Faculty Bibliography

Recent studies have demonstrated that mobile sampling can improve the spatial granularity of land use regression (LUR) models. Mobile sampling campaigns deploying low-cost (<$300) air quality sensors could potentially offer an inexpensive and practical approach to measure and model air pollution concentration levels. In this study, we developed LUR models for street-level fine particulate matter (PM_2.5) concentration levels in Seoul, South Korea. 169 h of data were collected from an approximately three week long campaign across five routes by ten volunteers sharing seven AirBeams, a low-cost ($250 per unit), smartphone-based particle counter, while geospatial data were extracted from OpenStreetMap, an open-source and crowd-generated geographical dataset. We applied and compared three statistical approaches in constructing the LUR models - linear regression (LR), random forest (RF), and stacked ensemble (SE) combining multiple machine learning algorithms - which resulted in cross-validation R² values of 0.63, 0.73, and 0.80, respectively, and identification of several pollution 'hotspots.' The high R² values suggest that study designs employing mobile sampling in conjunction with multiple low-cost air quality monitors could be applied to characterize urban street-level air quality with high spatial resolution, and that machine learning models could further improve model performance. Given this study design's cost-effectiveness and ease of implementation, similar approaches may be especially suitable for citizen science and community-based endeavors, or in regions bereft of air quality data and preexisting air monitoring networks, such as developing countries.

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.

Fine ambient particulate matter (PM2.5) is able to induce sympathetic activation and inflammation in the brain. However, direct evidence demonstrating an essential role of sympathetic activation in PM2.5-associated disease progression is lacking. We assess the contribution of α2B-adrenergic receptor (Adra2b) in air pollution-associated hypertension and behavioral changes in this study. Wild-type mice and Adra2b-transgenic mice overexpressing Adra2b in the brain (Adra2bTg) were exposed to concentrated PM2.5 or filtered air for 3 months via a versatile aerosol concentrator exposure system. Mice were fed with a high salt diet (4.0% NaCl) for 1 week at week 11 of exposure to induce blood pressure elevation. Intra-arterial blood pressure was monitored by radio-telemetry and behavior changes were assessed by open field, light-dark, and prepulse inhibition tests. PM2.5 exposure increased Adra2b in the brain of wild-type mice. Adra2b overexpression enhanced the anxiety-like behavior and high salt diet-induced blood pressure elevation in response to air pollution but not filtered air exposure. Adra2b overexpression induced upregulation of inflammatory genes such as TLR2, TLR4, and IL-6 in the brain exposed to PM2.5. In addition, there were increased frequencies of activated effector T cells and increased expression of oxidative stress-related genes, such as SOD1, NQO1, Nrf2, and Gclm in Adra2bTg mice compared with wild-type mice. Our results provide new evidence of distinct behavioral changes consistent with anxiety and blood pressure elevation in response to high salt intake and air pollution exposure, highlighting the importance of centrally expressed Adra2b in the vulnerability to air pollution exposure.

Indoor air pollution from bituminous coal combustion has been linked to the extremely high lung cancer rates of nonsmoking women in Xuan Wei County, Yunnan Province, China. Venting the smoke outdoors by installing chimneys was found to be effective at reducing the lung cancer risk in a cohort study of 21,232 farmers in central Xuan Wei. However, the lung cancer mortality rates in all 1.2 million residents of Xuan Wei have been increasing dramatically over the last four decades. It was higher than that in Yunnan Province and China overall, with significant heterogeneities in the geographic patterns of Xuan Wei. Intervention measures targeting certain types of coal or certain carcinogenic components in coal smoke need to be explored. To inform targeted intervention policies, it is essential to pinpoint the specific substance (particulate matter, organic extract, PAHs, free radicals, crystalline silica, and inorganic matter) that might account for the carcinogenicity of bituminous coal smoke. Exploring the underlying carcinogenesis mechanisms would also contribute to the intervention and control of the lung cancer epidemic in Xuan Wei, China. Here we review the suspected carcinogens and carcinogenesis mechanisms and discuss future research directions towards a better understanding of the etiology of lung cancer in Xuan Wei, China.

BACKGROUND:In Xuan Wei, China, the lung cancer mortality rate is rising significantly more than that of the nation overall. However, it remains unclear 1) if improved diagnosis can just partially explain this observation and how other local risk factors may be correlated with the lung cancer mortality rate and 2) how the lung cancer mortality rates differ within Xuan Wei and how these spatiotemporal patterns are linked with local risk factors. To increase etiological knowledge, this study evaluated the spatial and temporal distributions of the health effects (the lung cancer mortality rates) from 2011 to 2015. METHODS:Four steps of spatial analysis were applied, as follows: 1) hotspot analysis to determine the geographical patterns of lung cancer mortality, 2) spatially-weighted sum to identify areas with higher health risks, 3) bivariate statistical analysis to assess the overall correlation between coal mines and lung cancer mortality, and 4) geographically-weighted regression to test for correlations among different towns within Xuan Wei. RESULTS:Women had higher lung cancer mortality rates than those in men, with an increasing trend in both sexes over time. The incidence rates in Laibin Town were the highest in Xuan Wei every year. Over the 5-year study period, the lung cancer mortality was increasingly concentrated in Laibin, Shuanglong, and Longchang, where the smoky coal mines are most concentrated. The population-level health risks from the coal mine in Xuan Wei were mapped and divided into five types of risk areas (Type I - Type IV). Correlation analysis revealed that there was no significant correlation between lung cancer mortality as a whole and coal mine distribution during the 5-year study period. However, the geographically-weighted regression revealed a stronger correlation in medium (Type III) and second-lowest (Type IV) health risks. CONCLUSIONS:Xuan Wei lung cancer mortality has increased continuously since the third national retrospective surveys on the causes of death by the Ministry of Health of the People's Republic of China (2004-2005), especially for local women and residents over 35 years of age. Geographically, lung cancer in Xuan Wei showed unique spatiotemporal clustering. The local lung cancer mortality was significantly correlated with the smoky coal mine geographically. Some specific towns (Laibin, Shuanglong, and Longchang) within Xuan Wei manifested high correlations between lung cancer mortality and coal mines. The effects of coal mines on lung cancer mortality rates also spread geographically outward from these areas. Public health concern regarding lung cancer in Xuan Wei should prioritize higher-risk towns surrounded by smoking coal mines. Intervention strategies for particular toxic coal types require further studies on their chemical characteristics and mechanisms of carcinogenesis. Additional studies are also warranted to systematically examine the local environmental health risks related to coal industries and combustion air pollution and eventually to conduct early screening of lung cancer for local people who are more exposed to smoky coal in high-risk areas.

BACKGROUND:The popularity of electronic cigarettes (E-cigarettes) has risen considerably. Several studies have suggested that nicotine may affect insulin resistance, however, the impact of E-cigarette exposure on insulin resistance, an early measure of cardiometabolic risk, is not known. METHODS AND RESULTS/RESULTS:Using experimental animals and human data obtained from 3,989 participants of the United States National Health and Nutrition Examination Survey (NHANES), respectively, we assessed the association between E-cigarette and conventional cigarette exposures and insulin resistance, as modelled using the homeostatic model assessment of insulin resistance (HOMA-IR) and glucose tolerance tests (GTT). C57BL6/J mice (on standard chow diet) exposed to E-cigarette aerosol or mainstream cigarette smoke (MCS) for 12 weeks showed HOMA-IR and GTT levels comparable with filtered air-exposed controls. In the NHANES cohort, there was no significant association between defined tobacco product use categories (non-users; sole E-cigarette users; cigarette smokers and dual users) and insulin resistance. Compared with non-users of e-cigarettes/conventional cigarettes, sole E-cigarette users showed no significant difference in HOMA-IR or GTT levels following adjustment for age, sex, race, physical activity, alcohol use and BMI. CONCLUSION/CONCLUSIONS:E-cigarettes do not appear to be linked with insulin resistance. Our findings may inform future studies assessing potential cardiometabolic harms associated with E-cigarette use.

Tobacco smoke (TS) contains numerous cancer-causing agents, with polycyclic aromatic hydrocarbons (PAHs) and nitrosamines being most frequently cited as the major TS human cancer agents. Many lines of evidence seriously question this conclusion. To resolve this issue, we determined DNA adducts induced by the three major TS carcinogens: benzo(a)pyrene (BP), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanoe (NNK), and aldehydes in humans and mice. In mice, TS induces abundant aldehyde-induced γ-hydroxy-propano-deoxyguanosine (γ-OH-PdG) and α-methyl-γ-OH-PdG adducts in the lung and bladder, but not in the heart and liver. TS does not induce the BP- and NNK-DNA adducts in lung, heart, liver, and bladder. TS also reduces DNA repair activity and the abundance of repair proteins, XPC and OGG1/2, in lung tissues. These TS effects were greatly reduced by diet with polyphenols. We found that γ-OH-PdG and α-methyl-γ-OH-PdG are the major adducts formed in tobacco smokers' buccal cells as well as the normal lung tissues of tobacco-smoking lung cancer patients, but not in lung tissues of nonsmokers. However, the levels of BP- and NNK-DNA adducts are the same in lung tissues of smokers and nonsmokers. We found that while BP and NNK can induce BPDE-dG and O⁶-methyl-dG adducts in human lung and bladder epithelial cells, these inductions can be inhibited by acrolein. Acrolein also can reduce DNA repair activity and repair proteins. We propose a TS carcinogenesis paradigm. Aldehydes are major TS carcinogens exerting dominant effect: Aldehydes induce mutagenic PdG adducts, impair DNA repair functions, and inhibit many procarcinogens in TS from becoming DNA-damaging agents.

E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the burning process. It contains neither carcinogenic incomplete combustion byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E-cigarettes are promoted as safe and have gained significant popularity. In this study, instead of detecting nitrosamines, we directly measured DNA damage induced by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found mutagenic O6-methyldeoxyguanosines and γ-hydroxy-1,N2 -propano-deoxyguanosines in the lung, bladder, and heart. DNA-repair activity and repair proteins XPC and OGG1/2 are significantly reduced in the lung. We found that nicotine and its metabolite, nicotine-derived nitrosamine ketone, can induce the same effects and enhance mutational susceptibility and tumorigenic transformation of cultured human bronchial epithelial and urothelial cells. These results indicate that nicotine nitrosation occurs in vivo in mice and that E-cigarette smoke is carcinogenic to the murine lung and bladder and harmful to the murine heart. It is therefore possible that E-cigarette smoke may contribute to lung and bladder cancer, as well as heart disease, in humans.

Electronic cigarettes (e-cigarette) have emerged as a popular electronic nicotine delivery system (ENDS) in the last decade. Despite the absence of combustion products and toxins such as carbon monoxide (CO) and tobacco-specific nitrosamines (TSNA), carbonyls including short-chain, toxic aldehydes have been detected in e-cigarette-derived aerosols up to levels found in tobacco smoke. Given the health concerns regarding exposures to toxic aldehydes, understanding both aldehyde generation in e-cigarette and e-cigarette exposure is critical. Thus, we measured aldehydes generated in aerosols derived from propylene glycol (PG):vegetable glycerin (VG) mixtures and from commercial e-liquids with flavorants using a state-of-the-art carbonyl trap and mass spectrometry. To track e-cigarette exposure in mice, we measured urinary metabolites of 4 aldehydes using ULPC-MS/MS or GC-MS. Aldehyde levels, regardless of abundance (saturated: formaldehyde, acetaldehyde > unsaturated: acrolein, crotonaldehyde), were dependent on the PG:VG ratio and the presence of flavorants. The metabolites of 3 aldehydes - formate, acetate and 3-hydroxypropyl mercapturic acid (3-HPMA; acrolein metabolite) -- were increased in urine after e-cigarette aerosol and mainstream cigarette smoke (MCS) exposures, but the crotonaldehyde metabolite (3-hydroxy-1-methylpropylmercapturic acid, HPMMA) was increased only after MCS exposure. Interestingly, exposure to menthol-flavored e-cigarette aerosol increased the levels of urinary 3-HPMA and sum of nicotine exposure (nicotine, cotinine, trans-3'-hydroxycotinine) relative to exposure to a Classic Tobacco-flavored e-cigarette aerosol. Comparing these findings with aerosols of other ENDS and by measuring aldehyde-derived metabolites in human urine following exposure to e-cigarette aerosols will further our understanding of the relationship between ENDS use, aldehyde exposure and health risk.