Self-titration by experienced e-cigarette users: blood nicotine delivery and subjective effects.

RATIONALE: Self-titration is well documented in the tobacco literature. The extent to which e-cigarette users (vapers) self-titrate is unknown. OBJECTIVE: This study explored the effects of high and low nicotine strength liquid on puffing topography, nicotine delivery and subjective effects in experienced vapers. METHODS: Eleven experienced male vapers completed 60 min of ad libitum vaping under low (6 mg/mL) and high (24 mg/mL) nicotine liquid conditions in two separate sessions. Measurements included puffing topography (puff number, puff duration, volume of liquid consumed) and changes in plasma nicotine levels, craving, withdrawal symptoms, self-reported hit, satisfaction and adverse effects. RESULTS: Liquid consumption and puff number were higher and puff duration longer, in the low nicotine strength condition (all ps < 0.01). The mean difference in nicotine boost from baseline in the low condition was 8.59 (7.52) ng/mL, 16.99 (11.72) ng/mL and 22.03 (16.19) ng/mL at 10, 30 and 60 min, respectively. Corresponding values for the high condition were 33.77 (34.88) ng/mL, 35.48 (28.31) ng/mL and 43.57 (34.78) ng/mL (ps < 0.05). There were no statistically significant differences between conditions in self-reported craving, withdrawal symptoms, satisfaction, hit or adverse effects. CONCLUSIONS: Vapers engaged in compensatory puffing with lower nicotine strength liquid, doubling their consumption. Whilst compensatory puffing was sufficient to reduce craving and withdrawal discomfort, self-titration was incomplete with significantly higher plasma nicotine levels in the high condition.

Recent trends in children's exposure to second-hand smoke in England: cotinine evidence from the Health Survey for England.

AIMS: To examine changes in children's exposure to second-hand tobacco smoke in England since 1998. DESIGN: Repeated cross-sectional surveys of the general population in England. SETTING: The Health Survey for England. PARTICIPANTS: A total of 37 038 children participating in surveys from 1998 to 2012, 13 327 of whom were aged 4-15 years, had available cotinine and were confirmed non-smokers. MEASUREMENTS: The proportion of children with smoking parents; the proportion of children living in homes reported to be smoke-free; the proportion of children with undetectable concentrations of cotinine; linear and quadratic trend estimates of geometric mean cotinine across years. FINDINGS: By 2012, 87.3% of children lived in a home that was smoke-free {97.2% [95% confidence interval (CI) = 95.9-98.1] when parents were non-smokers, 61.3% (95% CI = 55.5-66.8) when one or both parents smoked}. A total of 68.6% (95% CI = 64.3-72.6%) of children had undetectable cotinine in 2012, up from 14.3% (95% CI = 12.7-16.0%) in 1998. There was a highly significant linear trend across years (with a small but significant quadratic term) to declining geometric mean cotinine in all children from 0.52 ng/ml (95% CI = 0.48-0.57) in 1998 to 0.11 ng/ml (95% CI = 0.10-0.12) in 2012. Children from routine/manual backgrounds were more exposed, but experienced similar gains across years to those from non-manual backgrounds. CONCLUSIONS: In England, children's exposure to second-hand smoke has declined by 79% since 1998, with continuing progress since smoke-free legislation in 2007. An emerging social norm in England has led to the adoption of smoke-free homes not only when parents are non-smokers, but also when they smoke.

Did smokefree legislation in England reduce exposure to secondhand smoke among nonsmoking adults? Cotinine analysis from the Health Survey for England.

BACKGROUND: On 1 July 2007, smokefree legislation was implemented in England, which made virtually all enclosed public places and workplaces smokefree. OBJECTIVES: We examined trends in and predictors of secondhand smoke exposure among nonsmoking adults to determine whether exposure changed after the introduction of smokefree legislation and whether these changes varied by socioeconomic status (SES) and by household smoking status. METHODS: We analyzed salivary cotinine data from the Health Survey for England that were collected in 7 of 11 annual surveys undertaken between 1998 and 2008. We conducted multivariate regression analyses to examine secondhand smoke exposure as measured by the proportion of nonsmokers with undetectable levels of cotinine and by geometric mean cotinine. RESULTS: Secondhand smoke exposure was higher among those exposed at home and among lower-SES groups. Exposure declined markedly from 1998 to 2008 (the proportion of participants with undetectable cotinine was 2.9 times higher in the last 6 months of 2008 compared with the first 6 months of 1998 and geometric mean cotinine declined by 80%). We observed a significant fall in exposure after legislation was introduced--the odds of having undetectable cotinine were 1.5 times higher [95% confidence interval (CI): 1.3, 1.8] and geometric mean cotinine fell by 27% (95% CI: 17%, 36%) after adjusting for the prelegislative trend and potential confounders. Significant reductions were not, however, seen in those living in lower-social class households or homes where smoking occurs inside on most days. CONCLUSIONS: We found that the impact of England's smokefree legislation on secondhand smoke exposure was above and beyond the underlying long-term decline in secondhand smoke exposure and demonstrates the positive effect of the legislation. Nevertheless, some population subgroups appear not to have benefitted significantly from the legislation. This finding suggests that these groups should receive more support to reduce their exposure.

Interlaboratory comparability of serum cotinine measurements at smoker and nonsmoker concentration levels: a round-robin study.

INTRODUCTION: Cotinine, the primary proximate metabolite of nicotine, is commonly measured as an index of exposure to tobacco in both active users of tobacco and nonsmokers with possible exposure to secondhand smoke (SHS). A number of laboratories have implemented analyses for measuring serum cotinine in recent years, but there have been few interlaboratory comparisons of the results. Among nonsmokers exposed to SHS, the concentration of cotinine in blood can be quite low, and extensive variability in these measurements has been reported in the past. METHODS: In this study, a group of seven laboratories, all experienced in serum cotinine analysis, measured eight coded serum pools with concentrations ranging from background levels of about 0.05 ng/ml to relatively high concentrations in the active smokers range. All laboratories used either gas-liquid chromatography with nitrogen-phosphorus detection or liquid chromatography with mass spectrometric detection. RESULTS: All seven laboratories reliably measured the cotinine concentrations in samples that were within the range of their methods. In each case, the results for the pools were correctly ranked in order, and no significant interlaboratory bias was observed at the 5% level of significance for results from any of the pools. DISCUSSION: We conclude that present methods of chromatographic analysis of serum cotinine, as used by these experienced laboratories, are capable of providing accurate and precise results in both the smoker and the nonsmoker concentration range.

Changes in environmental tobacco smoke (ETS) exposure over a 20-year period: cross-sectional and longitudinal analyses.

AIMS: To examine long-term changes in environmental tobacco smoke (ETS) exposure in British men between 1978 and 2000, using serum cotinine. DESIGN: Prospective cohort: British Regional Heart Study. SETTING: General practices in 24 towns in England, Wales and Scotland. PARTICIPANTS: Non-smoking men: 2125 studied at baseline [questionnaire (Q1): 1978-80, aged 40-59 years], 3046 studied 20 years later (Q20: 1998-2000, aged 60-79 years) and 1208 studied at both times. Non-smokers were men reporting no current smoking with cotinine < 15 ng/ml at Q1 and/or Q20. MEASUREMENTS: Serum cotinine to assess ETS exposure. FINDINGS: In cross-sectional analysis, geometric mean cotinine level declined from 1.36 ng/ml [95% confidence interval (CI): 1.31, 1.42] at Q1 to 0.19 ng/ml (95% CI: 0.18, 0.19) at Q20. The prevalence of cotinine levels < or = 0.7 ng/ml [associated with low coronary heart disease (CHD) risk] rose from 27.1% at Q1 to 83.3% at Q20. Manual social class and northern region of residence were associated with higher mean cotinine levels both at Q1 and Q20; older age was associated with lower cotinine level at Q20 only. Among 1208 persistent non-smokers, cotinine fell by 1.47 ng/ml (95% CI: 1.37, 1.57), 86% decline. Absolute falls in cotinine were greater in manual occupational groups, in the Midlands and Scotland compared to southern England, although percentage decline was very similar across groups. CONCLUSIONS: A marked decline in ETS exposure occurred in Britain between 1978 and 2000, which is likely to have reduced ETS-related disease risks appreciably before the introduction of legislation banning smoking in public places.

Assessing smoking status in children, adolescents and adults: cotinine cut-points revisited.

AIMS: To reassess saliva cotinine cut-points to discriminate smoking status. Cotinine cut-points that are in use were derived from relatively small samples of smokers and non-smokers 20 or more years ago. It is possible that optimal cut-points may have changed as prevalence and exposure to passive smoking have declined. DESIGN: Cross-sectional survey of the general population, with assessment of self-reported smoking and saliva cotinine. PARTICIPANTS: A total of 58 791 respondents aged 4 years and older in the Health Survey for England for the years 1996-2004 who provided valid saliva cotinine specimens. MEASURES: Saliva cotinine concentrations, demographic variables, self-reported smoking, presence or absence of smoking in the home, a composite index of social disadvantage derived from occupation, housing tenure and access to a car. FINDINGS: A cut-point of 12 ng/ml performed best overall, with specificity of 96.9% and sensitivity of 96.7% in discriminating confirmed cigarette smokers from never regular smokers. This cut-point also identified correctly 95.8% of children aged 8-15 years smoking six or more cigarettes a week. There was evidence of substantial misreport in claimed ex-smokers, especially adolescents (specificity 72.3%) and young adults aged 16-24 years (77.5%). Optimal cut-points varied by presence (18 ng/ml) or absence (5 ng/ml) of smoking in the home, and there was a gradient from 8 ng/ml to 18 ng/ml with increasing social disadvantage. CONCLUSIONS: The extent of non-smokers' exposure to other people's tobacco smoke is the principal factor driving optimal cotinine cut-points. A cut-point of 12 ng/ml can be recommended for general use across the whole age range, although different cut-points may be appropriate for population subgroups and in societies with differing levels of exposure to secondhand smoke.

Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement.

OBJECTIVE: To examine the associations between a biomarker of overall passive exposure to tobacco smoke (serum cotinine concentration) and risk of coronary heart disease and stroke. DESIGN: Prospective population based study in general practice (the British regional heart study). PARTICIPANTS: 4729 men in 18 towns who provided baseline blood samples (for cotinine assay) and a detailed smoking history in 1978-80. MAIN OUTCOME MEASURE: Major coronary heart disease and stroke events (fatal and non-fatal) during 20 years of follow up. RESULTS: 2105 men who said they did not smoke and who had cotinine concentrations < 14.1 ng/ml were divided into four equal sized groups on the basis of cotinine concentrations. Relative hazards (95% confidence intervals) for coronary heart disease in the second (0.8-1.4 ng/ml), third (1.5-2.7 ng/ml), and fourth (2.8-14.0 ng/ml) quarters of cotinine concentration compared with the first (> or = 0.7 ng/ml) were 1.45 (1.01 to 2.08), 1.49 (1.03 to 2.14), and 1.57 (1.08 to 2.28), respectively, after adjustment for established risk factors for coronary heart disease. Hazard ratios (for cotinine 0.8-14.0 nu > or = 0.7 ng/ml) were particularly increased during the first (3.73, 1.32 to 10.58) and second five year follow up periods (1.95, 1.09 to 3.48) compared with later periods. There was no consistent association between cotinine concentration and risk of stroke. CONCLUSION: Studies based on reports of smoking in a partner alone seem to underestimate the risks of exposure to passive smoking. Further prospective studies relating biomarkers of passive smoking to risk of coronary heart disease are needed.

Measuring nicotine intake in population surveys: comparability of saliva cotinine and plasma cotinine estimates.

Both plasma and saliva cotinine levels have been reported in surveys of smoking behavior, and it is of interest to know how closely these two measures correspond. Plasma and saliva specimens were gathered from a sample of 605 respondents in the 1998 Health Survey for England and assayed for cotinine by a well-proven gas chromatographic method. Plasma and saliva cotinine concentrations were highly correlated (r=.99). On average, concentrations in saliva were 25% higher than in plasma, and this ratio applied both at the low levels attributable to passive smoking and across the range of active smoking values. The ratio was somewhat lower in younger people than in older people and also varied significantly by body mass index but did not differ by gender. Calculation of the limits of agreement revealed substantial uncertainty in the predicted plasma value corresponding to a given saliva cotinine, and vice versa. For comparisons across subjects, the mean plasma cotinine level corresponding to a mean saliva cotinine level can be estimated with confidence, but at the level of the individual, considerable predictive uncertainty remains.