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

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

Changes in biomarkers of exposure and withdrawal symptom among Chinese adult smokers after completely or partially switching from combustible cigarettes to an electronic nicotine delivery system.

This study assessed changes in biomarkers of exposure (BoE) after 5 days of completely or partially switching to an electronic nicotine delivery system (ENDS) use, compared with continued use of combustible cigarettes and smoking abstinence among Chinese adult smokers. A randomized, open-label, parallel-arm study was conducted among Chinese adult smokers who were naive ENDS users. Forty-six subjects were randomized to 4 study groups (n = 11-12 per group): exclusive ENDS use, dual use of ENDS and cigarettes, exclusive cigarettes use, and smoking abstinence. Subjects were confined in clinic for 5 consecutive days and product use was ad libitum. Nicotine and its metabolites (cotinine and 3-hydroxycotinine), and BoEs (AAMA, CEMA, HEMA, HMPMA, 3-HPMA, SPMA, exhaled CO, and exhaled NO) were measured. Withdrawal symptom was measured using MNWS throughout the 5-day period. Six urine BoEs of volatile organic compounds decreased by 55.1-84.1% in the exclusive ENDS use group, which is similar to the smoking abstinence group (67.2-87.4%). The level of decrease was 56.8-70.4% in the dual use group and 10.7-39.0% in the cigarettes group. Urine total nicotine exposure had a non-significant increase in the exclusive ENDS use group, and plasma nicotine and cotinine showed a trend of increasing day by day. After completely or partially switching to ENDS use among Chinese smokers, exposure to selected toxicants were significantly decreased. The results of this study add to the body of evidence that exposure to toxic substance decreased among smokers after complete or partial switch from combustible cigarettes to ENDS use. As part of transition to experienced ENDS use, this study found that smokers of the initial stage who have no prior ENDS experience may increase nicotine intake after switching to ENDS use.

Sources of Tobacco Smoke Exposure and Their Associations With Serum Cotinine Levels Among US Children and Adolescents.

INTRODUCTION: We assessed tobacco smoke exposure (TSE) levels based on private and public locations of TSE according to race and ethnicity among US school-aged children ages 6-11 years and adolescents ages 12-17 years. AIMS AND METHODS: Data were from 5296 children and adolescents who participated in the National Health and Nutrition Examination Survey (NHANES) 2013-2018. Racial and ethnic groups were non-Hispanic white, black, other or multiracial, and Hispanic. NHANES assessed serum cotinine and the following TSE locations: homes and whether smokers did not smoke indoors (home thirdhand smoke [THS] exposure proxy) or smoked indoors (secondhand [SHS] and THS exposure proxy), cars, in other homes, restaurants, or any other indoor area. We used stratified weighted linear regression models by racial and ethnic groups and assessed the variance in cotinine levels explained by each location within each age group. RESULTS: Among 6-11-year-olds, exposure to home THS only and home SHS + THS predicted higher log-cotinine among all racial and ethnic groups. Non-Hispanic white children exposed to car TSE had higher log-cotinine (ß = 1.64, 95% confidence interval [CI] = 0.91% to 2.37%) compared to those unexposed. Non-Hispanic other/multiracial children exposed to restaurant TSE had higher log-cotinine (ß = 1.13, 95% CI = 0.23% to 2.03%) compared to those unexposed. Among 12-17-year-olds, home SHS + THS exposure predicted higher log-cotinine among all racial and ethnic groups, except for non-Hispanic black adolescents. Car TSE predicted higher log-cotinine among all racial and ethnic groups. Non-Hispanic black adolescents with TSE in another indoor area had higher log-cotinine (ß = 2.84, 95% CI = 0.85% to 4.83%) compared to those unexposed. CONCLUSIONS: TSE location was uniquely associated with cotinine levels by race and ethnicity. Smoke-free home and car legislation are needed to reduce TSE among children and adolescents of all racial and ethnic backgrounds. IMPLICATIONS: Racial and ethnic disparities in TSE trends have remained stable among US children and adolescents over time. This study's results indicate that TSE locations differentially contribute to biochemically measured TSE within racial and ethnic groups. Home TSE significantly contributed to cotinine levels among school-aged children 6-11 years old, and car TSE significantly contributed to cotinine levels among adolescents 12-17 years old. Racial and ethnic differences in locations of TSE were observed among each age group. Study findings provide unique insight into TSE sources, and indicate that home and car smoke-free legislation have great potential to reduce TSE among youth of all racial and ethnic backgrounds.

Serum Cotinine and Adverse Cardiovascular Outcomes: A Cross-sectional Secondary Analysis of the nuMoM2b Heart Health Study.

OBJECTIVE: We aimed to (1) compare serum cotinine with self-report for ascertaining smoking status among reproductive-aged women; (2) estimate the relative odds of adverse cardiovascular (CV) outcomes among women by smoking status; (3) assess whether the association between adverse pregnancy outcomes (APOs) and CV outcomes varies by smoking status. STUDY DESIGN: We conducted a cross-sectional study of the nuMoM2b Heart Health Study. Women attended a study visit 2 to 7 years after their first pregnancy. The exposure was smoking status, determined by self-report and by serum cotinine. Outcomes included incident chronic hypertension (HTN), metabolic syndrome (MetS), and dyslipidemia. Multivariable logistic regression estimated odds ratios (ORs) for each outcome by smoking status. RESULTS: Of 4,392 women with serum cotinine measured, 3,610 were categorized as nonsmokers, 62 as secondhand smoke exposure, and 720 as smokers. Of 3,144 women who denied tobacco smoke exposure, serum cotinine was consistent with secondhand smoke exposure in 48 (1.5%) and current smoking in 131 (4.2%) After adjustment for APOs, smoking defined by serum cotinine was associated with MetS (adjusted OR [aOR] = 1.52, 95% confidence interval [CI]: 1.21, 1.91) and dyslipidemia (aOR = 1.28, 95% CI: 1.01, 1.62). When stratified by nicotine exposure, nonsmokers with an APO in their index pregnancy had higher odds of stage 1 (aOR = 1.64, 95% CI: 1.32, 2.03) and stage 2 HTN (aOR = 2.92, 95% CI: 2.17, 3.93), MetS (aOR = 1.76, 95% CI: 1.42, 2.18), and dyslipidemia (aOR = 1.55, 95% CI: 1.25, 1.91) relative to women with no APO. Results were similar when smoking exposure was defined by self-report. CONCLUSION: Whether determined by serum cotinine or self-report, smoking is associated with subsequent CV outcomes in reproductive-aged women. APOs are also independently associated with CV outcomes in women. KEY POINTS: · Cotinine was detected in 5.7% of reported nonsmokers.. · Smoking and APOs were independently associated with CV health.. · Smoking was associated with MetS and dyslipidemia..

Multilevel Intervention for Low-Income Maternal Smokers in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

Objectives. To test the efficacy of Babies Living Safe and Smokefree (BLiSS), a multilevel intervention initiated in a citywide safety net health system to improve low-income maternal smokers' abstinence and reduce child tobacco smoke exposure. Methods. This randomized controlled trial in Philadelphia, Pennsylvania (2015-2020), recruited low-income maternal smokers who received a brief smoking intervention (Ask, Advise, Refer [AAR]) from nutrition professionals in the Special Supplemental Nutrition Program for Women, Infants, and Children before randomization to (1) a multilevel intervention (AAR + multimodal behavioral intervention [MBI]; n = 199) or (2) an attention control intervention (AAR + control; n = 197). Results. AAR + MBI mothers had significantly higher 12-month bioverified abstinence rates than did AAR + control mothers (odds ratio [OR] = 9.55; 95% confidence interval [CI] = 1.54, 59.30; P = .015). There were significant effects of time (b = -0.15; SE = 0.04; P < .001) and condition by time (b = -0.19; SE = 0.06; P < .001) on reported child exposure favoring AAR + MBI, but no group difference in child cotinine. Presence of other residential smokers was related to higher exposure. Higher baseline nicotine dependence was related to higher child exposure and lower abstinence likelihood at follow-up. Conclusions. The multilevel BLiSS intervention was acceptable and efficacious in a population that experiences elevated challenges with cessation. Public Health Implications. BLiSS is a translatable intervention model that can successfully improve efforts to address the persistent tobacco-related burdens in low-income communities. Trial Registration. Clinical Trials.gov identifier: NCT02602288. (Am J Public Health. 2022;112(3):472-481. https://doi.org/10.2105/AJPH.2021.306601).

Application of HPLC-QQQ-MS/MS and New RP-HPLC-DAD System Utilizing the Chaotropic Effect for Determination of Nicotine and Its Major Metabolites Cotinine, and trans-3'-Hydroxycotinine in Human Plasma Samples.

The routine techniques currently applied for the determination of nicotine and its major metabolites, cotinine, and trans-3'-hydroxycotinine, in biological fluids, include spectrophotometric, immunoassays, and chromatographic techniques. The aim of this study was to develop, and compare two new chromatographic methods high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS), and RP-HPLC enriched with chaotropic additives, which would allow reliable confirmation of tobacco smoke exposure in toxicological and epidemiological studies. The concentrations of analytes were determined in human plasma as the sample matrix. The methods were compared in terms of the linearity, accuracy, repeatability, detection and quantification limits (LOD and LOQ), and recovery. The obtained validation parameters met the ICH requirements for both proposed procedures. However, the limits of detection (LOD) were much better for HPLC-QQQ-MS/MS (0.07 ng mL-1 for trans-3'-hydroxcotinine; 0.02 ng mL-1 for cotinine; 0.04 ng mL-1 for nicotine) in comparison to the RP-HPLC-DAD enriched with chaotropic additives (1.47 ng mL-1 for trans-3'-hydroxcotinine; 1.59 ng mL-1 for cotinine; 1.50 ng mL-1 for nicotine). The extraction efficiency (%) was concentration-dependent and ranged between 96.66% and 99.39% for RP-HPLC-DAD and 76.8% to 96.4% for HPLC-QQQ-MS/MS. The usefulness of the elaborated analytical methods was checked on the example of the analysis of a blood sample taken from a tobacco smoker. The nicotine, cotinine, and trans-3'-hydroxycotinine contents in the smoker's plasma quantified by the RP-HPLC-DAD method differed from the values measured by the HPLC-QQQ-MS/MS. However, the relative errors of measurements were smaller than 10% (6.80%, 6.72%, 2.04% respectively).

Trans-placental transfer of nicotine: Modulation by organic cation transporters.

Nicotine is a highly addictive substance and harmful to the developing foetus. However, few studies have investigated the transporter mechanism responsible for regulating the transfer of nicotine across the blood-placental interface. A multiple in-vivo microdialysis system coupled to ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed to monitor simultaneously nicotine and cotinine in the blood, placenta, foetus, and amniotic fluid of pregnant rats. The pharmacological mechanism of nicotine transfer across the placenta was investigated by co-administering corticosterone, an inhibitor of organic cation transporters (OCTs) that partly mediate the exchange of nicotine across the placenta. The results revealed that intravenously administered nicotine (1 mg/kg) was rapidly metabolised to cotinine with a transformation ratio (AUCcotinine/AUCnicotine) of 0.67 ± 0.08, 0.21 ± 0.05, 0.25 ± 0.12, 0.31 ± 0.05 in maternal blood, placenta, amniotic fluid, and foetus, respectively. The tissue transformation ratios (AUCtissue/AUCblood) were 0.83 ± 0.16, 0.65 ± 0.17, 0.57 ± 0.13 for nicotine, and 0.25 ± 0.06, 0.24 ± 0.12, 0.26 ± 0.04 for cotinine at placenta, amniotic fluid and foetus, respectively. Following the co-administration of corticosterone (2 mg/kg), the tissue transformation ratio of nicotine was significantly reduced in the placenta but was significantly increased in the foetus. Levels of cotinine were not significantly altered by the administration of corticosterone. These findings implicate OCT in mediating the transfer of nicotine across the blood-placenta barrier. Understanding the mechanism of nicotine transfer through the placenta may inform therapeutic strategies to lessen the exposure of the developing foetus to nicotine in the maternal bloodstream.

Smoking cessation reduces systemic inflammation and circulating endothelin-1.

Smoking increases systemic inflammation and circulating endothelin-1 (ET-1), both of which contribute to an elevated risk of cardiovascular disease (CVD). The present study sought to test the hypothesis that a 12-week smoking cessation intervention would contribute to a long-term reduction in circulating ET-1, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). 30 individuals participated in a 12-week evidence-based smoking cessation program at Augusta University. Serum cotinine, plasma inflammatory cytokines, and plasma ET-1 were determined at baseline, immediately after the 12-week cessation program (end of treatment, EOT), and 12-months (12M) following the cessation program. Serum cotinine was significantly reduced (p < 0.001) at EOT and 12M following the smoking cessation program. Compared to BL (7.0 ± 1.6 pg/mL), TNF-α was significantly reduced at EOT (6.3 ± 1.5 pg/mL, p = 0.001) and 12M (5.2 ± 2.7 pg/mL, p < 0.001). ET-1 was significantly lower at EOT (1.9 ± 0.6 pg/mL, p = 0.013) and at 12M (2.0 ± 0.8 pg/mL, p = 0.091) following smoking cessation compared with BL (2.3 ± 0.6 pg/mL). BL concentrations of cotinine were significantly associated with basal ET-1 (r = 0.449, p = 0.013) and the change in cotinine at 12M following smoking cessation was significantly associated with the change in plasma ET-1 at 12M (r = 0.457, p = 0.011). Findings from the present pilot investigation demonstrate that a 12-week smoking cessation program reduces circulating concentrations of ET-1 and TNF-α for at least a year. The reduction in serum cotinine was associated with the decrease in circulating ET-1. The attenuation in ET-1 and inflammation may in part, contribute to the lower risk of CVD that is observed with smoking cessation.

Association between early gestation passive smoke exposure and neonatal size among self-reported non-smoking women by race/ethnicity: A cohort study.

Understanding implications of passive smoke exposure during pregnancy is an important public health issue under the Developmental Origins of Health and Disease paradigm. In a prospective cohort of low-risk non-smoking pregnant women (NICHD Fetal Growth Studies-Singletons, 2009-2013, N = 2055), the association between first trimester passive smoke exposure and neonatal size was assessed by race/ethnicity. Plasma biomarker concentrations (cotinine, nicotine) assessed passive smoke exposure. Neonatal anthropometric measures included weight, 8 non-skeletal, and 2 skeletal measures. Linear regression evaluated associations between continuous biomarker concentrations and neonatal anthropometric measures by race/ethnicity. Cotinine concentrations were low and the percent above limit of quantification varied by maternal race/ethnicity (10% Whites; 14% Asians; 15% Hispanics; 49% Blacks). The association between cotinine concentration and infant weight differed by race/ethnicity (Pinteraction = 0.034); compared to women of the same race/ethnicity, per 1 log-unit increase in cotinine, weight increased 48g (95%CI -44, 139) in White and 51g (95%CI -81, 183) in Hispanic women, but decreased -90g (95%CI -490, 309) in Asian and -93g (95%CI -151, -35) in Black women. Consistent racial/ethnic differences and patterns were found for associations between biomarker concentrations and multiple non-skeletal measures for White and Black women (Pinteraction<0.1). Among Black women, an inverse association between cotinine concentration and head circumference was observed (-0.20g; 95%CI -0.38, -0.02). Associations between plasma cotinine concentration and neonatal size differed by maternal race/ethnicity, with increasing concentrations associated with decreasing infant size among Black women, who had the greatest biomarker concentrations. Public health campaigns should advocate for reducing pregnancy exposure, particularly for vulnerable populations.

Tobacco smoke exposure and fractional exhaled nitric oxide levels among U.S. adolescents.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) can objectively guide clinical practice in the assessment, diagnosis, and treatment of eosinophilic airway inflammation. FeNO values may be affected by current smoking, but the role of tobacco smoke exposure (TSE) is understudied. OBJECTIVE: This study investigated the associations between biochemically validated and self-reported TSE and FeNO levels among U.S. nonsmoking adolescents without asthma. METHODS: National Health and Nutrition Examination Survey 2007-2012 data were used. TSE was assessed via serum cotinine and self-reported measures. We assessed FeNO continuously and using cutpoints of >35 ppb and >50 ppb to indicate likely eosinophilic inflammation in children and adults, respectively. We conducted linear and logistic regression adjusting for potential covariates. RESULTS: Overall, 34.0% of adolescents had low cotinine (0.05-2.99 ng/ml), 6.2% had high cotinine (≥3.00 ng/ml), and 11.9% had home TSE. Compared to adolescents with no/minimal cotinine, adolescents with high cotinine were at reduced odds to have FeNO >35 ppb (adjusted odds ratio [aOR] = 0.54, 95%CI = 0.43,0.69). Adolescents with low cotinine had lower FeNO values (ß = -2.05, 95%CI = -3.61,-0.49), and were also at decreased odds to have FeNO >35 ppb (aOR = 0.74, 95%CI = 0.66,0.83) and FeNO >50 ppb (aOR = 0.62, 95%CI = 0.53,0.72). Adolescents with home TSE were at reduced odds to have FeNO >50 ppb (aOR = 0.72, 95%CI = 0.57,0.91) than adolescents without home TSE. Adolescents with a higher number of cigarettes/day smoked inside their home were at reduced odds to have FeNO >35 ppb (OR = 0.98, 95%CI = 0.97,0.99) and FeNO >50 ppb (OR = 0.98, 95%CI = 0.96,0.99). CONCLUSIONS: TSE was associated with decreased FeNO levels. The addition of TSE may be clinically important when interpreting thresholds for FeNO.

Rapid, sensitive, and reliable quantitation of nicotine and its main metabolites cotinine and trans-3'-hydroxycotinine by LC-MS/MS: Method development and validation for human plasma.

New nicotine delivery products are gaining market share. For evaluation of their characteristics, toxicokinetic investigations are in current research focus. For reliable determination of blood plasma levels of nicotine and its main metabolites cotinine and trans-3'-hydroxycotinine, a quantitation method based on LC-ESI-MS/MS was developed and validated. Addition of isotope labeled internal standards prior to rapid sample preparation using protein precipitation with methanol was chosen for sample preparation. Different stationary phases were tested and phenyl-hexyl separation was found to be superior to HILIC, C18, and C8 stationary phases. Ion suppression effects caused by hydrophilic early eluting matrix were eliminated by the adjustment of an adequate retention utilizing a phenyl-hexyl separation stationary phase. Exchange of acetonitrile as organic mobile phase by methanol and elevation of pH value of aqueous mobile phase containing 5 mM NH4Ac to 4.50 improved the chromatographic resolution. The limits of quantitation for nicotine, cotinine, and hydroxycotinine were 0.15, 0.30, and 0.40 ng/mL, respectively. Linearity was proven by matrix matched calibration for the whole working range from 0.50 ng/mL to 35.0 ng/mL for nicotine and from 6.00 to 420 ng/mL for cotinine and hydroxycotinine (Mandel's fitting test with R2 > 0.995). Quality control samples at four different levels (0.50, 1.50, 17.5, 28.0 ng/mL for nicotine and 6.00, 18.0, 210, 336 ng/mL for cotinine and hydroxycotinine) in plasma were analyzed six times on three days. Mean accuracies ranged from 87.7% to 105.8% for nicotine, from 90.3% to 102.9% for cotinine, and from 99.9% to 109.9% for hydroxycotinine. Intra- and inter-day precisions (RSD %) were below 15% for all analytes (<20% for LLOQ). As proof of concept, the method was successfully applied to a real plasma sample from a cigarette smoking volunteer.

Serum levels of TGF-ß1, cytokines, angiogenic, and anti-angiogenic factors in pregnant women who smoke.

INTRODUCTION: Women who smoke during pregnancy have a reduced risk of preeclampsia. The mechanism of this association is poorly understood. Preeclampsia is an anti-angiogenic and inflammatory state. Transforming growth factor beta 1 (TGF-ß1) is a multi-functional anti-inflammatory cytokine that activates membrane bound endoglin on endothelial cells causing a myriad of vascular actions including vasorelaxation. The objective of the study was to determine serum levels of cytokines, angiogenic factors, placental growth factor (PlGF), TGF-ß-1 and anti-angiogenic factors, soluble endoglin (sEng) and soluble vascular endothelial growth factor 1 (sVEGFR1) in smoking and non-smoking pregnant women. METHODS: Using enzyme-linked immunosorbent and multiplex assays we prospectively analyzed serum levels of PIGF, TGF-ß1, sEng, sVEGFR1 and cytokines in normotensive pregnant smokers and non-smokers. Exclusion criteria included maternal hypertension, autoimmune disorders, rupture of membranes, evidence of labor and drug use. RESULTS: There were 59 women in the smoking and 66 in the non-smoking group. Compared to non-smoking mothers. maternal age was lower in smoking mothers with no significant difference in other demographic variables. There was no difference in levels of cytokines, anti-angiogenic factors and PlGF between the two groups. Median TGF-ß1 levels were significantly higher in the smoking group (8120 pg/mL vs 6040 pg/mL, p < 0.001) and remained significant after controlling for confounders. TGF-ß1 levels correlated positively with cotinine levels in the smoking group. CONCLUSIONS: We speculate that higher TGF-ß1 levels may explain the reduced incidence of preeclampsia in mothers who smoke by being available for action on maternal endothelium even after inactivation by circulating maternal sEng.

Blood lead levels and lung cancer mortality: An updated analysis of NHANES II and III.

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, Ptrend = 0.07; NHANES III: HR 11.2, 95% CI 2.1, 59.4 for ≥10.0 µg/dl vs. <2.5 µg/dl, Ptrend = 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.

Enhanced lung inflammatory response in whole-body compared to nose-only cigarette smoke-exposed mice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by a progressive and abnormal inflammatory response in the lungs, mainly caused by cigarette smoking. Animal models exposed to cigarette smoke (CS) are used to mimic human COPD but the use of different CS protocols makes it difficult to compare the immunological and structural consequences of using a nose-only or whole-body CS exposure system. We hypothesized that when using a standardized CS exposure protocol based on particle density and CO (carbon monoxide) levels, the whole-body CS exposure system would generate a more severe inflammatory response than the nose-only system, due to possible sensitization by uptake of CS-components through the skin or via grooming. METHODS: In this study focusing on early COPD, mice were exposed twice daily 5 days a week to CS either with a nose-only or whole-body exposure system for 14 weeks to assess lung function, remodeling and inflammation. RESULTS: At sacrifice, serum cotinine levels were significantly higher in the whole-body (5.3 (2.3-6.9) ng/ml) compared to the nose-only ((2.0 (1.8-2.5) ng/ml) exposure system and controls (1.0 (0.9-1.0) ng/ml). Both CS exposure systems induced a similar degree of lung function impairment, while inflammation was more severe in whole body exposure system. Slightly more bronchial epithelial damage, mucus and airspace enlargement were observed with the nose-only exposure system. More lymphocytes were present in the bronchoalveolar lavage (BAL) and lymph nodes of the whole-body exposure system while enhanced IgA and IgG production was found in BAL and to a lesser extent in serum with the nose-only exposure system. CONCLUSION: The current standardized CS-exposure protocol resulted in a higher internal load of serum cotinine in the whole-body exposure system, which was associated with more inflammation. However, both exposure systems resulted in a similar lung function impairment. Data also highlighted differences between the two models in terms of lung inflammation and remodelling, and potential sensitization to CS. Researchers should be aware of these differences when designing their future studies for an early intervention in COPD.

Racial disparities in intensity of smoke exposure and nicotine intake among low-dependence smokers.

BACKGROUND: Compared to white smokers, Black smokers are at disproportionately higher risk for smoking-related disease, despite consuming fewer cigarettes per day (CPD). To examine racial disparities in biobehavioral influences on smoking and disease risk, we analyzed the relationship between self-reported tobacco dependence and intensity of tobacco smoke exposure per cigarette, on the one hand, and intensity of nicotine intake per cigarette, on the other. METHODS: In 270 Black and 516 white smokers, smoke exposure was measured by expired carbon monoxide (CO), and nicotine intake was measured by plasma cotinine (COT) and cotinine+3'-hydroxycotinine ([COT + 3HC]). Using linear regression analyses, we analyzed how the Fagerström Test for Cigarette Dependence (FTCD) predicted intensity of smoke exposure per cigarette (CO/CPD) and intensity of nicotine intake per cigarette (COT/CPD; [COT + 3HC]/CPD), and how race moderated these relations. RESULTS: Overall, Black smokers consumed fewer CPD than white smokers and had higher levels of CO/CPD, COT/CPD, and [COT + 3HC]/CPD. These elevations were most pronounced at lower levels of dependence: amongst Black smokers, FTCD negatively predicted intensity of smoke exposure as measured by CO/CPD (B = -0.12, 95% CI = -0.18, -0.05, p = 0.0003) and intensity of nicotine intake as measured by [COT + 3HC]/CPD (B = -1.31, 95% CI = -2.15, -0.46, p = 0.002). CONCLUSIONS: Low-dependence Black smokers had higher intensities of both smoke exposure and nicotine intake per cigarette compared to similarly dependent white smokers, suggesting that measures of dependence, exposure, and intake underestimate incremental risk of each cigarette to Black smokers.

Nicotine e-cigarette vapor inhalation and self-administration in a rodent model: Sex- and nicotine delivery-specific effects on metabolism and behavior.

E-cigarettes, which deliver vaporized nicotine, have dramatically risen in popularity in recent years, despite many unanswered questions about safety, efficacy in reducing dependence, and overall impact on public health. Other factors, such as sex, also play an important role in determining behavioral and neurochemical responses to drugs of abuse. In these studies, we sought to develop a protocol for vaporized e-cigarette nicotine self-administration in rats, as a foundation to better understand the differing effects of nicotine exposure routes on behavior and physiological function. We report a novel method that elicits robust nicotine vapor self-administration in male and female rats. Our findings indicate that 5-mg/ml nicotine vape solution provides a high level of consistency in lever-pressing behavior for both males and females. Moreover, in male rats, we find that such e-cigarette nicotine vapor induces similar blood levels of nicotine's main metabolite, cotinine, as that found with intravenous nicotine self-administration. Therefore, the breathing pattern during vapor exposure in males leads to similar levels of titrated nicotine intake as with intravenous nicotine self-administration. Interestingly, a differential effect was found in the females, in which the same conditions of vapor exposure led to decreased cotinine levels with vapor compared to intravenous self-administration. Finally, differences in nicotine-mediated locomotion provide further support of the physiological effects of e-cigarette vapor inhalation. Taken together, our findings reveal important sex differences in nicotine intake based on the route of exposure, and we further establish a protocol for nicotine vapor self-administration in rats.

Analysis of Active and Passive Tobacco Exposures and Blood Pressure in US Children and Adolescents.

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.

Secondhand Smoke Exposure Among Nonsmoking Adults: United States, 2015-2018.

Secondhand smoke (SHS) exposure results when smoke from burning tobacco products is inhaled by nonsmokers (1,2). Acute respiratory effects, coronary heart disease, stroke, lung cancer, and premature death are associated with SHS exposure (2,3). There is no risk-free level of SHS exposure (1). The prevalence of SHS exposure declined by 71.2% from 1988 to 2014 (4). This report examines the prevalence of SHS exposure among nonsmoking U.S. adults in 2015-2018 based on blood levels of cotinine, a metabolite of nicotine. Trends in SHS exposure are also presented.

Tobacco smoke exposure enhances reward sensitivity in male and female rats.

RATIONALE: Systemic administration of the tobacco smoke constituent nicotine stimulates brain reward function in rats. However, it is unknown if the inhalation of tobacco smoke affects brain reward function. OBJECTIVES: These experiments investigated if exposure to smoke from high-nicotine SPECTRUM research cigarettes increases reward function and affects the rewarding effects of nicotine in adult male and female Wistar rats. METHODS: Reward function after smoke or nicotine exposure was investigated using the intracranial self-stimulation (ICSS) procedure. A decrease in reward thresholds reflects an increase in reward function. In the first experiment, the rats were exposed to tobacco smoke for 40 min/day for 9 days, and the rewarding effects of nicotine (0.03-0.6 mg/kg) were investigated 3 weeks later. In the second experiment, the dose effects of tobacco smoke exposure (40-min sessions, 1-4 cigarettes burnt simultaneously) on reward function were investigated. RESULTS: Tobacco smoke exposure did not affect the nicotine-induced decrease in reward thresholds or response latencies in male and female rats. Smoke exposure lowered the brain reward thresholds to a similar degree in males and females and caused a greater decrease in latencies in females. There was a positive relationship between plasma nicotine and cotinine levels and the nicotine content of the SPECTRUM research cigarettes. Similar smoke exposure conditions led to higher plasma nicotine and cotinine levels in female than male rats. CONCLUSION: These findings indicate that tobacco smoke exposure enhances brain reward function but does not potentiate the rewarding effects of nicotine in male and female rats.

Short-term effects of nicotine gum on facial detection in healthy nonsmokers: a pilot randomized controlled trial.

Objective: The main purpose of this study was to investigate short-term effects of nicotine gum on facial detection. Methods: Fourteen participants (mean age = 26.8 years, SD = 2.5 years; eight males) were enrolled in this pilot randomized controlled trial of nicotine gum administration (placebo, 2-mg and 4-mg doses). The participants were instructed to detect the location of a face when it was presented in a face/nonface pair on the screen. A repeated multivariate analysis of variance was conducted to analyze the results for reaction time and discrimination index. Demographics were used to explore significant association on facial detection. Bayesian analyses were also carried out considering maximum robustness to avoid bias. Results: The results indicated that the 2-mg dose resulted in faster reaction time and better discrimination than the 4-mg dose (p < 0.001). The 4-mg dose resulted in slower reaction time and lower discrimination index compared to both placebo (p < 0.01) and 2-mg doses (p < 0.001). Demographic data were not related to the outcomes. Conclusions: The results indicate that nicotine improved facial detection, but only at low doses (i.e., 2-mg), following a U-shaped curve. We trust future studies will continue to advance this research field, and if further work supports these preliminary findings, nicotine can act as therapeutic target in populations such as those with low vision.