The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation.

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).

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.

Quantifying carboxymethyl lysine and carboxyethyl lysine in human plasma: clinical insights into aging research using liquid chromatography-tandem mass spectrometry.

OBJECTIVE: The objective of this study was to establish a methodology for determining carboxymethyl lysine (CML) and carboxyethyl lysine (CEL) concentrations in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test results were also used for clinical aging research. METHODS: Human plasma samples were incubated with aqueous perfluorovaleric acid (NFPA), succeeded by precipitation utilizing trichloroacetic acid, hydrolysis facilitated by hydrochloric acid, nitrogen drying, and ultimate re-dissolution utilizing NFPA, followed by filtration. Cotinine-D3 was added as an internal standard. The separation was performed on an Agela Venusil ASB C18 column (50 mm × 4.6 mm, 5 µm) with a 5 mmol/L NFPA and acetonitrile/water of 60:40 (v/v) containing 0.15% formic acid. The multiple reaction monitoring mode was used for detecting CML, CEL, and cotinine-D3, with ion pairs m/z 205.2 > 84.1 (for quantitative) and m/z 205.2 > m/z 130.0 for CML, m/z 219.1 > 84.1 (for quantitative) and m/z 219.1 > m/z 130.1 for CEL, and m/z 180.1 > 80.1 for cotinine-D3, respectively. RESULTS: The separation of CML and CEL was accomplished within a total analysis time of 6 minutes. The retention times of CML, CEL, and cotinine-D3 were 3.43 minutes, 3.46 minutes, and 4.50 minutes, respectively. The assay exhibited linearity in the concentration range of 0.025-1.500 µmol/L, with a lower limit of quantification of 0.025 µmol/L for both compounds. The relative standard deviations of intra-day and inter-day were both below 9%, and the relative errors were both within the range of ±4%. The average recoveries were 94.24% for CML and 97.89% for CEL. CONCLUSION: The results indicate that the developed methodology is fast, highly sensitive, highly specific, reproducible, and suitable for the rapid detection of CML and CEL in clinical human plasma samples. The outcomes of the clinical research project on aging underscored the important indicative significance of these two indicators for research on human aging.

Chronic Exposure to E-Cigarettes Elevates CYP2A5 Activity, Protein Expression, and Cotinine-Induced Production of Reactive Oxygen Species in Mice.

Coumarin 7'-hydroxylase activity, a specific marker of CYP2A5 activity, and the protein level were measured in liver microsomes of male mice after chronic exposure to e-cigarettes (e-cigs) (2.4% nicotine). After exposure for 240 minutes per day for 5 days, the activity and the protein level in preproenkephalin (ppENK)-heterozygous [ppENK (+/-)] mice were significantly elevated (P <0.05) compared with the untreated control. This elevation was not due to deletion of the ppENK gene because the activity did not differ among untreated ppENK (+/-), ppENK (-/-), and wild-type ppENK (+/+) controls. Hence, the elevation can reasonably be attributed to nicotine exposure. The production of reactive oxygen species (ROS) upon incubation of the hepatic microsomes of these mice with cotinine was higher in microsomes from the e-cig-treated mice compared with the untreated controls (P < 0.01). Liquid chromatography mass spectrometry assay showed three oxidation products of cotinine, viz trans 3'-hydroxycotinine (3'-HC), 5'-hydroxycotinine (5'-HC), and cotinine N-oxide (CNO) in the plasma of these mice. The result identifies these three oxidation reactions as the source of the observed ROS and also shows that, in nicotine-treated mice, the appropriate "nicotine metabolite ratio" is (3'-HC + 5'-HC + CNO)/cotinine. The results suggest intriguing possibilities that 1) this metabolite ratio may correlate with plasma nicotine clearance and hence impact nicotine's psychoactive effects and 2) chronic e-cig treatment causes ROS-induced oxidative stress, which may play a major role in the regulation of CYP2A5 expression. Our present results clearly show that both the activity and the protein level of CYP2A5 are elevated by repeated exposure to nicotine. SIGNIFICANCE STATEMENT: Nicotine, the psychoactive ingredient of tobacco, is eliminated as the oxidation products of cotinine in reactions catalyzed by the enzymes CYP2A5 in mice and CYP2A6 in humans. This study shows that repeated exposure to e-cigarettes elevates the level of CYP2A5 and the formation of reactive oxygen species. The results suggest an intriguing possibility that CYP2A5 may be upregulated by chronic nicotine exposure due to oxidative stress caused by the oxidation of cotinine in this preclinical model of human smokers.

Inflammatory marker levels in children with tobacco smoke exposure.

BACKGROUND: Tobacco smoke exposure (TSE) has inflammatory and immunosuppressive effects which may be associated with altered levels of inflammatory markers and pediatric illnesses. OBJECTIVE: The primary objective was to examine the associations of cotinine-confirmed and parent-reported child TSE patterns and discharge diagnoses with C-reactive protein (CRP), IL-8, and IL-10 in 0-11-year-old pediatric emergency department (PED) patients who lived with ≥ 1 smoker. METHODS: Saliva samples were obtained from 115 children with a mean (SD) age of 3.5 (3.1) years during the PED visit (T0). Saliva was analyzed for cotinine, CRP, IL-8, and IL-10. Parents self-reported their children's TSE patterns; children's medical records were reviewed to identify and categorize discharge diagnoses. Linear regression models were utilized to find T0 associations of cotinine-confirmed and parent-reported child TSE patterns, and PED diagnoses with each inflammatory marker. All models were adjusted for child race/ethnicity, child sex, annual household income, and housing type. The TSE models also adjusted for child discharge diagnosis. RESULTS: At T0, the geometric mean (GeoM) of cotinine was 4.1 ng/ml [95 %CI = 3.2-5.2]; the GeoMs of CRP, IL-8, and IL-10 were 3,326 pg/ml [95 %CI = 2,696-4,105], 474 pg/ml [95 %CI = 386-583], and 1.1 pg/ml [95 %CI = 0.9-1.3], respectively. Parent-reported child TSE patterns were positively associated with ln-transformed CRP levels, while adjusting for the covariates (ß^ = 0.012 [95 %CI:0.004-0.020], p = 0.037). In the parent-reported child TSE pattern model, there were significant positive associations between the covariate of child age with CRP and IL-8 levels (p = 0.028 and p < 0.001, respectively). Children with a bacterial diagnosis had higher IL-8 levels (p = 0.002) compared to the other diagnosis groups. CONCLUSIONS: Results indicate that parent-reported child TSE increases the expression of CRP in ill children and supports prior work demonstrating that IL-8 is higher in children with TSE who have bacterial infections. These findings should be examined in future research with ill children with and without TSE.

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.

Gas chromatography-mass spectrometry determination of nicotine and cotinine in urine: A study of the effect of passive smoking.

RATIONALE: Recent data suggest that passive smoking has a risk comparable to active smoking. Passive smoking is considered dangerous in children and is suspected as a cause of asthma. However, some reports are opposing such claims, indicating the need for solid results and large-scale studies. This scientific work aims to develop a method for the determination of nicotine (NCOT) and major nicotine's metabolite cotinine (COT) in urine samples, using gas chromatography-mass spectrometry (GC-MS). METHODS: Analysis was performed using a gas chromatograph Agilent Technologies 7890A with an MS 5975C inert XL, EI/CI MSD with Triple-Axis detector. For sample preparation, liquid-liquid extraction was applied after an optimization study with different extraction media. Eventually, 1 mL of dichloromethane was selected for the extraction of 0.5 mL of urine. Suitable chromatographic conditions were found for the rapid and accurate determination of NCOT and COT. Injection of 2 µL was performed using GC-MS, and selected ion monitoring (SIM) analysis was performed with the following ions (m/z): 162 (quantifier ion) and 84, 133, 161 qualifier ions for NCOT, and 176 (quantifier ion) and 98, 118, 119, 147 qualifier ions for COT. Nicotine-D4 (NCOT-D4) and cotinine-D3 (COT-D3) were used as internal standards with quantifier ions 101 and 166, respectively. The retention time (Rt) for NCOT was 7.557 min and 9.743 min for COT. RESULTS: The method was validated following international principles, assessing characteristics such as absolute recovery, carryover, linearity, specificity, selectivity, accuracy, precision, and stability. The method showed a linear dynamic range from 0.5 to 50 ng/mL, and the limits of detection and quantification were for both NCOT and COT 0.2 and 0.5 ng/mL, respectively. Validation results were found satisfactory. Finally, the method was applied to the analysis of 60 clinical pediatric samples obtained from Aristotle University's pediatric clinic to check for possible exposure to smoke. Concentration levels ranged between 0.5 and 16.2 ng/mL for NCOT and between 1.0 and 25.1 ng/mL for COT. CONCLUSIONS: A rapid, sensitive, accurate, and simple method was developed and used as a tool for the confirmation of passive smoking in children. It is the first method applied to the analysis of such samples belonging to nonsmokers of young age. The total runtime of the GC-MS analysis was short (20 min), and the pretreatment protocol was simple, giving the ability for analysis of a large number of samples on a daily routine basis.

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. AIMS AND 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.

Association Between Secondhand Smoke Exposure and Nonalcoholic Fatty Liver Disease in the General U.S. Adult Nonsmoker Population.

INTRODUCTION: Smoking is a cause of nonalcoholic fatty liver disease (NAFLD), but the dose-response relationship between secondhand smoke exposure (SHS) and NAFLD is unclear. This study sought to determine the relationship between SHS and NAFLD risk among adult nonsmokers in the United States. AIMS AND METHODS: Data from 7412 adult nonsmokers aged ≥20 years who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 were used in this study. SHS was defined as a nonsmoker with a serum cotinine concentration of 0.05-10.00 ng/mL. NAFLD was identified using the U.S. fatty liver index (USFLI), hepatic steatosis index (HSI), and fatty liver index (FLI). Weighted multivariable logistic regression and restricted cubic spline models were applied to evaluate the relationship between SHS and NAFLD risk. RESULTS: The participants had a weighted mean age of 49.2 years, and 55.5% were female. SHS was associated with NAFLD (odds ratio [OR] 1.22; 95% confidence interval CI: 1.05 to 1.42), showing a linear dose-response relationship (natural log of cotinine level: OR 1.10, 95% CI: 1.05 to 1.17). Sensitivity analyses using different NAFLD definitions (HSI: OR 1.21, 95% CI: 1.01 to 1.46; FLI: OR 1.26, 95% CI: 1.06 to 1.49), excluding participants taking hepatotoxic drugs, and propensity score-adjusted analysis yielded similar results. The association between SHS and NAFLD was consistent in analyses stratified by age, sex, and race/ethnicity. CONCLUSIONS: Among this nationally representative sample of U.S. adults, SHS had a linear dose-response relationship with the risk of NAFLD, suggesting that measures to lower SHS might lower NAFLD risk. IMPLICATIONS: This study assessed the association between secondhand smoke exposure and the risk of nonalcoholic fatty liver disease (NAFLD) using data from 7412 adult nonsmokers aged 20 years or older who participated in the United States NHANES between 2007 and 2016. Secondhand smoke exposure was measured using serum cotinine levels. Three different noninvasive indexes were used to measure NAFLD. Secondhand smoke exposure was associated with an increased risk of NAFLD, with a linear dose-response relationship. The results of sensitivity analyses and subgroup analyses were consistent.

Prevalence of Underreported Nicotine Exposure Among US Nonsmoking Adults: A Comparison of Self-Reported Exposure and Serum Cotinine Levels From NHANES 2013-2020.

INTRODUCTION: Secondhand smoke (SHS) poses a significant health risk. However, individuals who do not smoke may be unaware of their exposure, thereby failing to take protective actions promptly. AIMS AND METHODS: We assessed the prevalence of underreported nicotine exposure in a nationally representative sample of US nonsmoking adults using data from the US National Health and Examination Survey. Individuals with underreported nicotine exposure were defined as those who reported no exposure to all tobacco products (traditional tobacco, nicotine replacements, and e-cigarettes) or SHS, yet had detectable levels of serum cotinine (>0.015 ng/mL). We fitted logistic regression models to determine sociodemographic and chronic condition factors associated with underreported nicotine exposure. RESULTS: Our analysis included 13 503 adults aged 18 years and older. Between 2013 and 2020, the prevalence of self-reported SHS exposure, serum cotinine-assessed nicotine exposure, and underreported nicotine exposure among US nonsmokers were 22.0%, 51.2%, and 34.6%, respectively. Remarkably, 67.6% with detectable serum cotinine reported no SHS exposure. Males, non-Hispanic blacks, individuals of other races (including Asian Americans, Native Americans, and Pacific Islanders), and those without cardiovascular diseases were more likely to underreport nicotine exposure than their counterparts. The median serum cotinine value was higher in respondents who reported SHS exposure (0.107 ng/mL) than in those who reported no exposure (0.035 ng/mL). We estimate that approximately 56 million US residents had underreported nicotine exposure. CONCLUSIONS: Over a third of US nonsmokers underreport their nicotine exposure, underlining the urgent need for comprehensive public awareness campaigns and interventions. Further research into sociodemographic determinants influencing this underreporting is needed. IMPLICATIONS: Understanding the extent of underreported nicotine exposure is crucial for developing effective public health strategies and interventions. It is imperative to bolster public consciousness about the risks associated with SHS. Additionally, surveillance tools should also incorporate measures of exposure to outdoor SHS and e-cigarette vapor to enhance the quality of data monitoring. Findings from this study can guide tobacco control initiatives and inform smoke-free air legislation.

Evaluation on the Sex-Specific Association Between Cigarette Smoke Exposure and Inflammation Markers-C-Reactive Protein and White Blood Cell Count.

INTRODUCTION: Cigarette smoke increases peripheral white blood cell (WBC) count. However, the dose-dependent association between smoking and C-reactive protein (CRP), an important inflammatory marker, has been reported as inconsistent. AIMS AND METHODS: Here, we evaluated the associations between smoking and CRP using both smoking questionnaires and urine cotinine as exposure markers. The Korea National Health and Nutrition Examination Survey data were used for analyzing the associations. Multiple regression analyses were performed to examine the associations between cigarette smoke exposure, as assessed by questionnaires and urine cotinine, and health effects, as measured by CRP and WBC count, controlling for potential confounders. The confounders, including age, sex, body mass index, blood pressure, cholesterol, glucose, alanine aminotransferase, and uric acid, were selected a priori based on the literature. RESULTS: A total of 11 435 participants were included for analysis. For the exposure-response relationship, the results indicated a significant increase in CRP levels in male smokers compared to male nonsmokers (p = .002), whereas no significant increase was found in female smokers compared to female nonsmokers (p = .680). For the dose-response relationship, a significant positive association was observed between urine cotinine and CRP in male smokers (p = .018), whereas no significant association was found in female smokers (p = .508). WBC count consistently showed significant exposure-response and dose-response relationships in both sexes. CONCLUSIONS: WBC count was found to be a consistent effect marker of cigarette smoke exposure, while the association between CRP level and smoking was inconsistent and varied by sex. The sex-specific response to cigarette smoke exposure warrants further exploration in future studies. IMPLICATIONS: Cigarette smoke exposure is known to increase inflammation and has been thought to increase CRP, a significant inflammation marker. However, recent studies have reported conflicting results regarding the dose-dependent association between cigarette smoke exposure and CRP. This study found that the association between smoking and CRP is inconsistent and varies by sex, showing significant exposure response in men but not in women. Furthermore, the study suggests that WBC count is a more consistent marker for cigarette smoke exposure.

Associations Between Childhood Trauma and Tobacco Use Outcomes in Adults after Overnight Abstinence.

INTRODUCTION: Childhood trauma is known to be associated with nicotine dependence, yet limited smoking outcomes have been examined and few studies have assessed associations between specific trauma subscales and smoking. Additionally, sex differences in trauma-smoking relations are understudied. This study examined associations between childhood trauma and several smoking-related outcomes in adults who smoke after overnight abstinence. AIMS AND METHODS: People who smoke (N = 205) completed self-report and biochemical assessments evaluating childhood trauma, affect, nicotine dependence, smoking urges, withdrawal, and plasma cortisol and cotinine levels. Smoking outcomes were compared between those with and without a history of moderate to severe childhood trauma among the total sample and by sex. RESULTS: Relative to those with no to minimal abuse, those with moderate to severe abuse had higher negative affect, withdrawal severity, and plasma cotinine levels. Exploratory analyses revealed that women were more likely than men to have urges to smoke for negative reinforcement and have higher withdrawal severity, but no interactions between abuse group and sex were observed. Examining specific trauma subscales, the moderate to severe emotional abuse group had more severe nicotine dependence, negative affect, and withdrawal compared to the no to minimal group. The moderate to severe sexual abuse group had more severe nicotine dependence and withdrawal compared to the no to minimal group. CONCLUSIONS: Exposure to childhood trauma is associated with more severe nicotine dependence, negative affect, withdrawal, and higher plasma cotinine levels. Findings also indicate that different types of trauma may differentially affect smoking behaviors. IMPLICATIONS: This study of adults who smoke finds that childhood trauma history may be a marker for smoking susceptibility and suggests that individuals with experiences of emotional and sexual abuse may require targeted forms of smoking cessation interventions. Moreover, findings suggest that smoking risks may differ for men and women. Findings inform public health interventions intended to reduce cigarette use in individuals with exposure to childhood trauma.

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.

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.

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.

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.

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.