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1. E-cigarette aerosol exposure of pulmonary surfactant impairs its surface tension reducing function

   https://doi.org/10.1371/journal.pone.0272475  

   Graham, Emma ; McCaig, Lynda ; Shui-Kei Lau, Gloria ; Tejura, Akash ; Cao, Anne ; Zuo, Yi Y. ; Veldhuizen, Ruud ( November 2022 , PLOS ONE)

   Jeyaseelan, Samithamby (Ed.)

   Introduction E-cigarette (EC) and vaping use continue to remain popular amongst teenage and young adult populations, despite several reports of vaping associated lung injury. One of the first compounds that EC aerosols comes into contact within the lungs during a deep inhalation is pulmonary surfactant. Impairment of surfactant’s critical surface tension reducing activity can contribute to lung dysfunction. Currently, information on how EC aerosols impacts pulmonary surfactant remains limited. We hypothesized that exposure to EC aerosol impairs the surface tension reducing ability of surfactant. Methods Bovine Lipid Extract Surfactant (BLES) was used as a model surfactant in a direct exposure syringe system. BLES (2ml) was placed in a syringe (30ml) attached to an EC. The generated aerosol was drawn into the syringe and then expelled, repeated 30 times. Biophysical analysis after exposure was completed using a constrained drop surfactometer (CDS). Results Minimum surface tensions increased significantly after exposure to the EC aerosol across 20 compression/expansion cycles. Mixing of non-aerosolized e-liquid did not result in significant changes. Variation in device used, addition of nicotine, or temperature of the aerosol had no additional effect. Two e-liquid flavours, menthol and red wedding, had further detrimental effects, resulting in significantly higher surface tension than the vehicle exposed BLES. Menthol exposed BLES has the highest minimum surface tensions across all 20 compression/expansion cycles. Alteration of surfactant properties through interaction with the produced aerosol was observed with a basic e-liquid vehicle, however additional compounds produced by added flavourings appeared to be able to increase inhibition. Conclusion EC aerosols alter surfactant function through increases in minimum surface tension. This impairment may contribute to lung dysfunction and susceptibility to further injury. 

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2. Intrauterine exposure to nicotine through maternal vaping disrupts embryonic lung and skeletal development via the Kcnj2 potassium channel

   https://doi.org/10.1016/j.ydbio.2023.06.002  

   Ozekin, Yunus H. ; Saal, Maxwell L. ; Pineda, Ricardo H. ; Moehn, Kayla ; Ordonez-Erives, Madison A. ; Delgado Figueroa, Maria F. ; Frazier, Caleb ; Korth, Kamryn M. ; Königshoff, Melanie ; Bates, Emily A. ; et al ( September 2023 , Developmental Biology)

   Smoking cigarettes during pregnancy is associated with adverse effects on infants including low birth weight, defective lung development, and skeletal abnormalities. Pregnant women are increasingly turning to vaping [use of electronic (e)-cigarettes] as a perceived safer alternative to cigarettes. However, nicotine disrupts fetal development, suggesting that like cigarette smoking, nicotine vaping may be detrimental to the fetus. To test the impact of maternal vaping on fetal lung and skeletal development in mice, pregnant dams were exposed to e-cigarette vapor throughout gestation. At embryonic day (E)18.5, vape exposed litter sizes were reduced and some embryos exhibited growth restriction compared to air exposed controls. Fetal lungs were collected for histology and whole transcriptome sequencing. Maternally nicotine vaped embryos exhibited histological and transcriptional changes consistent with impaired distal lung development. Embryonic lung gene expression changes mimicked transcriptional changes observed in adult mouse lungs exposed to cigarette smoke, suggesting that the developmental defects may be due to direct nicotine exposure. Fetal skeletons were analyzed for craniofacial and long bone lengths. Nicotine directly binds and inhibits the Kcnj2 potassium channel which is important for bone development. The length of the maxilla, palatal shelves, humerus, and femur were reduced in vaped embryos, which was further exacerbated by loss of one copy of the Kcnj2 gene. Nicotine vapor exposed Kcnj2KO/+ embryos also had significantly lower birth weights than unexposed animals of either genotype. Kcnj2 mutants had severely defective lungs with and without vape exposure, suggesting that potassium channels may be broadly involved in mediating the detrimental developmental effects of nicotine vaping. These data indicate that intrauterine nicotine exposure disrupts fetal lung and skeletal development likely through inhibition of Kcnj2. 

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3. In utero exposure to electronic-cigarette aerosols decreases lung fibrillar collagen content, increases Newtonian resistance and induces sex-specific molecular signatures in neonatal mice

   https://doi.org/10.1007/s43188-021-00103-3  

   Cahill, Kerin M. ; Gartia, Manas R. ; Sahu, Sushant ; Bergeron, Sarah R. ; Heffernan, Linda M. ; Paulsen, Daniel B. ; Penn, Arthur L. ; Noël, Alexandra ( April 2022 , Toxicological Research)

   Abstract Approximately 7% of pregnant women in the United States use electronic-cigarette (e-cig) devices during pregnancy. There is, however, no scientific evidence to support e-cig use as being ‘safe’ during pregnancy. Little is known about the effects of fetal exposures to e-cig aerosols on lung alveologenesis. In the present study, we tested the hypothesis that in utero exposure to e-cig aerosol impairs lung alveologenesis and pulmonary function in neonates. Pregnant BALB/c mice were exposed 2 h a day for 20 consecutive days during gestation to either filtered air or cinnamon-flavored e-cig aerosol (36 mg/mL of nicotine). Lung tissue was collected in offspring during lung alveologenesis on postnatal day (PND) 5 and PND11. Lung function was measured at PND11. Exposure to e-cig aerosol in utero led to a significant decrease in body weights at birth which was sustained through PND5. At PND5, in utero e-cig exposures dysregulated genes related to Wnt signaling and epigenetic modifications in both females (~ 120 genes) and males (40 genes). These alterations were accompanied by reduced lung fibrillar collagen content at PND5—a time point when collagen content is close to its peak to support alveoli formation. In utero exposure to e-cig aerosol also increased the Newtonian resistance of offspring at PND11, suggesting a narrowing of the conducting airways. At PND11, in females, transcriptomic dysregulation associated with epigenetic alterations was sustained (17 genes), while WNT signaling dysregulation was largely resolved (10 genes). In males, at PND11, the expression of only 4 genes associated with epigenetics was dysregulated, while 16 Wnt related-genes were altered. These data demonstrate that in utero exposures to cinnamon-flavored e-cig aerosols alter lung structure and function and induce sex-specific molecular signatures during lung alveologenesis in neonatal mice. This may reflect epigenetic programming affecting lung disease development later in life. 

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4. Smart Electronic Cigarettes with Built-in Aerosol Sensors

   https://doi.org/10.1109/SENSORS52175.2022.9967159  

   Jiang, Hao ( October 2022 , 2022 IEEE Sensors)

   This work introduces an emerging application of aerosol sensors integrated inside electronic cigarettes. Using the aerosol sensors, particle size distribution, aerosol temperature, and target chemicals of the generated aerosols are measured before the aerosol is inhaled by a user. When a hazardous aerosol is detected, the user will be warned immediately to stop vaping. With extensive sensor data collected from every puff, an electronic cigarette becomes a smart mobile device, capable of tracking and improving a user's vaping habits. Experimental results on a prototype are presented and have shown great promises towards minimizing the health risks of vaping. 

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5. Subtypes of Dual Users of Combustible and Electronic Cigarettes: Longitudinal Changes in Product Use and Dependence Symptomatology

   https://doi.org/10.1093/ntr/ntac151  

   Buu, Anne ; Tong, Zhaoxue ; Cai, Zhanrui ; Li, Runze ; Yang, James J. ; Jorenby, Douglas E. ; Piper, Megan E. ( June 2022 , Nicotine & Tobacco Research)

   Cross-sectional surveys found behavioral heterogeneity among dual users of combustible and electronic cigarettes. Yet, prior classification did not reflect dynamic interactions between cigarette and e-cigarette consumption, which may reveal changes in product-specific dependence. The contexts of dual use that could inform intervention were also understudied.

   This study conducted secondary analysis on 13 waves of data from 227 dual users who participated in a 2-year observational study. The k-means method for joint trajectories of cigarette and e-cigarette consumption was adopted to identify the subtypes of dual users. The time-varying effect model was used to characterize the subtype-specific trajectories of cigarette and e-cigarette dependence. The subtypes were also compared in terms of use contexts.

   The four clusters were identified: light dual users, predominant vapers, heavy dual users, and predominant smokers. Although heavy dual users and predominant smokers both smoked heavily at baseline, by maintaining vaping at the weekly to daily level the heavy dual users were able to considerably reduce cigarette use. Yet, the heavy dual users’ drop in cigarette dependence was not as dramatic as their drop in cigarette consumption. Predominant vapers appeared to engage in substitution, as they decreased their smoking and increased their e-cigarette dependence. They were also more likely to live in environments with smoking restrictions and report that their use of e-cigarettes reduced cigarette craving and smoking frequency.

   Environmental constraints can drive substitution behavior and the substitution behavior is able to be sustained if people find the substitute to be effective.

   This study characterizes subtypes of dual users based on the dynamic interactions between cigarette use and e-cigarette use as well as product-specific trajectories of dependence. The subtypes differ in not only sociodemographic characteristics but also contexts of cigarette and e-cigarette use. Higher motivation to use e-cigarettes to quit smoking and less permissive environment for smoking may promote substitution of cigarettes by e-cigarettes.

    

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