Faculty Bibliography

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.

BACKGROUND: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS: In 2010, the three leading risk factors for global disease burden were high blood pressure (7.0% [95% uncertainty interval 6.2-7.7] of global DALYs), tobacco smoking including second-hand smoke (6.3% [5.5-7.0]), and alcohol use (5.5% [5.0-5.9]). In 1990, the leading risks were childhood underweight (7.9% [6.8-9.4]), household air pollution from solid fuels (HAP; 7.0% [5.6-8.3]), and tobacco smoking including second-hand smoke (6.1% [5.4-6.8]). Dietary risk factors and physical inactivity collectively accounted for 10.0% (95% UI 9.2-10.8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0.9% (0.4-1.6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. FUNDING: Bill & Melinda Gates Foundation.

Background: Asthma is a growing epidemic in the United States. Associations of acute air pollution with asthma hospital admissions have been shown to be modified by co-morbid conditions. However, no known previous study has investigated the modifying effects of concurrent respiratory infections, specifically bronchitis and upper respiratory infection (URI), on these associations. Methods: Data for 105,914 unscheduled hospital admissions in New York City with a primary diagnosis of asthma were obtained for years 2003-2006. A Poisson generalized linear model was applied to determine the association of inter-quartile increases in daily ambient air pollution (i.e., PM2.5, NO2, SO2, and O3) exposures with asthma hospital admissions, after controlling for meteorological and temporal variables. Stratified analyses were conducted for admissions with secondary diagnoses of bronchitis and URI, respectively. Results: Air pollution associations of asthma admissions with a secondary diagnosis of bronchitis were significantly higher vs. admissions without a secondary diagnosis of bronchitis (e.g., PM2.5 risk ratios are 1.19 (95% CI = 1.07-1.30) with bronchitis vs. 1.05 (95% CI = 1.02-1.07) without bronchitis). However, secondary diagnoses of URI did not modify the associations of air pollutants with asthma hospital admissions. These results were observed across multiple pollutants and age groups. Discussion: There is an increased risk of air pollution related asthma hospital admission among individuals with bronchitis, but not with URI. The identification of differential risks based on infection of the bronchioles, but not the upper respiratory tract, provides an opportunity for further investigation into the mechanisms by which air pollution affects respiratory function

Background: Multi-city time-series and long-term cohort studies have reported associations between PM2.5 and both mortality and hospitalizations. However, the specific PM components most responsible for the observed associations have not been established. Objective: To identify PM2.5 sources responsible for both short- and long-term health effects. Methods: We examined both acute and long-term epidemiological associations across the U.S. Using Poisson modeling, daily mortality (years 2001-2006), and elderly hospitalizations (years 2000-2008) were associated with PM2.5 and its chemical components using EPA's CSN data in 150 U.S. cities, and separately for a 64 cities sub-set where PM2.5, its chemical constituents, and gaseous pollutant data were all available. Using the nationwide American Cancer Society CPS-II Cohort, we similarly investigated U.S. mortality associations with components of long-term PM2.5 exposures.. Results: Nationwide factor analyses identified seven major sources: Traffic, Soil, Coal combustion, Salt, Metals, Biogenic Burning, and Residual Oil combustion. The Traffic factor showed most consistent associations with daily all-cause mortality, and with CVD and respiratory hospitalizations. Our extended ACS cohort follow-up analyses (through 2004) indicated that Coal Combustion PM2.5 was most consistently associated with increased risk of IHD mortality. Soil or Wood burning sources were consistently not associated with any causes of mortality. Conclusions: Associations of components of PM2.5 and health varied by outcome (hospitalization vs. mortality), by cause (cardiac vs. respiratory), and between acute and long-term exposures. In general, acute morbidity and mortality associations were most related to traffic-related components, while chronic mortality was most strongly associated with long-term exposure to Coal Combustion PM2.5

Background. Particulate matter (PM) is a complex mixture of chemical constituents affecting health risks. However, current health-based PM standards are limited to mass concentrations. Objective. To conduct an integrated series of toxicology and epidemiology studies to determine which PM components are most influential. Methods. Using EPA's CSN data enabled us to study the influence of PM2.5 components on: 1) shortterm human morbidity and mortality in 150 US cities; and 2) annual mortality rates in 100 US cities. We also conducted: 3) a series of 6-month subchronic inhalation studies (6 h/d, 5 d/wk) of concentrated (10X) ambient air PM2.5 (CAPs) in ApoE-/- mice in five U.S. airsheds; and 4) we administered aliquots of PM10-2.5, PM2.5-0.2, and PM<0.2 samples from the same 5 airsheds to cells in vitro, and to mouse lungs in vivo by aspiration to determine their comparative acute effects. Results. Across all four substudies, fossil-fuel combustion sources were most consistently associated with both short- and long-term cardiovascular disease (CVD) effects. Daily human CVD mortality and hospital admissions, and cardiac function in the mice, were most closely associated with constituents from residual oil combustion and traffic, while annual human CVD mortality and aortic plaque progression in the mice were more closely associated with coal combustion effluents. Conclusions. 1) PM toxicity is driven by a complex interaction of particle size, study site, and season; 2) the most influential constituents vary with endpoint. These results can: 1) guide future research; selection of emission controls; and 3) optimization of the public health benefits