The complexities of ligand/receptor interactions: Exploring the role of molecular vibrations and quantum tunnelling.

Molecular vibrations and quantum tunneling may link ligand binding to the function of pharmacological receptors. The well-established lock-and-key model explains a ligand's binding and recognition by a receptor; however, a general mechanism by which receptors translate binding into activation, inactivation, or modulation remains elusive. The Vibration Theory of Olfaction was proposed in the 1930s to explain this subset of receptor-mediated phenomena by correlating odorant molecular vibrations to smell, but a mechanism was lacking. In the 1990s, inelastic electron tunneling was proposed as a plausible mechanism for translating molecular vibration to odorant physiology. More recently, studies of ligands' vibrational spectra and the use of deuterated ligand analogs have provided helpful information to study this admittedly controversial hypothesis in metabotropic receptors other than olfactory receptors. In the present work, based in part on published experiments from our laboratory using planarians as an experimental organism, I will present a rationale and possible experimental approach for extending this idea to ligand-gated ion channels.

Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case-control study.

Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.

Characterization of cotinine degradation in a newly isolated Gram-negative strain Pseudomonas sp. JH-2.

Cotinine, the primary metabolite of nicotine in the human body, is an emerging pollutant in aquatic environments. It causes environmental problems and is harmful to the health of humans and other mammals; however, the mechanisms of its biodegradation have been elucidated incompletely. In this study, a novel Gram-negative strain that could degrade and utilize cotinine as a sole carbon source was isolated from municipal wastewater samples, and its cotinine degradation characteristics and kinetics were determined. Pseudomonas sp. JH-2 was able to degrade 100 mg/L (0.56 mM) of cotinine with high efficiency within 5 days at 30 ℃, pH 7.0, and 1% NaCl. Two intermediates, 6-hydroxycotinine and 6-hydroxy-3-succinoylpyridine (HSP), were identified by high-performance liquid chromatography and liquid chromatograph mass spectrometer. The draft whole genome sequence of strain JH-2 was obtained and analyzed to determine genomic structure and function. No homologs of proteins predicted in Nocardioides sp. JQ2195 and reported in nicotine degradation Pyrrolidine pathway were found in strain JH-2, suggesting new enzymes that responsible for cotinine catabolism. These findings provide meaningful insights into the biodegradation of cotinine by Gram-negative bacteria.

Urine cotinine versus self-reported smoking and the risk of chronic kidney disease.

BACKGROUND AND HYPOTHESIS: Evidence on the role of smoking in the development of chronic kidney disease (CKD) has mostly relied on self-reported smoking status. We aimed to compare the associations of smoking status as assessed by self-reports and urine cotinine with CKD risk. METHODS: Using the PREVEND prospective study, smoking status was assessed at baseline using self-reports and urine cotinine in 4333 participants (mean age, 52 years) without a history of CKD at baseline. Participants were classified as never, former, light current and heavy current smokers according to self-reports and comparable cut-offs for urine cotinine. Hazard ratios (HRs) with 95% CIs were estimated for CKD. RESULTS: The percentages of self-reported and cotinine-assessed current smokers were 27.5% and 24.0%, respectively. During a median follow-up of 7.0 years, 593 cases of CKD were recorded. In analyses adjusted for established risk factors, the HRs (95% CI) of CKD for self-reported former, light current, and heavy current smokers compared with never smokers were 1.17 (0.95-1.44), 1.48 (1.10-2.00), and 1.48 (1.14-1.93), respectively. On further adjustment for urinary albumin excretion (UAE), the HRs (95% CI) were 1.07 (0.87-1.32), 1.26 (0.93-1.70), and 1.20 (0.93-1.57), respectively. For urine cotinine-assessed smoking status, the corresponding HRs (95% CI) were 0.81 (0.52-1.25), 1.17 (0.92-1.49), and 1.32 (1.02-1.71), respectively, in analyses adjusted for established risk factors plus UAE. CONCLUSION: Self-reported current smoking is associated with increased CKD risk, but dependent on UAE. The association between urine cotinine-assessed current smoking and increased CKD risk is independent of UAE. Urine cotinine-assessed smoking status may be a more reliable risk indicator for CKD incidence than self-reported smoking status.

Role of parental smoking and environmental tobacco smoke exposure in childhood cancer: A study using hair cotinine analysis and questionnaires.

OBJECTIVES: In the etiology of childhood cancers, many genetic and environmental factors play a role. One of these factors could be cigarette smoking, and the main source of tobacco smoke exposure of children is parental smoking. However, establishing a causal relationship between parental smoking and childhood cancers has proven challenging due to difficulties in accurately detecting tobacco smoke exposure METHODS: To address this issue, we used hair cotinine analysis and a questionnaire to get information about tobacco smoke exposures of pediatric cancer patients and healthy children. A total of 104 pediatric cancer patients and 99 healthy children participated in our study. Parental smoking behaviors (pre-conceptional, during pregnancy, and current smoking) and environmental tobacco smoke (ETS) exposures of children are compared. RESULTS: We have found no differences between two groups by means of maternal smoking behaviors. However, the rates of paternal pre-conceptional smoking and smoking during pregnancy were significantly low in cancer patients (p < .05). These data suggest that social desirability bias among fathers of cancer patients may have contributed to this discrepancy. According to questionnaire, cancer patients had significantly lower ETS exposures than healthy children (p < .05). However, ETS exposure assessment through cotinine analysis demonstrated that cancer patients had higher exposure to ETS compared to healthy children (p < .001). CONCLUSION: Our findings provide evidence supporting the potential role of smoking as a risk factor for childhood cancers. This study also revealed that questionnaires could cause biases. We suggest that cotinine analysis along with validated questionnaires can be used to prevent biases in studies of tobacco smoke in the etiology of childhood cancers.

Methoxsalen inhibits the acquisition of nicotine self-administration: attenuation by cotinine replacement in male rats.

INTRODUCTION: Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine is the major metabolite of nicotine that produces a myriad of neurobehavioral effects. Previous studies showed that cotinine supported self-administration in rats and rats with a history of cotinine self-administration exhibited relapse-like drug-seeking behavior, suggesting that cotinine may also be reinforcing. To date, whether cotinine may contribute to nicotine reinforcement remains unknown. Nicotine metabolism is mainly catalyzed by hepatic CYP2B1/2 enzymes in rats and methoxsalen is a potent CYP2B1/2 inhibitor. METHODS: The study examined nicotine metabolism, self-administration, and locomotor activity. The hypothesis is that methoxsalen inhibits nicotine self-administration and cotinine replacement attenuates the inhibitory effects of methoxsalen in male rats. RESULTS: Methoxsalen decreased plasma cotinine levels following a subcutaneous nicotine injection. Repeated daily methoxsalen treatments reduced the acquisition of nicotine self-administration, leading to fewer nicotine infusions, lower nicotine intake, and lower plasma cotinine levels. However, methoxsalen did not alter the maintenance of nicotine self-administration despite a significant reduction of plasma cotinine levels. Cotinine replacement by mixing cotinine with nicotine for self-administration dose-dependently increased plasma cotinine levels and enhanced the acquisition of self-administration. Neither basal nor nicotine-induced locomotor activity was altered by methoxsalen. CONCLUSIONS: These results indicate that methoxsalen inhibition of cotinine formation impaired the acquisition of nicotine self-administration, and cotinine replacement attenuated the inhibitory effects of methoxsalen on the acquisition of self-administration, suggesting that cotinine may contribute to the initial development of nicotine reinforcement. IMPLICATIONS: Smoking cessation medications targeting nicotine's effects are only moderately effective, making it imperative to better understand the mechanisms of nicotine misuse. Methoxsalen inhibited nicotine metabolism to cotinine and impaired the acquisition of nicotine self-administration. Cotinine replacement restored plasma cotinine and attenuated the methoxsalen inhibition of nicotine self-administration in rats. These results suggest that (1) the inhibition of nicotine metabolism may be a viable strategy in reducing the development of nicotine reinforcement, (2) methoxsalen may be translationally valuable, and (3) cotinine may be a potential pharmacological target for therapeutic development given its important role in the initial development of nicotine reinforcement.

Investigating the interplay of smoking, cardiovascular risk factors, and overall cardiovascular disease risk: NHANES analysis 2011-2018.

BACKGROUND: This study explores the intricate relationship between smoking, cardiovascular disease (CVD) risk factors and their combined impact on overall CVD risk, utilizing data from NHANES 2011-2018. METHODS: Participants were categorized based on the presence of CVD, and we compared their demographic, social, and clinical characteristics. We utilized logistic regression models, receiver operating characteristics (ROC) analysis, and the chi-squared test to examine the associations between variables and CVD risk. RESULTS: Significant differences in characteristics were observed between those with and without CVD. Serum cotinine levels exhibited a dose-dependent association with CVD risk. The highest quartile of cotinine levels corresponded to a 2.33-fold increase in risk. Smoking, especially in conjunction with lower HDL-c, significantly increases CVD risk. Combinations of smoking with hypertension, central obesity, diabetes, and elevated triglycerides also contributed to increased CVD risk. Waist-to-Height Ratio, Visceral Adiposity Index, A Body Shape Index, Conicity Index, Triglyceride-Glucose Index, Neutrophil, Mean platelet volume and Neutrophil to Lymphocyte ratio demonstrated significant associations with CVD risk, with varying levels of significance post-adjustment. When assessing the combined effect of smoking with multiple risk factors, a combination of smoking, central obesity, higher triglycerides, lower HDL-c, and hypertension presented the highest CVD risk, with an adjusted odds ratio of 14.18. CONCLUSION: Smoking, when combined with central obesity, higher triglycerides, lower HDL-c, and hypertension, presented the highest CVD risk, with an adjusted odds ratio of 14.18.

Early life exposure to secondhand tobacco smoke and eating behaviors at age 12 years.

BACKGROUND: Prenatal or early childhood secondhand tobacco smoke (SHS) exposure increases obesity risk. However, the potential mechanisms underlying this association are unclear, but obesogenic eating behaviors are one pathway that components of SHS could perturb. Our aim was to assess associations of prenatal and early childhood SHS exposure with adolescent eating behaviors. METHODS: Data came from a prospective pregnancy and birth cohort (N = 207, Cincinnati, OH). With multiple informant models, we estimated associations of prenatal (mean of 16 and 26 weeks of gestation maternal serum cotinine concentrations) and early childhood cotinine (average concentration across ages 12, 24, 36, and 48 months) with eating behaviors at age 12 years (Child Eating Behaviors Questionnaire). We tested whether associations differed by exposure periods and adolescent's sex. Models adjusted for maternal and child covariates. RESULTS: We found no statistically significant associations between cotinine measures and adolescent's eating behaviors. Yet, in females, prenatal cotinine was associated with greater food responsiveness (ß: 0.23; 95% CI: 0.08, 0.38) and lower satiety responsiveness (ß: -0.14; 95% CI: -0.26, -0.02); in males, prenatal and postnatal cotinine was related to lower food responsiveness (prenatal: ß: -0.25; 95% CI: -0.04, -0.06; postnatal: ß: -0.36; 95% CI: -0.06, -0.11). No significant effect modification by sex or exposure window was found for other eating behaviors. CONCLUSION: Prenatal and early childhood SHS exposures were not related to adolescent's eating behavior in this cohort; however, biological sex may modify these associations.

The longitudinal analysis for the association between smoking and the risk of depressive symptoms.

BACKGROUND: Despite high smoking rate in people with depressive symptoms, there is ongoing debate about relationship between smoking and depressive symptoms. METHODS: Study participants were 57,441 Korean men. We collected their baseline data between 2011 and 2012, and conducted follow-up from 2013 to 2019. They were categorized by smoking status (never: < 100 cigarettes smoking in life time, former: currently quitting smoking, and current smoker: currently smoking), smoking amount (pack/day and pack-year) and urine cotinine excretion. The development of depressive symptoms was determined in CES-D score ≥ 16. Cox proportional hazards model was used to analyze the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CI) for depressive symptoms in relation to smoking status, smoking amount, and urine cotinine excretion. RESULTS: During 6.7 years of median follow-up, the risk of depressive symptoms increased in order of never (reference), former (HR = 1.08, 95% CI: 1.01-1.15) and current smoker (HR = 1.24, 95% CI: 1.16-1.32). Among current smoker, the risk of depressive symptoms increased proportionally to daily smoking amount (< 1 pack; HR = 1.21, 95% CI: 1.13-1.29, and ≥ 1 pack; HR = 1.34, 95% CI: 1.23 - 1.45). This pattern of relationship was consistently observed for pack-year in former smoker and current smoker. Additionally, urine cotinine excretion was proportionally associated with the risk of depressive symptoms. CONCLUSION: Exposure to smoking was associated with the increased risk of depressive symptoms. Dose dependent relationship was observed between smoking amount and the risk of depressive symptoms.

Correlation analysis between smoke exposure and serum neurofilament light chain in adults: a cross-sectional study.

BACKGROUND: Smoke exposure is a prevalent and well-documented risk factor for various diseases across different organ systems. Serum neurofilament light chain (sNfL) has emerged as a promising biomarker for a multitude of nervous system disorders. However, there is a notable paucity of research exploring the associations between smoke exposure and sNfL levels. METHODS: We conducted a comprehensive analysis of the National Health and Nutrition Examination Survey (NHANES) cross-sectional data spanning the years 2013 to 2014. Serum cotinine levels were classified into the following three groups: < 0.05, 0.05-2.99, and ≥ 3 ng/ml. Multiple linear regression models were employed to assess the relationships between serum cotinine levels and sNfL levels. Additionally, we utilized restricted cubic spline analyses to elucidate the potential nonlinear relationship between serum cotinine and sNfL levels. RESULTS: A total of 2053 participants were included in our present research. Among these individuals, the mean age was 47.04 ± 15.32 years, and males accounted for 48.2% of the total study population. After adjusting the full model, serum cotinine was positively correlated with sNfl in the second group (ß = 0.08, 95%CI 0.01-0.15) and in the highest concentration of serum cotinine (ß = 0.10, 95%CI 0.01-0.19) compared to the group with the lowest serum cotinine concentrations. Current smokers, in comparison to non-smokers, exhibited a trend toward elevated sNfL levels (ß = 0.07, 95%CI 0.01-0.13). Furthermore, subgroup analyses revealed interactions between serum cotinine levels and different age groups (P for interaction = 0.001) and gender stratification (P for interaction = 0.015) on sNfL levels. CONCLUSION: The study suggested that serum cotinine was significantly and positively associated with sNfl levels in adult participants. Furthermore, current smokers tend to exhibit elevated sNfL levels. This research sheds light on the potential implications of smoke exposure on neurological function impairment and underscores the importance of further exploration in this area.

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

BACKGROUND/PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

Variability in the association of smoking status with the prevalence of diabetes mellitus in the Korean population according to different definitions of smoking status: analysis based on the Korea National Health and Nutrition Examination Survey (2014-2020).

We evaluated the association between smoking and diabetes, as well as the effects of gender differences and hidden smoking among females on this association using nationally representative data. Analyzing data from 44,049 individuals aged 19 and older, we utilized multivariable logistic regression to investigate associations, controlling for sociodemographic factors. Subgroup analysis based on smoking status determined factors associated with diabetes. To better our understanding of the smoking-diabetes relationship, we introduced a new variable, survey-cotinine verified smoking status (SCS). This study provides valuable insight by exploring the correlation between smoking and diabetes using different definitions of smoking status. Both male and female smokers showed correlations with diabetes according to cotinine-verified smoking status (OR: 1.22 and 1.48, respectively). According to smoking amount, cotinine-verified heavy smokers correlated with diabetes in males (OR: 1.37), while light smokers exhibited a negative correlation with diabetes in females for both cotinine-verified smoking status (OR: 0.60) and survey-cotinine verified status (OR: 0.58) Smoking was associated with diabetes in the overall population, with gender differences observed. When evaluating this association, we should consider variables of smoking amount, passive and intermittent smoking, and specifically, account for the influence of hidden smoking among females, particularly when utilizing self-reported questionnaires in Korea.

This study examines the association between smoking status and diabetes, focusing on gender-specific patterns, using a nationally representative sample. To increase the accuracy of smoking assessments, a new variable based on cotinine-determined smoking status is used. The study sheds light on the prevalence of under-reporting among female smokers in the Korean population, revealing important insights for future research and public health interventions. These findings underscore the importance of considering hidden smoking among women when investigating the relationship between smoking and diabetes, particularly when using self-reported questionnaires.

NHANES-based analysis of the correlation between leisure-time physical activity, serum cotinine levels and periodontitis risk.

OBJECTIVE: To investigate the association of leisure-time physical activity and serum cotinine levels with the risk of periodontitis in the general population and to further analyze the interaction between leisure-time physical activity and serum cotinine levels on the risk of periodontitis. METHODS: This was a cross-sectional study, extracting data from 9605 (56.19%) participants in the National Health and Nutrition Examination Survey (NHANES) database from 2009 to 2014, and analyzing the relationship and interaction effects of serum cotinine level, leisure time physical activity, and risk of periodontitis by weighted univariate logistic modeling; Effect sizes were determined using ratio of ratios (OR), 95% confidence intervals (95% CI). RESULTS: 5,397 (56.19%) of 9,605 participants had periodontitis; an increased risk of periodontitis was found in those in the leisure time physical activity intensity < 750 MET × min/week group (OR = 1.44, 95% CI: 1.17-1.78). Serum cotinine levels ≥ 0.05 ng/ml were associated with an increased risk of periodontitis (OR = 1.99, 95% CI: 1.69-2.33). The group with low leisure physical activity and serum cotinine levels ≥ 0.05 ng/ml had an increased risk of periodontitis compared to the group with high leisure physical activity and serum cotinine levels < 0.05 ng/ml (OR = 2.48, 95% CI: 1.88-3.27). Interaction metrics RERI = 0.90 (95% CI: 0.44-1.36) and API = 0.36 (95% CI: 0.18-0.55); CI for SI = 2.55 (95% CI: 1.03-6.28). for API 0.36. CONCLUSION: Leisure time physical activity intensity interacted with smoking exposure on periodontitis risk and may provide the general population with the opportunity to Increasing leisure-time physical activity and smoking cessation may provide recommendations for the general population.

Intensive Intervention on Smoking Cessation in Patients Undergoing Elective Surgery: The Role of Family Physicians.

Background and Objectives: The aim of this study was to determine the role of physicians in the intensive intervention and education regarding the smoking cessation of patients undergoing elective surgery under general anaesthesia. Materials and Methods: A randomised prospective study was conducted in family physicians' clinics in which smokers of both sexes, aged 21-65 years, without cognitive impairments, and who were not addicted to psychoactive substances voluntarily participated. Four weeks preoperatively, 120 smokers were randomised into two equal groups; the intervention group (IG) underwent an intervention for the purpose of smoking cessation and the control group (CG) underwent no intervention. Biochemical tests were performed in order to determine the smoking status of the participants in the phase of randomisation, one week preoperatively, as well as 40, 120, and 180 days and 12 months postoperatively. The examinees of the IG talked to the physician five times and received 140 telephone messages, leaflets, and motivational letters along with the pharmacotherapy, while the participants in the CG received little or no advice on smoking cessation. Results: The results of this study confirmed a significant influence of the intervention and education on the smoking abstinence in the IG compared to the CG (p < 0.001). The smokers in the IG had 7.31 (95% CI: 2.32-23.04) times greater odds of abstinence upon the 12-month follow-up than the smokers in the CG. The smokers in the IG who did not stop smoking had a lower degree of dependence and smoked fewer cigarettes (p < 0.0001) compared to those in the CG, as well as a multiple times higher prevalence of short- and long-term abstinence. Conclusions: It can be concluded that the intensive intervention and education can motivate patients preparing for elective surgery to stop smoking in the short- and long term.

Prolonged, physiologically relevant nicotine concentrations in the airways of smokers.

Nicotine from cigarette smoke is a biologically active molecule that has pleiotropic effects in the airway, which could play a role in smoking-induced lung disease. However, whether nicotine and its metabolites reach sustained, physiologically relevant concentrations on airway surfaces of smokers is not well defined. To address these issues, concentrations of nicotine, cotinine, and hydroxycotinine were measured by mass spectrometry (MS) in supernatants of induced sputum obtained from participants in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS), an ongoing observational study that included never smokers, former smokers, and current smokers with and without chronic obstructive pulmonary disease (COPD). A total of 980 sputum supernatants were analyzed from 77 healthy never smokers, 494 former smokers (233 with COPD), and 396 active smokers (151 with COPD). Sputum nicotine, cotinine, and hydroxycotinine concentrations corresponded to self-reported smoking status and were strongly correlated to urine measures. A cutoff of ∼8-10 ng/mL of sputum cotinine distinguished never smokers from active smokers. Accounting for sample dilution during processing, active smokers had airway nicotine concentrations in the 70-850 ng/mL (∼0.5-5 µM) range, and concentrations remained elevated even in current smokers who had not smoked within 24 h. This study demonstrates that airway nicotine and its metabolites are readily measured in sputum supernatants and can serve as biological markers of smoke exposure. In current smokers, nicotine is present at physiologically relevant concentrations for prolonged periods, supporting a contribution to cigarette-induced airway disease.

Prenatal and Childhood Smoke Exposure Associations with Cognition, Language, and Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To assess the relationships of prenatal and childhood smoke exposure with specific neurodevelopmental and behavioral problems during early childhood. STUDY DESIGN: A subsample (n = 386) of mother-child dyads from the Newborn Epigenetic Study (NEST) prebirth cohort participated in the study. Cotinine concentrations were used to objectively measure prenatal and childhood smoke exposure when youth were aged 3-13 years. Multivariable regression models were used to estimate associations of prenatal and childhood cotinine concentrations with performance on the National Institutes of Health (NIH) Toolbox and attention-deficit/hyperactivity disorder and behavioral symptoms, measured using the Behavior Assessment System for Children, 2nd edition (BASC-2). RESULTS: After adjusting for confounders, childhood cotinine concentrations were associated with poorer cognitive performance on tasks measuring cognitive flexibility (B = -1.29; P = .03), episodic memory (B = -0.97; P = .02), receptive language development (B = -0.58; P = .01), and inhibitory control and attention (B = -1.59; P = .006). Although childhood cotinine concentration was associated with higher levels of attention problems (B = 0.83; P = .004) on the BASC-2, after adjustment for confounders, the association is nonsignificant. Although associations for maternal cotinine concentrations were null, an interaction was detected between prenatal and childhood cotinine concentrations on the NIH Toolbox Picture Vocabulary Task (P = .02). CONCLUSIONS: Our findings suggest that childhood tobacco smoke exposure may lead to poorer attention regulation and language acquisition, complex visual processing ability, and attention problems.

Interaction between Serum Cotinine and Magnesium Intake with Childhood Asthma: A Cross-Sectional Study.

INTRODUCTION: Serum cotinine and magnesium intake are often associated with childhood asthma. This study evaluated the interaction between serum cotinine and magnesium intake and childhood asthma. METHODS: This cross-sectional study included 14,159 subjects from the National Health and Nutrition Examination Survey 2005-2018. Serum cotinine levels were classified according to the lower quartile: ≤0.2089 ng/mL as low level and >0.2089 ng/mL as high level. Magnesium intake was categorized as high (>98 mg/1,000 kcal) or low level (≤98 mg/1,000 kcal) based on the upper quartile. Weighted logistic regression analyses were adopted to analyze the association between cotinine, magnesium intake, and childhood asthma. Additionally, the combined effect of cotinine and magnesium intake on childhood asthma risk was examined. The stratified analyses were based on gender, body mass index, and family history of asthma to further examine the relationship between cotinine, magnesium intake, and childhood asthma. RESULTS: The prevalence of asthma was approximately 17.56%. Compared to low-level cotinine, high-level cotinine was associated with asthma (odds ratio [OR] = 1.25, 95% confidence interval (CI): 1.04-1.50). Low-level magnesium intake was related to asthma compared with high-level magnesium intake (OR = 1.21, 95% CI: 1.04-1.40). Using interaction analysis, we also found that the combined effect of cotinine and magnesium intake was associated with childhood asthma risk, and the interaction between high-level cotinine and low-level magnesium intake was associated with the highest risk of childhood asthma (OR = 1.35, 95% CI: 1.04-1.74). Additionally, this interaction was also found in males, overweight/non-overweight, and those with family history of asthma. CONCLUSION: There was an interaction between serum cotinine and magnesium intake on childhood asthma. The results suggested that implementing smoking bans in certain settings (e.g., communities, schools) and promoting the consumption of magnesium-rich foods may be effective strategies for preventing childhood asthma.

Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults.

OBJECTIVE: The study aimed to examine the relationship between secondhand smoke (SHS) exposure and severe headaches or migraine in never-smoking adults verified by serum cotinine. BACKGROUND: Current evidence about the association between self-reported SHS exposure and headaches or migraine is limited and contradictory. An important issue lies in the lack of actual SHS exposure assessment through biomarkers. METHODS: We conducted a cross-sectional study on 4560 never-smoking adults from the National Health and Nutrition Examination Survey (NHANES), 1999-2004. The SHS exposure was evaluated by measuring serum cotinine concentrations. The information regarding severe headaches or migraine was based on self-reporting. RESULTS: The overall prevalence rate of severe headaches or migraine was 20% (919/4560). After adjusting for relevant covariates, we found that heavy SHS exposure (serum cotinine at 1 to 10 ng/mL) was positively associated with severe headaches or migraine (OR: 2.02, 95% CI [1.19, 3.43]); however, no significant association was found between low SHS exposure (serum cotinine at 0.05 to 0.99 ng/mL) and severe headaches or migraine (OR: 1.15, 95% CI [0.91, 1.47]). Restricted cubic spline analysis showed that the natural logarithm of serum cotinine had a linear relationship with severe headaches or migraine (p = 0.335 for nonlinearity). Stratified analysis indicated that individuals with a BMI of <25 (p < 0.001 for interaction) and sedentary activity (p = 0.016 for interaction) modified the relationship between SHS exposure and severe headaches and migraine. Even after altering the definition of SHS exposure, excluding drugs that might affect the metabolism of serum cotinine, and multiple imputation, our sensitivity analysis results remained stable. CONCLUSIONS: The study demonstrated that heavy SHS exposure (serum cotinine at 1 to 10 ng/mL) had a significant positive association with severe headaches or migraine in never-smoking adults. Prospective studies are necessary to verify this relationship in the future.

Determination of soluble angiotensin-converting enzyme 2 in saliva samples and its association with nicotine.

INTRODUCTION: The Angiotensin-Converting Enzyme 2 (ACE2) is the main receptor of the SARS-CoV-2. There is contradictory evidence on how the exposure to nicotine may module the concentration of soluble ACE2 (sACE2). The aim of this study was to assess the association between nicotine and sACE2 concentrations in saliva samples. METHODS: Pooled analysis performed with data retrieved from two studies (n = 634 and n = 302). Geometric mean (GM) concentrations of sACE2, both total and relative to the total amount of protein in the sample, were compared according to sociodemographic variables and variables associated to nicotine. Multivariable linear regression models were fitted to explore the associations of sACE2 with nicotine adjusting for sex, age and body mass index. Spearman's rank-correlation coefficients were estimated between the concentrations of nicotine and cotinine, and pack-years, the concentration of relative sACE2 and the isoforms of sACE2. RESULTS: We observed a significant increase of 0.108‰ and 0.087 ng/µl in the relative and absolute salivary sACE2 GM concentrations, respectively, between the lowest and highest nicotine levels. Similar results were observed for cotinine. These associations did not change in the multivariable linear models. There was a low correlation of nicotine and cotinine concentration with the concentration of relative salivary sACE2 (rs = 0.153 and rs = 0.132, respectively), pack-years (rs = 0.222 and rs = 0.235, respectively) and with the concentration of isoform 40 KDa (rs = 0.193 and rs = 0.140, respectively). CONCLUSION: Salivary nicotine concentration seems to be limitedly associated with the concentration of sACE2.