Faculty Bibliography

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.

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.

BACKGROUND:Particle size-selective sampling refers to the collection of particles of varying sizes that potentially reach and adversely affect specific regions of the respiratory tract. Thoracic and respirable fractions are defined as the fraction of inhaled particles capable of passing beyond the larynx and ciliated airways, respectively, during inhalation. In an attempt to afford greater protection to exposed individuals, current size-selective sampling criteria overestimate the population means of particle penetration into regions of the lower respiratory tract. The purpose of our analyses was to provide estimates of the thoracic and respirable fractions for adults and children during typical activities with both nasal and oral inhalation, that may be used in the design of experimental studies and interpretation of health effects evidence. METHODS:We estimated the fraction of inhaled particles (0.5-20 μm aerodynamic diameter) penetrating beyond the larynx (based on experimental data) and ciliated airways (based on a mathematical model) for an adult male, adult female, and a 10 yr old child during typical daily activities and breathing patterns. RESULTS:Our estimates show less penetration of coarse particulate matter into the thoracic and gas exchange regions of the respiratory tract than current size-selective criteria. Of the parameters we evaluated, particle penetration into the lower respiratory tract was most dependent on route of breathing. For typical activity levels and breathing habits, we estimated a 50% cut-size for the thoracic fraction at an aerodynamic diameter of around 3 μm in adults and 5 μm in children, whereas current ambient and occupational criteria suggest a 50% cut-size of 10 μm. CONCLUSIONS:By design, current size-selective sample criteria overestimate the mass of particles generally expected to penetrate into the lower respiratory tract to provide protection for individuals who may breathe orally. We provide estimates of thoracic and respirable fractions for a variety of breathing habits and activities that may benefit the design of experimental studies and interpretation of particle size-specific health effects.

Air pollution contributes to acute exacerbations of asthma and the development of asthma in children and adults. Airway epithelial cells interface innate and adaptive immune responses, and have been proposed to regulate much of the response to pollutants. Thymic stromal lymphopoietin (TSLP) is a pivotal cytokine linking innate and Th2 adaptive immune disorders, and is upregulated by environmental pollutants, including ambient particulate matter (PM) and diesel exhaust particles (DEP). We show that DEP and ambient fine PM upregulate TSLP mRNA and human microRNA (hsa-miR)-375 in primary human bronchial epithelial cells (pHBEC). Moreover, transfection of pHBEC with anti-hsa-miR-375 reduced TSLP mRNA in DEP but not TNF-alpha-treated cells. In silico pathway evaluation suggested the aryl hydrocarbon receptor (AhR) as one possible target of miR-375. DEP and ambient fine PM (3 mug/cm(2)) downregulated AhR mRNA. Transfection of mimic-hsa-miR-375 resulted in a small downregulation of AhR mRNA compared with resting AhR mRNA. AhR mRNA was increased in pHBEC treated with DEP after transfection with anti-hsa-miR-375. Our data show that two pollutants, DEP and ambient PM, upregulate TSLP in human bronchial epithelial cells by a mechanism that includes hsa-miR-375 with complex regulatory effects on AhR mRNA. The absence of this pathway in TNF-alpha-treated cells suggests multiple regulatory pathways for TSLP expression in these cells.

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

The ability of tobacco smoke (TS) to modulate phase I and II enzymes and affect metabolism of tobacco carcinogens is likely an important factor in its carcinogenicity. For the first time several types of TS particulates (TSP) were compared in different primary cultured human oral epithelial cells (NOE) for their abilities to affect metabolism of the tobacco carcinogen, (BaP) to genotoxic products, and expression of drug metabolizing enzymes. TSP from, reference filtered (2RF4), mentholated (MS), reference unfiltered, (IR3), ultra low tar (UL), and cigarettes that primarily heat tobacco (ECL) were tested. Cells pretreated with TSP concentrations of 0.2-10 mug/ml generally showed increased rates of BaP metabolism; those treated with TSP concentrations above 10 mug/ml showed decreased rates. Effects of TSPs were similar when expressed on a weight basis. Weights of TSP/cigarette varied in the order: MS approximately IR3>2RF4>ECL>UL. All TSPs induced the phase I proteins, cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1), phase II proteins, NAD(P)H dehydrogenase quinone 1 (NQO1), and microsomal glutathione S-transferase 1 (MGST1), and additionally, hydroxysteroid (17-beta) dehydrogenase 2 (HSD17B2), as assessed by qRT-PCR. The pattern of gene induction at probable physiological levels favored activation over detoxification.

Ambient particulate matter, including diesel exhaust particles (DEP), promotes the development of allergic disorders. DEP increase oxidative stress and influence human bronchial epithelial cell (HBEC)-dendritic cell interactions via cytokines, including thymic stromal lymphopoietin (TSLP). Upregulation of TSLP results in Th2 responses. Using primary culture HBEC and human myeloid dendritic cell (mDC) cocultures, we show in this study that DEP upregulation of Th2 responses occurred via HBEC-dependent mechanisms that resulted from oxidative stress. Moreover, DEP-treated HBEC and ambient particulate matter-treated HBEC upregulated OX40 ligand (OX40L) and the Notch ligand Jagged-1 mRNA and expression on mDC. Upregulation of OX40L as well as Jagged-1 on mDC required HBEC and did not occur in the presence of N-acetylcysteine. Furthermore, OX40L and Jagged-1 upregulation was inhibited when HBEC expression of TSLP was silenced. Thus, DEP treatment of HBEC targeted two distinct pathways in mDC that were downstream of TSLP expression. Upregulation of OX40L and Jagged-1 by mDC resulted in mDC-driven Th2 responses. These studies expand our understanding of the mechanism by which ambient pollutants alter mucosal immunity and promote disorders such as asthma