Nicolle M. Krebs

Estimation of compliance with exclusive smoking of very low nicotine content cigarettes using plasma cotinine.

Regulations requiring a reduction of the nicotine content in cigarettes to minimally addictive levels could significantly reduce the public health impact of cigarette smoking. Clinical trials evaluating this strategy are ongoing and methods have been developed to use nicotine biomarkers to estimate compliance with use of very low nicotine content cigarettes (VLNCs). To date, these methods have not considered the potential contribution of nicotine absorption from environmental tobacco smoke (ETS) among research participants. This study used data from 100 randomly selected study completers in ongoing clinical trials of VLNCs (50 randomized to Usual Nicotine Content Cigarettes (UNCs) and 50 to VLNCs) to assess the use of plasma cotinine to estimate compliance. Plasma cotinine and smoking behavior were recorded at baseline after 2 weeks smoking UNC cigarettes, and then after 18 weeks of either continuing smoking UNCs or reducing the nicotine content such that the last 6 weeks comprised smoking VLNCs. Plasma cotinine remained stable (267 ng/ml) in the UNC group but reduced to 93 ng/ml in the VLNC group (p < 0.01). Compliance with smoking VLNCs was first estimated by comparing the cotinine per cigarette on VLNCs with UNCs after allowing for potential compensatory smoking. We found that 29 (58%) of the VLNC group were compliant. Adjusting for potential ETS exposure estimated 32 (64%) to be compliant. This latter group (n = 32) had a mean plasma cotinine on VLNCs of 7 ng/ml (range = 3-16.4 ng/ml). Adjusting for potential ETS exposure may improve identification of participants who plausibly complied with exclusive VLNC use.

Differences in nicotine dependence, smoke exposure and consumer characteristics between smokers of machine-injected roll-your-own cigarettes and factory-made cigarettes

BACKGROUND Consumption of machine-injected roll-your-own (RYO) filtered cigarettes made from pipe tobacco increased almost 7-fold from 2008 to 2011 in the United States. METHODS We used data from the Pennsylvania Adult Smoking Study to compare the differences in sociodemographic, smoking topography, nicotine dependence, and cotinine levels between 280 smokers using factory made (FM) cigarettes and 68 smokers using RYO cigarettes. RESULTS RYO smokers were older (41 vs. 37, P = 0.053), had significantly lower levels of income (P < 0.001) and education (P = 0.007), and were less likely to be fully employed (P = 0.009). RYO smokers consumed more cigarettes per day [CPD] (21 vs. 15, P < 0.001), and had a higher mean score on the Fagerström Test for Cigarette/Nicotine Dependence (5.2 vs. 4.1, P < 0.001). The main reasons for choosing RYO cigarettes were the lower cost (68%) and believed they are less harmful (12%). The average cost per pack of FM cigarettes was

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

5.74 vs.

Characteristics of Adult Cigarette Smokers Who “Relight” and the Effects of Exposure to Tobacco Smoke Constituents

1.13 for RYO. In multiple regression analyses, RYO smokers had significantly lower cotinine levels across all levels of CPD. Among smokers of king-size cigarettes, mean interpuff interval (P < 0.05) and total smoke duration (P < 0.01) per cigarette was significantly greater in RYO smokers. In laboratory measurements, RYO cigarettes contained more tobacco by weight than FM cigarettes, but weight varied by both tobacco and cigarette tube brands. CONCLUSIONS Machine-injected RYO cigarettes made from pipe tobacco are cheaper than FM cigarettes but may have higher abuse liability. Smokers who might otherwise reduce their cigarette consumption or quit altogether may continue to smoke RYO cigarettes due to their affordability.

Clinical trial recruitment of adult African American smokers from economically disadvantaged urban communities

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.

Cigarette Management System: An operating procedures guide to obtaining and managing investigational tobacco products for regulatory science research

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 5 cigarettes out of 20. Both relighters and non-relighters smoked a mean of 20 CPD (p=0.6). 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.

Ecological momentary assessment of smoking behaviors in native and converted intermittent smokers: Ecological Momentary Assessment and Intermittent Smokers

Abstract This investigation evaluated the effectiveness and challenges of multiple recruitment methods, described as proactive, reactive, and combination methods, among adult African American smokers (N = 527) from economically disadvantaged urban communities enrolled to test progressively reduced nicotine content investigational cigarettes. The study evaluated success using descriptive statistics to measure the volume of phone calls and percentage of eligible participants per method. Reactive and combination strategies effectively prompted participants to call about the study. Combination methods yielded the highest eligibility rates. Findings demonstrate the unique recruitment successes within this population across a range of recruitment methods and may inform improved methods to recruit and engage African Americans in clinical trials.

Income as a moderator of psychological stress and nicotine dependence among adult smokers

Investigational tobacco products, specifically variable nicotine content research cigarettes (SPECTRUM), are available through the National Institute of Drug Abuse Drug Supply Program. Randomized controlled trials using research cigarettes are intended to support tobacco regulatory science research. The current paper provides an in-depth look into managing research cigarettes for two multi-site clinical trials and the design of a computer-based Cigarette Management System (CMS). The paper provides guidance intended for any investigator using similar products on the operating procedures under Good Clinical Practice standards and describes features of the CMS. The CMS and procedures described have been field tested for the past three years and have dispensed over 160,000 cigarette packs to participants. The CMS can accommodate a range of practical issues with real-world study implementation making it a robust application that is scalable to any study.

Comparison of Puff Volume With Cigarettes per Day in Predicting Nicotine Uptake Among Daily Smokers

BACKGROUND AND OBJECTIVES About 22% of adult smokers in the U.S. are intermittent cigarette smokers (ITS). ITS can be further classified as native ITS who never smoked daily and converted ITS who formerly smoked daily but reduced to intermittent smoking. Ecological momentary assessment (EMA) was conducted to determine the behaviors and experiences that are associated with the decision to smoke. METHODS The study included 24 native ITS and 36 converted ITS (N = 60) from the Pennsylvania Adult Smoking Study. A baseline questionnaire, daily log, and an EMA smoking log that assessed emotions, activities, and smoking urges was filled out with each cigarette for 1 week to capture 574 smoking sessions. RESULTS Both groups had very low levels of cigarette dependence. Both groups were more tempted to smoke in positive or negative situations than situations associated with habituation. EMA showed that the most common emotional state during smoking sessions was positive (47%), followed by negative (32%), neutral (16%), and mixed (5%) emotions. Smokers were more likely to smoke during activities of leisure (48%) than during performative duties (29%), social (16%) or interactive occasions (7%). Converted ITS were more likely to smoke alone compared to native ITS (p < .001). DISCUSSION AND CONCLUSIONS ITS report minimal levels of dependence when captured on traditional scales of nicotine dependence, yet experience loss of autonomy and difficulty quitting. The majority of the ITS reported positive emotions and leisure activities while smoking, and smoked during the evening. SCIENTIFIC SIGNIFICANCE The current paper identifies environmental and behavioral factors that are associated with smoking among ITS in real time. (Am J Addict 2018;27:131-138).

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 Perceived stress and psychological distress are associated with more cigarette craving and withdrawal, higher nicotine dependence, and less success during quit attempts. Low income smokers have disproportionately higher rates of smoking and may be particularly vulnerable to the effects of stress on smoking dependence. The aim of the current study was to assess if lower income smokers have a stronger association between stress and nicotine dependence than higher income smokers. METHODS Data were obtained from the Pennsylvania Adult Smoking Study, which included 351 daily smokers. Subjects completed PhenX Toolkit and other self-report measures of socioeconomic factors, the 10-item Perceived Stress Scale, Kessler Psychological Distress Scale (K6), Fagerstrom Test for Nicotine Dependence (FTND), and the Hooked on Nicotine Checklist (HONC). Moderation analyses using linear regression examined income-related differences in the association between stress and nicotine dependence. RESULTS Income groups were categorized by an annual household income of