Heat or Burn? Impacts of intrauterine tobacco smoke and E-Cigarette vapor exposure on the offspring's health outcome

© 2018 by the authors. Maternal smoking during pregnancy leads to gestational complications and organ disorders in the offspring. As nicotine replacement therapy is often ineffective for smoking cessation, pregnant women turn to alternatives such as heat-not-burn tobacco and e-cigarettes. Recently, the popularly of e-cigarettes has been increasing especially among the youth and pregnant women, mainly due to the advertisements claiming their safety. This has even led to some clinicians recommending their use during pregnancy. E-cigarettes heat e-liquid to produce an aerosol (e-vapor), delivering flavorings and nicotine to the user. However, e-vapor also contains toxins such as formaldehyde along with heavy metals and carcinogenic nitrosamines. In addition, specific flavoring compounds such as diacetyl can be toxic themselves or decompose into toxic compounds such as benzaldehydes. These compounds can induce toxicity, inflammation and oxidative stress in the mothers and can accumulate in the developing fetus, affecting intrauterine development. Recent animal studies suggest that maternal e-vapor exposure during pregnancy could cause respiratory and neurological disorders in the offspring. This review will examine the available literature to shed light on the current understanding of this problem-to-be from lessons learned in animal models

Replacing smoking with vaping during pregnancy: Impacts on metabolic health in mice.

Smoking is a significant risk factor for the development of metabolic diseases. Due to social pressures to quit smoking, many pregnant women are vaping as an alternative nicotine source. However, the metabolic consequences of replacing tobacco cigarettes with e-cigarettes during pregnancy are unknown. Therefore, in the mothers and their offspring, we investigated the metabolic and hepatic impacts of replacing cigarette smoke with e-vapour during pregnancy. Female BALB/c mice were either air-exposed or cigarette smoke-exposed (SE) from six weeks before pregnancy until lactation. At mating, a subset of the SE mice were instead exposed to e-vapour. Markers of glucose and lipid metabolism were measured in the livers and plasma, from the mothers and their male offspring (13 weeks). In the SE mothers, plasma insulin levels were reduced, leading to downstream increases in hepatic gluconeogenesis and plasma non-esterified fatty acids (NEFA). In the e-vapour replacement mothers, these changes were not as significant. In the SE offspring, there was impaired glucose tolerance, and increased plasma NEFA and liver triglyceride concentrations. E-vapour replacement restored lipid homeostasis but did not improve glucose tolerance. Therefore, in a murine model, low dose e-cigarette replacement during pregnancy is less toxic than cigarette smoke

E-cigarettes damage the liver and alter nutrient metabolism in pregnant mice and their offspring.

Approximately 15% of pregnant women vape electronic cigarettes (e-cigarettes), exposing the fetus to a range of toxic compounds, including nicotine and by-products of e-cigarette liquid (e-liquid) pyrolysis. Owing to the recent emergence of these products, research mainly focuses on immediate users, and not on in utero exposure. Therefore, this study aimed to understand the impact of intrauterine e-cigarette vapor (e-vapor) exposure, with and without nicotine, on liver metabolic markers in the male offspring. E-vapor was generated using an e-cigarette filled with tobacco-flavored e-liquid (18 or 0 mg/mL nicotine). Female Balb/c mice were exposed to e-vapor for 6 weeks before mating, through gestation and lactation, without direct exposure to the offspring. Livers and plasma from dams and male offspring (13 weeks old) were examined. Exposure to nicotine-free e-vapor promoted metabolic changes and liver damage in both the dams and their offspring. Furthermore, exposure to nicotine-containing e-vapor did not cause liver damage but induced hepatic steatosis in the adult offspring. Therefore, maternal vaping is detrimental to both the dams and their offspring, with nicotine providing a potential protective effect

Total IgE Variability Is Associated with Future Asthma Exacerbations: A 1-Year Prospective Cohort Study.

BACKGROUND: Few prospective studies have investigated the relationship between IgE variability and risk for asthma exacerbations (AEs). OBJECTIVE: To explore the relationship between IgE variability and AEs. METHODS: Recruited patients with stable asthma underwent two serum total IgE tests within a month (at screening [baseline IgE] and at 1 month) to obtain the coefficient of variation (CV) of base 10 log-transformed IgE. Patients with IgE CV were divided into IgE CV-high and IgE CV-low cohorts based on the CV median and were observed within 12 months, during which the association between IgE variability and AEs was explored using a negative binomial regression model. RESULTS: The IgE CV levels obtained from 340 patients classified patients into two groups (n = 170 for the IgE CV-high and IgE CV-low groups, respectively) based on the serum total IgE CV median of 2.12% (quartiles 1 and 3: 0.98% and 3.91%, respectively). The IgE CV-high patients exhibited worse asthma control and lung function and more marked airway inflammation, and received more intensive medication use compared with IgE CV-low patients. The IgE CV-high patients exhibited increased rates of moderate-to-severe (adjusted rate ratio = 2.88; 95% confidence interval, 1.65-5.03; P < .001) and severe (adjusted rate ratio = 2.16; 95% confidence interval, 1.08-4.32; P = .029) AEs during the follow-up year compared with IgE CV-low patients. Furthermore, sputum IL-6 partially mediated the associations between IgE CV with moderate-to-severe and severe AEs. CONCLUSIONS: Variability in total serum IgE levels is an easily obtained and practical measure for predicting AEs. Future studies are needed to investigate whether IgE variability can be used to guide precision medicine in asthma

Modulation of neural regulators of energy homeostasis, and of inflammation, in the pups of mice exposed to e-cigarettes

© 2018 Background: Maternal smoking can lead to perturbations in central metabolic regulators such as neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) signalling components in offspring. With the growing interest in e-cigarettes as a tobacco replacement, this short report assessed central metabolic regulation in offspring of mouse dams exposed to e-cigarettes. We examined the impact of continuous use of e-cigarettes, and e-cigarette replacement of tobacco cigarettes during pregnancy. Supplementation of an antioxidant L-carnitine was also co-used with tobacco cigarette in the mother to determine whether the impact of maternal tobacco smoking was oxidative stress driven. Methods: Balb/c mice were exposed to either nicotine-containing (E-cig18) or nicotine-free (E-cig0) e-cigarette aerosols or tobacco smoke (SE) prior to mating and until their pups were weaned. After mating, two SE sub-groups were changed to E-cig18 exposure (Replacement), or supplementation L-carnitine while SE was continued. Male offspring were studied at weaning age. Results: The offspring of E-cig0 dams were the heaviest with the most body fat. Replacing SE with E-cig18 during pregnancy resulted in offspring with significantly less body fat. E-cig0 offspring had significantly increased mRNA expression of brain NPY and iNOS. Maternal SE upregulated mRNA expression of NPY, NPY Y1 receptor, POMC downstream components, and iNOS expression, which were normalised in Replacement offspring, but only partially normalised with maternal L-carnitine supplementation during gestation and lactation. Conclusions: Maternal exposure to either tobacco and nicotine-free e-cigarettes lead to disturbances in the level of central homeostatic control markers in offspring, suggesting that maternal exposure to e-cigarettes is not without risks

Seasonal differences in the photochemistry of the South Pacific: A comparison of observations and model results from PEM-Tropics A and B

A time-dependent photochemical box model is used to examine the photochemistry of the equatorial and southern subtropical Pacific troposphere with aircraft data obtained during two distinct seasons: the Pacific Exploratory Mission-Tropics A (PEM-Tropics A) field campaign in September and October of 1996 and the Pacific Exploratory Mission-Tropics B (PEM-Tropics B) campaign in March and April of 1999. Model-predicted values were compared to observations for selected species (e.g., NO2, OH, HO2) with generally good agreement. Predicted values of HO2 were larger than those observed in the upper troposphere, in contrast to previous studies which show a general underprediction of HO2 at upper altitudes. Some characteristics of the budgets of HOx, NOx, and peroxides are discussed. The integrated net tendency for O3 is negative over the remote Pacific during both seasons, with gross formation equal to no more than half of the gross destruction. This suggests that a continual supply of O3 into the Pacific region throughout the year must exist in order to maintain O3 levels. Integrated net tendencies for equatorial O3 showed a seasonality, with a net loss of 1.06×1011 molecules cm-2 s-1 during PEM-Tropics B (March) increasing by 50% to 1.60×1011 molecules cm-2 s-1 during PEM-Tropics A (September). The seasonality over the southern subtropical Pacific was somewhat lower, with losses of 1.21×1011 molecules cm-2 s-1 during PEM-Tropics B (March) increasing by 25% to 1.51×1011 molecules cm-2 s-1 during PEM-Tropics A (September). While the larger net losses during PEM-Tropics A were primarily driven by higher concentrations of O3, the ability of the subtropical atmosphere to destroy O3 was ∼30% less effective during the PEM-Tropics A (September) campaign due to a drier atmosphere and higher overhead O3 column amounts. Copyright 2001 by the American Geophysical Union

Maternal E-cigarette exposure in mice alters DNA methylation and lung cytokine expression in offspring

Copyright © 2018 by the American Thoracic Society E-cigarette usage is increasing, especially among the young, with both the general population and physicians perceiving them as a safe alternative to tobacco smoking. Worryingly, e-cigarettes are commonly used by pregnant women. As nicotine is known to adversely affect children in utero, we hypothesized that nicotine delivered via e-cigarettes would negatively affect lung development. To test this, we developed a mouse model of maternal e-vapor (nicotine and nicotine-free) exposure and investigated the impact on the growth and lung inflammation in both offspring and mothers. Female Balb/c mice were exposed to e-fluid vapor containing nicotine (18 mg/ml nicotine E-cigarette [E-cig18], equivalent to two cigarettes per treatment, twice daily,) or nicotine free (E-cig0 mg/ml) from 6 weeks before mating until pups weaned. Male offspring were studied at Postnatal Day (P) 1, P20, and at 13 weeks. The mothers were studied when the pups weaned. In the mothers' lungs, e-cigarette exposure with and without nicotine increased the proinflammatory cytokines IL-1b, IL-6, and TNF-a. In adult offspring, TNF-a protein levels were increased in both E-cig18 and E-cig0 groups, whereas IL-1b was suppressed. This was accompanied by global changes in DNA methylation. In this study, we found that e-cigarette exposure during pregnancy adversely affected maternal and offspring lung health. As this occurred with both nicotine-free and nicotine-containing e-vapor, the effects are likely due to by-products of vaporization rather than nicotine

An assessment of western North Pacific ozone photochemistry based on springtime observations from NASA's PEM-West B (1994) and TRACE-P (2001) field studies

The current study provides a comparison of the photochemical environments for two NASA field studies focused on the western North Pacific (PEM-West-B (PWB) and TRACE-P (TP)). These two studies were separated in calendar time by approximately 7 years. Both studies were carried out under springtime conditions, with PWB being launched in 1994 and TP being deployed in 2001 (i.e., 23 February - 15 March 1994 and 10 March-15 April 2001, respectively). Because of the 7-year time separation, these two studies presented a unique scientific opportunity to assess whether evidence could be found to support the Department of Energy\u27s projections in 1997 that increases in anthropogenic emissions from East Asia could reach 5%/yr. Such projections would lead one to the conclusion that a significant shift in the atmospheric photochemical properties of the western North Pacific would occur. To the contrary, the findings from this study support the most recent emission inventory data [Streets et al., 2003] in that they show no significant systematic trend involving increases in any O3 precursor species and no evidence for a significant shift in the level of photochemical activity over the western North Pacific. This conclusion was reached in spite of there being real differences in the concentration levels of some species as well as differences in photochemical activity between PWB and TP. However, nearly all of these differences were shown to be a result of a near 3-week shift in TP\u27s sampling window relative to PWB, thus placing it later in the spring season. The photochemical enhancements seen during TP were most noticeable for latitudes in the range of 25-45°N. Most important among these were increases in J(O1D), OH, and HO2 and values for photochemical ozone formation and destruction, all of which were typically two times larger than those calculated for PWB. A comparison of these airborne results with ozonesonde data from four Japanese stations provided further evidence showing that the 3-week shift in the respective sampling windows of PWB and TP was a likely cause for the differences seen in O3 levels and in photochemical activity between the two airborne studies. Copyright 2003 by the American Geophysical Union

Impact of maternal e-cigarette vapor exposure on renal health in the offspring

© 2019 New York Academy of Sciences. Maternal smoking during pregnancy is a significant risk factor of renal pathology in the offspring. E-cigarettes are perceived to be a safe option and are increasingly used by pregnant women either continuously during pregnancy or as a replacement for tobacco cigarettes. This study aimed to determine the effects of replacing tobacco cigarettes with e-cigarettes during pregnancy, and continuous e-cigarette use during pregnancy on the offspring's kidneys. Female Balb/c mice were exposed to either air (sham) or tobacco cigarette smoke (SE) for 6 weeks prior to mating, during gestation and lactation. A subset of the “SE group” received e-cigarette vapor (containing nicotine) after mating until pups weaned. Additional female mice were continuously exposed to e-vapor (either with or without nicotine) for 6 weeks prior to mating until pups weaned. Kidneys and urine from the male offspring were assessed at postnatal day 1, day 20 (weaning), and 13 weeks of age (adulthood). E-cigarette replacement was less detrimental to renal development and albuminuria than continuous SE during pregnancy. However, continuous e-vapor exposure during pregnancy increased markers of oxidative stress, inflammation, and fibrosis in the adult offspring, independent of nicotine. E-cigarette use during pregnancy confers future risk to the offspring's kidneys

Small Airway Dysfunction in Asthma Is Associated with Perceived Respiratory Symptoms, Non-Type 2 Airway Inflammation, and Poor Responses to Therapy.

BACKGROUND: Emerging evidence has indicated that small airway dysfunction (SAD) contributes to the clinical expression of asthma. OBJECTIVES: The aim of the study was to explore the relationships of SAD assessed by forced expiratory flow between 25 and 75% (FEF25-75%), with clinical and inflammatory profile and treatment responsiveness in asthma. METHOD: In study I, dyspnea intensity (Borg scale), chest tightness, wheezing and cough (visual analog scales, VASs), and pre- and post-methacholine challenge testing (MCT) were analyzed in asthma patients with SAD and non-SAD. In study II, asthma subjects with SAD and non-SAD underwent sputum induction, and inflammatory mediators in sputum were detected. Asthma patients with SAD and non-SAD receiving fixed treatments were prospectively followed up for 4 weeks in study III. Spirometry, Asthma Control Questionnaire (ACQ), and Asthma Control Test (ACT) were carried out to define treatment responsiveness. RESULTS: SAD subjects had more elevated ΔVAS for dyspnea (p = 0.027) and chest tightness (p = 0.032) after MCT. Asthma patients with SAD had significantly elevated interferon (IFN)-γ in sputum (p < 0.05), and Spearman partial correlation found FEF25-75% significantly related to IFN-γ and interleukin-8 (both having p < 0.05). Furthermore, multivariable regression analysis indicated SAD was significantly associated with worse treatment responses (decrease in ACQ ≥0.5 and increase in ACT ≥3) (p = 0.022 and p = 0.032). CONCLUSIONS: This study indicates that SAD in asthma predisposes patients to greater dyspnea intensity and chest tightness during bronchoconstriction. SAD patients with asthma are characterized by non-type 2 inflammation that may account for poor responsiveness to therapy