BackgroundElectronic cigarettes (e-cigarettes) are becoming increasingly popular with smokers worldwide. Users report buying them to help quit smoking, to reduce cigarette consumption, to relieve tobacco withdrawal symptoms, and to continue having a ‘smoking’ experience, but with reduced health risks. Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Methods ECLAT is a prospective 12-month randomized, controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model (‘Categoria’; Arbi Group Srl, Italy) compared to its non-nicotine choice. GroupA (n = 100) received 7.2 mg nicotine cartridges for 12 weeks; GroupB (n = 100), a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges; GroupC (n = 100) received no-nicotine cartridges for 12 weeks. The study consisted of nine visits during which cig/day use and exhaled carbon monoxide (eCO) levels were measured. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.ResultsDeclines in cig/day use and eCO levels were observed at each study visits in all three study groups (p<0.001 vs baseline), with no consistent differences among study groups. Smoking reduction was documented in 22.3% and 10.3% at week-12 and week-52 respectively. Complete abstinence from tobacco smoking was documented in 10.7% and 8.7% at week-12 and week-52 respectively. A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study. Participants’ perception and acceptance of the product under investigation was satisfactory.ConclusionIn smokers not intending to quit, the use of e-cigaretteswith or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects.Trial RegistrationClinicalTrials.gov NCT01164072 NCT01164072

Allergic diseases have reached epidemic proportions worldwide. An understanding of the cellular and soluble mediators that are involved in allergic inflammatory responses not only helps in understanding the mechanisms of current treatments, but is also important for the identification of new targets that are amenable to both small-molecule and biological interventions. There is now considerable optimism with regards to tackling the allergy epidemic in light of improvements in systemic and mucosal allergen-specific immunotherapy, the identification of key cytokines and their receptors that drive T-helper-2-cell polarization, a clearer understanding of the pathways of leukocyte recruitment and the signalling pathways that are involved in cell activation and mediator secretion, and new approaches to vaccine development.

Electronic cigarettes are a recent development in tobacco harm reduction. They are marketed as less harmful alternatives to smoking. Awareness and use of these devices has grown exponentially in recent years, with millions of people currently using them. This systematic review appraises existing laboratory and clinical research on the potential risks from electronic cigarette use, compared with the well-established devastating effects of smoking tobacco cigarettes. Currently available evidence indicates that electronic cigarettes are by far a less harmful alternative to smoking and significant health benefits are expected in smokers who switch from tobacco to electronic cigarettes. Research will help make electronic cigarettes more effective as smoking substitutes and will better define and further reduce residual risks from use to as low as possible, by establishing appropriate quality control and standards.

BackgroundCigarette smoking is a tough addiction to break. Therefore, improved approaches to smoking cessation are necessary. The electronic-cigarette (e-Cigarette), a battery-powered electronic nicotine delivery device (ENDD) resembling a cigarette, may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption. Efficacy and safety of these devices in long-term smoking cessation and/or smoking reduction studies have never been investigated.MethodsIn this prospective proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers (unwilling to quit) experimenting the 'Categoria' e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend a total of five study visits: at baseline, week-4, week-8, week-12 and week-24. Product use, number of cigarettes smoked, and exhaled carbon monoxide (eCO) levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.ResultsSustained 50% reduction in the number of cig/day at week-24 was shown in 13/40(32.5%) participants; their median of 25 cigs/day decreasing to 6 cigs/day (p < 0.001). Sustained 80% reduction was shown in 5/40(12.5%) participants; their median of 30 cigs/day decreasing to 3 cigs/day (p = 0.043). Sustained smoking abstinence at week-24 was observed in 9/40(22.5%) participants, with 6/9 still using the e-Cigarette by the end of the study. Combined sustained 50% reduction and smoking abstinence was shown in 22/40 (55%) participants, with an overall 88% fall in cigs/day. Mouth (20.6%) and throat (32.4%) irritation, and dry cough (32.4%) were common, but diminished substantially by week-24. Overall, 2 to 3 cartridges/day were used throughout the study. Participants' perception and acceptance of the product was good.ConclusionThe use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit (http://ClinicalTrials.gov number NCT01195597).

Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle.Direct airway challenges have been used widely and are well standardised. They are highly sensitive, but not specific to asthma and can be used to exclude current asthma in a clinic population. Indirect bronchial stimuli, in particular exercise, hyperventilation, hypertonic aerosols, as well as adenosine, may reflect more directly the ongoing airway inflammation and are therefore more specific to identify active asthma. They are increasingly used to evaluate the prevalence of bronchial hyperresponsiveness and to assess specific problems in patients with known asthma, e.g. exercise-induced bronchoconstriction, evaluation before scuba diving.Direct bronchial responsiveness is only slowly and to a modest extent, influenced by repeated administration of inhaled steroids. Indirect challenges may reflect more closely acute changes in airway inflammation and a change in responsiveness to an indirect stimulus may be a clinically relevant marker to assess the clinical course of asthma. Moreover, some of the indirect challenges, e.g. hypertonic saline and mannitol, can be combined with the assessment of inflammatory cells by induction of sputum.

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<b><i>Background:</i></b> An international expert panel convened by the Independent Scientific Committee on Drugs developed a multi-criteria decision analysis model of the relative importance of different types of harm related to the use of nicotine-containing products. <b><i>Method:</i></b> The group defined 12 products and 14 harm criteria. Seven criteria represented harms to the user, and the other seven indicated harms to others. The group scored all the products on each criterion for their average harm worldwide using a scale with 100 defined as the most harmful product on a given criterion, and a score of zero defined as no harm. The group also assessed relative weights for all the criteria to indicate their relative importance. <b><i>Findings:</i></b> Weighted averages of the scores provided a single, overall score for each product. Cigarettes (overall weighted score of 100) emerged as the most harmful product, with small cigars in second place (overall weighted score of 64). After a substantial gap to the third-place product, pipes (scoring 21), all remaining products scored 15 points or less. <b><i>Interpretation:</i></b> Cigarettes are the nicotine product causing by far the most harm to users and others in the world today. Attempts to switch to non-combusted sources of nicotine should be encouraged as the harms from these products are much lower.

Cigarette smoking and asthma interact to induce important adverse effects on clinical, prognostic and therapeutic outcomes. This review examines recent evidence on the harmful effects of smoking in asthma, possible underlying inflammatory mechanisms for this altered response, management options for these patients and potential future therapeutic directions. Active smokers, particularly females, are at risk of developing asthma. Prevalence rates for smoking in asthma are relatively close to those found in the general population. Smokers with asthma experience worse asthma control than nonsmokers with asthma. Mechanisms for the adverse effects of smoking in asthma include altered airway inflammation and corticosteroid insensitivity. Quitting smoking can improve symptoms and lung function, but the low rates of smoking cessation highlights the need for improved strategies for managing these patients. Clinical trials assessing new therapies for asthma need to enrol smokers to identify treatments that are effective in the asthma smoking phenotype.