The serotonin transporter 5-HTTLPR polymorphism and treatment response to nicotine patch: follow-up of a randomized controlled trial.

In this follow-up of a randomized placebo-controlled clinical trial of nicotine replacement transdermal patch for smoking cessation, 741 smokers of European ancestry who were randomized to receive active patch or placebo patch were genotyped for the serotonin transporter gene-linked polymorphic region. The study setting was a primary care research network in Oxfordshire, United Kingdom. The primary outcome measures were biochemically verified sustained abstinence from cigarette smoking at end of treatment and 24-week follow-up. The main effect of genotype was not associated with sustained abstinence from smoking at either end of treatment (SL: p=.33; SS: p=.81) or 24-week follow-up (SL: p=.05; SS: p=.21), and we found no evidence for a genotypextreatment interaction effect. In summary, despite the theoretically important contribution of serotonin neurotransmission to smoking cessation, the serotonin transporter gene was not associated with treatment response to nicotine patch for smoking cessation in this primary care-based trial.     

Severity of nicotine dependence moderates performance on perceptual-motor tests of attention.

Acute abstinence from cigarette smoking by nicotine-dependent smokers has been linked with cognitive deficits, but the role of nicotine dependence per se in these effects is not known. We therefore tested the relationships of nicotine dependence and smoking history with performance in perceptual-motor, timed tests of attention. Nicotine-dependent smokers (n = 37) and nonsmokers (n = 48), 18-55 years old, took both the d2 Test of Attention and the Digit Symbol Test on each of 2 test days. For smokers, testing on one day began after ad libitum smoking (<45 min since last cigarette); and on the other day, it began after overnight abstinence (>13 hr since last cigarette). On each test day, there were two test blocks with an intervening break, when only the smokers each smoked one cigarette. There were no significant effects of abstinence or of smoking one cigarette on the performance of smokers; however, across conditions, the smokers' performance on both tests correlated negatively with severity of nicotine dependence but not lifetime cigarette consumption or cigarette craving. Smokers with high nicotine dependence performed more slowly on both tests than less dependent smokers or nonsmokers. The findings suggest that severity of nicotine dependence and slowness in perceptual-motor tasks of attention share an underlying basis.     

Transdermal nicotine use in postmenopausal women: does the treatment efficacy differ in women using and not using hormone replacement therapy?

This study of postmenopausal female smokers (N = 94) asked: During short-term smoking abstinence, do the beneficial effects of transdermal nicotine replacement therapy (NRT) on acute symptomatology (i.e., withdrawal, cigarette craving, smoking urges, mood, depressive symptoms, motor speed, and reaction time) differ in women who use and do not use hormone replacement therapy (HRT)? Participants were recruited according to HRT and non-HRT use (self-selecting), then randomized within strata to active nicotine or placebo nicotine patch. After 1 baseline week of smoking, participants quit smoking for 2 weeks. Women received cessation counseling and were monitored for abstinence. Dependent measures were collected during five clinic visits. Two-way analysis of covariance (ANCOVA) were run on change scores for dependent variables, with nicotine patch group (active/placebo) and HRT group (HRT/non-HRT) as independent variables and age as a covariate. No interactions were found between HRT and patch condition, but both showed specific effects. During the first abstinent week, women on active nicotine patch (compared with placebo) experienced less severe withdrawal, greater reductions in cigarette cravings, and lower (more favorable) Factor 1 scores on the Questionnaire of Smoking Urges. During the second abstinent week, women using HRT (compared with the non-HRT group) exhibited better mood (Profile of Mood States scores) and less depression (Beck Depression Inventory scores). These results suggest the following: First, the efficacy of transdermal nicotine replacement is not adversely modified by women's HRT use; second, ovarian hormones might influence women's responses to smoking cessation, and thus should be considered in developing effective strategies for women to quit smoking.     

Rate of nicotine onset from nicotine replacement therapy and acute responses in smokers.

The subjective and reinforcing effects of drugs of abuse may depend partly on their rate of onset, with faster acting formulations typically producing stronger effects than slower ones. In this within-subjects study, we examined the acute effects of nicotine replacement therapy via nicotine nasal spray (fast delivery) vs. transdermal nicotine patch (slow delivery) on craving, withdrawal, cardiovascular responses, subjective ratings, and reinforcing effects of smoking. Smokers (N=30) not seeking treatment participated in three sessions, each after overnight smoking abstinence, involving 14-mg nicotine (Nicoderm) or placebo patch, followed 4 hr later by intermittent administration of nicotine (Nicotrol) or placebo nasal spray. Specifically, the three group comparisons were nicotine patch condition (with placebo spray), nicotine spray condition (with placebo patch), and placebo condition (placebo spray and patch). Nicotine patch and nicotine spray were never administered in the same session. Blood nicotine levels were similar between nicotine patch and nicotine spray conditions, by design. Heart rate and systolic blood pressure were higher following nicotine spray vs. the other conditions, as hypothesized. However, other than reductions in craving related to nicotine spray and patch at some points, no differences between conditions were observed in withdrawal, subjective effects of sprays and smoking, or smoking reinforcement assessed by a computer task. Thus, under these acute conditions, the speed of nicotine delivery from nasal spray vs. patch differentially affected cardiovascular responses and perhaps craving but did not influence withdrawal, subjective ratings, and smoking reinforcement.     

Treating smokers before the quit date: can nicotine patches and denicotinized cigarettes reduce cravings?

The present study investigated whether treatment with the combination of denicotinized cigarettes and 21-mg nicotine patch for 2 weeks before a designated quit date could lessen cravings for smoking, thereby helping smokers abstain from smoking. The study was a randomized controlled clinical trial conducted at Roswell Park Cancer Institute, Buffalo, New York, in 2004 and 2005. Patients included 98 adult heavy smokers (using 20 or more cigarettes/day). Half of the subjects received 2 weeks of combination of denicotinized cigarettes (Quest 3) and 21-mg nicotine patch for 2 weeks before the quit date. The remaining smokers were switched to light cigarettes (Quest 1) during the 2 weeks before the quit date. After the quit date, all subjects received counseling for smoking cessation and were provided nicotine patches for up to 8 weeks after the quit date. Self-reported cravings for smoking, withdrawal symptoms, and smoking abstinence were measured at predetermined intervals using phone-based surveys and in clinical visits. The group that used denicotinized cigarettes and nicotine patch before quitting reported less frequent and less intense cravings for cigarettes in the 2 weeks before and after the designated quit date. Self-reported withdrawal symptoms and quit rates did not differ significantly between the groups. The use of a denicotinized cigarette combined with the nicotine patch appears to lessen cravings to smoke in the immediate postcessation period. A larger, better-powered study is needed to test if this treatment combination has merit for increasing quit rates.     

Subjective and physiological responses to smoking cues in smokers with schizophrenia.

The prevalence of smoking is high among people with schizophrenia. Although several research groups are developing smoking treatments for these smokers, abstinence rates to date have been modest. Methodological tools such as cue exposure are useful in clinical research with smokers in general, but the value of these paradigms with smokers with schizophrenia has yet to be established. The aim of the present study was to determine the subjective and physiological effects of exposure to in vivo smoking cues in smokers with schizophrenia. A total of 25 heavy smokers with schizophrenia or schizoaffective disorder were assessed while nonabstinent and after 2-hr smoking abstinence. Urge to smoke, mood, nicotine withdrawal symptoms, heart rate, and blood pressure were measured during a precue relaxation period, after exposure to neutral cues, and after exposure to smoking cues. Results indicate that both exposure to smoking cues and brief abstinence increased urge levels, nicotine withdrawal symptom levels, and negative affect. Abstinence did not amplify the effects of cues on urges or other cue reactivity measures. These results indicate that smoking cue reactivity laboratory models may be useful for investigating potential smoking treatments for, or neurobiological contributions to, smoking behavior in smokers with schizophrenia.     

A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation

A randomized double-blind, active controlled, parallel group, multi-center phase II clinical trial was conducted to evaluate the efficacy of reduced-nicotine cigarettes as a novel smoking cessation treatment (under Investigational Device Exemption 69,185). The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking. Treatment consisted of Quest brand of cigarettes (Quest 1, 2, and 3), which respectively deliver 0.59+/-0.06, 0.3+/-0.05, and less than 0.05 mg nicotine, either alone or in combination with nicotine replacement therapy (NRT). The primary endpoint was 4 weeks of continuous abstinence (Weeks 7-10), with additional follow-up at 3 and 6 months. Adult men and women smokers (N = 346), motivated to quit, were randomized to one of three treatment groups: Quest plus NRT (NRT pretreatment 2 weeks before, and NRT after the quit date), Quest plus placebo patch, or active control plus NRT (conventional cigarette, followed by NRT after quit date). Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%). Quest plus placebo patch yielded an abstinence rate similar to that of the active control plus NRT (16.4% vs. 21.9%). No serious adverse events were attributable to the investigational product. Quest plus NRT offers promise as a new smoking cessation treatment.     

Smokers' expectancies for nicotine replacement therapy vs. cigarettes.

Smokers (N=188) recruited from the local community completed a questionnaire that measured expected outcomes of using cigarettes, nicotine gum, nicotine patch, and nicotine nasal spray. Expectancy questions relating to negative affect, craving, weight, and health risks were derived from the Smoking Consequences Questionnaire-Adult. As predicted, smokers held much greater expectancies that cigarettes help control negative affect, craving, and weight relative to nicotine replacement therapy (NRT). All NRT products were expected to cause fewer health risks than cigarette smoking. As predicted, smokers held strong negative affect reduction expectancies for cigarette smoking. For NRT, although still relatively low, craving reduction was the strongest expectancy. Individuals who had experience using the nicotine patch had greater positive expectancies for NRT. Greater positive expectancies for NRT were correlated with more immediate plans to quit smoking. In summary, cigarette smokers' positive expectancies about cigarettes do not appear to generalize to NRT products, which may limit their use and effectiveness.     

Waterpipe smoking and nicotine exposure: a review of the current evidence.

The waterpipe, also known as shisha, hookah, narghile, goza, and hubble bubble, has long been used for tobacco consumption in the Middle East, India, and parts of Asia, and more recently has been introduced into the smokeless tobacco market in western nations. We reviewed the published literature on waterpipe use to estimate daily nicotine exposure among adult waterpipe smokers. We identified six recent studies that measured the nicotine or cotinine levels associated with waterpipe smoking in four countries (Lebanon, Jordan, Kuwait, and India). Four of these studies directly measured nicotine or cotinine levels in human subjects. The remaining two studies used smoking machines to measure the nicotine yield in smoking condensate produced by the waterpipe. Meta-analysis of the human data indicated that daily use of the waterpipe produced a 24-hr urinary cotinine level of 0.785 microg/ml (95% CI = 0.578-0.991 microg/ml), a nicotine absorption rate equivalent to smoking 10 cigarettes/day (95% CI = 7-13 cigarettes/day). Even among subjects who were not daily waterpipe smokers, a single session of waterpipe use produced a urinary cotinine level that was equivalent to smoking two cigarettes in one day. Estimates of the nicotine produced by waterpipe use can vary because of burn temperature, type of tobacco, waterpipe design, individual smoking pattern, and duration of the waterpipe smoking habit. Our quantitative synthesis of the limited human data from four nations indicates that daily use of waterpipes produces nicotine absorption of a magnitude similar to that produced by daily cigarette use.     

Long-term changes in sleep and depressive symptoms of smokers in abstinence.

Few studies have evaluated the impact of smoking cessation on objective measures of sleep. The present study assessed the long-term effects of tobacco smoking abstinence on sleep and depression. A total of 15 chronic smokers with Hamilton Rating Scale for Depression (HAM-D) scores of less than 9 were evaluated. Subjects were screened for baseline data when they were smoking chronically. They underwent a 5-week psychological treatment for tobacco smoking, after which their depressive symptoms and sleep architecture were evaluated at 1, 2, 4, 6, 9, and 12 months of abstinence. We report the results of the seven patients who completed 1 year of evaluations and of those patients who achieved only partial abstinence. Polysomnographic recordings were taken, level of depression was measured with the HAM-D, and urinary cotinine levels also were evaluated. HAM-D scores were analyzed with and without sleep items. Nicotine abstinence reduced latency to rapid eye movement (REM) sleep and increased HAM-D scores, suggesting that chronic smokers have depressive symptoms that may be controlled by nicotine administration.     

Smoking cessation patterns in methadone-maintained smokers.

To determine predictors of smoking cessation duration in a randomized clinical trial, we assigned participants to nicotine patch (8-12 weeks) plus either (a) a baseline tailored brief motivational intervention, a quit date behavioral skills counseling session, and a relapse prevention follow-up session, or (b) brief advice using the National Cancer Institute's 4A's model. A total of 383 smokers from five methadone maintenance treatment centers in Rhode Island were enrolled, of whom 312 (82%) completed 6-month follow-up assessments. The primary outcome was longest period of self-reported abstinence during follow-up. Participants were on average 40.5 years of age; 51.9% were male, and 77.6% were White. In multivariate analysis controlling for demographics, nicotine dependence, depressive symptoms, and smoking-related symptoms, we found longer periods of abstinence in persons reporting at least one 24-hr quit attempt in the year prior to baseline (OR = 1.97, p = .003), in those anticipating success in cessation (OR = 1.33, p = .024), and in those with a greater percentage of nicotine patch use days (OR = 2.78, p<.001). Past quit attempts, self-efficacy, and constant nicotine replacement were associated with duration of abstinence among methadone-maintained smokers. Attention to these domains in future intervention studies may improve treatment success.     

The nicotine dependence syndrome scale: a multidimensional measure of nicotine dependence.

We report the development of a new multidimensional questionnaire to measure nicotine dependence, based on Edwards's syndromal conceptualization of dependence. We present three studies. In study 1, we administered the Nicotine Dependence Syndrome Scale (NDSS) to 317 smokers in a smoking cessation study. Factor analysis of the NDSS revealed five factors: Drive (craving and withdrawal, and subjective compulsion to smoke), priority (preference for smoking over other reinforcers), tolerance (reduced sensitivity to the effects of smoking), continuity (regularity of smoking rate), and stereotypy (invariance of smoking). A single overall score based on the first principal component, NDSS-T, was retained as a single core measure of dependence. The NDSS showed promising psychometric properties: NDSS-T and factor scores showed strong associations with dependence-relevant measures, even when we controlled for scores on the Fagerstr?m Tolerance Questionnaire (FTQ); and the NDSS predicted urges when smoking, withdrawal in acute abstinence, and outcome in cessation. The five factor scores showed differential patterns of correlations with external validators, supporting the multidimensionality of the measure. In study 2, we revised the NDSS to expand some subscales and administered it to 802 smokers in a cessation study. The same five factors were extracted, the internal reliability of some subscales was improved, and the factor scores again showed associations with dependence-relevant validators, which were largely maintained when we controlled for FTQ scores. In study 3, with 91 smokers in a cessation trial, we established that the test-retest reliability of the subscales was adequate. Thus, the NDSS presents a valid multidimensional assessment of nicotine dependence that may expand on current measures.     

Sex differences in long-term smoking cessation rates due to nicotine patch

Compared to men, women may be at greater risk for smoking-related diseases and have greater difficulty quitting smoking. Sex differences in medication response could guide treatment for smoking cessation to improve women's quit rates. We conducted a meta-analysis of the 14 placebo-controlled nicotine patch trials (N = 6,250) for which long-term (6 months) clinical outcome results could be determined separately by sex. This analysis updated a meta-analysis of 11 of these trials that found no significant sex differences due to nicotine patch. The increase in quitting due to the nicotine vs. placebo patch was only about half as large in women as in men. Pooled absolute quit rates at 6 months for nicotine and placebo patch, respectively, were 20.1% and 10.8% in men, and 14.7% and 10.1% in women. The odds ratio for quitting due to nicotine vs. placebo patch was lower in women (OR = 1.61) than in men (OR = 2.20), with an interaction odds ratio of 1.40 (95% CI = 1.02-1.93, p = .04). This sex difference did not vary significantly by whether or not formal counseling was provided. Poorer outcomes in women vs. men treated with nicotine patch suggests that increasing the quit rates of women smokers may require supplementing patch treatment or use of other medications.     

The impact of smoking cessation on objective and subjective markers of sleep: review, synthesis, and recommendations.

Sleep disturbance is commonly reported as a prominent subjective symptom by quitting smokers. However, little research on this issue has used objective measures of sleep quality. Previous research has relied mainly on retrospective report of sleep disturbance, with few studies investigating sleep during the initial period after quitting tobacco use. Studies that have used objective measurements suggest that sleep fragmentation is a common occurrence during the withdrawal period. In sleep medicine, sleep disturbance is viewed as a consequence of frequent arousals and is now considered to have particularly deleterious daytime consequences, including sleepiness and dysphoric mood. Recent work also indicates that such awakenings affect the cardiovascular system by providing repetitive bursts of sympathetic nervous system activation, possibly contributing to elevated levels of cardiovascular and cerebrovascular morbidity. Pharmacological treatments designed to facilitate smoking cessation are ineffective for sustained abstinence in many smokers, which may be related to sleep disturbance. Indeed, preliminary evidence suggests that the administration of nicotine replacement therapy (NRT) or bupropion can result in disrupted sleep, particularly in women. However, to better understand the role that nicotine withdrawal and bupropion or NRT treatment, independently and in combination, might play in sleep disturbance, it is necessary to develop a better understanding of the nature of the sleep disturbance than can be provided by self-report. This is particularly important for the development of treatment approaches targeted to ameliorate sleep disruption as part of an overall smoking cessation strategy. The present review seeks to report the current state of knowledge based on extant findings and argues for the need to conduct more detailed polysomnographic investigations of the potentially vicious cycle of smoking cessation leading to sleep disturbances that may prove iatrogenic to sustained cessation.     

Effects of low nicotine content cigarettes on smoke intake.

Cigarettes with selective reductions in nicotine delivery have been considered as potential tools to prevent or treat nicotine dependence or to reduce harm by virtue of reduced nicotine and nitrosamine delivery. An important question is whether individuals smoke these products more intensively, as has been shown to occur with ventilated-filter cigarettes. To investigate this issue, we compared conventional highly ventilated filter cigarettes, having very low tar and nicotine yields when smoked by Federal Trade Commission method (1 mg tar, 2 mg carbon monoxide [CO],.2 mg nicotine), with low nicotine content cigarettes, manufactured from a genetically modified strain of tobacco, which had higher tar but lower nicotine yield (14 mg tar, 13 mg CO,.02 mg nicotine). A total of 16 cigarette smokers participated in two 8-hr sessions (order counterbalanced) during which they smoked each type of cigarette ad libitum. Expired-air CO, plasma nicotine, and smoking topography measures were collected. Subjects showed significant increases in smoking when using the highly ventilated filter cigarettes, and puff volume was significantly greater than with the low nicotine content cigarettes. Subjects achieved an expired-air CO level 74% as high as with the low nicotine content cigarettes; the latter produced CO levels similar to those measured at baseline when subjects smoked their habitual brands of cigarettes. Plasma nicotine levels obtained when subjects smoked the highly ventilated filter cigarettes also were significantly higher than when they smoked the low nicotine content cigarettes. These results indicate that the delivery of substantial amounts of smoke, with selective reductions in nicotine yield, appears to prevent compensatory smoking behavior. Further studies should determine whether similar results are obtained in naturalistic environments.     

The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination.

Whereas the smoking prevalence rates in the general population are declining, rates among people diagnosed with attention-deficit/hyperactivity disorder (ADHD) continue to be elevated. Previous research has shown that nicotine may improve attention and mood, suggesting that nicotine may help ameliorate the attentional and emotional problems associated with ADHD. The present study examined the effects of nicotine with and without stimulant medication on ADHD symptoms, moods, and arousal in the everyday lives of smokers with ADHD. A total of 10 smokers with ADHD who were being treated with stimulant medication were asked to abstain from smoking while participating in the study. Participants underwent four conditions in randomized order: (a) Nicotine patch+stimulant medication, (b) nicotine patch only, (c) placebo patch+stimulant medication, and (d) placebo patch only. Each condition continued for 2 days, during which self-reports of ADHD symptoms and moods were obtained using electronic diaries. Lightweight ambulatory monitors recorded cardiovascular activity at each diary entry. Smoking abstinence was verified by expired carbon monoxide and salivary cotinine analysis. Results showed that nicotine patches and stimulant medication alone and in combination reduced difficulty concentrating and core ADHD symptoms compared with placebo patch only. Borderline improvement in impatience and self-control was seen with nicotine patch administration primarily on day 1. Nicotine patches also tended to elevate systolic and diastolic blood pressure compared with placebo patch during day 2. The findings suggest that smokers with ADHD experience nicotine-related reductions in ADHD symptoms during their everyday lives.     

Cigarette nicotine yields and nicotine intake among Japanese male workers

OBJECTIVES: To analyse brand nicotine yield including "ultra low" brands (that is, cigarettes yielding less-than-or-equal 0.1 mg of nicotine by Federal Trade Commission (FTC) methods) in relation to nicotine intake (urinary nicotine, cotinine and trans-3'-hydroxycotinine) among 246 Japanese male smokers. DESIGN: Cross sectional study. SETTING: Two companies in Osaka, Japan. SUBJECTS: 130 Japanese male workers selected randomly during their annual regular health check up and 116 Japanese male volunteers taking part in a smoking cessation programme. MAIN OUTCOME MEASUREMENTS: Subjects answered a questionnaire about smoking habits. Following the interview, each participant was asked to smoke his own cigarette and, after extinguishing it, to blow expired air into an apparatus for measuring carbon monoxide concentration. Urine was also collected for the assays of nicotine metabolites. RESULTS: We found wide variation in urinary nicotine metabolite concentrations at any given nicotine yield. Based on one way analysis of variance (ANOVA), the urinary nicotine metabolite concentrations of ultra low yield cigarette smokers were significantly lower compared to smokers of high (p = 0.002) and medium yield cigarettes (p = 0.017). On the other hand, the estimated nicotine intake per ultra low yield cigarette smoked (0.59 mg) was much higher than the 0.1 mg indicated by machine. CONCLUSIONS: In this study of Japanese male smokers, actual levels of nicotine intake bore little relation to advertised nicotine yield levels. Our study reinforces the need to warn consumers of inappropriate advertisements of nicotine yields, especially low yield brands.     

Acute effects of cigarette smoking on global cerebral blood flow in overnight abstinent tobacco smokers.

We examined whether cerebral vascular reactivity to 5% CO2/95% O2 would be a useful, independent measure of effects of tobacco smoking on global cerebral blood flow (gCBF). The acute effects during smoking one's favorite brand of cigarettes were determined after overnight tobacco abstinence. Positron emission tomography was used to quantitatively measure gCBF using H(2)15O in 10 right-handed young-adult male volunteer tobacco smokers. After a 12-hr abstinence, gCBF measurements were repeated six times at 15-min intervals: First baseline, 5% CO2/95% O2 inhalation, first cigarette smoking, second baseline, 5% CO2/95% O2 inhalation, and second cigarette smoking. Surprisingly, no significant change was seen in mean gCBF during smoking compared with baseline. However, the increase in arterial plasma concentration of nicotine correlated inversely with gCBF. Out of 19 smoking sessions, gCBF increased in 7, decreased in 7, and was unchanged in 5 sessions. The gCBF increased during smoking when baseline gCBF was relatively low, whereas gCBF decreased when baseline gCBF was relatively high. Both vascular reactivity and estimated gCBF plus arterial nicotine concentrations were useful measures to predict the changes in measured gCBF. These individual differences result in important bimodal effects of smoking on the brains of different young adult tobacco smokers.     

Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behaviour, nicotine and carbon monoxide exposure, and motivation to quit

OBJECTIVE: To monitor the effect of a novel nicotine delivery device that may produce fewer carcinogens (Eclipse) on cigarette smoking, carbon monoxide and nicotine concentrations, and motivation to give up smoking. The smoker's own brand of cigarette and a nicotine replacement product (Nicotrol inhaler) were used as comparisons. DESIGN: After baseline data were recorded, smokers were randomised to either Eclipse or inhaler for two weeks and then switched to the other product for another two weeks. Thereafter a second baseline was obtained. SETTING AND PARTICIPANTS: Fifty smokers were included and data are reported for the 40 with complete data sets. The smokers were not trying to quit but were interested in trying a new product to reduce their risk. They visited a smoking clinic 10 times during the six week period of the trial. INTERVENTION: No counselling to aid reduction by Eclipse or inhaler was given. MAIN OUTCOME MEASURES: At each visit smoking status and carbon monoxide concentrations were recorded. In half of the visits withdrawal symptoms, attitudes towards smoking, heart rate, and blood nicotine concentrations were also recorded. RESULTS: Eclipse use decreased the number of cigarettes smoked per day (cpd) from 19.1 cpd at baseline to 2.1 cpd (p < 0.001), but increased carbon monoxide concentrations in parts per million (ppm) from 21.0 ppm to 33.0 ppm (p < 0.001). A similar decrease in cigarettes smoked per day was seen with the Nicotrol inhaler, from 19.1 cpd to 4.8 cpd (p < 0.001), but carbon monoxide decreased from 21.0 ppm to 12.7 ppm (p < 0.001). The blood nicotine concentration remained fairly stable with Eclipse, increasing slightly from 16.8 ng/ml to 18.0 ng/ml, while for the inhaler a significant drop was noted, from 16.8 ng/ml to 12. 2 ng/ml (p < 0.002). Craving and withdrawal did not increase with Eclipse. Few significant adverse events occurred with Eclipse. CONCLUSIONS: Eclipse can dramatically decrease cigarette consumption without causing withdrawal symptoms or decreases in nicotine concentrations or motivation to quit altogether. Unlike the inhaler, Eclipse produces an increase in carbon monoxide concentration. Thus Eclipse may not be a safer cigarette.     

Urine cotinine as an index of smoking status in smokers during 96-hr abstinence: comparison between gas chromatography/mass spectrometry and immunoassay test strips.

Biomarkers such as carbon monoxide (CO) and cotinine (a nicotine metabolite) are used in tobacco cessation studies to assess smoking status. CO is easy to assess, is inexpensive, and provides immediate results. However, the short half-life of CO may limit its ability to identify smokers who have abstained for several hours. Quantitative methods (e.g., gas chromatography/mass spectrometry, or GC/MS) for measuring urine cotinine, which has a longer half-life, are valid and reliable, though costly and time consuming. Recently developed semiquantitative urine cotinine measurement techniques (i.e., urine immunoassay test strips, or ITS) address these disadvantages, though the value of ITS as a means of identifying abstaining smokers has not been evaluated. The present study examined ITS as a measure of smoking status in temporarily abstaining smokers. A total of 236 breath and urine samples were collected from smokers who participated in two separate studies involving three independent, 96-hr (i.e., Monday-Friday), Latin-square-ordered, abstinence or smoking conditions; a minimum 72-hr washout separated each condition. Each urine sample was analyzed with GC/MS and ITS. Under these study conditions, CO demonstrated moderate sensitivity (83.1%) and strong specificity (100%), whereas ITS assessment showed strong sensitivity (98.5%) and weak specificity (58.5%). In this study of short-term abstinence, ITS classified as nonabstinent nearly half of the samples collected from abstaining smokers. However, it classified nearly all nonabstinent smokers as currently smoking. Validation of ITS using GC/MS results from smokers undergoing more than 96 hr of abstinence may be valuable.