Showing papers by "Neal L. Benowitz published in 2016"

Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes

Abstract: Author(s): St Helen, Gideon; Havel, Christopher; Dempsey, Delia A; Jacob, Peyton; Benowitz, Neal L | Abstract: AimsTo measure the systemic retention of nicotine, propylene glycol (PG) and vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics.DesignE-cigarette users recruited over the internet participated in a 1-day research ward study. Subjects took 15 puffs from their usual brand of e-cigarette. Exhaled breath was trapped in gas-washing bottles and blood was sampled before and several times after use.SettingSan Francisco, California, USA.ParticipantsThirteen healthy, experienced adult e-cigarette users (six females and seven males).MeasurementsPlasma nicotine was analyzed by gas chromatography-mass spectrometry (GC-MS/MS) and nicotine, VG and PG in e-liquids and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective effects were assessed.FindingsE-cigarettes delivered an average of 1.33 (0.87-1.79) mg [mean and 95% confidence interval (CI)] of nicotine, and 93.8% of the inhaled dose, 1.22 (0.80-1.66) was systemically retained. Average maximum plasma nicotine concentration (Cmax ) was 8.4 (5.4-11.5) ng/ml and time of maximal concentration (Tmax ) was 2-5 minutes. One participant had Tmax of 30 minutes. 84.4% and 91.7% of VG and PG, respectively, was systemically retained. Heart rate increased by an average of 8.0 beats per minute after 5 minutes. Withdrawal and urge to smoke decreased and the e-cigarettes were described as satisfying.ConclusionsE-cigarettes can deliver levels of nicotine that are comparable to or higher than typical tobacco cigarettes, with similar systemic retention. Although the average maximum plasma nicotine concentration in experienced e-cigarette users appears to be generally lower than what has been reported from tobacco cigarette use, the shape of the pharmacokinetic curve is similar, suggesting addictive potential.

E-cigarette use results in suppression of immune and inflammatory-response genes in nasal epithelial cells similar to cigarette smoke

Abstract: Exposure to cigarette smoke is known to result in impaired host defense responses and immune suppressive effects. However, the effects of new and emerging tobacco products, such as e-cigarettes, on...

The Past, Present, and Future of Nicotine Addiction Therapy

Abstract: The tobacco addiction treatment field is progressing through innovations in medication development, a focus on precision medicine, and application of new technologies for delivering support in real time and over time. This article reviews the evidence for combined and extended cessation pharmacotherapy and behavioral strategies including provider advice, individual counseling, group programs, the national quitline, websites and social media, and incentives. Healthcare policies are changing to offer cessation treatment to the broad population of smokers. With knowledge of the past and present, this review anticipates what is likely on the horizon in the clinical and public health effort to address tobacco addiction.

Smoking cessation, version 1.2016 clinical practice guidelines in oncology

Abstract: Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.

Nicotine Delivery and Vaping Behavior During ad Libitum E-cigarette Access.

Abstract: Author(s): St Helen, Gideon; Ross, Kathryn C; Dempsey, Delia A; Havel, Christopher M; Jacob, Peyton; Benowitz, Neal L | Abstract: ObjectiveTo characterize vaping behavior and nicotine intake during ad libitum e-cigarette access.MethodsThirteen adult e-cigarette users had 90 minutes of videotaped ad libitum access to their usual e-cigarette. Plasma nicotine was measured before and every 15 minutes after the first puff; subjective effects were measured before and after the session.ResultsAverage puff duration and interpuff interval were 3.5±1.4 seconds (±SD) and 118±141 seconds, respectively. 12% of puffs were unclustered puffs while 43%, 28%, and 17% were clustered in groups of 2-5, 6-10, and g10 puffs, respectively. On average, 4.0±3.3 mg of nicotine was inhaled; the maximum plasma nicotine concentration (Cmax) was 12.8±8.5 ng/mL. Among the 8 tank users, number of puffs was positively correlated with amount of nicotine inhaled, Cmax, and area under the plasma nicotine concentration-time curve (AUC0→90min) while interpuff interval was negatively correlated with Cmax and AUC0→90.ConclusionVaping patterns differ from cigarette smoking. Plasma nicotine levels were consistent with intermittent dosing of nicotine from e-cigarettes compared to the more bolus dosing from cigarettes. Differences in delivery patterns and peak levels of nicotine achieved could influence the addictiveness of e-cigarettes compared to conventional cigarettes.

Tobacco Consumption and Toxicant Exposure of Cigarette Smokers Using Electronic Cigarettes.

Abstract: Author(s): Pulvers, Kim; Emami, Ashley S; Nollen, Nicole L; Romero, Devan R; Strong, David R; Benowitz, Neal L; Ahluwalia, Jasjit S | Abstract: BackgroundThere is considerable debate about the benefits and risks of electronic cigarettes (ECs). To better understand the risk-benefit ratio of ECs, more information is needed about net nicotine consumption and toxicant exposure of cigarette smokers switching to ECs.MethodsForty cigarette smokers (≥1 year of smoking) interested in switching to ECs but not necessarily quitting smoking were enrolled in a 4-week observational study and provided an e-Go C non-variable battery and refillable atomizers and choice of eight flavors in 12 or 24 mg nicotine dosage. Measurement of urinary cotinine (metabolite of nicotine), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a pulmonary carcinogen), and eight volatile organic compounds (VOCs) that are toxic tobacco smoke constituents was conducted at baseline and week 4.ResultsAll participants with follow-up data (92.5%) reported using the study EC. Of the 40 smokers, 16 reported no cigarettes at week 2 (40%) and six continued to report no cigarettes at week 4 (15%). Change in nicotine intake over the 4 weeks was non-significant (p = .90). Carbon monoxide (p l .001), NNAL (p l .01) and metabolites of benzene (p l .01) and acrylonitrile (p = .001) were significantly decreased in the study sample. Smokers switching exclusively to ECs for at least half of the study period demonstrated significant reductions in metabolites of ethylene oxide (p = .03) and acrylamide (p l .01).ConclusionSmokers using ECs over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, NNAL, and two out of eight measured VOC metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.ImplicationsThis study extends current literature by measuring change in smoking dependence and disease-associated biomarkers, NNAL and a panel of eight common VOCs that are toxic tobacco smoke constituents in smokers who switch to ECs. The findings support the idea of harm reduction, however some levels of toxicant exposure are still of clinical concern, particularly for dual users. Extrapolation of these results must be careful to separate the different toxic exposure results for exclusive switchers versus dual cigarette + EC users, and not to equate harm reduction with the idea that using ECs is harmless.

Thirdhand smoke contamination in hospital settings: assessing exposure risk for vulnerable paediatric patients

Abstract: Background Tobacco has regained the status of the world9s number two killer behind heart/vascular disease. Thirdhand smoke (THS) residue and particles from secondhand smoke (SHS) are suspected health hazards (eg, DNA damage) that are likely to contribute to morbidity and mortality, especially in vulnerable children. THS is easily transported and deposited indoors, where it persists and exposes individuals for months, creating potential health consequences in seemingly nicotine-free environments, particularly for vulnerable patients. We collected THS data to estimate infant exposure in the neonatal ICU (NICU) after visits from household smokers. Infant exposure to nicotine, potentially from THS, was assessed via assays of infant urine. Methods Participants were mothers who smoked and had an infant in the NICU (N=5). Participants provided surface nicotine samples from their fingers, infants’ crib/incubator and hospital-provided furniture. Infant urine was analysed for cotinine, cotinine9s major metabolite: trans -3′-hydroxycotinine (3HC) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the nicotine-derived and tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Results Incubators/cribs and other furniture had detectable surface nicotine. Detectable levels of cotinine, 3HC and NNAL were found in the infants’ urine. Discussion THS appears to be ubiquitous, even in closely guarded healthcare settings. Future research will address potential health consequences and THS-reduction policies. Ultimately, hospital policies and interventions to reduce THS transport and exposure may prove necessary, especially for immunocompromised children.

Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking

Abstract: Rate of nicotine metabolism has been identified as an important factor influencing nicotine intake and can be estimated using the nicotine metabolite ratio (NMR), a validated biomarker of CYP2A6 enzyme activity Individuals who metabolize nicotine faster (higher NMR) may alter their smoking behavior to titrate their nicotine intake in order to maintain similar levels of nicotine in the body compared to slower nicotine metabolizers There are known racial differences in the rate of nicotine metabolism with African Americans on average having a slower rate of nicotine metabolism compared to Whites The goal of this study was to determine if there are racial differences in the relationship between rate of nicotine metabolism and measures of nicotine intake assessed using multiple biomarkers of nicotine and tobacco smoke exposure Using secondary analyses of the screening data collected in a recently completed clinical trial, treatment-seeking African American and White daily smokers (10 or more cigarettes per day) were grouped into NMR quartiles so that the races could be compared at the same NMR, even though the distribution of NMR within race differed The results indicated that rate of nicotine metabolism was a more important factor influencing nicotine intake in White smokers Specifically, Whites were more likely to titrate their nicotine intake based on the rate at which they metabolize nicotine However, this relationship was not found in African Americans Overall there was a greater step-down, linear type relationship between NMR groups and cotinine or cotinine/cigarette in African Americans, which is consistent with the idea that differences in blood cotinine levels between the African American NMR groups were primarily due to differences in CYP2A6 enzyme activity without titration of nicotine intake among faster nicotine metabolizers

Thirdhand smoke: State of the science and a call for policy expansion

Abstract: Author(s): Northrup, Thomas F; Jacob, Peyton; Benowitz, Neal L; Hoh, Eunha; Quintana, Penelope JE; Hovell, Melbourne F; Matt, Georg E; Stotts, Angela L

Estimations and predictors of non-compliance in switchers to reduced nicotine content cigarettes.

Abstract: Background and Aims Clinical trials on the impact and safety of reduced nicotine content cigarettes (RNCs) are ongoing, and an important methodological concern is participant compliance with smoking only RNCs. Our aims were to measure non-compliance biochemically with urine cotinine (COT) and total nicotine equivalents (TNEs), compare with self-reported non-compliance and identify associated covariates. Design Secondary analysis of a double-blind, parallel, randomized clinical trial. Setting Research centers from the United States, enrolling participants from June 2013 to July 2014. Participants Volunteer sample of 242 participants (55% Caucasian), average age of 41.2 years, smoking at least five cigarettes per day (CPD). Intervention Smoking very low nicotine cigarettes (VLNCs; 0.4 mg nicotine/g tobacco) for 6 weeks. Measurements The primary outcome was biochemically verified non-compliance, measured as thresholds of COT/CPD and TNE/CPD ratios, considering changes in nicotine content from conventional levels to VLNCs, and as an absolute threshold of week 6 TNEs. Self-reported non-compliance was measured via daily phone calls. Key predictors included age, sex, race, menthol preference, nicotine metabolite ratio, time to first cigarette, dependence, CPD, TNEs, tar level and cigarette evaluation. Findings Estimates of non-compliance with smoking the VLNCs exclusively include: the biochemical ratios (both 78%), the week 6 TNE threshold (76%) and self-report (39%). Of the key covariates, age, dependence and cigarette evaluations of satisfaction were significant; for age, younger participants more likely to be non-compliant [P = 0.01; odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96–0.99]. Dependence was associated significantly with self-reported non-compliance (P = 0.01; OR = 1.28, 95% CI = 1.06–1.55). Cigarette evaluations of satisfaction were associated significantly with non-compliance (P = 0.001; OR = 0.71, 95% CI = 0.61–0.82). Conclusions Among smokers volunteering to smoke only very low nicotine cigarettes for 6 weeks, non-compliance was common and biochemical assessments detected more cases of non-compliance than self-report. Despite high levels of non-compliance, smokers reduced their intake of nicotine by an average of 60%.

Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries.

Abstract: Introduction: Metabolic enzyme variation and other patient and environmental characteristics influence smoking behaviors, treatment success, and risk of related disease. Population-specific variation in metabolic genes contributes to challenges in developing and optimizing pharmacogenetic interventions. We applied a custom genome-wide genotyping array for addiction research (Smokescreen), to three laboratory-based studies of nicotine metabolism with oral or venous administration of labeled nicotine and cotinine, to model nicotine metabolism in multiple populations. The trans-3′-hydroxycotinine/cotinine ratio, the nicotine metabolite ratio (NMR), was the nicotine metabolism measure analyzed.

An Electronic Cigarette Vaping Machine for the Characterization of Aerosol Delivery and Composition.

Abstract: Author(s): Havel, Christopher M; Benowitz, Neal L; Jacob, Peyton; St Helen, Gideon | Abstract: IntroductionCharacterization of aerosols generated by electronic cigarettes (e-cigarettes) is one method used to evaluate the safety of e-cigarettes. While some researchers have modified smoking machines for e-cigarette aerosol generation, these machines are either not readily available, not automated for e-cigarette testing or have not been adequately described. The objective of this study was to build an e-cigarette vaping machine that can be used to test, under standard conditions, e-liquid aerosolization and nicotine and toxicant delivery.MethodsThe vaping machine was assembled from commercially available parts, including a puff controller, vacuum pump, power supply, switch to control current flow to the atomizer, three-way value to direct air flow to the atomizer, and three gas dispersion tubes for aerosol trapping. To validate and illustrate its use, the variation in aerosol generation was assessed within and between KangerTech Mini ProTank 3 clearomizers, and the effect of voltage on aerosolization and toxic aldehyde generation were assessed.ResultsWhen using one ProTank 3 clearomizer and different e-liquid flavors, the coefficient of variation (CV) of aerosol generated ranged between 11.5% and 19.3%. The variation in aerosol generated between ProTank 3 clearomizers with different e-liquid flavors and voltage settings ranged between 8.3% and 16.3% CV. Aerosol generation increased linearly at 3-6V across e-liquids and clearomizer brands. Acetaldehyde, acrolein, and formaldehyde generation increased markedly at voltages at or above 5V.ConclusionThe vaping machine that we describe reproducibly aerosolizes e-liquids from e-cigarette atomizers under controlled conditions and is useful for testing of nicotine and toxicant delivery.ImplicationsThis study describes an electronic cigarette vaping machine that was assembled from commercially available parts. The vaping machine can be replicated by researchers and used under standard conditions to generate e-cigarette aerosols and characterize nicotine and toxicant delivery.

Nicotine and Anatabine Exposure from Very Low Nicotine Content Cigarettes

Abstract: Author(s): Denlinger, Rachel L; Smith, Tracy T; Murphy, Sharon E; Koopmeiners, Joseph S; Benowitz, Neal L; Hatsukami, Dorothy K; Pacek, Lauren R; Colino, Cirielle; Cwalina, Samantha N; Donny, Eric C | Abstract: Objectives:Research using very low nicotine content (VLNC) cigarettes has shown that participants underreport use of non-study cigarettes. Biomarkers of nicotine exposure could be used to verify compliance with VLNC cigarettes. This study aimed to characterize biomarkers of exposure when participants exclusively use VLNC cigarettes. Methods:23 participants stayed in a hotel that permitted smoking for 5 days and 4 nights. They were provided 2 packs of VLNC cigarettes each day (0.4 mg of nicotine/g of tobacco; Spectrum cigarettes) and did not have access to other tobacco products. 24-hour urine samples were collected to assess exposure to nicotine and anatabine. Results:After 4 days of exclusive use, the geometric means for urinary total cotinine, total nicotine equivalents (TNE), and anatabine were 1.13 nmol/ml (92% reduction), 3.17 nmol/ml (94% reduction) and 0.0031 nmol/ml (93% reduction). The population estimates of the 95th percentile of cotinine, TNE, and anatabine levels were 2.69, 6.41, and 0.0099 nmol/ml, respectively. Conclusions:Study participants exclusively smoking 0.4 mg/g Spectrum cigarettes are unlikely to have biomarker values above these levels. The data presented here will be valuable to researchers conducting research on use of VLNC cigarettes.

Disposition kinetics and metabolism of nicotine and cotinine in African American smokers: impact of CYP2A6 genetic variation and enzymatic activity.

Abstract: Author(s): Benowitz, Neal L; St Helen, Gideon; Dempsey, Delia A; Jacob, Peyton; Tyndale, Rachel F | Abstract: ObjectiveThe rate of nicotine metabolism, determined primarily by CYP2A6 activity, influences tobacco dependence and smoking-induced disease risk. The prevalence of CYP2A6 gene variants differs by race, with greater numbers in African Americans compared with Caucasians. We studied nicotine disposition kinetics and metabolism by the CYP2A6 genotype and enzymatic activity, as measured by the nicotine metabolite ratio (NMR), in African American smokers.MethodsParticipants were administered intravenous infusions of deuterium-labeled nicotine and cotinine. Plasma and urine concentrations of nicotine and metabolites were measured and pharmacokinetic parameters were estimated.ResultsPharmacokinetic parameters and urine metabolite excretion data were analyzed by CYP2A6 genotype and by NMR. A number of gene variants were associated with markedly reduced nicotine and cotinine clearances. NMR was strongly correlated with nicotine (r=0.72) and cotinine (r=0.80) clearances. Participants with higher NMR excreted significantly greater nicotine C-oxidation and lower non-C-oxidation products compared with lower NMR participants.ConclusionCYP2A6 genotype, NMR, and nicotine pharmacokinetic data may inform studies of individual differences in smoking behavior and biomarkers of nicotine exposure.

Nicotine Replacement, Topography, and Smoking Phenotypes of E-cigarettes.

Abstract: Author(s): Strasser, Andrew A; Souprountchouk, Valentina; Kaufmann, Amanda; Blazekovic, Sonja; Leone, Frank; Benowitz, Neal L; Schnoll, Robert A | Abstract: ObjectivesLittle is known about the degree of nicotine replacement across first-generation e-cigarette brands, how e-cigarettes are used, and if there is variation across brands in relevant smoking phenotypes. The objective of this project was to collect data that are critical to better understanding, use, and exposure when using e-cigarettes, which may then inform clinical trials and tobacco regulatory policy.MethodsTwenty-eight cigarette smokers were randomized to use one of 5 popular brands of e-cigarettes for a 10-day study. Day 1 (own cigarette brand) data established baseline levels for cotinine, carbon monoxide (CO), topography, cigarette liking, withdrawal, and craving. Participants returned on Days 5 and 10 to reassess these measures while exclusively using e-cigarettes.ResultsCompared to cigarette smoking, e-cigarettes provided significantly lower nicotine levels (25%-50%), reduced CO exposure, and lower ratings of liking (p l .05). Topography significantly differed between cigarette and e-cigarette sessions (p l .05). All brands significantly reduced withdrawal and craving (p l .05). There were no significant brand differences in outcome measures associated with exposure or use.ConclusionsE-cigarettes are not liked as much as cigarettes, provide significantly lower nicotine replacement, reduce CO exposure, and mitigate withdrawal and craving. The patterns of use significantly differ compared to cigarette smoking.

Urine Cotinine Screening Detects Nearly Ubiquitous Tobacco Smoke Exposure in Urban Adolescents.

Abstract: Author(s): Benowitz, Neal L; Jain, Shonul; Dempsey, Delia A; Nardone, Natalie; Helen, Gideon St; Jacob, Peyton | Abstract: IntroductionRoutine biochemical assessment of tobacco smoke exposure could lead to more effective interventions to reduce or prevent secondhand smoke (SHS)-related disease in adolescents. Our aim was to determine using urine cotinine (major nicotine metabolite) measurement the prevalence of tobacco smoke exposure among adolescents receiving outpatient care at an urban public hospital.MethodsSurplus urine was collected in 466 adolescents attending pediatric or urgent care clinics at Zuckerberg San Francisco General Hospital, serving families with lower levels of income and education, in 2013-2014. The majority were Hispanic or African American. Urine cotinine cut points of 0.05 to 0.25 ng/ml, 0.25 to 30 ng/ml, and 30 ng/ml were used to classify subjects as light SHS or thirdhand smoke exposed, SHS or light/intermittent active users, and active tobacco users, respectively.ResultsAmong subjects 87% were exposed, including 12% active smoking, 46% SHS and 30% lightly exposed. The SHS exposed group adjusted geometric mean cotinine values were significantly higher in African Americans (1.48 ng/ml) compared to other groups (0.56-1.13 ng/ml).ConclusionsIn a city with a low smoking prevalence (12%), a large majority (87%) of adolescents seen in a public hospital clinic are exposed to tobacco. This is much higher than reported in national epidemiological studies of adolescents, which used a plasma biomarker. Since SHS is associated with significant respiratory diseases and parents and adolescents underreport exposure to SHS, routine biochemical screening should be considered as a tool to reduce SHS exposure. The clinical significance of light exposure needs to be investigated.ImplicationsUrine biomarker screening found that a large majority (87%) of adolescents treated in an urban public hospital are exposed to tobacco. Since SHS is associated with significant respiratory diseases and parents and adolescents underreport exposure to SHS, routine biochemical screening should be considered as a tool to reduce SHS exposure.

The influence of puff characteristics, nicotine dependence, and rate of nicotine metabolism on daily nicotine exposure in African American smokers.

Abstract: Background: African American (AA) smokers experience greater tobacco-related disease burden than Whites, despite smoking fewer cigarettes per day (CPD). Understanding factors that influence daily nicotine intake in AA smokers is an important step towards decreasing tobacco-related health disparities. One factor of interest is smoking topography, or the study of puffing behavior. Aims: 1) To create a model using puff characteristics, nicotine dependence, and nicotine metabolism to predict daily nicotine exposure, and 2) to compare puff characteristics and nicotine intake from two cigarettes smoked at different times to ensure the reliability of the puff characteristics included in our model. Methods: 60 AA smokers smoked their preferred brand of cigarette at two time points through a topography device. Plasma nicotine, expired CO, and changes in subjective measures were measured before and after each cigarette. Total nicotine equivalents (TNE) was measured from 24-hour urine collected during ad lib smoking. Results: In a model predicting daily nicotine exposure, total puff volume, CPD, sex, and menthol status were significant predictors, (R2= .44, p < .001). Total puff volume was significantly greater and inter-puff intervals were significantly shorter after ad lib smoking compared to the first cigarette of the day, but puffing behaviors for both cigarettes were highly correlated (r range= .69-.89, p <.001) within-subjects. Conclusion: This is the first study, to our knowledge, to show that puff characteristics of individual cigarettes are predictive of daily nicotine intake. Impact: These findings enhance our understanding of the relationship between smoking behavior and nicotine intake in AA smokers.

Acute Effect of Hookah Smoking on the Human Coronary Microcirculation

Abstract: Hookah (water pipe) smoking is a major new understudied epidemic affecting youth. Because burning charcoal is used to heat the tobacco product, hookah smoke delivers not only nicotine but also large amounts of charcoal combustion products, including carbon-rich nanoparticles that constitute putative coronary vasoconstrictor stimuli and carbon monoxide, a known coronary vasodilator. We used myocardial contrast echocardiography perfusion imaging with intravenous lipid shelled microbubbles in young adult hookah smokers to determine the net effect of smoking hookah on myocardial blood flow. In 9 hookah smokers (age 27 ± 5 years, mean ± SD), we measured myocardial blood flow velocity (β), myocardial blood volume (A), myocardial blood flow (A × β) as well as myocardial oxygen consumption (MVO2) before and immediately after 30 minutes of ad lib hookah smoking. Myocardial blood flow did not decrease with hookah smoking but rather increased acutely (88 ± 10 to 120 ± 19 a.u./s, mean ± SE, p = 0.02), matching a mild increase in MVO2 (6.5 ± 0.3 to 7.6 ± 0.4 ml·minute(-1), p <0.001). This was manifested primarily by increased myocardial blood flow velocity (0.7 ± 0.1 to 0.9 ± 0.1 second(-1), p = 0.01) with unchanged myocardial blood volume (133 ± 7 to 137 ± 7 a.u., p = ns), the same pattern of coronary microvascular response seen with a low-dose β-adrenergic agonist. Indeed, with hookah, the increased MVO2 was accompanied by decreased heart rate variability, an indirect index of adrenergic overactivity, and eliminated by β-adrenergic blockade (i.v. propranolol). In conclusion, nanoparticle-enriched hookah smoke either is not an acute coronary vasoconstrictor stimulus or its vasoconstrictor effect is too weak to overcome the physiologic dilation of coronary microvessels matching mild cardiac β-adrenergic stimulation.

Fetal Exposure to Carcinogens With Tobacco Use in Pregnancy: Phase 1 MAW Study Findings.

Abstract: Author(s): Flanagan, Christie A; Koller, Kathryn R; Wolfe, Abbie W; Thomas, Timothy K; Benowitz, Neal L; Renner, Caroline C; Hughes, Christine; Hatsukami, Dorothy K; Bronars, Carrie; Murphy, Neil J; Day, Gretchen; Decker, Paul A; Patten, Christi A | Abstract: IntroductionThe high prevalence of smoking and smokeless tobacco (ST) use during pregnancy in Alaska Native (AN) women is concerning due to the detrimental effects of these products to the mother and the developing fetus. We sought to correlate maternal cotinine levels with fetal exposure to a tobacco-specific carcinogen to incorporate in a biomarker feedback intervention to motivate tobacco cessation during pregnancy.MethodsDemographic and tobacco use data were collected from a convenience sample of pregnant AN smokers, ST users, and non-users. Maternal and neonatal urine were collected at delivery. Maternal urine cotinine and neonatal urine total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a tobacco-specific carcinogen) levels in smokers and ST users were analyzed and their correlations determined by Spearman correlation coefficients.ResultsDuring 2012-2014, we enrolled 64 non-users, 54 smokers, and 30 ST (20 homemade iqmik; 10 commercial ST) users (n = 148). Analyses of paired maternal-infant urine samples obtained for 36 smokers demonstrated a moderate to strong correlation (r = 0.73, P l .001) between maternal cotinine and infant NNAL levels. The correlation was not significant for 25 iqmik users (r = 0.36, P = .17) or 9 commercial ST users (r = 0.60, P = .09). No analysis was conducted for 55 non-users with cotinine and NNAL levels l limits of quantification.ConclusionsThere is a moderate to strong correlation between maternal smoking and fetal exposure to the tobacco-specific carcinogen NNAL.ImplicationsThe correlation between maternal smoking and fetal carcinogen exposure may provide an education tool to help motivate smoking cessation among pregnant AN women. Further investigation is warranted to determine correlations between maternal commercial ST and iqmik use and neonatal NNAL.

Minoxidil-Associated Pleuropericardial Effusion.

Abstract: University of California San Francisco School ofMedicine, San Francisco, CA, USA; Department ofMedicine, University ofCalifornia San Francisco, San Francisco, CA, USA; Departments of Medicine, Biopharmaceutical Sciences, Psychiatry, and Clinical Pharmacy, University of California San Francisco, San Francisco, CA, USA; PGY3, Internal Medicine Residency, University of California San Francisco, San Francisco, CA, USA.

Nicotine Metabolite Ratio Is Associated With Lozenge Use But Not Quitting in Smokeless Tobacco Users

Abstract: Author(s): Ebbert, Jon O; Severson, Herbert H; Danaher, Brian G; Benowitz, Neal L; Schroeder, Darrell R | Abstract: IntroductionThe nicotine metabolite ratio (NMR) of 3'-hydroxycotinine to cotinine is a noninvasive marker of the rate of nicotine metabolism. Fast metabolism (ie, a high NMR) is associated with lower cigarette smoking abstinence rates using transdermal nicotine replacement. We evaluated whether the NMR can be used to predict self-reported nicotine lozenge use and tobacco abstinence among smokeless tobacco users treated for tobacco dependence.MethodsThis was a secondary analysis of data from one arm of a large trial. Participants received quitting support materials and 4-mg nicotine lozenges by mail plus three coaching phone calls. Saliva kits were mailed for collection of saliva samples, which were analyzed for cotinine and 3'-hydroxycotinine. Self-reported tobacco and lozenge use were assessed at 3 months. Analyses were performed using Spearman rank correlation and logistic regression.ResultsOf the 160 saliva collection kits mailed, 152 were returned. The NMR was not significantly correlated with the baseline amount of smokeless tobacco used, the number of years of tobacco use, or the level of tobacco dependence as measured by the Severson Smokeless Tobacco Dependency Scale. The NMR was positively correlated with lozenge use (r = 0.21, P = .015), but it did not predict self-reported 7-day point prevalence abstinence at 3 months.ConclusionsFast metabolizers may need to self-administer more nicotine replacement in the form of nicotine lozenges to achieve the same clinical response achieved by slower metabolizers using fewer lozenges.

“You have the right to protect your health”: Perceptions of Secondhand Smoke and Exposure Mitigation Strategies in Low-Income Patients With Heart Disease, San Francisco, 2011–2012

Abstract: We examined the understanding of the harms of secondhand smoke (SHS) exposure among low-income, hospitalized adults with cardiovascular disease. Participants were 15 nonsmokers reporting daily SHS exposure and 15 light or nondaily cigarette smokers. We coded responses from audiotaped semistructured interviews for themes. No participant spontaneously identified heart risks related to SHS exposure. Strategies to avoid SHS included verbal requests to not smoke and physically avoiding smoke; both smokers and nonsmokers prioritized politeness over urgency. Most participants thought a blood test quantifying SHS exposure would be clinically useful. Health education, assertiveness communication training, and protective policies (eg, smoke-free multiunit housing) also were supported.