Nicotine Delivery of a Menthol-Flavored Heat-not-Burn Tobacco Product During Directed Use.

INTRODUCTION: IQOS was authorized by the U.S. Food and Drug Administration (FDA) as a modified-risk tobacco product. We conducted a pharmacokinetic study evaluating the nicotine delivery and subjective effects of IQOS use among current menthol cigarette smokers to better understand if IQOS is an acceptable cigarette alternative in light of the proposed menthol cigarette ban. AIMS AND METHODS: Participants were adult smokers of >4 menthol cigarettes per day. After 14-hour nicotine abstinence, participants were provided an IQOS device and menthol heatstick to puff every 20 seconds for a total of 14 puffs. Blood samples were collected at baseline and during active use to calculate nicotine boost from baseline to peak concentration. Nicotine withdrawal symptoms were collected before and after IQOS use. In addition, a modified Product Evaluation Scale for IQOS was collected after use. RESULTS: Participants (n = 8) were a mean age of 43.9 years, 63% were female, 88% identified as White, and they smoked a mean of 17.1 menthol cigarettes per day. After IQOS use, the mean nicotine boost obtained was 15.96 ng/mL (SD = 6.91) (range 9.31 to 30.55 ng/mL). Most (75%) participants reported enjoying use of the product "a lot" or greater and more than half (62.5%) reported reduced cigarette cravings. Most participants reported no side effects after use; however, two experienced dry mouth, three experienced dizziness, one experienced throat irritation, and one experienced headache. CONCLUSION: We found that directed use (14 puffs) of menthol IQOS delivered a mean nicotine boost of 15.96 ng/mL which reduced craving for a cigarette. The majority of participants enjoyed use of IQOS and reported mild side effects. IMPLICATIONS: Menthol IQOS delivered a sufficient dose of nicotine perceived as satisfying by menthol cigarette smokers and it reduced craving with mild side effects. Menthol IQOS has potential to serve as a less harmful alternative for menthol cigarette smokers. The availability of modified risk products like IQOS should be considered by FDA's Comprehensive Plan for Tobacco and Nicotine Regulation.

The effects of reduced nicotine content cigarettes on biomarkers of nicotine and toxicant exposure, smoking behavior and psychiatric symptoms in smokers with mood or anxiety disorders: A double-blind randomized trial.

BACKGROUND: The U.S. Food and Drug Administration and the government of New Zealand have proposed a reduction of the nicotine content in cigarettes to very low levels. This study examined the potential effects of this regulation in smokers with affective disorders. METHODS: In a randomized controlled parallel group trial conducted at two sites in the USA (Penn State University, Hershey, PA and Massachusetts General Hospital, Boston, MA) 188 adult smokers with a current (n = 118) or lifetime (n = 70) anxiety or unipolar mood disorder, not planning to quit in the next 6 months, were randomly assigned (1:1) to smoke either Usual Nicotine Content (UNC) (11.6 mg nicotine/cigarette) research cigarettes, or Reduced Nicotine Content (RNC) research cigarettes where the nicotine content per cigarette was progressively reduced to 0.2 mg in five steps over 18 weeks. Participants were then offered the choice to either receive assistance to quit smoking, receive free research cigarettes, or resume using their own cigarette brand during a 12-week follow-up period. Main outcomes were biomarkers of nicotine and toxicant exposure, smoking behavior and dependence and severity of psychiatric symptoms. The pre-registered primary outcome was plasma cotinine. RESULTS: A total of 143 (76.1%) randomized participants completed the randomized phase of the trial, 69 (73.4%) in the RNC group and 74 (78.8%) in the UNC group. After switching to the lowest nicotine content cigarettes, compared to smokers in the UNC group, at the last randomized visit the RNC group had significantly lower plasma cotinine (metabolite of nicotine): difference between groups, -175.7, 95% CI [-218.3, -133.1] ng/ml. Urine NNAL (metabolite of NNK, a lung carcinogen), exhaled carbon-monoxide, cigarette consumption, and cigarette dependence were also significantly lower in the RNC group than the UNC group. No between-group differences were found on a range of other biomarkers (e.g. 8-isoprostanes) or health indicators (e.g. blood pressure), or on 5 different psychiatric questionnaires, including the Kessler K6 measure of psychological distress. At the end of the subsequent 12-week treatment choice phase, those randomized to the RNC group were more likely to have quit smoking, based on initial intent-to-treat sample, n = 188 (18.1% RNC v 4.3% UNC, p = 0.004). CONCLUSION: Reducing nicotine content in cigarettes to very low levels reduces some toxicant exposures and cigarette addiction and increases smoking cessation in smokers with mood and/or anxiety disorders, without worsening mental health. TRIAL REGISTRATION: TRN: NCT01928758, registered August 21, 2013.

Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial.

INTRODUCTION: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute. METHODS: This four-arm parallel-group, randomized, placebo-controlled trial took place at two academic medical centers in the United States (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N = 520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8, or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization. RESULTS: At 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI = 1.9-104.9] and 3.5 [95% CI = 1.2-10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130). CONCLUSIONS: When smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute. IMPLICATIONS: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.

The role played by health resistance, coping response, and smoke damage perceptions in smoking threat appeal campaigns.

Threat appeal campaigns have been widely used to induce people to change their bad smoking habits by adopting a better approach in favor of a healthier lifestyle. Social marketers who create this kind of messages tend to believe in the persuasive power of fear arousal. For most people, fear has an important consequence on behavior, leading them to search for means of deleting or coping with the unhealthy behavior. As demonstrated by the Ordered Protection Motivation Model, individual differences such as health resistance play an important role in determining, or not, a change of behavior when faced with the threat. This study explores the relationship between health resistance and attitude towards smoking behavior and examines the mediating impact of coping response and smoke damage perception in a sample of 260 university students, smokers and non-smokers. Results highlight that health resistance has an important direct effect on smoking attitude, but, it seems to be mitigated by the smoke severity of the damage shown in graphic images. The comparison between smokers and nonsmokers allowed us to understand the role of reactance in these two groups, and the significance that anti-smoking campaigns assume. Our results offer important suggestions for future decisions about social threat appeals campaigns.

Measurement of Electronic Cigarette Frequency of Use Among Smokers Participating in a Randomized Controlled Trial.

BACKGROUND: The United States Food and Drug Administration has prioritized understanding the dependence potential of electronic cigarettes (e-cigs). Dependence is often estimated in part by examining frequency of use; however measures of e-cig use are not well developed because of varying product types. This study used an e-cig automatic puff counter to evaluate the value of self-reported e-cig use measures in predicting actual use (puffs). METHODS: Data were collected from a two-site randomized placebo-controlled trial evaluating the effects of e-cigs on toxicant exposure in smokers attempting to reduce their cigarette consumption. Participants randomized to an e-cig condition self-reported their e-cig frequency of use (times per day-one "time" consists of around 15 puffs or lasts around 10 minutes) on the Penn State Electronic Cigarette Dependence Index (PSECDI) and kept daily diary records of the number of puffs per day from the e-cig automatic puff counter. A linear mixed-effects model was used to determine the predictive value of the times per day measure. Correlations were used to further investigate the relationship. RESULTS: A total of 259 participants with 1165 observations of e-cig use were analyzed. Self-reported e-cig use in times per day was a significant predictor of e-cig puffs per day (p < .01). The Spearman correlation between measures was r equal to .58. Examination of individual participant responses revealed some potential difficulties reporting and interpreting times per day because of the difference in use patterns between cigarettes and e-cigs. CONCLUSION: This study provides evidence that the self-reported PSECDI measure of times per day is a significant predictor of actual frequency of e-cig puffs taken. IMPLICATIONS: Self-reported measures of e-cig frequency of use are predictive of actual use, but quantifying e-cig use in patterns similar to cigarettes is problematic.

Changes in E-Cigarette Use Behaviors and Dependence in Long-term E-Cigarette Users.

INTRODUCTION: Little is known about the effects of long-term e-cigarette use, particularly the risks of relapse to cigarette smoking or increased dependence. METHODS: In a 2012-2014 baseline online e-cigarette survey, 1,863 respondents consented to participate in future research. A follow-up online survey was conducted in 2017-2018 to assess changes in e-cigarette use behaviors and e-cigarette-related dependence. For both surveys, exclusive e-cigarette use was defined as only using e-cigarettes in the past 7 days, and poly use was defined as using both e-cigarettes and other tobacco or nicotine products in the past 7 days. The Penn State Electronic Cigarette Dependence Index (PSECDI) score was calculated for each study subject and was used to evaluate e-cigarette dependence. Paired t-tests or Pearson correlation coefficients were used to examine changes in e-cigarette use behaviors or PSECDI scores between baseline and follow-up. Baseline and follow-up survey data were analyzed in January 2019. RESULTS: A total of 494 subjects provided complete data on both surveys. At baseline, 402 subjects (81.4%) were exclusive e-cigarette users, and 71 subjects (14.4%) were poly users. Among baseline exclusive e-cigarette users, the majority (88.3%) continued using e-cigarettes exclusively, but 37 users (9.2%) became poly users and 1 returned to cigarette smoking at follow-up. Among baseline poly users, 60.6% became exclusive e-cigarette users at follow-up. The mean PSECDI score remained similar over time (8.4 at baseline vs 8.3 at follow-up). CONCLUSIONS: Findings suggest that the risk of relapse to cigarette smoking is low, and e-cigarette-related dependence remains stable in long-term e-cigarette users.

Nicotine absorption during electronic cigarette use among regular users.

BACKGROUND: The capability of electronic cigarette devices (e-cigs) to deliver nicotine is key to their potential to replace combustible cigarettes. We compared nicotine delivery and subjective effects associated with the use of two classes of e-cigarettes and cigarettes. METHODS: 14 e-cigarette users were instructed to vape their own e-cigarette device every 20 seconds for 10 minutes while blood was drawn at 1, 2, 4, 6, 8, 10,12, and 15 minutes after initiating vaping. Users rated withdrawal symptoms and side effects before and after vaping. E-cigarette devices were classified as first-generation (same size as cigarette, no activation button) or advanced (larger than cigarette with an activation button). Separately, 10 cigarette smokers completed a similar protocol. Fisher's Exact Test and two-sided t-tests were used as appropriate to determine differences in outcomes between first-generation e-cigarette users, advanced e-cigarette users, and smokers. RESULTS: Compared to first-generation devices, advanced devices were associated with greater serum nicotine Cmax (ng/ml) (11.5 v. 2.8, p = 0.0231) and greater nicotine boost (ng/ml) (10.8 v. 1.8, p = 0.0177). Overall, e-cigarettes users experienced a significant reduction in withdrawal and craving, although there were no significant differences between users of first-generation and advanced devices. Comparing e-cigarettes overall to cigarettes, cigarettes were associated with greater Cmax (25.9 v. 9.0, p = 0.0043) and greater nicotine boost (21.0 v. 8.2, p = 0.0128). CONCLUSIONS: Advanced e-cigarettes delivered significantly more nicotine than first-generation devices but less than combustible cigarettes. Overall, e-cigarette use was associated with a reduction in withdrawal and craving with no reported side effects. The wide variation in nicotine absorption from different e-cigarette devices should be considered in studies of e-cigarettes for smoking cessation.

Effect of Cigarette Rod Length on Smokers Switching to SPECTRUM Cigarettes.

Objectives: Cigarettes vary in rod length but are generally thought of as a constant unit. In this study, we evaluated whether the rod length of participants' usual brand cigarettes affected their perceptions and smoking habits when switching to SPECTRUMs. Methods: Data were analyzed for 341 participants smoking their own brand cigarettes for one week and after switching to normal nicotine content (11.6 mg) SPECTRUMs for 2 weeks. Changes in perceptions of cigarette attributes and biomarkers of smoke exposure were evaluated using linear mixed models among 3 groups: usual length short (ULS, 72 mm); medium/king (ULM, ~84 mm); and long (ULL ≥ 100 mm). Results: Among the 3 cigarette length groups, only ULL smokers' rated SPECTRUMs significantly less strong, harder to draw, lower in taste, and lower in enjoyment (p < .03) compared to usual brand. Among all groups, satisfaction was significantly lower for SPECTRUMs (p < .02). Cigarettes per day (CPD) increased significantly more for ULL (+4.75 CPD) as compared to ULM (+1.38 CPD) (p < .001). When switching to SPECTRUMs, cotinine-per-cigarette decreased among all groups, and exhaled carbon monoxide increased significantly in ULL and ULM smokers (p < .001). Conclusion: People who smoked long cigarettes had the largest changes in perceptions and use when switching to SPECTRUM research cigarettes.

Characteristics of Adult Cigarette Smokers Who "Relight" and the Effects of Exposure to Tobacco Smoke Constituents.

INTRODUCTION: About half of smokers relight their cigarette, a habit that is a risk factor for chronic bronchitis and possibly lung cancer. Little is known about the characteristics of smokers who relight and their dependence on nicotine. It is unknown whether relighting affects exposure to tobacco smoke constituents. This study examined the characteristics of relighters of usual brand cigarettes and whether relighting affects exposure to selected tobacco smoke constituents. METHODS: We explored relighting status and frequency, using baseline data from 248 adult smokers participating in studies of reduced nicotine cigarettes in relation to demographic and cigarette characteristics, smoking behaviors, nicotine dependence, biomarkers of exposure (exhaled carbon monoxide, blood cotinine), and biomarkers of oxidative stress (ratio of oxidized/reduced glutathione). RESULTS: 69.4% (n = 172) of subjects reported relighting, and they relit an average of five cigarettes out of 20. Both relighters and non-relighters smoked a mean of 20 cigarettes per day (p = .6). Relighting was significantly associated with higher nicotine dependence, use of longer rod cigarettes, older age, lower income, and unemployment. There were no significant associations between relighting and blood cotinine, exhaled carbon monoxide or measures of oxidized/reduced blood glutathione. CONCLUSIONS: The majority of subjects were relighters, who had higher levels of nicotine dependence than non-relighters. Relighters had similar levels of plasma cotinine and exhaled carbon monoxide to non-relighters. IMPLICATIONS: No study has compared the cigarette characteristics and biomarkers of exposure of adult cigarette smokers who relight with those who do not. Relighting behavior was common in our sample and was associated with low income, not currently working, higher nicotine dependence, cigarette rod length, daily cigarette use years, and a lifetime history of depressed mood.

Pulmonary and other health effects of electronic cigarette use among adult smokers participating in a randomized controlled smoking reduction trial.

BACKGROUND: There is limited evidence about the effects of dual electronic cigarette (e-cig) and combustible cigarette use on lung health or other health outcomes. Studies that have evaluated these outcomes have not included estimates of e-cig or cigarette exposure in the analyses. MATERIALS AND METHODS: Data analyzed were from 263 smokers participating in a randomized controlled trial designed to encourage participants to reduce their combustible cigarette use by substituting with an e-cig or a non-electronic cigarette substitute (cig-sub). t-tests were used to evaluate changes from baseline at 1 month and 3 months in lung function, blood pressure, pulse, exhaled carbon monoxide, and weight. Linear mixed effects models were used to test associations between health outcomes and study product group, including exposure to the study products (e-cig and cig-sub times used and days used in the past 7 days) and cigarettes per day (CPD). RESULTS: There were few significant differences between the groups for lung function indices at any time point in the unadjusted analyses. There were significant reductions in diastolic blood pressure and pulse at 1 month in the unadjusted analyses for those in the e-cig group compared to the cig-sub group. CPD decreased significantly more for the e-cig group than for the cig-sub group at both time points. There were no significant associations between any measured health outcomes and group in the linear mixed effects models. CONCLUSION: E-cig use did not contribute to significant changes in health outcome markers as compared with use of a non-electronic cig-sub.

Pilot Randomized Trial of an Automated Smoking Cessation Intervention via Mobile Phone Text Messages as an Adjunct to Varenicline in Primary Care.

OBJECTIVE: Varenicline is a safe and effective aid to smoking cessation but most trials have involved frequent visits or intensive behavioral support unlike that typically provided in primary care. The current study examined if motivational text messages, sent via cellphone, would increase quit rates in smokers being treated with varenicline and 3 brief sessions in a family practice setting. METHODS: This study was a randomized controlled, parallel-group smoking cessation trial. Intervention group participants (n = 74) received daily motivational text messages, additional texted tips in response to keywords, and weekly study questions while control group participants (n = 76) received only weekly study questions. Both groups received individualized counseling. Self-reported non-smoking and exhaled breath CO <10ppm were used to validate smoking abstinence at 3 weeks and 12 weeks. RESULTS: Overall, 30.7% (46/150) of participants were abstinent at the 12 week follow-up and the abstinence rate did not differ between groups (INT 31.1% v. CON 30.3%, p = .91). The only predictor of abstinence at 12 weeks was use of varenicline during a previous quit attempt (p = .01). Intervention group participants were more likely to rate the text messaging program as good or excellent (p < .01), to recommend a similar program to family or friends (p < .01), and to complete positive smoking cessation activities (p = .04), when compared with the control group. CONCLUSION: Although there were no differences in quit rates between the intervention and control group, intervention group participants rated the text messaging system more favorably, were more likely to recommend the program to others, and were more likely to complete positive smoking cessation activities.

Tobacco Use Among Middle and High School Students in Pennsylvania.

We analyzed data from the 2014-2015 Pennsylvania Youth Tobacco Survey to determine prevalence of tobacco use among middle and high school students. For the first time, questions on current (past 30-day) use of electronic cigarettes (e-cigarettes) were included in the survey. For current use, e-cigarettes were the most commonly used tobacco product among middle school students (2.3%; 95% confidence interval [CI], 1.4%-3.2%), and cigarettes were the most commonly used tobacco product among high school students (11.0%; 95% CI, 8.1%-13.8%). Given the changing landscape of tobacco products, collection of comprehensive data on tobacco use, including frequency, is important for monitoring behaviors among adolescents.

Acceptability of SPECTRUM Research Cigarettes among Participants in Trials of Reduced Nicotine Content Cigarettes.

OBJECTIVES: SPECTRUM research cigarettes (SPECTRUMs) are being used in trials evaluating the effects of switching to reduced nicotine content (RNC) cigarettes. Because smokers have a high brand affinity, we evaluated if they were willing to switch and continue smoking normal nicotine content (NNC) SPECTRUMs. METHODS: We asked smokers (N = 341) to rate their own brand of cigarettes and NNC SPECTRUMs (after 2 weeks of use) using subjective measures including satisfaction, reward, taste, and craving reduction. We measured plasma cotinine, exhaled carbon monoxide (CO), and cigarettes per day (CPD), and recorded reasons for dropping out. RESULTS: After 2 weeks, 95% of participants chose to continue using SPECTRUMs for an additional 18 weeks. Moreover, 67% said SPECTRUMs were as good as or better than their own brand, and 65% said they would consider purchasing them. Ratings of satisfaction, reward, and craving reduction were 10%-15% lower on SPECTRUMs than on their own brand (p < .01). There were no differences in these ratings between menthol and non-menthol smokers. CONCLUSIONS: Menthol and non-menthol SPECTRUMs are acceptable to smokers. Lower SPECTRUM ratings were likely due to brand switching and did not hinder study retention.

The Use of Self-Directed Relapse Prevention Booklets to Assist in Maintaining Abstinence After a 6-Week Group Smoking Cessation Treatment Program: A Randomized Controlled Trial.

BACKGROUND: Identifying effective relapse prevention interventions is a vital step to help smokers maintain abstinence for the long term. AIMS: The purpose of this study is to determine if providing recently quit smokers with self-directed relapse prevention booklets is effective at maintaining abstinence after intensive group smoking cessation treatment. METHOD: Two hundred and twenty-five participants were randomized to receive Forever Free (FF) relapse prevention booklets or a control booklet (Surgeon General's report, SG) at the end of a 6-week group treatment program. Participants were then contacted by phone to assess whether they had read the materials. Smoking status was assessed 6 months after their target quit date. Primary analyses focused on the 115 participants who quit at the end of treatment. RESULTS: There was no difference in the 6-month quit rate between groups (40.7% quit FF vs. 44.6% quit SG, p = .67). The FF group read a significantly smaller proportion of the materials versus the control booklet (20.0% read most or all of FF vs. 72.0% of SG, p < .001). CONCLUSION: Forever Free self-directed relapse prevention booklets did not reduce relapse or enhance cessation over general tobacco and health information when added to intensive group smoking cessation treatment. However, this study lacked power to detect a small but clinically meaningful positive effect.

Changes in resting state functional brain connectivity and withdrawal symptoms are associated with acute electronic cigarette use.

Resting state functional brain connectivity (rsFC) may be an important neuromarker of smoking behavior. Prior research has shown, among cigarette smokers, that nicotine administration alters rsFC within frontal and parietal cortices involved in executive control, as well as striatal regions that drive reward processing. These changes in rsFC have been associated with reductions in withdrawal symptom severity. We currently have a limited understanding of how rsFC is affected by the use of electronic cigarettes (ecigs), an increasingly popular class of products, the members of which deliver nicotine with varying effectiveness. The current study used fMRI to determine the effects of ecig use on rsFC and withdrawal symptoms. Independent component, dual regression, and permutation analyses were conducted on rsFC collected from ecig users before and after an ecig use episode (n=9) that occurred after 14h of nicotine abstinence. Similar to the known effects of nicotine administration, ecig use decreased rsFC of two clusters in the right frontal pole and frontal medial cortex with an attentional control salience network, and decreased rsFC of five clusters in the left thalamus, insula, and brain stem with a reward network encompassing the striatum. Ecig use increased inverse coupling between the prefrontal reward network and the right frontoparietal executive control network. Reductions in craving and difficulty with concentration were correlated with decreases in coupling strength between reward and executive control networks. These preliminary results suggest that the effects of ecig use on rsFC are similar to those seen with nicotine administration in other forms. In order to gain insight into the addictive potential of ecigs, further research is needed to understand the neural influence of ecigs across the range of nicotine delivery within this class of products.

Reduced nicotine content cigarettes in smokers of low socioeconomic status: study protocol for a randomized control trial.

BACKGROUND: The Family Smoking Prevention and Tobacco Control Act gave the Food and Drug Administration jurisdiction over the regulation of all tobacco products, including their nicotine content. Under this act, a major strategy to reduce harm from cigarette tobacco is lowering the nicotine content without causing unintended adverse consequences. Initial research on reduced nicotine content (RNC) cigarettes has shown that smokers of these cigarettes gradually decrease their smoking frequency and biomarkers of exposure. The effectiveness of this strategy needs to be demonstrated in different populations whose response to RNC cigarettes might be substantially mediated by personal or environmental factors, such as low socioeconomic status (SES) populations. This study aims to evaluate the response to a reduced nicotine intervention in low SES smokers, as defined here as those with less than 16 years of education, by switching smokers from high nicotine commercial cigarettes to RNC cigarettes. METHODS/DESIGN: Adults (N = 280) who have smoked five cigarettes or more per day for the past year, have not made a quit attempt in the prior month, are not planning to quit, and have less than 16 years of education are recruited into a two-arm, double-blinded randomized controlled trial. First, participants smoke their usual brand of cigarettes for 1 week and SPECTRUM research cigarettes containing a usual amount of nicotine for 2 weeks. During the experimental phase, participants are randomized to continue smoking SPECTRUM research cigarettes that contain either (1) usual nicotine content (UNC) (11.6 mg/cigarette) or (2) RNC (11.6 to 0.2 mg/cigarette) over 18 weeks. During the final phase of the study, all participants are offered the choice to quit smoking with nicotine replacement therapy, continue smoking the research cigarettes, or return to their usual brand of cigarettes. The primary outcomes of the study include retention rates and compliance with using only research cigarettes and no use of other nicotine-containing products. Secondary outcomes are tobacco smoke biomarkers, nicotine dependence measures, smoking topography, stress levels, and adverse health consequences. DISCUSSION: Results from this study will provide information on whether low SES smokers can maintain a course of progressive nicotine reduction without increases in incidence of adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01928719 . Registered on 21 August 2013.

Measurement of exhaled breath carbon monoxide in clinical practice: A study of levels in Central Pennsylvania community members.

BACKGROUND AND PURPOSE: Exhaled breath carbon monoxide (eBCO) reading is a useful tool for nurse practitioners to evaluate smoking status and other exposures to carbon monoxide (CO) to identify risk for cancer and chronic disease. This study aimed to measure one community's eBCO and identify potential environmental factors that may affect eBCO among nonsmokers. METHODS: Data collected by convenience sampling at community health events included self-reported tobacco use and potential CO exposure. Means and frequency calculations describe the sample, two-sided t-tests determine differences in continuous variables, and chi-square tests determine differences in frequencies of CO levels between nontobacco users exposed to additional CO from their environment and nontobacco users who were not. CONCLUSION: As expected, smokers have significantly higher mean eBCO than nonsmokers (20.1 ppm vs. 4.4 ppm, p < .001). The self-reported nonsmokers (16.2%) had an elevated eBCO (>6 ppm), although there were no environmental factors that explained a higher eBCO. IMPLICATIONS FOR PRACTICE: Measuring eBCO provides an opportunity for the nurse practitioner to engage in a conversation about the impact of smoking and other environmental factors that contribute to eBCO and health. Keeping record of patients' smoking status and eBCO in their medical record is a valuable measure of the nurse practitioner's delivery of this care.

A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol.

BACKGROUND: The U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT) in four phases over 34 weeks. METHODS: Adult smokers (N = 200) of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General). Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg). After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a) Usual Nicotine Content (11.6 mg); or (b) Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a) quit smoking with assistance, (b) continue smoking free research cigarettes, or (c) return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 1-hydroxypyrene, oxidative stress biomarkers including 8-isoprostanes, measures of psychiatric symptoms (e.g., depression, anxiety), smoking behavior and dependence (e.g., cigarette consumption, quit attempts), and health effects (e.g., blood pressure, respiratory symptoms). DISCUSSION: Results from this study will inform FDA on the potential effects of regulating the nicotine content of cigarettes and help determine whether smokers with mood and/or anxiety disorders can safely transition to significantly reduced nicotine content cigarettes. TRIAL REGISTRATION: TRN: NCT01928758 , registered August 21, 2013.