Urinary Cotinine Measurements Research Articles

The Relationship between Maternal Smoking and Infant Birth Weight: Improving Accuracy through Urine Cotinine Analysis and Effective Medical Record Strategies.

We conducted a study to determine if antenatally collected maternal urine cotinine (a metabolite of nicotine) measurements can be used to assess the neonatal impact of nicotine exposure during pregnancy. This was a prospective longitudinal cohort of mother-infant dyads. Only term singleton pregnancies were included. The primary outcome measure was the correlation between maternal urine cotinine and infant birth weight. We analysed data from 238 mother-neonate dyads. Smoking habits were recorded during routine prenatal check-ups and urine samples were collected to measure cotinine and creatinine levels. Urine cotinine was detected in 50.4% (120/238) of women from the whole cohort, but only 16% (38/238) self-reported as smokers (chi-square 39.7, p < 0.0001), and these women had significantly smaller babies (p = 0.010). There was a significant negative correlation between maternal urine cotinine and birth weight (Spearman's coefficient = -0.0226, p = 0.013). Female babies born to women with nicotine in their urine were significantly smaller (p = 0.001). Infant birth weight significantly reduced in mothers with exposure to nicotine during pregnancy. The number of women exposed to nicotine during late pregnancy (measured in urine) was markedly higher than self-reported and national smoking percentages, suggesting an urgent need for an improvement in medical record reporting on smoking habits to better assess neonatal outcomes.

The Association Between Cotinine-Verified Smoking Status and Risk of Gallstones: A Cohort Study.

Previous epidemiological data on the association between cigarette smoking and risk of gallstone development remain controversial, and most relevant studies have relied on self-reported questionnaires. We aimed to elucidate this association using both an objective biomarker of tobacco exposure (urinary cotinine) and a self-reported questionnaire. We analyzed 221,721 asymptomatic adults who underwent abdominal ultrasonography and urinary cotinine measurement between January 2011 and December 2016. Cotinine-verified current smokers were defined as participants with urinary cotinine levels ≥50 ng/mL. The mean age of the study population was 35.9 years, and the proportion of men was 55.8%. The proportions of self-reported and cotinine-verified current smokers were 21.3% and 21.2%, respectively. After adjusting for confounding factors, self-reported current smoking was associated with an increased risk of gallstone development [adjusted odds ratio (aOR) 1.14; 95% confidence interval (95%CI), 1.04-1.25]. Moreover, among the current smokers, the risk of gallstone development increased with an increase in the amount of cigarette smoking (<20 and ≥20 pack-years vs. never smoked; aOR=1.11 and 1.25; 95%CI: 1.01-1.22 and 1.07-1.45, respectively). Cotinine-verified current smoking was also associated with an increased risk of gallstone development (aOR=1.16; 95%CI: 1.07-1.25). Among the self-reported never or former smokers, the cotinine-verified current smokers (aOR=1.20; 95%CI: 1.01-1.44) showed a significantly higher risk of gallstones than cotinine-verified never smokers. Cotinine-verified and self-reported current smoking were independent risk factors for gallstones, suggesting a distinct role of tobacco smoking in gallstone development.

Predicting Time to Return to Cannabis Use After a Cessation Attempt: Impact of Cumulated Exposure to Nicotine-Containing Products

Objective: Cannabis is frequently co-used with tobacco/nicotine products, especially among young adults. Little is known about the effects of this co-use on cannabis cessation outcomes. Within a sample of young adults using cannabis frequently (current use of ≥5 days/week in the past 3 months), this study aimed to (a) document sources of exposure to tobacco/nicotine products, whether used simultaneously with cannabis or on different occasions, (b) examine if the level of cumulated exposure to tobacco/nicotine (self-reported or from biochemical testing) could predict time to cannabis lapse during a cannabis abstinence period, and (c) explore the relationship between nicotine/tobacco exposure and time to cannabis lapse according to tobacco cigarette smoking status. Method: Urine cotinine measures and self-reported data on use of different tobacco/nicotine products, collected from 32 participants (aged 19 to 23), were analyzed to predict time to lapse during a 2-week period of attempted abstinence from cannabis, controlling for cannabis dependence and sex. Results: Half of participants (56.3%) used at least one tobacco/nicotine product. Higher urine cotinine, representing higher cumulated tobacco/nicotine exposure, was related to a higher risk of lapsing (Hazard Ratio [HR] = 1.64; 95%CI [1.04, 2.58]). The risk of lapsing was even higher ([HR] = 3.46; 95%CI [1.17, 10.25]) among heavily tobacco/nicotine exposed (&gt;600 ng/mL, urine cotinine) participants than among unexposed (&lt;50 ng/mL) or lightly/moderately exposed (50-600 ng/mL) participants. Among those smoking cigarettes (solely or in combination with other products), there was no relation between cotinine level and time to lapse, likely due to a reduced variability in abstinence probability and a high likelihood of lapse observed for higher cotinine levels, mainly achieved by cigarette use. Conclusions: With a rapidly changing landscape of tobacco/nicotine use, our results underscore the need to consider all sources of tobacco/nicotine exposure to fully understand the specific and cumulative contributions of tobacco/nicotine to cannabis cessation outcomes.

Association between secondhand smoke exposure and incident heart failure: The Multi-Ethnic Study of Atherosclerosis (MESA).

There are no studies on the association between secondhand smoke (SHS) exposure and incident heart failure (HF). This cohort study aimed to examine the associations of self-reported and urinary cotinine-assessed SHS exposure with incident HF. This study included 5548 non-active smoking participants aged 45-84 years and free of known cardiovascular diseases and HF at baseline who self-reported SHS exposure time in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000-2002). A cohort subset of 3376 non-active smoking participants underwent urinary cotinine measurements. HF events were verified by medical records or death certificates and ascertained from baseline through 2019. Multivariable Cox proportional hazards regression analysis was used with adjustment for demographic variables, traditional cardiovascular risk factors, physical activity, tobacco pack-years and medications. During a median follow-up of 17.7 years, 353 and 196 HF events were identified in the self-report cohort and cohort subset, respectively. In the self-report cohort, compared with the SHS unexposed group (0 h/week), the highest tertile of the SHS exposed group (7-168 h/week) was not associated with incident HF (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.49-1.00; p = 0.052). In contrast, in the cohort subset, participants with detectable urinary cotinine >7.07 ng/ml had a higher risk of incident HF than those with undetectable urinary cotinine ≤7.07 ng/ml (HR 1.45, 95% CI 1.03-2.06; p = 0.034). There were no significant heterogeneities in HF risk by age, sex, race/ethnicity, or past smoking status. Secondhand smoke exposure reflected by modestly increased urinary cotinine (>7.07 ng/ml) rather than self-report in non-active smokers was associated with a 40-50% higher risk of any HF event.

Association between parental smoking and child exposure to environmental tobacco smoke in Israel

BackgroundEnvironmental tobacco smoke (ETS) exposure in children can cause delayed lung development and lifelong cardiovascular damage. The aim of this study was to measure ETS exposure in children in Israel in 2020–2021 using urinary cotinine (UC) measurements and to assess correlates of ETS exposure, including parental smoking.MethodsIn the framework of the National Human Biomonitoring Program, spot urine samples and questionnaire data were collected from 166 children aged 4–12 years, during the years 2020–2021. We collected urine samples in 233 adults, 69 of whom were parents of children included in the study. Parents of participating children were asked about parental smoking, child’s exposure to ETS and smoking policy at home. Cotinine and creatinine were measured in urine. Creatinine-adjusted and unadjusted urine cotinine (UC) geometric means were calculated. Associations between potential correlates and UC concentrations were analyzed in univariate and multivariate analyses. For 69 child-parent pairs, correlation between child and parental UC was analyzed.ResultsBased on urinary cotinine measurement, 65.2% of children of smokers are exposed to ETS, compared to 20.7% of children in non-smoking families. Greater numbers of smokers living in the home (beta = 1.27, p < 0.01), and low maternal education (beta = − 2.32, p < 0.01) were associated with higher levels of UC in a multivariate analysis. Spearman correlations showed a positive moderate correlation between UC in 69 child–parent pairs (r = 0.52, p < 0.01).ConclusionsIn order to reduce child exposure to ETS, smoking parents should be urgently targeted for smoking cessation and smoke-free home interventions. Further interventions are needed to protect all children from ETS.

Simultaneous Measurement and Distribution Analysis of Urinary Nicotine, Cotinine, Trans-3′-Hydroxycotinine, Nornicotine, Anabasine, and Total Nicotine Equivalents in a Large Korean Population

Measurement of multiple nicotine metabolites and total nicotine equivalents (TNE) might be a more reliable strategy for tobacco exposure verification than measuring single urinary cotinine alone. We simultaneously measured nicotine, cotinine, 3-OH cotinine, nornicotine, and anabasine using 19,874 urine samples collected from the Korean National Health and Nutrition Examination Survey. Of all samples, 18.6% were positive for cotinine, 17.4% for nicotine, 17.3% for nornicotine, 17.6% for 3-OH cotinine, and 13.2% for anabasine. Of the cotinine negative samples, less than 0.3% were positive for all nicotine metabolites, but not for anabasine (5.7%). The agreement of the classification of smoking status by cotinine combined with nicotine metabolites was 0.982–0.994 (Cohen’s kappa). TNE3 (the molar sum of urinary nicotine, cotinine, and 3-OH cotinine) was most strongly correlated with cotinine compared to the other nicotine metabolites; however, anabasine was less strongly correlated with other biomarkers. Among anabasine-positive samples, 30% were negative for nicotine or its metabolites, and 25% were undetectable. Our study shows that the single measurement of urinary cotinine is simple and has a comparable classification of smoking status to differentiate between current smokers and non-smokers relative to the measurement of multiple nicotine metabolites. However, measurement of multiple nicotine metabolites and TNE3 could be useful for monitoring exposure to low-level or secondhand smoke exposure and for determining individual differences in nicotine metabolism. Geometric or cultural factors should be considered for the differentiation of tobacco use from patients with nicotine replacement therapy by anabasine.

Comparison of secondhand smoking exposure between self-report and creatinine-corrected urine cotinine: Result from Korean NHANES 2009–2018

Second-hand smoking (SHS) is usually examined by self-report (SR). However, there is a possibility that SR may not accurately measure SHS exposure. This study aimed to identify yearly trends and gender differences in SHS by SR and cotinine. We used data from the 2009-2018 Korea National Health and Nutrition Examination Survey (KNHANES) and included adults aged 19 years and older. We analyzed data of 47,907 respondents on SHS exposures in the past week and of 23,572 respondents who had both urine cotinine and creatinine measurements. SHS exposure was defined as those who answered 'yes' to whether or not they were exposed to smoking by SR. We performed descriptive analysis, Average annual percentage change (AAPC), and multiple regression analysis. All analyses were weighted reflecting the multi-stratified cluster sampling. Exposure to SHS indoors at the work place (WSHS) (2009: 44.8%, 2018: 12.3%), indoors at home (HSHS) (2009: 14.1%, 2018: 3.9%), and indoors at public places (PSHS) (2013: 55.6%, 2018: 15.4%) decreased steadily over the years. WSHS and PSHS exposure was higher for males but HSHS was higher for females. However, the concentration of cotinine-to-creatinine ratio (Co/Cr) was higher among females regardless of SHS exposure status and environment. Multiple regression analysis showed that among males, the association between Co/Cr education level and WSHS was the strongest, and among females, the association was the strongest with HSHS. In addition, home exposure to SHS intensified the differences in Co/Cr levels between males and females. Our study confirmed that cotinine-induced SHS showed different results by year and gender compared to SR. In particular, Co/Cr level in females was higher than in males regardless of exposure by SR, suggesting that SR did not correctly evaluate SHS. To reflect reality more accurately, biomarkers should be monitored along with SR.

DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort

Prenatal tobacco exposure (PTE) and prenatal alcohol exposure (PAE) have been associated with an increased risk of delayed neurodevelopment in children as well as differential newborn DNA methylation (DNAm). However, the biological mechanisms connecting PTE and PAE, DNAm, and neurodevelopment are largely unknown. Here we aim to determine whether differential DNAm mediates the association between PTE and PAE and neurodevelopment at 6 (N = 112) and 24 months (N = 184) in children from the South African Drakenstein Child Health Study. PTE and PAE were assessed antenatally using urine cotinine measurements and the ASSIST questionnaire, respectively. Cord blood DNAm was measured using the EPIC and 450 K BeadChips. Neurodevelopment (cognitive, language, motor, adaptive behavior, socioemotional) was measured using the Bayley Scales of Infant and Toddler Development, Third Edition. We constructed methylation risk scores (MRS) for PTE and PAE and conducted causal mediation analysis (CMA) with these MRS as mediators. Next, we conducted a high-dimensional mediation analysis to identify individual CpG sites as potential mediators, followed by a CMA to estimate the average causal mediation effects (ACME) and total effect (TE). PTE and PAE were associated with neurodevelopment at 6 but not at 24 months. PTE MRS reached a prediction accuracy (R2) of 0.23 but did not significantly mediate the association between PTE and neurodevelopment. PAE MRS was not predictive of PAE (R2 = 0.006). For PTE, 31 CpG sites and eight CpG sites were identified as significant mediators (ACME and TE P < 0.05) for the cognitive and motor domains at 6 months, respectively. For PAE, 16 CpG sites and 1 CpG site were significant mediators for the motor and adaptive behavior domains at 6 months, respectively. Several of the associated genes, including MAD1L1, CAMTA1, and ALDH1A2 have been implicated in neurodevelopmental delay, suggesting that differential DNAm may partly explain the biological mechanisms underlying the relationship between PTE and PAE and child neurodevelopment.

Epigenetic Mediation of Prenatal Tobacco and Alcohol Exposure and Infant Neurodevelopment in a South African Birth Cohort: A High-Dimensional Mediation Analysis

BACKGROUND AND AIMS Prenatal tobacco exposure (PTE) and prenatal alcohol exposure (PAE) have been associated with an increased risk of delayed neurodevelopment in children as well as differential newborn DNA methylation (DNAm). However, the biological mechanisms connecting PTE and PAE, DNAm, and neurodevelopment are largely unknown. Here we aim to determine whether differential DNAm in cord blood mediates the association between PTE and PAE and neurodevelopment in 113 children of 6 months of age from the South African Drakenstein Child Health Study. METHODS PTE and PAE were assessed antenatally using urine cotinine measurements and the ASSIST questionnaire, respectively. DNAm was measured from cord blood using the EPIC and 450K BeadChips. Neurodevelopment was measured at 6 months across five domains (cognitive, language, motor, adaptive behavior, socioemotional) using the Bayley Scale of Infant and Toddler Development, Third Edition. We conducted a high-dimensional mediation analysis using a novel approach called the divide-aggregate composite null test (DACT), followed by causal mediation analysis to estimate the average causal mediation effects (ACME) and total effect (TE). RESULTS In this population, 35% of mothers actively smoked and 23% of mothers consumed alcohol during pregnancy. We identified 31 CpG sites and 8 CpG sites to have a significant mediating effect (ACME and TE P &amp;#x3c;0.05) between PTE and cognitive and motor development, respectively. For PAE, 16 CpG sites and 1 CpG site had a significant mediating effect on motor and adaptive behavior development, respectively. CONCLUSIONS These findings suggest that changes in the methylome may in part explain the biological mechanisms underlying the relationship between PTE and PAE and infant neurodevelopment. The identification of significant CpG sites could provide novel insights for early detection of disease and potential prevention targets in translational research and community interventions in at-risk populations. KEYWORDS: epigenomics; mediation analysis; neurodevelopment; prenatal smoking; prenatal alcohol exposure

Smoking and Radiation-induced Skin Injury: Analysis of a Multiracial, Multiethnic Prospective Clinical Trial

IntroductionSmoking during breast radiotherapy (RT) may be associated with radiation-induced skin injury (RISI). We aimed to determine if a urinary biomarker of tobacco smoke exposure is associated with increased rates of RISI during and after breast RT. Patients and MethodsWomen with Stage 0-IIIA breast cancer treated with breast-conserving surgery or mastectomy followed by RT to the breast or chest wall with or without regional nodal irradiation were prospectively enrolled on a multicenter study assessing acute/late RISI. 980 patients with urinary cotinine (UCot) measurements (baseline and end-RT) were categorized into three groups. Acute and late RISI was assessed using the ONS Acute Skin Reaction scale and the LENT-SOMA Criteria. ResultsLate Grade 2+ and Grade 3+ RISI occurred in 18.2% and 1.9% of patients, respectively—primarily fibrosis, pain, edema, and hyperpigmentation. Grade 2+ late RISI was associated with UCot group (P= 006). Multivariable analysis identified UCot-based light smoker/secondhand smoke exposure (HR 1.79, P= .10) and smoking (HR 1.60, p = .06) as non-significantly associated with an increased risk of late RISI. Hypofractionated breast RT was associated with decreased risk of late RISI (HR 0.51, P=.03). UCot was not associated with acute RISI, multivariable analysis identified race, obesity, RT site/fractionation, and bra size to be associated with acute RISI. ConclusionsTobacco exposure during breast RT may be associated with an increased risk of late RISI without an effect on acute toxicity. Smoking cessation should be encouraged prior to radiotherapy to minimize these and other ill effects of smoking.

The association between cotinine-measured smoking intensity and sleep quality.

INTRODUCTIONCigarette smoking is suggested to be associated with sleep problems. This study evaluated the quantitative association between urinary cotinine-verified smoking intensity and sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI).METHODSThis was a cross-sectional study of 189970 participants from the Kangbuk Samsung Health Study recruited between 2016 and 2018. Logistic regression analysis adjusted for covariates was performed to estimate the association between urinary cotinine levels assessed by quartiles and poor sleep quality, defined as global PSQI score >5.RESULTSThe odds ratios (OR) and 95% confidence intervals (CI) for poor sleep quality comparing the highest urinary cotinine quartile to non-smokers were: 1.23 (95% CI: 1.16–1.30) for overall, 1.19 (95% CI: 1.12–1.26) for males, and 1.55 (95% CI: 1.29–1.87) for females. Among self-reported never smokers, cotinineverified smokers had higher odds for decreased sleep quality compared to cotinineverified never smokers with OR of 1.26 (95% CI: 1.08–1.46).CONCLUSIONSElevated urinary cotinine levels were associated with poor sleep quality in relatively young and middle-aged South Korean adults. Higher odds for poor sleep quality among cotinine-verified smokers who self-reported as never smokers also demonstrate the value of quantitative measurement of urinary cotinine. Prospective studies are warranted to clarify the cause-effect relationship between smoking and sleep quality.

Hand nicotine as an independent marker of thirdhand smoke pollution in children's environments

BackgroundHand nicotine (HN) levels measure children's exposure to tobacco smoke pollutants from thirdhand and secondhand smoke. HN is associated with urinary and salivary cotinine, but the associations of HN with other tobacco smoke exposure (TSE) markers remain unknown. ObjectivesWe compared levels of HN and four urinary TSE biomarkers: cotinine, trans-3′-hydroxycotinine (3HC), nicotelline N-oxides, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and children's sociodemographic and TSE patterns. We also examined if HN is a plausible pathway for children's exposure to active smoking. MethodsData were collected from 175 non-smoking patients (Mean (SD) age = 5.4 (3.4) years) who lived with ≥1 cigarette smoker(s). HN and TSE biomarker levels were determined using LC-MS/MS. Multivariate and multivariable regression analyses were conducted to examine associations between TSE markers and parent-reported measures, controlling for sociodemographics. ResultsOf the five markers of TSE, cotinine (R2 = 0.221; p = 0.003) and HN (R2 = 0.247; p = 0.001) showed the strongest overall associations. Of the five markers, only cotinine showed significantly higher levels among Black children (β^=0.307,p<0.05) independent of age, reported exposure, and home smoking bans. Cotinine (β^=0.010,p<0.05), NNAL (β^=0.012,p<0.05), and HN (β^=0.011,p<0.05) showed significant positive associations with reported exposure independent of race, age, and home smoking bans. NNAL (β^=−0.285,p<0.05) and HN (β^=−0.336,p<0.05), but not cotinine, 3HC, and N-oxides, showed significantly lower levels among children who lived in homes with smoking bans. Child age, hand surface area, home smoking ban, and reported exposure independently accounted for 21 % of the variance in HN levels (p = 0.002). HN accounted for 30 % of the variance in cotinine independent of child race and child age. DiscussionHN levels were associated with modifiable tobacco-related behaviors and shows promise as a marker of sources of THS pollution in a child's environment not captured by measurement of urinary cotinine alone. HN levels provide additional information about TSE, complementing other biomarkers when assessing children's overall TSE.

In-utero exposure to indoor air pollution or tobacco smoke and cognitive development in a South African birth cohort study

Background and AimsThere is increasing evidence indicating that air pollution exposure is associated with neuronal damage. Since pregnancy is a critical window of vulnerability, air pollution exposure during this period could have adverse effects on neurodevelopment. This study aims 1) to analyze associations of prenatal exposure to indoor air pollution (particulate matter with diameters ≤10 μm, PM10) and tobacco smoke with neurodevelopment and 2) to determine whether these associations are mediated by deviations of epigenetic gestational age from chronological gestational age (ΔGA). MethodsData of 734 children from the South African Drakenstein Child Health Study were analyzed. Prenatal PM10 exposure was measured using devices placed in the families' homes. Maternal smoking during pregnancy was determined by maternal urine cotinine measures. The Bayley Scales of Infant and Toddler Development III (BSID-III) was used to measure cognition, language and motor development and adaptive behavior at two years of age. Linear regression models adjusted for maternal age, gestational age, sex of child, ancestry, birth weight/length, and socioeconomic status were used to explore associations between air pollutants and BSID-III scores. A mediation analysis was conducted to analyze if these associations were mediated by ΔGA using DNA methylation measurements from cord blood. ResultsAn increase of one interquartile range in natural-log transformed PM10 (lnPM10; 1.58 μg/m3) was significantly associated with lower composite scores in cognition, language, and adaptive behavior sub-scores (composite score β-estimate [95%-confidence interval]: −0.950 [−1.821, −0.120]). Maternal smoking was significantly associated with lower adaptive behavior scores (−3.386 [−5.632, −1.139]). Associations were not significantly mediated by ΔGA (e.g., for PM10 and cognition, proportion mediated [p-value]: 4% [0.52]). ConclusionWe found an association of prenatal exposure to indoor air pollution (PM10) and tobacco smoke on neurodevelopment at two years of age, particularly cognition, language, and adaptive behavior. Further research is needed to understand underlying biological mediators.

Abstract 10114: Secondhand Tobacco Smoke Exposure, Urine Cotinine, and Risk of Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis

Importance: Secondhand tobacco smoke (SHS) exposure may reduce heart rate variability and has been associated with atrial fibrillation (AF), but the association of SHS with AF has not been confirmed using objective measures for both SHS and incident AF events. Objectives: To investigate the association of self-reported and objective SHS exposure amounts with incident AF. Design: Cohort study. Setting: The Multi-Ethnic Study of Atherosclerosis (MESA) included 6 USA sites. We used follow-up data from the first visit (2000-2002) through 2015. Participants: The study sample consisted of 5,730 participants, aged 45-84 years and free of known AF and other cardiovascular diseases at baseline, who self-reported SHS exposure time in hours per week. We also selected a cohort subset of 3,237 current non-smoking participants who received spot urine cotinine measurements at baseline (2000-2002). Exposures: Self-reported SHS exposure time (whole cohort) and urine cotinine levels (cohort subset). Main Outcomes and Measures: AF events were identified using Medicare claims, hospital records and electrocardiographic findings. A multivariable Cox proportional hazards regression model was used with simultaneous adjustment for demographic factors, educational level, health insurance status, active smoking status, tobacco pack-years, traditional cardiovascular risk factors, depressive symptoms and medications. Results: During a median follow-up of 14.0 years, 856 and 452 AF events were identified in the overall and the cohort subset, respectively. No association of SHS exposure time or urine cotinine with incident AF was found. However, a higher AF risk with greater urine cotinine (8.53-442.0 ng/mL) compared with lower urine cotinine (≤7.07 ng/mL) was observed in never smokers [hazard ratios (HR): 1.60 (95% confidence intervals (CI): 1.16, 2.19)], but not in former smokers [HR: 0.88 (95% CI: 0.63, 1.23)] (p-value for multiplicative interaction: 0.009 and for additive interaction: 0.017, respectively). Conclusions and Relevance: Objectively measured greater SHS exposure expressed by urine cotinine might be associated with 1.6-fold higher risk of incident AF in never smokers.

Repetitive transcranial magnetic stimulation for smoking cessation: apivotal multicenter double-blind randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double-blind RCT in 262 chronic smokers meeting DSM-5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of dailybilat-eral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue-induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four-week continuous quit rate (CQR) until Week 18 in the intent-to-treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent-to-treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X2 =5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X2 =7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid insmok-ing cessation for adults.

In-utero exposure to indoor air pollution or tobacco smoke and cognitive development in a South African birth cohort study

BACKGROUND AND AIM: There is increasing evidence indicating that air pollution exposure is associated with neuronal damage. Since pregnancy is a critical window of vulnerability, air pollution exposure during this period could have adverse effects on neurodevelopment. This study aims 1) to analyze associations of prenatal exposure to indoor air pollution (particulate matter with diameters ≤10μm, PM10) and tobacco smoke on neurodevelopment and 2) to determine if these associations are mediated by deviations of epigenetic gestational age from chronological gestational age (ΔGA). METHODS: Data of 734 children from the South African Drakenstein Child Health Study were analyzed. Antenatal PM10 exposure was measured using devices placed in the families’ homes. Maternal smoking during pregnancy was determined by maternal urine cotinine measures. Bayley Scales of Infant Development were used to measure cognition, language, motor, and adaptive behavior development at two years of age. Overall composite scores were calculated as the average of the four sub-scores. Linear regression models adjusted for maternal age, gestational age, sex of child, ancestry, birth weight/length, and socioeconomic status were used to explore associations. A mediation analysis was conducted to analyze if the associations were mediated by ΔGA using DNA methylation measurements from cord blood. RESULTS:An increase of one interquartile range in PM10 (54.40μg/m3) was significantly associated with lower cognition sub-scores (β-estimate [95%-confidence interval]: -0.01 [-0.22, 0.00]). Maternal smoking was significantly associated with lower overall composite scores (-1.84 [-3.52, -0.16]) and lower adaptive behavior sub-scores (-3.39 [-5.63, -1.14]). Other scores were not associated with PM10 or smoking. Associations were not significantly mediated by ΔGA (e.g., for PM10 and cognition, proportion mediated [95%-confidence interval]: 1% [-18, -20%]). CONCLUSIONS:We found an association of prenatal exposure to indoor air pollution (PM10) and tobacco smoke on neurodevelopment at 2 years of age. Further research is needed to understand underlying biological mediators. KEYWORDS: Air pollution, Particulate matter, Neurodevelopmental outcomes, Environmental epidemiology, Epigenomics

The risk of colorectal neoplasm in ex- and never-smokers according to urinary cotinine level.

To investigate the relationship between urinary cotinine and colorectal neoplasm (CRN).The participants in the health screening cohort of the National Cancer Center who underwent screening colonoscopy between June 2007 and December 2009 were included. A total of 8121 subjects who underwent urinary cotinine measurement within 14 days from the index colonoscopy were included. Cotinine positivity was defined as having a urinary cotinine level ≥50 ng/mL. Follow-up colonoscopy data were collected by reviewing the patients’ medical records.Patients were classified according to their urinary cotinine level and self-reported smoking status, and the number of patients with cotinine positivity was 1960 (24.1%). There was no significant difference in the cumulative CRN and advanced CRN (ACRN) risks according to the self-reported smoking status. However, cotinine positivity at the time of index colonoscopy was an independent risk factor for CRN (hazard ratio [HR]= 1.23, P = .006) in follow-up colonoscopy. Moreover, in never- and ex-smokers, cotinine positivity was an independent risk factor for CRN (HR = 1.95, P = .019; HR = 2.12, P = .003, respectively) and ACRN (HR = 8.89, P < .001; HR = 5.03, P = .003) during follow-up colonoscopy. The cumulative incidence of CRN and ACRN was higher in the cotinine-positive never- and ex-smokers than in the cotinine-negative never- and ex-smokers (P < .001 and P = .008, respectively).CRN or ACRN is more likely to occur at follow-up colonoscopy in the urinary cotinine-positive never- and ex-smokers than in the urinary cotinine-negative group. Therefore, urinary cotinine measurements may provide useful information on never- or ex-smokers undergoing screening colonoscopy.

Transcranial Magnetic Stimulation for Smoking Cessation

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method that is increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help treat addictions, but evaluation is required in a multicenter randomized controlled trial (RCT). METHODS: Here, we tested in chronic smokers whether repeated bilateral rTMS of the lateral prefrontal and insular cortices reduces cigarette craving and consumption and increases quit rates. This multicenter RCT included 14 sites and 262 chronic smokers who received Active or Sham rTMS. Participants received three weeks of daily rTMS sessions following cue-induced craving and were monitored up to four months. The primary outcome was the four-week continuous quit rate (CQR) measured by daily smoking diaries and verified by urine cotinine measures. Secondary outcome measures included changes in cigarette consumption and craving. This trail is registered at ClinicalTrials.gov, number NCT02126124. RESULTS: In the intent to treat analysis set, CQR was 19·4% following Active and 8·7% following Sham rTMS (χ 2 = 5·655, p=0·017). Among completers (N=169), CQR was 28·0% and 11·7%, respectively (χ 2 = 7·219, p=0·007). CQR within the first six weeks was 25·3% (Active) and 6·4% (Sham) (χ 2 = 11·885, p=0·0006), of which 63% (Active) and 50% (Sham) remained abstinent for at least four months (χ 2 =8·46, p=0·003). Significant between-group differences in cigarette consumption and craving emerged as early as two weeks into treatment. CONCLUSIONS: This study establishes a safe treatment protocol that promotes smoking cessation by stimulating the relevant brain circuits. It represents the first large multicenter RCT of brain stimulation for addiction medicine. Funded by: BrainsWay Declaration of Interest: Oscar Morales occasional reports consult work for Brainsway; Dr. Tendler reports personal fees from Brainsway, other from Advanced Mental Health Care Inc./DTMS Center LLC, outside the submitted work; Dr. Roth reports personal fees from Brainsway, outside the submitted work; In addition, Dr. Roth has a patent US 7,407,478 with royalties paid; Mr. Deutsch reports personal fees from Brainsway, during the conduct of the study; personal fees from Brainsway, outside the submitted work; David Feifel reports he is a member of Brainsway's Scientific Advisory Board (non-compensated); Dr. Duffy reports other from Brainsway, during the conduct of the study; other from Alivation Health LLC and Alivation Research LLC, outside the submitted work; Prof. Abraham Zangen is an inventor of Deep TMS coils which were patented by the NIH and other academic institutions where Abraham Zangen worked. These patents were licensed to BrainsWay and Abraham Zangen receives royalties from these patents. In addition Prof. Zangen serves as consultant for BrainsWay and has finanacial insterests in BrainsWay; Dr. Todder reports other from BRAINSWAY, during the conduct of the study; all other authors have nothing to disclose. Ethical Approval:The trial protocol (Supplementary Materials; SM 1.1) was approved by local institutional review boards and was registered at clinicaltrials.gov (NCT02126124). The study was conducted in the United States (12 sites) and Israel (two sites), with active enrollment from August 2014 through August 2019. The trial was supported by industry (BrainsWay).

A Mobile Health Intervention for Adolescents Exposed to Secondhand Smoke: Pilot Feasibility and Efficacy Study.

BackgroundSecondhand smoke (SHS) exposure in children and adolescents has adverse health effects. For adolescents of lower socioeconomic status (SES), exposure is widespread, evidenced in the measurement of urinary cotinine, a major metabolite of nicotine. Direct intervention with exposed children has been proposed as a novel method, yet there is minimal evidence of its efficacy. Combining this approach with a mobile health (mHealth) intervention may be more time and cost-effective and feasible for adolescent populations.ObjectiveIn this pilot study, we assessed the feasibility and preliminary evidence of efficacy of a 30-day text message–based mHealth intervention targeted at reducing SHS exposure in adolescent populations of low SES.MethodsFor the study, 14 nonsmoking and nonvaping participants between the ages of 12-21 years exposed to SHS were enrolled. The intervention consisted of a daily text message sent to the participants over the course of a month. Text message types included facts and information about SHS, behavioral methods for SHS avoidance, or true-or-false questions. Participants were asked to respond to each message within 24 hours as confirmation of receipt. Feasibility outcomes included completion of the 30-day intervention, receiving and responding to text messages, and feedback on the messages. Efficacy outcomes included a reduction in urinary cotinine, accuracy of true-or-false responses, and participants’ perceptions of effectiveness.ResultsOf the 14 participants that were enrolled, 13 completed the intervention. Though not required, all participants had their own cell phones with unlimited text messaging plans. Of the total number of text messages sent to the 13 completers, 91% (372/407) of them received on-time responses. Participant feedback was generally positive, with most requesting more informational and true-or-false questions. In terms of efficacy, 54% (6/11) of participants reduced their cotinine levels (however, change for the group overall was not statistically significant (P=.33) and 45% (5/11) of participants increased their cotinine levels. Of the total number of true-or-false questions sent across all completers, 77% (56/73) were answered correctly. Participants’ ratings of message effectiveness averaged 85 on a scale of 100.ConclusionsIn this pilot study, the intervention was feasible as the majority of participants had access to a cell phone, completed the study, and engaged by responding to the messages. The efficacy of the study requires further replication, as only half of the participants reduced their cotinine levels. However, participants answered the majority of true-or-false questions accurately and reported that the messages were helpful.

Effectiveness of ongoing face-to-face anti-tobacco intervention in children with asthma.

Background: Interventions to help parents quit smoking may yield important benefits for children with asthma. Children's exposure to environmental tobacco smoke can be measured by reporting of an adult in the household and testing the child's biomarker, e.g., cotinine. Objective: The aim of the study was to assess the effectiveness of "face-to-face" intervention carried out since 2016 in families with children diagnosed with asthma 3 years after beginning the anti-tobacco intervention. Methods: This study was a follow-up to an interventional study that assessed the effectiveness of direct patient education versus educational leaflets alone about parental tobacco smoking. The patients with asthma (ages 4-17 years) enrolled in our original intervention study conducted in 2016 were under the care of the allergy outpatient clinic. The active group was individually educated about the harmful effects of environmental tobacco smoke on their children. The control group included patients and parents, among whom only leaflets were distributed. After 3 years of ongoing intervention, in patients from both groups, exposure to tobacco smoking was evaluated with a questionnaire addressed to parents and/or caregivers and measurement of cotinine in children's urine. The forced expiratory volume in the first second of expiration and fractional exhaled nitric oxide levels were measured. Results: Seventy participants completed the study: 37 in the active group and 33 in the control group. In the active group, 27% of the parents quit smoking entirely compared with 9.4% of parents in the control group. In the group of active intervention, a significant decrease in the cotinine level (p < 0 .001) and the number of cigarettes smoked daily were observed (p < 0.001) 3 years after the active intervention compared with values right after the intervention. In the control group, there were no significant changes in the above-mentioned parameters. Conclusion: "Face-to-face" intervention among families with smokers were effective and lowered cotinine levels in children with asthma and the number of cigarettes smoked assessed 3 years after the intervention.