[Show abstract][Hide abstract] ABSTRACT: Smoking remains the leading cause of preventable morbidity and mortality. Our review highlights research from 2013 to 2015 on the treatment of cigarette smoking, with a focus on heart patients and cardiovascular outcomes.
Seeking to maximize the reach and effectiveness of existing cessation medications, current tobacco control research has demonstrated the safety and efficacy of combination treatment, extended use, reduce-to-quit strategies, and personalized approaches to treatment matching. Further, cytisine has gained interest as a lower-cost strategy for addressing the global tobacco epidemic. On the harm reduction front, snus and electronic nicotine delivery systems are being widely distributed and promoted with major gaps in knowledge of the safety of long-term and dual use. Quitlines, comparable in outcome to in-person treatment, make cessation counseling available on a national scale, though use rates remain relatively low. Employee reward programs are gaining attention given the high costs of tobacco use to employers; sustaining quit rates postpayment, however, has proven challenging.
Evidence-based cessation treatments exist. Broader dissemination, adoption, and implementation are key to addressing the tobacco epidemic. The cardiology team has a professional obligation to advance tobacco control efforts and can play an important role in achieving a smoke-free future.
Current opinion in cardiology 07/2015; DOI:10.1097/HCO.0000000000000204 · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.
PLoS ONE 07/2015; 10(7):e0126113. DOI:10.1371/journal.pone.0126113 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CHRNA5-A3-B4 variants, rs16969968, rs588765 and rs578776, are consistently associated with tobacco consumption among smokers, but the association with smoking cessation is less consistent. Among the studies that reported significant associations with cessation, the effects were observed in smokers treated with placebo treatment in some studies and conversely in those receiving active pharmacological therapy (bupropion and nicotine replacement therapies) in others. Thus, it remains unclear whether CHRNA5-A3-B4 is a useful marker for optimizing smoking cessation. Using data from 654 Caucasian smokers treated with placebo, nicotine patch or varenicline, we investigated whether CHRNA5-A3-B4 variants were associated with smoking cessation outcomes, and whether there were significant genotype-by-treatment or haplotype-by-treatment interactions. We observed no significant associations between CHRNA5-A3-B4 variants and smoking cessation, despite replicating previous associations with baseline tobacco consumption. At end of treatment the effect size on smoking cessation in the placebo, patch and varenicline groups for rs16969968 [GG vs. GA+AA] was OR = 0.66 (P = 0.23), OR = 1.01 (P = 0.99), and OR = 1.30 (P = 0.36) respectively, of rs588765 [CC vs. CT+TT] was OR = 0.96 (P = 0.90), OR = 0.84 (P = 0.58), and OR = 0.74 (P = 0.29) respectively, and for rs578776 [GG vs. GA+AA] on smoking cessation was OR = 1.02 (P = 0.95), OR = 0.75 (P = 0.35), and OR = 1.20 (P = 0.51) respectively. Furthermore, we observed no associations with cessation using the CHRNA5-A3-B4 haplotype (constructed using rs16969968 and rs588765), nor did we observe any significant genotype-by-treatment interactions, with or without adjusting for the rate of nicotine metabolism (all P>0.05). We also observed no significant genetic associations with 6 month or 12 month smoking abstinence. In conclusion, we found no association between CHRNA5-A3-B4 variants and smoking cessation rates in this clinical trial; however, as expected, significant associations with baseline tobacco consumption were replicated. Our data suggest that CHRNA5-A3-B4 gene variants do not exhibit a robust association with smoking cessation and are unlikely to be useful for clinically optimizing smoking cessation pharmacotherapy for Caucasian smokers.
PLoS ONE 05/2015; 10(5):e0128109. DOI:10.1371/journal.pone.0128109 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association between cigarette smoke exposure and the acute respiratory distress syndrome in patients with the most common acute respiratory distress syndrome risk factors of sepsis, pneumonia, and aspiration has not been well studied. The goal of this study was to test the association between biomarker-confirmed cigarette smoking and acute respiratory distress syndrome in a diverse cohort.
Tertiary care center.
Four hundred twenty-six critically ill patients with acute respiratory distress syndrome risk factors (excluding trauma and transfusion) INTERVENTIONS:: None.
We obtained smoking histories and measured urine 4-(methylnitrosamino)-1-(3-pyridyl)-1--butanol (a biomarker of cigarette smoke exposure) on urine samples obtained at the time of study enrollment. The association between cigarette smoke exposure and acute respiratory distress syndrome differed based on acute respiratory distress syndrome risk factor (p < 0.02 for interaction). In patients with nonpulmonary sepsis as the primary acute respiratory distress syndrome risk factor (n = 212), 39% of those with acute respiratory distress syndrome were current smokers by history compared with 22% of those without acute respiratory distress syndrome (odds ratio, 2.28; 95% CI, 1.24-4.19; p = 0.008). Likewise, cigarette smoke exposure as measured by urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was significantly associated with acute respiratory distress syndrome in this group. The increased risk of acute respiratory distress syndrome in nonpulmonary sepsis was restricted to patients with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels consistent with active smoking and was robust to adjustment for other acute respiratory distress syndrome predictors. Cigarette smoke exposure as measured by history or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was not associated with acute respiratory distress syndrome in patients with other risk factors (e.g., pneumonia and aspiration).
Cigarette smoking measured both by history and biomarker is associated with an increased risk of acute respiratory distress syndrome in patients with nonpulmonary sepsis. This finding has important implications for tobacco product regulation and for understanding the pathogenesis of acute respiratory distress syndrome.
Critical care medicine 05/2015; DOI:10.1097/CCM.0000000000001089 · 6.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Cardiovascular disease is the leading cause of death, and smoking cessation is a key component of secondary cardiovascular disease risk prevention efforts.
Objectives: To examine the relationships between demographic, clinical and health factors, history and patterns of smoking, nicotine dependence, withdrawal symptoms, and willingness (i.e., readiness) to
quit smoking after hospital discharge among adult Jordanian men who were cigarette smokers and were admitted to the hospital with a cardiovascular disease diagnosis.
Methods: This cross-sectional study recruited 118 adult men smokers from three hospitals in Jordan during 2011. Data were collected using structured interviews and medical record abstraction.
Results: The mean age of smokers was 50.7 (±6.7) years and they smoked at least one cigarette per day for an average of 28.8 years (±7.0). Currently they smoke an average of 28.9 (±8.0) cigarettes a day. About a quarter (24.6%, n = 29) had previously made a quit attempt that lasted at least 24 hours. Smokers were considered highly nicotine dependent if they had scores of > 6 (out of 10) on the Fagerström Test for Nicotine Dependence scale. The average nicotine dependence score was significantly higher in the high versus low nicotine dependence group (6.9 vs. 4.1). The number of cigarettes smoked daily was significantly higher in
the high compared to the low nicotine dependence group (30.7 cigarettes vs. 23.4). Logistic regression showed smokers who had someone available to encourage quitting smoking “at least sometimes” were more likely to quit smoking after hospital discharge, and smokers who had sufficient personal income to support self were less likely to quit smoking after hospital discharge, while controlling for all other variables.
Conclusions: The very high nicotine dependence of these men indicates that there is an urgent need for education, counseling and behavioral interventions, and pharmacological therapies, to achieve successful smoking cessation. Study findings lay the basis for development of appropriate smoking cessation programs in Jordan.
[Show abstract][Hide abstract] ABSTRACT: Smokeless tobacco products, such as moist snuff or chewing tobacco, contain many of the same carcinogens as tobacco smoke; however the impact on children of indirect exposure to tobacco constituents via parental smokeless tobacco use is unknown. As part of the California Childhood Leukemia Study, dust samples were collected from 6 homes occupied by smokeless tobacco users, 6 homes occupied by active smokers, and 20 tobacco-free homes. To assess children's potential for exposure to tobacco constituents, vacuum-dust concentrations of five tobacco-specific nitrosamines, including N'-nitrosonornicotine [NNN] and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK], as well as six tobacco alkaloids, including nicotine and myosmine were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We used generalized estimating equations derived from a multivariable marginal model to compare levels of tobacco constituents between groups, after adjusting for a history of parental smoking, income, home construction date, and mother's age and race/ethnicity. The ratio of myosmine:nicotine was used as a novel indicator of the source of tobacco contamination, distinguishing between smokeless tobacco products and tobacco smoke. Median dust concentrations of NNN and NNK were significantly greater in homes with smokeless tobacco users compared to tobacco-free homes. In multivariable models, concentrations of NNN and NNK were 4.8-fold and 6.9-fold higher in homes with smokeless tobacco users compared to tobacco-free homes. Median myosmine:nicotine ratios were lower in homes with smokeless tobacco users (1.8%) compared to homes of active smokers (7.7%), confirming that cigarette smoke was not the predominant source of tobacco constituents in homes with smokeless tobacco users. Children living with smokeless tobacco users may be exposed to carcinogenic tobacco-specific nitrosamines via contact with contaminated dust and household surfaces.
Chemical Research in Toxicology 03/2015; 28(5). DOI:10.1021/acs.chemrestox.5b00040 · 4.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A number of candidate gene and genome-wide association studies have identified significant associations between single nucleotide polymorphisms, particularly in FTO and MC4R, and body weight. However, the association between copy number variation and body weight is less understood. Anabolic androgenic steroids, such as testosterone, can regulate body weight. In humans, UDP-glucuronosyltransferase 2B17 (UGT2B17) metabolizes testosterone to a metabolite, which is readily excreted in urine. We investigate the association between genetic and phenotypic variation in UGT2B17 and body weight.
UGT2B17 deletion was genotyped and in-vivo UGT2B17 enzymatic activity (as measured by the 3-hydroxycotinine glucuronide to free 3-hydroxycotinine ratio) was measured in 400 Alaska Native individuals and 540 African Americans.
In Alaska Native people, UGT2B17 deletion was strongly associated with lower BMI in male individuals (P<0.001), but not in female individuals, consistent with testosterone being a male dominant steroid. The sex-specific association between UGT2B17 deletion and lower BMI was also observed in African Americans (P=0.01 in male individuals). In both populations, UGT2B17 deletion was significantly associated with lower measured in-vivo UGT2B17 activity. In male individuals, lower in-vivo UGT2B17 activity was associated with lower BMI, as observed in the sex-specific genotypic association.
These data suggest that UGT2B17 deletion leads to reduced UGT2B17 activity, and lower BMI in male individuals. This is consistent with the hypothesis that reduced UGT2B17-mediated testosterone excretion results in higher testosterone levels. Future studies could confirm this hypothesis by directly measuring serum testosterone levels.
Pharmacogenetics and Genomics 03/2015; 25(5). DOI:10.1097/FPC.0000000000000135 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent years, new products have entered the marketplace that complicate decisions about tobacco control policies and prevention in the workplace. These products, called electronic cigarettes (e-cigarettes) or electronic nicotine delivery systems, most often deliver nicotine as an aerosol for inhalation, without combustion of tobacco. This new mode of nicotine delivery raises several questions about the safety of the product for the user, the effects of secondhand exposure, how the public use of these products should be handled within tobacco-free and smoke-free air policies, and how their use affects tobacco cessation programs, wellness incentives, and other initiatives to prevent and control tobacco use. In this article, we provide a background on e-cigarettes and then outline key policy recommendations for employers on how the use of these new devices should be managed within worksite tobacco prevention programs and control policies.
Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 03/2015; 57(3):334-43. DOI:10.1097/JOM.0000000000000420 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Differences in carcinogen exposure from different cigarette products could contribute to differences in smoking-associated cancer incidence among Chinese compared with US smokers.
Urine concentrations of metabolites of nicotine, the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and polycyclic aromatic hydrocarbon metabolites (PAHs) were compared in 238 Chinese and 203 US daily smokers.
Comparing Chinese versus US smokers, daily nicotine intake and nicotine intake per cigarette smoked were found to be similar. When normalised for cigarettes per day, urine NNAL excretion was fourfold higher in US smokers, while the excretion of urine metabolites of the PAHs fluorene, phenanthrene and pyrene metabolites was 50% to fourfold higher in Chinese smokers (all, p<0.0001). Similar results were seen when NNAL and PAHs excretion was normalised for daily nicotine intake.
Patterns of carcinogen exposure differ, with lower exposure to TSNA and higher exposure to PAHs in Chinese compared with US smokers. These results most likely reflect country differences in cigarette tobacco blends and manufacturing processes, as well as different environmental exposures.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Tobacco Control 12/2014; DOI:10.1136/tobaccocontrol-2014-051945 · 5.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] 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%. Comprehensive toxicology serum testing revealed FA, naproxen, trazodone, and cotinine. The 4-FA urine level was 64,000 ng/ml and serum level was 118 ng/ml. With slow recovery, the patient was discharged after 2 weeks of hospitalization. Discussion. Although no previously reported 4-FA clinical poisoning cases have been published for comparison, by examining 4-FA pharmacology compared with other stimulant drugs, and given this patient's presentation and echocardiogram suggestive of reverse takotsubo cardiomyopathy we suspect the toxic mechanism was an acute cardiomyopathy caused by 4-FA catecholamine-induced myocarditis and/or small vessel myocardial ischemia. Conclusion. Recreational use of 4-FA may present with life threatening toxicity including cardiomyopathy, cardiogenic shock, and pulmonary edema.