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.

Climate change-induced environmental stressors, including ambient particulate matter (PM_2.5) and extreme heat stress (HS), pose serious health risks, particularly for neurodegenerative diseases. PM_2.5 exacerbates cardiovascular and neurodegenerative conditions, while HS increases mortality and worsens air pollution. Combined exposure may amplify these effects, especially in vulnerable populations at risk for Alzheimer's disease (AD). In our experimental study using a mouse model of early-onset Alzheimer's disease (EOAD), we explored the combined effects of extreme weather conditions, particularly exposure to ambient PM_2.5 and HS. Our research indicated that even short, repeated exposure to these environmental stressors disrupts brain energy metabolism and mitochondrial respiratory functions, which we found to be associated with altered hippocampal synaptic functions. Additionally, we find that key mechanisms associated with impaired intestinal permeability and gut dysbiosis are affected, supporting the hypothesis that exposure to climate change communication may also disrupt the gut-brain axis, as in part evidenced in our study by peripheral changes in immune and inflammatory signaling. Moreover, despite significant disruptions in metabolic and immune-inflammatory pathways, we observed no acceleration of cognitive decline in the young asymptomatic EOAD mice subjected to short, repeated exposure to extreme heat and environmental PM_2.5. These findings highlight the potential role of climate change in promoting risk factors like neuroinflammation and gut-brain axis dysfunction due to gut microbiome dysbiosis in the onset and progression of AD, particularly in asymptomatic individuals at risk for developing the condition.

The objective of this study is to investigate the potential mutagenic effects of the exposure of mice to aerosols produced from the component liquids of an electronic nicotine delivery system (ENDS). The use of electronic cigarettes (e-cigs) and ENDSs has increased tremendously over the past two decades. From what we know to date, ENDSs contain much lower levels of known carcinogens than tobacco smoke. While conventional tobacco smoke is a well-established mutagen, little is known about the mutagenicity of ENDS aerosols. Here, we report the mutagenic effects of a 3-month whole body exposure of C57 lacI mice (BigBlue^TM) to filtered air (AIR) or ENDS aerosols in several tissues. Aerosols were generated from a 50/50 vegetable glycerin (VG)/propylene glycol (PG) mixture with and without nicotine. The results revealed that in the lung, bladder urothelial tissue, and tongue, mutagenesis was significantly greater in the VG/PG/nicotine group than in the AIR group. In all organs except the bladder, mutagenesis in the VG/PG only group was similar to those exposed to AIR. In the bladder, mutagenesis in the VG/PG group was elevated compared to that in the AIR group. In the liver, mutagenesis was modestly elevated in the VG/PG/nicotine group, but the elevation failed to reach statistical significance. Overall, there were no consistent differences in mutagenesis between the sexes. The results of this study suggest that exposure to e-cig aerosols containing nicotine represents a risk factor for carcinogenesis in several organ systems, and exposure to VG/PG alone may be a risk factor for bladder cancer.

BACKGROUND:Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence. METHODS:In 91 early-stage (Stage IA/IB) LUAD-patients with extensive follow-up, we used 16s rRNA gene sequencing and host RNA-sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples. RESULTS:23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways. CONCLUSIONS:Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83). IMPACT/CONCLUSIONS:This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.