Lung microbial and host genomic signatures as predictors of prognosis in early-stage adenocarcinoma.

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: 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.

Seventy-five years of impactful environmental and occupational health research at the Nelson Institute of Environmental Medicine at New York University.

Founded in 1947 as the Institute of Industrial Medicine, the Nelson Institute and Department of Environmental Medicine at New York University (NYU) Grossman School of Medicine (NYUGSOM) was supported by a National Institute of Environmental Health Science (NIEHS) Center Grant for over 56 years. Nelson Institute researchers generated 75 years of impactful research in environmental and occupational health, radiation effects, toxicology, and cancer. Environmental health research is continuing at NYUGSOM in its departments of medicine and population health. The objective of this historical commentary is to highlight the major achievements of the Nelson Institute and the department in the context of its history at facilities in Sterling Forest, Tuxedo, NY and Manhattan, NY. Aspects of our discussion include leadership, physical facilities, and research in many areas, including air pollution, health effects of environmental radiation exposures, inhalation toxicology methodology, carcinogenesis by chemicals, metals, and hormones, cancer chemoprevention, human microbiome, ecotoxicology, epidemiology, biostatistics, and community health concerns. The research of the institute and department benefited from unique facilities, strong leadership focused on team-based science, and outstanding investigators, students, and staff. A major lasting contribution has been the training of hundreds of graduate students and postdoctoral fellows, many of whom have been and are training the next generation of environmental and occupational health researchers at various institutions.

Toxicological assessment of E-cigarette flavored E-liquids aerosols using Calu-3 cells: A 3D lung model approach.

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.

From Augmented to Virtual Reality in Plastic Surgery: Blazing the Trail to a New Frontier.

BACKGROUND: Augmented reality (AR) and virtual reality (VR)-termed mixed reality-have shown promise in the care of operative patients. Currently, AR and VR have well-known applications for craniofacial surgery, specifically in preoperative planning. However, the application of AR/VR technology to other reconstructive challenges has not been widely adopted. Thus, the purpose of this investigation is to outline the current applications of AR and VR in the operative setting. METHODS: The literature pertaining to the use of AR/VR technology in the operative setting was examined. Emphasis was placed on the use of mixed reality technology in surgical subspecialities, including plastic surgery, oral and maxillofacial surgery, colorectal surgery, neurosurgery, otolaryngology, neurosurgery, and orthopaedic surgery. RESULTS: Presently, mixed reality is widely used in the care of patients requiring complex reconstruction of the craniomaxillofacial skeleton for pre- and intraoperative planning. For upper extremity amputees, there is evidence that VR may be efficacious in the treatment of phantom limb pain. Furthermore, VR has untapped potential as a cost-effective tool for microsurgical education and for training residents on techniques in surgical and nonsurgical aesthetic treatment. There is utility for mixed reality in breast reconstruction for preoperative planning, mapping perforators, and decreasing operative time. VR has well- documented applications in the planning of deep inferior epigastric perforator flaps by creating three-dimensional immersive simulations based on a patient's preoperative computed tomography angiogram. CONCLUSION: The benefits of AR and VR are numerous for both patients and surgeons. VR has been shown to increase surgical precision and decrease operative time. Furthermore, it is effective for patient-specific rehearsal which uses the patient's exact anatomical data to rehearse the procedure before performing it on the actual patient. Taken together, AR/VR technology can improve patient outcomes, decrease operative times, and lower the burden of care on both patients and health care institutions.

A combination of three antioxidants decreases the impact of rural particulate pollution in Normal human keratinocytes.

OBJECTIVE: It is well established that exposure of human skin to airborne pollution, particularly in the form of particulate matter sized 2.5 µm (PM2.5 ), 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: Normal human epidermal keratinocytes were exposed to a rural-derived source of PM2.5 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: Pre-treatment of keratinocytes with the antioxidant preparation in the absence of PM2.5 reduced baseline levels of MMP-1, IL-6 and CYP1A1 and reduced PM2.5 -induced increases in all four endpoints, MMP-1, IL-6, CXCL10 and CYP1A1. Antioxidants significantly increased NRF2 protein in the presence of PM2.5 , indicating a protective response. RNA-seq interrogation of antioxidant-treated cells further showed increased expression of NRF2 inducible genes. The expression of CYP1A1 and genes related to aryl hydrocarbon activation were induced by PM2.5 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.

OBJECTIF: Il est bien établi que l'exposition de la peau humaine à la pollution atmosphérique, en particulier sous forme de particules d'une taille de 2,5 µm (PM2,5 ), est associée à un stress oxydatif, à des dommages à l'ADN et à une inflammation entraînant des signes prématurés de vieillissement cutané. Étant donné que la plupart des dommages résultent du stress oxydatif, nous avons examiné les effets d'une composition topique contenant trois antioxydants dans un système de modèle in vitro afin d'évaluer le potentiel d'amélioration du vieillissement prématuré. L'utilisation de plusieurs antioxydants a été intéressante en raison de la composition typique des produits thérapeutiques de soin de la peau. Il est important de déterminer l'efficacité de plusieurs antioxydants combinés et de développer un test à court terme pour des tests d'efficacité à plus grande échelle. MÉTHODES: Des kératinocytes épidermiques humains normaux ont été exposés à une source de PM2,5 rurale en présence et en l'absence d'un mélange antioxydant de resvératrol, de niacinamide et de peptide GHK. Les critères d'évaluation liés à l'inflammation, au vieillissement prématuré et à la carcinogénicité ont été surveillés après 5 heures d'exposition et comprenaient l'IL-6, CXCL10, MMP-1 et le NRF2. Les gènes exprimés de manière différentielle ont été surveillés par séquençage de l'ARN. RÉSULTATS: Le prétraitement des kératinocytes par la préparation antioxydante en l'absence de PM2,5 a réduit les taux initiaux de MMP-1, IL-6 et de CYP1A1 et a réduit les augmentations induites par les PM2,5 dans les quatre critères d'évaluation, MMP-1, IL-6, CXCL10 et CYP1A1. Les antioxydants ont significativement augmenté la protéine NRF2 en présence de PM2,5 , ce qui indique une réponse protectrice. L'interrogation des séquences d'ARN des cellules traitées par antioxydants a également montré une expression accrue des gènes inductibles par NRF2. L'expression du CYP1A1 et des gènes liés à l'activation des hydrocarbures aryles a été induite par les PM2,5 et supprimée par les antioxydants. CONCLUSIONS: Les voies de signalisation spécifiques connues pour être corrélées à l'inflammation cutanée et au vieillissement ont été examinées en fonction de leur adéquation à l'utilisation dans les tests d'efficacité pour la prévention des lésions cutanées dues à la pollution des hydrocarbures ambiants. Les critères d'évaluation examinés après seulement 5 heures d'exposition fournissent une méthode utile pouvant être utilisée pour un dépistage à haut débit. Les résultats obtenus renforcent le principe selon lequel une préparation antioxydante multiple, appliquée par voie topique, peut réduire la signalisation pro-inflammatoire et les dommages cellulaires et ainsi réduire le vieillissement prématuré de la peau résultant de l'exposition à la pollution atmosphérique d'origine rurale.

Untargeted Metabolomics to Characterize the Urinary Chemical Landscape of E-Cigarette Users.

The health and safety of using e-cigarette products (vaping) have been challenging to assess and further regulate due to their complexity. Inhaled e-cigarette aerosols contain chemicals with under-recognized toxicological profiles, which could influence endogenous processes once inhaled. We urgently need more understanding on the metabolic effects of e-cigarette exposure and how they compare to combustible cigarettes. To date, the metabolic landscape of inhaled e-cigarette aerosols, including chemicals originated from vaping and perturbed endogenous metabolites in vapers, is poorly characterized. To better understand the metabolic landscape and potential health consequences of vaping, we applied liquid chromatography-mass spectrometry (LC-MS) based nontargeted metabolomics to analyze compounds in the urine of vapers, cigarette smokers, and nonusers. Urine from vapers (n = 34), smokers (n = 38), and nonusers (n = 45) was collected for verified LC-HRMS nontargeted chemical analysis. The altered features (839, 396, and 426 when compared smoker and control, vaper and control, and smoker and vaper, respectively) among exposure groups were deciphered for their structural identities, chemical similarities, and biochemical relationships. Chemicals originating from e-cigarettes and altered endogenous metabolites were characterized. There were similar levels of nicotine biomarkers of exposure among vapers and smokers. Vapers had higher urinary levels of diethyl phthalate and flavoring agents (e.g., delta-decalactone). The metabolic profiles featured clusters of acylcarnitines and fatty acid derivatives. More consistent trends of elevated acylcarnitines and acylglycines in vapers were observed, which may suggest higher lipid peroxidation. Our approach in monitoring shifts of the urinary chemical landscape captured distinctive alterations resulting from vaping. Our results suggest similar nicotine metabolites in vapers and cigarette smokers. Acylcarnitines are biomarkers of inflammatory status and fatty acid oxidation, which were dysregulated in vapers. With higher lipid peroxidation, radical-forming flavoring, and higher level of specific nitrosamine, we observed a trend of elevated cancer-related biomarkers in vapers as well. Together, these data present a comprehensive profiling of urinary biochemicals that were dysregulated due to vaping.

Effects of electronic cigarettes and hookah (waterpipe) use on home air quality.

INTRODUCTION: A major site of secondhand smoke exposure for children and adults is the home. Few studies have evaluated the impact of e-cigarette or hookah use on home air quality, despite evidence finding toxic chemicals in secondhand e-cigarette aerosols and hookah smoke. We assessed the effect of e-cigarette and hookah use on home air quality and compared it with air quality in homes where cigarettes were smoked and where no smoking or e-cigarette use occurred. METHODS: Non-smoking homes and homes where e-cigarettes, hookah or cigarettes were used were recruited in the New York City area (n=57) from 2015 to 2019. Particulate matter with diameter less than 2.5 µm (PM2.5), black carbon and carbon monoxide (CO) were measured during a smoking or vaping session, both in a 'primary' smoking room and in an adjacent 'secondary' room where no smoking or vaping occurred. Log transformed data were compared with postanalysis of variance Tukey simultaneous tests. RESULTS: Use of hookah significantly increased PM2.5 levels compared with non-smoking homes, in both the primary and secondary rooms, while use of e-cigarettes increased PM2.5 levels only in primary rooms. Additionally, in-home use of hookah resulted in greater CO concentrations than the use of cigarettes in primary rooms. CONCLUSIONS: Use of e-cigarettes or hookah increases air pollution in homes. For hookah, increases in PM2.5 penetrated even into rooms adjacent to where smoking occurs. Extending smoke-free rules inside homes to include e-cigarette and hookah products is needed to protect household members and visitors from passive exposure to harmful aerosols and gases.

Long-Term Trends in Secondhand Smoke Exposure in High-Rise Housing Serving Low-Income Residents in New York City: Three-Year Evaluation of a Federal Smoking Ban in Public Housing, 2018-2021.

INTRODUCTION: In July 2018, the U.S. Department of Housing and Urban Development passed a rule requiring public housing authorities to implement smoke-free housing (SFH) policies. We measured secondhand smoke (SHS) exposure immediately before, and repeatedly up to 36 months post-SFH policy implementation in a purposeful sample of 21 New York City (NYC) high-rise buildings (>15 floors): 10 NYC Housing Authority (NYCHA) buildings subject to the policy and 11 privately managed buildings in which most residents received housing vouchers (herein "Section 8"). AIMS AND METHODS: We invited participants from nonsmoking households (NYCHA n = 157, Section-8 n = 118) to enroll in a longitudinal air monitoring study, measuring (1) nicotine concentration with passive, bisulfate-coated filters, and (2) particulate matter (PM2.5) with low-cost particle sensors. We also measured nicotine concentrations and counted cigarette butts in common areas (n = 91 stairwells and hallways). We repeated air monitoring sessions in households and common areas every 6 months, totaling six post-policy sessions. RESULTS: After 3 years, we observed larger declines in nicotine concentration in NYCHA hallways than in Section-8, [difference-in-difference (DID) = -1.92 µg/m3 (95% CI -2.98, -0.87), p = .001]. In stairwells, nicotine concentration declines were larger in NYCHA buildings, but the differences were not statistically significant [DID= -1.10 µg/m3 (95% CI -2.40, 0.18), p = .089]. In households, there was no differential change in nicotine concentration (p = .093) or in PM2.5 levels (p = .385). CONCLUSIONS: Nicotine concentration reductions in NYCHA common areas over 3 years may be attributable to the SFH policy, reflecting its gradual implementation over this time. IMPLICATIONS: Continued air monitoring over multiple years has demonstrated that SHS exposure may be declining more rapidly in NYCHA common areas as a result of SFH policy adherence. This may have positive implications for improved health outcomes among those living in public housing, but additional tracking of air quality and studies of health outcomes are needed. Ongoing efforts by NYCHA to integrate the SFH policy into wider healthier-homes initiatives may increase policy compliance.

Feasibility of low-cost particle sensor types in long-term indoor air pollution health studies after repeated calibration, 2019-2021.

Previous studies have explored using calibrated low-cost particulate matter (PM) sensors, but important research gaps remain regarding long-term performance and reliability. Evaluate longitudinal performance of low-cost particle sensors by measuring sensor performance changes over 2 years of use. 51 low-cost particle sensors (Airbeam 1 N = 29; Airbeam 2 N = 22) were calibrated four times over a 2-year timeframe between 2019 and 2021. Cigarette smoke-specific calibration curves for Airbeam 1 and 2 PM sensors were created by directly comparing simultaneous 1-min readings of a Thermo Scientific Personal DataRAM PDR-1500 unit with a 2.5 µm inlet. Inter-sensor variability in calibration coefficient was high, particularly in Airbeam 1 sensors at study initiation. Calibration coefficients for both sensor types trended downwards over time to < 1 at final calibration timepoint [Airbeam 1 Mean (SD) = 0.87 (0.20); Airbeam 2 Mean (SD) = 0.96 (0.27)]. We lost more Airbeam 1 sensors (N = 27 out of 56, failure rate 48.2%) than Airbeam 2 (N = 2 out of 24, failure rate 8.3%) due to electronics, battery, or data output issues. Evidence suggests degradation over time might depend more on particle sensor type, rather than individual usage. Repeated calibrations of low-cost particle sensors may increase confidence in reported PM levels in longitudinal indoor air pollution studies.

Passive exposure to e-cigarette emissions is associated with worsened mental health.

BACKGROUND: Cigarette smoking, secondhand cigarette smoke (SHS) exposure, and e-cigarette use ("vaping") are each associated with increased rates of depressive symptoms and other internalizing mental health disorders. The prevalence of vaping has increased greatly, yet the mental health correlates of secondhand exposure to e-cigarette emissions are as yet to be investigated. This study examined the potential adverse mental health outcomes associated with different tobacco exposures (direct and passive), with a particular focus on the mental health correlates of secondhand exposure to e-cigarette emissions. METHODS: The Population Assessment of Tobacco and Health Study data collected from a sample of 16,173 Wave 4 adults were used to test the hypothesis that secondhand e-cigarette emissions exposure is associated with increased odds of internalizing mental health disorders. Individuals were categorized as exclusive cigarette smokers, exclusive e-cigarette users, cigarette and e-cigarette dual users, exclusive noncombustible tobacco users, secondhand smoke exposed non-users, secondhand e-cigarette emissions exposed non-users, and non-users with no current SHS/secondhand e-cigarette aerosol exposure. Adjusted weighted logistic regression analysis was used to investigate the association between exposure type and internalizing problems as assessed by scores on the Global Appraisal of Individual Needs-Short Screener (GAIN-SS), a widely used instrument for assessing mental health problems. RESULTS: Cigarette smokers (AOR = 2.53, 95% CI: 2.19-2.92), e-cigarette users (AOR = 3.14, 2.41-4.09), dual users (AOR = 3.37, 2.85-4.00), noncombustible tobacco users (AOR = 1.48, 1.01-2.17), SHS exposed non-users (AOR = 1.63, 1.37-1.94), and secondhand e-cigarette emissions exposed non-users (AOR = 1.43, 1.03-1.99) were each associated with increased odds of moderate to severe internalizing mental health problems as compared to unexposed non-users. Odds of internalizing problems among SHS and secondhand e-cigarette emissions exposed non-users did not differ (p = 0.46). CONCLUSIONS: This is the first study, to our knowledge, to identify an association between recent secondhand exposure to e-cigarette emissions and mental health problems, and the risk is comparable to that of SHS. Corroboration of this relationship needs further research to explicate directionality and mechanisms underlying this association.

The Effect of Floor Height on Secondhand Smoke Transfer in Multiunit Housing.

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.

Exhalation of alternative tobacco product aerosols differs from cigarette smoke-and may lead to alternative health risks.

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: 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.

Electronic Cigarette Use Promotes a Unique Periodontal Microbiome.

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.

Electronic cigarette use enriches periodontal pathogens.

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-1ß, 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.

Carcinogenic biomarkers of exposure in the urine of heated tobacco product users associated with bladder cancer: A systematic review.

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.

E-Cigarette Toxicology.

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.

Portable air cleaner use and biomarkers of inflammation: A systematic review and meta-analysis.

Fine particulate matter air pollution (PM2.5) is a major contributor to cardiovascular morbidity and mortality, potentially via increased inflammation. PM2.5 exposure increases inflammatory biomarkers linked to cardiovascular disease, including CRP, IL-6 and TNFα. Portable air cleaners (PACs) reduce individual PM2.5 exposure but evidence is limited regarding whether PACs also reduce inflammatory biomarkers. We performed a systematic review and meta-analysis of trials evaluating the use of PACs to reduce PM2.5 exposure and inflammatory biomarker concentrations. We identified English-language articles of randomized sham-controlled trials evaluating high efficiency particulate air filters in non-smoking, residential settings measuring serum CRP, IL-6 and TNFα before and after active versus sham filtration, and performed meta-analysis on the extracted modeled percent change in biomarker concentration across studies. Of 487 articles identified, we analyzed 14 studies enrolling 778 participants that met inclusion criteria. These studies showed PACs reduced PM2.5 by 61.5 % on average. Of the 14 included studies, 10 reported CRP concentrations in 570 participants; these showed active PAC use was associated with 7 % lower CRP (95 % CI: -14 % to 0.0 %, p = 0.05). Nine studies of IL-6, with 379 participants, showed active PAC use was associated with 13 % lower IL-6 (95 % CI: [-23 %, -3 %], p = 0.009). Six studies, with 269 participants, reported TNF-α and demonstrated no statistical evidence of difference between active and sham PAC use. Portable air cleaners that reduce PM2.5 exposure can decrease concentrations of inflammatory biomarkers associated with cardiovascular disease. Additional studies are needed to evaluate clinical outcomes and other biomarkers.

E-Cigarette Use, Systemic Inflammation, and Depression.

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: Nationally representative NHANES data from 2015-2018 were used (n = 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: Depression occurred in 16.7% of all e-cigarette users vs. 5.0% of those who never used e-cigarettes (p < 0.001). In adjusted analyses, the following elevated ORs were found: all current e-cigarette users with CRP <8 = 3.37 (95% CI: 2.06, 5.51) vs. CRP ≥8 = 6.70 (2.48, 18.11); exclusive e-cigarette users with CRP <8 = 1.91 (0.78, 4.69) vs. those with CRP ≥8 = 5.09 (1.44, 18.02); and dual users with CRP <8 = 4.31 (2.35, 7.89) vs. those with CRP ≥8 = 7.37 (1.85, 29.41). These ORs indicate that depression is associated with each category of e-cigarette use; however, we found this association did not vary by systemic inflammation level (interaction p-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.

Alternative tobacco products use and its impact on urologic health - will the lesser evil still be evil? A commentary and review of literature.

INTRODUCTION: Alternative tobacco products, including electronic cigarettes (e-cigarettes) and non-combustible tobacco products or heat-not-burn (HNB) products, are substitutes to conventional combustible cigarettes with the potential to impact urologic health, similar to traditional smoking. Most urologists, however, have limited knowledge of these products and are unfamiliar with their potential health implications. We conducted a review to assess the impact of e-cigarettes and HNB products on urologic health. MATERIAL AND METHODS: A bibliographic search covering the period up to April, 2021 was conducted using MEDLINE®/PubMed® and Google Scholar. Articles were reviewed and categorized based on the potential impact on erectile dysfunction, semen quality, lower urinary tract symptoms, genitourinary malignancies, and smoking cessation. Data were extracted, analyzed and summarized. RESULTS: Mature data on the long-term impact of e-cigarette and HNB product use on urologic health are lacking. E-cigarette and HNB vapors appear to contain decreased concentrations of chemicals responsible for erectile dysfunction compared to tobacco smoke but may play a role through endothelial damage. Use of e-cigarettes is associated with lower sperm counts. No definitive data has shown a link between e-cigarette or HNB product use and lower urinary tract symptoms. Multiple carcinogens including those specifically linked to bladder cancer have been identified in the urine of e-cigarette and HNB product users. Limited data suggest e-cigarettes may aid in smoking cessation. CONCLUSIONS: Urologists may benefit from understanding the urologic health concerns surrounding e-cigarettes and HNB product use and patients may benefit from being properly educated.