Plasma Nicotine Concentrations Research Articles

Simulation of electronic nicotine delivery systems (ENDS) aerosol dosimetry and nicotine pharmacokinetics

Electronic nicotine delivery systems (ENDS) heat a liquid solution typically containing propylene glycol, vegetable glycerin, water, nicotine, and flavor chemicals to deliver an aerosol to the user. ENDS aerosols are complex, multi-constituent mixtures of droplets and vapors. Lung dosimetry predictions require mechanistic models that account for the physico-chemical properties of the constituents and thermodynamic processes of the aerosol as it travels through the respiratory tract and deposits in lung airways. In this study, a model formulated to predict ENDS aerosol deposition in the oral cavity and lung airways was linked with a physiologically-based pharmacokinetic (PBPK) model to predict nicotine pharmacokinetics (PK) as a function of product characteristics and puff topography. Predicted plasma nicotine PK compared favorably with available experimental data and captured the rapid increase in plasma levels followed by a clearance phase after ENDS use. E-liquid nicotine concentration and puff duration substantially increased nicotine lung deposition and plasma nicotine levels. Increasing the puff duration from 1 to 5 s while assuming a constant aerosol flow rate resulted in an ∼5-fold increase in nicotine lung deposition (45.0 µg to 243.7 µg) and increased maximum plasma nicotine concentrations from 4.7 ng/mL to 25.0 ng/mL; increasing the e-liquid nicotine concentration from 1 % to 5 % yielded increases in nicotine lung deposition (41.0 µg to 204.5 µg) and maximum plasma nicotine concentration (4.2 ng/mL to 21.1 ng/mL). Model predictions demonstrate the sensitivity of ENDS aerosol lung deposition and plasma nicotine profiles to user behavior and allow for quantification of constituent deposition and nicotine absorption after ENDS use.

Constraining electronic nicotine delivery systems (ENDS) nicotine dose by controlling nicotine flux at a limited puff duration.

Nicotine flux, the rate of electronic nicotine delivery system (ENDS) nicotine emission, is important in determining ENDS abuse liability. However, flux does not account for user behavior, including puff duration. Along with nicotine flux, puff duration limits the dose of nicotine that can be inhaled. Controlling both flux and puff duration allows regulators to constrain nicotine dose effectively. This study examined the effects of differing ENDS nicotine fluxes (by manipulating liquid nicotine concentration and holding device power constant), with user puff duration limited to 2 s. Participants (N = 32) completed four sessions, each session differing by nicotine flux (no flux, low flux, cigarettelike flux, and high flux conditions). Participants completed two ENDS use bouts in each session while puff duration was limited to 2 s. Plasma nicotine concentration, heart rate, and subjective effects were measured. At higher flux, higher plasma nicotine concentration and higher heart rate were observed. Moreover, higher fluxes decreased ratings of craving and urge to use nicotine and increased positive subjective effects, such as calmness. This study demonstrates that by manipulating nicotine flux and limiting puff duration, nicotine dose can be controlled. Subsequent research should demonstrate the effects of manipulating puff duration systematically. Results underscore the importance of targeting both flux and puff duration for ENDS regulation, intended to reduce abuse liability while maintaining the potential to facilitate transitions from cigarettes to ENDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assessment of human abuse potential of an unflavored, sucralose-sweetened electronic cigarette in combustible cigarette smokers.

Despite the popularity of electronic cigarettes (ECIGs), limited research has examined the role of sweeteners, independent of other flavors, in shaping ECIG human abuse potential (HAP). This study examined the effects of sucralose and nicotine in unflavored ECIG liquid solutions to provide a basic understanding of the effects of sweeteners on ECIG HAP compared to combustible cigarettes. Individuals who smoked cigarettes daily (N = 14) completed five within-subject, Latin-square ordered study sessions that differed by product used: (a) own-brand combustible cigarettes (OB), (b) 0 mg/mL nicotine, unsweetened liquid, (c) 0 mg/mL nicotine, sucralose-sweetened liquid, (d) 15 mg/mL nicotine, unsweetened liquid, and (e) 15 mg/mL nicotine, sucralose-sweetened liquid. Participants completed subjective questionnaires and behavioral tasks following a 10-puff directed use bout during which puff topography was measured, and blood was sampled for later measurement of plasma nicotine concentration. On average, the OB condition had a greater increase in plasma nicotine concentration and produced more pronounced subjective effects compared to the ECIG conditions. The 15 mg/mL nicotine ECIGs delivered significantly more nicotine and produced greater drug effects and reductions in tobacco abstinence symptoms than the 0 mg/mL nicotine ECIGs. Sucralose-containing solutions increased ECIG product appeal, puff duration, and puff volume during the 10-puff directed bout. Findings revealed greater HAP for OB cigarettes relative to all ECIGs tested and suggest that adding sucralose and nicotine elevates ECIG HAP via different mechanisms; sucralose appears to influence HAP through product appeal, while nicotine influences HAP through drug effects and tobacco/nicotine abstinence symptom suppression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Small pouches, but high nicotine doses-nicotine delivery and acute effects after use of tobacco-free nicotine pouches.

Tobacco-free nicotine pouches are new nicotine products for oral consumption. They can contain very high nicotine amounts that have not been addressed with clinical studies yet. Thus, nicotine delivery, effects on craving, and side effects were assessed using pouches with up to 30mg nicotine. In this single-center, five-arm, crossover study, 15 regular cigarette smokers consumed tobacco-free nicotine pouches from different brands with 6, 20, and 30mg for 20min. Comparators were nicotine-free pouches and tobacco cigarettes. At baseline and predefined time points over a study period of 240min, plasma nicotine concentrations, effects on cigarette craving, and side effects were assessed. Cardiovascular parameters including arterial stiffness were measured using a MobilOGraph. Consumption of 30mg nicotine pouches has led to a higher nicotine uptake compared with the cigarette (Cmax: 29.4 vs 15.2ng/mL; AUC: 45.7 vs 22.1ng/mL × h). Nicotine uptake in the acute phase was rapid during use of the 30mg pouch and cigarette. Extraction rate of nicotine differed between pouches. Use of all products has reduced acute cigarette craving, even the nicotine-free pouch. During consumption of the cigarette and the pouches with 20 and 30mg, heart rate increased about 27, 12, and 25 bpm, respectively. Parameters for arterial stiffness were elevated and all pouches have induced mouth irritations. The pouches with 30mg nicotine had overall the strongest side effects and may induce addiction. As craving was also reduced by products with less nicotine, it is questionable whether such high nicotine contents should be allowed on the market. A limit of nicotine content is warranted. The nicotine release rate varies across products and needs to be known to estimate the nicotine delivery.

Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial.

Many oral nicotine pouch (ONP) brands use synthetic nicotine, which typically contains a racemic (50:50) mixture of nicotine's two stereoisomers: S-nicotine and R-nicotine. Because tobacco-derived nicotine contains more than 99% S-nicotine, the effects of R-nicotine in humans are not well known. We compared systemic nicotine exposure and product appeal of ONPs containing more than 99% S-nicotine versus racemic nicotine. N = 18 adult smokers (Mage = 45 years, 66.7% male, 77.8% White) enrolled in a three-visit single-blind, randomized crossover study. During each visit, participants used one wintergreen-flavored, 3mg nicotine ONP for 30min following at least12h nicotine abstinence. Study ONP #1 contained more than 99% S-nicotine and the other two study ONPs contained racemic nicotine (collapsed for analyses). Plasma nicotine assessments and measures of withdrawal relief occurred at t = 0, 5, 15, 30, 60, and 90min; measures of product appeal were assessed following ONP use. Using the ONP with more than 99% S-nicotine resulted in greater plasma nicotine concentration from 15 to 90min (p < .0001) and greater maximum plasma nicotine concentration than the ONPs with racemic nicotine (M = 9.9ng/mL [SD = 2.5] vs. M = 5.7ng/mL [SD = 2.8], respectively; p < .0001). Product liking and withdrawal relief were similar across ONPs, although participants reported more "bad effects" when using the ONP with more than 99% S-nicotine. Participants reported few subjective differences in ONPs according to nicotine stereoisomer, but plasma nicotine concentration was greater for ONPs using more than 99% S-nicotine. ONPs with more than 99% S-nicotine (vs. racemic nicotine) might be better substitutes for cigarettes, but research into other ONP characteristics (eg flavors, freebasenicotine) is needed to inform regulation. Little is known about the effects of racemic (vs. S-) nicotine in humans. In a sample of adults who smoke cigarettes, we identified that oral nicotine pouches containing racemic nicotine exposed participants to less nicotine than oral nicotine pouches containing only S-nicotine, but both types of oral nicotine pouches held similar, moderate appeal. Additional research evaluating the roles that flavorings, total nicotine concentration, and freebase nicotine play in the abuse liability of oral nicotine pouches would inform comprehensive product regulations to support public health.

Plasma Nicotine Pharmacokinetics of Oral Nicotine Pouches Across Varying Flavours and Nicotine Content *

SUMMARY Background In recent years several nicotine products have been introduced that aim to offer smokers an alternative to cigarettes. As well as having fewer toxicants than combustible cigarettes, such nicotine products must be able to deliver nicotine efficiently. The aim of this study was to determine and compare the pharmacokinetics of nicotine absorption from nine oral tobacco-free smokeless nicotine pouches with varying nicotine content and flavours. Methods In a randomised, open-labelled, controlled, crossover clinical study, nicotine pharmacokinetics and product-liking were compared between nine nicotine pouches (Velo, BAT; 4- or 7-mg nicotine per pouch and in eight flavours). During a 10-day confinement period, 42 healthy adult participants, who were current smokers of combustible cigarettes, used a single study product once each day during a 45-min use period following overnight nicotine abstinence. Results Maximum plasma nicotine concentration and area under curve for nicotine concentration versus time 180 min after the start of study product use were significantly greater for the 7-mg than for the 4-mg Velo pouches (p &lt; 0.0001). These values did not differ between flavours among the 7-mg Velo nicotine pouches after adjustment for multiple comparisons (both p &gt; 0.003). The median time to maximum plasma nicotine concentrations and mean product-liking scores were similar regardless of nicotine content and flavour. Conclusions Regardless of flavour, nicotine pouches with the same nicotine content and formulation produce similar pharmacokinetic parameters and can deliver nicotine efficiently. Nicotine pouches could be a satisfying alternative for smokers switching from conventional cigarettes. [Contrib. Tob. Nicotine Res. 32 (2023) 130–139]

Investigation of the relationship between nicotine and cotinine concentrations in human biological samples by a GC-MS method

In this study, a gas chromatography-mass spectrometry method was developed for the determination of nicotine and cotinine wherein human plasma, urine, and saliva. In addition, it was aimed to determine statistically the correlation between nicotine and cotinine levels in urine and saliva samples and nicotine and cotinine levels in blood samples. The limit of quantification was ≤0.83 ng/mL and precision were ≤4.91 and accuracy (RE%) was between (-4.93) and 4.90. Recovery was detected between 95.4% and 104.7%. The method was employed to determining the nicotine and cotinine concentrations in plasma, saliva, and urine total of 91 samples belong to non-smokers (n=37) and active smokers (n=54) who were healthy (n=65) and COPD patients (n=27) and the statistical relationship within the nicotine and cotinine values of the samples were investigated. It was found a correlation (r=0.752, p≤0.01) between plasma and saliva cotinine levels and estimation equation calculated as y=1.56x+43.24. Also, the correlation between plasma and urine cotinine levels was found (r=0.787, p≤0.01) by the equation that y=0.31x+34.59. The results show that by accurately determining the amount of cotinine in both saliva and urine, the exposure risks of both active smokers and those exposed to cigarette smoke with the ETS can be estimated.

Part two: an unblinded, parallel, randomized study to assess nicotine pharmacokinetics of four Vuse Solo ENDS flavors in smokers

We report the findings from a randomized, parallel study designed to evaluate nicotine pharmacokinetics (PK) following 10 min of ad libitum use of electronic nicotine delivery system (ENDS) in four flavor variants. Subjects were randomized an investigational product (IP) and blood samples were collected for PK assessments during a test session. Primary endpoints were baseline-adjusted values of maximum plasma nicotine concentration (Cmax) and area under the nicotine concentration-vs-time curve up to 60 min (AUCnic0–60). Baseline-adjusted mean Cmax ranged from 6.53 to 8.21 ng/mL, and mean AUCnic0–60 ranged from 206.87 to 263.52 ng min/mL for all ENDS IPs. Results of geometric mean Cmax and AUCnic0–60 values were within 95% confidence intervals (CI) among the ENDS IP flavor variants tested.

Usage Pattern and Nicotine Delivery during Ad Libitum Consumption of Pod E-Cigarettes and Heated Tobacco Products.

Many different nicotine delivery products, such as e-cigarettes (e-cigs) or heated tobacco products (HTPs), are available on the market. To better understand these products, it is crucial to learn how consumers use them and how much nicotine they deliver. Therefore, a pod e-cig, an HTP, and a conventional cigarette (CC) were each used by 15 experienced users of the respective product category for 90 min without special use instructions ("ad libitum"). Sessions were video recorded to analyze usage patterns and puff topography. At defined time points, blood was sampled to determine nicotine concentrations, and subjective effects were inquired about using questionnaires. During the study period, the CC and HTP groups averaged the same number of consumption units (both 4.2 units). In the pod e-cig group, the highest number of puffs was taken (pod e-cig 71.9; HTP: 52.2; CC: 42.3 puffs) with the most extended mean puff duration (pod e-cig: 2.8 s; HTP: 1.9 s; CC: 1.8 s). Pod e-cigs were predominantly used with single puffs or in short clusters of 2-5 puffs. The maximum plasma nicotine concentration was highest for CCs, followed by HTPs, and then pod e-cigs with 24.0, 17.7, and 8.0 ng/mL, respectively. Craving was reduced by all products. The results suggest that the high nicotine delivery known for tobacco-containing products (CCs and HTPs) may not be needed for non-tobacco-containing products (pod e-cigs) to satisfy cravings in experienced users.

Interactive effects of protonated nicotine concentration and device power on ENDS nicotine delivery, puff topography, and subjective effects.

Electronic nicotine delivery systems (ENDSs) produce an aerosol by heating a liquid that often contains nicotine. The nicotine can be protonated that may make the aerosol easier to inhale than freebase nicotine. This study's purpose is to determine, in cigarette smokers and ENDS users, the effects of three concentrations of protonated nicotine aerosolized at two different power settings. Forty-five participants (22 cigarette smokers and 23 ENDS users) completed some or all of six sessions that varied by liquid nicotine concentration (10, 15, or 30 mg/ml protonated nicotine) and device power (15 or 30 W). Participants took 10 puffs from each product and then used each product for 90 min ad libitum. Plasma nicotine concentration, subjective effects, and puff topography were measured. Results showed increases in plasma nicotine concentration in all conditions, with greater plasma nicotine increases in higher watt, higher nicotine concentration conditions, as well as greater nicotine delivery for ENDS users compared to cigarette smokers. For puff topography, puff duration and volume decreased as nicotine concentration and power increased, and ENDS users took longer and larger puffs than cigarette smokers. Participants rated the higher watt, higher nicotine concentration conditions as harsher and with more throat hit. Overall, these results suggest that device characteristics and liquid constituents interact to influence users' plasma nicotine delivery and should be considered together when regulating ENDS. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Electronic hookah vaping reduces plasma concentrations of nitrate/nitrite and increases systemic oxidative stress

Abstract Background Electronic (e-) hookah–a new category of vaping devices–has increased in use among young adults in recent years. E-hookahs utilize the placement of e-bowls on traditional water pipes, allowing the flavored aerosol to pass through a water-filled base before being inhaled. Though advertised as a safe tobacco alternative, e-hookahs deliver flavored nicotine by creating an aerosol of fine particles and other free radicals that may increase cardiovascular disease risk. While acute e-hookah vaping impairs endothelial function, the underlying mechanism is not completely understood. Purpose To determine the mechanistic involvement of nitric oxide (NO) and oxidative stress underlying the acute e-hookah induced endothelial dysfunction. Methods Healthy young adult chronic hookah smokers (n=7; 26±1 years of age, 24.4±0.8 kg-m2; mean ±SE) were randomized to vape two 30-minute sessions of flavored e-hookah and sham vaping, separated by a 7-day washout period. Flow-mediated dilation (FMD) of the brachial artery was performed with the use of ultrasound. Circulating plasma nitrite/nitrate (NOx), as an index of nitric oxide (NO) concentration, and lipid peroxidation marker 8-isoprostane concentrations, as well as smoking exposure biomarkers (plasma nicotine and exhaled carbon monoxide) were measured before and after the vaping sessions. Results As compared to unchanged parameters with sham vaping (p=ns), e-hookah vaping induced an acute reduction in FMD by −27±3% (pre- vs. post-vaping, p&amp;lt;0.001), suggesting impairment in endothelial function. These vascular changes were accompanied by significant reductions in circulating plasma levels of NOx and increases in 8-iso prostaglandin F2a levels (−41±11% and +28±11%, respectively; p&amp;lt;0.001). Plasma nicotine concentrations increased 4-fold more after vaping e-hookah, whereas exhaled CO levels did not change (p=ns). Conclusions Our data demonstrate that e-hookah vaping transiently increases systemic oxidative stress and decreases NOx levels, the latter implies reduced NO bioavailability and is in line with the observed impairment in endothelial function, expressed by acute FMD reductions. Thus, in contrast to the unsubstantiated beliefs that e-hookah vaping is benign, in overtly healthy young adults, e-hookah vaping causes acute vascular functional impairment, likely mediated by oxidative stress. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of California Tobacco-Related Disease Research Program, University of California

A Comparison of Use Topography and Nicotine Pharmacokinetics Among Loose and Portioned Smokeless Tobacco Users.

Moist snuff smokeless tobacco (ST) products are available in the United States in both "loose" and "portioned" (ie, pouched) formats, but no published study to date has clinically evaluated the associations between ST format, use behavior, and nicotine exposure. Participants used their usual brand of ST (loose ST [n = 30] or portioned ST [n = 20]) during an experimental visit wherein use behavior and plasma nicotine pharmacokinetic parameters were measured following single use (first hour of the session) and ad libitum use (remaining 7 h of the session). Participants' ST products were chemically characterized prior to use for pH and nicotine content. The average amount per use (2.99 vs. 1.52 g; p = .005) and total amount used (11.45 vs. 5.4 g; p = .002) were significantly higher among the loose ST group. Maximum plasma nicotine concentration (Cmax; 33.4 vs. 19.1 ng/ml) and area under the nicotine concentration versus time curve (AUC) were significantly higher for the loose ST group for the first hour (1474.8 vs. 807.2 min* ng/ml; p = .003) and throughout the 8-hour session (15827.9 vs. 8155.3 min* ng/ml; p < .001). Significant associations were observed between free nicotine content and first use Cmax (rs = .488, loose ST group) and AUC0-1 h (rs = 0.448, loose ST group; rs = .441, portioned ST group). The loose ST group used more product and had a greater average deposition time per use than the portioned ST group. Nicotine exposure was more strongly associated with free nicotine content than total nicotine content. To our knowledge, the current investigation was the first study to date to clinically evaluate the associations between usual-brand smokeless format, use behavior, and nicotine exposure. We observed meaningful differences in use behavior and subsequent nicotine exposure between loose and portioned ST users. Further, we observed that nicotine exposure was more strongly associated with free nicotine content than total nicotine content.

Pathophysiology of nicotine, place of nicotine substitutes and electronic cigarettes in plastic surgery: A review of the literature

Smokers are more likely to undergo postoperative complications after plastic surgeries. Our main purpose was to update nicotine's effects after plastic surgeries and assess whether nicotine-replacement therapy and vaping are safe enough to be recommended in peri-operatory circumstances. We set up a literature review including 40 documents from 1986 to 2020 available on Pubmed. Nicotine has undeniable detrimental effects on patients undergoing plastic surgeries like cutaneous necrosis, skin flap failure and surgical site infection. Nevertheless, this toxicity seems to depend on the plasma concentration of nicotine and thus on the way of administration. While smoking is definitely harmful, nicotine replacement therapies (NRT) like patches and gums do not appear to increase postoperative risks based on available studies. The situation is different with the electronic cigarette since the pharmacokinetic parameters are close to those of the traditional cigarette. Even if powerful studies are lacking because the device is recent, preliminary in vitro studies and case reports suggest non-zero surgical risks for e-cigarette users. It seems more appropriate to suggest stopping all nicotine intake before and after plastic surgery. However, if strict cessation is not achievable, it appears preferable to use nicotine replacement therapies rather than e-cigarettes and most of all tobacco.

Effect of menthol/mint-flavored pods on young JUUL E-cigarette users’ subjective experience, puffing behavior, and nicotine exposure: A pilot study

BackgroundRecent regulations have banned all flavors except menthol/mint and classic tobacco from pod-based e-cigarette devices such as JUUL. However, menthol/mint flavor can present a potential risk given its increasing popularity among young people in the US and its puffing and nicotine-enhancing properties. This study examines the impact of menthol/mint flavor manipulation on users’ puffing behavior, subjective experience, and nicotine exposure among young people. MethodsJUUL users (n = 33, 18–24 years) attended two 60-min ad libitum e-cigarette use sessions (menthol/mint flavor vs. classic tobacco flavor) in a cross-over design. Puff topography and plasma nicotine concentration were measured, and participants completed subjective experience questionnaires. ResultsFollowing the use of the menthol/mint-flavored pod, increases were observed in measures of satisfaction, pleasurable/interest to use, willingness to use again, enjoyment, urge to vape, product appeal, taste, and concentration (p < .05 for all). For example, compared to the classic tobacco flavor, participants experienced significantly more satisfaction of the product (4.24 vs. 3.09; p = .001) and sensation enjoyment of the product (3.55 vs. 2.48; p = .002) when using the menthol/mint flavor. While means of the plasma nicotine boost and puff parameters were lower in the classic tobacco condition compared to the menthol/mint flavor condition, no statistical significance was observed between the two conditions (p > .05 for all). ConclusionsResults of this pilot study suggest that menthol/mint-flavor increases e-cigarette usersʼ subjective experience significantly. Regulating menthol/mint flavor is a potentially promising strategy to curb e-cigarette use among young people.

Prenatal E‐Cigarette Use Disrupts Blood‐Brain Barrier (BBB) Integrity and Induces Pro‐Inflammatory Cytokines in Postnatal Brain

PurposeElectronic cigarette (e‐Cig) is often considered as a safer alternative to smoking for pregnant women however, its potential toxic effect on neonatal health warrants further investigation. Toxic effects of prenatal tobacco smoking on postnatal health have been reported in several studies however, regarding thorough investigation of e‐Cig exposure during pregnancy is currently unavailable. Due to the staggering growth in e‐Cig usage among pregnant women (10%), it has become critical to explore the consequences of maternal e‐cig use on postnatal health outcomes. Hence, in this study, we have evaluated the consequences of prenatal e‐Cig use during pregnancy on postnatal blood‐brain barrier (BBB) integrity, proinflammatory cytokine levels and behavioral outcomes in offspring.MethodPregnant CD1 mice (E5) were exposed to e‐Cig vapor (2.4% nicotine) till postnatal day (PD) 7. Weight of the offspring was measured up to PD 90. Nicotine and cotinine concentration in plasma and brain were measured in PD 7 offspring by LC‐MS/MS. The expression level of structural elements of the BBB including, tight junction proteins (ZO‐1, claudin‐5, occludin), astrocyte (GFAP), pericyte (PDGFRβ) and basement membrane (Laminin α1, Laminin α4) were analyzed in offspring using western blot and immunohistochemistry at PD 7, PD 23, PD 45 and PD 90. The expression level of pro‐inflammatory cytokines (IL‐1α, IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐10, IL‐12, IL‐17α, KC, LIX, MIP‐2 and TNF‐α) in brain were measured at PD 7 and PD 90. To evaluate behavioral outcomes, open field test, novel object recognition test and morris water maze test were performed on adolescent and adult offspring.ResultsReduced body weight was observed in e‐Cig exposed offspring at all time points till PD 90 compared to control (P &lt;0.05). Plasma concentration of nicotine and cotinine in PD 7 offspring was 3.215 ng/mL and 3.373 ng/mL respectively whereas in brain, these two concentrations were 43.72 ng/mL and 1.123 ng/mL respectively. Significantly reduced expression of brain tight junction proteins and GFAP were observed in male and female offspring at PD 7, PD 23, PD 45 and PD 90 (P &lt;0.05). Moreover, higher level of brain IL‐1α, IL‐6, IL‐7, IL‐10, IL‐17α, KC and TNF‐α was found in prenatally e‐cig exposed offspring at PD 7. However, only IL‐6 and IL‐17α were observed at higher levels in brain for prenatally e‐cig exposed adult offspring at PD 90 (P &lt;0.05). Additionally, disrupted motor, learning and memory function were observed in prenatally e‐Cig exposed adolescent and adult offspring.ConclusionOur findings suggest that prenatal e‐Cig exposure induces potential neurotoxic effects on neonates by disrupting postnatal blood‐brain barrier integrity and inducing proinflammatory brain cytokines which may result in alteration in neurological, cerebrovascular, and behavioral outcomes.

PD53-08 E-CIGARETTE EXPOSURE IN MICE PROMOTES CHANGES IN DNA METHYLATION OF THE BLADDER UROTHELIUM

You have accessJournal of UrologyCME1 May 2022PD53-08 E-CIGARETTE EXPOSURE IN MICE PROMOTES CHANGES IN DNA METHYLATION OF THE BLADDER UROTHELIUM Ibardo Zambrano, Ujjawal Manocha, Weida Gong, Yi-Hsuan Tsai, Manhua Zhu, Melissa Herman, Marc Bjurlin, and William Kim Ibardo ZambranoIbardo Zambrano More articles by this author , Ujjawal ManochaUjjawal Manocha More articles by this author , Weida GongWeida Gong More articles by this author , Yi-Hsuan TsaiYi-Hsuan Tsai More articles by this author , Manhua ZhuManhua Zhu More articles by this author , Melissa HermanMelissa Herman More articles by this author , Marc BjurlinMarc Bjurlin More articles by this author , and William KimWilliam Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002630.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To date, no group has studied the epigenetic effects of e-cigarettes (EC) on the urothelium. DNA methylation changes appear to be one of the earliest events in bladder tumorigenesis and can be readily found in normal urothelium adjacent to bladder tumors. EC exposure causes urothelial hyperplasia in mice but not bladder tumors. We Vtherefore asked whether EC exposure results in early field alterations of DNA methylation in the bladder urothelium. METHODS: Mice (4 females, 4 males; 35 weeks old) were exposed to 12% nicotine in 1:1 polyethylene glycol: vegetable glycerol or vehicle daily: 3 hr sessions, 3 sec vape duration, 10 min interval between vapes. Plasma nicotine and cotinine serum concentrations were measured using LC-MS. Reduced-representation bisulfite sequencing (RRBS) was performed using DNA from microdissected urothelium harvested at 4 weeks (Zymo Research Kit). Number of loci covered by each sample was determined and data was filtered to only include loci with >10 reads. Differentially methylated loci were determined (p<0.01). Gene Set Enrichment Analysis was performed to contextualize the DNA methylation changes. RESULTS: No significant adverse events were observed in the mice during the exposure period to either vehicle or nicotine. Acute and repeated exposure resulted in significantly higher levels of nicotine and cotinine serum concentration in the nicotine vs. the vehicle group (Figure 1). No bladder tumors formed. RRBS analysis demonstrated that EC exposure resulted in hypermethylation of the promoters of 665 genes and hypomethylation of 285 genes after accounting for sex (p <0.05) Pathway analysis showed enrichment of MYC target genes in hypomethylated regions and enrichment of genes associated with oxidative phosphorylation, cilium assembly, and ciliopathies in hypermethylated loci. CONCLUSIONS: Significant changes of DNA methylation were observed in mice exposed to ECS vapor vs. vehicle control. EC metabolites in urine may result in aberrant methylation patterns in the bladder urothelium. Results are suggestive of a pre-malignant phenotype driven by EC exposure via stimulation of MYC targets and silencing of genes responsible for establishing primary cilia. Loss of primary cilia in epithelial cells has been associated with loss of cell polarity and increased cell migration. Source of Funding: NCI Geographical Management of Cancer Health Disparities Program (3P30-CA016086), UNC Lineberger Innovation Award 2020 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e912 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ibardo Zambrano More articles by this author Ujjawal Manocha More articles by this author Weida Gong More articles by this author Yi-Hsuan Tsai More articles by this author Manhua Zhu More articles by this author Melissa Herman More articles by this author Marc Bjurlin More articles by this author William Kim More articles by this author Expand All Advertisement PDF DownloadLoading ...

The Effects of Pictorial Health Warning Label on Waterpipe (Low- and High-Frequency) Smokers' Experiences, Toxicant Exposures, and Puffing Behavior.

Pictorial health warning label (PHWL) is an effective risk communication measure among cigarette smokers. However, there is a lack of knowledge regarding the effect of PHWL on low- and high-frequency waterpipe (WP) smokers. This study examined the effects of PHWL on puffing behavior, subjective experiences, and toxicant exposures among low- and high-frequency WP smokers in the United States (US). Sixty current (past-month) WP smokers (low-frequency; n = 30 and high-frequency; n = 30) completed two 45-min ad libitum WP smoking sessions in a cross-over design study (WP with no-PHWL vs. WP with PHWL). We compared the mean differences of puff topography, expired carbon monoxide (eCO), plasma nicotine concentration, and subjective experiences between the two smoking groups. Mean age of low-frequency smokers was 21.5years and high-frequency smokers was 21.3years. Compared to high-frequency, low-frequency smokers had significant reduction in average total smoking time [mean difference (SD) = -7.6 (10.2) min vs. -2.6 (6.7) min, p = 0.03] and number of puffs [mean difference (SD) = -33.37 (70.7) vs. -0.70 (29.2), p = 0.02] following exposure to PHWL compared to no-PHWL condition. Post-session subjective experiences were lower among high-frequency smokers compared to low-frequency smokers following smoking WP with PHWL compared to the no-PHWL session (puff liking -1.2 vs. -0.5; puff satisfaction -1.0 vs. -0.3; craving reduction -0.5 vs. 1.2) (p < 0.05 for all). Our findings indicate that placing PHWL on the WP device may be a promising strategy with differential effectiveness among WP smokers: low-frequency (reduce puffing behaviors) and high-frequency (reduce smoking experience).

Green Tobacco Sickness: A Review

It is still an unknown fact among many that tobacco harvesters are at a potential at a risk of suffering from “Green Tobacco Sickness (GTS)”, with its prevalence seen mostly among Asian and South American tobacco harvesters. These harvesters working in hot, wet conditions are likely to develop GTS, as in such climatic conditions, the wetness and high humidity causes nicotine to reside on the surfaces of the leaves, while the high ambient temperature increases skin absorption, thereby increasing plasma nicotine concentrations by 30-45%. Patients suffering from GTS report nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, cough with or without expectoration, breathlessness and occasional reduction in blood pressure or heart rate. GTS is self-limiting and of short duration and hence treatment is not always necessary and not often sought by the harvesters. This review educates readers about GTS as well as encourages their participation in making tougher regulations in their respective countries for the control of this disease.

A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette.

Background and ObjectivesNicotine pouches (NPs) are a relatively new type of oral smokeless tobacco-free nicotine product. Currently, few data are available on the nicotine pharmacokinetics or subjective effects of NP use. The objective of this study was to determine and compare the pharmacokinetics of nicotine absorption into the blood from different NP variants and a combustible cigarette.MethodsIn a randomised, controlled, crossover clinical study, nicotine pharmacokinetics and subjective effects were compared among commercially available NPs (five different brands; 6–10 mg nicotine/pouch) and a combustible cigarette. During an 8-day confinement period, 35 healthy adult participants who were current dual users of snus and combustible cigarettes used one study product each day for a defined period following overnight nicotine abstinence.ResultsNicotine maximum plasma concentration (Cmax) and area under the plasma concentration-time curve between 0 and 6 h (AUC0–6h) were significantly greater for the Lyft 10 mg NP than for the cigarette (both p < 0.0001), while the other NPs had Cmax and AUC0–6h values that were either greater than or similar to those of the cigarette. Plasma nicotine concentration was not associated with the nicotine contents of the NPs. Time to reach maximum plasma concentration (Tmax) was higher for all NPs (60–65 min) than for the cigarette (7 min). Regarding subjective effects, liking and intent to use product again scores were higher for the cigarette than for any NP and were lowest for the NP with the lowest nicotine content.ConclusionsThis study provides important insight into nicotine pharmacokinetics and subjective effects during NP use, and demonstrates that NPs can provide nicotine in amounts sufficient to replicate cigarette smokers' nicotine uptake following a switch from conventional cigarettes to these potentially less harmful NP products. Further studies are required to ascertain how physical characteristics of NPs other than nicotine content may affect nicotine delivery, pharmacokinetics and subjective responses.ISRCTN Clinical Trial RegistryISRCTN17828518.

Abstract 11207: Electronic Hookah Vaping with and Without Nicotine: Insights into Vascular Function and Plasma Fibrinogen

Introduction: Electronic nicotine delivery systems (ENDS) are growing quickly in the United States, particularly among youth. Electronic (e-) hookahs are a new category of vaping devices in which the e-bowl is combined with and placed on a traditional waterpipe, allowing the flavored aerosol to pass through a water-filled base before being carried through the hose into the user’s mouth. E-hookah vaping with flavored nicotine acutely impairs endothelial function. However, the relative contribution of flavorings vs. nicotine on e-hookah vaping associated vascular dysfunction is unclear. Methods: In a randomized cross-over design study, we investigated the acute effect of flavored e-hookah with and without nicotine and sham vaping, among a cohort of 9 healthy young adult chronic hookah smokers (27±1 years, mean ±SE), on endothelial function, measured by brachial artery flow-mediated dilation (FMD). Fibrinogen, a major plasma protein coagulation factor, as well as smoking exposure biomarkers (plasma nicotine and expired carbon monoxide levels) were collected before and after the sessions. Results: Vaping e-hookah with nicotine induced an acute reduction in FMD (from 6.9±0.9 to 5.2±0.8%, pre- vs. post- vaping, p&lt;0.001), suggesting impairment in endothelial function and increased plasma fibrinogen (+14.5±4.1 mg/dL, p&lt;0.001). Though vaping e-hookah in the absence of nicotine did not significantly impair endothelial function (p = ns), it significantly induced an increase in plasma fibrinogen levels (+20.9±7.4 mg/dL, p&lt;0.001), higher than levels induced after vaping e-hookah with nicotine. Plasma nicotine concentrations increased 4-fold more after vaping e-hookah with nicotine, whereas no changes were observed after vaping e-hookah without nicotine or sham-vaping (p = ns). Exhaled CO levels did not change across all three vaping sessions. Conclusions: In healthy young adults, our findings to date suggest that while vaping e-hookah with nicotine induces an unfavorable effect on the vasculature, non-nicotine constituents generated from heating the flavored e-hookah aerosol cannot be ignored. Further plans are needed to elucidate the long-term vascular implications of vaping non-nicotine flavored constituents.