Saliva Cotinine Concentrations Research Articles

Comparison of a Daily Smartphone App and Retrospective Questionnaire Measures of Adherence to Nicotine Replacement Therapy Among Pregnant Women: Observational Study.

Few studies have investigated how to best measure adherence to smoking cessation medications, but continuous usage measures are recommended. In this first study of its kind, we compared methods for measuring adherence to nicotine replacement therapy (NRT) among pregnant women, investigating the completeness and validity of data collected from daily assessments using a smartphone app versus data collected from retrospective questionnaires. Women aged ≥16 years who were daily smokers and <25 weeks pregnant were offered smoking-cessation counseling and encouraged to use NRT. For 28 days after setting a quit date (QD), women were asked to report NRT use daily to a smartphone app and to questionnaires administered in person or remotely at 7 and 28 days. For both data collection methods, we provided up to £25 (~US $30) as compensation for the time taken providing research data. Data completeness and NRT use reported to the app and in questionnaires were compared. For each method, we also correlated mean daily nicotine doses reported within 7 days of the QD with Day 7 saliva cotinine concentrations. Of the 438 women assessed for eligibility, 40 participated and 35 accepted NRT. More participants (31/35) submitted NRT usage data to the app by Day 28 (median 25, IQR 11 days) than completed the Day 28 questionnaire (24/35) or either of the two questionnaires (27/35). Data submitted to the app showed a lower reported duration of NRT use compared to that indicated in the questionnaire (median for app 24 days, IQR 10.25; median for questionnaire 28 days, IQR 4.75; P=.007), and there appeared to be specific cases of overreporting to the questionnaire. Mean daily nicotine doses between the QD and Day 7 were lower when calculated using app data (median for app 40 mg, IQR 52.1; median for questionnaire 40 mg, IQR 63.1; P=.001), and some large outliers were evident for the questionnaire. Mean daily nicotine doses, adjusted for cigarettes smoked, were not associated with cotinine concentrations for either method (app rs=0.184, P=.55; questionnaire rs=0.031, P=.92), but the small sample size meant that the analysis was likely underpowered. Daily assessment of NRT use via a smartphone app facilitated more complete data (a higher response rate) than questionnaires, and reporting rates over 28 days were encouraging among pregnant women. App data had better face validity; retrospective questionnaires appeared to overestimate NRT use for some participants.

Factors associated with secondhand smoke exposure among non-smoking employees in the workplace: A cross-sectional study in Qingdao, China.

ObjectiveThis study was conducted to describe secondhand smoke (SHS) exposure among non-smoking employees in the workplace, and identify factors related to SHS exposure in Qingdao.MethodsThe study participants covered key non-smoking places stipulated in the “Qingdao City Smoking Control Regulations,” which included three categories: restaurants, bars, and office buildings. Airborne nicotine concentration in the workplace and saliva cotinine concentration of employees were measured. The questionnaire included employees’ demographic factors, smoke-free measures in the workplace, employers’ tobacco hazard knowledge, and attitudes towards smoke-free policy.ResultsA total of 222 non-smoking employees and 46 non-smoking employers were included in the study. The median concentrations of airborne nicotine and salivary cotinine were 0.389 μg/m3 and 0.575 ng/mL, respectively. Educational status, average number of workplace smokers per day, exposure time to SHS in the workplace, and whether smoking and non-smoking areas were divided significantly related to airborne nicotine concentration. Age, educational status, exposure time to SHS in the workplace, tobacco control training and publicity, and whether the employers support the “Qingdao Tobacco Control Regulation” were significantly related to salivary cotinine concentration.ConclusionsDespite the implementation of the “Qingdao Smoking Control Regulations” in 2013, the workplace remains an important location for SHS exposure. Interventions such as raising workers’ awareness of the risks associated with SHS exposure through health education and developing smoking prevention and cessation programs to reduce SHS exposure in the workplace are urgently needed.

Acute Effects of Nicotine on Physiological Responses and Sport Performance in Healthy Baseball Players.

There is interest in whether nicotine could enhance attention in sporting performance, but evidence on the acute effect of nicotine on physical response and sports performance in baseball players remains scant. This was an observational study to examine whether nicotine gum chewed before exercise could provide acute effects on physiological responses and sport performance. Accordingly, heart rate variability (HRV), saliva cotinine concentration and α-amylase activity, cognitive function, muscle strength, and baseball-hitting performance were measured. Thirteen healthy male non-smoker baseball players were recruited. Conducting two sequences with 7-day intervals, they chewed nicotine gum (nicotine group) or flavor-matched placebo gum (placebo group) for 30 min. HRV and saliva analyses were conducted before gum consumption (S1), after gum consumption (S2), and after test completion (S3). Cognitive, muscle strength, and baseball-hitting performance tests were performed after nicotine or placebo gum chewing. The outcomes of all assessed variables were compared within and between the groups. Significant changes in HRV, α-amylase, testosterone, and cortisol were observed in the nicotine group at S2 and S3 (p < 0.05). Compared with the placebo group, the nicotine group exhibited enhanced motor reaction times, grooved pegboard test (GPT) results on cognitive function, and baseball-hitting performance, and small effect sizes were noted (d = 0.47, 0.46 and 0.41, respectively). Nicotine could induce changes in endocrine and sympathetic nerve activity and enhance cognitive function and baseball-hitting performance. However, no increase in muscle strength was observed after nicotine intake.

Assessment of nicotine delivery and uptake in users of various tobacco/nicotine products

Today various tobacco and nicotine products are available, many of them can be regarded as potentially risk-reduced products when compared to the most frequently used product, combustible cigarettes (CCs). A commonality of these products is that they deliver nicotine, although in quite different amounts and uptake routes, the most common of which are inhalation through the lung and absorption through the oral mucosa. Product-specific nicotine delivery as well as the subject-related use patterns are important factors which determine the pharmacokinetics and achieved internal dose levels of the alkaloid. The latter two parameters are highly relevant for the long-term product loyalty and, consequently, for the implicated health risks, since the risk-reduced products will replace CCs in the long-term only when users will experience a similar level of satisfaction. We measured nicotine and its major metabolites in plasma, saliva and urine samples collected in a controlled clinical study with habitual users (10 per group) of CCs, electronic cigarettes (ECs), heated tobacco products (HTP), oral tobacco (OT), and nicotine replacement therapy (NRT). Non-users (NU) of any tobacco/nicotine products served as (negative) control group. Moderate to strong correlations were observed between the daily consumption and the urinary nicotine equivalents (comprising nicotine and its 10 major metabolites, Nic + 10) or plasma and saliva cotinine concentrations. The average daily nicotine dose as measured by the urinary excretion of Nic + 10 (reflecting approximately 95 % of the absorbed nicotine) amounted to 17 and 22 mg/24 h for smokers (CC) and OT users, respectively, while it was in the range of 6–12 mg/24 h for users of ECs, HTP and NRT products, with high inter-individual variations in each user group. The individual daily nicotine intake, which was calculated by applying product-specific models, showed none to good agreement with the corresponding internal nicotine dose measured by Nic + 10 excretion. Possible reasons for the observed deviations between calculated and objectively measured nicotine doses are discussed.

Comparison of saliva cotinine and exhaled carbon monoxide concentrations when smoking and after being offered dual nicotine replacement therapy in pregnancy.

Background and AimsAlthough English Stop Smoking Services routinely offer dual nicotine replacement therapy (NRT) to help pregnant women to quit smoking, little is known about how nicotine and tobacco smoke exposures following this compare with that from smoking. We compared, in pregnant women when smoking and after being offered dual NRT, saliva cotinine and exhaled carbon monoxide (CO) concentrations and numbers of daily cigarettes smoked.Design and SettingSecondary analysis of data from three sequential, observational, mixed‐methods cohort studies conducted as part of the Nicotine Replacement Effectiveness and Delivery in Pregnancy programme. Participants were recruited on‐line or in Nottingham University Hospitals (UK) antenatal clinics between June 2019 and September 2020.ParticipantsForty pregnant women, who agreed to try stopping smoking.InterventionParticipants were offered dual NRT, agreed a smoking quit date and received an intervention to improve adherence to NRT.MeasurementsSaliva cotinine and exhaled CO concentrations and reported number of cigarettes smoked per day.FindingsThere were no differences in saliva cotinine concentrations at baseline and day 7 post quit date [n = 20, mean difference = −32.31 ng/ml, 95% confidence interval (CI) = −68.11 to 3.5 ng/ml; P = 0.074, Bayes factor = 0.04]. There were reductions in the reported number of cigarettes smoked per day (n = 26, mean difference = −7 cigarettes, 95% CI = −8.35 to −5.42 cigarettes, P < 0.001) and concurrently in exhaled CO concentrations (n = 17, ratio of geometric means = 0.30 p.p.m., 95% CI = 0.17–0.52 p.p.m.; P < 0.001).ConclusionPregnant women who smoke and are offered dual nicotine replacement therapy (NRT) appear to show no change in their exposure to cotinine compared with their pre‐NRT exposure levels but they report smoking fewer cigarettes, as validated by reductions in exhaled carbon monoxide concentrations.

Identifying the Best Questions for Rapid Screening of Secondhand Smoke Exposure Among Children.

Many children suffer from secondhand smoke exposure (SHSe), which leads to a variety of negative health consequences. However, there is no consensus on how clinicians can best query parents for possible SHSe among children. We employed a data-driven approach to create an efficient screening tool for clinicians to quickly and correctly identify children at risk for SHSe. Survey data from mothers and biospecimens from children were ascertained from the Neurodevelopment and Improving Children's Health following Environmental Tobacco Smoke Exposure (NICHES) study. Included were mothers and their children whose saliva were assayed for cotinine (n = 351 pairs, mean child age = 5.6 years). Elastic net regression predicting SHSe, as indicated from cotinine concentration, was conducted on available smoking-related questions and cross-validated with 2015-2016 National Health and Nutrition Examination Survey (NHANES) data to select the most predictive items of SHSe among children (n = 1670, mean child age = 8.4 years). Answering positively to at least one of the two final items ("During the past 30 days, did you smoke cigarettes at all?" and "Has anyone, including yourself, smoked tobacco in your home in the past 7 days?") showed area under the curve = .82, and good specificity (.88) and sensitivity (.74). These results were validated with similar items in the nationally representative NHANES sample, area under the curve = .82, specificity = .78, and sensitivity = .77. Our data-driven approach identified and validated two items that may be useful as a screening tool for a speedy and accurate assessment of SHSe among children. The current study used a rigorous data-driven approach to identify questions that could reliably predict SHSe among children. Using saliva cotinine concentration levels as a gold standard for determining SHSe, our analysis employing elastic net regression identified two questions that served as good classifier for distinguishing children who might be at risk for SHSe. The two items that we validated in the current study can be readily used by clinicians, such as pediatricians, as part of screening procedures to quickly identify whether children might be at risk for SHSe.

Real-world exposure to graphic warning labels on cigarette packages in US smokers: The CASA randomized trial protocol

BackgroundThe US lags behind >120 countries in implementing graphic warning labels (GWLs) on cigarette packs. US courts prevented implementation of FDA's 2012 rule requiring GWLs citing the need for more evidence on effectiveness. After more research, in 2020, the FDA proposed a revised rule mandating GWLs. This trial will test how the introduction of GWLs influence cognitions and behavior in US smokers. MethodTo investigate the “real-world” impact of GWLs in US smokers, we are conducting a randomized trial involving a 3-month intervention and 8-month follow-up. The study recruited California smokers between September 2016 through December 2019 and randomly assigned them into 3 groups (1) Blank Pack devoid of any cigarette branding; (2) GWL Pack featuring 1 of 3 rotating images added to blank pack; or (3) their usual Standard US Pack. Throughout the 3-month intervention, participants purchased study-packaged cigarettes and reported daily cognitions and behavior through ecological momentary assessments. We will validate self-reported tobacco use with saliva cotinine concentrations following the 3-month intervention and 8-month follow-up. ResultsThe trial enrolled 359 participants (average age 39 years; average cigarette consumption half a pack/day). The 3 study groups were balanced on age, gender, race-ethnicity, education and income (17% low income) as well as on smoking related variables. ConclusionsThis 3-month real-world randomized trial will test the effect of repackaging cigarettes from standard US packs to GWL plain packs on smokers' perceptions of the risks of smoking, their perception of the appeal of their cigarettes, and on their smoking behavior.

The Association Between E-Cigarette Use Behaviors and Saliva Cotinine Concentration Among Healthy E-Cigarette Users in Malaysia.

Electronic cigarettes (e-cigarettes) have rapidly increased in popularity within the last 2 years in Malaysia. The study aims to understand the association between e-cigarette use behaviors and salivary cotinine (a CYP2AA metabolite of nicotine) concentration to inform the development of future e-cigarette control policies. A convenience sample of saliva from 144 e-cigarette users was obtained between November and December 2015. The study participants used refill liquid containing between 0 and 12 mg/ml of nicotine. The overall median cotinine concentration of the study participants was 81.1 ng/ml (interquartile range = 8.5-195.8). Among the zero-nicotine and single e-cigarette users, the median cotinine level was 51.1 (interquartile range = 8.20-125.35) ng/ml. Factors significantly associated with a higher salivary cotinine concentration were dual use of e-cigarettes and tobacco cigarettes, regular and daily e-cigarette use, a longer duration of e-cigarette use, using a higher amount of e-liquid, and a shorter duration to finish a refill. Multivariate analysis revealed that e-cigarette use of 1-6 and 6-12 months (but not 1 month and below) was significantly associated with a higher cotinine concentration. Cotinine found in zero-nicotine e-liquids implies the importance of stringent regulatory governance for the consistency of labeled nicotine content of e-cigarette liquid in the market. Zero-nicotine e-cigarette users should also be informed of the likelihood of environmental exposure to tobacco smoke. Future studies conducted on larger samples are warranted to validate the association between duration of e-cigarette use and salivary cotinine concentration as well as to investigate underlying mechanisms.

Assessment of the accuracy of salivary cotinine readings from NicAlert strips against a liquid chromatography tandem mass spectrometry assay in self-reported non-smokers who passed carbon monoxide but failed NicAlert validation.

NicAlert produces semi-quantitative assessments of cotinine levels in saliva or urine for verification of smoking abstinence. This study aimed to assess the accuracy of NicAlert readings against a liquid chromatography tandem mass spectrometry assay in smokers who had passed expired-air carbon monoxide (CO) verification but failed NicAlert verification. Comparison of NicAlert readings against readings from a reference assay using liquid chromatography tandem mass spectrometry. Geneva, Switzerland. Self-reported non-smokers (n=92) who in previous testing had CO of 0-3 parts per million (indicating no recent smoking) and reported not using any nicotine product, but had NicAlert readings ≥1 (indicating smoking). NicAlert produces readings of 0, 1 and 2+, which are reported by the manufacturer to correspond to saliva cotinine concentrations of 0-10ng/ml (indicating not smoking), 10-30ng/ml and 30+ ng/ml, respectively. Liquid chromatography tandem mass spectrometry was used as the reference. For 82 participants with a NicAlert reading of 1, only two of the liquid chromatography tandem mass spectrometry values were within the purported range of 10-30ng/ml; 71 were below 4ng/ml and half the values were below 0.5ng/ml. Two of the eight participants with NicAlert readings of 2 had laboratory values within the designated range. Neither of the two participants with NicAlert readings of 3 had a cotinine value within the designated range. In people who had passed carbon monoxide verification, NicAlert readings yielded a very high false-positive rate in detecting levels of cotinine indicative of smoking.

Saliva cotinine concentrations in pregnant women who smoke and use nicotine patches.

Background and AimsDue to concerns about increased exposure to nicotine, pregnant women using nicotine replacement therapy (NRT) to stop smoking are usually advised to stop using NRT if they relapse to smoking. This study investigated whether this is justified. We compared changes in saliva cotinine from baseline to 2 weeks post‐target quit date pregnant smokers who relapsed to smoking and continued to use their patches having been assigned to use nicotine patches or placebo.Design and SettingControlled pre–post design stratified by intervention condition from the ‘Study of Nicotine Patch in Pregnancy’, a randomized, placebo‐controlled trial.ParticipantsA sample of 268 pregnant women, assigned placebo (n = 122) or nicotine (n = 146) patches, who returned for further supplies of patches and who reported any smoking in the week prior to a visit at 2 weeks after their target quit date.MeasurementsSaliva cotinine concentrations were measured at baseline and 2 weeks after participants’ target quit dates. Any smoking in the previous week was assessed by self‐report, validated by expired air carbon monoxide (CO).FindingsThere was no change in saliva cotinine concentrations between baseline and 2 weeks post‐target quit date in saliva cotinine concentration in the nicotine patch group [ratio of geometric means = 0.94, 95% confidence interval (CI) = 0.83 to 1.07; P = 0.37, Bayes factor = 0.15]. However, there was a reduction in reported number of cigarettes smoked/day (mean difference −6, 95% CIs −7 to −5, P < 0.001) and in CO concentrations (mean difference −3.0 parts per million, 95% CIs −4.2 to −1.9, P < 0.001). These changes were not significantly different from changes in the placebo group except for cigarette consumption, which reduced more in the nicotine group (P = 0.046).ConclusionsIn women trying to stop smoking with the aid of a nicotine patch but having smoked at 2 weeks post‐target quit, their nicotine concentration did not change from baseline, but they reported smoking fewer cigarettes and had lower carbon monoxide concentrations.

Tobacco smoke exposure in early life and adolescence in relation to lung function.

Maternal smoking during pregnancy is associated with impaired lung function among young children, but less is known about long-term effects and the impact of adolescents' own smoking. We investigated the influence of maternal smoking during pregnancy, secondhand smoke exposure and adolescent smoking on lung function at age 16 years.The BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) birth cohort collected information on participants' tobacco smoke exposure through repeated questionnaires, and measured saliva cotinine concentrations at age 16 years. Participants performed spirometry and impulse oscillometry (IOS) at age 16 years (n=2295).Exposure to maternal smoking during pregnancy was associated with reduced forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio of −1.1% (95% CI −2.0 to −0.2%). IOS demonstrated greater resistance at 5–20 Hz (R5–20) in participants exposed to maternal smoking during pregnancy. Adolescents who smoked had reduced FEV1/FVC ratios of −0.9% (95% CI −1.8 to −0.1%) and increased resistance of 6.5 Pa·L–1·s (95% CI 0.7 to 12.2 Pa·L–1·s) in R5–20. Comparable associations for FEV1/FVC ratio were observed for cotinine concentrations, using ≥12 ng·mL−1 as a cut-off for adolescent smoking.Maternal smoking during pregnancy was associated with lower FEV1/FVC ratios and increased airway resistance. In addition, adolescent smoking appears to be associated with reduced FEV1/FVC ratios and increased peripheral airway resistance.

Estimation of Saliva Cotinine Cut-Off Points for Active and Passive Smoking during Pregnancy-Polish Mother and Child Cohort (REPRO_PL).

A reliable assessment of smoking status has significant public health implications and is essential for research purposes. The aim of this study was to determine optimal saliva cotinine cut-off values for smoking during pregnancy. The analyses were based on data from 1771 women from the Polish Mother and Child Cohort. Saliva cotinine concentrations were assessed by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS). The saliva cotinine cut-off value for active smoking was established at 10 ng/mL (sensitivity 96%, specificity 95%) and for passive smoking at 1.5 ng/mL (sensitivity 63%, specificity 71%). About 5% of the self-reported non-smoking women were classified as smokers based on the cotinine cut-off value. Significantly more younger, single, and less educated self-reported non-smokers had a cotinine concentration higher than 10 ng/mL compared to those who were older, married, and who had a university degree. Close to 30% of the non-smokers who indicated that smoking was not allowed in their home could be classified as exposed to passive smoking based on the cut-off value. The study suggests that self-reported smoking status is a valid measure of active smoking, whereas in the case of passive smoking, a combination of questionnaire data and biomarker verification may be required.

Fetal exposure to tobacco: nicotine and cotinine concentration in amniotic fluid and maternal saliva

Objective: Fetal exposure to tobacco constituents is a risk factor for negative birth outcomes. We aimed to determine the relationships between nicotine and cotinine concentrations in amniotic fluid and maternal saliva.Methods: As part of a therapeutic trial, 42 pregnant smokers agreed to sample amniotic fluid (8 samples from amniocentesis, 34 at birth). Their smoking characteristics were collected along with the newborns’ birth outcomes.Results: The median concentrations [IQR] in amniotic fluid and saliva were 11 [7–31] and 38 [7–174] μg/L for nicotine and 72 [22–123] μg/L and 55 [17–109] μg/L for cotinine, respectively. Multivariate models showed that saliva cotinine concentration predicted amniotic fluid nicotine and cotinine concentrations (R2 = 0.398, p < 0.0001 and R2 = 0.708, p < 0.0001 respectively). Amniotic fluid nicotine or cotinine concentration was not associated with birth weight. In multivariate analysis, the time elapsed since the last cigarette was the only variable associated with increased birth weight (R2 = 0.237, p = 0.002).Conclusions: Maternal saliva sampling for the determination of cotinine concentration is of interest to monitor fetal exposure to nicotine of any origin. Nevertheless, the time elapsed since the last cigarette was a better predictor of birth weight than the biomarkers’ concentrations in amniotic fluid or maternal saliva.

Implications of Misclassification Errors in Empirical Studies of Adolescent Smoking Behaviours.

Misclassification errors in a dependent variable can introduce attenuation bias to covariate effects in a binary choice model. Misreporting of smoking behaviours by adolescents has been widely documented. However, the consequence in empirical studies of adolescent smoking participation has received little attention. This study uses the Health Survey for England (HSE) to investigate the extent and implication of misclassification errors in self-reported smoking among adolescents aged 11-15years. The HSE contains both a self-reported smoking component and an objective measure of smoking obtained from saliva cotinine assays. Saliva cotinine concentration ≥12ng/ml is considered the 'true' indicator of adolescent smoking participation against which self-reported smoking is compared. The findings show that smoking is misreported in this age group, resulting in a downwards bias of marginal effect estimates. Given the widespread use of self-reported smoking data, this study explores the performance of the Hausman, Abrevaya and Scott-Morton-modified maximum likelihood estimation (HAS approach) in recovering true estimates of covariate effects. In this context, the HAS approach performs better when the misclassification probabilities are treated as constants compared with when they are treated as conditionally dependent parameters. Copyright © 2016 John Wiley & Sons, Ltd.

Relationships between nicotine and cotinine concentrations in maternal milk and saliva.

Breastfeeding may be impaired due to nicotine excreted into the milk of smoking mothers. We investigated the relationships between nicotine and cotinine concentrations in maternal milk and saliva among breastfeeding smokers. The 41 mothers reported their cigarette consumption between waking up and milk and saliva sampling. The median sampling time took place four days after delivery. Nicotine and cotinine concentrations were determined by liquid chromatography and UV detection, after a single-step saliva or three-step milk liquid-to-liquid extraction. The median (interquartile range) concentrations in milk and saliva were 7 (6-22) and 27 (4-207) μg/L for nicotine and 24 (5-111) and 22 (4-120) μg/L for cotinine, respectively. Milk cotinine was positively associated with saliva cotinine (p < 0.0001) and cigarette consumption (p = 0.039) and inversely associated with the time since the last cigarette (p = 0.0004, model R(2) = 0.90). Milk nicotine was associated with saliva nicotine concentration (p = 0.0017) and cigarette consumption (p = 0.0023, model R(2) = 0.63). Saliva nicotine concentration was not a very good estimate of milk nicotine concentration in breastfeeding mothers. Saliva cotinine concentration may be used instead of milk cotinine concentration to estimate tobacco or nicotine exposure among breastfed neonates or infants.

Prevalence of NRT use and associated nicotine intake in smokers, recent ex-smokers and longer-term ex-smokers.

BackgroundNicotine replacement therapy (NRT) is used by smokers wanting to reduce their smoking and to quit. However, there are very little data on nicotine intake associated with NRT use in representative population samples. This study aimed to provide estimates for NRT use and associated nicotine exposure among smokers, recent and longer-term ex-smokers in England, a country with a permissive regulatory regime for nicotine substitution.MethodsIn the Smoking Toolkit Study, a monthly series of representative household surveys of adults aged 16+ in England, current and recent ex-smokers who agreed to be re-contacted were followed up 6 months later and standard socio-demographic and smoking characteristics assessed (N = 5,467, response rate 25.1%). A random sub-sample (N = 1,614; 29.5%) also provided saliva, analysed for cotinine.ResultsThe sample followed up was broadly representative of the original sample. At follow-up, 11.8% (95%CI 10.9–12.8, N = 565) of current smokers, 34.8% (95%CI 28.9–41.3, N = 77) of recent (≤3 months) ex-smokers, and 7.8% (95%CI 5.6–10.6, N = 36) of longer-term (>3 months) ex-smokers reported using NRT. Smokers who used NRT had similar saliva cotinine concentrations to smokers who did not use NRT (mean ± sd = 356.0±198.6 ng/ml vs. 313.1±178.4 ng/ml). Recent ex-smokers who used NRT had levels that were somewhat lower, but not significantly so, than current smokers (216.7±179.3 ng/ml). Longer-term ex-smokers using NRT had still lower levels (157.3±227.1 ng/ml), which differed significantly from smokers using NRT (p = 0.024).ConclusionsConcurrent use of nicotine replacement therapy while smoking is relatively uncommon and is not associated with higher levels of nicotine intake. Among ex-smokers, NRT use is common in the short but not longer-term and among longer-term users is associated with lower nicotine intake than in smokers.

EPA-1706 – Tobacco dependence in patients with Leber's hereditary optic neuropathy

Introduction Leber hereditary optic neuropathy (LHON), an inherited mitochondriopathy, can result in progressive degeneration of retinal ganglial cells and thus in worsening and even loss of vision. Smoking is probably the most important risk factor for the onset and progression of the disease. Objectives/Aims To assess the smoking history and status of LHON patients to determine the need for tobacco cessation programmes in this collective. Methods From November 2011 to January 2012, 27 LHON patients completed a standardised questionnaire including Fagerstrom Test for Nicotine Dependence (FTND), age when smoking started and quit attempts. Smoking history was confirmed by measuring expired carbon monoxide and saliva levels of nicotine and cotinine. Results Twenty men (74%) and 7 women (26%) were evaluated. The average age at disease onset was 29 years. Fifteen (56%) of the participants were smokers at the time of the evaluation, 3 (11%) had quit smoking after diagnosis of LHON and 9 (33%) had never smoked. Saliva nicotine and cotinine concentration correlated significantly with the degree of physical dependence (p Conclusions Even after being informed of the probability of blindness if they continued to smoke, only 3 of 18 patients quit smoking. Further studies need to assess the effects of integrating smoking cessation programmes into the treatment offered to patients with manifest LHON. Also, the role of smoking in the onset and progression of the disease needs to be validated to optimise prevention and treatment measures for carriers and LHON patients.

Good relationship between saliva cotinine kinetics and plasma cotinine kinetics after smoking one cigarette

This study investigated the relationship between plasma and saliva cotinine kinetics after smoking one cigarette and the relationship between cotinine kinetics and estimated nicotine intake, which was calculated as mouth level exposure (MLE) of nicotine, from smoking two test cigarettes with different nicotine yields. This study was conducted in 16 healthy adult Japanese smokers, who did not have null nor reduced-activity alleles of CYP2A6, with a quasi-randomized crossover design of smoking a low-tar cigarette or a high-tar cigarette. Saliva cotinine showed similar concentration profiles to plasma cotinine, and all of the calculated pharmacokinetic parameters of cotinine showed the same values in plasma and saliva. The Cmax and AUC of cotinine showed almost the same dose-responsiveness to the estimated MLE of nicotine between plasma and saliva, but the tmax and t1/2 of cotinine were not affected by the estimated MLE of nicotine in either plasma or saliva. The results show that saliva cotinine kinetics reflects plasma cotinine kinetics, and measurement of saliva cotinine concentration gives the same information as plasma cotinine on the nicotine intake. Thus, saliva cotinine would be a good and less-invasive exposure marker of cigarette smoke, reflecting the plasma cotinine concentration and kinetics.

A selective reversible monoamine oxidase B inhibitor in smoking cessation: effects on its own and in association with transdermal nicotine patch

Monoamine oxidase B (MAO-B) activity is reduced in smokers. A MAO-B inhibitor alone or co-administered with nicotine may mimic the effects of smoking and be a candidate drug for smoking cessation. This study aims to determine the efficacy and safety of EVT302, a selective reversible MAO-B inhibitor, alone and on top of nicotine patch (NP) in smoking cessation. This was a randomised, double blind, placebo-controlled phase II, multicentre trial. Smokers (≥10 cigarettes/day) received either EVT302 (N = 145) or placebo (N = 145), or EVT302 (N = 61) or placebo (N = 61) on top of open label NP 21 mg/day for 8 weeks. The main comparison was between EVT302 and placebo without NP. The primary outcome measure was end-of-treatment 4-week continuous abstinence rate (CAR). point prevalence abstinence rate, saliva cotinine concentrations in the groups without NP, urge to smoke, nicotine withdrawal symptoms and assessment of subjective effects of cigarettes. The 4-week CAR was 15.2 % in the placebo, 17.2 % in the EVT302, 26.8 % in the NP + placebo and 32.8 % in the NP + EVT302 groups, respectively. There was no difference between EVT302 and placebo either alone (adjusted OR: 1.45, 95 % CI: 0.65-3.26) or when co-administered with NP. No statistically significant difference occurred for the secondary outcome measures. The selective, reversible MAO-B inhibitor EVT302 was not superior to placebo in helping smokers quit, in line with data with selegiline and confirms that MAO-B inhibitors are not effective in smoking cessation. Co-administration of NP does not provide a supplementary benefit.

Variation in saliva cotinine as a function of self-reported attempts to reduce cigarette consumption

Cotinine is an accurate objective marker of nicotine intake. There is very little information on its stability over time or as a function of self-reported attempts at smoking reduction. This study aimed to assess the stability of saliva cotinine concentrations over a 3-month period, as a function of self-reported attempts to reduce cigarette consumption, using data from a general population sample of English smokers. Six-hundred and ninety-one smokers from a population sample of English smokers provided saliva samples for cotinine analysis on two occasions 3 months apart. Data on cigarette consumption, whether smokers reported that they were attempting to cut down consumption and concurrent use of nicotine replacement therapy (NRT), were also collected on both occasions. The 'test-retest' measure of cotinine stability was 0.76, and the simple correlation was 0.73. Smokers not using NRT who reported cutting down on one occasion but not the other showed a small reduction in cigarette consumption at the time they were cutting down (1.1 cig per day, p = 0.013) but no significant difference in saliva cotinine concentrations (mean reduction = 13.4 ng/ml, p = 0.39). Saliva cotinine concentrations show moderate-to-high stability within subjects over a 3-month period. Smokers' reports of attempting to cut down their smoking are associated with small daily cigarette consumption decreases but no detectable change in nicotine intake.