Faculty Bibliography

The New York City (NYC) subway is the main mode of transport for over 5 million passengers on an average weekday. Therefore, airborne pollutants in the subway stations could have a significant impact on commuters and subway workers. This study looked at black carbon (BC) and particulate matter concentrations (PM2.5) in selected subway stations in Manhattan. BC and PM2.5 levels were measured in real time using a Micro-Aethalometer and a PDR-1500 Data RAM, respectively. Simultaneous samples were also collected on quartz filters for Organic and Elemental carbon (OC/EC) analysis and on Teflon filters for gravimetric and trace element analysis. In the underground subway stations, mean real time BC concentrations ranged from 5 to 23 microg/m3, with 1 minute average peaks >100 microg/m3, while real time PM2.5 levels ranged from 35 to 200 microg/m3. Mean EC levels ranged from 9 to 12.5 microg/m3. At street level on the same days, the mean BC and PM2.5 concentrations were below 3 microg/m3 and 10 microg/m3, respectively. This study shows that both BC soot and PM levels in NYC's subways are considerably higher than ambient urban street levels, and further monitoring and investigation of BC and PM subway exposures are warranted.

Abstract Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles.

The purpose of this review is to examine the rapidly expanding literature regarding the effects of prenatal tobacco and postnatal secondhand smoke (SHS) exposure on child health and development. Mechanisms of SHS exposure are reviewed, including critical periods during which exposure to tobacco products appears to be particularly harmful to the developing fetus and child. The biological, biochemical, and neurologic effects of the small fraction of identified components of SHS are described. Research describing these adverse effects of both in utero and childhood exposure is reviewed, including findings from both animal models and humans. The following adverse physical outcomes are discussed: sudden infant death syndrome, low birth weight, decreased head circumference, respiratory infections, otitis media, asthma, childhood cancer, hearing loss, dental caries, and the metabolic syndrome. In addition, the association between the following adverse cognitive and behavioral outcomes and such exposures is described: conduct disorder, attention-deficit/hyperactivity disorder, poor academic achievement, and cognitive impairment. The evidence supporting the adverse effects of SHS exposure is extensive yet rapidly expanding due to improving technology and increased awareness of this profound public health problem. The growing use of alternative tobacco products, such as hookahs (a.k.a. waterpipes), and the scant literature on possible effects from prenatal and secondhand smoke exposure from these products are also discussed. A review of the current knowledge of this important subject has implications for future research as well as public policy and clinical practice.

Susceptibility to chronic beryllium disease (CBD) is linked to certain HLA-DP molecules, including HLA-DP2. To elucidate the molecular basis of this association, we exposed mice transgenic (Tg) for HLA-DP2 to beryllium oxide (BeO) via oropharyngeal aspiration. As opposed to WT mice, BeO-exposed HLA-DP2 Tg mice developed mononuclear infiltrates in a peribronchovascular distribution that were composed of CD4(+) T cells and included regulatory T (Treg) cells. Beryllium-responsive, HLA-DP2-restricted CD4(+) T cells expressing IFN-gamma and IL-2 were present in BeO-exposed HLA-DP2 Tg mice and not in WT mice. Using Be-loaded HLA-DP2-peptide tetramers, we identified Be-specific CD4(+) T cells in the mouse lung that recognize identical ligands as CD4(+) T cells derived from the human lung. Importantly, a subset of HLA-DP2 tetramer-binding CD4(+) T cells expressed forkhead box P3, consistent with the expansion of antigen-specific Treg cells. Depletion of Treg cells in BeO-exposed HLA-DP2 Tg mice exacerbated lung inflammation and enhanced granuloma formation. These findings document, for the first time to our knowledge, the development of a Be-specific adaptive immune response in mice expressing HLA-DP2 and the ability of Treg cells to modulate the beryllium-induced granulomatous immune response.

Occupational exposure limits (OELs) are important tools for managing worker exposures to chemicals; however, hazard data for many engineered nanomaterials (ENMs) are insufficient for deriving OELs by traditional methods. Technical challenges and questions about how best to measure worker exposures to ENMs also pose barriers to implementing OELs. New varieties of ENMs are being developed and introduced into commerce at a rapid pace, further compounding the issue of OEL development for ENMs. A Workshop on Strategies for Setting Occupational Exposure Limits for Engineered Nanomaterials, held in September 2012, provided an opportunity for occupational health experts from various stakeholder groups to discuss possible alternative approaches for setting OELs for ENMs and issues related to their implementation. This report summarizes the workshop proceedings and findings, identifies areas for additional research, and suggests potential avenues for further progress on this important topic.

Particulates from air pollution are implicated in causing or exacerbating respiratory and systemic cardiovascular diseases and are thought to be among the leading causes of morbidity and mortality. However, the contribution of ambient particulate matter to diseases affecting the pulmonary circulation, the right heart, and especially pulmonary hypertension is much less documented. Our own work and that of other groups has demonstrated that prolonged exposure to antigens via the airways can cause severe pulmonary arterial remodeling. In addition, vascular changes have been well documented in a typical disease of the airways, asthma. These experimental and clinical findings link responses in the airways with responses in the lung's vasculature. It follows that particulate air pollution could cause, or exacerbate, diseases in the pulmonary circulation and associated pulmonary hypertension. This perspective details the literature for support of this concept. Data regarding the health effects of particulate matter from air pollution on the lung's vasculature, with emphasis on the lung's inflammatory responses to particulate matter deposition and pulmonary hypertension, are discussed. A deeper understanding of the health implications of exposure to ambient particulate matter will improve our knowledge of how to improve the management of lung diseases, including diseases of the pulmonary circulation. As man-made ambient particulate air pollution is typically linked to economic growth, a better understanding of the health effects of exposure to particulate air pollution is expected to integrate the global goal of achieving healthy living for all.

INTRODUCTION: U.S. adolescents increasingly use alternative tobacco products (ATPs), including hookah. No study has previously assessed correlates of adolescent hookah use in a nationally representative sample. METHODS: Cross-sectional, nationally representative data of adolescents from the 2011 National Youth Tobacco Survey (NYTS) were used. Student demographics and their use of, exposure to, and beliefs about tobacco were examined as correlates of hookah use. RESULTS: Of adolescents nationwide, 7.3% reported ever trying hookah and 2.6% reported using hookah within the past month. Increasing age was associated with trying hookah, but not current hookah use. Sex was unassociated with hookah use. Asians were most likely to have tried hookah; Hispanics and those of another race reported greater current hookah use. Hookah use increased with perceived ease of access to and willingness to try tobacco. Students with a hookah user at home were more likely to have tried hookah and to currently use hookah. Current cigarette use was not associated with current hookah use (odds ratio [OR] = 1.3, 95% CI = 0.8-2.1), but was associated with trying hookah (OR = 1.5, 95% CI = 1.1-2.2). Non-cigarette tobacco use was associated with trying hookah (OR = 2.7, 95% CI = 2.1-3.5) and current hookah use (OR = 4.8, 95% CI = 2.7-8.7). CONCLUSIONS: A sizeable minority of U.S. adolescents use hookah, particularly those living with hookah users, those who use other ATPs, and those who perceive tobacco as easily accessible. Current cigarette use was not associated with current hookah use. Future studies assessing the dangers of hookah use and interventions to curb this emerging problem appear warranted.

Tobacco use, primarily in the form of cigarettes, is the leading cause of preventable morbidity and mortality in the United States (U.S.). The adverse effects of tobacco use began to be recognized in the 1940's and new hazards of active smoking and secondhand smoke (SHS) exposure from cigarettes continue to be identified to this day. This has led to a sustained and wide-ranging array of highly effective regulatory, public health, and clinical efforts that have been informed by extensive scientific data, resulting in marked decreases in the use of cigarettes. Unfortunately, the dramatic recent decline in cigarette use in the U.S., has been accompanied by an upsurge in adolescent and young adult use of new, non-cigarette tobacco and nicotine-delivery products, commonly referred to as alternative tobacco products (ATPs). Commonly used ATPs include hookah, cigars, smokeless tobacco, and electronic cigarettes. While there have been a number of review articles that focus on adult ATP use, the purpose of this review is to provide an overview of what is, and is not known about emerging ATP use among U.S. adolescents on a national scale; as well as to identify research gaps in knowledge, and discuss future health and policy needs for this growing public health concern. This paper is not meant to systemically review all published survey data, but to present clear depiction of selected ATP usage in youth populations using national survey data.

Abstract Particulate matter (PM) varies in chemical composition and mass concentration based on a number of factors including location, season, source and particle size. The aim of this study was to evaluate the in vitro and in vivo toxicity of coarse and fine PM simultaneously collected at three rural and two urban sites within the metropolitan New York City (NYC) region during two seasons, and to assess how particle size and elemental composition affect toxicity. Human pulmonary microvascular endothelial (HPMEC-ST1.6R) and bronchial epithelial (BEAS-2B) cell lines were exposed to PM (50 mug/mL) and analyzed for reactive oxygen species (ROS). Mice (FVB/N) were exposed by oropharyngeal aspiration to 50 microg PM, and lavage fluid was analyzed for total protein and PMN influx. The ROS response was greater in the HPMEC-ST1.6R cell line compared to BEAS-2B cells, but the responses were significantly correlated (p < 0.01). The ROS response was affected by location, locale and the location:size interaction in both cell lines, and an additional association for size was observed from HPMEC-ST1.6R cells. Urban fine PM generated the highest ROS response. In the mouse model, inflammation was associated with particle size and by a season:size interaction, with coarse PM producing greater PMN inflammation. This study showed that the aerodynamic size, locale (i.e. urban versus rural), and site of PM samples affected the ROS response in pulmonary endothelial and epithelial cells and the inflammatory response in mice. Importantly, these responses were dependent upon the chemical composition of the PM samples.