10-dB increase in exposure was associated with an odds ratio (OR) of 1.14 [95% confidence interval (CI), 1.01-1.29]. The exposure-response relationships were similar for road traffic noise and stronger for men with an OR of 1.54 (95% CI, 0.99-2.40) in the highest exposure category (> 65 dB; p(trend) = 0.008). CONCLUSIONS: Our results indicate excess risks of hypertension related to long-term noise exposure, primarily for night-time aircraft noise and daily average road traffic noise.

Acute effects of night-time noise exposure on blood pressure in populations living near airports.

AIMS: Within the framework of the HYENA (hypertension and exposure to noise near airports) project we investigated the effect of short-term changes of transportation or indoor noise levels on blood pressure (BP) and heart rate (HR) during night-time sleep in 140 subjects living near four major European airports. METHODS AND RESULTS: Non-invasive ambulatory BP measurements at 15 min intervals were performed. Noise was measured during the night sleeping period and recorded digitally for the identification of the source of a noise event. Exposure variables included equivalent noise level over 1 and 15 min and presence/absence of event (with LAmax > 35 dB) before each BP measurement. Random effects models for repeated measurements were applied. An increase in BP (6.2 mmHg (0.63-12) for systolic and 7.4 mmHg (3.1, 12) for diastolic) was observed over 15 min intervals in which an aircraft event occurred. A non-significant increase in HR was also observed (by 5.4 b.p.m.). Less consistent effects were observed on HR. When the actual maximum noise level of an event was assessed there were no systematic differences in the effects according to the noise source. CONCLUSION: Effects of noise exposure on elevated subsequent BP measurements were clearly shown. The effect size of the noise level appears to be independent of the noise source.

Chlorination disinfection by-products and risk of congenital anomalies in England and Wales.

BACKGROUND: Increased risk of various congenital anomalies has been reported to be associated with trihalomethane (THM) exposure in the water supply. OBJECTIVES: We conducted a registry-based study to determine the relationship between THM concentrations and the risk of congenital anomalies in England and Wales. METHODS: We obtained congenital anomaly data from the National Congenital Anomalies System, regional registries, and the national terminations registry; THM data were obtained from water companies. Total THM (< 30, 30 to < 60, > or =60 microg/L), total brominated exposure (< 10, 10 to < 20, > or =20 microg/L), and bromoform exposure (< 2, 2 to < 4, > or =4 microg/L) were modeled at the place of residence for the first trimester of pregnancy. We included 2,605,226 live births, stillbirths, and terminations with 22,828 cases of congenital anomalies. Analyses using fixed- and random-effects models were performed for broadly defined groups of anomalies (cleft palate/lip, abdominal wall, major cardiac, neural tube, urinary and respiratory defects), a more restricted set of anomalies with better ascertainment, and for isolated and multiple anomalies. Data were adjusted for sex, maternal age, and socioeconomic status. RESULTS: We found no statistically significant trends across exposure categories for either the broadly defined or more restricted sets of anomalies. For the restricted set of anomalies with isolated defects, there were significant (p < 0.05) excess risks in the high-exposure categories of total THMs for ventricular septal defects [odds ratio (OR) = 1.43; 95% confidence interval (CI), 1.00-2.04] and of bromoform for major cardiovascular defects and gastroschisis (OR = 1.18; 95% CI, 1.00-1.39; and OR = 1.38; 95% CI, 1.00-1.92, respectively). CONCLUSION: In this large national study we found little evidence for a relationship between THM concentrations in drinking water and risk of congenital anomalies.

Respiratory effects of exposure to diesel traffic in persons with asthma.

BACKGROUND: Air pollution from road traffic is a serious health hazard, and people with preexisting respiratory disease may be at increased risk. We investigated the effects of short-term exposure to diesel traffic in people with asthma in an urban, roadside environment. METHODS: We recruited 60 adults with either mild or moderate asthma to participate in a randomized, crossover study. Each participant walked for 2 hours along a London street (Oxford Street) and, on a separate occasion, through a nearby park (Hyde Park). We performed detailed real-time exposure, physiological, and immunologic measurements. RESULTS: Participants had significantly higher exposures to fine particles (<2.5 microm in aerodynamic diameter), ultrafine particles, elemental carbon, and nitrogen dioxide on Oxford Street than in Hyde Park. Walking for 2 hours on Oxford Street induced asymptomatic but consistent reductions in the forced expiratory volume in 1 second (FEV1) (up to 6.1%) and forced vital capacity (FVC) (up to 5.4%) that were significantly larger than the reductions in FEV1 and FVC after exposure in Hyde Park (P=0.04 and P=0.01, respectively, for the overall effect of exposure, and P<0.005 at some time points). The effects were greater in subjects with moderate asthma than in those with mild asthma. These changes were accompanied by increases in biomarkers of neutrophilic inflammation (sputum myeloperoxidase, 4.24 ng per milliliter after exposure in Hyde Park vs. 24.5 ng per milliliter after exposure on Oxford Street; P=0.05) and airway acidification (maximum decrease in pH, 0.04% after exposure in Hyde Park and 1.9% after exposure on Oxford Street; P=0.003). The changes were associated most consistently with exposures to ultrafine particles and elemental carbon. CONCLUSIONS: Our observations serve as a demonstration and explanation of the epidemiologic evidence that associates the degree of traffic exposure with lung function in asthma.

Down syndrome in births near landfill sites.

OBJECTIVES: The aim of the study was to examine the risk of giving birth to a child with Down syndrome associated with residence near landfill sites in England and Wales. METHODS: A 2-km zone around 6289 landfill sites processing special (hazardous), non-special and unknown waste type was used to indicate exposure. Postcodes within the 2-km zone were classified as 'exposed' and people living beyond 2 km comprised the reference population. Health outcome data were Down syndrome registrations from a national registry including 21 cytogenetic laboratories in England and Wales, for the years 1989 to 1998. With a Bayesian regression model, we calculated relative risks for the population living within 2 km of landfill sites relative to the reference population, assuming a common relative risk for all landfill sites. Adjustments were made for major confounders. RESULTS: There were 4640 cases of Down syndrome within 2 km of a landfill site. We found no excess risks of Down syndrome related to landfill sites. Adjustment for socio-economic status (SES) did not influence our estimates. There were no differences in risk between hazardous waste sites and other landfill sites. CONCLUSION: We found no excess risk of Down syndrome in populations living near landfill sites.