Association of magnesium deficiency, tobacco smoke exposure and hypertension in children and adolescents: evidence from the NHANES 2007-2018.

BACKGROUND: Recent studies suggested that the combination of tobacco smoke exposure (TSE) and dietary nutrients intake may be related to a higher or lower risk of hypertension. However, the relationship between dietary magnesium (Mg) intake, TSE and the odds of hypertension remain unclear. This study aimed to evaluate the association of TSE, dietary Mg intake and the odds of hypertension among children and adolescents. METHOD: Data of this study were extracted from the National Health and Nutrition Examination Surveys (NHANES) 2007-2018. Dietary Mg intake was calculated as the average of two days of dietary and supplementations intake. Serum cotinine concertation ≥ 0.05 µg/L or at least one-person smoking in the household was considered as exposing to the tobacco smoke. The weighted univariate and multivariate logistic regression models were utilized to explore the associations of dietary Mg intake, TSE and the odds of hypertension among children and adolescents with the evaluation index of odds ratio (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on different age, gender and overweight were further assessed these associations. RESULTS: A total of 7,122 children and adolescents aged 8-17 years old and with the blood pressure measurement were included. Of which, 948 (13.31%) had hypertension. After adjusting all covariates, we observed children and adolescents exposed to tobacco smoke was related to higher odds of hypertension (OR = 1.34, 95%CI: 1.01-1.78); children and adolescents not reached the dietary Mg references intakes was related to higher odds of hypertension (OR = 1.48, (95%CI: 1.11-1.97); compared to children and adolescents non-TSE and reached the DRIs of Mg, those not reached the DRIs of Mg and exposed to tobacco smoke have the highest odds of hypertension (OR = 1.94, 95%CI: 1.30-2.89, P for trend = 0.002). These associations of dietary Mg intake, TSE and hypertension remain robust after the stratified analysis based on age, gender and overweight was conducted. CONCLUSION: Our findings suggested there were a robust association between dietary Mg intake, TSE and hypertension in children and adolescents. Those children and adolescents with deficiency dietary Mg intake and exposed to tobacco smoke may have the high odds of hypertension. More restrictions on smoking as well as Mg supplementation in the prevention and treatment of hypertension among children and adolescents might be justified.

Association between serum cotinine and total testosterone in adult males based on NHANES 2011-2016.

The relationship between smoking and testosterone levels in adult males remains a topic of ongoing debate. Serum cotinine is considered a reliable marker of both smoking intensity and exposure to tobacco smoke. Therefore, we aim to examine the association between serum cotinine levels and total testosterone concentrations in adult males using data from the U.S. National Health and Nutrition Examination Survey (NHANES) database. Our study assessed the relationship between serum cotinine and total testosterone using weighted linear regression models and subgroup analysis. A fully adjusted model with smooth curve fitting was employed to investigate the potential nonlinear association between serum cotinine and total testosterone. Threshold effects were analyzed to identify the inflection point between serum cotinine and total testosterone. Indeed, a total of 7797 participants were included in our study. After adjusting for potential confounding variables, the findings indicate a positive association between serum cotinine levels and total testosterone levels (ß: 0.05, 95%CI: 0.02, 0.09). Furthermore, applying smoothed curve fitting analysis and threshold effects, an inflection point was detected at a serum cotinine level of 487 ng/ml. Above this threshold, total testosterone levels declined with increasing serum cotinine levels. In conclusion, the findings of our study suggest a positive association between elevated serum cotinine levels and total testosterone levels in adult men. However, it is essential to note that this association may be reversed at excessively high serum cotinine concentrations.

Differential effects of environmental exposures on clinically relevant endophenotypes between sexes.

Sex and gender differences play a crucial role in health and disease outcomes. This study used data from the National Health and Nutrition Examination Survey to explore how environmental exposures affect health-related traits differently in males and females. We utilized a sex-stratified phenomic environment-wide association study (PheEWAS), which allowed the identification of associations across a wide range of phenotypes and environmental exposures. We examined associations between 272 environmental exposures, including smoking-related exposures such as cotinine levels and smoking habits, and 58 clinically relevant blood phenotypes, such as serum albumin and homocysteine levels. Our analysis identified 119 sex-specific associations. For example, smoking-related exposures had a stronger impact on increasing homocysteine, hemoglobin, and hematocrit levels in females while reducing serum albumin and bilirubin levels and increasing c-reactive protein levels more significantly in males. These findings suggest mechanisms by which smoking exposure may pose higher cardiovascular risks and greater induced hypoxia for women, and greater inflammatory and immune responses in men. The results highlight the importance of considering sex differences in biomedical research. Understanding these differences can help develop more personalized and effective health interventions and improve clinical outcomes for both men and women.

Serum cotinine levels and adolescents' sleep health outcomes from NHANES 2005 to 2018.

The association between tobacco smoke exposure and sleep has been widely discussed, but the correlation between serum cotinine levels and sleep health outcomes in adolescents has not been well described. This study aimed to further evaluate the association between serum cotinine levels and sleep health outcomes in adolescents using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. This cross-sectional study included participants aged 16-19 years from the NHANES 2005-2018. A weighted multivariate logistic regression model was used for the primary analysis. A restricted cubic spline (RCS) model was employed to investigate the non-linear association between serum cotinine levels and trouble sleeping. Subgroup analyses based on population characteristics were also conducted. In total, 2630 participants were included, which are representative of the 11.5 million US adolescents. Higher serum cotinine levels (≥ 3 ng/ml) were significantly associated with trouble sleeping in the fully adjusted model (odds ratio [OR] 1.817). The RCS model revealed a non-linear relationship between serum cotinine levels and trouble sleeping. Subgroup analyses indicated that this relationship was consistent and stable across various population characteristics. Serum cotinine levels are associated with sleep health outcomes in adolescents, with high serum cotinine levels being linked to increased trouble sleeping and longer or shorter sleep duration.

Effect of dietary antioxidant quality score on tobacco smoke exposure and asthma in children and adolescents: a cross-sectional study from the NHANES database.

BACKGROUND: Asthma is a common non-communicable disease in children, and airway inflammation is the main pathological change of asthma. Tobacco smoke exposure (TSE) can cause systematic inflammation and oxidative stress, which may further aggravate the progression of asthma. Dietary antioxidants can relieve the inflammation and oxidative stress in human body. This study aims to assess the effect of overall antioxidant capacity of dietary intake, evaluating by dietary antioxidant quality score (DAQS), in the association between TSE and childhood asthma. METHODS: Data of this cross-sectional study were extracted from the National Health and Nutrition Examination Surveys (NHANES) 2007-2018. DAQS was calculated based on the daily dietary intake of selenium, zinc, magnesium, vitamin A, C and E. TSE was measured by serum cotinine concentration. The weighted univariate and multivariate logistic regression models were employed to evaluate the role of DAQS in the association between TSE and asthma among children and adolescents. Subgroup analysis was conducted to further evaluate the association based on gender. RESULTS: Totally 11,026 children and adolescents were included, of whom 1,244 (11.28%) had asthma. After adjusted all covariates, TSE was associated with the high odds of childhood asthma (OR = 1.26, 95%CI = 1.05-1.52). Among children exposed to tobacco smoke, those with higher DAQS level (OR = 1.15, 95%CI: 0.88-1.50) had a reduced risk of asthma compared with those children with lower DAQS level (OR = 1.43, 1.08-1.89), especially among girls (OR = 1.42, 95%CI: 0.93-2.17). CONCLUSION: High DAQS may have a moderating effect on asthma in children; that is, the higher DAQS, the lower the odds of asthma in children who exposed to tobacco smoke. Our study provides a reference for developing more targeted strategies for prevention and treatment of asthma in children.

Association between serum cotinine and muscle mass: results from NHANES 2011-2018.

PURPOSE: Recently, the detrimental effect of cigarette smoking on muscle metabolism has attracted much attention, but the relationship between cigarette smoking and muscle mass is poorly understood. Thus, this study investigated the association between exposure to cigarette smoke, defined based on serum cotinine, and muscle mass in the US population. METHODS: We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2018 for analysis. Data on serum cotinine, muscle mass (quantified by appendicular skeletal muscle mass index, ASMI), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum cotinine and ASMI. Subgroup analyses were stratified by gender, race and smoking status. When nonlinearity was detected, the threshold effects were analyzed using a two-piecewise linear regression model. RESULTS: In total, 8004 participants were included for analysis. The serum level of cotinine was negatively associated with ASMI in the fully adjusted model. Furthermore, comparing participants in the highest vs. the lowest tertile of serum cotinine, we found that ASMI decreased by 0.135 Kg/m2. In subgroup analysis stratified by gender and race, the association between serum cotinine and ASMI remained significant in all genders and races. In addition, the association remained significant among current and former smokers, but not among those who never smoked. Smooth curve fittings showed nonlinear relationships between serum cotinine and ASMI, with the inflection points identified at 356 ng/mL. CONCLUSIONS: Our study revealed that serum cotinine was negatively related to muscle mass. This finding improves our understanding of the deleterious effects of cigarette smoking on muscle mass and highlights the importance of smoking cessation for muscle health.

Association between serum cotinine levels and urinary incontinence in adults in the United States: a population-based cross-sectional analysis.

Environmental tobacco smoke (ETS) exposure has been shown to be associated with a variety of diseases, but evidence regarding the association between it and urinary incontinence (UI) is limited. Cotinine, a metabolite of nicotine in the human body, can more accurately quantify the level of human exposure to tobacco smoke. The study utilized data from seven survey cycles (2007-March 2020 Pre-pandemic) of the National Health and Nutrition Examination Survey (NHANES) program. Weighted multivariable logistic regression analysis, subgroup analysis, interaction tests, smooth curve fitting, and threshold effect models were used to analyze the relationship between serum cotinine and UI. Additionally, a 1:1 nearest neighbor propensity score matching (PSM) method was employed to minimize the impact of confounding factors. Before and after PSM, serum cotinine levels were higher in individuals with UI than those without (P < 0.05). Both before and after PSM, UI was positively correlated with serum cotinine levels, with a significantly increased risk of urinary incontinence when serum cotinine levels were in the Q3 range (before PSM: OR = 1.89, 95% CI = 1.59-2.24; after PSM: OR = 1.60, 95% CI = 1.28-2.00). Smooth curve fitting before and after PSM showed an approximate J-shaped non-linear dose-response relationship between log-transformed serum cotinine levels and UI. This study indicates that among American adults, there is a positive relationship between serum cotinine levels and UI, which is also significant in self-reported non-smoking populations. Therefore, reducing exposure to environmental tobacco smoke (e.g., avoiding second-hand smoke) in work and daily life may help alleviate the occurrence of UI, and serum cotinine levels have the potential to be a tool for predicting the degree of risk of developing UI.

Association of electronic-cigarette, number of cigarettes, and marijuana use with high-risk Human Papillomavirus (HPV) among men and women: A cross-sectional analysis of a nationally representative sample.

BACKGROUND: Smoking is associated with an increased risk of HPV infection. However, the use of e-cigarettes and marijuana, number of cigarettes, and serum cotinine concentrations in relation with HPV (6, 11, 16, 18) and high-risk HPV (16 or 18) infections in underserved and understudied populations remain poorly understood. METHODS: Data included 687 males and 664 females among whom 489 were White, 375 were Black and 342 were Hispanics from the NHANES 2013-2016 with HPV and high-risk HPV infections. Smoking history included current and past smokers, number of cigarettes, use of e-cigarettes, marijuana, and serum cotinine levels. Weighted multivariable-adjusted logistic regression models were conducted. RESULTS: High-risk HPV infection was associated with current smoking history plus ≥ 20 cigarettes/day (OR=1.92, 95 % CI=1.09, 3.37) in the overall population. E-cigarettes use (5 days) was positively associated with high-risk HPV infection (OR=2.43, 95 % CI=1.13, 5.22) in the overall population, with similar findings with e-cigarette (past 30 days) among women and Whites. CONCLUSION: High number of cigarettes, e-cigarette usage and marijuana were associated with HPV and high-risk HPV infections in the overall population. Most of these associations remained significant when stratified by gender and race/ethnicity. Increasing use of e-cigarettes and marijuana in these population warrants further investigation for the prevention of HPV infection and related cancers.

Association between tobacco smoke exposure and serum parathyroid hormone levels among US adults (NHANES 2003-2006).

Tobacco smoke exposure has been demonstrated to impede bone remodeling and diminish bone density, yet research regarding its correlation with parathyroid hormone (PTH) remains limited. This study aims to investigate the relationship between tobacco smoke exposure and serum PTH levels in adults aged 20 years and older. This study included 7,641 participants from two cycles of the National Health and Nutrition Examination Survey (NHANES, United States, 2003- 2006). Reflect tobacco smoke exposure through serum cotinine levels, and use an adjusted weighted multivariate linear regression model to test the independent linear relationship between serum cotinine and PTH. Stratified analysis was conducted to validate the sensitivity of the conclusions. Smooth curve fitting and threshold effect analysis were performed to assess the non-linear relationship. After comprehensive adjustment using weighted multivariate regression analysis, a negative correlation was found between serum cotinine and PTH levels. The interaction p-values in subgroup analyses were all greater than 0.05. Moreover, smooth curve fitting indicated a non-linear relationship between serum cotinine and PTH, with a turning point observed. Our research indicates that tobacco smoke exposure is negatively correlated and independent of serum parathyroid hormone levels, indicating that long-term tobacco smoke exposure may lead to parathyroid dysfunction in adults.

Random survival forest for predicting the combined effects of multiple physiological risk factors on all-cause mortality.

Understanding the combined effects of risk factors on all-cause mortality is crucial for implementing effective risk stratification and designing targeted interventions, but such combined effects are understudied. We aim to use survival-tree based machine learning models as more flexible nonparametric techniques to examine the combined effects of multiple physiological risk factors on mortality. More specifically, we (1) study the combined effects between multiple physiological factors and all-cause mortality, (2) identify the five most influential factors and visualize their combined influence on all-cause mortality, and (3) compare the mortality cut-offs with the current clinical thresholds. Data from the 1999-2014 NHANES Survey were linked to National Death Index data with follow-up through 2015 for 17,790 adults. We observed that the five most influential factors affecting mortality are the tobacco smoking biomarker cotinine, glomerular filtration rate (GFR), plasma glucose, sex, and white blood cell count. Specifically, high mortality risk is associated with being male, active smoking, low GFR, elevated plasma glucose levels, and high white blood cell count. The identified mortality-based cutoffs for these factors are mostly consistent with relevant studies and current clinical thresholds. This approach enabled us to identify important cutoffs and provide enhanced risk prediction as an important basis to inform clinical practice and develop new strategies for precision medicine.

Secondhand Nicotine Absorption From E-Cigarette Vapor vs Tobacco Smoke in Children.

Importance: With the prevalence of e-cigarette use (vaping) increasing worldwide, there are concerns about children's exposure to secondhand vapor. Objective: To compare nicotine absorption among children who are (1) exposed to secondhand tobacco smoke only or (2) exposed to secondhand vapor only with (3) those exposed to neither. Design, Setting, and Participants: The US Continuous National Health and Nutrition Examination Survey (NHANES) is a repeat cross-sectional survey. Participants are interviewed in their homes and, several days after, visit a mobile examination center to provide biological specimens. This study uses data from a nationally representative sample of US households from 2017 to 2020. Participants were children aged 3 to 11 years with serum cotinine levels incompatible with current firsthand nicotine use (ie, <15 µg/L). The final analysis was conducted on January 9, 2024. Exposures: Reported exposure to secondhand smoke or vapor indoors in the past 7 days (only secondhand smoke, only secondhand vapor, or neither). Covariates included age, sex, ethnicity, family income, body weight, and height. Main Outcomes and Measures: The primary outcome was serum cotinine concentration, an objective biomarker of nicotine absorption. Geometric mean cotinine levels and 95% CIs were calculated using log-normal tobit regression, accounting for the complex survey design and weights. Results: The mean (SD) age of the 1777 children surveyed was 7.4 (2.6) years, 882 (49.6%) were female, and 531 (29.9%) had family incomes below the poverty level. Nicotine absorption, as indexed by serum cotinine level, was highest among children only exposed to secondhand smoke (0.494 µg/L µg/L; 95% CI, 0.386-0.633 µg/L), followed by those exposed only to secondhand vapor (0.081 µg/L; 95% CI, 0.048-0.137 µg/L), equating to 83.6% (95% CI, 71.5%-90.5%; P < .001) lower nicotine absorption. Among children with no reported secondhand exposure, the geometric mean cotinine level was 0.016 µg/L (95% CI, 0.013-0.021 µg/L), or 96.7% (95% CI, 95.6%-97.6%; P < .001) lower than for those with exposure to secondhand smoke. Results were similar after covariate adjustment. Conclusions and Relevance: In this cross-sectional study of US children, nicotine absorption was much lower in children who were exposed to secondhand vapor vs secondhand smoke, but higher than in those exposed to neither. These findings suggest that switching from smoking to vaping indoors may substantially reduce, but not eliminate, children's secondhand exposure to nicotine and other noxious substances.

Determination of cotinine and 3-hydroxynicotinine in human serum by liquid chromatography-tandem mass spectrometry and its application.

In this study, we developed a method for determining cotinine and 3-hydroxycotinine in human serum and established a methodology for an in-depth study of tobacco exposure and health. After the proteins in the human serum samples were precipitated with acetonitrile, they were separated on a ZORBAX SB-Phenyl column with a mobile phase of methanol encompassing 0.3% formic acid-water encompassing 0.15% formic acid. The measurement was performed on an API5500 triple quadrupole mass spectrometer in the multiple reaction monitoring mode. Cotinine, 3-hydroxycotinine, and cotinine-d3 isotope internal standards were held for 2.56 minutes, 1.58 minutes, and 2.56 minutes, respectively. In serum, the linear range was 0.05 to 500 ng·mL-1 for cotinine and 0.50 to 1250 ng·mL-1 for 3-hydroxycotinine. The lower limit of quantification (LLOQ) was 0.05 ng·mL-1 and 0.5 ng·mL-1 for cotinine and 3-hydroxycotinine, respectively. The intra-day and inter-day relative standard deviations were <11%, and the relative errors were within ±â€…7%. Moreover, the mean extraction recoveries of cotinine and 3-hydroxycotinine were 98.54% and 100.24%, respectively. This method is suitable for the rapid determination of cotinine and 3-hydroxycotinine in human serum because of its rapidity, sensitivity, strong specificity, and high reproducibility. The detection of cotinine levels in human serum allows for the identification of the cutoff value, providing a basis for differentiation between smoking and nonsmoking populations.

Associations between smoking, sex steroid hormones, trouble sleeping, and depression among U.S. adults: a cross-sectional study from NHANES (2013-2016).

BACKGROUND: Dose-response and nonlinear relationships of cigarette exposure with sleep disturbances and depression are warranted, and the potential mechanism of sex hormones in such associations remains unclear. METHODS: Cigarette exposure, trouble sleeping, and depression were assessed by standard questionnaires, and the levels of cotinine and sex steroid hormones were determined among 9900 adults from the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression, logistic regression, and mediation models were conducted to evaluate the associations between smoking, sex steroid hormones, trouble sleeping, and depression. RESULTS: With never smokers as a reference, current smokers had a higher prevalence of trouble sleeping (OR = 1.931, 95% CI: 1.680, 2.219) and depression (OR = 2.525, 95% CI: 1.936, 3.293) as well as testosterone level (ß = 0.083, 95% CI: 0.028, 0.140). Pack-years of smoking and cigarettes per day were positively associated with the prevalence of trouble sleeping and depression as well as testosterone level (Ptrend <0.05). The restricted cubic spline model showed linear relationships of cotinine with trouble sleeping, depression, and testosterone. The positive associations of cigarettes per day with trouble sleeping and depression were greater in females than that in males (Pmodification <0.05). However, the potential role of sex hormones was not observed in the association of cotinine with trouble sleeping or depression (Pmediation >0.05). CONCLUSION: Smoking may induce sex hormone disturbance and increase the risk of sleep problems and depression symptoms, and ceasing smoking may reduce the risk of such complications.

Relation Between Exposure to Tobacco Smoke Assessed by Serum Cotinine Concentration and Questionnaire Method, and Serum Renalase Concentration-the Importance of the Coexistence of Arterial Hypertension and Other Cardiovascular Diseases.

Exposure to tobacco smoke (ETS) is one of the main risk factors for cardiovascular disease (CVD). Renalase is a protein that may play a role in the pathogenesis of CVD. The aim of the study was to assess the relationship between ETS and serum renalase concentration. A group of 109 patients was recruited for this study (49.7 ± 14.7 years). In accordance with the questionnaire, patients were divided into the following subgroups: subgroup A- declaring themselves active smokers (n = 36), subgroup B- declaring themselves non-smokers and exposed to environmental tobacco smoke (n = 35), subgroup C- declaring themselves non-smokers and not exposed to environmental tobacco smoke (n = 38). The same patients were divided based on cotinine concentration into the following subgroups: subgroup D- active smokers (n = 42), subgroup E- non-smokers exposed to environmental tobacco smoke (n = 66), and subgroup F- non-smokers not exposed to environmental tobacco smoke (n = 1). Serum cotinine concentration and serum renalase concentration were measured using ELISA tests. Serum renalase concentration was statistically significantly higher in subgroup C than in subgroups A and B and in subgroup E and F than in D. There was a negative correlation between serum cotinine concentration and serum renalase concentration (r = -0.41, p < 0.05). Regression analysis showed that higher BMI, higher diastolic blood pressure, coronary artery disease and higher serum cotinine concentration are independent risk factors of lower serum renalase concentration. The questionnaire method of assessing exposure to tobacco smoke was characterized by high sensitivity, but only moderate specificity, especially in terms of assessing environmental exposure to tobacco smoke. In summary, the study showed an independent relationship between exposure to tobacco smoke and lower serum renalase concentration.

Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013-2016.

OBJECTIVE: To estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers). DESIGN: Cross-sectional analysis. SETTING: US National Health and Nutrition Examination Survey, 2013-2016. OUTCOME MEASURES: Serum sex hormone measures included total testosterone (TT) and oestradiol (E2), sex hormone-binding globulin (SHBG), the ratio of TT and E2 and free androgen index (FAI). Isotope dilution-liquid chromatography tandem mass spectrometry was used to measure serum TT and E2. SHBG was measured using immunoassay. The ratio of TT and E2 and FAI were calculated. SHS exposure was defined as serum cotinine concentration of 0.05-10 ng/mL. PARTICIPANTS: A total of 622 female participants aged ≥20 years were included in the analysis. RESULTS: For never smokers, a doubling of serum cotinine concentration was associated with a 2.85% (95% CI 0.29% to 5.47%) increase in TT concentration and a 6.29% (95% CI 0.68% to 12.23%) increase in E2 in fully adjusted models. The never smokers in the highest quartile (Q4) of serum cotinine level exhibited a 10.30% (95% CI 0.78% to 20.72%) increase in TT concentration and a 27.75% (95% CI 5.17% to 55.17%) increase in E2 compared with those in the lowest quartile (Q1). For former smokers, SHBG was reduced by 4.36% (95% CI -8.47% to -0.07%, p for trend=0.049) when the serum cotinine level was doubled, and the SHBG of those in Q4 was reduced by 17.58% (95% CI -31.33% to -1.07%, p for trend=0.018) compared with those in Q1. CONCLUSION: SHS was associated with serum sex hormone concentrations among female adults. In never smokers, SHS was associated with increased levels of TT and E2. In former smokers, SHS was associated with decreased SHBG levels.

Association between secondhand smoke exposure and rheumatoid arthritis in US never-smoking adults: a cross-sectional study from NHANES.

While smoking is widely acknowledged as a risk factor for rheumatoid arthritis (RA), the connection between secondhand smoke (SHS) exposure and RA in never-smoking adults remains limited and inconsistent. This study aims to explore and quantify this association using serum cotinine levels. We conducted a cross-sectional study with 14,940 adults who self-report as never smokers, using National Health and Nutrition Examination Survey data from 1999 to 2018. Based on previous literature, SHS exposure was categorized into four groups according to serum cotinine levels. Compared to individuals in the unexposed group (serum cotinine < 0.05 ng/mL), the adjusted odds ratio (OR) for RA was 1.37 (95% CI 1.14-1.64, p = 0.001) in the low exposure group (serum cotinine at 0.05 to 0.99 ng/mL) after adjusting for covariates. However, no significant association was found in the moderate exposure group (serum cotinine at 1 to 10 ng/mL) or the heavy exposure group (serum cotinine ≥ 10 ng/mL). Furthermore, we detected a non-linear, positively saturated correlation between the cotinine levels after log2 transformation and RA, with a turning point at approximately - 2.756 ng/mL (OR = 1.163, 95% CI 1.073-1.261, p = 0.0002). The stability of the results was confirmed by subgroup analysis.

Association between serum cotinine and hepatic steatosis and liver fibrosis in adolescent: a population-based study in the United States.

Tobacco exposure is known to be associated with a higher prevalence and incidence of liver diseases. Cotinine, a metabolite of nicotine, is a typical indicator of tobacco exposure. However, the relationship of serum cotinine levels with hepatic steatosis and liver fibrosis remains controversial and these relationships need more research to explored in American teenagers. Cross-sectional data included 1433 participants aged 12-19 from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020 were thoroughly used for this study. The linear relationships between serum cotinine levels and the Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) were examined using multiple linear regression models. Subgroup analysis, interaction tests, and nonlinear interactions were also carried out. Serum cotinine levels > 2.99 ng/ml [ß = 0.41 (0.07, 0.76), p = 0.018] and 0.05-2.99 ng/ml [ß = 0.24 (0.00, 0.49), p = 0.048] showed a significant positive connection with LSM in multivariate linear regression analysis when compared to serum cotinine levels ≤ 0.05 ng/ml (p for trend = 0.006). Moreover, we discovered an inverted U-shaped association of log2-transformed cotinine with LSM with an inflection point of 4.53 using a two-stage linear regression model. However, according to multiple regression analysis, serum cotinine and CAP did not significantly correlate (p = 0.512). In conclusion, this study demonstrated that smoking cessation and keep away from secondhand smoking may beneficial for liver health in American teenagers.

Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants.

BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (n=123) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.

Nicotinic Receptor Alpha-5 Subunit Gene Polymorphism is Associated With Heavy Smoking Under a Range of Nicotine Dosing Conditions.

INTRODUCTION: This study aimed to assess the role of the rs16969968 variant of nicotinic receptor alpha-5 subunit in regulating smoking behavior and nicotine intake in response to nicotine manipulations among dependent smokers in a naturalistic environment. AIMS AND METHODS: Sixty-nine adults (19 females) smoking 10 or more cigarettes per day (CPD) were asked to complete four 2-week study phases during which they smoked exclusively one of two types of Spectrum nicotine research cigarettes (FTC nicotine yield 0.8 and 1.6 mg, respectively), their usual brand of cigarettes, or their usual brand of cigarettes while wearing a 21-mg nicotine patch. Measurements included rs16969968 genotype, number of CPD, smoking topography, and plasma cotinine. RESULTS: Compared to controls (G/G carriers), A allele carriers reported smoking 4 to 5 more CPD across all conditions (all ps < .05). Mean total smoke volume per day and cotinine were greater in A allele carriers than in controls (ps = .05, .046, respectively). No significant genotype differences were found in smoking compensation indices for the switch from medium to high-nicotine-yield cigarettes. Nicotine patch-induced reductions in cigarettes smoked per day and total smoke volume per day showed significant interactions between genotype and pre-patch levels, with heavier smokers showing greater effects of genotype (p = .052 and p = .006, respectively). CONCLUSIONS: Results suggest that the rs16969968 variants regulate the heaviness of smoking primarily by their impact on daily numbers of cigarettes smoked, but no genotype differences were found in smoking compensation after switching from medium to high-nicotine cigarettes. IMPLICATIONS: The differences in daily cigarette consumption between rs16969968 risk-allele carriers and controls are shown to be consistent regardless of manipulations of cigarette nicotine content and transdermal nicotine supplementation and markedly greater among dependent smokers than those observed in the general smoker populations. G/G allele carriers, relative to A allele carriers, appeared to be more sensitive to the nicotine patch manipulation, reducing their smoking to a greater extent. These findings support continued efforts in the development of personalized intervention strategies to reduce the rs16969968-conveyed genetic propensity for heavy smoking.

Association of secondhand smoke exposure with all-cause mortality and cardiovascular death in patients with hypertension: Insights from NHANES.

BACKGROUND AND AIM: The impact of environmental chemical exposure on blood pressure (BP) is well-established. However, the relationship between secondhand smoke exposure (SHSE) and mortality in hypertensive patients in the general population remains unclear. METHODS AND RESULTS: This cohort study included US adults in the National Health and Nutrition Examination Survey from 2007 to 2018. All-cause mortality and cause-specific mortality outcomes were determined by associating them with the National Death Index records. Cox proportional risk models were used to estimate hazard ratios (HRs) for all-cause mortality and cardiovascular disease (CVD) mortality, and 95% confidence intervals (CIs) for SHSE. The cohort included 10,760 adult participants. The mean serum cotinine level was 0.024 ng/mL. During a mean follow-up period of 76.9 months, there were 1729 deaths, including 469 cardiovascular disease deaths recorded. After adjusting for lifestyle factors, BMI, hypertension duration, medication use, and chronic disease presence, the highest SHSE was significantly associated with higher all-cause and CVD mortality. CONCLUSIONS: This study demonstrates that higher SHSE is significantly associated with higher all-cause mortality and CVD mortality. Further research is necessary to elucidate the underlying mechanisms.