Jacques Le Houezec

A Self-Administered Questionnaire to Measure Dependence on Cigarettes: The Cigarette Dependence Scale

A valid measure of dependence on cigarettes is a useful tool for clinicians and researchers. The aim of this study was to develop a new, self-administered measure of cigarette dependence, and to assess its validity. The content of the instrument was generated in qualitative surveys. A long version (114 items) was tested on the internet in 3009 smokers. Subsamples provided retest data after 18 days (n=578), follow-up data after 45 days (n=990) and saliva cotinine (n=105). The study resulted in a 12-item scale labelled the Cigarette Dependence Scale (CDS-12), and in a 5-item version of this scale (CDS-5). Except for tolerance, CDS-12 covers the main components of DSM-IV and ICD-10 definitions of dependence: compulsion, withdrawal symptoms, loss of control, time allocation, neglect of other activities, and persistence despite harm. CDS-5 has similar measurement properties but less comprehensive content. Both scales had a high test–retest reliability (r⩾0.83), and a high internal consistency (Cronbachs α⩾0.84). CDS-12 scores were higher in daily smokers than in occasional smokers (+1.3SD units), and were associated with the strength of the urge to smoke during the last quit attempt (R2⩾0.25), and with saliva cotinine (R2⩾0.17). CDS-12 and CDS-5 scores decreased in daily smokers who switched to occasional smoking at 18-day retest. Dependence scores did not predict smoking abstinence at follow-up. In conclusion, CDS-12 and CDS-5 are reliable measures of cigarette dependence which fulfill several criteria of content validity and construct validity and are sensitive to change over time.

Tobacco, nicotine and harm reduction

ISSUES Tobacco smoking, sustained by nicotine dependence, is a chronic relapsing disorder, which in many cases results in lifelong cigarette use and consequent death of one out of two lifelong smokers from a disease caused by their smoking. Most toxicity due to cigarette smoking is related to the burning process. APPROACH Models of harm reduction applied to tobacco suggest that use of non-combustible, less toxic, nicotine-containing products as a substitute for cigarette smoking would reduce the death toll arising from tobacco use. Available options include medicinal nicotine and smokeless tobacco products. KEY FINDINGS The potential role of nicotine replacement therapy (NRT) products in a harm reduction strategy is currently severely restricted by strict regulations on dose, safety and potential addictiveness. As a result, NRT products are designed to provide much less nicotine, and deliver it to the brain more slowly, than cigarettes, which are widely accessible and poorly regulated. Smokeless tobacco (snus) has proved to be an acceptable reduced hazard alternative to smoking in Sweden, but supply of snus is illegal elsewhere in the European Union. IMPLICATIONS To increase accessibility and reach more smokers, barriers to the use of NRT use need to be removed and more effective NRTs need urgently to be developed. Smokeless tobacco could also play an important role in harm reduction, but current European Union regulations and concerns over exploitation by tobacco companies currently preclude wider use. CONCLUSION To improve public health there is an urgent need for an appropriate regulatory framework and regulatory authority at the European level, controlling both tobacco and nicotine products to ensure that the least harmful products are the most accessible.

Regulation in the face of uncertainty: the evidence on electronic nicotine delivery systems (e-cigarettes).

Tobacco smoking is the largest single preventable cause of many chronic diseases and death. Effective treatments exist; however, few smokers use them and most try to quit by themselves. Most of the tobacco cigarette’s toxicity is related to the combustion process. Models of harm reduction applied to tobacco suggest that switching from inhalation of combustible products to a noncombustible nicotine delivery product would likely result in a vast reduction in tobacco-related death and illness. Currently available evidence raises no doubt that electronic cigarettes (e-cigs) are by far less harmful than smoking (although probably not absolutely safe) and have the potential to be the most effective tobacco harm reduction products due to their unique property of resembling smoking and providing satisfaction to the user. A lot of controversy is surrounding e-cigs and their regulation, much of which is based on the precautionary principle. Although monitoring and further research is definitely needed, the arguments used to implement severe restrictions or bans are mostly hypothetical, weakly supported by evidence, and, in some cases, derived from mispresentation or misinterpretation of the study findings. Regulators should keep in mind that the target population is smokers who want to reduce or quit their deadly tobacco consumption. To achieve this goal, smokers should be honestly informed on the relative harmfulness of the different products. E-cigs are not tobacco products and are not used as medications. For this reason, a specific regulatory scheme is needed, separate from tobacco or medicinal products regulation. Regulation should implement specific quality criteria for products, rules for the exclusion of chemicals of reasonable concern, and appropriate testing for possible contaminants. Additionally, manufacturing standards derived from the food industry should be implemented and adjusted for specific conditions related to e-cigs. Finding the appropriate balance between safety and acceptability of use by smokers will be important in achieving the maximum public health benefit. Labeling should be specified, with warnings about exposure to skin or through ingestion and discouragement of use by nonsmokers, related to the presence of nicotine. Finally, advertising and marketing should not be banned, but appropriately regulated in order to encourage use by the intended population while avoiding use by never-smokers. E-cigs should be appealing to smokers (but not to nonsmokers), while availability and pricing should be strong competitive advantages of e-cigs relative to tobacco cigarettes.

Smoking cessation or reduction with nicotine replacement therapy: a placebo-controlled double blind trial with nicotine gum and inhaler

BackgroundEven with effective smoking cessation medications, many smokers are unable to abruptly stop using tobacco. This finding has increased interest in smoking reduction as an interim step towards complete cessation.MethodsThis multi-center, double-blind placebo-controlled study evaluated the efficacy and safety of nicotine 4 mg gum or nicotine 10 mg inhaler in helping smokers (N = 314) to reduce or quit smoking. It included smokers willing to control their smoking, and participants could set individual goals, to reduce or quit. The study was placebo-controlled, randomized in a ratio of 2:1 (Active:Placebo), and subjects could choose inhaler or gum after randomization. Outcome was short-term (from Week 6 to Month 4) and long-term (from Month 6 to Month 12) abstinence or reduction. Abstinence was defined as not a single cigarette smoked and expired CO readings of <10 ppm. Smoking reduction was defined as a reduction in number of cigarettes per day by 50% or more versus baseline, verified by a lower-than-baseline CO reading at each visit during the same periods.ResultsSignificantly more smokers managed to quit in the Active group than in the Placebo group. Sustained abstinence rates at 4 months were 42/209 (20.1%) subjects in the Active group and 9/105 (8.6%) subjects in the Placebo group (p = 0.009). Sustained abstinence rates at 12 months were 39/209 (18.7%) and 9/105 (8.6%), respectively (p = 0.019). Smoking reduction did not differ between the groups, either at short-term or long-term. Twelve-month reduction results were 17.2% vs. 18.1%, respectively. No serious adverse events were reported.ConclusionIn conclusion, treatment with 10 mg nicotine inhaler or 4 mg nicotine chewing gum resulted in a significantly higher abstinence rate than placebo. In addition a large number of smokers managed to reduce their cigarette consumption by more than 50% compared to baseline.

Should e-cigarettes be regulated as a medicinal device?

There are more than 1 billion smokers worldwide. About half of individuals who continue smoking will die prematurely because of toxins in tobacco smoke. Over the past few years, smokers in economically developed countries have been showing growing interest in electronic cigarettes (ECs) that are designed to deliver nicotine without these toxins. Initial reactions to ECs focused on potential risks. Increasingly though, commentators are pointing out that there is little indication of harm, whereas the potential benefi ts are substantial. Research into switching from cigarettes to snus (Swedish smokeless tobacco) and into long-term use of nicotinereplacement treatments (NRTs) shows that, except in pregnancy, nicotine intake from a non-smoked source is associated with low or no health risks. The chemicals that make cigarettes dangerous are either absent in ECs or present only in trace concentrations. Europe is now at an important crossroad. One possible path ahead is to continue to regulate ECs as any other consumer product. The other path, currently under consideration by the proposed Updated Tobacco Products Directive of the European Commission is to regulate them as medicinal devices. The main arguments for such regulation include consumer safety, the need for precise product labelling, and equal terms on which to compete with NRTs. Strict controls would also restrict the development and spread of ECs and alleviate a concern that if ECs fl ourish, this would renormalise smoking. If such medicinal regulation had no other consequence, these arguments might have some merit. The unintended consequences, however, could be severe and none of the above arguments are strong. One, in terms of the safety of ECs, there is no credible risk that normally used ECs can poison the user with nicotine. Much more dangerous chemicals such as bleach rely on packaging and common sense rather than on medicinal licensing. Another aspect of safety is the presence of unauthorised dangerous compounds. In Europe, EC users are already protected by general product and safety regulations and labelling requirements. For example, medicinal licensing is not needed to ensure toys do not contain lead. Of course, it is possible that some unexpected ill eff ects of ECs might emerge, but the key point is that compared with hypothetical risks that seem unlikely in view of current knowledge about ECs, we know the product ECs are replacing is seriously dangerous. If any new risks emerge, then appropriately tighter regulation can be implemented. Two, there are questions about the need for precise labelling of nicotine content. Nicotine delivery from ECs is determined not just by the nicotine content in the liquid of ECs, but also by characteristics of heating elements and other technical features and even more so by the individual’s frequency and depth of inhalations. Nicotine concentrations in liquid, therefore, have only a very rough relation to how much nicotine a user absorbs. As with cigarettes, such labelling conveys little useful information to users. Three, in terms of market competition, ECs are a consumer product competing with cigarettes. The success of ECs would be detrimental to sales not just of cigarettes but also of smoking cessation products. Protection of such markets, however, should not be high on the public health agenda. Four, regarding attracting non-smokers and renormalising smoking, so far there are very few cases of never smokers using ECs regularly whereas many smokers have switched to ECs. These electronic products have not been attracting children, and, although sales to children should be banned, medicinal licensing is not needed to achieve this aim. Many of the never smokers are likely to try smoking tobacco, so it would be neither surprising nor a public health problem if some tried ECs instead. It is diffi cult to understand how use of ECs would imply that cigarettes are also acceptable. The two are clearly diff erent. Availability of a safer alternative to cigarettes is likely to strengthen rather than weaken denormalisation of smoking. There are three main arguments against mandatory medicinal licensing of ECs, apart from the most obvious one that they are consumer products rather than medicines. One, medicinal licensing requirements would hinder further EC development, which is essential for ECs to become a full replacement for cigarettes. Small improvements would require new licensing applications, the innovation timescale would increase Sh ei la Te rry /S cie nc e Ph ot o Li br ar y

Testing the Cigarette Dependence Scale in 4 samples of daily smokers: Psychiatric clinics, smoking cessation clinics, a smoking cessation website and in the general population

AIM To assess the properties of the Cigarette Dependence Scale (CDS-12) in various samples of daily smokers and to provide reference scores in a general population sample. METHODS Surveys in 4 samples of daily cigarette smokers: psychiatric out-patients in Geneva, Switzerland (n=226), clients of smoking cessation clinics in France (n=370), visitors of a French-language smoking cessation website (n=13,697) and a representative sample of the general population of Geneva (n=292). RESULTS In all 4 samples, Cronbachs alpha coefficients were >0.87 and factor analyses indicated that CDS-12 was unidimensional. CDS-12 was slightly skewed towards higher values, and it was associated with expired carbon monoxide, but this association was not strong (9% of variance explained, p<0.001). CDS-12 scores were highest in clients of smoking cessation clinics (mean=47.7, SD=10.2), followed by psychiatric patients (mean=44.4, SD=8.4), visitors of smoking cessation websites (mean=43.3, SD=11.6) and the general population sample (mean=36.9, SD=12.3). Except for tolerance, each element in the DSM-IV and ICD-10 definitions of dependence is reflected by at least one item in CDS-12, even though the match with these definitions is sometimes indirect. CONCLUSIONS This paper presents reference scores and validity and reliability tests for CDS-12 in a diversity of samples of daily smokers. This information should be useful to clinicians and researchers.

A critique of a WHO-commissioned report and associated article on electronic cigarettes

The World Health Organization (WHO) recently commissioned a report reviewing evidence on electronic cigarettes and making policy recommendations. A version of it was subsequently published as an academic paper. We identify important errors in the description and interpretation of the studies reviewed, and find many of its key conclusions misleading.

Pharmacotherapies and harm-reduction options for the treatment of tobacco dependence

Introduction: Tobacco dependence, a chronic relapsing condition, requires repeated interventions and multiple attempts to quit. Areas covered: Strategies for assisting smoking cessation include behavioural counselling and pharmacotherapy. Three drugs are currently used as first-line pharmacotherapy: nicotine replacement therapy (NRT), bupropion and varenicline. Compared to placebo, the drug effect varies from RR = 2.27 for varenicline, to 1.69 for bupropion, and 1.60 for any form of NRT. Cytisine (similar to varenicline) has a RR = 3.98 compared to placebo (two trials). Second-line pharmacotherapies include nortriptyline and clonidine. This review also offers an overview of pipeline developments. Expert opinion: Effective medications exist, and clinicians should encourage and offer treatment to every smoker. However, most smokers try to quit by themselves, with only about 3% quitting successfully each year. Alternative interventions are needed. Harm reduction has not received much support to date. Safer alternative to tobacco smoking (smoke-free products, long-term use of cessation drugs, or electronic cigarettes) could save lives and reduce the burden of tobacco-related deaths and diseases. Despite some encouragement to develop a research agenda for e-cigarettes, particularly on the safety issues, too little attention has been brought to this area of research.

Prevalence and correlates of current daily use of electronic cigarettes in the European Union: analysis of the 2014 Eurobarometer survey

The study purpose was to analyze current daily and current daily nicotine-containing electronic cigarette (EC) use in the European Union (EU). Special Eurobarometer 429, a cross-sectional survey performed in a representative sample of 28 member states of the EU in November and December of 2014, was analyzed. The prevalence of current daily and current daily nicotine-containing EC use was 1.08% (95% CI 0.95–1.20%) and 1.00% (95% CI 0.88–1.12%), respectively, and was mainly observed in current and former smokers. Minimal current daily (0.08%, 95% CI 0.03–0.12%) and current daily nicotine-containing EC use (0.04%, 95% CI 0.01–0.08%) was observed among never smokers. Smoking cessation with the help of ECs was reported by 47.12% (95% CI 41.28–52.96%) of current daily and 49.14% (95% CI 43.12–55.17%) of current daily nicotine-containing EC users. Additionally, 33.18% (95% CI 27.67–38.69%) and 31.40% (95% CI 25.80–36.99%) reported reduction in smoking consumption, respectively. The strongest correlates of daily EC use were being current and former smokers. In the EU in late 2014, current daily EC use was predominantly observed in current and former smokers and was associated with high self-reported rates of smoking cessation and reduction. Current daily EC use by never smokers was extremely infrequent.

Risks of Attempting to Regulate Nicotine Flux in Electronic Cigarettes

In their recent analysis, Shihadeh and Eissenberg1 support that by regulating nicotine flux in electronic cigarettes (ECs) could be a valuable tool in the regulatory process that would increase effectiveness and reduce the chance for abuse liability. Herein, we present the view that such a regulation could endanger the effectiveness of e-cigarettes as smoking substitutes. Nicotine Delivery From Tobacco Cigarettes Although tobacco cigarettes deliver 1–3mg of nicotine (from about 14mg in each rod), the levels of daily nicotine intake may vary considerably between users. This is partly attributed to a substantial variability in nicotine intake per cigarette caused by different smoking intensity.2 It is also possible to smoke more than one cigarette consecutively, further avoiding the limitation of the tobacco cigarette rod standardized design. Therefore, smokers can adjust cigarette use based on personal needs, while it is extremely unlikely for smoking to cause nicotine intoxication or overdose. Nicotine Delivery From ECs Electronic cigarettes differ remarkably from tobacco cigarettes in terms of nicotine delivery. There is no standardized unit of consumption. Consumers usually report their daily consumption in milliliters of liquid,3 which cannot be directly compared with daily cigarette consumption. The variability in equipment design and potential, and the range of nicotine content in EC liquids provide consumers with the ability to adjust use patterns and nicotine intake. Surveys of dedicated EC users (which were all former smokers) have shown that high nicotine levels are important especially for the initiation of EC use.3,4 Although nicotine delivery to the aerosol can be similar or higher than tobacco cigarettes,5,6 clinical studies of EC use have shown that the nicotine absorption potential is significantly lower compared with tobacco cigarettes, even when new generation devices are used.7 This is mostly attributed to the low speed of nicotine absorption, and clearly indicates that nicotine intoxication is highly unlikely when ECs are used as intended. Therefore, despite the ability to adjust use patterns, ECs are currently not as efficient as tobacco cigarettes in nicotine delivery. We propose that the comparison between ECs and tobacco cigarettes would be similar to comparing, respectively a car with a large selection of powerful (in selected cases) engines (i.e., nicotine delivery to the aerosol) but very heavy structure (i.e., reduced rate of absorption for a given nicotine content per puff), with a car with less variability and lower-powered engines but very lightweight structure. With current technology, overall performance (i.e., nicotine delivery to the bloodstream) is definitely in favor of the tobacco cigarette, and smokers may be unable to adequately satisfy their nicotine cravings with EC use despite the ability to adjust use patterns. The Pleasure Factor in EC Use It is physiologically plausible to support that nicotine induces pleasure and reduces anxiety in smokers.8 The pleasure factor has been largely neglected and marginalized by the tobacco control movement which is usually following the pathology paradigm framework for nicotine use.9 Perceived pleasure should not be a reason for anyone to initiate smoking (due to exposure to known risks for health damage) or EC use (due to exposure to yet unknown, although evidently much lower than smoking, risk). However, it should be considered and evaluated when discussing about smoking substitution. Surveys indicate that pleasure could be a potential reason for smokers to choose and maintain long-term EC use.3,10 This is probably one of the main reasons for the enormous variability of different flavors available in EC liquids,10 and could explain the variability of devices with different characteristics, design, and properties. The recent development and marketing of atomizers with adjustable airflow probably reflects the different preferences by users, and the effort of manufacturers to create products which can be customized based on self-preference. Since the main objective should always be elimination of smoking, the pleasure effect could be an advantage of ECs over other products which should be welcomed if it contributes to smoking reduction or cessation. Further studies are needed to examine this aspect. Is There a Need to Regulate Nicotine Flux in ECs? Based on the evidence presented above, and with current technological evolution, it is our opinion that regulating nicotine flux in ECs, in terms of restricting usage patterns (e.g., restrict puff duration or apply a minimum interpuff interval), is unnecessary. It carries the potential risk of reducing ECs’ efficacy as smoking substitutes, while it provides no benefit in terms of safety. There is already the example of regulatory decisions by the European Union, which defined an upper limit of 20mg/ml nicotine concentration in EC liquids (http://ec.europa.eu/health/tobacco/docs/dir_201440_en.pdf) based on information about potential nicotine delivery to the aerosol.6 They failed to recognize that both effectiveness and abuse liability are determined by nicotine absorption (speed and amount delivered to the blood stream) rather than nicotine delivery to the aerosol. As a result, it is possible that such a restriction could exclude some smokers from effectively using ECs as smoking substitutes. Research on nicotine flux could become an essential tool in the development of more effective EC products and in informing consumers about the characteristics of each device so that they make appropriate choices. There are two options for ECs development: (a) using higher nicotine concentration in liquid and (b) improving the absorption rate. The former results in intense (and, for many users, unbearable) throat irritation (“throat hit”), added to the irritation induced by the humectants in the aerosol (propylene glycol and glycerol). The latter may occur from adjusting use behavior (e.g., taking longer and deeper puffs, although this may make the use tiring), adjusting power delivery (which leads to more liquid consumption and aerosol production per given puff duration) and reformulating EC liquids in order to deliver and deposit nicotine more effectively into the lungs. It is possible that improvement in nicotine delivery efficacy could make ECs more addictive. This is not a concern for smokers (who are already nicotine-dependent) but for nonsmokers who may adopt EC use. However, this raises an important ethical issue: should a product, which is probably beneficial for a part of the population (smokers), be restricted (which could result in reduced efficacy as a smoking substitute) because some other parts of the population (nonsmokers) decide to voluntarily adopt its use and expose themselves to a new (even minor) risk? Measures such as proper education, regulation of advertising, and prohibition of promotion and sales to nonsmoking youth could effectively ensure that ECs will not be used by nonsmokers without restricting their potential to substitute smoking.