Electrocardiographic Changes Associated with Smoking and Smoking Cessation: Outcomes from a Randomized Controlled Trial

Introduction

Cardiovascular disease (CVD) can be detected and quantified by analysis of the electrocardiogram (ECG); however the effects of smoking and smoking cessation on the ECG have not been characterized.

Methods

Standard 12-lead ECGs were performed at baseline and 3 years after subjects enrolled in a prospective, randomized, placebo-controlled clinical trial of smoking cessation pharmacotherapies. ECGs were interpreted using the Minnesota Code ECG Classification. The effects of (i) smoking burden on the prevalence of ECG findings at baseline, and (ii) smoking and smoking cessation on ECG changes after 3 years were investigated by multivariable and multinomial regression analyses.

Results

At baseline, 532 smokers were (mean [SD]) 43.3 (11.5) years old, smoked 20.6 (7.9) cigarettes/day, with a smoking burden of 26.7 (18.6) pack-years. Major and minor ECG criteria were identified in 87 (16.4%) and 131 (24.6%) of subjects, respectively. After adjusting for demographic data and known CVD risk factors, higher pack-years was associated with major ECG abnormalities (p = 0.02), but current cigarettes/day (p = 0.23) was not. After 3 years, 42.9% of subjects were abstinent from smoking. New major and minor ECG criteria were observed in 7.2% and 15.6% of subjects respectively, but in similar numbers of abstinent subjects and continuing smokers (p>0.2 for both). Continuing smokers showed significant reduction in current smoking (–8.4 [8.8] cigarettes/day, p<0.001) compared to baseline.

Conclusions

In conclusion, major ECG abnormalities are independently associated with lifetime smoking burden. After 3 years, smoking cessation was not associated with a decrease in ECG abnormalities, although cigarettes smoked/day decreased among continuing smokers.     

Obesity and Smoking: Comparing Cessation Treatment Seekers With the General Smoking Population

Obesity and smoking represent the leading preventable causes of morbidity and mortality in the United States. This study compared the prevalence of obesity among smokers seeking cessation treatment (n = 1,428) vs. a general population (n = 4,081) of never smokers, former smoker, and current smokers. Data from treatment‐seeking smokers in the Wisconsin Smokers' Health Study (WSHS) and individuals who completed the National Health and Nutrition Examination Survey (NHANES) 2005–2006 were pooled and obesity rates and other health characteristics were compared. The prevalence of obesity was significantly higher among WSHS treatment‐seeking smokers (36.8%) vs. NHANES current smokers (29.6%), but the obesity rates of WSHS treatment‐seeking smokers did not differ from NHANES former smokers (36.5%) or never smokers (36.5%). Treatment‐seeking smokers were more likely to be female and to have higher educational attainment compared to NHANES participants. Analysis of health characteristics revealed that treatment‐seeking smokers had higher levels of dietary fiber and vitamin C and lower blood levels of total cholesterol, triglycerides, and fasting glucose compared to NHANES current smokers. Results suggest that treatment‐seeking smokers may have a different health profile than current smokers in the general population. Health care providers should be aware of underlying heath issues, particularly obesity, in patients seeking smoking cessation treatment.     

Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking

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.     

Transitions in Smoking Behaviour and the Design of Cessation Schemes

The intake of nicotine by smoking cigarettes is modelled by a dynamical system of differential equations. The variables are the internal level of nicotine and the level of craving. The model is based on the dynamics of neural receptors and the way they enhance craving. Lighting of a cigarette is parametrised by a time-dependent Poisson process. The nicotine intake rate is assumed to be proportional with the parameter of this stochastic process. The effect of craving is damped by a control mechanism in which awareness of the risks of smoking and societal measures play a role. Fluctuations in this damping may cause transitions from smoking to non-smoking and vice versa. With the use of Monte Carlo simulation the effect of abrupt and gradual cessation therapies are evaluated. Combination of the two in a mixed scheme yields a therapy with a duration that can be set at wish.     

Socioeconomic Inequalities in Smoking and Smoking Cessation Due to a Smoking Ban: General Population-Based Cross-Sectional Study in Luxembourg

This study aimed to measure changes in socioeconomic inequalities in smoking and smoking cessation due to the 2006 smoking ban in Luxembourg. Data were derived from the PSELL3/EU-SILC (Panel Socio-Economique Liewen Zu Letzebuerg/European Union—Statistic on Income and Living Conditions) survey, which was a representative survey of the general population aged ≥16 years conducted in Luxembourg in 2005, 2007, and 2008. Smoking prevalence and smoking cessation due to the 2006 smoking ban were used as the main smoking outcomes. Two inequality measures were calculated to assess the magnitude and temporal trends of socioeconomic inequalities in smoking: the prevalence ratio and the disparity index. Smoking cessation due to the smoking ban was considered as a positive outcome. Three multiple logistic regression models were used to assess social inequalities in smoking cessation due to the 2006 smoking ban. Education level, income, and employment status served as proxies for socioeconomic status. The prevalence of smoking decreased by 22.5% between 2005 and 2008 (from 23.1% in 2005 to 17.9% in 2008), but socioeconomic inequalities in smoking persisted. Smoking prevalence decreased by 24.2% and 20.2% in men and women, respectively; this difference was not statistically significant. Smoking cessation in daily smokers due to the 2006 smoking ban was associated with education level, employment status, and income, with higher percentages of quitters among those with a lower socioeconomic status. The decrease in smoking prevalence after the 2006 law was also associated with a reduction in socioeconomic inequalities, including differences in education level, income, and employment status. Although the smoking ban contributed to a reduction of such inequalities, they still persist, indicating the need for a more targeted approach of smoke-free policies directed toward lower socioeconomic groups.     

A Stochastic Model of Smoking Behavior Under a Cessation Program

A stochastic model describing the movements, resulting from a smoking cessation program, of a cohort of individuals from the smoking to the non‐smoking compartment is proposed. The distribution and first two moments of the number of smokers are derived.     

E-Cigarettes and Smoking Cessation: Evidence from a Systematic Review and Meta-Analysis

Background

E-cigarettes are currently being debated regarding their possible role in smoking cessation and as they are becoming increasingly popular, the research to date requires investigation.

Objectives

To investigate whether the use of e-cigarettes is associated with smoking cessation or reduction, and whether there is any difference in efficacy of e-cigarettes with and without nicotine on smoking cessation.

Data Sources

A systematic review of articles with no limit on publication date was conducted by searching PubMed, Web of Knowledge and Scopus databases.

Methods

Published studies, those reported smoking abstinence or reduction in cigarette consumption after the use of e-cigarettes, were included. Studies were systematically reviewed, and meta-analyses were conducted using Mantel-Haenszel fixed-effect and random-effects models. Degree of heterogeneity among studies and quality of the selected studies were evaluated.

Results

Six studies were included involving 7,551 participants. Meta-analyses included 1,242 participants who had complete data on smoking cessation. Nicotine filled e-cigarettes were more effective for cessation than those without nicotine (pooled Risk Ratio 2.29, 95%CI 1.05-4.97). Amongst 1,242 smokers, 224 (18%) reported smoking cessation after using nicotine-enriched e-cigarettes for a minimum period of six months. Use of such e-cigarettes was positively associated with smoking cessation with a pooled Effect Size of 0.20 (95%CI 0.11-0.28). Use of e-cigarettes was also associated with a reduction in the number of cigarettes used.

Limitations

Included studies were heterogeneous, due to different study designs and gender variation. Whilst we were able to comment on the efficacy of nicotine vs. non-nicotine e-cigarettes for smoking cessation, we were unable to comment on the efficacy of e-cigarettes vs. other interventions for cessation, given the lack of comparator groups in the studies included in this meta-analysis.

Conclusions

Use of e-cigarettes is associated with smoking cessation and reduction. More randomised controlled trials are needed to assess effectiveness against other cessation methods.     

Bayesian Inference for Smoking Cessation with a Latent Cure State

Summary .  We present a Bayesian approach to modeling dynamic smoking addiction behavior processes when cure is not directly observed due to censoring. Subject-specific probabilities model the stochastic transitions among three behavioral states: smoking, transient quitting, and permanent quitting (absorbent state). A multivariate normal distribution for random effects is used to account for the potential correlation among the subject-specific transition probabilities. Inference is conducted using a Bayesian framework via Markov chain Monte Carlo simulation. This framework provides various measures of subject-specific predictions, which are useful for policy-making, intervention development, and evaluation. Simulations are used to validate our Bayesian methodology and assess its frequentist properties. Our methods are motivated by, and applied to, the Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention study, a large (29,133 individuals) longitudinal cohort study of smokers from Finland.     

Smoking Cessation Reverses DNA Double-Strand Breaks in Human Mononuclear Cells

Objective

Cigarette smoking is a major risk factor for atherosclerotic cardiovascular disease, which is responsible for a significant proportion of smoking-related deaths. However, the precise mechanism whereby smoking induces this pathology has not been fully delineated. Based on observation of DNA double-strand breaks (DSBs), the most harmful type of DNA damage, in atherosclerotic lesions, we hypothesized that there is a direct association between smoking and DSBs. The goal of this study was to investigate whether smoking induces DSBs and smoking cessation reverses DSBs in vivo through examination of peripheral mononuclear cells (MNCs).

Approach and Results

Immunoreactivity of oxidative modification of DNA and DSBs were increased in human atherosclerotic lesions but not in the adjacent normal area. DSBs in human MNCs isolated from the blood of volunteers can be detected as cytologically visible “foci” using an antibody against the phosphorylated form of the histone H2AX (γ-H2AX). Young healthy active smokers (n = 15) showed increased γ-H2AX foci number when compared with non-smokers (n = 12) (foci number/cell: median, 0.37/cell; interquartile range [IQR], 0.31–0.58 vs. 4.36/cell; IQR, 3.09–7.39, p<0.0001). Smoking cessation for 1 month reduced the γ-H2AX foci number (median, 4.44/cell; IQR, 4.36–5.24 to 0.28/cell; IQR, 0.12–0.53, p<0.05). A positive correlation was noted between γ-H2AX foci number and exhaled carbon monoxide levels (r = 0.75, p<0.01).

Conclusions

Smoking induces DSBs in human MNCs in vivo, and importantly, smoking cessation for 1 month resulted in a decrease in DSBs to a level comparable to that seen in non-smokers. These data reinforce the notion that the cigarette smoking induces DSBs and highlight the importance of smoking cessation.     

Analysis of Factors That Determine Weight Gain during Smoking Cessation Therapy

Cigarette smokers are generally known to gain weight after quitting smoking, and such weight gain is thought to contribute to the worsening of glucose tolerance. While smoking cessation therapy such as nicotine replacement is useful to minimize post-cessation weight gain, substantial gain occurs even during the therapy. The purpose of the present study was to identify factors associated with weight gain during smoking cessation therapy. We evaluated 186 patients(132 males and 54 females)who visited our outpatient clinic for smoking cessation, and successfully achieved smoking abstinence. We performed gender-adjusted regression analysis for the rate of BMI increase from the beginning of cessation to 3 months after initiation. Furthermore, we performed multivariate analysis to investigate factors that determine the BMI increase after smoking cessation. The mean BMI significantly (p<0.0001) increased from 23.5±3.6 kg/m² at the initial consultation to 23.9±3.8 kg/m² at 3 months after the start of therapy. There was no significant difference in the extent of BMI increase between nicotine patch and varenicline therapy groups. Factors significantly correlated with the %BMI increase at 3 months after the start of therapy were triglyceride (p = 0.0006, βa = 0.260), high-density lipoprotein cholesterol (p = 0.0386, βa = −0.168), daily cigarette consumption (p = 0.0385, βa = 0.154), and the Fagerström Test for Nicotine Dependence (FTND) score (p = 0.0060, βa = 0.203). Stepwise multivariate analysis demonstrated that triglyceride and the FTND score were the factors determining the post-cessation BMI increase and that the FTND score was the strongest one. The present study demonstrated that smokers with a high FTND score are more likely to gain weight during smoking cessation therapy. Thus, smokers with a high nicotine dependency may require intervention against weight gain in the cessation clinic.     

Long-Term Benefits of Smoking Cessation on Gastroesophageal Reflux Disease and Health-Related Quality of Life

ObjectiveSmoking is associated with gastroesophageal reflux disease (GERD). Varenicline, a nicotinic receptor partial agonist, is used to aid smoking cessation. The purpose of this study was to prospectively examine the long-term benefits of smoking cessation on GERD and health-related quality of life (HR-QOL).MethodsPatients treated with varenicline were asked to fill out a self-report questionnaire about their smoking habits, gastrointestinal symptoms, and HR-QOL before and 1 year after smoking cessation. The prevalence of GERD, frequency of symptoms, and HR-QOL scores were compared. We also investigated associations between clinical factors and newly-developed GERD.ResultsA total of 141 patients achieved smoking cessation (success group) and 50 did not (failure group) at 1 year after the treatment. The GERD improvement in the success group (43.9%) was significantly higher than that in the failure group (18.2%). The frequency of reflux symptoms significantly decreased only in the success group. There were no significant associations between newly developed GERD and clinical factors including increased body mass index and successful smoking cessation. HR-QOL significantly improved only in the success group.ConclusionsSmoking cessation improved both GERD and HR-QOL. Smoking cessation should be recommended for GERD patients.     

血管回声跟踪技术评价戒烟前后对动脉弹性影响的临床研究

目的:血管回声跟踪(echo-tracking,ET)技术探讨长期吸烟及戒烟对颈总动脉(common carotid artery,CCA)及肱动脉(brachial artery,BA)弹性的影响.方法:受试者为吸烟组(80例,男性,46±岁)和正常对照组(25例,男性,45±6岁),戒烟组在戒烟六个月后,根据戒烟情况将受试者分为成功戒烟组(23人)、部分戒烟组(25人)、戒烟失败组(32人),应用ET技术检测各吸烟组戒烟前及戒烟六个月后CCA及BA弹性(僵硬度β、弹性模量Ep、脉搏波传导速度PWVβ)的变化,同时检测每日吸烟量、吸烟指数、血脂、血糖、血压等各项指标,并与正常对照组比较.结果:(1)正常对照组与各吸烟组戒烟前及戒烟后血脂、血糖、血压、体重指数等指标比较均无统计学差异(P＞0.05).(2)各吸烟组戒烟前每日吸烟量、吸烟指数等指标比较均无统计学差异(P＞0.05).(3)各吸烟组戒烟前CCA及BA的β、Ep、PWVβ较正常对照组均明显增高,具有显著统计学差异(P＜0.001).(4)各吸烟组戒烟后,成功戒烟组CCA及BA的β、Ep、PWVβ与正常对照组无统计学差异(P＞0.05),成功戒烟组CCA及BA的β、Ep、PWVβ较戒烟失败组减低,具有统计学差异(P＜0.05,P＜0.01),部分戒烟组CCA及BA的β、Ep、PWVβ与正常对照组有统计学差异(P＜0.05).结论:吸烟引起CCA及BA弹性减低,成功戒烟可使CCA及BA弹性改善,BA改善效果更明显.     

Lung and Heart Diseases Are Better Predicted by Pack-Years than by Smoking Status or Duration of Smoking Cessation in HIV Patients

Background

The objective of this study was to assess the relationship of pack-years smoking and time since smoking cessation with risk of lung and heart disease.

Methods

We investigated the history of lung and heart disease in 903 HIV-infected patients who had undergone thoracic computed tomography (CT) imaging stratified by smoking history. Multimorbidity lung and heart disease (MLHD) was defined as the presence of ≥ 2 clinical or subclinical lung abnormalities and at least one heart abnormality.

Results

Among 903 patients, 23.7% had never smoked, 28.7% were former smokers and 47.6% were current smokers. Spirometry indicated chronic obstructive pulmonary disease in 11.4% of patients and MLHD was present in 53.6%. Age, male sex, greater pack-years smoking history and smoking cessation less than 5 years earlier vs. more than 10 years earlier (OR 2.59, 95% CI 1.27–5.29, p = 0.009) were independently associated with CT detected subclinical lung and heart disease. Pack-years smoking history was more strongly associated with MLHD than smoking status (p<0.001).

Conclusions

MLHD is common even among HIV-infected patients who never smoked and pack- years smoking history is a stronger predictor than current smoking status of MLHD. A detailed pack-years smoking history should be routinely obtained and smoking cessation strategies implemented.     

Focus: Addiction: Smoking Use and Cessation Among People with Serious Mental Illness

Smoking rates in people with serious mental illness (SMI) are disproportionately high compared to the general population. It is a leading contributor to the early mortality in this population. Smoking cessation rates are low in this group, though patients are motivated to quit. Unfortunately, health care providers do not always prioritize smoking cessation for this population. This review provides an overview of prevalence rates, biological effects that maintain smoking, and evidence-based treatments for smoking cessation in SMI. In addition, objective and qualitative data from a chart review of 78 patients with SMI prescribed smoking cessation treatment at one community mental health center are described. Of these, 30 (38.5 percent) were found to either quit (16/78) or reduce (14/78) smoking. Varenicline appeared to be particularly effective. Review of the literature and results of this study suggest that smoking cessation pharmacotherapies are effective for SMI patients and should be offered to those who smoke.     

早期戒烟大鼠肺病理及炎性介质变化

目的观察早期戒烟后大鼠肺组织病理及炎性介质表达变化规律。方法选用Wistar雄性大鼠80只,随机分为对照组及早期戒烟后0天、1周、2周、4周、6周、8周、12周组。采用酶联免疫吸附方法测定各组大鼠血清中IL-8的蛋白质含量,S-P免疫组化学方法检测肺组织NF-κB p65的表达,并光镜下观察HE染色切片、对大鼠气道炎症进行病理学评分。结果早期戒烟组大鼠可见气道上皮细胞纤毛发生粘连、倒伏,上皮细胞空泡变形、坏死、增生,炎症细胞浸润;其血清IL-8浓度、肺组织NF-κB的表达及气道炎症病理评分在戒烟后各时相点较未吸烟对照组明显升高,有统计学意义（P〈0.05）。早期戒烟组大鼠血清IL-8的浓度、肺组织NF-κB的表达及肺组织病理炎症评分在戒烟后略有上升、且在戒烟后8周达到高峰,但随后在戒烟12周时可见IL-8的浓度有下降趋势,肺组织病理炎症反应有所减轻。结论早期戒烟大鼠在戒烟早期虽可见炎症反应略有加重,但随戒烟时间延长,仍可见炎症反应有所减轻。因此,提倡及早且坚持戒烟。     

A Cost-Utility Analysis of Lung Cancer Screening and the Additional Benefits of Incorporating Smoking Cessation Interventions

Background

A 2011 report from the National Lung Screening Trial indicates that three annual low-dose computed tomography (LDCT) screenings for lung cancer reduced lung cancer mortality by 20% compared to chest X-ray among older individuals at high risk for lung cancer. Discussion has shifted from clinical proof to financial feasibility. The goal of this study was to determine whether LDCT screening for lung cancer in a commercially-insured population (aged 50–64) at high risk for lung cancer is cost-effective and to quantify the additional benefits of incorporating smoking cessation interventions in a lung cancer screening program.

Methods and Findings

The current study builds upon a previous simulation model to estimate the cost-utility of annual, repeated LDCT screenings over 15 years in a high risk hypothetical cohort of 18 million adults between age 50 and 64 with 30+ pack-years of smoking history. In the base case, the lung cancer screening intervention cost $27.8 billion over 15 years and yielded 985,284 quality-adjusted life years (QALYs) gained for a cost-utility ratio of $28,240 per QALY gained. Adding smoking cessation to these annual screenings resulted in increases in both the costs and QALYs saved, reflected in cost-utility ratios ranging from $16,198 per QALY gained to $23,185 per QALY gained. Annual LDCT lung cancer screening in this high risk population remained cost-effective across all sensitivity analyses.

Conclusions

The findings of this study indicate that repeat annual lung cancer screening in a high risk cohort of adults aged 50–64 is highly cost-effective. Offering smoking cessation interventions with the annual screening program improved the cost-effectiveness of lung cancer screening between 20% and 45%. The cost-utility ratios estimated in this study were in line with other accepted cancer screening interventions and support inclusion of annual LDCT screening for lung cancer in a high risk population in clinical recommendations.     

One-Year Effects of Project EX in Spain: A Classroom-Based Smoking Prevention and Cessation Intervention Program

Background

Tobacco use prevalence rates are high among Spanish adolescents. Programming to counteract tobacco use is needed.

Methods and Findings

The current study provides a one-year follow-up outcome evaluation of Project EX, an eight-session classroom-based curriculum. The intervention was tested using a randomized controlled trial with 1,546 Spanish students, involving three program and three control schools. Compared to the control condition, the program condition revealed a greater reduction in nicotine dependence (p < .05) and CO ppm levels (p < .001), and lower consumption of cigarettes at last month (p = .03).

Conclusions

Long-term outcomes of the Project EX classroom-based program are promising for adolescent prevention and possibly cessation in Spain.     

Smoking Cessation Induces Profound Changes in the Composition of the Intestinal Microbiota in Humans

Background

The human intestinal microbiota is a crucial factor in the pathogenesis of various diseases, such as metabolic syndrome or inflammatory bowel disease (IBD). Yet, knowledge about the role of environmental factors such as smoking (which is known to influence theses aforementioned disease states) on the complex microbial composition is sparse. We aimed to investigate the role of smoking cessation on intestinal microbial composition in 10 healthy smoking subjects undergoing controlled smoking cessation.

Methods

During the observational period of 9 weeks repetitive stool samples were collected. Based on abundance of 16S rRNA genes bacterial composition was analysed and compared to 10 control subjects (5 continuing smokers and 5 non-smokers) by means of Terminal Restriction Fragment Length Polymorphism analysis and high-throughput sequencing.

Results

Profound shifts in the microbial composition after smoking cessation were observed with an increase of Firmicutes and Actinobacteria and a lower proportion of Bacteroidetes and Proteobacteria on the phylum level. In addition, after smoking cessation there was an increase in microbial diversity.

Conclusions

These results indicate that smoking is an environmental factor modulating the composition of human gut microbiota. The observed changes after smoking cessation revealed to be similar to the previously reported differences in obese compared to lean humans and mice respectively, suggesting a potential pathogenetic link between weight gain and smoking cessation. In addition they give rise to a potential association of smoking status and the course of IBD.