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Frontiers in Endocrinology 2023Tobacco exposure is considered to be a risk factor for reduced bone mineral density (BMD), which may result in osteopenia. Cotinine, a metabolite of nicotine, is...
BACKGROUND
Tobacco exposure is considered to be a risk factor for reduced bone mineral density (BMD), which may result in osteopenia. Cotinine, a metabolite of nicotine, is commonly utilized as a marker of tobacco exposure. Nevertheless, there are limited clinical data on the associations between osteoporosis (OP) or osteopenia and smoking status or serum cotinine level.
METHODS
We thoroughly examined the NHANES cross-sectional data from 2005 to 2010, 2013 to 2014, and 2017 to 2018. Multivariate logistic regression models were applied to assess the associations among smoking status and serum cotinine levels as well as OP and osteopenia. The relationships between serum cotinine level and OP and osteopenia were also assessed using the restricted cubic spline (RCS) method.
RESULTS
A total of 10,564 participants were included in this cross-sectional study. The mean age of the study population was 64.85 ± 9.54 years, and the patients were predominantly male (51.9%). We found that the relationships between higher serum cotinine levels (≥3 ng/ml) and the prevalence of osteoporosis (Model 1: OR=2.27 [1.91-2.69]; Model 2: OR=2.03 [1.70-2.43]; Model 3: OR=2.04 [1.70-2.45]; all for trend <0.001) remained significant after adjustment for covariates by applying the lowest serum cotinine levels (<0.05 ng/ml) as the reference. Similar results were observed for current smokers, who were more likely to develop OP compared with nonsmokers (Model 1: OR=2.30 [1.90-2.79]; Model 2: OR=2.16 [1.77-2.64]; Model 3: OR=2.16 [1.77-2.65]). Moreover, higher serum cotinine levels were found to be strongly and positively correlated with the prevalence of osteopenia (OR=1.60 [1.42-1.80]). A similar relationship was observed between current smokers and the prevalence of osteopenia compared with nonsmokers (OR=1.70 [1.49-1.94]). RCS regression also showed that serum cotinine levels were nonlinearly and positively correlated with OP and osteopenia, with inflection points of 5.82 ng/ml and 3.26 ng/ml, respectively.
CONCLUSION
This study showed that being a smoker was associated with the prevalence of OP or osteopenia compared with being a nonsmoker and that there was a strong nonlinear positive dose-response relationship between serum cotinine levels and OP and osteopenia.
Topics: Humans; Male; Aged; Middle Aged; Female; Smoking; Cotinine; Cross-Sectional Studies; Tobacco Smoke Pollution; Nutrition Surveys; Osteoporosis; Bone Diseases, Metabolic
PubMed: 36817605
DOI: 10.3389/fendo.2023.1074574 -
Annals of Global Health 2021Smoking is one of the modifiable risk factors for adverse maternal and neonatal outcomes and is associated with low birth weight, preterm birth, respiratory, antepartum...
BACKGROUND
Smoking is one of the modifiable risk factors for adverse maternal and neonatal outcomes and is associated with low birth weight, preterm birth, respiratory, antepartum and intrapartum stillbirth, and perinatal death as well as long-term morbidity in offspring and sudden unexpected infant death. The rate of smoking in low- and middle-income countries is still relevantly high, and Jordan is no exception.
OBJECTIVE
To investigate the effect of active and passive smoking during pregnancy on adverse pregnancy outcomes.
METHODS
The case-control study was conducted in Jordan in June 2020. Healthy women with full-term singleton pregnancy (n = 180) were interviewed and stratified into three groups: Group I, active smokers; Group II, passive smokers; and Group III, nonsmokers. The study variables included demographic data, current pregnancy history, cotinine level of mothers and newborns, and perinatal outcomes. Statistical analysis was performed using the application package IBM SPSS 25. Various algorithms of statistical analysis were used depending on the type of distribution of feature and data quality. The threshold for statistical significance was set at < 0.05.
RESULTS
Active smokers had significantly lower gestational age at delivery compared to passive and nonsmoking women ( = 0.038 and = 0.003, respectively). Neonates from active smoking mothers had significantly lower birth weight compared to neonates from passive and nonsmoking women ( = 0.016 and = 0.019, respectively), significantly lower head and chest circumferences compared to babies from passive smokers ( < 0.001 and = 0.036, respectively), and significantly lower first-minute Apgar score compared to those from nonsmoking women ( = 0.023). The urine cotinine level was significantly higher in both active and passive smoking women (both < 0.01), and it was significantly higher in newborns who had been exposed to smoking in utero despite maternal active or passive smoking status (both < 0.001). There was a weak negative correlation between urine cotinine level and birth weight: = -0.14 for maternal cotinine level and = -0.15 for neonate cotinine level.
CONCLUSIONS
The current study illustrated that smoking during pregnancy leads to offspring with reduced birth weight, birth length, and head and chest circumference; reduces delivery gestational age; and lowers the first-minute Apgar score. Our study findings highlight the need for further research issued to smoking effects on perinatal outcomes, the implementation of actions to develop cessation interventions in the preconception period, and an evaluation of useful interventions to enhance a smoking-free environment during pregnancy.
Topics: Birth Weight; Case-Control Studies; Developing Countries; Female; Humans; Infant, Newborn; Maternal Exposure; Pregnancy; Premature Birth; Smoking; Tobacco Smoke Pollution
PubMed: 34900622
DOI: 10.5334/aogh.3384 -
BMC Public Health Aug 2023Even though cadmium (Cd) exposure and cellular senescence (telomere length) have been linked in previous studies, composite molecular aging biomarkers are more...
INTRODUCTION
Even though cadmium (Cd) exposure and cellular senescence (telomere length) have been linked in previous studies, composite molecular aging biomarkers are more significant and reliable factors to consider when examining the connection between metal exposure and health outcomes. The purpose of this research was to assess the association between urinary cadmium (U-Cd) and whole-body aging (phenotypic age).
METHODS
Phenotypic age was calculated from chronological age and 9 molecular biomarkers. Multivariate linear regression models, subgroup analysis, and smoothing curve fitting were used to explore the linear and nonlinear relationship between U-Cd and phenotypic age. Mediation analysis was performed to explore the mediating effect of U-Cd on the association between smoking and phenotypic age.
RESULTS
This study included 10,083 participants with a mean chronological age and a mean phenotypic age of 42.24 years and 42.34 years, respectively. In the fully adjusted model, there was a positive relationship between U-Cd and phenotypic age [2.13 years per 1 ng/g U-Cd, (1.67, 2.58)]. This association differed by sex, age, and smoking subgroups (P for interaction < 0.05). U-Cd mediated a positive association between serum cotinine and phenotypic age, mediating a proportion of 23.2%.
CONCLUSIONS
Our results suggest that high levels of Cd exposure are associated with whole-body aging.
Topics: Adult; Humans; Aging; Cadmium; Cotinine; Mediation Analysis; Nutrition Surveys; Male; Female
PubMed: 37653508
DOI: 10.1186/s12889-023-16643-2 -
Cancer Medicine Jun 2021Previous analyses within the National Health and Nutrition Examination Survey (NHANES) II and III cycles suggested an association between blood lead levels (BLLs) and...
Previous analyses within the National Health and Nutrition Examination Survey (NHANES) II and III cycles suggested an association between blood lead levels (BLLs) and lung cancer mortality, although the evidence was limited by small case numbers. To clarify this relationship, we conducted updated analyses of 4,182 and 15,629 participants in NHANES II and III, respectively, (extending follow-up 20 and 8 years) aged ≥20 with BLL measurements and mortality follow-up through 2014. We fit multivariable Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) relating BLLs and lung cancer with adjustment for smoking and other factors. We did not observe an overall association between BLLs and lung cancer after adjustment for smoking (both surveys) and serum cotinine and environmental tobacco smoke exposure (NHANES III), although suggestive associations were observed among women (NHANES II: HR 2.7, 95% CI 0.7, 10.0 for ≥20.0 µg/dl vs. <10.0 µg/dl, P = 0.07; NHANES III: HR 11.2, 95% CI 2.1, 59.4 for ≥10.0 µg/dl vs. <2.5 µg/dl, P = 0.04). After stratifying on smoking status, an association with elevated BLLs was observed in NHANES II only among former smokers (HR 3.2, 95% CI 1.3, 8.0 for ≥15 vs. <15 µg/dl) and in NHANES III only among current smokers (HR 1.7, 95% CI 1.1, 2.8 for ≥5 vs. <5 µg/dl). In summary, we found elevated BLLs to be associated with lung cancer mortality among women in both NHANES II and III. Given the absence of an association among non-smokers, we cannot rule out residual confounding as an explanation for our findings.
Topics: Adult; Confidence Intervals; Cotinine; Ex-Smokers; Female; Humans; Lead; Lung Neoplasms; Male; Middle Aged; Nutrition Surveys; Proportional Hazards Models; Sex Factors; Smokers; Smoking; Tobacco Smoke Pollution
PubMed: 33963676
DOI: 10.1002/cam4.3943 -
Cells Apr 2020Cigarette smoke is a known exacerbator of age-related pathologies, such as cardiovascular disease (CVD), atherosclerosis, and cellular aging (senescence). However, the... (Review)
Review
Cigarette smoke is a known exacerbator of age-related pathologies, such as cardiovascular disease (CVD), atherosclerosis, and cellular aging (senescence). However, the role of nicotine and its major metabolite cotinine is yet to be elucidated. Considering the growing amount of nicotine-containing aerosol use in recent years, the role of nicotine is a relevant public health concern. A number of recent studies and health education sites have focused on nicotine aerosol-induced adverse lung function, and neglected cardiovascular (CV) impairments and diseases. A critical review of the present scientific literature leads to the hypothesis that nicotine mediates the effects of cigarette smoke in the CV system by increasing MAPK signaling, inflammation, and oxidative stress through NADPH oxidase 1 (Nox1), to induce vascular smooth muscle cell (VSMC) senescence. The accumulation of senescent VSMCs in the lesion cap is detrimental as it increases the pathogenesis of atherosclerosis by promoting an unstable plaque phenotype. Therefore, nicotine, and most likely its metabolite cotinine, adversely influence atherosclerosis.
Topics: Animals; Atherosclerosis; Cardiovascular System; Cellular Senescence; Disease Models, Animal; Humans; Nicotine; Tobacco Use
PubMed: 32331221
DOI: 10.3390/cells9041035 -
Tobacco Control May 2020With high rates of use and uncertain consequences, valid electronic cigarette (e-cigarette) use frequency and addiction measures for adolescents are needed. This...
BACKGROUND AND OBJECTIVES
With high rates of use and uncertain consequences, valid electronic cigarette (e-cigarette) use frequency and addiction measures for adolescents are needed. This cross-sectional study examined correlations for multiple measures of adolescent e-cigarette use with nicotine exposure quantified with salivary cotinine levels.
METHODS
Adolescents (N=173, age 13-18) who reported past-month e-cigarette use were recruited from the San Francisco Bay Area. Participants self-reported: (1) days of e-cigarette use in a typical month, (2) number of e-cigarette sessions in a typical day (sessions per day; SPD) and the (3) E-Cigarette Addiction Severity Index (EASI). Participants also completed the 10-item Penn State Electronic Cigarette Dependence Index (ECDI), which we examined in full and as a 2-item Heaviness of Vaping Index (HVI; the sum of the ECDI items on use frequency and time to first vaping on wakening). Sessions per month (SPM) were calculated using days per month and SPD. Cotinine levels, SPD and SPM were log-transformed.
RESULTS
Among frequency measures, SPM correlated most strongly with cotinine (r=0.59), followed closely by days per month (r=0.58) and SPD (r0.57), p<0.001. Among dependence measures, the EASI correlated most strongly with cotinine (r0.51), closely followed by the ECDI and HVI (r's=0.50), all p's<0.001.
CONCLUSIONS
Adolescents' reports of frequency of e-cigarette use and degree of addiction correlated significantly with cotinine as a biomarker of nicotine exposure. We recommend the EASI and days per month as brief general measures. SPM and the ECDI are more extensive measures that may yield a more nuanced understanding of use.
Topics: Adolescent; Behavior, Addictive; Biomarkers; Cotinine; Cross-Sectional Studies; Electronic Nicotine Delivery Systems; Female; Humans; Male; Nicotine; Saliva; San Francisco; Self Report; Severity of Illness Index; Smoking; Substance-Related Disorders; Tobacco Products; Vaping
PubMed: 31079033
DOI: 10.1136/tobaccocontrol-2018-054900 -
Frontiers in Neuroscience 2023Animal survival depends on cognitive abilities such as learning and memory to adapt to environmental changes. Memory functions require an enhanced activity and... (Review)
Review
Animal survival depends on cognitive abilities such as learning and memory to adapt to environmental changes. Memory functions require an enhanced activity and connectivity of a particular arrangement of engram neurons, supported by the concerted action of neurons, glia, and vascular cells. The deterioration of the cholinergic system is a common occurrence in neurological conditions exacerbated by aging such as traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), Alzheimer's disease (AD), and Parkinson's disease (PD). Cotinine is a cholinergic modulator with neuroprotective, antidepressant, anti-inflammatory, antioxidant, and memory-enhancing effects. Current evidence suggests Cotinine's beneficial effects on cognition results from the positive modulation of the α7-nicotinic acetylcholine receptors (nAChRs) and the inhibition of the toll-like receptors (TLRs). The α7nAChR affects brain functions by modulating the function of neurons, glia, endothelial, immune, and dendritic cells and regulates inhibitory and excitatory neurotransmission throughout the GABA interneurons. In addition, Cotinine acting on the α7 nAChRs and TLR reduces neuroinflammation by inhibiting the release of pro-inflammatory cytokines by the immune cells. Also, α7nAChRs stimulate signaling pathways supporting structural, biochemical, electrochemical, and cellular changes in the Central nervous system during the cognitive processes, including Neurogenesis. Here, the mechanisms of memory formation as well as potential mechanisms of action of Cotinine on memory preservation in aging and neurological diseases are discussed.
PubMed: 37255751
DOI: 10.3389/fnins.2023.1179611 -
JAMA Network Open Feb 2021Hypertension is a leading cause of cardiovascular disease in adults; preclinical associations between hypertension and cardiovascular disease are seen in childhood....
IMPORTANCE
Hypertension is a leading cause of cardiovascular disease in adults; preclinical associations between hypertension and cardiovascular disease are seen in childhood. Nicotine is a known toxin, but its association with pediatric hypertension is unclear.
OBJECTIVE
To test the hypothesis that tobacco exposure is associated with the presence of elevated blood pressure in US children and adolescents and that this association is dose dependent.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used data from the 2007 to 2016 National Health and Nutrition Examination Survey (NHANES), a population-based nationally representative sample of US children and adolescents. Children were eligible if they were aged 8 to 19 years at the time of participation in the main NHANES study. Exclusion criteria included those of the main NHANES study, inability to complete testing, or missing questionnaires. Of the 10 143 participants in NHANES aged 8 to 19 during the study years, 8520 were included in the analysis. Analysis was conducted from October 12, 2019, to July 9, 2020.
EXPOSURES
Tobacco exposure, defined as serum cotinine levels greater than 0.05 µg/L, or reporting living with a smoker or smoking themselves.
MAIN OUTCOMES AND MEASURES
Elevated blood pressure, classified as greater than 90% for a child's age, sex, and height according to the 2017 American Academy of Pediatrics Clinical Practice Guidelines. The a priori hypothesis that there is a positive association between tobacco exposure and elevated blood pressure in the study population was tested. Analysis included logistic regression with adjustment for possible confounders. Subgroup and sensitivity analyses were conducted.
RESULTS
A total of 8520 children were included in the analysis, representing 41 million US children. The mean (SD) age of the participants was 13.1 (0.05) years, 51% (95% CI, 49%-52%) were male, and 58% (95% CI, 54%-62%) were non-Hispanic White individuals. Participants with any tobacco smoke exposure were more likely than those without exposure to be older (mean [SD] age, 13.3 [0.07] years vs 12.8 [0.06] years), male (53% [95% CI, 51%-55%] vs 49% [95% CI, 47%-50%]), and non-Hispanic Black individuals (19% [95% CI, 16%-22%] vs 10% [95% CI, 8%-12%]). The odds of having elevated blood pressure was 1.31 (95% CI, 1.06-1.61) for any tobacco exposure after adjustment; odds were similar across subgroups and remained significant in multiple sensitivity analyses.
CONCLUSIONS AND RELEVANCE
This study suggests that tobacco exposure is associated with elevated blood pressure in US children and adolescents. This modifiable risk factor represents a target for further research into reducing hypertension in children and adolescents.
Topics: Adolescent; Black or African American; Age Distribution; Blood Pressure; Child; Cotinine; Female; Hispanic or Latino; Humans; Hypertension; Male; Sex Distribution; Tobacco Smoke Pollution; Tobacco Smoking; United States; White People; Young Adult
PubMed: 33620445
DOI: 10.1001/jamanetworkopen.2020.37936 -
Scientific Reports Apr 2021We examined the associations of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of new-onset HL. This cohort study was...
We examined the associations of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of new-onset HL. This cohort study was performed in 293,991 Korean adults free of HL who underwent a comprehensive screening examination and were followed for up to 8.8 years. HL was defined as a pure-tone average of thresholds at 0.5, 1.0, and 2.0 kHz ≥ 25 dB in both ears. During a median follow-up of 4.9 years, 2286 participants developed new-onset bilateral HL. Self-reported smoking status was associated with an increased risk of new-onset bilateral HL. Multivariable-adjusted HRs (95% CIs) for incident HL comparing former smokers and current smokers to never-smokers were 1.14 (1.004-1.30) and 1.40 (1.21-1.61), respectively. Number of cigarettes, pack-years, and urinary cotinine levels were consistently associated with incident HL. These associations were similarly observed when introducing changes in smoking status, urinary cotinine, and other confounders during follow-up as time-varying covariates. In this large cohort of young and middle-aged men and women, smoking status based on both self-report and urinary cotinine level were independently associated with an increased incidence of bilateral HL. Our findings indicate smoking is an independent risk factor for HL.
Topics: Adult; Cohort Studies; Cotinine; Female; Follow-Up Studies; Hearing Loss; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Self Report; Smoking
PubMed: 33854107
DOI: 10.1038/s41598-021-87531-1 -
Innovation (Cambridge (Mass.)) May 2021Nicotine is the principal alkaloid of tobacco often manufactured into cigarettes and belongs to a highly addictive class of drugs. Nicotine attenuates the...
Nicotine is the principal alkaloid of tobacco often manufactured into cigarettes and belongs to a highly addictive class of drugs. Nicotine attenuates the neuroinflammation induced by microglial activation. However, the molecular target(s) underlying anti-inflammatory action of nicotine has not been fully understood. Considering the psychoactive substances morphine, cocaine, and methamphetamine act as xenobiotic-associated molecular patterns and can be specifically sensed by the innate immune receptor Toll-like receptor 4 (TLR4), here we sought to delineate whether nicotine and/or its metabolite cotinine may be recognized by the innate immune system via myeloid differentiation protein 2 (MD2), an accessory protein of TLR4 that is responsible for ligand recognition. MD2-intrinsic fluorescence titrations, surface plasmon resonance, and competitive displacement binding assays with curcumin (MD2 probe) demonstrated that both nicotine and cotinine targeted the lipopolysaccharide (LPS; TLR4 agonist) binding pocket of MD2 with similar affinities. The cellular thermal shift assay indicated that nicotine binding increased, while cotinine binding decreased, MD2 stability. These biophysical binding results were further supported by simulations. In keeping with targeting MD2, both nicotine and cotinine inhibited LPS-induced production of nitric oxide and tumor necrosis factor alpha (TNF-α) and blocked microglial activation. Neither a pan nicotinic acetylcholine receptor (nAChR) inhibitor nor RNAi for nAChRs abolished the suppressive effect of nicotine- and cotinine-induced neuroinflammation. These data indicate that TLR4 inhibition by nicotine and cotinine at the concentrations tested in BV-2 cells is independent of classic neuronal nAChRs and validate that MD2 is a direct target of nicotine and cotinine in the inhibition of innate immunity.
PubMed: 34557761
DOI: 10.1016/j.xinn.2021.100111