Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic.

NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

Pharmacotherapies to enhance smoking cessation during pregnancy.

Smoking during pregnancy is a significant public health concern. Maternal smoking increases the risk of spontaneous abortion, low birth weight, premature delivery, sudden infant death syndrome and learning and behavioral problems in the offspring. Unfortunately, the majority of pregnant women do not quit smoking during pregnancy. Although pharmacotherapy may improve smoking cessation rates in pregnancy, very few studies exist that have studied the safety and efficacy of medications to treat pregnant smokers. This article reviews the available safety and efficacy data for the use in pregnancy of the five first-line therapies and two second-line therapies that are recommended for smoking cessation in non-pregnant smokers. Other promising nicotine replacement therapies are also reviewed. Ultimately, the choice whether to use pharmacotherapy for smoking cessation should be made jointly by the pregnant smoker and her health care provider. This article reviews factors that may be considered when prescribing pharmacotherapy to pregnant smokers (i.e. the role of behavioral counseling, identification of appropriate patients, potential advantages and disadvantages of each of the pharmacotherapies, proposed monitoring strategies, dose and duration and goals of treatment). More research regarding the safety and efficacy of pharmacotherapy during pregnancy is needed to define the risk/benefit profile of each medication for use in smoking cessation in pregnant women.

Impact of smoking cessation on ambulatory blood pressure and heart rate in postmenopausal women.

BACKGROUND: Smoking and hypertension interact to increase the incidence of cardiovascular disease; however, little is known about the effects of smoking cessation on blood pressure (BP) control. We prospectively evaluated the impact of smoking cessation on clinic and ambulatory BP and heart rate (HR) in stage 1 hypertensive and normotensive postmenopausal women. METHODS: A total of 66 women were randomly assigned using a 3:1 randomization scheme to immediate smoking cessation or to a wait list control group. Clinic and ambulatory BP and HR, and 24-h urinary catecholamine concentrations were obtained at baseline and again at 6 weeks. Carbon monoxide levels and self-report were used to assess compliance with smoking cessation. RESULTS: Ambulatory monitoring showed that the awake SBP decreased by 3.6+/-1.9 mm Hg in the treated subjects who quit smoking (n=19), whereas in the control group (n=15) there was an increase of 1.7+/-2.4 mm Hg (P=.045). Awake HR decreased after smoking cessation by 7+/-1 beats/min and did not change (0+/-1 beat/min) in the control group (P=.001). Blood pressure and HR did not significantly change during sleep after smoking cessation. Changes in the awake HR correlated with changes in urinary epinephrine concentrations (r= 0.58, P=.001), and norepinephrine concentrations (r= 0.45, P=.001), There was no significant change in clinic systolic BP, diastolic BP, or HR between groups. CONCLUSIONS: Smoking cessation reduces systolic BP and HR during the daytime, when patients typically smoke. These hemodynamic changes are due in part to reductions in sympathetic nervous system activity.

Nicotine replacement prescription practices of obstetric and pediatric clinicians.

OBJECTIVE: To assess smoking cessation counseling and nicotine replacement therapy prescription and recommendation practices among obstetric and pediatric providers. METHODS: We sent out a self-administered survey to 61 obstetric and pediatric nurse practitioners and physicians at six community health centers in the Boston area. RESULTS: Obstetric providers were more likely to view smoking cessation counseling as their responsibility in treating pregnant women than pediatric providers did in treating infants with mothers who smoked (mean +/- standard deviation [95% confidence interval] 4.5 +/- 0.76 [4.2, 4.8] versus 4.0 +/- 0.8 [3.7, 4.3] on a five-point scale; P <.05). Obstetric providers believed that smoking cessation counseling was more effective than did pediatric providers (3.45 +/- 1.1 [3.0, 3.9] versus 2.8 +/- 0.8 [2.5, 3.1] on a five-point scale; P <.05) and were more likely to report provision of cessation assistance than pediatric providers (63% [44%, 82%] versus 17% [5%, 29%]; P <.05). Obstetric providers were more likely to prescribe or recommend over-the-counter nicotine replacement therapy than pediatric providers (44% [25%, 63%] versus 11% [1%, 21%], P =.004). Reasons for not prescribing nicotine replacement differed according to specialty; however, perceived lack of efficacy was not a typical reason given by clinicians in either specialty. Only two of 47 practitioners who did not prescribe or recommend those therapies listed that as a factor in their decisions. CONCLUSION: We found that nicotine replacement therapies are commonly prescribed or recommended to pregnant smokers by obstetric providers, but less commonly to lactating women by pediatric providers.

Effects of transdermal nicotine or smoking on nicotine concentrations and maternal-fetal hemodynamics.

OBJECTIVE: To compare nicotine concentrations and fetal middle cerebral artery resistance indices (RIs) during 21-mg transdermal nicotine use with these values during maternal smoking. METHODS: In this randomized, crossover study, participants smoked approximately 20 cigarettes daily and were between 24 and 36 weeks' gestation. Subjects were randomized to transdermal nicotine or to smoking ad libitum for 8 hours. One week later, they crossed over to the other condition. Maternal plasma nicotine concentrations and hemodynamic measurements were obtained before and after the onset of smoking or patch placement. RESULTS: Area under the plasma nicotine concentration-time curve during patch use was similar to continued smoking (93 versus 89 ng-hour/mL, respectively) (P = .77). The mean (standard error [SE] change in the middle cerebral artery RI from baseline to 4 hours later was similar during patch use and smoking: -.002 (0.008) versus -.02 (0.015), respectively (P = .3). The study had greater than 80% power to detect a 25% difference in nicotine concentrations and a change of 2 standard deviations in the middle cerebral artery RI between conditions. An unexpected finding was that of a loss of fetal heart rate (FHR) reactivity in 5/8 tracings after patch placement versus 1/6 tracings after smoking (P = .12). The baseline FHR increased by a mean (SE) of 8 (4) beats per minute with loss of reactivity in the patch condition, compared with a decrease of 3 (3) beats per minute without loss of reactivity (P = .05). CONCLUSION: Eight-hour use of 21-mg transdermal nicotine yields nicotine concentrations and middle cerebral artery RIs similar to those produced by hourly smoking in pregnant smokers.

Effects of short-term use of nicotine gum in pregnant smokers.

OBJECTIVES: To compare blood concentrations of nicotine and cotinine and maternal and fetal hemodynamic effects resulting from use of nicotine gum versus cigarette smoking in pregnant smokers. METHODS: Pregnant women (24 to 36 weeks' gestation) who smoked chronically were randomly assigned with a 1:2 randomization scheme to either a group that smoked cigarettes (n = 10) or to a group that stopped smoking and chewed at least six pieces of nicotine gum (2 mg nicotine per piece) per day (n = 19). Blood nicotine and cotinine concentrations, maternal heart rate and blood pressure, uterine resistance index, and fetal heart rate and umbilical artery resistance index were obtained before and after one cigarette was smoked at baseline and after 5 continuous days of either chewing gum or smoking. RESULTS: A significant reduction from baseline in nicotine (p < 0.0001) and cotinine (p < 0.0025) concentrations was observed in those who chewed nicotine gum compared with those who smoked cigarettes. No significant differences in the changes in maternal or fetal hemodynamic parameters from baseline to estimated time of peak nicotine exposure were observed between those who smoked cigarettes and those who chewed nicotine gum. CONCLUSION: Short-term use of nicotine gum delivers less nicotine than usual cigarette smoking in pregnant women.