Ake Westin - Academia.edu (original) (raw)

Papers by Ake Westin

Clinical Pharmacology & Therapeutics, 2019

Tobacco use is a major health concern. To assist smoking cessation, nicotine replacement therapy ... more Tobacco use is a major health concern. To assist smoking cessation, nicotine replacement therapy (NRT) is used to reduce nicotine craving. We quantitatively described the relationship between nicotine pharmacokinetics (PKs) from NRTs and momentary craving, linking two different pharmacodynamic (PD) scales for measuring craving. The dataset comprised retrospective data from 17 clinical studies and included 1,077 adult smokers with 39,802 craving observations from four formulations: lozenge, gum, mouth spray, and patch. A PK/PD model was developed that linked individual predicted nicotine concentrations with the categorical and visual analogue PD scales through a joint bounded integer model. A maximum effect model, accounting for acute tolerance development, successfully related nicotine concentrations to momentary craving. Results showed that all formulations were similarly effective in reducing craving, albeit with a fourfold lower potency for the patch. Women were found to have a h...

Journal of Pharmacokinetics and Pharmacodynamics, 2018

An exposure-response (ER) model relating nicotine plasma concentration to momentary craving acros... more An exposure-response (ER) model relating nicotine plasma concentration to momentary craving across different nicotine replacement therapy (NRT) formulations

Clinical Pharmacology & Therapeutics, Dec 1, 2005

Background: Smoking reduction may provide a harm-reduction alternative treatment for smokers who ... more Background: 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. Methods: This randomized, double-blind, placebo-controlled trial involved 364 smokers who were not ready to quit but were willing to reduce their smoking intensity. Participants received either 4-mg nicotine gum (n ‫؍‬ 184) or placebo gum (n ‫؍‬ 180) as desired for up to 12 months. The primary outcome was sustained smoking reduction, which was defined as a decrease in daily cigarette consumption of at least 50% compared with baseline. Secondary measures included point-prevalence abstinence, intention to quit, and cardiovascular risk markers. Results: At 4 months, the sustained smoking reduction rate in the nicotine gum group was twice that of the placebo group (15.8% versus 6.7%, P ‫؍‬ .008). Point-prevalence abstinence was 6.6% for the nicotine gum group and 2.2% for the placebo group (P ‫؍‬ .07). At 13 months, there was a significant difference in the smoking reduction rate for the nicotine (8.2%) and placebo (2.8%) groups (P ‫؍‬ .036). At month 13, the abstinence rates were 12% and 4.5% for the nicotine and placebo groups, respectively (P ‫؍‬ .012). Concomitant use of nicotine gum and cigarette smoking was well tolerated. Carbon monoxide levels decreased significantly (P ‫؍‬ .01). Conclusion: Nicotine gum may be an efficacious harm-reduction alternative for smokers who are not ready to quit and may promote smoking cessation, the ultimate goal in the treatment of tobacco dependence. (Clin Pharmacol Ther 2005;78:689-96.

Archives of internal medicine, Nov 28, 1994

Nicotine replacement therapies have proved to be of value in smoking cessation. However, not all ... more Nicotine replacement therapies have proved to be of value in smoking cessation. However, not all smokers can use the nicotine gum or nicotine patch owing to side effects. In addition, the absorption of nicotine from these formulas is slow compared with smoking. A nicotine nasal spray delivers nicotine more rapidly. The objective of this study was to evaluate the efficacy and safety of the nicotine nasal spray for smoking cessation. Subjects were recruited through advertisements in newspapers and among patients referred to the smoking cessation clinic at Sahlgren's Hospital, Göteborg, Sweden. Two hundred forty-eight smokers were treated in small groups with eight counseling sessions over 6 weeks. At their first group session, subjects were randomized to a group receiving nicotine spray (n = 125), 0.5 mg of nicotine per single spray, or to a placebo group (n = 123). The procedure was double blind. Success rates were measured up to 12 months. The nonsmoking status was verified by expired carbon monoxide less than 10 ppm. Significantly more subjects in the nicotine group were continuously abstinent for 12 months than in the placebo group (27% vs 15%; odds ratio, 2.16; 95% confidence interval, 1.15 to 4.12). Ten of the 34 abstinent subjects in the nicotine group used the spray for 1 year. Mild or moderate side effects were rather frequent for both sprays, but they were significantly more for the nicotine spray. Subjects with high scores (> 7) on Fagerström's tolerance questionnaire had a significantly lower success rate with placebo than with the nicotine spray. For subjects with low scores, there was no difference. Nicotine nasal spray in combination with group treatment is an effective aid to smoking cessation.

The European respiratory journal, Jul 1, 1997

The objective of the study was to evaluate the therapeutic efficacy of nicotine nasal solution (N... more The objective of the study was to evaluate the therapeutic efficacy of nicotine nasal solution (NNS) for smoking cessation from the stopping day up to 3 months. We also followed the participants for 2 yrs after ceasing smoking to assess what happens after stopping using NNS. In a placebo-controlled, double-blind, 2 yr prospective study, 157 smokers were given either NNS, one dose containing 1 mg of nicotine per 100 µL (n=79), or placebo (n=78). Treatment was continued for up to 1 yr. One day after quitting smoking, the average number of daily doses was 11 in the group assigned NNS and 14 in the group assigned the placebo, and after 6 weeks, 14 and 6 doses, respectively, among abstinent participants still using spray. After 3 months, 65% of the abstainers in the nicotine group were still using the NNS. The abstinence rates were 51, 39 and 29% after 6 weeks, 3 and 6 months, respectively, as compared to 24, 19 and 18% in the placebo group (p=0.0003; p=0.003; p=0.050). The proportion abstinent at the 1 yr (25 vs 17%) and 2 yr follow-ups (19 vs 14%) was higher among those assigned to the nicotine than to the placebo group, but not significantly so for the numbers used in the study. In conclusion, the use of nicotine nasal spray significantly increased the abstinence rate during the first 6 months following the quitting day.

Nicotine & Tobacco Research, Aug 1, 2006

Many smokers are not ready to quit but are interested in changing their smoking behavior, particu... more 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.

Addiction, Oct 1, 2003

To test the effect of nicotine gum and placebo in smokers not motivated or not able to quit smoki... more To test the effect of nicotine gum and placebo in smokers not motivated or not able to quit smoking with regard to smoking reduction and smoking cessation. This randomized study evaluated nicotine gum versus placebo for up to 1 year in 411 healthy smokers highly motivated to reduce cigarette use. Smoking reduction was defined as self-reported daily smoking less than 50% of baseline and any decrease (1 p.p.m. or more) in carbon monoxide. Pulmonary department, Copenhagen, Denmark. The overall success rate for sustained smoking reduction was significantly higher at all time-points for active versus placebo gum (6.3% versus 0.5% after 24 months). Nicotine gum achieved significantly higher point prevalence cessation rates than placebo at 12 and 24 months [11.2% versus 3.9% (odds ratio = 3.1; 95% CI, 1.4-7.2 and 9.3% versus 3.4% (odds ratio = 2.9; 95% CI, 1.2-7.1), respectively]. There was a linear relationship between decrease in number of daily cigarettes and decrease in plasma cotinine, exhaled carbon monoxide and plasma thiocyanate, with significantly greater reduction in the nicotine gum group after 4 and 12 months (maximum treatment duration) but not after 24 months. The decrease in toxin intake was smaller than the decline in daily cigarette consumption, suggesting that compensatory smoking occurred. Nicotine gum promoted cessation in this population of smokers unwilling to quit. Among reducers, the toxin intake correlated with reduced cigarette consumption although some compensatory smoking occurred.

BMJ, Aug 21, 1999

Objective To determine whether attempts to prevent weight gain will increase success rates for st... more 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.

Nicotine & Tobacco Research, Nov 1, 2002

We have recently published efficacy and safety data of a study using an oral nicotine inhaler in ... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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.

Nicotine & Tobacco Research, Aug 1, 2001

This open study examined the effect of smoking reduction and smoking cessation on established car... more 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.

Nicotine & Tobacco Research, May 22, 2014

introduction: Nicotine replacement therapy (NRT) aids smoking reduction and cessation. Although N... more 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 one 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%). Conclusion: 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.

Tobacco Control, Sep 1, 1995

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2014

Nicotine replacement therapy (NRT) aids smoking reduction and cessation. Although NRT is effectiv... more 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. 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. Cotinine levels that...

Clinical pharmacology and therapeutics, 2005

Smoking reduction may provide a harm-reduction alternative treatment for smokers who are not read... more 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. This randomized, double-blind, placebo-controlled trial involved 364 smokers who were not ready to quit but were willing to reduce their smoking intensity. Participants received either 4-mg nicotine gum (n = 184) or placebo gum (n = 180) as desired for up to 12 months. The primary outcome was sustained smoking reduction, which was defined as a decrease in daily cigarette consumption of at least 50% compared with baseline. Secondary measures included point-prevalence abstinence, intention to quit, and cardiovascular risk markers. At 4 months, the sustained smoking reduction rate in the nicotine gum group was twice that of the placebo group (15.8% versus 6.7%, P = .008). Point-prevalence abstinence was 6.6% for the nicotine gum group and 2.2% for the placebo group (P = .07). At 1...

BMJ (Clinical research ed.), Jan 5, 2000

To determine whether use of an oral nicotine inhaler can result in long term reduction in smoking... more 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. Double blind, randomised, placebo controlled trial. Four month trial with a two year follow up. Two university hospital pulmonary clinics in Switzerland. 400 healthy volunteers, recruited through newspaper advertisements, willing to reduce their smoking but unable or unwilling to stop smoking immediately. Active or placebo inhaler as needed for up to 18 months, with participants encouraged to limit their smoking as much as possible. 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. 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; Fisher's test). Corresponding figures after two yea...

Respiratory Medicine, 2006

Introduction: Individuals exposed both to cigarette smoke and respiratory pollutants at work incu... more Introduction: Individuals exposed both to cigarette smoke and respiratory pollutants at work incur a greater risk of development of airway hyperresponsiveness (AHR) and accelerated decline in forced expiratory volume in 1 s (FEV 1) than that incurred by subjects undergoing each exposure separately. We examined whether smoking cessation or smoking reduction improves AHR and thereby slows down the decline in FEV 1 in occupationally exposed workers. Methods: We examined 165 workers (137 males and 28 females) participating in a smoking cessation programme. Nicotine tablets were used for smoking cessation or smoking reduction. Respiratory symptoms were assessed by questionnaire, FEV 1 by spirometry and AHR by methacholine challenge test. At 1 year, subjects were classified into quitters, reducers, or continuing smokers. Results: Sixty-seven subjects completed the study (32 quitters; 17 reducers; 18 continuing smokers). Respiratory symptoms improved markedly in quitters (Po0:001 for all comparisons) and less so in reducers (P values between 0.163 and 0.027). At 1 year, FEV 1 had slightly but significantly improved in quitters (P ¼ 0:006 vs. smokers; P ¼ 0:038 vs. reducers) and markedly deteriorated in reducers and continuing

Nicotine & Tobacco Research, 2002

Nicotine & Tobacco Research, 2005

The present study examined the effect of smoking reduction and cessation on asthma regulation and... more 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.