Puff-by-puff sensory evaluation of a low to middle tar medium nicotine cigarette designed to maintain nicotine delivery to the smoker

Puff-by-puff assessments of a range of sensory and subjective attributes were made for three cigarettes, with tar and nicotine yields of: 10.0 and 1.4; 17.0 and 1.7; and 8.8 and 0.8 mg/cigarette, respectively. Seven attributes were assessed: mouth impact, throat impact, chest effect, roughness, intensity of flavour, satisfaction and quality of flavour. Significant differences between the three cigarettes were obtained for most of these attributes. Principal component analysis of the data revealed three principal components related to the cigarettes under investigation. Components 1 and 2 accounted for approximately 47 and 28% of the total variance and component 3 only added a further 7%. Principal component 1 was a complex combination of intensity-related characteristics, i.e. mouth and throat impact, chest effect, intensity of flavour, roughness, while quality of flavour and satisfaction contributed to the separation of samples on principal component 2. However, the two major components could not be defined simply in terms of the yields of tar and nicotine for the products determined on a smoking machine.     

The influence of changing nicotine to tar ratios on human puffing behaviour and perceived sensory response

Rationale Smokers modify their smoking behaviour when switching from their usual product to higher or lower tar and nicotine-yield cigarettes.Objective The aims of the current study were to assess the influence of varying nicotine yields at constant tar yield on human puffing measures, nicotine deliveries under human smoking conditions and the sensory response to mainstream cigarette smoke. These assessments would allow an evaluation of the degree of compensation and the various possible causes of changes, if any.Methods The participants were 13 regular smokers of commercial or hand-rolled cigarettes. They were tested with four cigarettes, which exhibited a wide range of nicotine to 'tar' ratios at a relatively constant 'tar' yield. Their smoking behaviour was monitored by placing the test cigarettes into an orifice-type holder/flowmeter attached to a custom-built smoker behaviour analyser. In addition, a comprehensive sensory evaluation of the products was carried out.Results The differences in the nicotine to tar ratios of the samples did not significantly influence the puffing behaviour patterns, i.e. puff number and interval, total and average puff volume, integrated pressure and puff duration. Additionally the pre- to post-exhaled CO boosts were not significantly influenced by the experimental samples used in the study. However, the nicotine yields obtained by the smokers were significantly influenced by the machine-smoked nicotine yields or the nicotine to tar ratios of the samples. The machine-smoked nicotine yields were highly correlated with the nicotine yields obtained under human smoking conditions. For the sensory evaluation, there was only a significant difference between the samples in the intensity of the impact.Conclusion These observations imply that these puffing variables are not controlled by the nicotine yield of the cigarette.     

Relationship between cigarette format and mouth-level exposure to tar and nicotine in smokers of Russian king-size cigarettes

Differences in length and circumference of cigarettes may influence smoker behaviour and exposure to smoke constituents. Superslim king-size (KSSS) cigarettes (17 mm circumference versus 25 mm circumference of conventional king-size [KS] cigarettes), have gained popularity in several countries, including Russia. Some smoke constituents are lower in machine-smoked KSSS versus KS cigarettes, but few data exist on actual exposure in smokers. We investigated mouth-level exposure (MLE) to tar and nicotine in Russian smokers of KSSS versus KS cigarettes and measured smoke constituents under machine-smoking conditions. MLE to tar was similar for smokers of 1 mg ISO tar yield products, but lower for smokers of 4 mg and 7 mg KSSS versus KS cigarettes. MLE to nicotine was lower in smokers of 4 mg KSSS versus KS cigarettes, but not for other tar bands. No gender differences were observed for nicotine or tar MLE. Under International Organization for Standardization, Health Canada Intense and Massachusetts regimes, KSSS cigarettes tended to yield less carbon monoxide, acetaldehyde, nitric oxide, acrylonitrile, benzene, 1,3-butadiene and tobacco-specific nitrosamines, but more formaldehyde, than KS cigarettes. In summary, differences in MLE were observed between cigarette formats, but not systematically across pack tar bands.     

Lack of effect of menthol level and type on smokers’ estimated mouth level exposures to tar and nicotine and perceived sensory characteristics of cigarette smoke

Menthol can reduce sensory irritation and it has been hypothesised that this could result in smokers of mentholated cigarettes taking larger puffs and deeper post-puff inhalations thereby obtaining higher exposures to smoke constituents than smokers of non-mentholated cigarettes. The aim of our study was to use part-filter analysis methodology to assess the effects of cigarette menthol loading on regular and occasional smokers of mentholated cigarettes. We measured mouth level exposure to tar and nicotine and investigated the effects of mentholation on smokers’ sensory perceptions such as cooling and irritation. Test cigarettes were produced containing no menthol and different loadings of synthetic and natural l-menthol at 1 and 4 mg ISO tar yields. A target of 100 smokers of menthol cigarettes and 100 smokers who predominantly smoked non-menthol cigarettes from both 1 and 4 mg ISO tar yield categories were recruited in Poland and Japan. Each subject was required to smoke the test cigarette types of their usual ISO tar yield. There were positive relationships between menthol loading and the perceived ‘strength of menthol taste’ and ‘cooling’ effect. However, we did not see marked menthol-induced reductions in perceived irritation or menthol-induced increases in mouth level exposure to tar and nicotine.     

Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm

Rationale Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated.Objective This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = denicotinized) cigarettes.Methods In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette.Results The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices.Conclusions These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies.     

Free-base nicotine in tobacco products. Part I. Determination of free-base nicotine in the particulate phase of mainstream cigarette smoke and the relevance of these findings to product design parameters

The free-base nicotine (FBN) content of mainstream cigarette smoke (MSS) has been discussed in the peer-reviewed literature and popular press. It has been alleged that manufacturers adjust product design features to increase the percentage of total nicotine (TN) in the MSS gas–vapor phase that is unprotonated [P_g,nic(%)] and/or the fraction of nicotine in the MSS total particulate matter (TPM) that is unprotonated (FBN/TN). Our research showed the Health Canada Intensive smoking conditions negated the effects of blend and cigarette design features reported to raise the pH of TPM collected under ISO or US FTC conditions. Our research also showed that when additive-free Canadian cigarettes were smoked under ISO conditions, the FBN/TN ratio increased as the tar/nicotine ratio decreased. Our findings are in line with other studies that have questioned allegations of a relationship between use of ammonia and its compounds as tobacco additives and amounts of unprotonated nicotine in MSS. In addition, the experimental work demonstrated how use of solid-phase microextraction to estimate FBN can yield erroneously high results due to improper conditioning and/or smoking of the cigarettes. Our research showed that there is no longer any scientific support for regulators to require smoke pH and FBN determinations on cigarette products.     

The effect of a nicotine patch on cigarette craving over the course of the day: results from two randomized clinical trials

ABSTRACT

Objectives: The objective of this analysis was to assess the efficacy of a 21?mg/24-h nicotine patch for the reduction of craving throughout the waking day, compared both to placebo, and to a 15?mg/16-h patch differing pharmacokinetic profile over the day. The primary end-point was craving during the evening hours, because previous research suggested that smoking relapse was particularly likely at that time.

Research design and methods: Data were drawn from two similar randomized clinical trials among nicotine-dependent smokers who were quitting smoking: Study 1 compared the 21?mg/24-h patch to a placebo patch, while Study 2 compared the 21?mg/24-h patch to a 15?mg/16-h nicotine patch. In both studies, subjects (Study 1: n?=?102; Study 2: n?=?244) were prompted by an electronic diary to rate their craving multiple times per day during a 1?week baseline period, and for up to 2?weeks after quitting. For analysis, the day was divided into five blocks: morning (up to 10:59 a.m.), mid-day (11:00 a.m.–1:59 p.m.), afternoon (2:00 p.m.–4:59 p.m.), evening (5:00 p.m.–8:59 p.m.), and late night (9:00 p.m. onwards). The individual craving ratings were divided into three intervals based on time since quitting: Days 1–3, 4–7, and 8–14.

Results: The 21?mg/24-h nicotine patch resulted in significantly lower craving during all post-quit intervals, at each time of day, both compared to placebo (Study 1), and compared to the 15?mg/16-h nicotine patch (Study 2). Study 2 saw a significant treatment by interval interaction: in later time intervals, the difference in craving experience between 24- and 16-h patch conditions shrunk – while remaining significantly different – as overall levels of craving experienced by subjects in the two groups dropped. Adverse events reported in both studies tended to be mild and transient, consistent with the well characterized adverse event profile of nicotine patches.

Conclusions: Study 1 demonstrated that a 21?mg/24-h patch was effective in reducing craving throughout the day, including the evening period when relapse risk is heightened. A further study comparing the 21?mg/24-h patch to a 15?mg/16-h nicotine patch found that craving was significantly lower at all times of day for smokers using the 21?mg/24-h patch. The studies were limited in that craving was only monitored for the first 2?weeks of quitting (when craving is most prominent), and cannot elucidate the impact of patch use on craving outside of this time. Also, there was substantial attrition of the sample over time, partly due to relapse in all conditions.     

The relationship between smoking machine derived tar yields and biomarkers of exposure in adult cigarette smokers in the US

Comprehensive data on human exposure to smoke constituents from different machine-measured tar yield cigarettes is limited. Methods: This study used a stratified, cross-sectional, multi-center design to estimate biomarkers of exposure (BOE) from nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene, CO, acrolein, and 1,3-butadiene and their relationship to tar yield categories of cigarette in adult smokers in the U.S. 3625 adults smokers were enrolled into four tar categories 2.9 mg (T1), 3.0–6.9 mg (T2), 7.0–12.9 mg (T3), and 13.0 mg (T4). Biomarkers were measured in blood (carboxyhemoglobin, 4-aminobiphenyl-hemoglobin (4-ABP-Hb)-adducts, serum cotinine) and 24 h urine (nicotine and five metabolites, calculated as nicotine equivalents (NE), NNAL, 1-OH-pyrene, 3-HPMA, MHBMA and DHBMA). Data were analyzed using analysis of covariance (ANCOVA). Results: Tar was a significant factor for most biomarkers in the ANCOVA models. The largest least square mean differences between tar categories was 35% for NE per day, 28% for NE per cigarette, 36% for serum cotinine, 42% for NNAL per day, 29% for NNAL per cigarette, 26% for 1-OHP, 24% for COHb, 14% for 3-HPMA and 40% for 4-ABP-Hb. Variability in BOE ranged from 41% to 154% CV. Conclusions: There was a statistically significant effect of machine-measured tar yield on most BOE, which were generally lower with lower tar yield.     

Evaluation of the mood and physical symptoms scale (MPSS) to assess cigarette withdrawal

Rationale The mood and physical symptoms scale (MPSS) was developed in the early 1980s to assess cigarette withdrawal symptoms, and variants of it have been used for 20 years. To date, no paper has been published on the properties of the scale.Objectives To evaluate psychometric properties of MPSS and the interrelationship between the key tobacco withdrawal symptoms.Methods The core elements of the MPSS involve 5-point ratings of depressed mood, irritability, restlessness, difficulty concentrating and hunger and 6-point ratings of strength of urges to smoke and time spent with these urges. The data set chosen for analysis was well suited to the task in that it involved a relatively large sample, abstinence was defined as not a puff for 24 h biochemically verified, participants were not using any medication that would have reduced withdrawal discomfort (e.g. nicotine patch), the abstinence rate was very high resulting in minimal bias due to attrition, and ratings were provided on three occasions prior to abstinence. The study involved 111 smokers setting a target quit date of whom 106 attempted abstinence and 96 achieved it.Results The MPSS items were stable prior to abstinence and sensitive to abstinence. Post-abstinence increases in mood and physical symptoms demonstrated a high level of internal coherence. Ratings of urges to smoke correlated highly with changes in mood and other symptoms. Ratings of hunger correlated less well with the scale as a whole and may involve some distinct processes.Conclusions The MPSS meets the key requirements of a cigarette withdrawal scale. Although urge to smoke/craving was not included in the list of DSM-IV withdrawal symptoms, it should be regarded as forming part of the withdrawal syndrome.     

Effects of instructions on responses to the nicotine patch: a laboratory study

Rationale Smokers have weak positive expectancies for nicotine replacement therapies relative to smoking (Juliano and Brandon, Nicotine Tob Res, 6:569–574, 2004). Objectives This study investigated if a manipulation designed to alter expectancies for the nicotine patch was effective in increasing positive expectancies for the patch and influencing smoking cessation outcomes during a 2-day abstinence period. Materials and methods Smokers (n = 72) were randomly assigned to receive information that emphasized either patch benefits (n = 25) or standard patch information including side effects (n = 25). Participants wore placebo patches but were told that the patches contained nicotine. A control condition (n = 22) was informed that they received placebo patches while given standard patch information to independently test the effect of the nicotine-dose instructional set on abstinence outcomes. Results Benefits information significantly increased positive expectancies for the patch and promoted positive mood during the abstinence period relative to the side effects information. Nicotine-dose instructions resulted in fewer lapsed cigarettes and higher ratings of patch helpfulness than placebo instructions. In particular, women’s smoking behavior appeared to be more influenced by nicotine instructions than that of men. Conclusions The results of this preliminary study suggest that information provided to smokers about patch effects and nicotine content may influence behavioral and subjective outcomes of patch use.     

Evaluation of the information processing and mood effects of a transdermal nicotine patch

 The purpose of this study was to determine whether a transdermal nicotine patch will produce the same effects on performance and mood as cigarette smoking. The nicotine patch improved attentional processing and produced some improvements in memory. It produced the calming effects of smoking and induced feelings of happiness which were increased with smoking. These effects were obtained 6 h after application of the patch, showing that acute tolerance for these behavioural effects had not developed completely, if at all, after exposure to nicotine, although it is still possible that tolerance might occur with longer exposure. Received: 16 June 1997/Final version: 1 August 1997     

A computerized exposure system for animal models to optimize nicotine delivery into the brain through inhalation of electronic cigarette vapors or cigarette smoke

Pre-clinical studies investigated the effects of chronic exposure to nicotine on lungs, kidneys and brains using animal models. Most of these studies delivered nicotine into the circulatory and central nervous systems (CNS) through intraperitoneal injection or oral consumption methods. Few studies used inhalation machine system for nicotine delivery into brains in rodents to mimic human exposure to cigarettes. However, finding a more accurate and clinically relevant method of nicotine delivery is critical. A computerized inhalation machine has been designed (SciReq) and is currently employed in several institutions. The computerized machine delivers electronic (e)-cigarette vapor as well as tobacco smoke to rodents using marketed e-cigarette devices or tobacco cigarettes. This provides evidence about clinical effects of nicotine delivery by traditional methods (combustible cigarettes) and new methodologies (e-cigarettes) in physiological systems. Potential neurobiological mechanisms for the development of nicotine dependence have been determined recently in mice exposed to e-cigarette vapors in our laboratory using SciReq system. In this review article, the discussion focuses on the efficiency and practical applicability of using this computerized inhalation exposure system in inducing significant changes in brain protein expression and function as compared to other nicotine delivery methods. The SciReq inhalation system utilized in our laboratory and others is a method of nicotine delivery to the CNS, which has physiological relevance and mimics human inhalant exposures. Translation of the effects of inhaled nicotine on the CNS into clinical settings could provide important health considerations.     

Looking for boomerang effects: a pre-post experimental study of the effects of exposure of youth to television advertising for nicotine replacement therapy and Zyban

In the context of concerns about unintended "boomerang" influences of advertising, this study aimed to examine effects of nicotine replacement therapy (NRT) and Zyban advertising on youth perceptions of the ease of quitting, health risks of smoking and future intentions to smoke. 718 youth aged 14-16years were randomly allocated to view four television ads promoting either: NRT; Zyban; non-pharmaceutical cessation services (telephone Quitline); or non-cessation messages on sun protection. Questionnaire measures were administered before and after viewing ads. There were no effects of advertising exposure on perceived health effects of smoking or intentions to smoke. Compared with the sun protection ads, but not the Quitline ads, those exposed to NRT ads reported stronger perceptions about the ease of quitting, but non-susceptible non-smokers primarily drove this difference. This study suggests that exposure to NRT and Zyban advertising in an experimental context does not reliably influence youth smoking-related beliefs, especially those vulnerable to becoming regular smokers.     

A randomised,crossover study on an electronic vapour product,a nicotine inhalator and a conventional cigarette. Part B: Safety and subjective effects

An Electronic Vapour Product (EVP) has been evaluated for short-term safety parameters and subjective effects in a 2-part study, in smokers. Part 1 compared the EVP with unflavoured (UF) and flavoured (FL) e-liquid at 2.0% nicotine to a conventional cigarette (CC; JPS Silver King Size, 0.6 mg) and a licensed nicotine inhalator (Nicorette^®, 15 mg). Part 2 assessed the effect of increasing concentrations of nicotine in the e-liquid used with the EVP (0%, 0.4%, 0.9%, 2.0%). The study was designed as a randomised, controlled, crossover trial. Outcomes included adverse events (AEs), vital signs, exhaled carbon monoxide (CO), clinical laboratory parameters, smoking urges and withdrawal symptoms. In both study parts, only mild non-serious AEs were reported. No major differences were observed in AEs between the EVPs and Nicorette^®. Exhaled CO levels only increased for CC. All products appeared to decrease smoking urges and nicotine withdrawal symptom scores to a similar extent. The EVP had a similar short-term safety profile to Nicorette^® and relieved smoking urges and nicotine withdrawal symptoms to a similar extent as Nicorette^® and CC. Unlike nicotine replacement therapies, the EVP may offer an alternative for those finding it difficult to quit the behavioural and sensorial aspects of smoking.     

Aspects of the design protocol and the statistical methods for analysis of tar,nicotine and carbon monoxide yields in cigarette smoke that can affect the measurement variability within collaborative studies

Statistical principles described in ISO 5725–1 (1994) are a robust basis for evaluating cigarette smoke data from collaborative studies under the ISO 3308 machine smoking and for specifying the criteria for the removal of outlier data and determination of mean yields and their variability. However, the standard only provides recommendations on outlier removal that should be taken into account by experts who undertake data interpretation. The potential for over-interpretation of data from small numbers of laboratories is highlighted and recommendations made to deal with this possibility.     

Comparison of the impact of the Tobacco Heating System 2.2 and a cigarette on indoor air quality

The impact of the Tobacco Heating System 2.2 (THS 2.2) on indoor air quality was evaluated in an environmentally controlled room using ventilation conditions recommended for simulating “Office”, “Residential” and “Hospitality” environments and was compared with smoking a lit-end cigarette (Marlboro Gold) under identical experimental conditions. The concentrations of eighteen indoor air constituents (respirable suspended particles (RSP) < 2.5 μm in diameter), ultraviolet particulate matter (UVPM), fluorescent particulate matter (FPM), solanesol, 3-ethenylpyridine, nicotine, 1,3-butadiene, acrylonitrile, benzene, isoprene, toluene, acetaldehyde, acrolein, crotonaldehyde, formaldehyde, carbon monoxide, nitrogen oxide, and combined oxides of nitrogen) were measured. In simulations evaluating THS 2.2, the concentrations of most studied analytes did not exceed the background concentrations determined when non-smoking panelists were present in the environmentally controlled room under equivalent conditions. Only acetaldehyde and nicotine concentrations were increased above background concentrations in the “Office” (3.65 and 1.10 μg/m³), “Residential” (5.09 and 1.81 μg/m³) and “Hospitality” (1.40 and 0.66 μg/m³) simulations, respectively. Smoking Marlboro Gold resulted in greater increases in the concentrations of acetaldehyde (58.8, 83.8 and 33.1 μg/m³) and nicotine (34.7, 29.1 and 34.6 μg/m³) as well as all other measured indoor air constituents in the “Office”, “Residential” and “Hospitality” simulations, respectively.