The Elimination Half-Life of Urinary Cotinine in Children of Tobacco-Smoking Mothers

doi:10.1006/pupt.1998.0153

Pulmonary Pharmacology & Therapeutics

Volume 11, Issue 4, August 1998, Pages 287-290

https://doi.org/10.1006/pupt.1998.0153 Get rights and content

Abstract

Exposure to environmental tobacco smoke (ETS) is strongly associated with childhood morbidity. Cotinine, the major metabolite of nicotine, is a useful marker of tobacco smoke exposure. Cotinine levels in infants are higher than in older children or adults exposed to the same reported quantity of ETS. One hypothesis to explain this difference is that the urinary elimination half-life of cotinine is different between infants and older children. Urine was collected at admission, 12, 24 and 48 h, cotinine levels were subsequently measured and then standardized by correcting for creatinine excretion. Urinary elimination half-life of cotinine was calculated in 31 infants and 23 older children. The median half-life was 28.3 h (range 6.3–258.5 h) in infants, and 27.14 h (range 9.7–99.42 h) in older children. A Mann–Whitney U test showed no significant difference in the median half-life of cotinine between the two age groups (P=0.18). Multivariate linear regression analysis demonstrated no significant relationship between half-life of cotinine and corrected cotinine level (P=0.24). Our results support the hypothesis that higher cotinine levels in infants is due to greater exposure, rather than slower metabolism of cotinine.

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Cited by (46)

Urinary cotinine and exposure to passive smoke in children and adolescents in Germany – Human biomonitoring results of the German Environmental Survey 2014–2017 (GerES V)
2023, Environmental Research
Passive smoking is a preventable and significant cause of many serious health problems, with children being particularly at risk. In the fifth German Environmental Survey (GerES V), conducted from 2014 to 2017, information reflecting the extent of passive smoke exposure in children and adolescents was collected by interview-based questionnaires and human biomonitoring (HBM) analyses of cotinine in urine from 2260 participants, aged 3–17 years. Based on these population-representative data, we describe current passive smoke exposure stratified by different subgroups and identify specific exposure determinants using multivariate logistic regression. The questionnaire data revealed that 42% of children and adolescents lived with at least one smoker in the household. Quantifiable concentrations of cotinine could be detected in 56% of the participants. The overall median concentration of cotinine was 0.2 μg/L, with children and adolescents of low socioeconomic status found to be a group particularly affected by passive smoke with higher cotinine concentrations (median = 1.2 μg/L). In the multiple analysis, the most significant predictor of cotinine levels derived from the questionnaire was passive smoking at home (odds ratio (OR) 13.07 [95CI: 4.65, 36.70]). However, parental smoking and passive smoking among friends and relatives could also be identified as independent factors influencing elevated cotinine levels. The comparison between the previous cycle GerES IV (2003–2006) on 3–14-year-olds and GerES V shows that tobacco smoke exposure of children decreased significantly. This decrease is likely an effect of extensive non-smoker protection laws being enforced 2007–2008 on federal and state level. This is reflected by a halving of urinary cotinine concentrations. Nevertheless, our results indicate that passive smoke is still a relevant source of harmful pollutants for many children and adolescents in Germany, and thus support the need for further efforts to reduce passive smoke exposure, especially in the private environment.
Use of a physiologically-based pharmacokinetic model to explore the potential disparity in nicotine disposition between adult and adolescent nonhuman primates
2020, Toxicology and Applied Pharmacology
Citation Excerpt :
Urinary clearance rates (half-lives) of cotinine in newborns whose mothers smoked tobacco have been reported (Etzel et al., 1985; Dempsey et al., 2000). In other studies, infants and youth were exposed to second hand smoke, then placed in a smoke-free environment before urine collection, and the urinary clearance of cotinine was calculated from the collected samples (Collier et al., 1994; Leong et al., 1998). These reported urinary half-lives were quite variable and conflicting, reflecting the shortcomings in using these opportunistic methods.
The widespread use and high abuse liability of tobacco products has received considerable public health attention, in particular for youth, who are vulnerable to nicotine addiction. In this study, adult and adolescent squirrel monkeys were used to evaluate age-related metabolism and pharmacokinetics of nicotine after intravenous administration. A physiologically-based pharmacokinetic (PBPK) model was created to characterize the pharmacokinetic behaviors of nicotine and its metabolites, cotinine, trans-3′-hydroxycotinine (3′-OH cotinine), and trans-3′-hydroxycotinine glucuronide (3′-OH cotinine glucuronide) for both adult and adolescent squirrel monkeys. The PBPK nicotine model was first calibrated for adult squirrel monkeys utilizing in vitro nicotine metabolic data, plasma concentration-time profiles and cumulative urinary excretion data for nicotine and metabolites. Further model refinement was conducted when the calibrated adult model was scaled to the adolescents, because adolescents appeared to clear nicotine and cotinine more rapidly relative to adults. More specifically, the resultant model parameters representing systemic clearance of nicotine and cotinine for adolescent monkeys were approximately two- to three-fold of the adult values on a per body weight basis. The nonhuman primate PBPK model in general captured experimental observations that were used for both model calibration and evaluation, with acceptable performance metrics for precision and bias. The model also identified differences in nicotine pharmacokinetics between adolescent and adult nonhuman primates which might also be present in humans.
Effects of Smoking Exposure in Infants on Gastroesophageal Reflux as a Function of the Sleep–Wakefulness State
2018, Journal of Pediatrics
Citation Excerpt :
In infants from nonsmoking mothers, paternal smoking was the most significantly related determinant of measurable levels of urinary cotinine. In neonates, Etzel et al found an averaged cotinine half-life of 68 hours (range: 37-160 hours), whereas Leong et al found a median half-life of 28.3 hours (range: 6-259 hours) in infants.60,61 In the present study, our assay's limit of detection (1 ng/mL) enabled us to measure any exposure to nicotine.
To determine whether perinatal smoking exposure is associated with gastroesophageal reflux (GER)-related changes in sleep-wakefulness states in neonates.
Thirty-one neonates, referred for the investigation of suspected GER, were recruited and underwent multichannel impedance–pH monitoring and synchronized 8- to 12-hour polysomnography. The infants' exposure to tobacco smoke was estimated by means of a urine cotinine assay. The total number, frequency (h⁻¹), and mean duration (minutes) of GER-pH (reflux events detected by the pH electrode only) and GER-imp (reflux events with bolus movement detected by impedance) events were determined. Intergroup differences (smoking-exposed group vs nonexposed group) were probed with nonparametric, unpaired Mann–Whitney U tests. A χ² test was used to assess a possible intergroup difference in bolus retrograde migration during GER-imp events.
According to the urine cotinine assay, 21 of the 31 neonates had been exposed to cigarette smoke during the perinatal period. The number (and frequency) of GER-imp was significantly greater (P = .016) in the exposed group (29 [0-90]) than in the nonexposed group (12 [2-35]). Migration of the esophageal bolus from the distal segment to the most proximal segment was significantly more frequent (P = .016) in the exposed group (83% of GER) than in the nonexposed group (41%). The GER pattern associated with smoking exposure was particularly obvious during Rapid eye movement sleep.
The more frequent occurrence and greater proximal migration of GER-imp in the smoking-exposed group (especially during rapid eye movement sleep) may have clinical relevance. Smoking exposure is a preventable risk factor for limiting the occurrence of GER in neonates.
Gender differences in cadmium and cotinine levels in prepubertal children
2015, Environmental Research
Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age–sex groups: boys (6–8 years, 9–10 years and 11 years old), and girls (6–7 years, 8–9 years, 10–11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10–0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80–39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6–7 year old girls, 11 year old boys and 10–11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.
Medico-social aspects of patients with bronchial asthma
2015, Kontakt
Citation Excerpt :
Nicotine metabolite cotinine is a bio-marker of nicotine changes. It is half-life for breaking down was longer (17–24 h) than nicotine (2–3 h) [73,74]. Cotinine (nicotine metabolite) can be detected in urine, saliva, blood and hair [75].
In the past three decades, there was a visible increase regarding asthma prevalence and allergic diseases all around the world, especially in countries with a Western lifestyle, so called westernization. Bronchial asthma affects the quality of life of asthmatic and his family. The health determinants have an impact on the onset and development of bronchial asthma. The cause of an allergy is a combination of 50% of genetic factors and an additional 50% involving environmental factors. The onset and development of atopy and asthma is dependent on many factors, such as environmental factors (indoor and outdoor air pollution, domestic animals, allergens, tobacco smoke, hormones, endotoxins) and personal factors (gender, smoking, obesity, food, diet, breastfeeding, development of lungs). There is confirmation of major association of asthma with low birth weight, mothers’ family background, which interacts with socio-economic status. The development of asthma affects increased intake of sodium, decreased intake of fruit, vegetables and fish. A positive effect has the intake of coffee (caffeine) and vitamin C. Exposure to harmful substances has been associated with workplace factors (occupational asthma), residential housing and lifestyle habits, which depend on social status. It was discovered, that there is an association between asthma and being overweight as well. Maternal stress during pregnancy, stress in the family, maternal anxiety, lack of functioning within family, may also be a trigger for the onset and development of asthma. Poorly controlled bronchial asthma increases direct and indirect health care costs, limits asthmatics at work as well as in their daily life. Precautions and stabilization of this disease can also insure the knowledge of the various medico-social aspects of patients with bronchial asthma.
Perinatal nicotine/smoking exposure and carotid chemoreceptors during development
2013, Respiratory Physiology and Neurobiology
Citation Excerpt :
The authors did not find any effect of maternal smoking on the ventilatory response to hypoxia in either active or quiet sleep at any age, although arousal responses were depressed during quiet sleep. Lewis and Bosque (1995) found that the ventilatory responses to hypoxia (13%, 15% and 17% O2) were similar in smoking-exposed and non-exposed infants studied at 8–12 weeks of age. Nevertheless, these authors found that a higher proportion of infants of smokers failed to awake upon the hypoxic challenge, when compared with control infants.
Tobacco smoking is still a common habit during pregnancy and is the most important preventable cause of many adverse perinatal outcomes. Prenatal smoking exposure can produce direct actions of nicotine in the fetus with the disruption of body and brain development, and actions on the maternal–fetal unit by causing repeated episodes of hypoxia and exposure to many toxic smoke products (such as carbon monoxide). Specifically, nicotine through binding to nicotinic acetylcholine receptors have ubiquitous effects and can affect carotid chemoreception development through structural, functional and neuroregulatory alterations of the neural circuits involved in the chemoafferent pathway, as well as by interfering with the postnatal resetting of the carotid bodies. Reduced carotid body chemosensitivity and tonic activity have thus been reported by the majority of the human and animal studies. This review focuses on the effects of perinatal exposure to tobacco smoke and nicotine on carotid chemoreceptor function during the developmental period. A description of the effects of smoking and nicotine on the control of breathing related to carotid body activity, and of the possible physiopathological mechanisms at the origin of these disturbances is presented.

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^f1: Author for correspondence.

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Regular ArticleThe Elimination Half-Life of Urinary Cotinine in Children of Tobacco-Smoking Mothers

Abstract

Regular Article
The Elimination Half-Life of Urinary Cotinine in Children of Tobacco-Smoking Mothers