Urinary Cotinine Concentrations Research Articles

Active smoking in urban households: An association between urinary cotinine metabolite level and serum eGFR concentration.

Smoking stands as a primary contributor to preventable deaths globally and is linked to an increased risk of developing kidney failure and other diseases. A few studies have focused on the negative correlation between serum cotinine and estimated glomerular filtration rate (eGFR), indicating decreased kidney function. This study investigated the associations between urinary cotinine metabolite concentration and serum eGFR among active smokers in urban households. This was a cross-sectional study of active smokers in urban households' community Bangkok, Thailand from January to April 2023. The study involved 85 participants aged ≥18 years who were active smokers. Both urinary cotinine and serum eGFR concentrations were used as biomarkers. Independent sample t-tests were used to compare the urinary cotinine metabolite based on differences in the characteristic variable. We used multiple linear regression to test the association between cotinine metabolite and characteristics variables. Spearman's analysis was used to test the correlation between cotinine metabolite and eGFR concentration. The association between urinary cotinine metabolite and serum eGFR concentration decreased with increasing cotinine concentrations (r= -0.223, p=0.041), suggesting a decline in kidney function. However, this study found no significant difference between urinary cotinine metabolite and characteristic variables (p>0.05). Additionally, those who smoked for ≥10 years (117.40 ± 89.80 ng/mL), smoked ≥10 cigarettes per day (117.40 ± 89.80 ng/mL) and used conventional cigarettes (124.53 ± 115.10 ng/mL). The results of the multiple linear regression models analysis indicated that those who were smokers for ≥10 years (β=0.076; 95% CI: -31.575-59.715) and those who were smoked ≥10 cigarettes/day (β=0.126; 95% CI: -65.636-18.150) were not associated with urinary cotinine metabolite level. This study shows that the urinary cotinine metabolite level is associated with serum eGFR concentration among active smokers in urban households. The current study suggests that clinical identification and a prospective cohort study are needed before robust conclusions about how tobacco affects kidney efficiency.

Effect of children secondhand smoke exposure associated with GABA concentration: Influence from parents who are extremely heavy smokers in urban households

BackgroundSecondhand smoke (SHS) poses the most considerable health risk to children in urban households. However, limited evidence exists regarding the impact of children exposure to SHS on gamma-aminobutyric acid (GABA) levels. This study aimed to investigate the level of cotinine and GABA and their association with variables related to children exposed to SHS. MethodsA cross-sectional analysis was conducted to assess urinary cotinine and GABA levels in respondents. The study involved 85 participants aged 2–4 years who resided with parents exhibiting heavy smoking habits in urban households in Bangkok, Thailand. Urinary cotinine and GABA concentrations were utilized as biomarkers and measured using an enzyme-linked immunosorbent assay kit. An independent t-test was employed to compare contributing factors with urinary cotinine metabolites. Spearman's correlation test was utilized to assess the relationship between cotinine metabolites and GABA concentration. ResultsThe study found a correlation between urinary cotinine metabolites and GABA concentration among children's (r = 0.260, p-value = 0.016), particularly influenced by parents exhibiting extreme heavy smoking in urban households. Male children exhibited significantly higher urinary cotinine metabolite concentrations than females (p-value = 0.040). Moreover, significantly elevated levels of cotinine metabolites (57.37 ± 10.27 ng/ml) were observed in households where parents engaged in extreme heavy smoking. ConclusionsThis research establishes a link between urinary cotinine metabolite levels and GABA concentration among children exposed to extreme heavy smoking by their parents in urban households. Consequently, smoking might impact neurobehavioral effects, potentially leading to insomnia. The study emphasizes the importance of promoting and safeguarding non-smokers from exposure to SHS in indoor workplaces, public spaces, and households, advocating for the implementation of smoke-free public health regulations.

Association between cigarette smoke exposure and urinary bladder cancer in Scottish terriers in a cohort study

Canine urothelial carcinoma (UC) initially responds favorably to treatment, but is ultimately lethal in most cases. Research to identify modifiable risk factors to prevent the cancer is essential. The high breed-associated risk for UC, e.g. 20-fold higher in Scottish terriers, can facilitate this research. The objective was to identify environmental and host factors associated with UC in a cohort of Scottish terriers. Information was obtained through dog owner questionnaires for 120 Scottish terriers ≥ 6 years old participating in a bladder cancer screening study, with comparisons made between dogs that did or did not develop UC during the 3 years of screening. Univariable models were constructed, and variables with P < 0.20 were included when building the multivariable model, and then removed using a backward stepwise procedure. P < 0.05 was considered statistically significant. Urine cotinine concentrations were measured by liquid chromatography-mass spectrometry to further investigate potential cigarette smoke exposure. Biopsy-confirmed UC which was found in 32 of 120 dogs, was significantly associated with the dogs living in a household with cigarette smokers (odds ratio [OR], 6.34; 95 % confidence intervals [CI], 1.16–34.69; P = 0.033), living within a mile of a marsh or wetland (OR, 21.23; 95 % CI, 3.64–123.69; P = 0.001), and history of previous bladder infections (OR, 3.87; 95 % CI, 1.0–14.98; P = 0.050). UC was diagnosed in 18 of 51 dogs (35.3 %) with quantifiable cotinine concentrations, and six of 40 dogs (15.0 %) without quantifiable cotinine concentrations in their urine (P = 0.0165). In conclusion, the main modifiable risk factor for UC in this cohort of dogs was exposure to second-hand tobacco smoke.

Effects of environmental health literacy-based interventions on indoor air quality and urinary concentrations of polycyclic aromatic hydrocarbons, volatile organic compounds, and cotinine: A randomized controlled trial

Indoor air pollution (IAP) caused by particulate matter (PM), aromatic and volatile chemicals is one of the leading causes of adverse reproductive health effects, such as infertility, decreased gestational age, and low birth weight. It is well documented that environmental health literacy (EHL) can promote reductions in IAP and the level of environmental pollutants in the body. We conducted randomized control trial to evaluate the effect of EHL-based intervention on the indoor air quality and urinary levels of polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), and cotinine in reproductive aged women in Korea. The concentration of indoor PM2.5, PM10, CO2, and total VOCs (measured with a personal air quality monitoring device) as well as the urinary concentrations of PAHs, VOCs, and cotinine were measured in an experimental (n = 32) and control group (n = 31). The geometric mean concentrations of 2-NAP, tt-MA, and cotinine were 4.74, 82.82, and 0.60 μg/L respectively. The EHL intervention resulted in significant differences between experimental and control groups in the level of tt-MA (z = −1.44, p = .031), cotinine (z = −1.07, p = .015) in urine and PM2.5 (z = 56.39, p < .01), PM10 (z = 57.85, p < .01), CO2 (z = 8.92, p < .01), and total VOCs (z = 10.11, p < .01) of indoor air, and the mean score of EHL (z = 6.30, p < .01). Our results show the value in developing EHL interventions to reduce exposure to air pollutants originating from indoor activity and daily-life materials. Further studies are required to find ways to optimize general EHL for use in populations around the world.

Verifying the accuracy of self-reported smoking behavior in female volunteer soldiers

Smoking rates in the military are evaluated through questionnaire surveying. Because the accurate identification of smokers facilitates the provision of smoking cessation services, this study conducted urine cotinine concentration testing to verify the accuracy of self-reported smoking behavior by female volunteer soldiers and analyzed the effects of second-hand smoking on urine cotinine concentrations. This study is a cross-sectional study conducted using purposive sampling on female volunteer soldiers receiving training at the Taichung Recruit Training Center in May 2014. This study simultaneously collected questionnaires and urine samples, and urine samples were analyzed with an enzyme-linked immunosorbent assay. The self-reported smoking rate of female volunteer soldiers was 19.3%, whereas the smoking rate as determined by urine cotinine concentration testing was 26.3%, indicating an overall underestimation of 7.0%. Chi-square (χ2) goodness of fit test results indicated that the distribution of self-reported smoking behaviors and that verified from urine cotinine concentration testing were significantly different. The sensitivity of self-reported smoking behavior was 66.7% with a specificity of 97.6%. There was no significant association between second-hand smoking and urine cotinine concentrations. Questionnaire survey self-reporting methods could underestimate the smoking behavior of female volunteer soldiers and routine testing with biochemical verification is necessary.

Passive exposure to electronic cigarette aerosol in pregnancy: A case study of a family

BackgroundPassive exposure to the aerosols of electronic cigarettes (e-cigarettes) has been little studied. We assessed this exposure in late pregnancy in a woman and her 3-year-old child, exposed through e-cigarette use by another household member. MethodsThis prospective longitudinal case study involved a family unit consisting of an e-cigarette user, a pregnant woman who delivered an infant during the study, and the couple's older 3-year-old son. At 31, 36, and 40 weeks of the pregnancy, we measured biomarkers (nicotine metabolites, tobacco-specific nitrosamines, propanediols, glycerol, and metals) in the urine and hair of all three participants and in the saliva of the adults, in cord blood at delivery, and in the breast milk at the postpartum period. ResultsSamples from the e-cigarette user showed quantifiable concentrations of all analytes assessed (maximum urinary cotinine concentration, 4.9 ng/mL). Among samples taken from the mother, nicotine and its metabolites were found mainly in urine and also in saliva and hair, but not in cord blood. During the postpartum period, we found cotinine concentrations of 2.2 ng/mL in the mother's urine and 0.22 ng/mL in breast milk; 1,2-propanediol was generally detected in urine and saliva, but not in cord blood or breast milk. The maximum urinary cotinine concentration in the 3-year-old child was 2.6 ng/mL and propanediols also were detected in his urine. Nitrosamines were not detected in samples taken from the mother or the 3-year-old. Metals found in the refill liquid were detected at low levels in both the mother and the 3-year-old. ConclusionsWe detected low but not negligible concentrations of e-cigarette–related analytes (including cord blood and breast milk) in an exposed pregnant non-user and in a 3-year-old child also living in the home. Passive exposure to e-cigarette aerosols cannot be disregarded and should be assessed in larger observational studies.

Biomarkers of Exposure and Potential Harm in Exclusive Users of Nicotine Pouches and Current, Former, and Never Smokers: Protocol for a Cross-sectional Clinical Study.

BackgroundTobacco harm reduction (THR) aims to reduce the health burden of cigarettes by encouraging smokers to switch to using alternative tobacco or nicotine products. Nicotine pouches (NPs) are smokeless, tobacco-free, oral products that may be beneficial as part of a THR strategy.ObjectiveThis 2-center, cross-sectional confinement study conducted in Denmark and Sweden aimed to determine whether biomarkers of exposure (BoEs) to tobacco toxicants and biomarkers of potential harm (BoPHs) in exclusive users of NPs show favorable differences compared with current smokers.MethodsParticipants were healthy NP users (target n=100) and current, former, or never smokers (target n=40 each), as confirmed by urinary cotinine and exhaled carbon monoxide concentrations. During a 24-hour confinement period, participants were asked to use their usual product (NP or cigarette) as normal, and BoEs and BoPHs were measured in blood and 24-hour urine samples, with compliance determined using anabasine, anatabine, and N-(2-cyanoethyl)valine. BoEs and BoPHs were compared between NP users and current, former, and never smokers. Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (BoE to nicotine-derived nitrosamine ketone) and urinary 8-epi-prostaglandin F2α type III, exhaled nitric oxide, blood carboxyhemoglobin, white blood cell count, soluble intercellular adhesion molecule-1, and high-density lipoprotein cholesterol (BoPHs) were evaluated as primary outcomes. Other measures included urinary 11-dehydrothromboxane B2, forced expiratory volume, carotid intima-media thickness, self-reported quality of life, and oral health.ResultsThe results of this study were received in mid-2022 and will be published in late 2022 to early 2023.ConclusionsThe results of this study will provide information on toxicant exposure and biomarkers associated with the development of smoking-related diseases among users of NPs compared with smokers, as well as on the potential role of NPs in THR.Trial RegistrationInternational Standard Randomised Controlled Trial Number (ISRCTN) ISRCTN16988167; https://www.isrctn.com/ISRCTN16988167International Registered Report Identifier (IRRID)DERR1-10.2196/39785

Diagnostic Performance Evaluation of the Novel Index Combining Urinary Cotinine and 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Smoking Status Verification and Usefulness for Trend Monitoring of Tobacco Smoking Exposure.

During the last decade in Korea, urinary cotinine concentrations in non-current smokers have decreased, making it difficult to distinguish secondhand smoke (SHS) exposure from nonsmokers because of overlapping values between non-current smokers with and without SHS exposure. Additionally, the importance of smoking status verification to avoid misclassification is increasing with the increased use of e-cigarettes. We developed a novel index combining urinary cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and evaluated its diagnostic performance for the classification of smoking status using the KNHANES VII dataset. A total of 10,116 and 5575 Korean participants aged >19 years with measured urinary cotinine concentrations were enrolled in a training set and validation set, respectively. When using 4.0 as the cutoff value for distinguishing current smokers from non-current smokers, urinary cotinine∙NNAL showed a better diagnostic performance than urinary cotinine or urinary NNAL. Among e-cigarette users, urinary cotinine∙NNAL showed more accurate classification rates than urinary NNAL. Furthermore, urinary cotinine∙NNAL had measurable values in non-current smokers, whereas urinary cotinine had unmeasurable values in one-fourth of all participants. This study shows that urinary cotinine∙NNAL might be a useful biomarker for smoking status verification and trend monitoring of tobacco smoking exposure with increased use of e-cigarettes.

Evaluating association of smoking status during pregnancy with adverse birth outcomes using urinary cotinine concentration: The Japan environment and Children's study (JECS)

Urinary cotinine concentration (UCC) reflects smoking status. However, in pregnant women, its association with adverse birth outcomes related to fetal growth is not widely known. Thus, we aimed to explore this relationship by focusing on dose–response relationships. We investigated 86,638 pregnant women enrolled between 2011 and 2014 in a prospective cohort study in Japan and observed three birth outcomes (preterm birth, low birth weight, and small-for-gestational age). We measured UCC in the second or third trimester, and categorized the participants using cut-off values (negative cotinine concentration, passive cotinine concentration, and active cotinine concentration corresponding to non-smokers, passive smokers, and active smokers, respectively). Logistic regression analyses were conducted to evaluate the risks, and dose–response relationships were visualized using restricted cubic spline curves. Analyses based on self-reported smoking status were also performed. We found that in low active and highly active cotinine concentrations, the adjusted odds ratios (aORs) of birth outcomes were significantly increased (preterm birth, 1.24 [95% CI 1.06–1.46], 1.39 [95% CI 1.19–1.62]; low birth weight, 1.40 [95% CI 1.24–1.58], 2.27 [95% CI 2.05–2.53]; small-for-gestational age, 1.35 [95% CI 1.19–1.52], 2.39 [95% CI 2.16–2.65]). Restricted cubic spline curves demonstrated risk elevations in the active cotinine concentration range. Our research revealed dose–response relationships between UCC during pregnancy and the risks of preterm birth, low birth weight, and small-for-gestational age. Measurement of UCC to ascertain smoking status during pregnancy may be a useful approach for predicting the risks of these birth outcomes.

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)

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.

Analysis of the Accuracy and Related Factors of Self-Reported Smoking Status according to Urinary Cotinine Concentration in Adolescents: The KoNEHS Cycle (2015~2017)

Analysis of the Accuracy and Related Factors of Self-Reported Smoking Status according to Urinary Cotinine Concentration in Adolescents: The KoNEHS Cycle (2015~2017)

Situations of Passive Smoking by Urine Cotinine Levels and Recognition of Passive Smoking in High School Students -Effectiveness of Smoking Prevention Education Using a Video Made by High School Students

We investigated a situation of passive smoking and its damaging effects among high school students. Urine cotinine concentration was measured and quantified. Additionally, we evaluated the awareness of passive smoking and smoking regulations in high school students, and the educational effect on passive smoking using a questionnaire survey and educational videos produced by high school students. We conducted a self-reporting questionnaire survey with high school students before and after watching the video produced by the high school students. We gathered the scores of the Kano Social Nicotine Dependence Questionnaire (KTSND) and awareness of smoking restrictions. Consent was obtained through the questionnaire before watching the video and collecting urine samples. Urine cotinine concentrations from 54 samples were evaluated and indicated within the low value. The KTSND score significantly decreased for those who responded to both questionnaires, after watching the video. Furthermore, analysis of the KTSND questionnaire items showed a significant decrease in scores for lifestyle, stress, and smoking location. This suggests that the video produced in this study has a certain amount of educational effect on passive smoking and that the student-led educational method is effective. The survey using the KTSND revealed that there were some students who were not exposed to passive smoking, but instead had high smoking tolerance. Going forward, it will be necessary to promote education on passive smoking and smoking prevention by incorporating the video lecture and urine cotinine concentration was measured, as in this study, to encourage behavior that decreases passive smoking among high school students.

Assessment of passive human exposure to tobacco smoke by environmental and biological monitoring in different public places in Wuhan, central China.

Passive exposure to tobacco smoke is a global public health problem, while there are few data on public place monitoring and general population exposure assessment in central China. This study aimed to examine the levels of airborne nicotine (n=256) in ten kinds of different public places in Wuhan, central China, and assess short-term and long-term smoke exposure in 340 non-smokers aged 18-67 who worked in these public places using tobacco biomarkers [i.e., cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), respectively]. The highest median concentration of airborne nicotine (17.0μg/m3) was observed in internet cafes, approximately 304-fold of the lowest value found in nurseries (55.9ng/m3). Among the other studied public places, restaurants had the highest median concentrations (ng/m3) of airborne nicotine (3,120), followed by subway stations (810), hotels (624), government officess (286), middle schools (269), health institutions (268), public institutions (190), and primary schools (140). Urinary cotinine and NNAL were found in almost all the participants, and the highest concentrations were found in non-smokers from the internet cafes [specific gravity (SG)-corrected urinary median concentrations: 23.1ng/mL, geometric mean (GM): 24.1ng/mL, range: 0.62-1679ng/mL] for cotinine and 104pg/mL (GM: 97.6pg/mL, range: 32.3-236pg/mL) for NNAL, respectively]. Urinary cotinine concentrations in male non-smokers (median: 2.02ng/mL) were significantly higher than those in female non-smokers (1.44) (P<0.01). Participants aged 18-27 were detected with the highest urinary cotinine and NNAL concentrations. Urinary cotinine and NNAL concentrations were significantly correlated with daily and monthly working hours, respectively. Besides, a positive correlation was observed between log-transformed urinary concentrations of cotinine and NNAL (r=0.32, P<0.001). This is the first time to report matched data on airborne nicotine and urinary cotinine/NNAL among employees in different public places. This study demonstrated ubiquitous exposure to environmental tobacco smoke in the studied public places.

Effect of Second-Hand Smoke Exposure on Establishing Urinary Cotinine-Based Optimal Cut-Off Values for Smoking Status Classification in Korean Adults.

Regulations for banning smoking in indoor public places and workplaces have increased worldwide in recent years. A consecutive Korean National Health and Nutrition Examination Survey (KNHANES) between 2008 and 2018 showed a trend toward significant decreases in self-reported tobacco smoke exposure and measured urinary cotinine concentrations. We established and compared each optimal cut-off value for assessing the effect of second-hand smoke (SHS) exposure on establishing urinary cotinine-based cut-off values for smoking status classification in a population setting controlled for racial and cultural diversity, using four KNHANES datasets consisting of the 2008, 2011, 2014, and 2018 surveys. A total of 18,229 Korean participants aged >19 years with measured urinary cotinine concentrations were enrolled. Self-reports of current smoking status showed that the prevalence of current smokers decreased from 22.9% to 18.2% between 2008 and 2018. During this period, the median value of urinary cotinine in nonsmokers decreased from 5.86 µg/L to 0.48 µg/L, whereas the median value showed no remarkable decrease in current smokers. The AUC-based optimal cut-off values of urinary cotinine concentration for distinguishing current smokers from nonsmokers decreased from 86.5 µg/L to 11.5 µg/L. Our study showed that decreased SHS exposure would result in decreased optimal cut-off values for distinguishing current smokers from nonsmokers. In addition, the study suggests that the range of urinary cotinine concentration to define SHS exposure for the trend monitoring of populationof SHS exposure is appropriate between 0.30 µg/L and 100 µg/L. In addition, our study showed the importance of determination of cotinine concentration, which would have allowed us to avoid mistakes in qualification to the study group in an increased use of e-cigarette setting.

Home gardens and distances to nature associated with behavior problems in alpine schoolchildren: Role of secondhand smoke exposure and biomarkers

Behavior problems in children are shaped by a complex intertwining of environmental, social, and biological factors. This study investigated whether more nature exposure was associated with less behavior problems and whether these associations were mediated by differences in secondhand smoke in the home, sleep problems, adiposity, and inflammation. We used cross-sectional data collected from 1251 schoolchildren (8-12 years old) in the Tyrol region of Austria and Italy. Information on sociodemographics, lifestyle, perinatal data, and housing conditions was obtained by questionnaire. Behavior problems in the past school year were rated by teachers using the Needleman questionnaire for classroom performance. We estimated nature exposure using a comprehensive naturalness index called "distance to nature" (D2N). This was calculated in several buffer sizes around the child's home and school. Presence of a home garden was assessed by self-report. Data on potential mediators including parental smoking in the home, child's urinary cotinine concentrations, sleep problems, body mass index, and urinary neopterin concentrations were also collected. Structural equation modeling was used to examine the multiple pathways between nature exposure and behavior problems. Children who lived in a home with a garden and those whose school was closer to nature exhibited less school behavior problems. The effect of proximity to nature from the school was directly associated with less behavior problems, and the effect of a home garden on behavior problems acted indirectly through a lower likelihood of secondhand smoke exposure. Associations were in unexpected directions between behavior problems and residential proximity to nature and depended on the outcome and context. Natural environments in school and home surroundings might be beneficial for school conduct and performance. Lower secondhand smoke exposure at home might be a pathway between home gardens and children's behavioral problems. Associations with residential proximity to nature in this study were in unexpected directions and warrant further investigation. These findings serve as a point of departure for investigating how proximal nature might activate health supportive pathways in children and simultaneously confer childhood health benefits via positive behavioral changes in their parents.

Optimum Urine Cotinine and NNAL Levels to Distinguish Smokers from Non-Smokers by the Changes in Tobacco Control Policy in Korea from 2008 to 2018.

We examined the age- and sex-specific distributions of biomarkers of tobacco smoke exposure to determine the optimal cutoffs to distinguish smokers from non-smokers over the last 10 years in Korea, during which smoking prevalence and secondhand smoke (SHS) exposure declined due to changes in tobacco control policy. We analyzed data from the Korea National Health and Nutrition Examination Survey on creatinine-adjusted urinary cotinine (2008-2018; 33 429 adults: 15 653 males and 17 776 females) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; 2016-2018; 6337 adults: 3091 males and 3246 females). We determined the optimal cutoffs and confidence intervals (CIs) to distinguish smokers from non-smokers using receiver operator characteristic curve analysis and bootstrapping (1000 resamples). The optimal cutoff values of creatinine-adjusted urine cotinine and NNAL concentration were 20.9 ng/mg (95% CI: 20.8-21.0, sensitivity: 96.6%, specificity: 93.8%) and 8.9 pg/mg (95% CI: 8.8-8.9, sensitivity: 94.0%, specificity: 94.7%), respectively, in 2016-2018. The optimal cutoffs of both biomarkers increased with age and were higher in females than in males for NNAL concentration. In both sexes, the optimal cutoff of urine cotinine continuously declined over the study period. The optimal cotinine cutoff declined along with smoking prevalence and levels of SHS exposure due to enforcement of tobacco control policies, including smoke-free ordinances and tax increases. Monitoring of biomarkers of tobacco exposure appears necessary for verification of smoking status and regulatory use. Our results based on nationally representative data suggest that a large decrease in the optimal cutoff value of urine cotinine to distinguish smokers from non-smokers was caused by decreases in smoking prevalence and SHS exposure following enforcement of tobacco control policies over the last 10 years. We determined the optimal cutoff values of urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which were not previously reported in representative population in Asia, to enable more accurate estimation of exposure to tobacco smoke and proper assessment of disease risks. Gender- and age-specific differences in the optimal cutoffs require further study. Monitoring of biomarkers of tobacco smoke exposure seems necessary for verification of smoking status and regulatory use.

Association between Fathers' Use of Heated Tobacco Products and Urinary Cotinine Concentrations in Their Spouses and Children.

Heated tobacco products (HTPs) have become increasingly popular among smokers, especially among young adults in Japan in recent years. Assessments of secondhand tobacco smoke (SHS) exposure due to HTPs are scarce. The present study aimed to assess the urinary levels of total nicotine metabolites (TNMs) of non-smoking spouses and their children following SHS exposure due to their fathers’ use of HTPs. A total of 41 families including 129 participants were recruited between 2018 and 2021. The number of non-smoking spouses and children of the fathers who smoke combustion cigarettes, the fathers who use HTPs, and the fathers who are non-users or have never smoked was 27, 66, and 36, respectively. The urinary levels of TNMs, including cotinine (Cot) and 3′-hydroxycotinine (3-OHCot), were measured using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The spouses and children of fathers who use HTPs had significantly higher levels of TNMs in their urine compared to those with fathers who were non-smokers or non-users. The current study is the first to assess SHS exposure due to HTP use, and to suggest the importance of strategies to prevent exposure to SHS from HTP use in public places and educational strategies to protect non-smokers from secondhand HTP aerosol exposure in households and other private places.

Maternal Urinary Cotinine Concentrations During Pregnancy Predict Infant BMI Trajectory After Birth: Analysis of 89617 Mother-Infant Pairs in the Japan Environment and Children's Study.

BackgroundClinical or epidemiological conclusions remain undecided on the direct effects of active and second-hand smoking during pregnancy on childhood obesity. Urinary cotinine (UC) concentration, an accurate and quantitative marker for smoking, may elucidate the dose-dependent relationship between smoking during pregnancy and childhood obesity. To analyze the relationship between UC concentration and smoking questionnaire (SQ) classes for active and second-hand smoking in pregnant mothers and trajectory of infant Kaup index (body mass index: BMI).MethodsThis multicenter prospective cohort study was conducted using a list-wise complete set of 35829 among 89617 mother-infant singleton pairs, recruited between 2011 and 2014, in the Japan Environment and Children’s Study (JECS). Pairs were categorized according to UC levels (1 to 4 classes) or SQ (0 to 4 classes).ResultsMaternal BMI at delivery was the highest in UC class 4 (highest). Maternal and paternal education of ≥16 years and annual household income were lowest in UC class 4. Infant BMI was lower at birth, but trends in BMI and ΔBMI were higher from six to 36 months step-wise in the UC classes. The above tendency was observed in the list-wise complete dataset but was emphasized after multiple imputations and corrections of cofounders. UC concentration in five SQ classes largely fluctuated, and the relationship between SQ classes and trends in BMI and ΔBMI was not statistically significant.ConclusionInfants from high UC mothers had a low BMI at birth, increasing from six to 36 months of age. UC concentrations, but not smoking questionnaire classes, predict infant BMI trajectory, suggesting that active and second-hand smoking affect child obesity in a dose-dependent manner.

Assessing tobacco smoke exposure in pregnancy from self-report, urinary cotinine and NNAL: a validation study using the New Hampshire Birth Cohort Study

ObjectivesAccurate assessment of tobacco smoke exposure is key to evaluate its effects. We sought to validate and establish cut-offs for self-reported smoking and secondhand smoke (SHS) exposure during pregnancy using...

Dose–response relationships between maternal urinary cotinine and placental weight and ratio of placental weight to birth weight: The Japan Environment and Children's Study

IntroductionStudies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. MethodsOur analysis used information of 91,049 mother–child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, −1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. ResultsPlacental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. ConclusionPlacental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.