Nicotine concentrations with electronic cigarette use: effects of sex and flavor.

INTRODUCTION: This study examined overall changes in nicotine concentrations when using a popular e-cigarette and 18 mg/mL nicotine e-Juice, and it further explored effects of sex and flavorings on these concentrations. METHODS: We recruited nontreatment-seeking smokers who were willing to try e-cigarettes for 2 weeks and abstain from cigarette smoking. Subjects were randomized to either menthol tobacco or non-menthol tobacco-flavored e-cigarette use for 7-10 days, and the next week they were crossed over to the other condition. On the last day of e-cigarette use of each flavor, subjects completed a laboratory session in which they used the e-cigarette for 5 min ad libitum. Nicotine concentrations were obtained 5 min before and 5, 10, 15, 20, and 30 min after the onset of e-cigarette use. RESULTS: Twenty subjects completed at least 1 monitoring session. Nicotine concentrations significantly increased from baseline to 5 min by 4 ng/mL at the first laboratory session (p < .01) and by 5.1 ng/mL at the second laboratory session (p < .01). Combining sessions, there were no main effects of sex or preferred flavor (based on smoking history) on changes in nicotine concentrations. After adding preferred flavor, sex, and visit order to the model, there was a significant preferred flavor by sex interaction (p < .01), such that women who received nonpreferred flavors had lower nicotine concentrations and rated their e-cigarette as less likeable (p < .01). CONCLUSION: We found nicotine concentrations significantly increase after e-cigarette use for 5 min, and flavor may impact nicotine concentrations with e-cigarette use in women.

NIH electronic cigarette workshop: developing a research agenda.

BACKGROUND: Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices deliver nicotine along with other constituents, including flavorants, via an inhalable aerosol. Their uptake is rapidly increasing in both adults and youths, primarily among current smokers. Public debate is increasing on how these devices should be regulated and used, yet only limited peer-reviewed research exists. To develop a informed policy for e-cigarettes, their effects on human behavior, physiology, and health need to be understood. PURPOSE: This paper describes proceedings from a National Institutes of Health-sponsored workshop, which was held in November 2013, to identify research needs related to the effects of e-cigarettes. Discussion topics included e-cigarette risks and abuse potential; the potential role for e-cigarettes in harm reduction and smoking cessation; unintended consequences of e-cigarette use, such as becoming a gateway to conventional cigarettes; and dual use of both e-cigarettes and conventional cigarettes. RESULTS AND CONCLUSIONS: The research needs identified by the workshop participants included the following: standards to measure the contents and emissions of e-cigarettes; biomarkers of exposure; physiological effects of e-cigarettes on tissues and organ systems, including pulmonary and cardiovascular; information on e-cigarette users, how the devices are used, and identification of the best tools to assess these measures; factors that drive use and influence patterns of use; and appropriate methods for evaluating a potential role for e-cigarettes in smoking or nicotine cessation. To understand fully the challenges and the opportunities that e-cigarettes represent, expertise will be needed in basic, behavioral, translational, and clinical sciences.

Effects of varenicline, nicotine or placebo on depressive symptoms in postmenopausal smokers.

BACKGROUND: Varenicline carries a black box warning for neuropsychiatric adverse events. OBJECTIVE: We examined varenicline use and past history of major depressive disorder (MDD) on depressive symptoms during smoking cessation. METHOD: This is a secondary analysis of two smoking cessation studies in 152 postmenopausal women who received placebo or nicotine patch, or 78 women who received varenicline with relaxation. Lifetime history of MDD (LH-MDD) was assessed at baseline and women with current MDD were excluded. Center for Epidemiologic Study Depression scale (CESD) measured depressive symptoms at baseline, 6 and 12 weeks. RESULTS: Baseline CESD scores were 5.3 + 4.4. Those with a LH-MDD reported higher CESD scores (p > .001). Those taking varenicline reported lower scores over all time periods compared to nicotine or placebo (p < .01). The differences between varenicline and the other treatments remained when controlling for LH-MDD, indicating an independent effect. CESD scores were associated with concurrent smoking status (p < .001), and with withdrawal symptoms (p < .001). CONCLUSION: CESD score were lower in those receiving varenicline, whether this is due to an anti-depressant effect, subject selection, use of relaxation or another cause is unknown. Varenicline does not increase depressive symptoms during smoking cessation in postmenopausal women without current MDD. Subjects with a LH-MDD are susceptible to developing depressive symptoms during smoking cessation, regardless of pharmacologic aid. SCIENTIFIC SIGNIFICANCE: Pharmacologic aids did not increase depression symptoms in this select population of postmenopausal women without current depression. Smoking cessation does increase depressive symptoms in those with LH-MDD, though the degree of increase was not clinically meaningful.

Prenatal tobacco prevention and cessation interventions for women in low- and middle-income countries.

Although the prevalence of tobacco use is decreasing in many high-income countries, it is increasing in many low- and middle-income countries. The health and economic burden of increasing tobacco use and dependence is predictable and will have devastating effects in countries with limited resources, particularly for vulnerable populations such as pregnant women. We sought to review effective tobacco prevention and intervention strategies for decreasing tobacco use and secondhand smoke exposure before and during pregnancy in high-, middle-, and low-income countries. We reviewed several types of interventions, including population-level efforts (increasing tobacco prices, implementing tobacco control policies), community interventions, clinical interventions, and pharmacological treatments. A second purpose of this report is to present findings of an international expert working group that was convened to review the evidence and to establish research priorities in the following areas: (a) preventing the uptake and reducing tobacco use among girls and women of reproductive age; and (b) reducing tobacco use and secondhand smoke exposure among pregnant women. The working group considered the evidence on existing interventions in terms of burden of disease, intervention impact, intervention costs, feasibility of integration into existing services, uniqueness of the contribution, and overall feasibility. Finally, we present the working group's recommendations for intervention research priorities.

Predictors of adverse events among pregnant smokers exposed in a nicotine replacement therapy trial.

OBJECTIVE: The purpose of this study was to determine the contribution of randomization to nicotine replacement therapy (NRT), sociodemographic and psychosocial factors, and pregnancy and medical history to serious perinatal adverse events among pregnant smokers. STUDY DESIGN: We performed a retrospective review of all medical records for participants in the Baby Steps Trial. Data that were abstracted from 157 records were combined with baseline characteristics for logistic regression modeling of serious adverse events and adjusted for covariates. RESULTS: Serious adverse events occurred in 17% (9/52 pregnancies) and 31% (33/105 pregnancies) of participants in the control and NRT arms, respectively. Black race, adverse pregnancy history, and use of analgesic medication during pregnancy were significant predictors (P = .02, .04, and .01, respectively). Remaining covariates, which included randomization to NRT, were not statistically significant. CONCLUSION: Although race, poor pregnancy history, and use of analgesics were associated with serious adverse events, randomization to NRT during pregnancy was not a significant factor. Further research is needed to examine the safety of analgesic medications during pregnancy.

What do we know about the role of pharmacotherapy for smoking cessation before or during pregnancy?

SIGNIFICANCE: Given the substantial health risks of smoking during pregnancy, and the potential of pharmacotherapy to enhance quit rates, a need exists to examine the utility of pharmacotherapy for smoking cessation during pregnancy. LITERATURE REVIEW: We briefly review the first-line medications that are recommended for smoking cessation in nonpregnant adults. Additionally, we review the toxicity of tobacco smoke and the potential risks of pharmacotherapy as evidenced by animal studies. We review in more detail studies conducted in pregnant women, including (a) observational studies, (b) short-term safety and longer term uncontrolled studies, and (c) randomized controlled clinical trials (both effectiveness and efficacy studies). DISCUSSION: Because the safety and efficacy of pharmacotherapy for smoking cessation during pregnancy have not been established, no definitive recommendations can be made on the topic. Effectiveness trials have shown that nicotine replacement therapy (NRT) enhances smoking cessation during pregnancy, but efficacy trials have not shown an advantage for NRT compared with placebo treatment. Small sample size or poor medication compliance (with either the dose or the duration of treatment) may contribute to lack of efficacy in placebo-controlled NRT trials. However, these trials showed that NRT did not adversely affect birth outcomes and increased birth weight. Based on these findings and the fact that all medications have some risk, psychosocial interventions should be the first treatment option for pregnant smokers. Additional research is needed to determine fully the risks and benefits of the various pharmacotherapies for smoking cessation during pregnancy.

Adherence to nicotine replacement therapy among pregnant smokers.

INTRODUCTION: This secondary analysis examined the association between adherence to nicotine replacement therapy (NRT) and smoking cessation among pregnant smokers enrolled in Baby Steps, an open-label randomized controlled trial testing cognitive-behavioral therapy (CBT) versus CBT plus NRT. METHOD: The analysis included only women who received NRT for whom we had complete data (N = 104). Data came from daily calendars created from recordings of counseling sessions and from telephone surveys at baseline and 38 weeks gestation. RESULTS: Overall, 29% of the 104 women used NRT for the recommended 6 weeks and 41% used NRT as directed in the first 48 hr after a quit attempt. Ordinal logistic regression modeling indicated that using NRT as directed in the first 48 hr and having made a previous quit attempt were the strongest predictors of longer NRT use. Univariate analyses suggested that primigravid women and women who used NRT longer were more likely to report quitting at 38 weeks gestation. DISCUSSION: Findings indicated that adherence to NRT is low among pregnant smokers, but adherence was a predictor of cessation. Future trials should emphasize adherence, particularly more days on NRT, to promote cessation during pregnancy.

Nicotine replacement and behavioral therapy for smoking cessation in pregnancy.

BACKGROUND: This study examines whether adding nicotine replacement therapy (NRT) to cognitive-behavioral therapy (CBT) for pregnant smokers increases rates of smoking cessation. METHODS: An open-label randomized trial (Baby Steps, n=181) of CBT-only versus CBT+NRT (choice of patch, gum, or lozenge; 1:2 randomization) was used. Data were collected from 2003 through 2005; analyses were conducted in 2006 and 2007. Outcomes were biochemically validated self-reported smoking status at 7 weeks post-randomization, 38 weeks gestation, and 3 months postpartum. RESULTS: Women in the CBT+NRT arm were almost three times more likely than women in the CBT-only arm to have biochemically validated cessation at both pregnancy time points (after 7 weeks: 24% vs 8%, p=0.02; at 38 weeks gestation: 18% vs 7%, p=0.04), but not at 3 months postpartum (20% vs 14%, p=0.55). Recruitment was suspended early by an Independent Data and Safety Monitoring Board when an interim analysis found a higher rate of negative birth outcomes in the CBT+NRT arm than in the CBT-only arm. In the final analysis, the difference between the arms in rate of negative birth outcomes was 0.09 (p=0.26), when adjusted for previous history of preterm birth. CONCLUSIONS: The addition of NRT to CBT promoted smoking cessation in pregnant women. This effect did not persist postpartum. More data are needed to determine safety parameters and to confirm the efficacy of NRT use during pregnancy.

Alcohol and tobacco cessation in alcohol-dependent smokers: analysis of real-time reports.

Alcohol-tobacco interactions and relapse precipitants were examined among alcohol-dependent smokers in a trial of concurrent alcohol and tobacco treatment. After discharge from treatment, participants completed 14 days of electronic diary (ED) assessments of mood, self-efficacy, urges to drink or smoke, and drinking and smoking behavior. ED data revealed an increase in frequency of alcohol urges after smoking episodes. Drinking relapse episodes were predicted by prior ED ratings of low self-efficacy to resist drinking and high urge to smoke. Smoking relapse episodes were predicted by high urge to smoke and high negative, high arousal mood. Results support a cross-substance cue reactivity model of multiple substance use and a limited-strength model, but not a cross-substance coping model.

Concurrent brief versus intensive smoking intervention during alcohol dependence treatment.

Alcohol dependent smokers (N=118) enrolled in an intensive outpatient substance abuse treatment program were randomized to a concurrent brief or intensive smoking cessation intervention. Brief treatment consisted of a 15-min counseling session with 5 min of follow-up. Intensive intervention consisted of three 1-hr counseling sessions plus 8 weeks of nicotine patch therapy. The cigarette abstinence rate, verified by breath carbon monoxide, was significantly higher for the intensive treatment group (27.5%) versus the rate for the brief treatment group (6.6%) at 1 month after the quit date but not at 6 months, when abstinence rates fell to 9.1% for the intensive treatment group and 2.1% for the brief treatment group. Smoking treatment assignment did not significantly impact alcohol outcomes. Although intensive smoking treatment was associated with higher rates of short-term tobacco abstinence, other, perhaps more intensive, smoking interventions are needed to produce lasting smoking cessation in alcohol dependent smokers.

Effects of nicotine deprivation on urges to drink and smoke in alcoholic smokers.

AIM: This study examined the effect of nicotine deprivation on alcohol and smoking urges in a sample of alcohol-dependent smokers in early recovery. DESIGN: Using a within-subjects design, participants underwent two cue-reactivity laboratory sessions in which they rated their urges for alcohol and cigarettes during the following three trials: baseline, neutral cue and mood induction combined with alcohol beverage cue exposure. One session was completed after 34 hours of nicotine deprivation and another in a non-deprived state. PARTICIPANTS: Forty alcohol-dependent heavy smokers recruited from a substance abuse day treatment program. MEASUREMENTS: Self-reported urge to drink, urge to smoke and salivation. FINDINGS: Results showed that during the non-deprived session, alcohol cue presentations were associated with significant increases in urges to drink and urges to smoke. Acute nicotine deprivation led to increased smoking urges, but was not associated with increased urges to drink alcohol. CONCLUSIONS: Findings suggest that the acute effects of smoking cessation are unlikely to increase risk of relapse to alcohol in alcoholic patients who are undergoing treatment.

Effects of smoking cessation on body composition in postmenopausal women.

BACKGROUND: Smoking cessation is associated with weight gain, but the effects of smoking cessation on measures of body composition (BC) have not been adequately evaluated. The purpose of this study is to examine the effects of 16 months of cigarette abstinence on areas of BC measured by dual-energy x-ray absorptiometry (DXA). METHODS: One hundred fifty-two postmenopausal women participated in a smoking cessation study using the nicotine patch. Secondary analyses were conducted on data from 119 subjects (age 56 +/- 7 years, range 41-78 years) who had had DXA scans at baseline and 16 months later. Participants were classified either as quitters (self-reported cigarette abstinence confirmed with exhaled carbon monoxide [co]

Smoking cessation during alcohol treatment: a randomized trial of combination nicotine patch plus nicotine gum.

AIMS: The primary aim was to compare the efficacy of smoking cessation treatment using a combination of active nicotine patch plus active nicotine gum versus therapy consisting of active nicotine patch plus placebo gum in a sample of alcohol-dependent tobacco smokers in an early phase of out-patient alcohol treatment. A secondary aim was to determine whether or not there were any carry-over effects of combination nicotine replacement on drinking outcomes. DESIGN: Small-scale randomized double-blind placebo-controlled clinical trial with 1-year smoking and drinking outcome assessment. SETTING: Two out-patient substance abuse clinics provided a treatment platform of behavioral alcohol and smoking treatment delivered in 3 months of weekly sessions followed by three monthly booster sessions. PARTICIPANTS: Participants were 96 men and women with a diagnosis of alcohol abuse or dependence and smoking 15 or more cigarettes per day. INTERVENTION: All participants received open-label transdermal nicotine patches and were randomized to receive either 2 mg nicotine gum or placebo gum under double-blind conditions. FINDINGS: Analysis of 1-year follow-up data revealed that patients receiving nicotine patch plus active gum had better smoking outcomes than those receiving patch plus placebo gum on measures of time to smoking relapse and prolonged abstinence at 12 months. Alcohol outcomes were not significantly different across medication conditions. CONCLUSIONS: Results of this study were consistent with results of larger trials of smokers without alcohol problems, showing that combination therapy (nicotine patch plus gum) is more effective than monotherapy (nicotine patch) for smoking cessation.

Olfactory and gustatory sensory changes to tobacco smoke in pregnant smokers.

Models of smoking behavior change include addiction, social, and behavioral concepts. The purpose of this study was to explore the prevalence of two biologic factors, olfactory and gustatory responses to tobacco smoke, as potentially powerful contributors to smoking behavior change among pregnant women. Data were obtained from 209 pregnant smokers. The majority of women reported olfactory (62%) and gustatory (53%) aversions to tobacco. Aversions first appeared during the first trimester of pregnancy. Women who experienced olfactory aversions were more likely also to experience gustatory aversions. Olfactory aversions were associated with women smoking less. Aversions to tobacco smoke are common among pregnant smokers, are associated with women smoking less, and could help explain pregnant women's smoking patterns.

Challenges and solutions for recruiting pregnant smokers into a nicotine replacement therapy trial.

Improvements in smoking cessation interventions for pregnant smokers are needed. One major step is to examine the potential effectiveness of nicotine replacement therapy (NRT). The potential benefits of providing pregnant women with NRT to help them quit smoking are still unknown; early interventions to test the effectiveness and efficacy are vital to advancing the field. This paper describes recruitment efforts for a multiclinic trial to test the effectiveness of NRT use in addition to behavioral therapy in promoting cessation during pregnancy. The biggest challenge is recruiting sufficient numbers of pregnant women. This paper discusses specific obstacles for recruitment and solutions. Knowing the potential pitfalls to recruiting pregnant women into these trials can lead to better studies and thus improved outcomes.

Seizure associated with sleep deprivation and sustained-release bupropion.

This case report describes a generalized seizure associated with sustained-release bupropion use and sleep deprivation. The subject, a 31-year-old female smoker, was participating in a clinical trial evaluating an investigational medication for smoking cessation that used sustained-release bupropion as an active control. After 5 weeks of bupropion use, the subject experienced a generalized tonic clonic seizure after staying up nearly all night packing and moving to a new residence. The patient had no other risk factors for seizures. We suggest that sleep deprivation may add to the risk of bupropion-associated seizures.

Effect of maternal smoking on fetal catecholamine concentrations at birth.

The aim of this study was to compare catecholamine concentrations in the fetal umbilical artery cord blood from the offspring of smokers versus the offspring of nonsmokers. Pregnant women who were self-identified as smokers (>/=10 cigarettes per day throughout pregnancy) or nonsmokers were recruited for study participation. Maternal blood was collected for cotinine concentrations. Umbilical artery cord blood was collected at delivery for arterial pH and catecholamine concentrations. Cord blood was obtained from 51 subjects, including 21 smokers and 30 nonsmokers. Median epinephrine concentrations [304 pg/mL versus 597 pg/mL (Mann-Whitney U = 170; p = 0.006)] and median norepinephrine concentrations [3148 pg/mL versus 6558 pg/mL (Mann-Whitney U = 191; p = 0.006)] were significantly lower in smokers compared with nonsmokers, respectively. After controlling for gestational age, route of delivery, and arterial pH, log-transformed epinephrine concentrations between smokers and nonsmokers were statistically significant (p = 0.03), with a similar trend for log-transformed norepinephrine concentrations (p = 0.07). Analyses of the data using cotinine <20 ng/mL to classify nonsmokers also showed differences in epinephrine concentrations between groups (p = 0.02). These results are consistent with results from animal studies showing that catecholamine concentrations may be affected by prenatal nicotine exposure. Further studies are needed to validate these findings and to examine the specific mechanism by which these differences may arise.