The goal of the study was to examine the association between biomarkers and environmental measures of second hand smoke (SHS) with caregiver, i.e. parent or legal guardian, report of household smoking behavior and morbidity measures among children with asthma. Baseline data were drawn from a longitudinal intervention for 126 inner city children with asthma, residing with a smoker. Most children met criteria for moderate to severe persistent asthma (63%) versus mild intermittent (20%) or mild persistent (17%). Household smoking behavior and asthma morbidity were compared with child urine cotinine and indoor measures of air quality including fine particulate matter (PM2.5) and air nicotine (AN). Kruskal–Wallis, Wilcoxon rank-sum and Spearman rho correlation tests were used to determine the level of association between biomarkers of SHS exposure and household smoking behavior and asthma morbidity. Most children had uncontrolled asthma (62%). The primary household smoker was the child's caregiver (86/126, 68%) of which 66 (77%) were the child's mother. Significantly higher mean PM2.5, AN and cotinine concentrations were detected in households where the caregiver was the smoker (caregiver smoker: PM2.5 μg/m3: 44.16, AN: 1.79 μg/m3, cotinine: 27.39 ng/ml; caregiver non-smoker: PM2.5: 28.88 μg/m3, AN: 0.71 μg/m3, cotinine:10.78 ng/ml, all P ≤ 0.01). Urine cotinine concentrations trended higher in children who reported 5 or more symptom days within the past 2 weeks (>5 days/past 2 weeks, cotinine: 28.1 ng/ml vs. <5 days/past 2 weeks, cotinine: 16.2 ng/ml; P = 0.08). However, environmental measures of SHS exposures were not associated with asthma symptoms. Urban children with persistent asthma, residing with a smoker are exposed to high levels of SHS predominantly from their primary caregiver. Because cotinine was more strongly associated with asthma symptoms than environmental measures of SHS exposure and is independent of the site of exposure, it remains the gold standard for SHS exposure assessment in children with asthma.
Asthma; Children; Cotinine; Particulate matter; Air Nicotine
To explore the relationship between environmental tobacco smoke (ETS) exposure and behavior among inner-city children with significant asthma.
We analyzed baseline data for 200 children 4 to 10 years old who were enrolled in an asthma program. Environmental tobacco smoke exposure was measured by the child’s salivary cotinine level. Caregivers completed the 28-item Behavior Problem Index (BPI). Positive responses were summed for a total BPI score, and children with scores >14 were considered to have significant behavior problems. We conducted Student t tests and multivariate regression analyses to determine the association of children’s cotinine levels with BPI scores.
Overall, 56% of children were male, 65% were black, and 72% had Medicaid. Mean cotinine level was 1.47 ng/mL. Overall, 30% of children had total BPI scores >14. Children with cotinine values >1.47 ng/mL had significantly higher scores compared with children with lower cotinine values on total BPI (12.5 vs 10.2), as well as externalizing (9.0 vs 7.2), antisocial (2.3 vs 1.7), and immature (2.1 vs 1.6) subscales. In a multivariate model, log cotinine remained independently associated with externalizing (P = .04), headstrong (P = .04), and antisocial behavior (P = .04).
Cotinine levels are independently associated with problem behaviors among this sample of urban children with asthma.
behavior; childhood asthma; environmental smoke exposure; inner-city
Environmental tobacco smoke (ETS) causes increased morbidity among children with asthma, however pediatricians do not consistently screen and counsel families of asthmatic children regarding ETS. An index score based on parent report of exposure could help providers efficiently screen for ETS.
1) To develop an index measure of ETS based on parent self-report of smoking behaviors; 2) To determine whether the index score is associated with children’s present and future cotinine levels.
Data were drawn from a community intervention for inner-city children with persistent asthma (n=226, response rate 72%). Measures of child salivary cotinine and parent self-reported ETS-related behaviors were obtained at baseline and 7–9 months later. To develop the index score, we used a 15-fold cross-validation method on 70% of our data that considered combinations of smoke exposure variables, controlling for demographics. We chose the most parsimonious model that minimized the mean square predictive error. The resulting index score included primary caregiver smoking and home smoking ban status. We validated our model on the remaining 30% of data. ANOVA and multivariate analyses were used to determine the association of the index score with children’s cotinine levels.
54% of asthmatic children lived with ≥1 smoker and 51% of caregivers reported a complete home smoking ban. The children’s mean baseline cotinine was 1.55ng/ml (range 0.0–21.3). Children’s baseline and follow-up cotinine levels increased as scores on the index measure increased. In a linear regression, the index score was significantly and positively associated with children’s cotinine measurements at baseline (p<.001, model R2=.37) and 7–9 months later (p<.001, R2=.38).
An index measure with combined information regarding primary caregiver smoking and household smoking restrictions helps to identify asthmatic children with the greatest exposure to ETS, and can predict children who will have elevated cotinine levels 7–9 months later.
Environmental tobacco smoke; asthma; children; primary care; screening
smoking is a major cause of respiratory morbidity in children. However,
few studies give accurate estimates of the health effects of passive
smoking in children with asthma using an objective measure of exposure.
The effects of passive smoking using salivary cotinine levels to
measure exposure were investigated.
METHODS—A sample of
438 children aged 2-12 years with asthma who had a parent who smoked
were recruited in Tayside and Fife, Scotland. Health service contacts
for asthma, assessed from GP case records, were used as a proxy for morbidity.
U-shaped relationship was found between the salivary cotinine level and
health service contacts for asthma: compared with low cotinine levels
those with moderate cotinine levels had a reduced contact rate
(relative rate (RR) = 0.91, 95% confidence interval (CI) 0.80 to
1.05), whereas high cotinine levels were associated with an increased
rate of contact (RR = 1.19, 95% CI 1.05 to 1.37). In contrast, a
strong association was seen with the amount the parent reported smoking
in front of the child: the higher the level the fewer visits were made
for asthma (RR for everyday exposure = 0.66, 95% CI 0.56 to 0.77).
This effect was not seen for non-respiratory visits. Demographic
factors, age of child, and number of children in the family all had a
powerful effect on the number of visits for asthma. The parents'
perception of asthma severity was associated with visit frequency
independent of actual severity (derived from drug treatment).
of parental smoking in the home are associated with a reduction in
health care contacts for asthma. This could be due to a lack of
awareness of asthma symptoms among heavy smokers or a reluctance to
visit the GP. Children with asthma who have parents who smoke heavily
may not be receiving adequate management.
Our aim was to understand the strength of association between parental smoking and child environmental tobacco smoke (ETS) exposure in order to inform the development of future tobacco control policies. ETS was measured using child cotinine levels below the active smoking threshold.
Participants were drawn from the Avon Longitudinal Study of Parents and Children and included 3,128 participants at age 7 years and 1,868 participants at age 15 years. The primary outcome was cotinine levels of nonsmoking children, to investigate the relationship between maternal smoking and child cotinine levels. The secondary outcome was cotinine levels of all individuals to investigate the relationship between child smoking and child cotinine levels. Maternal and child smoking behavior was assessed by self-report questionnaire. We adjusted for several sociodemographic variables.
We found an association between maternal smoking and child cotinine at age 7 years (mean cotinine = 1.16ng/ml serum, ratio of geometric means = 3.94, 95% CI = 2.86–5.42) and at age 15 years (mean cotinine = 0.94ng/ml serum, ratio of geometric means = 5.26, 95% CI = 3.06–9.03), after adjustment for potential confounders.
The magnitude of this association for children whose mothers were heavy smokers was comparable with the quantity of half the levels of cotinine observed among children who were irregular (i.e., nonweekly) active smokers, and it was greater than five times higher than that seen in nonsmoking children whose mothers didn’t smoke. This provides further evidence for the importance of public health interventions to reduce smoking exposure in the home.
Home and car smoking bans implemented by caregivers are important approaches to reducing children’s secondhand smoke (SHS) exposure and attendant health risks. Such private smoking bans are usually informal and are subject to individuals’ interpretation, observation, and recall. Relying on a single reporter may lead to misclassification of bans in families.
To determine (1) proportion of families with discordant reports of bans; (2) association between parent–child report agreement and SHS exposure; and (3) whether including a second reporter of bans improves prediction of child SHS exposure.
In each of 386 participating families a preteen and a parent reported separately on their home and car smoking bans, and agreement was determined. ANOVA, chi-square, and multiple regression were used to determine relationships between SHS exposure (measured by urine cotinine and reported exposure) and home/car smoking bans reported by preteens and parents.
In 19% of families, reports disagreed for home smoking bans; 30% for car smoking bans. Families who agreed on the presence of a ban had the lowest exposure, families who agreed on the absence of a ban had the highest exposure, and intermediate exposure for those who disagreed. Parent and child reports of bans each explained significant, unique variance in child SHS exposure.
Due to relatively high prevalence of discordant reporting, a more accurate classification of home/car bans may result from including multiple reporters.
Objective To examine the association between a biomarker of exposure to secondhand smoke (salivary cotinine concentration) and cognitive impairment.
Design Cross sectional analysis of a national population based study.
Setting Stratified random sample of households throughout England.
Participants 4809 non-smoking adults aged 50 years or more from the 1998, 1999, and 2001 waves of the Health Survey for England who also participated in the 2002 wave of the English Longitudinal Study of Ageing and provided saliva samples for cotinine assay and a detailed smoking history.
Main outcome measure Cognitive impairment as defined by the lowest 10% of scores on a battery of neuropsychological tests.
Results Participants who did not smoke, use nicotine products, or have salivary cotinine concentrations of 14.1 ng/ml or more were divided into four equal size groups on the basis of cotinine concentrations. Compared with the lowest fourth of cotinine concentration (0.0-0.1 ng/ml) the odds ratios (95% confidence intervals) for cognitive impairment in the second (0.2-0.3 ng/ml), third (0.4-0.7 ng/ml), and highest fourths (0.8-13.5 ng/ml) were 1.08 (0.78 to 1.48), 1.13 (0.81 to 1.56), and 1.44 (1.07 to 1.94; P for trend 0.02), after adjustment for a wide range of established risk factors for cognitive impairment. A similar pattern of associations was observed for never smokers and former smokers.
Conclusions Exposure to secondhand smoke may be associated with increased odds of cognitive impairment. Prospective nationally representative studies relating biomarkers of exposure to cognitive decline and risk of dementia are needed.
OBJECTIVE--To assess the contribution of passive exposure to tobacco smoke to the development of middle ear underpressure and effusion. DESIGN--Cross sectional observational study. SETTING--One third of the primary schools in Edinburgh. SUBJECTS--892 Children aged 6 1/2 to 7 1/2 were examined, and satisfactory tympanograms were obtained in 872. Results of assay of salivary cotinine concentrations were available for 770 children, and satisfactory tympanograms were available for 736 of these. END POINT--Correlation of the prevalence of middle ear underpressure and effusion with concentrations of the marker of nicotine, cotinine, in the saliva of the children. MEASUREMENTS AND MAIN RESULTS--Middle ear pressure and compliance were measured in both ears by impedance tympanometry. Salivary cotinine concentrations were assayed by gas-liquid chromatography. Cotinine concentrations increased with the number of smokers in the household. Girls had higher concentrations than boys, and children living in rented housing had higher concentrations than those living in housing owned by their parents. There was a trend towards more abnormal tympanometric findings with increasing cotinine concentration, the odds ratio for a doubling of the cotinine concentration being 1.14 (95% confidence interval 1.03 to 1.27). After adjustment for the sex of the child and housing tenure the odds ratio for a doubling of the cotinine concentration was 1.13 (1.00 to 1.28). CONCLUSIONS--The results of this study are consistent with those of case-control studies of children attending for an operation to relieve middle ear effusion. They indicate that the disease should be added to the list of recognised hazards associated with passive smoking. About one third of the cases of middle ear effusion in this study were statistically attributable to exposure to tobacco smoke.
There is a lack of data describing the exposure of Malaysian schoolchildren to Secondhand Smoke (SHS). The aim of this study is to identify factors influencing schoolchildren's exposures to SHS in Malaysia.
This cross-sectional study was carried out to measure salivary cotinine concentrations among 1064 schoolchildren (10-11 years) attending 24 schools in Malaysia following recent partial smoke-free restrictions. Parents completed questionnaires and schoolchildren provided saliva samples for cotinine assay.
The geometric mean (GM) salivary cotinine concentrations for 947 non-smoking schoolchildren stratified by household residents' smoking behaviour were: for children living with non-smoking parents 0.32 ng/ml (95% CI 0.28-0.37) (n = 446); for children living with a smoker father 0.65 ng/ml (95% CI 0.57-0.72) (n = 432); for children living with two smoking parents 1.12 ng/ml (95% CI 0.29-4.40) (n = 3); for children who live with an extended family member who smokes 0.62 ng/ml (95% CI 0.42-0.89) (n = 33) and for children living with two smokers (father and extended family member) 0.71 ng/ml (95% CI 0.40-0.97) (n = 44). Parental-reported SHS exposures showed poor agreement with children's self-reported SHS exposures. Multiple linear regression demonstrated that cotinine levels were positively associated with living with one or more smokers, urban residence, occupation of father (Armed forces), parental-reported exposure to SHS and education of the father (Diploma/Technical certificate).
This is the first study to characterise exposures to SHS using salivary cotinine concentrations among schoolchildren in Malaysia and also the first study documenting SHS exposure using salivary cotinine as a biomarker in a South-East Asian population of schoolchildren. Compared to other populations of similarly aged schoolchildren, Malaysian children have higher salivary cotinine concentrations. The partial nature of smoke-free restrictions in Malaysia is likely to contribute to these findings. Enforcement of existing legislation to reduce exposure in public place settings and interventions to reduce exposure at home, especially to implement effective home smoking restriction practices are required.
Secondhand smoke; salivary cotinine; schoolchildren; self-reported smoke exposure; smoke-free legislation; enzyme-immunoassay method
This cross-sectional study aimed to examine the association between self-reported exposure status to second-hand smoke and urinary cotinine level in pregnant nonsmokers.
Materials and Methods
We recruited pregnant nonsmokers from the prenatal care clinics of a university hospital and two community health centers, and their urinary cotinine concentrations were measured.
Among a total of 412 pregnant nonsmokers, the proportions of self-reported exposure to second-hand smoke and positive urinary cotinine level were 60.4% and 3.4%, respectively. Among those, 4.8% of the participants who reported exposure to second-hand smoke had cotinine levels of 40 ng/mL (the kappa value = 0.029, p = 0.049). Among those who reported living with smokers (n = 170), "smoking currently permitted in the whole house" (vs. not permitted at home) was associated with positive urinary cotinine in the univariable analysis. Furthermore, this variable showed a significant association with positive urinary cotinine in the stepwise multiple logistic regression analysis [Odds ratio (OR), 15.6; 95% Confidence interval (CI) = 2.1-115.4].
In the current study, the association between self-reported exposure status to second-hand smoke and positive urinary cotinine in pregnant nonsmokers was poor. "Smoking currently permitted in the whole house" was a significant factor of positive urinary cotinine in pregnant nonsmokers. Furthermore, we suggest that a complete smoking ban at home should be considered to avoid potential adverse effects on pregnancy outcomes due to second-hand smoke.
Passive smoking; pregnant women; cotinine
BACKGROUND: Previous studies of the effects of passive exposure to smoke on spirometric indices in children have largely relied on questionnaire measures of exposure. This may have resulted in underestimation of the true effect of passive smoking. Biochemical measures offer the opportunity to estimate recent exposure directly. METHODS: The relation between spirometric indices and passive exposure to tobacco smoke was examined in a large population sample of 5-7 year old children from 10 towns in England and Wales. The effects of passive exposure to smoke on lung function were assessed by means of both salivary cotinine concentration and questionnaire measurements of exposure. Analyses of the relation between spirometric values and cotinine concentrations were based on 2511 children and of the relation between spirometric values and questionnaire measures on 2000 children. RESULTS: Cotinine concentration was negatively associated with all spirometric indices after adjustment for confounding variables, which included age, sex, body size, and social class. The strongest association was with mid expiratory flow rate (FEF50), the fall between the bottom and top fifths of the cotinine distribution being 6%, equivalent to a reduction of 14.3 (95% confidence limits (CL) 8.6, 20.0) ml/s per ng/ml cotinine. Salivary cotinine concentrations were strongly related to exposure to cigarette smoke at home but 88% of children who were from non-smoking households and not looked after by a smoker had detectable cotinine concentrations, 5% being in the top two fifths of the cotinine distribution. A composite questionnaire score based on the number of regular sources of exposure was as strongly related to mid and end expiratory flow rates as the single cotinine measure. The fall in FEF50 per smoker to whom the child was exposed was 51.0 (26.5, 75.5) ml/s. The relationships between the questionnaire score and forced vital capacity (FVC) or forced expiratory volume in one second (FEV1) were not statistically significant. CONCLUSIONS: These effects of passive smoking on respiratory function are consistent with the results of previous studies and, although small in absolute magnitude, may be important if the effects of exposure are cumulative. In children aged 5-7 years the use of a single salivary cotinine concentration as a marker of passive exposure to smoke resulted in clear relationships between exposure and FVC and FEV1, whereas the associations were much weaker and not significant when based on the questionnaire score. The associations between exposure and mid or end expiratory flow rates were of similar magnitude for cotinine concentration and the questionnaire score. The use of salivary cotinine concentration in longitudinal studies may help to determine the extent to which these effects are cumulative or reversible.
Objective: To investigate whether the Irish smoking ban has had an impact on secondhand smoke (SHS) exposures for hospitality workers.
Design, setting, and participants: Before and after the smoking ban a cohort of workers (n = 35) from a sample of city hotels (n = 15) were tested for saliva cotinine concentrations and completed questionnaires. Additionally, a random sample (n = 20) of city centre bars stratified by size (range 400–5000 square feet), were tested for air nicotine concentrations using passive samplers before and after the ban.
Main outcome measures: Salivary cotinine concentrations (ng/ml), duration of self reported exposures to secondhand smoke, air nicotine (µg/cubic metre).
Results: Cotinine concentrations reduced by 69%, from 1.6 ng/ml to 0.5 ng/ml median (SD 1.29; p < 0.005). Overall 74% of subjects experienced decreases (range 16–99%), with 60% showing a halving of exposure levels at follow up. Self reported exposure to SHS at work showed a significant reduction from a median 30 hours a week to zero (p < 0.001). There was an 83% reduction in air nicotine concentrations from median 35.5 µg/m3 to 5.95 µg/m3 (p < 0.001). At baseline, three bars (16%) were below the 6.8 µg/m3 air nicotine significant risk level for lung cancer alone; at follow up this increased to 10 (53%).
Conclusions: Passive smoking and associated risks were significantly reduced but not totally eliminated. Exposure to SHS is still possible for those working where smoking is still allowed and those working where smoke may migrate from outdoor areas. Further research is required to assess the true extent and magnitude of these exposures.
To investigate whether parents of asthmatic children would stop smoking or alter their smoking habits to protect their children from environmental tobacco smoke.
Randomised controlled trial.
Tayside and Fife, Scotland.
501 families with an asthmatic child aged 2-12 years living with a parent who smoked.
Parents were told about the impact of passive smoking on asthma and were advised to stop smoking or change their smoking habits to protect their child’s health.
Main outcome measures
Salivary cotinine concentrations in children, and changes in reported smoking habits of the parents 1 year after the intervention.
At the second visit, about 1 year after the baseline visit, a small decrease in salivary cotinine concentrations was found in both groups of children: the mean decrease in the intervention group (0.70 ng/ml) was slightly smaller than that of the control group (0.88 ng/ml), but the net difference of 0.19 ng/ml had a wide 95% confidence interval (−0.86 to 0.48). Overall, 98% of parents in both groups still smoked at follow up. However, there was a non-significant tendency for parents in the intervention group to report smoking more at follow up and to having a reduced desire to stop smoking.
A brief intervention to advise parents of asthmatic children about the risks from passive smoking was ineffective in reducing their children’s exposure to environmental tobacco smoke. The intervention may have made some parents less inclined to stop smoking. If a clinician believes that a child’s health is being affected by parental smoking, the parent’s smoking needs to be addressed as a separate issue from the child’s health.
Key messagesMany asthmatic children are exposed to high levels of environmental tobacco smokeA brief intervention informing parents of asthmatic children on the harmful effects of passive smoking did not lead to a reduction in exposure of their children to tobacco smokeLow rates of smoking cessation were found in both the intervention group and the control groupSome parents may have been less inclined to stop smoking after the interventionBrief interventions requesting smokers to stop for another person’s health seem ineffective
Characterizing and comparing the determinant of cotinine concentrations in different populations should facilitate a better understanding of smoking patterns and addiction. This study describes and characterizes determinants of salivary cotinine concentration in a sample of Spanish adult daily smoker men and women.
A cross-sectional study was carried out between March 2004 and December 2005 in a representative sample of 1245 people from the general population of Barcelona, Spain. A standard questionnaire was used to gather information on active tobacco smoking and passive exposure, and a saliva specimen was obtained to determine salivary cotinine concentration. Two hundred and eleven adult smokers (>16 years old) with complete data were included in the analysis. Determinants of cotinine concentrations were assessed using linear regression models.
Salivary cotinine concentration was associated with the reported number of cigarettes smoked in the previous 24 hours (R2 = 0.339; p < 0.05). The inclusion of a quadratic component for number of cigarettes smoked in the regression analyses resulted in an improvement of the fit (R2 = 0.386; p < 0.05). Cotinine concentration differed significantly by sex, with men having higher levels.
This study shows that salivary cotinine concentration is significantly associated with the number of cigarettes smoked and sex, but not with other smoking-related variables.
Awareness of the negative effects of smoking on children's health prompted a decrease in the self-reporting of parental tobacco use in periodic surveys from most industrialized countries. Our aim is to assess changes between ETS exposure at the end of pregnancy and at 4 years of age determined by the parents' self-report and measurement of cotinine in age related biological matrices.
The prospective birth cohort included 487 infants from Barcelona city (Spain). Mothers were asked about maternal and household smoking habit. Cord serum and children's urinary cotinine were analyzed in duplicate using a double antibody radioimmunoassay.
At 4 years of age, the median urinary cotinine level in children increased 1.4 or 3.5 times when father or mother smoked, respectively. Cotinine levels in children's urine statistically differentiated children from smoking mothers (Geometric Mean (GM) 19.7 ng/ml; 95% CI 16.83–23.01) and exposed homes (GM 7.1 ng/ml; 95% CI 5.61–8.99) compared with non-exposed homes (GM 4.5 ng/ml; 95% CI 3.71–5.48). Maternal self-reported ETS exposure in homes declined in the four year span between the two time periods from 42.2% to 31.0% (p < 0.01). Nevertheless, most of the children considered non-exposed by their mothers had detectable levels of cotinine above 1 ng/mL in their urine.
We concluded that cotinine levels determined in cord blood and urine, respectively, were useful for categorizing the children exposed to smoking and showed that a certain increase in ETS exposure during the 4-year follow-up period occurred.
OBJECTIVE--To examine the importance of parental smoking on passive exposure to tobacco smoke in children and the social and geographical patterns of exposure. DESIGN--Cross sectional study. SETTING--Schools in 10 towns in England and Wales; five towns with high adult cardiovascular mortality and five with low rates. SUBJECTS--4043 children aged 5-7 years of European origin. MAIN OUTCOME MEASURES--Salivary cotinine concentration and parents self reported smoking habits. RESULTS--1061 (53.0%) children were exposed to cigarette smoke at home or by an outside carer. Geometric mean cotinine rose from 0.29 (95% confidence interval 0.28 to 0.31) ng/ml in children with no identified exposure to 4.05 (3.71 to 4.42) ng/ml in households where both parents smoked and 9.03 (6.73 to 12.10) ng/ml if both parents smoked more than 20 cigarettes a day. The effect of mothers' smoking was greater than that of fathers', especially at high levels of consumption. After adjustment for known exposures geometric mean cotinine concentrations rose from 0.52 ng/ml in social class I to 1.36 ng/ml in social class V (P < 0.0001); and were doubled in high mortality towns compared with the low mortality towns (P = 0.002). In children with no identified exposure similar trends by social class and town were observed and the cotinine concentrations correlated with the prevalence of parental smoking, both between towns (r = 0.69, P = 0.02) and between schools within towns (r = 0.50, P < 0.001). CONCLUSIONS--Mothers' smoking is more important that fathers' despite the lower levels of smoking by mothers. Children not exposed at home had low cotinine concentration, the level depending on the prevalence of smoking in the community.
The level of cotinine in biological specimens, such as serum, urine, and saliva, measured by gas or liquid chromatography is the most validated and reliable indicator of exposure to tobacco smoke. However, chromatographic methods are not always suitable for all types of situations.
We validated a commercially available enzyme-linked immunosorbent assay (ELISA) that uses a polyclonal antibody to cotinine as a practical alternative to chromatographic methods.
The cotinine antibody cross-reacts to 3-hydroxycotinine (3HC) and its glucuronide, thus generating a value for immunoreactive (IR) cotinine, which is a complex comprising cotinine, 3HC, and 3HC-glucuronide. The levels of IR cotinine in the urine of kindergarten children closely correlated with those of cotinine measured by gas chromatography–mass spectrometry (GC–MS) and reflected the smoking behavior of their parents more precisely than cotinine levels determined by GC–MS.
Our findings showed that the cotinine-based ELISA can be a practical biomarker of exposure to tobacco smoke.
Electronic supplementary material
The online version of this article (doi:10.1007/s12199-009-0129-2) contains supplementary material, which is available to authorized users.
Cotinine; ELISA; Environmental tobacco smoke; 3-Hydroxycotinine
To measure exposure to second‐hand smoke (SHS) in New Zealand bars before and after comprehensive smoke‐free legislation enacted on 10 December 2004.
Cotinine is the main specific metabolite of nicotine and a well‐established biomarker for SHS exposure. We measured cotinine levels in saliva of non‐smoking volunteers before and after a 3 h visit to 30 randomly selected bars in 3 cities across the country. Two measures of cotinine before the smoke‐free law change during winter and spring 2004, and two follow‐up measurements in the same volunteers and venues during winter and spring 2005, were included.
Before the smoke‐free law change, in all bars and in all volunteers, exposure to SHS was evident with an average increase in saliva cotinine of 0.66 ng/ml (SE 0.03 ng/ml). Increases in cotinine correlated strongly with the volunteers' subjective observation of ventilation, air quality and counts of lit cigarettes. However, even venues that were judged to be “seemingly smoke free” with “good ventilation” produced discernable levels of SHS exposure. After the law change, there remained some exposure to SHS, but at much lower levels (mean saliva cotinine increase of 0.08 ng/ml, SE 0.01 ng/ml). Smoking indoors in bars was almost totally eliminated: in 2005 only one lit cigarette was observed in 30 visits.
Comprehensive smoke‐free legislation in New Zealand seems to have reduced exposure of bar patrons to SHS by about 90%. Residual exposures to SHS in bars do not result from illicit smoking indoors.
Plasma or saliva cotinine concentrations are used widely as biomarkers of secondhand smoke (SHS) exposure and have been associated with the risk of SHS-related disease. Concentrations of cotinine and other nicotine metabolites are considerably higher in urine than in plasma or saliva, making chemical analysis easier. In addition, urine is often more convenient to collect in some SHS exposure studies. The optimal use of nicotine metabolites in urine, singly or in combination, with or without correction for urine creatinine concentration, to estimate plasma cotinine concentration with low-level nicotine exposure has not been determined.
We dosed 36 nonsmokers with 100, 200, or 400 μg deuterium-labeled nicotine (simulating exposure to SHS) by mouth daily for 5 days and then measured plasma and urine cotinine and metabolites at various intervals over 24 hr.
A plasma cotinine concentration of 1 ng/ml corresponds on average to a daily intake of 100 μg nicotine. Cotinine concentrations in urine averaged four to five times those in plasma. Correction of urine cotinine for creatinine concentration improved the correlation between urine and plasma cotinine. Measuring multiple cotinine metabolites in urine did not improve the correlation with plasma cotinine, compared with the use of urine cotinine alone.
Measurement of urine cotinine corrected for creatinine concentration appears to be the best predictor of plasma cotinine.
Cotinine concentration in various body fluids is considered to be among the most useful markers of nicotine exposure currently available. Despite the prevailing consensus concerning cotinine's usefulness, cotinine's large intrasubject variability has led some to question the value of a single-point measurement. Several individual differences (for example, age, race, sex, and so forth) may affect cotinine excretion, and a peculiar nonlinearity between the number of cigarettes smoked and cotinine concentration has been reported previously in the literature. The purpose of this investigation was to examine the nature of the association between cotinine and reported number of cigarettes smoked after adjustment for the relationship between cotinine and age, a key individual difference known to affect drug absorption, distribution, metabolism, excretion, and tissue sensitivity. The authors examined the relationship between saliva cotinine and daily cigarette consumption in 116 smokers (mean age = 37.4 years; average number of cigarettes smoked daily = 20.1) who logged each cigarette into a hand-held computer as part of a study on the accuracy of recall. The Pearson correlation between saliva cotinine and the logged number of cigarettes smoked in the previous 17 hours (the time window corresponding to the half-life of cotinine) accounted for significantly more of the variance in cotinine than did the average logged number of cigarettes smoked daily during 5 days. Age was also significantly associated with cotinine levels. Further examination of the relationship between cotinine and amount smoked in the previous 17 hours revealed evidence for a significant nonlinear component.(ABSTRACT TRUNCATED AT 250 WORDS)
Rationale: Ambient particulate matter concentrations have been positively associated with urinary leukotriene E4 (LTE4) levels and albuterol usage in children with asthma but interactions with environmental tobacco smoke (ETS) exposure have not been demonstrated despite obvious exposure to both pollutants in an urban setting.
Objectives: To assess the health effects of concurrent ETS and ambient particulate matter exposure in children with asthma.
Methods: Albuterol usage and LTE4 levels were monitored in 82 urban schoolchildren with asthma over three consecutive fall to spring school periods. Concentrations of morning maximum ambient particulate matter <2.5 μm in aerodynamic diameter (mmPM2.5) and urine cotinine levels were also measured daily.
Measurements and Main Results: Albuterol usage and LTE4 were related to mmPM2.5 concentrations on days when urine cotinine levels were low (<10 ng/ml/mg creatinine); on these days, mean albuterol usage and LTE4 increased up to 5 or 6% per 10 μg/m3 increase in mmPM2.5. In contrast, no significant relationship was observed when cotinine was high, although mean albuterol usage and LTE4 levels were greater in this case. Model fits for LTE4 levels as a function of mmPM2.5 concentrations were improved when mmPM2.5 concentrations were logged, suggesting a nonlinear dose–response relationship between particulate matter exposure concentrations and airway mediators of asthma, for which the relationship tends to flatten at higher concentrations.
Conclusions: This study suggests that ETS modifies the acute effects of low-level ambient PM2.5 exposure on childhood asthma. This negative interaction, the smaller effect of particulate matter exposure in children exposed to higher ETS, may be related to a nonlinear dose–response relationship between asthma mediators and particulate exposures.
air pollution; leukotriene E4; asthma; interaction; environmental tobacco smoke
To identify factors associated with motivation to quit smoking among parents of urban children with asthma.
We analyzed data from parents who smoke and had a child enrolled in the School-Based Asthma Therapy trial. We assessed asthma symptoms, children's cotinine, and parent smoking behaviors. Motivation to quit smoking was assessed by a 10-point continuous measure (1=not at all motivated; 10=very motivated).
209 parents smoked (39% of sample), and children's mean cotinine was 2.48 ng/ml. Motivation to quit was on average 6.9, and 47% of parents scored ≥8 on the scale. Parents who believed their child's asthma was not under good control, and parents who strongly agreed their child's asthma symptoms would decrease if they stopped smoking had higher motivation to quit compared to their counterparts (p <.05). In a multivariate analysis, parents who believed their child's asthma was not under control had more than twice the odds of reporting high motivation to quit.
Parents' perception of the risks of smoking to their child with asthma is associated with motivation to quit.
Raising awareness about the effect of smoking and quitting on children's asthma might increase motivation to quit among parents.
Asthma; parents; children; smoking cessation; motivation; environmental tobacco smoke
Exposure to environmental tobacco smoke (ETS) is a major cause of morbidity and mortality among U.S. children. Despite African-American children’s having a lower reported exposure to tobacco compared to whites, they suffer disproportionately from tobacco-related illnesses and have higher levels of serum cotinine than white children. The goal of this study was to test whether African-American children have higher levels of serum and hair cotinine, after accounting for ETS exposure and various housing characteristics. We investigated the level of cotinine in both hair and serum in a sample of 222 children with asthma. Using a previously validated survey for adult smokers, we assessed each child’s exposure to ETS. We collected detailed information on the primary residence, including home volume, ventilation, and overall home configuration. Despite a lower reported ETS exposure, African-American children had higher mean levels of serum cotinine (1.41 ng/mL vs. 0.97 ng/mL; p = 0.03) and hair cotinine (0.25 ng/mg vs. 0.07 ng/mg; p < 0.001) compared with white children. After adjusting for ETS exposure, housing size, and other demographic characteristics, serum and hair cotinine levels remained significantly higher in African-American children (β = 0.34, p = 0.03) than in white children (β = 1.06, p < 0.001). Housing volume was significantly associated with both serum and hair cotinine but did not fully explain the race difference. Our results demonstrate that, despite a lower reported exposure to ETS, African-American children with asthma had significantly higher levels of both serum and hair cotinine than did white children. Identifying causes and consequences of increased cotinine may help explain the striking differences in tobacco-related illnesses.
African American; asthma; cotinine; ETS; housing
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 (≥ 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 ν ≥ 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.
To examine the association between objectively measured second–hand-smoke (SHS) exposure and incident CVD death, and assess the extent to which this association can be explained through novel circulating markers of inflammation and haemostasis.
Existing evidence suggests there is an association between SHS and cardiovascular disease (CVD) risk, although the mechanisms remain poorly understood.
In a prospective study of 13,443 participants living in England and Scotland [aged 53.5, (SD 12.6 yrs), 52.3% women] we measured salivary cotinine (an objective marker of SHS exposure) and novel CVD biomarkers (C-reactive protein, fibrinogen) at baseline.
20.8% of the sample had high SHS exposure based on elevated levels of salivary cotinine (0.71 – 14.99 ng/mL). During a mean follow-up of 8 years, there were 1221 all-cause deaths and 364 CVD deaths. High SHS was associated with all-cause (age adjusted HR= 1.25, 95% CI, 1.02 – 1.53) and CVD death (age adjusted HR= 1.21, 95% CI, 0.85 – 1.73). High SHS was also associated with elevated CRP, which explained 48% of the association between SHS and CVD death. The excess risk of CVD associated with active smoking was exaggerated in relation to self report (age adjusted HR= 3.27, 95% CI, 2.48 – 4.31) compared with objective assessment (age adjusted HR= 2.44, 95% CI, 1.75 – 3.40).
Among a large representative sample of British adults we observed elevated levels of low grade inflammation in otherwise healthy participants exposed to high SHS, and this partly explained their elevated risk of CVD death.
cotinine; inflammation; nicotine; passive smoke; mortality; epidemiology