Faculty Bibliography

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic cigarette (e-cigarette) vaping has surpassed conventional cigarette smoking among adolescents and young adults in the United States and beyond. This review describes the experimental and clinical evidence of e-cigarette toxicity and deleterious health effects. Adverse health effects related to e-cigarette aerosols are influenced by several factors, including e-liquid components, physical device factors, chemical changes related to heating, and health of the e-cigarette user (e.g., asthmatic). Federal, state, and local regulations have attempted to govern e-cigarette flavors, manufacturing, distribution, and availability, particularly to underaged youths. However, the evolving e-cigarette landscape continues to impede timely toxicological studies and hinder progress made toward our understanding of the long-term health consequence of e-cigarettes. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

OBJECTIVES/OBJECTIVE:The goals of this study were to assess the air quality in subway systems in the northeastern United States and estimate the health risks for transit workers and commuters. METHODS: RESULTS: DISCUSSION/CONCLUSIONS:

BACKGROUND:E-cigarette use (vaping) is an emerging public health problem. Depression has been found to be associated with e-cigarette use, and vaping and depression are each associated with elevated systemic inflammation. To date, the role of inflammation in the relationship between vaping and depression has not been explored. OBJECTIVE:To assess the independent associations between e-cigarette use, depression, and inflammation, and to investigate whether the likelihood of depression among current e-cigarette users is associated with systemic inflammation. METHODS:= 4961). Systemic inflammation was defined as serum C-reactive protein (CRP) ≥ 8.0 mg/L. Depressed individuals were characterized by a score ≥ 10 on the Patient Health Questionnaire-9 (PHQ-9). Current e-cigarette users were defined as individuals who vaped at least once in the past 30 days and these individuals were stratified by use: exclusive users (reported smoking less than 100 combustible cigarettes in their lifetime), dual users (reported current use of electronic and combustible cigarettes), and e-cigarette users who were previous smokers. Bivariate analyses were used to assess independent associations between vaping, depression, and inflammation; and weighted logistic regression analyses adjusting for BMI, sex, and economic status were used to determine the odds ratios (ORs) for depression by e-cigarette category stratified by differential CRP levels. RESULTS:-values > 0.05). CONCLUSION:While a pattern of greater ORs for depression among e-cigarette users with elevated CRP provides provocative findings that might suggest a potential role of inflammation in the association between vaping and depression, we failed to find evidence that inflammation clearly moderates this association. While it is possible that depression among e-cigarette users may be influenced by systemic inflammation, a reproduction of the current study is necessary among a larger cohort to elucidate the effect of inflammation on depression among e-cigarette users.

BACKGROUND:Particle matter (PM) has been associated with increased morbidity and mortality rates across the world. This study was designed to test the hypotheses that pyrotechnic firework displays introduce significant amounts of toxic metals into the atmosphere and are hazardous to human health. Size-selective emissions from 10 different fireworks displays were collected during particle generation in a dynamic, stainless steel chamber and tested for toxicity in cells. A subset of 2 particle types were tested in vivo in mice. At doses that did not produce cytotoxicity in an LDH assay, in vitro reactive oxygen species (ROS) formation was measured in bronchial epithelial airway (BEAS-2B) and human pulmonary microvascular endothelial (HPMEC-ST1.6R) cell lines treated with size-fractionated particles from the emissions of fireworks. RESULTS:sample for the fireworks type producing the greatest in vitro ROS response in BEAS-2B cells contained ~ 40,000 and ~ 12,000 ppm of lead and copper, respectively. This sample also produced the greatest inflammatory response (i.e., increased neutrophils in bronchoalveolar lavage fluid) in mice. CONCLUSIONS:These findings demonstrate that pyrotechnic display particles can produce adverse effects in mammalian cells and lungs, thus suggesting that further research is needed to expand our understanding of the contribution of metal content to the adverse health effects of fireworks particles. This information will lead to the manufacture of safer fireworks.

BACKGROUND:With the number of annual global travelers reaching 1.2 billion, many individuals encounter greater levels of air pollution when they travel abroad to megacities around the world. This study's objective was to determine if visits to cities abroad with greater levels of air pollution adversely impacts cardiopulmonary health. METHODS:Thirty-four non-smoking, adult, healthy participants who traveled abroad to selected cities from the NYC metropolitan area were pre-trained to measure lung function, blood pressure, heart rate/variability, and record symptoms before, during, and after traveling abroad. Outdoor PM2.5 concentrations were obtained from central monitors in each city. Associations between PM exposure concentrations and cardiopulmonary health endpoints were analyzed using a mixed effects statistical design. RESULTS:East and South Asian cities had significantly higher PM2.5 concentrations compared to pre-travel NYC PM2.5 levels, with maximum concentrations reaching 503 μg/m3. PM exposure-related associations for lung function were statistically significant and strongest between evening FEV1 and same day morning PM2.5 concentrations: a 10 μg/m3 increase in outdoor PM2.5 was associated with a mean decrease of 7 ml. Travel to a highly polluted city (PM2.5 > 100 μg/m3) was associated with a 209 ml reduction in evening FEV1 compared to a low polluted city (PM2.5 < 35 μg/m3). In general, participants who traveled to East and South Asian cities experienced increased respiratory symptoms/scores and changes in heart rate and heart rate variability. CONCLUSIONS:Exposure to increased levels of PM2.5 in cities abroad caused small but statistically significant acute changes in cardiopulmonary function and respiratory symptoms in healthy young adults. These data suggest that travel-related exposure to increased PM2.5 adversely impacts cardiopulmonary health, which may be particularly important for travelers with pre-existing respiratory or cardiac disease.

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.

Food carts are common along streets in cities throughout the world. In North America, food cart vendors generally use propane, charcoal, or both propane and charcoal (P and C) for food preparation. Although cooking emissions are known to be a major source of indoor air pollution, there is limited knowledge on outdoor cooking's impact on the ambient environment and, in particular, the relative contribution of the different cooking fuels. This field study investigated the air pollution the public is exposed to in the micro-environment around 19 food carts classified into 3 groups: propane, charcoal, and P and C carts. Concentrations near the food carts were measured using both real-time and filter-based methods. Mean real-time concentrations of PM_2.5, BC_2.5, and particle counts were highest near the charcoal food carts: 196 μg/m³, 5.49 μg/m³, and 69,000 particles/cm³, respectively, with peak exposures of 1520 μg/m³, 67.9 μg/m³, and 235,000 particles/cm³, respectively. In order of pollution emission impacts: charcoal > P and C > propane carts. Thus, significant differences in air pollution emissions occurred in the vicinity of mobile food carts, depending on the fuel used in food preparation. Local air pollution polices should consider these emission factors in regulating food cart vendor operations.

OBJECTIVE:), is associated with oxidative stress, DNA damage and inflammation, leading to premature signs of skin aging. Because much of the damage results from oxidative stress, we examined the effects of a topical composition containing three antioxidants in an in vitro model system to assess the potential for amelioration of premature aging. The use of multiple antioxidants was of interest based on the typical composition of therapeutic skincare products. It is important to determine the efficacy of multiple antioxidants together and develop a short-term assay for larger scale efficacy testing. METHODS:in the presence and absence of an antioxidant mixture of resveratrol, niacinamide and GHK peptide. Endpoints related to inflammation, premature aging and carcinogenicity were monitored after 5 h of exposure and included IL-6, CXCL10, MMP-1 and NRF2. Differentially expressed genes were monitored by RNA-seq. RESULTS:and suppressed by antioxidants. CONCLUSIONS:Specific signalling pathways known to be correlated with skin inflammation and aging were examined based on their suitability for use in efficacy testing for the prevention of skin damage due to ambient hydrocarbon pollution. Endpoints examined after only 5 h of exposure provide a useful method amenable to high through-put screening. The results obtained reinforce the concept that a multiple antioxidant preparation, topically applied, may reduce pro-inflammatory signalling and cellular damage and thereby reduce premature skin aging due to exposure to rural-derived airborne pollution.

Scientific progress and ethical considerations are increasingly shifting the toxicological focus from in vivo animal models to in vitro studies utilizing physiologically relevant cell cultures. Consequently, we evaluated and validated a three-dimensional (3D) model of the human lung using Calu-3 cells cultured at an air-liquid interface (ALI) for 28 days. Assessment of seven essential genes of differentiation and transepithelial electrical resistance (TEER) measurements, in conjunction with mucin (MUC5AC) staining, validated the model. We observed a time-dependent increase in TEER, genetic markers of mucus-producing cells (muc5ac, muc5b), basal cells (trp63), ciliated cells (foxj1), and tight junctions (tjp1). A decrease in basal cell marker krt5 levels was observed. Subsequently, we utilized this validated ALI-cultured Calu-3 model to investigate the adversity of the aerosols generated from three flavored electronic cigarette (EC) e-liquids: cinnamon, vanilla tobacco, and hazelnut. These aerosols were compared against traditional cigarette smoke (3R4F) to assess their relative toxicity. The aerosols generated from PG/VG vehicle control, hazelnut and cinnamon e-liquids, but not vanilla tobacco, significantly decreased TEER and increased lactate dehydrogenase (LDH) release compared to the incubator and air-only controls. Compared to 3R4F, there were no significant differences in TEER or LDH with the tested flavored EC aerosols other than vanilla tobacco. This starkly contrasted our expectations, given the common perception of e-liquids as a safer alternative to cigarettes. Our study suggests that these results depend on flavor type. Therefore, we strongly advocate for further research, increased user awareness regarding flavors in ECs, and rigorous regulatory scrutiny to protect public health.