Longitudinal association between e-cigarette use and respiratory symptoms among US adults: Findings from the Population Assessment of Tobacco and Health Study Waves 4-5.

BACKGROUND: We assessed longitudinal effects of e-cigarette use on respiratory symptoms in a nationally representative sample of US adults by combustible tobacco smoking status. METHODS: We analyzed Waves 4-5 public-use data from the Population Assessment of Tobacco and Health Study. Study sample included adult respondents who reported no diagnosis of respiratory diseases at Wave 4, and completed Waves 4-5 surveys with no missing data on analytic variables (N = 15,291). Outcome was a validated index of functionally important respiratory symptoms based on 7 wheezing/cough questions (range 0-9). An index score of ≥2 was defined as having important respiratory symptoms. Weighted lagged logistic regression models were performed to examine the association between e-cigarette use status at Wave 4 (former/current vs. never use) and important respiratory symptoms at Wave 5 by combustible tobacco smoking status (i.e., never/former/current smokers), adjusting for Wave 4 respiratory symptom index, sociodemographic characteristics, secondhand smoke exposure, body mass index, and chronic disease. RESULTS: Among current combustible tobacco smokers, e-cigarette use was associated with increased odds of reporting important respiratory symptoms (former e-cigarette use: adjusted odds ratio [AOR] = 1.39, 95% confidence interval [CI]: 1.07-1.81; current e-cigarette use: AOR = 1.55, 95% CI: 1.17-2.06). Among former combustible tobacco smokers, former e-cigarette use (AOR = 1.51, 95% CI: 1.06-2.15)-but not current e-cigarette use (AOR = 1.59, 95% CI: 0.91-2.78)-was associated with increased odds of important respiratory symptoms. Among never combustible tobacco smokers, no significant association was detected between e-cigarette use and important respiratory symptoms (former e-cigarette use: AOR = 1.62, 95% CI: 0.76-3.46; current e-cigarette use: AOR = 0.82, 95% CI: 0.27-2.56). CONCLUSIONS: The association between e-cigarette use and respiratory symptoms varied by combustible tobacco smoking status. Current combustible tobacco smokers who use e-cigarettes have an elevated risk of respiratory impairments.

Effects of chronic secondhand smoke exposure on cardiovascular regulation and the role of soluble epoxide hydrolase in mice.

Background: Secondhand smoke (SHS) is a significant risk factor for cardiovascular morbidity and mortality with an estimated 80% of SHS-related deaths attributed to cardiovascular causes. Public health measures and smoking bans have been successful both in reducing SHS exposure and improving cardiovascular outcomes in non-smokers. Soluble epoxide hydrolase (sEH) inhibitors have been shown to attenuate tobacco exposure-induced lung inflammatory responses, making them a promising target for mitigating SHS exposure-induced cardiovascular outcomes. Objectives: The objectives of this study were to determine 1) effects of environmentally relevant SHS exposure on cardiac autonomic function and blood pressure (BP) regulation and 2) whether prophylactic administration of an sEH inhibitor (TPPU) can reduce the adverse cardiovascular effects of SHS exposure. Methods: Male C57BL/6J mice (11 weeks old) implanted with BP/electrocardiogram (ECG) telemetry devices were exposed to filtered air or 3 mg/m3 of SHS (6 hr/d, 5 d/wk) for 12 weeks, followed by 4 weeks of recovery in filtered air. Some mice received TPPU in drinking water (15 mg/L) throughout SHS exposure. BP, heart rate (HR), HR variability (HRV), baroreflex sensitivity (BRS), and BP variability were determined monthly. Results: SHS exposure significantly decreased 1) short-term HRV by ∼20% (p < 0.05) within 4 weeks; 2) overall HRV with maximum effect at 12 weeks (-15%, p < 0.05); 3) pulse pressure (-8%, p < 0.05) as early as week 4; and 4) BRS with maximum effect at 12 weeks (-11%, p < 0.05). Four weeks of recovery following 12 weeks of SHS ameliorated all SHS-induced cardiovascular detriments. Importantly, mice exposed to TPPU in drinking water during SHS-related exposure were protected from SHS cardiovascular consequences. Discussion: The data suggest that 1) environmental relevant SHS exposure significantly alters cardiac autonomic function and BP regulation; 2) cardiovascular consequences from SHS can be reversed by discontinuing SHS exposure; and 3) inhibiting sEH can prevent SHS-induced cardiovascular consequences.

Youth E-Cigarette Use and Functionally Important Respiratory Symptoms: The Population Assessment of Tobacco and Health (PATH) Study Waves 3 and 4.

Respiratory effects of e-cigarette use among youth are not fully understood. This study investigated the longitudinal association between e-cigarette use and a validated index of functionally important respiratory symptoms among US youth. Data from Waves 3-4 of the Population Assessment of Tobacco and Health Study were analyzed. The sample included youth (aged 12-17) without asthma at baseline (Wave 3), who completed a follow-up survey (Wave 4), and were not missing data for analytic variables (n = 3899). Exposure was e-cigarette use status (never, former, or current) at baseline. The outcome was a respiratory symptom index based on responses for seven wheezing items at Wave 4. An index of ≥2 was defined as having functionally important respiratory symptoms. Lagged logistic regression models examined the association between baseline e-cigarette use and functionally important respiratory symptoms at follow-up by combustible tobacco use status (never or ever), and controlling for baseline covariates. At baseline, 13.7% of participants reported former e-cigarette use, and 4.3% reported current use. Baseline e-cigarette use did not increase the odds of having functionally important respiratory symptoms at follow-up regardless of combustible tobacco use status. Future research on larger populations of e-cigarette users with longer follow-up periods will improve our understanding of the respiratory risks associated with e-cigarette use among youth.

Passive exposure to e-cigarette emissions is associated with worsened mental health.

BACKGROUND: Cigarette smoking, secondhand cigarette smoke (SHS) exposure, and e-cigarette use ("vaping") are each associated with increased rates of depressive symptoms and other internalizing mental health disorders. The prevalence of vaping has increased greatly, yet the mental health correlates of secondhand exposure to e-cigarette emissions are as yet to be investigated. This study examined the potential adverse mental health outcomes associated with different tobacco exposures (direct and passive), with a particular focus on the mental health correlates of secondhand exposure to e-cigarette emissions. METHODS: The Population Assessment of Tobacco and Health Study data collected from a sample of 16,173 Wave 4 adults were used to test the hypothesis that secondhand e-cigarette emissions exposure is associated with increased odds of internalizing mental health disorders. Individuals were categorized as exclusive cigarette smokers, exclusive e-cigarette users, cigarette and e-cigarette dual users, exclusive noncombustible tobacco users, secondhand smoke exposed non-users, secondhand e-cigarette emissions exposed non-users, and non-users with no current SHS/secondhand e-cigarette aerosol exposure. Adjusted weighted logistic regression analysis was used to investigate the association between exposure type and internalizing problems as assessed by scores on the Global Appraisal of Individual Needs-Short Screener (GAIN-SS), a widely used instrument for assessing mental health problems. RESULTS: Cigarette smokers (AOR = 2.53, 95% CI: 2.19-2.92), e-cigarette users (AOR = 3.14, 2.41-4.09), dual users (AOR = 3.37, 2.85-4.00), noncombustible tobacco users (AOR = 1.48, 1.01-2.17), SHS exposed non-users (AOR = 1.63, 1.37-1.94), and secondhand e-cigarette emissions exposed non-users (AOR = 1.43, 1.03-1.99) were each associated with increased odds of moderate to severe internalizing mental health problems as compared to unexposed non-users. Odds of internalizing problems among SHS and secondhand e-cigarette emissions exposed non-users did not differ (p = 0.46). CONCLUSIONS: This is the first study, to our knowledge, to identify an association between recent secondhand exposure to e-cigarette emissions and mental health problems, and the risk is comparable to that of SHS. Corroboration of this relationship needs further research to explicate directionality and mechanisms underlying this association.

Exhalation of alternative tobacco product aerosols differs from cigarette smoke-and may lead to alternative health risks.

BACKGROUND: Variation in alternative tobacco product (ATP) constituents, heating potential, and consumer behaviors have made it difficult to characterize their health risks. To date, most toxicity studies of ATPs have used established cigarette endpoints to inform study design. Furthermore, to assess where ATPs fall on the tobacco harm continuum, with cigarettes representing maximum potential risk, studies have tended to compare the relative biological responses to ATPs against those due to cigarettes. OBJECTIVES: 1) To characterize the exhalation profiles of two popular ATPs: electronic cigarettes (e-cigarettes) and hookah waterpipes (hookah) and 2) to determine if ATP exhalation patterns were representative of cigarette exhalation patterns. METHODS: Exhalation patterns were recorded (mouth only, nose only, or both mouth and nose) among individuals observed in the New York City tri-state area using a recognizable tobacco product (cigarette, e-cigarette, or hookah). Cigarette smokers and e-cigarette vapers were observed on city streets; water-pipe smokers were observed inside Manhattan hookah bars. RESULTS: E-cigarette vapers practiced exclusive nasal exhalation at far higher rates than did cigarette smokers (19.5% vs 4.9%). Among vapers, e-cigarette device type was also significantly associated with exhalation profile. Overall, cigarette smokers exhaled from their nose approximately half to one-third as often as ATP users (hookah and e-cigarettes, respectively). CONCLUSIONS: Nasal exhalation of tobacco emissions appears to be a shared characteristic across several types of ATPs. It is therefore plausible that ATP-specific consumer behaviors may foster unique upper respiratory health consequences that have not been observed in smokers. Thus, product-specific behaviors should inform the prioritization of biological endpoints used in studies evaluating ATP toxicity and health effects.

E-Cigarette Toxicology.

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic cigarette (e-cigarette) vaping has surpassed conventional cigarette smoking among adolescents and young adults in the United States and beyond. This review describes the experimental and clinical evidence of e-cigarette toxicity and deleterious health effects. Adverse health effects related to e-cigarette aerosols are influenced by several factors, including e-liquid components, physical device factors, chemical changes related to heating, and health of the e-cigarette user (e.g., asthmatic). Federal, state, and local regulations have attempted to govern e-cigarette flavors, manufacturing, distribution, and availability, particularly to underaged youths. However, the evolving e-cigarette landscape continues to impede timely toxicological studies and hinder progress made toward our understanding of the long-term health consequence of e-cigarettes.

Secondhand Smoke Decreased Excitability and Altered Action Potential Characteristics of Cardiac Vagal Neurons in Mice.

Background: Secondhand smoke (SHS), a major indoor pollutant, is a significant risk factor for cardiovascular morbidity and mortality including arrhythmias and sudden cardiac death. Exposure to SHS can produce autonomic imbalance, as evidenced by reduced heart rate variability (HRV)-a clinical metric of cardiac vagal regulation. Currently, the mechanisms through which SHS changes the vagal preganglionic neuronal inputs to the heart to produce this remains unknown. Objectives: To characterize the effect of SHS on both the excitability and action potential (AP) characteristics of anatomically identified cardiac vagal neurons (CVNs) in the nucleus ambiguus and examine whether SHS alters small conductance calcium-activated potassium (SK) channel activity of these CVNs. Methods: Adult male mice were exposed to four weeks of filtered air or SHS (3 mg/m3) 6 h/day, 5 day/week. Using patch-clamp recordings on identified CVNs in brainstem slices, we determined neuronal excitability and AP characteristics with depolarizing step- and ramp-current injections. Results: Four weeks of SHS exposure reduced spiking responses to depolarizing current injections and increased AP voltage threshold in CVNs. Perfusion with apamin (20 nM) magnified these SHS-induced effects, suggesting reduced SK channel activity may serve to minimize the SHS-induced decreases in CVNs excitability. Medium afterhyperpolarization (a measurement of SK channel activity) was smaller in the SHS group, further supporting a lower SK channel activity. AP amplitude, rise rate, fast afterhyperpolarization amplitude (a measurement of voltage-gated channel activity), and decay rate were higher in the SHS group at membrane voltages more positive to 0 mV, suggesting altered inactivation properties of voltage-dependent channels underlying APs. Discussion: SHS exposure reduced neuronal excitability of CVNs with compensatory attenuation of SK channel activity and altered AP characteristics. Neuroplasticity of CVNs could blunt regulatory cardiac vagal signaling and contribute to the cardiovascular consequences associated with SHS exposure, including reduced HRV.

E-Cigarette Use, Systemic Inflammation, and Depression.

BACKGROUND: E-cigarette use (vaping) is an emerging public health problem. Depression has been found to be associated with e-cigarette use, and vaping and depression are each associated with elevated systemic inflammation. To date, the role of inflammation in the relationship between vaping and depression has not been explored. OBJECTIVE: To assess the independent associations between e-cigarette use, depression, and inflammation, and to investigate whether the likelihood of depression among current e-cigarette users is associated with systemic inflammation. METHODS: Nationally representative NHANES data from 2015-2018 were used (n = 4961). Systemic inflammation was defined as serum C-reactive protein (CRP) ≥ 8.0 mg/L. Depressed individuals were characterized by a score ≥ 10 on the Patient Health Questionnaire-9 (PHQ-9). Current e-cigarette users were defined as individuals who vaped at least once in the past 30 days and these individuals were stratified by use: exclusive users (reported smoking less than 100 combustible cigarettes in their lifetime), dual users (reported current use of electronic and combustible cigarettes), and e-cigarette users who were previous smokers. Bivariate analyses were used to assess independent associations between vaping, depression, and inflammation; and weighted logistic regression analyses adjusting for BMI, sex, and economic status were used to determine the odds ratios (ORs) for depression by e-cigarette category stratified by differential CRP levels. RESULTS: Depression occurred in 16.7% of all e-cigarette users vs. 5.0% of those who never used e-cigarettes (p < 0.001). In adjusted analyses, the following elevated ORs were found: all current e-cigarette users with CRP <8 = 3.37 (95% CI: 2.06, 5.51) vs. CRP ≥8 = 6.70 (2.48, 18.11); exclusive e-cigarette users with CRP <8 = 1.91 (0.78, 4.69) vs. those with CRP ≥8 = 5.09 (1.44, 18.02); and dual users with CRP <8 = 4.31 (2.35, 7.89) vs. those with CRP ≥8 = 7.37 (1.85, 29.41). These ORs indicate that depression is associated with each category of e-cigarette use; however, we found this association did not vary by systemic inflammation level (interaction p-values > 0.05). CONCLUSION: While a pattern of greater ORs for depression among e-cigarette users with elevated CRP provides provocative findings that might suggest a potential role of inflammation in the association between vaping and depression, we failed to find evidence that inflammation clearly moderates this association. While it is possible that depression among e-cigarette users may be influenced by systemic inflammation, a reproduction of the current study is necessary among a larger cohort to elucidate the effect of inflammation on depression among e-cigarette users.

Secondhand Smoke Exposure Impairs Ion Channel Function and Contractility of Mesenteric Arteries.

Cigarette smoke, including secondhand smoke (SHS), has significant detrimental vascular effects, but its effects on myogenic tone of small resistance arteries and the underlying mechanisms are understudied. Although it is apparent that SHS contributes to endothelial dysfunction, much less is known about how this toxicant alters arterial myocyte contraction, leading to alterations in myogenic tone. The study's goal is to determine the effects of SHS on mesenteric arterial myocyte contractility and excitability. C57BL/6J male mice were randomly assigned to either filtered air (FA) or SHS (6 h/d, 5 d/wk) exposed groups for a 4, 8, or 12-weeks period. Third and fourth-order mesenteric arteries and arterial myocytes were acutely isolated and evaluated with pressure myography and patch clamp electrophysiology, respectively. Myogenic tone was found to be elevated in mesenteric arteries from mice exposed to SHS for 12 wk but not for 4 or 8 wk. These results were correlated with an increase in L-type Ca2+ channel activity in mesenteric arterial myocytes after 12 wk of SHS exposure. Moreover, 12 wk SHS exposed arterial myocytes have reduced total potassium channel current density, which correlates with a depolarized membrane potential (Vm). These results suggest that SHS exposure induces alterations in key ionic conductances that modulate arterial myocyte contractility and myogenic tone. Thus, chronic exposure to an environmentally relevant concentration of SHS impairs mesenteric arterial myocyte electrophysiology and myogenic tone, which may contribute to increased blood pressure and risks of developing vascular complications due to passive exposure to cigarette smoke.

The Use of Percent Change in RR Interval for Data Exclusion in Analyzing 24-h Time Domain Heart Rate Variability in Rodents.

While epidemiological data support the link between reduced heart rate variability (HRV) and a multitude of pathologies, the mechanisms underlying changes in HRV and disease progression are poorly understood. Even though we have numerous rodent models of disease for mechanistic studies, not being able to reliably measure HRV in conscious, freely moving rodents has hindered our ability to extrapolate the role of HRV in the progression from normal physiology to pathology. The sheer number of heart beats per day (>800,000 in mice) makes data exclusion both time consuming and daunting. We sought to evaluate an RR interval exclusion method based on percent (%) change of adjacent RR intervals. Two approaches were evaluated: % change from "either" and "both" adjacent RR intervals. The data exclusion method based on standard deviation (SD) was also evaluated for comparison. Receiver operating characteristic (ROC) curves were generated to determine the performance of each method. Results showed that exclusion based on % change from "either" adjacent RR intervals was the most accurate method in identifying normal and abnormal RR intervals, with an overall accuracy of 0.92-0.99. As the exclusion value increased (% change or SD), the sensitivity (correctly including normal RR intervals) increased exponentially while the specificity (correctly rejecting abnormal RR intervals) decreased linearly. Compared to the SD method, the "either" approach had a steeper rise in sensitivity and a more gradual decrease in specificity. The intersection of sensitivity and specificity where the exclusion criterion had the same accuracy in identifying normal and abnormal RR intervals was 10-20% change for the "either" approach and ∼ 1 SD for the SD-based exclusion method. Graphically (tachogram and Lorenz plot), 20% change from either adjacent RR interval resembled the data after manual exclusion. Finally, overall (SDNN) and short-term (rMSSD) indices of HRV generated using 20% change from "either" adjacent RR intervals as the exclusion criterion were closer to the manual exclusion method with lower subject-to-subject variability than those generated using the 2 SD exclusion criterion. Thus, 20% change from "either" adjacent RR intervals is a good criterion for data exclusion for reliable 24-h time domain HRV analysis in rodents.

Perinatal exposure of mice to the pesticide DDT impairs energy expenditure and metabolism in adult female offspring.

Dichlorodiphenyltrichloroethane (DDT) has been used extensively to control malaria, typhus, body lice and bubonic plague worldwide, until countries began restricting its use in the 1970s. Its use in malaria control continues in some countries according to recommendation by the World Health Organization. Individuals exposed to elevated levels of DDT and its metabolite dichlorodiphenyldichloroethylene (DDE) have an increased prevalence of diabetes and insulin resistance. Here we hypothesize that perinatal exposure to DDT disrupts metabolic programming leading to impaired metabolism in adult offspring. To test this, we administered DDT to C57BL/6J mice from gestational day 11.5 to postnatal day 5 and studied their metabolic phenotype at several ages up to nine months. Perinatal DDT exposure reduced core body temperature, impaired cold tolerance, decreased energy expenditure, and produced a transient early-life increase in body fat in female offspring. When challenged with a high fat diet for 12 weeks in adulthood, female offspring perinatally exposed to DDT developed glucose intolerance, hyperinsulinemia, dyslipidemia, and altered bile acid metabolism. Perinatal DDT exposure combined with high fat feeding in adulthood further impaired thermogenesis as evidenced by reductions in core temperature and in the expression of numerous RNA that promote thermogenesis and substrate utilization in the brown adipose tissue of adult female mice. These observations suggest that perinatal DDT exposure impairs thermogenesis and the metabolism of carbohydrates and lipids which may increase susceptibility to the metabolic syndrome in adult female offspring.

The impact of EDTA on the rate of accumulation and root/shoot partitioning of cadmium in mature dwarf sunflowers.

In addition to increasing the mobility of metal ions in the soil solution, chelating agents such as EDTA have been reported to alter both the total metal accumulated by plants and its distribution within the plant structures. Here, mature Mini-Sun Hybrid dwarf sunflowers exposed to 300 µM Cd(2+) in hydroponic solution had initial translocation rates of at least 0.12 mmol kg(-1)h(-1) and reached leaf saturation levels within a day when a 3-fold molar excess of EDTA was used. EDTA also promoted cadmium transfer from roots to the shoots. A threefold excess of EDTA increased the translocation factor (TF) 100-fold, resulting in cadmium levels in the leaves of 580 µg g(-1) and extracting 1400 µg plant(-1). When plants were exposed to dissolved cadmium without EDTA, the vast majority of the metal remained bound to the exterior of the root. The initial accumulation could be successfully modeled with a standard biosorption pseudo second-order kinetic equation. Initial accumulation rates ranged from 0.0359 to 0.262 mg g(-1)min(-1). The cadmium binding could be cycled, and did not show evidence of saturation under the experimental conditions employed, suggesting it might be a viable biosorbant for aqueous cadmium.

Bis[2,2'-(2-amino-ethyl-imino)-di(ethyl-ammonium)] di-µ-sulfido-bis[disulfido-stannate(IV)].

The asymmetric unit of the title compound, (C(6)H(20)N(4))(2)[Sn(2)S(6)], comprises half of a [Sn(2)S(6)](4-) anion and a diprotonated tris-(2-amino-eth-yl)amine cation. The anion lies on an inversion center, while the atoms of the cation occupy general positions. An intra-molecular N-H⋯N hydrogen bond is observed in the cation. In the crystal, strong N-H⋯S hydrogen bonding between the terminal sulfur atoms of the anion and the protonated amine N atoms of the cations result in a three-dimensional network.