Faculty Bibliography

INTRODUCTION: There is epidemiological evidence that metal contaminants may play a role in the development of atherosclerosis and its complications. Moreover, a recent clinical trial of a metal chelator had a surprisingly positive result in reducing cardiovascular events in a secondary prevention population, strengthening the link between metal exposure and cardiovascular disease (CVD). This is, therefore, an opportune moment to review evidence that exposure to metal pollutants, such as arsenic, lead, cadmium, and mercury, is a significant risk factor for CVD. METHODS: We reviewed the English-speaking medical literature to assess and present the epidemiological evidence that 4 metals having no role in the human body (xenobiotic), mercury, lead, cadmium, and arsenic, have epidemiologic and mechanistic links to atherosclerosis and CVD. Moreover, we briefly review how the results of the Trial to Assess Chelation Therapy (TACT) strengthen the link between atherosclerosis and xenobiotic metal contamination in humans. CONCLUSIONS: There is strong evidence that xenobiotic metal contamination is linked to atherosclerotic disease and is a modifiable risk factor.

Recent changes in the global climate system have resulted in excess mortality and morbidity, particularly among susceptible individuals with preexisting cardiopulmonary disease. These weather patterns are projected to continue and intensify as a result of rising CO2 levels, according to the most recent projections by climate scientists. In this Pulmonary Perspective, motivated by the American Thoracic Society Committees on Environmental Health Policy and International Health, we review the global human health consequences of projected changes in climate for which there is a high level of confidence and scientific evidence of health effects, with a focus on cardiopulmonary health. We discuss how many of the climate-related health effects will disproportionally affect people from economically disadvantaged parts of the world, who contribute relatively little to CO2 emissions. Last, we discuss the financial implications of climate change solutions from a public health perspective and argue for a harmonized approach to clean air and climate change policies.

Particulate matter (PM*), an ambient air criteria pollutant, is a complex mixture of chemical components; particle sizes range from nanometer-sized molecular clusters to dust particles that are too large to be aspirated into the lungs. Although particle composition is believed to affect health risks from PM exposure, our current health-based air quality standards for PM are limited to (1) the mass concentrations of PM2.5 (particles 2.5 microm or smaller in aerodynamic diameter), which are largely attributable to combustion products; and (2) PM10 (10 microm or smaller), which includes larger-sized mechanically generated dusts. Both of these particle size fractions are regulated under the National Ambient Air Quality Standards (NAAQS) and both have been associated with excess mortality and morbidity. We conducted four studies as part of HEI's integrated National Particle Component Toxicity (NPACT) Initiative research program. Since 1999, the Chemical Speciation Network (CSN), managed by the U.S. Environmental Protection Agency (U.S; EPA), has routinely gathered air monitoring data every third or sixth day for the concentrations of numerous components of PM2.5. Data from the CSN enabled us to conduct a limited time-series epidemiologic study of short-term morbidity and mortality (Ito study); and a study of the associations between long-term average pollutant concentrations and annual mortality (Thurston study). Both have illuminated the roles of PM2.5 chemical components and source-related mixtures as potentially causal agents. We also conducted a series of 6-month subchronic inhalation exposure studies (6 hours/day, 5 days/week) of PM2.5 concentrated (nominally) 10 x from ambient air (CAPs) with apolipoprotein E-deficient (ApoE(-/-)) mice (a mouse model of atherosclerosis) (Chen study). The CAPs studies were conducted in five different U.S. airsheds; we measured the daily mass concentrations of PM2.5, black carbon (BC), and 16 elemental components in order to identify their sources and their roles in eliciting both short- and long-term health-related responses. In addition, from the same five air-sheds we collected samples of coarse (PM10-2.5), fine (PM2.5-0.2), and ultrafine (PM0.2) particles. Aliquots of these samples were administered to cells in vitro and to mouse lungs in vivo (by aspiration) in order to determine their comparative acute effects (Gordon Study). The results of these four complementary studies, and the overall integrative analyses, provide a basis for guiding future research and for helping to determine more targeted emission controls for the PM components most hazardous to acute and chronic health. Application of the knowledge gained in this work may therefore contribute to an optimization of the public health benefits of future PM emission controls. The design of each NPACT study conducted at NYU was guided by our scientific hypotheses, which were based on our reviews of the background literature and our experience in conducting studies of associations between ambient PM and health-related responses. These hypotheses guided the development and conduct of the four studies. Hypothesis 1. Coarse, fine, and ultrafine PM are each capable of producing acute health effects of public health concern, but the effects may differ according to particle size and composition. (Applies to all studies.) Hypothesis 2. Long-term PM2.5 exposures are closely associated with chronic health effects. (Applies to studies 1 and 4.) Hypothesis 3. The source-apportionment techniques that we have developed and refined in recent years provide a useful basis for identifying major categories of sources of PM in ambient air and specific chemical components that have the greatest impacts on a variety of acute and chronic health effects. (Applies to all studies.) Hypothesis 4. The health effects due to ambient PM exposures can best be seen in sensitive subgroups within overall human populations and in animal models of such populations. (Applies to studies 1, 3, and 4.) Overall, the studies have demonstrated that the toxicity of PM is driven by a complex interaction of particle size range, geographic location, source category, and season. These findings suggest that the components of PM--associated with certain categories of sources--are responsible for the observed adverse health effects. Most importantly, the responsible components and source categories vary with the health-related endpoints being assessed. Across all studies, fossil-fuel combustion source categories were most consistently associated with both short- and long-term adverse effects of PM2.5 exposure. The components that originate from the Residual Oil Combustion and Traffic source categories were most closely associated with short-term effects; and components from the Coal Combustion category were more closely associated with long-term effects.

RATIONALE: Although substantial scientific evidence suggests that chronic exposure to ambient air pollution contributes to premature mortality, uncertainties exist in the size and consistency of this association. Uncertainty may arise from inaccurate exposure assessment. OBJECTIVES: To assess the associations of three types of air pollutants (fine particulate matter, ozone [O3], and nitrogen dioxide [NO2]) with the risk of mortality in a large cohort of California adults using individualized exposure assessments. METHODS: For fine particulate matter and NO2, we used land use regression models to derive predicted individualized exposure at the home address. For O3, we estimated exposure with an inverse distance weighting interpolation. Standard and multilevel Cox survival models were used to assess the association between air pollution and mortality. MEASUREMENTS AND MAIN RESULTS: Data for 73,711 subjects who resided in California were abstracted from the American Cancer Society Cancer Prevention II Study cohort, with baseline ascertainment of individual characteristics in 1982 and follow-up of vital status through to 2000. Exposure data were derived from government monitors. Exposure to fine particulate matter, O3, and NO2 was positively associated with ischemic heart disease mortality. NO2 (a marker for traffic pollution) and fine particulate matter were also associated with mortality from all causes combined. Only NO2 had significant positive association with lung cancer mortality. CONCLUSIONS: Using the first individualized exposure assignments in this important cohort, we found positive associations of fine particulate matter, O3, and NO2 with mortality. The positive associations of NO2 suggest that traffic pollution relates to premature death.

IMPORTANCE Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.

The impact of air pollution on fetal growth remains controversial, in part, because studies have been limited to sub-regions of the United States with limited variability. No study has examined air pollution impacts on neonatal health care utilization. We performed descriptive, univariate and multivariable analyses on administrative hospital record data from 222,359 births in the 2000, 2003 and 2006 Kids Inpatient Database linked to air pollution data drawn from the US Environmental Protection Agency's Aerometric Information Retrieval System. In this study, air pollution exposure during the birth month was estimated based on birth hospital address. Although air pollutants were not individually associated with mean birth weight, a three-pollutant model controlling for hospital characteristics, demographics, and birth month identified 9.3% and 7.2% increases in odds of low birth weight and very low birth weight for each mug/m(3) increase in PM(2.5) (both P<0.0001). PM(2.5) and NO(2) were associated with -3.0% odds/p.p.m. and +2.5% odds/p.p.b. of preterm birth, respectively (both P<0.0001). A four-pollutant multivariable model indicated a 0.05 days/p.p.m. NO(2) decrease in length of the birth hospitalization (P=0.0061) and a 0.13 days increase/p.p.m. CO (P=0.0416). A $1166 increase in per child costs was estimated for the birth hospitalization per p.p.m. CO (P=0.0002) and $964 per unit increase in O(3) (P=0.0448). A reduction from the 75th to the 25th percentile in the highest CO quartile for births predicts annual savings of $134.7 million in direct health care costs. In a national, predominantly urban, sample, air pollutant exposures during the month of birth are associated with increased low birth weight and neonatal health care utilization. Further study of this database, with enhanced control for confounding, improved exposure assessment, examination of exposures across multiple time windows in pregnancy, and in the entire national sample, is supported by these initial investigations.Journal of Exposure Science and Environmental Epidemiology advance online publication, 23 January 2013; doi:10.1038/jes.2012.124.