Showing papers by "Neal L. Benowitz published in 2014"

Levels of selected carcinogens and toxicants in vapour from electronic cigarettes

Abstract: Significance Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e–cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals. Materials and methods Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods. Results We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9–450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product. Conclusions Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.)

E-Cigarettes: A Scientific Review

Abstract: Electronic cigarettes (e-cigarettes) are products that deliver a nicotine-containing aerosol (commonly called vapor) to users by heating a solution typically made up of propylene glycol or glycerol (glycerin), nicotine, and flavoring agents (Figure 1) invented in their current form by Chinese pharmacist Hon Lik in the early 2000s.1 The US patent application describes the e-cigarette device as “an electronic atomization cigarette that functions as substitutes [sic] for quitting smoking and cigarette substitutes ” (patent No. 8,490,628 B2). By 2013, the major multinational tobacco companies had entered the e-cigarette market. E-cigarettes are marketed via television, the Internet, and print advertisements (that often feature celebrities)2 as healthier alternatives to tobacco smoking, as useful for quitting smoking and reducing cigarette consumption, and as a way to circumvent smoke-free laws by enabling users to “smoke anywhere.”3 Figure 1. Examples of different electronic cigarette (e-cigarette) products. Reproduced from Grana et al.1 There has been rapid market penetration of e-cigarettes despite many unanswered questions about their safety, efficacy for harm reduction and cessation, and total impact on public health. E-cigarette products are changing quickly, and many of the findings from studies of older products may not be relevant to the assessment of newer products that could be safer and more effective as nicotine delivery devices. In addition, marketing and other environmental influences may vary from country to country, so patterns of use and the ultimate impact on public health may differ. The individual risks and benefits and the total impact of these products occur in the context of the widespread and continuing availability of conventional cigarettes and other tobacco products, with high levels of dual use of e-cigarettes and conventional cigarettes at the same time among adults4–8 and youth.9–11 It is important to assess e-cigarette toxicant exposure and …

Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit

Abstract: Aims We reviewed available research on the use, content and safety of electronic cigarettes (EC), and on their effects on users, to assess their potential for harm or benefit and to extract evidence that can guide future policy. Methods Studies were identified by systematic database searches and screening references to February 2014. Results EC aerosol can contain some of the toxicants present in tobacco smoke, but at levels which are much lower. Long-term health effects of EC use are unknown but compared with cigarettes, EC are likely to be much less, if at all, harmful to users or bystanders. EC are increasingly popular among smokers, but to date there is no evidence of regular use by never-smokers or by non-smoking children. EC enable some users to reduce or quit smoking. Conclusions Allowing EC to compete with cigarettes in the market-place might decrease smoking-related morbidity and mortality. Regulating EC as strictly as cigarettes, or even more strictly as some regulators propose, is not warranted on current evidence. Health professionals may consider advising smokers unable or unwilling to quit through other routes to switch to EC as a safer alternative to smoking and a possible pathway to complete cessation of nicotine use.

Electronic Cigarettes A Policy Statement From the American Heart Association

Abstract: For decades, advocacy for tobacco control has been a priority of the American Heart Association (AHA). In partnership with major public health organizations, the association has made major strides in tobacco use prevention and cessation by prioritizing evidence-based strategies such as increasing excise taxes; passing comprehensive smoke-free air laws; facilitating US Food and Drug Administration (FDA) authority to regulate tobacco, including comprehensive tobacco cessation treatment within healthcare plans; and supporting adequate funding of comprehensive tobacco control programs in different states. These tobacco control efforts have cut in half the youth smoking rate from 1997 to 2007 and have saved >8 million lives in the past 50 years.1 However, the work is far from done and has stalled, especially for people living below the poverty line, those with mental illnesses,2 and those with low educational attainment.3 Unless current trends reverse, ≈5.6 million children alive today in the United States will die prematurely of smoking-related diseases.1 Even now, cigarette smoking kills nearly half a million Americans each year, and an additional 16 million individuals suffer from smoking-related illness, which costs the United States $289 billion dollars annually in direct medical care and other economic costs.1 This statement reviews the latest science concerning one of the newest classes of products to enter the tobacco product landscape—electronic cigarettes (e-cigarettes), also called electronic nicotine delivery systems (ENDS)—and provides an overview on design, operations, constituents, toxicology, safety, user profiles, public health, youth access, impact as a cessation aid, and secondhand exposure. On the basis of the current evidence, we provide policy recommendations in key areas of tobacco control such as clean indoor air laws, taxation, regulation, preventing youth access, marketing and advertising to youth, counseling for cessation, surveillance, and defining e-cigarettes in state laws. The statement concludes by outlining a future …

Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health

Abstract: Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered – Thirdhand smoke (THS) – the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.

Emerging Nicotine Delivery Products. Implications for Public Health

Abstract: The idea of clean nicotine delivery systems that would satisfy nicotine craving and promote smoking cessation has been considered as a possible public health tool for many years. Nicotine medications have been useful for smoking cessation but have not found widespread popularity among smokers, perhaps because of slow nicotine delivery and other sensory characteristics that differ from cigarettes. Traditional smokeless tobacco delivers as much nicotine as cigarettes and has been advocated for harm reduction but contains carcinogenic nitrosamines and has not been proven to promote cessation. Furthermore, there is concern that dual use of smokeless tobacco and cigarettes may inhibit quitting smoking. Newer oral dissolvable tobacco products contain lower levels of toxicants than other smokeless tobacco but also deliver much less nicotine and have not been popular with consumers. Electronic cigarettes that aerosolize nicotine without generating toxic tobacco combustion products have become quite popular and hold promise as a way to attract smokers away from cigarettes, although efficacy in promoting smoking cessation has not yet been demonstrated. There are concerns about safety of long-term use, and there is evidence that youth, including nonsmokers, are taking up e-cigarette use. E-cigarettes are marketed for use when one cannot smoke conventional cigarettes, and such use might result in more persistent cigarette smoking. Although their benefits and risks are being vigorously debated, e-cigarettes or other clean nicotine delivery devices could play an important role as an adjunct to a U.S. Food and Drug Administration regulatory intervention to make cigarettes less addictive and in this context could contribute to the end of cigarette smoking and smoking-induced disease.

Nicotine and Carcinogen Exposure after Water Pipe Smoking in Hookah Bars

Abstract: Background: Water pipe tobacco smoking is spreading globally and is increasingly becoming popular in the United States, particularly among young people. Although many perceive water pipe smoking to be relatively safe, clinical experimental studies indicate significant exposures to tobacco smoke carcinogens following water pipe use. We investigated biomarkers of nicotine intake and carcinogen exposure from water pipe smoking in the naturalistic setting of hookah bars. Methods: Fifty-five experienced water pipe users were studied before and after smoking water pipe in their customary way in a hookah bar. Urine samples were analyzed for nicotine, cotinine, the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and mercapturic acid metabolites of volatile organic compounds (VOC). Results: We found an average 73-fold increase in nicotine, 4-fold increase in cotinine, 2-fold increase in NNAL, and 14% to 91% increase in VOC mercapturic acid metabolites immediately following water pipe smoking. We saw moderate to high correlations between changes in tobacco-specific biomarkers (nicotine, cotinine, and NNAL) and several mercapturic acid metabolites of VOCs. Conclusion: Water pipe smoking in a hookah bar is associated with significant nicotine intake and carcinogen exposure. Impact: Given the significant intake of nicotine and carcinogens, chronic water pipe use could place users at increased risk of cancer and other chronic diseases. Cancer Epidemiol Biomarkers Prev; 23(6); 1–12. ©2014 AACR .

Children's exposure to secondhand and thirdhand smoke carcinogens and toxicants in homes of hookah smokers.

Abstract: Introduction: We examined homes of hookah-only smokers and nonsmokers for levels of indoor air nicotine (a marker of secondhand smoke) and indoor surface nicotine (a marker of thirdhand smoke), child uptake of nicotine, the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and the toxicant acrolein by analyzing their corresponding metabolites cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL) and 3-hydroxypropylmercapturic acid.

A Comparison of Nicotine Biomarkers and Smoking Patterns in Daily and Nondaily Smokers

Abstract: Background: Nondaily or intermittent smokers (ITS) are increasingly common, but how much nicotine, if any, ITS take in and how quickly they metabolize it has not yet been studied. Methods: We compared carbon monoxide (CO), urinary cotinine, and nicotine metabolism [nicotine metabolite ratio (NMR): 3-hydroxycotinine:cotinine] in 224 ITS and 222 daily smokers (DS). Effects of gender and ethnicity were examined. Results: DS had higher cotinine concentrations than ITS (1,396 ± 69 vs. 478 ± 44 ng/mL), attributable to higher cigarettes per day (CPD). In both groups, cotinine rose more slowly as CPD increased. There were no differences in cotinine between White (WH) and African American (AA) DS; among ITS, AA cotinine was over twice that of WH. Among DS, CO was significantly higher among WH than AA smokers, but significantly lower among WH ITS than AA ITS. Although AA ITS smoked more than WH ITS (CPD: 4.13 ± 0.55 vs. 3.31 ± 0.41), this did not account for the observed cotinine nor CO differences. There were no differences in NMR by group or race, nor any gender effects. Conclusions: At comparable CPD, DS' and ITS' intake of nicotine per cigarette was similar, as were their rates of nicotine metabolism. Among ITS, AA smokers smoke more and take in more nicotine per cigarette than WH ITS, consistent with the view of ITS as a heterogeneous group. Impact: Differences in nicotine intake per cigarette and metabolism likely cannot account for differences in DS and ITS smoking. Future studies should explore ethnic differences in ITS smoking. Cancer Epidemiol Biomarkers Prev; 23(7); 1264–72. ©2014 AACR .

Prevalence and impact of active and passive cigarette smoking in acute respiratory distress syndrome.

Abstract: Objective Cigarette smoke exposure has recently been found to be associated with increased susceptibility to trauma- and transfusion-associated acute respiratory distress syndrome (ARDS). We sought to determine 1) the prevalence of cigarette smoke exposure in a diverse multi-center sample of ARDS patients, and 2) whether cigarette smoke exposure is associated with severity of lung injury and mortality in ARDS.

Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response in African-American smokers.

Abstract: Associations between CHRNA5-A3-B4 variants and smoking behaviors exist; however, the association with smoking abstinence is less understood, particularly that among African Americans. In 1,295 African Americans enrolled in two clinical trials, we investigated the association between CHRNA5-A3-B4 and smoking abstinence. The rs2056527(A) allele was associated with lower abstinence with active pharmacotherapy (during treatment: odds ratio (OR) = 0.42, P < 0.001; end of treatment (EOT): OR = 0.55, P = 0.004), or with nicotine gum alone (during treatment: OR = 0.31, P < 0.001; EOT: OR = 0.51, P = 0.02), but not significantly with bupropion, although similar directions and magnitudes were observed (during treatment: OR = 0.54, P = 0.05; EOT: OR = 0.59, P = 0.08). In addition, the rs588765(T) allele was associated with abstinence with gum during treatment (OR = 2.31, P < 0.01). The SNP rs16969968 occurred at a low frequency and was not consistently associated with abstinence. CHRNA5-A3-B4 variants were not associated with tobacco consumption, and adjustments for smoking behaviors did not alter the associations with smoking abstinence. Together, our data suggest that among African Americans, CHRNA5-A3-B4 variants are not associated with baseline smoking but can influence smoking abstinence during active pharmacotherapy.

Intake of Toxic and Carcinogenic Volatile Organic Compounds from Secondhand Smoke in Motor Vehicles

Abstract: Background: Volatile organic compounds (VOC) from tobacco smoke are associated with cancer, cardiovascular, and respiratory diseases. The objective of this study was to characterize the exposure of nonsmokers to VOCs from secondhand smoke (SHS) in vehicles using mercapturic acid metabolites. Methods: Fourteen nonsmokers were individually exposed in the backseat to one hour of SHS from a smoker seated in the driver's seat who smoked three cigarettes at 20-minute intervals in a stationary car with windows opened by 10 cm. Baseline and 0- to 8-hour postexposure mercapturic acid metabolites of nine VOCs were measured in urine. Air-to-urine VOC ratios were estimated on the basis of respirable particulate matter (PM2.5) or air nicotine concentration, and lifetime excess risk (LER) of cancer death from exposure to acrylonitrile, benzene, and 1,3-butadiene was estimated for adults. Results: The greatest increase in 0- to 8-hour postexposure concentrations of mercapturic acids from baseline was MHBMA-3 (parent, 1,3-butadiene; 2.1-fold), then CNEMA (acrylonitrile; 1.7-fold), PMA (benzene; 1.6-fold), MMA (methylating agents; 1.6-fold), and HEMA (ethylene oxide; 1.3-fold). The LER of cancer death from exposure to acrylonitrile, benzene, and 1,3-butadiene in SHS for 5 hours a week ranged from 15.5 × 10−6 to 28.1 × 10−6 for adults, using air nicotine and PM2.5 to predict air VOC exposure, respectively. Conclusion: Nonsmokers have significant intake of multiple VOCs from breathing SHS in cars, corresponding to health risks that exceed the acceptable level. Impact: Smoking in cars may be associated with increased risks of cancer, respiratory, and cardiovascular diseases among nonsmokers. Cancer Epidemiol Biomarkers Prev; 23(12); 2774–82. ©2014 AACR .

Novel CYP2A6 variants identified in African Americans are associated with slow nicotine metabolism in vitro and in vivo

Abstract: Objective Nicotine, the main addictive ingredient in tobacco, is metabolically inactivated to cotinine primarily by the hepatic enzyme CYP2A6. Substantial genetic variation in the CYP2A6 gene results in large variation in the rates of nicotine metabolism which in turn alters smoking behaviours (e.g., amount of cigarettes smoked, risk for dependence and success in smoking cessation). The goal of this study was to identify and characterize novel variants in CYP2A6.

Biomarkers of secondhand smoke exposure in automobiles

Abstract: Objectives The objectives of this study were: (1) to characterise the exposure of non-smokers exposed to secondhand smoke (SHS) in a vehicle using biomarkers, (2) to describe the time course of the biomarkers over 24 h, and (3) to examine the relationship between tobacco biomarkers and airborne concentrations of SHS markers. Methods Eight non-smokers were individually exposed to SHS in cars with fully open front windows and closed back windows over an hour from a smoker who smoked three cigarettes at 20 min intervals. The non-smokers sat in the back seat on the passenger side, while the smoker sat in the driver9s seat. Plasma cotinine and urine cotinine, 3-hydroxycotinine (3HC) and 4-(methylnitrosoamino)-(3-pyridyl)-1-butanol (NNAL) were compared in samples taken at baseline (BL) and several time-points after exposure. Nicotine, particulate matter (PM 2.5 ) and carbon monoxide (CO) were measured inside and outside the vehicle and ventilation rates in the cars were measured. Results Average plasma cotinine and the molar sum of urine cotinine and 3HC (COT+3HC) increased four-fold, urine cotinine increased six-fold and urine NNAL increased ∼27 times compared to BL biomarker levels. Plasma cotinine, urine COT+3HC and NNAL peaked at 4–8 h post-exposure while urine cotinine peaked within 4 h. Plasma cotinine was significantly correlated to PM 2.5 (Spearman correlation r s =0.94) and CO (r s =0.76) but not to air nicotine. The correlations between urine biomarkers, cotinine, COT+3HC and NNAL, and air nicotine, PM 2.5 and CO were moderate but non-significant (r s range = 0.31–0.60). Conclusions Brief SHS exposure in cars resulted in substantial increases in levels of tobacco biomarkers in non-smokers. For optimal characterisation of SHS exposure, tobacco biomarkers should be measured within 4–8 h post-exposure. Additional studies are needed to better describe the relationship between tobacco biomarkers and environmental markers of SHS.

Multiple risk-behavior profiles of smokers with serious mental illness and motivation for change.

Abstract: Practices to prevent disease and promote health are key to addressing the current U.S. health-care crisis (Fani Marvasti & Stafford, 2012). Largely driven by hospital costs and chronic care conditions, the Agency for Health Care Research and Quality estimates that 20% of the U.S. population accounts for 80% of total health-care expenditures (Conwell & Cohen, 2005; Stanton, 2006), and mental health disorders rank among the top five most costly conditions in terms of total health-care spending (Stanton, 2006). Individuals with serious mental illness (SMI) have high levels of acute health-care utilization and, relative to age- and gender-matched controls, are at greater risk for heart disease, cancer, and lung disease (Miller, Paschall, & Svendsen, 2006; Sokal et al., 2004). Many of these chronic illnesses are largely preventable through health-behavior change. In particular, the elevated prevalence of tobacco use in this vulnerable population is increasingly recognized as a major health concern (J. J. Prochaska, 2011; Schroeder & Morris, 2010), and recent trials have demonstrated success with treating tobacco dependence in smokers with SMI while supporting their mental health recovery (Hall et al., 2006; J. J. Prochaska et al., 2008; McFall et al., 2010; Tsoi, Porwal, & Webster, 2010). Risk behaviors tend to co-occur, however, and most smokers (90%) in the general population carry additional cardiovascular and cancer-related risk behaviors, including poor diet, low activity levels, high stress, and heavy alcohol and illicit drug use (Fine, Philogene, Gramling, Coups, & Sinha, 2004; Pronk et al., 2004; Kendzor et al., 2008). The negative health effects can be additive or synergistic, as seen with the neurotoxic and carcinogenic effects of combined chronic tobacco and heavy alcohol use (Xu et al., 2007; Durazzo, Gazdzinski, Banys, & Meyerhoff, 2004). For some risk behaviors, such as smoking, even low levels are dangerous (Schane, Ling, & Glantz, 2010). Smokers struggling with multiple risk behaviors have greater levels of nicotine dependence, indicating the need for more intensive tobacco-treatment interventions (Sherwood, Hennrikus, Jeffery, Lando, & Murray, 2001). Excess risks lead to excess health-care costs and lost productivity (Goetzel et al., 1998). In psychiatry, risk behaviors also are treatment relevant—cigarette smoking induces the metabolism and decreases blood levels of some psychotropics (Kroon, 2007); antipsychotics, mood stabilizers, and antidepressants can impact sleep quality and contribute to high cardiometabolic risk, including obesity, hypertension, and hyperglycemia (Amiel, Mangurian, Ganguli, & Newcomer, 2008; De Hert et al., 2011; Dent et al., 2012; Newcomer, 2005). Investigating relationships among health-risk behaviors is important for identifying the populations at highest risk and prioritizing interventions. The research conducted to date provides an initial indication of behavioral clustering and understanding of subgroups at elevated risk. Among U.S. adults, predictors of engagement in multiple risk behaviors include lower educational level, higher mental distress, ethnic minority status, and being uninsured (Fine et al., 2004; Pronk et al., 2004; Kendzor et al., 2008; de Vries et al., 2008; Berrigan, Dodd, Troiano, Krebs-Smith, & Barbash, 2003). Though research in this area is limited, with poor access to treatment and prevention services and exposure to stress and discrimination (Lawrence & Kisely, 2010), we anticipated individuals with SMI would engage in multiple risk behaviors. There is growing evidence to suggest that interventions that target two or more health behaviors can effectively generate behavior change (J. O. Prochaska, 2008). Recent population-based multiple health behavior change studies have demonstrated population-wide improvements across a range of behaviors, including smoking, high-fat diet, high-risk sun exposure, physical activity, and stress (J. O. Prochaska et al., 2008). Studies aimed at secondary prevention (e.g., among individuals diagnosed with cardiovascular disease or diabetes), have been particularly effective in successfully promoting multiple behavior change (Emmons et al., 2005; Ketola, Sipila, & Makela, 2002; Norris, Engelgau, & Venkat Narayan, 2001; Ornish et al., 1998). Further, interventions that effectively impact change in one health behavior can promote changes in additional untreated health behaviors, providing evidence for paired motivational processes for behavior change (Johnson et al., 2008). The existing studies, however, have largely focused on the general population and have not included clinical samples with SMI; they have been limited in the number of behaviors assessed; and they have only examined risk level and not motivation to change. Although extant single behavior interventions in SMI samples have been successful in reducing tobacco use (Hall et al., 2006; McFall et al., 2010; Tsoi et al., 2010), decreasing weight and body fat (Faulkner, Cohn, & Remington, 2007; Hassapidou et al., 2011), and promoting physical activity (Vancampfort et al., 2010), we are unaware of research examining the extent to which individuals with SMI are ready and able to address multiple risk behaviors for change. The transtheoretical model (TTM) has been applied to understand the process of multiple risk behavior change. TTM conceptualizes behavior change as a progression through a series of stages: precontemplation (the individual has no intention of changing the risk behavior in the next 6 months); contemplation (the individual intends to change in the next 6 months but not in the next 30 days); preparation (individual intends to change in the next 30 days); action, (individual meets the behavioral goal for ≤6 months); and maintenance (individual meets the behavioral goal for ≥6 months; J. O. Prochaska & DiClemente, 1983). TTM may be especially well-suited for efforts addressing multiple risk behaviors because it assumes individuals may not be ready to take action immediately and it tailors intervention strategies accordingly. Further, interventions built upon the TTM have demonstrated success with smokers with mental illness (Hall et al., 2006). The current exploratory study examined the frequency of engagement in multibehavioral risks, motivation to change behavior, and correlates of multiple risks among adult smokers with SMI. Ten risk behaviors in addition to tobacco use were studied, with risk status defined consistent with Healthy people 2020 goals for the nation (U.S. Department of Health & Human Services, 2010). We anticipated that smokers with SMI would carry additional risk behaviors; however, we also anticipated heterogeneity in patterns of engagement. An understanding of the frequencies of risks and patterns of clustering can help with prioritizing intervention targets and potentially packaging behavior-change programs. To inform health-promotion interventions for adults with SMI, we used latent class analysis (LCA) to identify typologies based on individuals' risk statuses on the 10 behaviors assessed and further examined the identified group probabilities in relation to demographic, tobacco, other substance use, and psychiatric characteristics.

Cardiogenic shock after use of fluoroamphetamine confirmed with serum and urine levels

Abstract: Context. 4-Fluoroamphetamine (4-FA) is a para-substituted phenethylamine-type synthetic stimulant that has in recent years gained popularity through internet blogs and market share according to confiscated drug data. No serious toxicity has previously been reported. We report a case of a young man who developed severe toxicity and cardiogenic shock after using 4-FA, with laboratory confirmation. Case details. An 18-year-old man presented to the emergency department with vomiting, shortness of breath, chest tightness, and altered mental status about 5 h after using a new and unfamiliar street drug. Two days prior, he had received naltrexone intramuscular injection as part of an opioid addiction treatment program and was taking fluoxetine and trazodone. Five hours after presentation, he developed cardiogenic shock requiring intraaortic balloon pump, inotropic and ventilatory support. An echocardiogram showed left ventricular (LV) hypokinesia, sparing the apex and ejection fraction (EF) = 10%. Compre...

Particulate mass and polycyclic aromatic hydrocarbons exposure from secondhand smoke in the back seat of a vehicle

Abstract: Context Exposure to secondhand smoke (SHS) has been reduced in the USA by banning smoking in public places. These restrictions have not had the same effect on children9s exposure to SHS as adults suggesting that children are exposed to SHS in locations not covered by bans, such as private homes and cars. Objectives Assess exposure to SHS in the backseat of a stationary vehicle where a child would sit, quantify exposures to fine particulates (PM2.5), polycyclic aromatic hydrocarbons (PAH), carbon monoxide (CO) and nicotine. Estimate the impact on a child9s mean daily exposure to PM2.5. Methods SHS exposures in stationary vehicles with two different window configurations were monitored. A volunteer smoked three cigarettes in a one-hour period for twenty-two experiments. PM2.5, CO, nicotine and PAH where measured in the backseat of the vehicle. 16 PAH compounds were measured for in gas and particle phases as well as real-time particle phase concentrations. Results The mean PAH concentration, 1325.1 ng/m 3 , was larger than concentrations measured in bars and restaurants were smoking is banned in many countries. We estimate that a child spending only ten minutes in the car with a smoker at the mean PM2.5 concentration measured in the first window configuration −1697 mg/m 3 – will cause a 30% increase to the daily mean PM2.5 personal average of a child. Conclusions Estimates made using the measured data and previously reported PM2.5 daily mean concentrations for children in California showing that even short exposure periods are capable of creating large exposure to smoke.

Organic cation transporter variation and response to smoking cessation therapies

Abstract: Author(s): Bergen, Andrew W; Javitz, Harold S; Krasnow, Ruth; Michel, Martha; Nishita, Denise; Conti, David V; Edlund, Christopher K; Kwok, Pui-Yan; McClure, Jennifer B; Kim, Richard B; Hall, Sharon M; Tyndale, Rachel F; Baker, Timothy B; Benowitz, Neal L; Swan, Gary E | Abstract: IntroductionWe evaluated chr6q25.3 organic cation transporter gene (SLC22A1, SLC22A2, SLC22A3) variation and response to smoking cessation therapies. The corresponding proteins are low-affinity transporters of choline, acetylcholine and monoamines, and smoking cessation pharmacotherapies expressed in multiple tissues.MethodsWe selected 7 common polymorphisms for mega-regression analysis. We assessed additive model association of polymorphisms with 7-day point prevalence abstinence overall and by assigned pharmacotherapy at end of treatment and at 6 months among European-ancestry participants of 7 randomized controlled trials adjusted for demographic, population genetic, and trial covariates.ResultsInitial results were obtained in 6 trials with 1,839 participants. Nominally statistically significant associations of 2 SLC22A2 polymorphisms were observed: (1) with rs316019 at 6 months, overall ([c.808TgG; p.Ser270Ala], OR = 1.306, 95% CI = 1.034-1.649, p = .025), and among those randomized to nicotine replacement therapy (NRT) (OR = 1.784, 95% CI = 1.072-2.970, p = .026); and (2) with rs316006 (c.1502-529AgT) among those randomized to varenicline (OR = 1.420, 95% CI = 1.038-1.944, p = .028, OR = 1.362, 95% CI = 1.001-1.853, p = .04) at end of treatment and 6 months. Individuals randomized to NRT from a seventh trial were genotyped for rs316019; rs316019 was associated with a nominally statistically significant effect on abstinence overall at 6 months among 2,233 participants (OR = 1.249, 95% CI = 1.007-1.550, p = .043).ConclusionsThe functional OCT2 Ser270Ala polymorphism is nominally statistically significantly associated with abstinence among European-ancestry treatment-seeking smokers after adjustments for pharmacotherapy, demographics, population genetics, and without adjustment for multiple testing of 7 SNPs. Replication of these preliminary findings in additional randomized controlled trials of smoking cessation therapies and from multiple continental populations would describe another pharmacogenetic role for SLC22A2/OCT2.

Gene Variants in CYP2C19 Are Associated with Altered In Vivo Bupropion Pharmacokinetics but Not Bupropion-Assisted Smoking Cessation Outcomes

Abstract: Bupropion is used clinically to treat depression and to promote smoking cessation. It is metabolized by CYP2B6 to its active metabolite hydroxybupropion, yet alterations in CYP2B6 activity have little impact on bupropion plasma levels. Furthermore, less than 10% of a bupropion dose is excreted as urinary bupropion and its characterized metabolites hydroxybupropion, threohydrobupropion, and erythrohydrobupropion, suggesting that alternative metabolic pathways may exist. In vitro data suggested CYP2C19 could metabolize bupropion. The current study investigated the impact of functional CYP2C19 genetic variants on bupropion pharmacokinetics and treatment outcomes. In 42 healthy volunteers, CYP2C19*2 (a reduced activity allele) was associated with higher bupropion area under the plasma concentration-time curve (AUC), but similar hydroxybupropion AUC. The mean bupropion AUC was 771 versus 670 hours⋅ng/ml in individuals with and without CYP2C19*2, respectively (P = 0.017). CYP2C19*2 was also associated with higher threohydrobupropion and erythrohydrobupropion AUC (P < 0.005). Adjusting for CYP2B6 genotype did not alter these associations, and CYP2C19 variants did not alter the utility of the hydroxybupropion/bupropion ratio as a measure of CYP2B6 activity. Finally, in a clinical trial of 540 smokers, CYP2C19 genotype was not associated with smoking cessation outcomes, supporting the hypothesis that bupropion response is mediated by hydroxybupropion, which is not altered by CYP2C19. In conclusion, our study reports the first in vivo evidence that reduced CYP2C19 activity significantly increases the steady-state exposure to bupropion and its reductive metabolites threohydrobupropion and erythrohydrobupropion. These pharmacokinetic changes were not associated with differences in bupropion's ability to promote smoking cessation in smokers, but may influence the side effects and toxicity associated with bupropion.

Clinical significance of early smoking withdrawal effects and their relationships with nicotine metabolism: preliminary results from a pilot study.

Abstract: Introduction: Although the early time course of smoking withdrawal effects has been characterized, the clinical significance of early withdrawal symptoms and their predictors are unknown. This study evaluated the relationships of early smoking withdrawal effects with quit attempt outcomes and the rate of nicotine metabolism. Methods: Eleven treatment-seeking smokers abstained from smoking for 4 hr in the laboratory before a quit attempt. Withdrawal measures included heart rate, sustained attention, and self-report. Following baseline assessment, withdrawal measures were administered every 30 min. At the conclusion of the 4-hr early withdrawal session, participants received a brief smoking cessation intervention and then returned 1 week and 12 weeks later for outcome assessments that included biochemically confirmed smoking abstinence, cigarettes smoked in the past 24 hr, and self-reported withdrawal symptoms. The rate of nicotine metabolism was estimated at intake with the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine) measured in saliva. Results: Greater self-reported negative affect and concentration difficulty during early withdrawal, most notably anxiety, were related with poorer quit attempt outcomes. There was some indication that although a faster increase in craving and greater hunger during early withdrawal were associated with more favorable outcomes, a greater decrease in heart rate during this time was associated with poorer outcomes. Faster nicotine metabolism was related to a faster increase in anxiety but a slower increase in craving during early withdrawal. Conclusions: These findings lend support to the clinical significance of early smoking withdrawal effects. The rate of nicotine metabolism may be a useful predictor of early withdrawal symptoms. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.

Cotinine and tobacco-specific carcinogen exposure among nondaily smokers in a multiethnic sample

Abstract: Author(s): Khariwala, Samir S; Scheuermann, Taneisha S; Berg, Carla J; Hayes, Rashelle B; Nollen, Nicole L; Thomas, Janet L; Guo, Hongfei; Ahluwalia, Jasjit S; Benowitz, Neal L | Abstract: BackgroundNondaily smoking has increased among current U.S. smokers during the past decade and is practiced by a significant percentage of smokers. Although research in nondaily smoking has grown, little is known about levels of exposure to tobacco toxicants among nondaily smokers and their variation across ethnic groups.MethodsWe examined urinary levels of cotinine and a tobacco-specific nitrosamine (NNAL) in community participants. Associations between the biomarker data and smoking characteristics were evaluated with Spearman's correlation analysis.ResultsParticipants included 28 Blacks, 4 Latinos, and 25 Whites who smoked at least 1 cigarette on 4-24 days in the past 30 days. Participants averaged 3.3 (SD = 2.1) cigarettes per day (cpd) on days smoked, they smoked an average of 13.0 (SD = 5.4) days in the past month, and they smoked nondaily for 10.5 (SD = 10.5) years. Median levels of creatinine-normalized cotinine and NNAL were 490.9 ng/mg and 140.7 pg/mg, respectively. NNAL and cotinine were highly correlated (r = .84); NNAL and cotinine were modestly correlated with cpd (r = .39 and r = .34; all p values l.05). The number of days smoked per month was not associated with any biomarker levels.ConclusionsOur findings demonstrate that nondaily smokers are, on average, exposed to significant levels of nicotine and carcinogenic nitrosamines, with exposures of 40%-50% of those seen in daily smokers. This level of exposure suggests a significant health risk. Nicotine and carcinogen exposure is most closely related to number of cigarettes smoked per day but not to number of days per month of smoking.

Variation in P450 oxidoreductase (POR) A503V and flavin-containing monooxygenase (FMO)-3 E158K is associated with minor alterations in nicotine metabolism, but does not alter cigarette consumption.

Abstract: The rates of nicotine metabolism differ widely, even after controlling for genetic variation in the major nicotine-metabolizing enzyme, CYP2A6. Genetic variants in an additional nicotine-metabolizing enzyme, flavin-containing monooxygenase (FMO)-3, and an obligate microsomal CYP-supportive enzyme, cytochrome P450 oxidoreductase (POR), were investigated. We examined the impact of FMO3 E158K and POR A503V before and after stratifying by CYP2A6 metabolism group. In 130 nonsmokers of African descent who received 4 mg oral nicotine, FMO3 158K trended toward slower nicotine metabolism in reduced CYP2A6 metabolizers (P=0.07) only, whereas POR 503V was associated with faster CYP2A6 activity (nicotine metabolite ratio) in normal (P=0.03), but not reduced, CYP2A6 metabolizers. Neither FMO3 158K nor POR 503V significantly altered the nicotine metabolic ratio (N=659), cigarette consumption (N=667), or urine total nicotine equivalents (N=418) in smokers of African descent. Thus, FMO3 E158K and POR A503V are minor sources of nicotine metabolism variation, insufficient to appreciably alter smoking.

it is important that interpretation of the evidence and communication with policy makers and the public is not distorted by a priori judgements.

Abstract: The reason is obvious: the association could easily be due to a preexisting disposition on the part of the people concerned. To date, studies that have been claimed as addressing the gateway issue in relation to e-cigarettes have not in fact done so. 1 Moreover, warnings about a rapid rise in e-cigarette use among the young have been based on the proportion of young people who report ever having tried an e-cigarette, not the proportion of current users. 15 In England, the proportion of current users in people who have not smoked regularly remains extremely small at 0.2%. 8 THe NeeD fOR ObjeCTIvITy This brings us back to the question as to why some individuals and bodies involved in public health are so opposed to e-cigarettes. It may be a concern over how things might turn out in the future given commercial incentives, puritanical ethics, distaste for any industry profiting from a psychoactive drug, inappropriate application of a medical rather than a public health model, or even just a gut feeling that e-cigarettes are bad. Whatever the reasons, it is important that interpretation of the evidence and communication with policy makers and the public is not distorted by a priori judgements. 16