Faculty Bibliography

To identify biomarkers of exposure present in Heated Tobacco Products (HTPs) users' urine which are associated with bladder cancer and to compare quantitative biomarker levels to those seen in combustible cigarette users. A systematic literature review was conducted in December 2020 with no date limits. Relevant studies that reported quantitative urinary biomarker of exposure in HTP users were included. Biomarkers and their parent compounds were classified by carcinogenicity according to the International Agency for Research on Cancer Monographs and were cross-referenced with the Collaborative on Health and the Environment Toxicant and Disease Database to determine associations with bladder cancer. Our literature search identified 561 articles and 30 clinical trial reports. 11 studies met inclusion criteria. These studies identified 29 biomarkers of exposure present in HTP users' urine, which reflect exposure to 21 unique parent compounds. Of these parent compounds, 14 are carcinogens and 10 have a known link to bladder cancer. HTP users' biomarkers of exposure were present at lower levels than combustible cigarette users but higher than never-smokers. Biomarkers of exposure to bladder carcinogens are present in the urine of HTP users. While levels of these biomarkers appear to be lower than combustible cigarette users, chronic urothelial exposure to bladder carcinogens is concerning and degree of bladder cancer risk remains unknown. Further long-term study is needed to elucidate the bladder cancer risk of HTP use.

The effect of electronic cigarette (e-cigarette) smoking, especially its long-term impact on oral health, is poorly understood. Here, we conducted a longitudinal clinical study with two study visits, 6 months apart, to investigate the effect of e-cigarette use on the bacterial community structure in the saliva of 101 periodontitis patients. Our data demonstrated that e-cigarette use altered the oral microbiome in periodontitis patients, enriching members of the Filifactor, Treponema, and Fusobacterium taxa. For patients at the same periodontal disease stage, cigarette smokers and e-cigarette smokers shared more similarities in their oral bacterial composition. E-cigarette smoking may have a similar potential as cigarette smoking at altering the bacterial composition of saliva over time, leading to an increase in the relative abundance of periodontal disease-associated pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum. The correlation analysis showed that certain genera, such as Dialister, Selenomonas, and Leptotrichia in the e-cigarette smoking group, were positively correlated with the levels of proinflammatory cytokines, including IFN-γ, IL-1β, and TNF-α. E-cigarette use was also associated with elevated levels of proinflammatory cytokines such as IFN-γ and TNF-α, which contribute to oral microbiome dysbiosis and advanced disease state. This article is protected by copyright. All rights reserved.

Secondhand smoke (SHS) exposure remains a major public health concern in the United States. Homes have become the primary source of SHS exposure, with elevated risks for residents of multiunit housing. Though this differential risk is well-documented, little is known about whether SHS exposure varies by floor height. The aim of this study was to examine whether SHS accumulates in higher floors of multiunit housing. Using validated passive nicotine sampling monitors, we sampled air nicotine concentrations on multiple floors of 21 high-rise (>15 floors) buildings in New York City. Within the buildings, measurements were collected in three locations: non-smoking individual apartments, hallways and stairwells. Measurements were collected in two winter and two summer waves to account for potential seasonality effects. We analyzed the percent of filters with detectable nicotine and quantified nicotine concentration (µg/m³). Higher floor levels were positively associated with both airborne nicotine measures, with some variation by location and season observed. In winter, the trends were statistically significant in apartments (floors ≤7: 0.022 µg/m³; floors 8-14: 0.026 µg/m³; floors ≥15: 0.029 µg/m³; p = 0.011) and stairwells (floors ≤7: 0.18 µg/m³; floors 8-14: 0.19 µg/m³; floors ≥15: 0.59 µg/m³; p = 0.006). These findings can inform interventions to mitigate the SHS exposure of residents in multiunit housing.

Electronic cigarettes (e-cigs) have become prevalent as an alternative to conventional cigarette smoking, particularly in youth. E-cig aerosols contain unique chemicals which alter the oral microbiome and promote dysbiosis in ways we are just beginning to investigate. We conducted a 6-month longitudinal study involving 84 subjects who were either e-cig users, conventional smokers, or nonsmokers. Periodontal condition, cytokine levels, and subgingival microbial community composition were assessed, with periodontal, clinical, and cytokine measures reflecting cohort habit and positively correlating with pathogenic taxa (e.g., Treponema, Saccharibacteria, and Porphyromonas). α-Diversity increased similarly across cohorts longitudinally, yet each cohort maintained a unique microbiome. The e-cig microbiome shared many characteristics with the microbiome of conventional smokers and some with nonsmokers, yet it maintained a unique subgingival microbial community enriched in Fusobacterium and Bacteroidales (G-2). Our data suggest that e-cig use promotes a unique periodontal microbiome, existing as a stable heterogeneous state between those of conventional smokers and nonsmokers and presenting unique oral health challenges. IMPORTANCE Electronic cigarette (e-cig) use is gaining in popularity and is often perceived as a healthier alternative to conventional smoking. Yet there is little evidence of the effects of long-term use of e-cigs on oral health. Conventional cigarette smoking is a prominent risk factor for the development of periodontitis, an oral disease affecting nearly half of adults over 30 years of age in the United States. Periodontitis is initiated through a disturbance in the microbial biofilm communities inhabiting the unique space between teeth and gingival tissues. This disturbance instigates host inflammatory and immune responses and, if left untreated, leads to tooth and bone loss and systemic diseases. We found that the e-cig user's periodontal microbiome is unique, eliciting unique host responses. Yet some similarities to the microbiomes of both conventional smokers and nonsmokers exist, with strikingly more in common with that of cigarette smokers, suggesting that there is a unique periodontal risk associated with e-cig use.

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.

BACKGROUND:Variation in alternative tobacco product (ATP) constituents, heating potential, and consumer behaviors have made it difficult to characterize their health risks. To date, most toxicity studies of ATPs have used established cigarette endpoints to inform study design. Furthermore, to assess where ATPs fall on the tobacco harm continuum, with cigarettes representing maximum potential risk, studies have tended to compare the relative biological responses to ATPs against those due to cigarettes. OBJECTIVES/OBJECTIVE:1) To characterize the exhalation profiles of two popular ATPs: electronic cigarettes (e-cigarettes) and hookah waterpipes (hookah) and 2) to determine if ATP exhalation patterns were representative of cigarette exhalation patterns. METHODS:Exhalation patterns were recorded (mouth only, nose only, or both mouth and nose) among individuals observed in the New York City tri-state area using a recognizable tobacco product (cigarette, e-cigarette, or hookah). Cigarette smokers and e-cigarette vapers were observed on city streets; water-pipe smokers were observed inside Manhattan hookah bars. RESULTS:E-cigarette vapers practiced exclusive nasal exhalation at far higher rates than did cigarette smokers (19.5% vs 4.9%). Among vapers, e-cigarette device type was also significantly associated with exhalation profile. Overall, cigarette smokers exhaled from their nose approximately half to one-third as often as ATP users (hookah and e-cigarettes, respectively). CONCLUSIONS:Nasal exhalation of tobacco emissions appears to be a shared characteristic across several types of ATPs. It is therefore plausible that ATP-specific consumer behaviors may foster unique upper respiratory health consequences that have not been observed in smokers. Thus, product-specific behaviors should inform the prioritization of biological endpoints used in studies evaluating ATP toxicity and health effects.

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.

CONTEXT/BACKGROUND:Use of electronic cigarettes (e-cigarettes) has rapidly increased despite unclear longitudinal health effects. Once thought to be a safer alternative to tobacco smoke, it is possible that e-cigarettes expose the user to similar carcinogenic byproducts during the vaping process. These toxicants are metabolized and excreted in the urine, and may have oncogenic implications for bladder urothelium. OBJECTIVE:To characterize and summarize known urinary carcinogenic biomarkers in e-cigarette users as they relate to the risk of developing bladder cancer. EVIDENCE ACQUISITION/METHODS:A systematic literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and included PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). Relevant articles published in peer-reviewed journals, through January 2019, that reported on urinary biomarkers in e-cigarettes users were included. Parent compounds and urinary biomarkers were classified according to the International Agency for Research on Cancer Monographs on the Evaluation of Carcinogenic Risks to Humans and cross referenced using the Collaborative on Health and the Environment, Toxicant and Disease Database to determine a link to bladder cancer, grouped by strength of evidence. EVIDENCE SYNTHESIS/RESULTS:Our initial search identified 1385 articles, 22 of which met final inclusion criteria and were included for analysis. In summation, these studies described 40 different parent compounds and four metals found in the urine of e-cigarette users. Since each parent compound can be metabolized several different ways, 63 unique toxicant or carcinogenic metabolite biomarkers were identified. Compared with nonuser controls, e-cigarette users had higher concentrations of urinary biomarkers of several carcinogenic compounds linked to bladder cancer. The majority of studies were limited by heterogeneous reporting and a dearth of control individuals who had never smoked. CONCLUSIONS:Biomarkers of carcinogens, several with a strong link to bladder cancer, are present in the urine of e-cigarette users. Long-term implications of urothelial exposure to these toxicants are unknown but concerning, given the similarities to tobacco smoke and its established relationship with bladder cancer. Further study on the urological safety of e-cigarettes is necessary. PATIENT SUMMARY/UNASSIGNED:Our review shows that several carcinogens that have a known link to bladder cancer are present in the urine of electronic cigarette (e-cigarette) users. Further study on the urological safety of e-cigarettes is necessary.

To provide insights into the cause of e-cigarette (e-cig) associated lung injury, we examined the effects of propylene glycol (PG) and glycerol (G), two common solvent carriers used to deliver nicotine/flavor, on markers of oxidative stress and inflammation in female B6C3F1 mice which had been used successfully in tobacco smoke (TS)-induced lung carcinogenesis. Mice exposed to air and TS were used as negative and positive controls, respectively. Using LC-MS/MS, we showed that PG/G alone, in the absence of nicotine, significantly increased the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG or its tautomer 8-oxodG), a biomarker of DNA oxidative damage, in lung and plasma of mice; moreover, addition of nicotine (12 and 24 mg/mL) in e-cig liquid appears to suppress the levels of 8-oxodG. Exposure to e-cig aerosols or TS induced nonsignificant increases of plasma C-reactive protein (CRP), a biomarker of inflammation; nonetheless, the levels of fibronectin (FN), a biomarker of tissue injury, were significantly increased by e-cig aerosols or TS. Although preliminary, our data showed that exposure to e-cig aerosols induced a higher score of lung injury than did control air or TS exposure. Our results indicate that the B6C3F1 mouse model may be suitable for an in-depth examination of the impact of e-cig on lung injury associated with oxidative stress and inflammation and this study adds to the growing evidence that the use of e-cig can lead to lung damage.