Åke Westin

Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety.

Abstract Objectives: To determine whether use of an oral nicotine inhaler can result in long term reduction in smoking and whether concomitant use of nicotine replacement and smoking is safe. Design: Double blind, randomised, placebo controlled trial. Four month trial with a two year follow up. Setting: Two university hospital pulmonary clinics in Switzerland. Participants: 400 healthy volunteers, recruited through newspaper advertisements, willing to reduce their smoking but unable or unwilling to stop smoking immediately. Intervention: Active or placebo inhaler as needed for up to 18 months, with participants encouraged to limit their smoking as much as possible. Main outcome measures: Number of cigarettes smoked per day from week six to end point. Decrease verified by a measurement of exhaled carbon monoxide at each time point compared with measurement at baseline. Results: At four months sustained reduction of smoking was achieved in 52 (26%) participants in the active group and 18 (9%) in the placebo group (P<0.001; Fishers test). Corresponding figures after two years were 19 (9.5%) and 6 (3.0%) (P=0.012). Conclusion: Nicotine inhalers effectively and safely achieved sustained reduction in smoking over 24 months. Reduction with or without nicotine substitution may be a feasible first step towards smoking cessation in people not able or not willing to stop abruptly.

Effect of smoking reduction and cessation on cardiovascular risk factors

This open study examined the effect of smoking reduction and smoking cessation on established cardiovascular risk factors. Fifty-eight healthy adult smokers (smoking >or=15 cigarettes/day for at least 3 years) were provided with nicotine nasal spray (to be used ad libitum) and asked to stop smoking. The primary goal during the first 8 weeks, however, was to reduce their daily smoking by at least 50%. Subjects were then followed for another 8 weeks; at this point, 33 participants had successfully stopped smoking. Cardiovascular risk factors including fibrinogen, hemoglobin, hematocrit, triglycerides, and cholesterol were measured at baseline and at 9 and 17 weeks. After 8 weeks of smoking reduction, the mean number of cigarettes smoked per day had decreased from 21.5 +/- 0.6 (baseline) to 10.8 +/- 0.6 (p < 0.001). This was accompanied by significant improvements in fibrinogen (from 2.9 +/- 0.1 g/l at baseline to 2.6 +/- 0.1 g/l, p = 0.011), white blood cells (from 7.0 +/- 0.4 to 6.2 +/- 0.3 x 10(9)/l, p = 0.005) and the high-density/low-density lipoprotein (HDL/LDL) ratio (0.33 +/- 0.03 to 0.37 +/- 0.03, p < 0.005). Following 8 weeks of abstinence from smoking, the mean white blood cell count was further reduced (to 6.1 +/- 0.3 x 10(9)/l, p = 0.026 vs. baseline) and there were also significant improvements in HDL (from 1.16 +/- 0.06 mmol/l at baseline to 1.32 +/- 0.06, p < 0.001) and LDL (from 3.78 +/- 0.16 mmol/l at baseline to 3.52 +/- 0.17, p = 0.015). In conclusion, 8 weeks of smoking reduction resulted in clinically significant improvements in established cardiovascular risk factors. These improvements were even greater after an additional period of abstinence from smoking.

Smoking reduction treatment with 4‐mg nicotine gum: A double‐blind, randomized, placebo‐controlled study

Smoking reduction may provide a harm‐reduction alternative treatment for smokers who are not ready to quit smoking. This study evaluated the efficacy of nicotine gum in helping smokers reduce or quit smoking.

Effects of smoking cessation and reduction in asthmatics.

The present study examined the effect of smoking reduction and cessation on asthma regulation and biomarkers of exposure to cigarette smoke. In a prospective open design, we allocated 220 asthmatics among three groups: (a) Smoking reduction (reducers), with the aim of smoking fewer than seven cigarettes per day, (b) complete smoking cessation (abstainers), or (c) continuation of usual smoking (continuing smokers). Subjects used nicotine chewing gum or an oral nicotine inhaler to promote reduction and cessation. We monitored changes in the biomarkers carbon monoxide, cotinine, and thiocyanate, and in peak flow, medicine use, bronchial reactivity, and asthma symptoms. The analysis used the three outcome groups, regardless of original allocation to treatment groups. At 4 months, analysis of abstainers (n = 27), reducers (n = 33), and continuing smokers (n = 50) showed marked, statistically significant decreases in expired carbon monoxide of 17 ppm (abstainers) and 15 ppm (reducers); in plasma cotinine of 124 ng/ml (abstainers) and 122 ng/ml (reducers); and in plasma thiocyanate of 5.03 ng/ml (abstainers) and 3.74 ng/m (reducers). For abstainers, we observed improvements in the asthma-specific quality-of-life score, and reductions in self-reported day and night use of rescue beta2-agonists, in doses of inhaled corticosteroids, in daytime asthma symptoms, and in bronchial hyperreactivity. For reducers, smaller improvements occurred for night use of rescue beta2-agonists, doses of inhaled corticosteroids, and bronchial hyperreactivity. Smoking cessation resulted in a marked decrease in three biomarkers of cigarette smoke inhalation and improved asthma regulation, whereas smoking reduction had a less pronounced effect on biomarkers and only a small effect on asthma regulation.

Influence of long-term smoking reduction on health risk markers and quality of life

We have recently published efficacy and safety data of a study using an oral nicotine inhaler in smoking reduction. The current analysis was undertaken to assess the secondary objectives of the trial: the influence of long-term smoking reduction on health risk markers. Four hundred healthy volunteers, unable or unwilling to stop smoking immediately, were enrolled in a double-blind, randomized, placebo-controlled trial in smoking reduction; 310 were evaluable up to 2 years. Participants were randomized to active or placebo inhalers as needed for up to 18 months, with subjects encouraged to reduce their smoking as much as possible; counseling took place over a 2-year period. For the current prospective cohort study, the number of daily cigarettes, carbon monoxide (CO), cotinine, cardiovascular risk factors, pulmonary function tests, and quality of life were compared between successful reducers (n = 25) and unsuccessful reducers (control group, n = 285). Success was defined as a reduction of daily cigarettes of at least 50% from week 6 to 2 years, verified by a decrease in exhaled CO at all visits compared with baseline. At 2 years, successful reducers showed a significantly greater decrease in cotinine levels (60% vs. 1%, p < 0.001), cholesterol/high-density lipoprotein (HDL) ratios (-2.42 vs. -1.67, p = 0.025), hemoglobin concentrations (-5.67 vs. -1.34 g/l, p = 0.023), pulse rate (-3.7 vs. +1.0 bpm, p = 0.043), and significantly improved general health score (9.40 vs. 2.34, p = 0.049); whereas no difference was found in forced expiratory volume during 1 s (FEV1) and forced vital capacity (FVC) compared with controls. The benefits of long-term smoking reduction of at least 50% of daily cigarettes were not offset by compensatory smoking, and the marked decrease in markers of smoke exposure had a positive influence on several cardiovascular risk markers and quality of life assessments.

Open randomised trial of intermittent very low energy diet together with nicotine gum for stopping smoking in women who gained weight in previous attempts to quit

Abstract Objective: To determine whether attempts to prevent weight gain will increase success rates for stopping smoking. Design: 16 week, open, randomised study with 1 year follow up. Setting: Obesity unit. Subjects: 287 female smokers who had quit smoking before but started again because of weight concerns. Intervention: Combination of a standard smoking cessation programme with nicotine gum and a behavioural weight control programme including a very low energy diet. A control group was treated with the identical programme but without the diet. Main outcome measure: Sustained cessation of smoking. Results: After 16 weeks, 68/137 (50%) women had stopped smoking in the diet group versus 53/150 (35%) in the control group (P=0.01). Among these women, weight fell by mean 2.1 (95% confidence interval 2.9 to 1.3) kg in the diet group but increased by 1.6 (0.9 to 2.3) kg in the control group (P<0.001). After 1 year the success rates in the diet and control groups were 38/137 (28%) and 24/150 (16%) respectively (P<0.05), but there was no statistical difference in weight gain. Conclusions: Combining the smoking cessation programme with an intervention to control weight helped women to stop smoking and control weight.

Efficacy of the nicotine inhaler in smoking reduction: A double-blind, randomized trial

Many smokers are not ready to quit but are interested in changing their smoking behavior, particularly if such a change is associated with a reduction in health risk. The present study evaluated the efficacy of the nicotine inhaler in reducing smoking. Exploratory studies assessed whether reduction in smoking was associated with reduction in markers of disease risk. A total of 429 healthy smokers (smoking at least 20 cigarettes/day) were randomly assigned to either nicotine-containing or placebo inhalers, which subjects were allowed to use ad libitum for up to 1 year. The nicotine inhaler was significantly superior to placebo in achieving reduction in daily cigarette consumption by at least 50% after 4 months, compared with baseline (18% vs. 8%, p = .004). Active treatment promoted smoking cessation: 8% of subjects in the nicotine group and 1% in the placebo group were abstinent at month 15. Throughout the study, smoking reduction, per se, independent of treatment group, was associated with a statistically significant decrease in exhaled carbon monoxide and serum cotinine and thiocyanate. Smoking reduction also improved established risk markers for cardiovascular disease over 4 months. The incidence of adverse events did not differ significantly between the active and placebo groups. The most common treatment-related adverse events were throat irritation and cough. In conclusion, the nicotine inhaler can help smokers who are unable or unwilling to quit to reduce daily cigarette consumption, which may be a health benefit on its own and may further promote quitting.

Symptoms of nicotine toxicity in subjects achieving high cotinine levels during nicotine replacement therapy.

INTRODUCTION Nicotine replacement therapy (NRT) aids smoking reduction and cessation. Although NRT is effective and safe, some smokers may achieve high nicotine levels. The purpose of this study was to determine the incidence and severity of nicotine-related adverse events in subjects with levels of cotinine, a metabolite of nicotine, that increased by >50% compared with baseline smoking in controlled clinical trials of NRT. METHODS Data from participants in randomized, double-blind, controlled trials of various formulations of NRT (Nicorette®), including patch, gum, oral inhaler, sublingual tablet, nasal spray, mouth spray, and combinations, were extracted from a clinical database. Eligible studies were performed between 1989 and 2010. In addition to baseline, at least 1 subsequent plasma or salivary cotinine concentration was measured, and adverse events were recorded simultaneously. Of 28 eligible studies, 24 were smoking cessation studies and 4 were smoking reduction studies. RESULTS Cotinine levels that increased by >50% above baseline were recorded during treatment in 746 of 7,120 subjects (10.5%). Nausea was reported in 16 subjects (0.2% of the total, upper 99% confidence limit [CL] 0.4%), vomiting in 2 subjects (0.0%, upper 99% CL 0.1%), palpitations in 5 subjects (0.1%, upper 99% CL 0.2%), dizziness in 11 subjects (0.2%; upper 99% CL 0.3%), and headache in 35 subjects (0.5%, upper 99% CL 0.7%). CONCLUSIONS Typical symptoms indicating nicotine overdose together with high cotinine levels were rare during treatment with NRT. These findings support the safety of NRT for smoking cessation or reduction.