Predicting the pulmonary effects of long-term e-cigarette use: are the clouds clearing?

Commercially available since 2007, e-cigarettes are a popular electronic delivery device of ever-growing complexity. Given their increasing use by ex-smokers, smokers and never-smokers, it is important to evaluate evidence of their potential pulmonary effects and predict effects of long-term use, since there has been insufficient time to study a chronic user cohort. It is crucial to evaluate indicators of harm seen in cigarette use, and those potentially unique to e-cigarette exposure. Evaluation must also account for the vast variation in e-cigarette devices (now including at least five generations of devices) and exposure methods used in vivo and in vitro.Thus far, short-term use cohort studies, combined with in vivo and in vitro models, have been used to probe for the effects of e-cigarette exposure. The effects and mechanisms identified, including dysregulated inflammation and decreased pathogen resistance, show concerning overlaps with the established effects of cigarette smoke exposure. Additionally, research has identified a signature of dysregulated lipid processing, which is unique to e-cigarette exposure.This review will evaluate the evidence of pulmonary effects of, and driving mechanisms behind, e-cigarette exposure, which have been highlighted in emerging literature, and highlight the gaps in current knowledge. Such a summary allows understanding of the ongoing debate into e-cigarette regulation, as well as prediction and potential mitigation of future problems surrounding e-cigarette use.

Health Promotion Media Exposure and Student Compliance Toward Smoke-Free School Regulation In Sleman Yogyakarta

The number of adolescent smokers in Indonesia are increasing with the highest prevalence on age 15-19. Implementation of smoke-free schools (SFS) aims to reduce adolescent smokers and protect school residents from cigarette smoke exposure. Public Senior High School 1 Cangkringan, Sleman has declared a SFS since 2019 by providing health promotion media such as posters and stickers in the school area. This study describes the implementation of SFS and to determine the relationship between health promotion media exposure and student compliance toward SFS regulations using quantitative methods with a cross-sectional design. Data collection was carried out through observation with checklists and online surveys with a google form. Sampling using accidental sampling method to 155 respondents and data analysis using SPSS version 17 with Chi-Square test. All respondents stated that the implementation of SFS is good and the results of observations showed that the input, process, and output indicators of SFS implementation had been fulfilled. Most of the students (83.2%) were exposed to high-level health promotion and 98,1% students obeyed the SFS regulations, There was a relationship between exposure to health promotion media in the form of posters with student compliance with SFS regulations ρ value ≤ α (0.004 ≤ 0.05). In conclusion, the high exposure to health promotion media has implications for the high compliance of students to SFS regulations.

Prenatal and Postnatal Cigarette Smoke Exposure Is Associated With Increased Risk of Exacerbated Allergic Airway Immune Responses: A Preclinical Mouse Model

Increased exposure to household air pollution and ambient air pollution has become one of the world’s major environmental health threats. In developing and developed countries, environmental cigarette smoke (CS) exposure is one of the main sources of household air pollution (HAP). Moreover, results from different epidemiological and experimental studies indicate that there is a strong association between HAP, specifically CS exposure, and the development of allergic diseases that often persists into later life. Here, we investigated the impact of prenatal and postnatal CS exposure on offspring susceptibility to the development of allergic airway responses by using a preclinical mouse model. Pregnant BALB/c mice were exposed to either CS or air during pregnancy and lactation and in order to induce allergic asthma the offspring were sensitized and challenged with house dust mite (HDM). Decreased lung function parameters, like dynamic compliance and pleural pressure, were observed in PBS-treated offspring born to CS-exposed mothers compared to offspring from air-exposed mothers. Maternal CS exposure significantly increased the HDM-induced airway eosinophilia and neutrophilia in the offspring. Prenatal and postnatal CS exposure increased the frequency of Th2 cells in the lungs of HDM-treated offspring compared to offspring born to air-exposed mothers. Offspring born to CS-exposed mothers showed increased levels of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid compared to offspring from air-exposed mothers. Ex-vivo restimulation of lung cells isolated from HDM-treated offspring born to CS-exposed mothers also resulted in increased IL-4 production. Finally, serum immunoglobulins levels of HDM-specific IgE and HDM-specific IgG1 were significantly increased upon a HDM challenge in offspring born to CS-exposed mothers compared to offspring from air-exposed mothers. In summary, our results reveal a biological plausibility for the epidemiological studies indicating that prenatal and postnatal CS exposure increases the susceptibility of offspring to allergic immune responses.

Effects of Cigarette Smoke Exposure on Placental Global DNA Methylation and 8-hydroxy-2’-deoxyguanosine Levels in Mother-new-born Binomials

Background: Smoking is practiced worldwide for both men and women, and it is associated with different diseases and deleterious effects on gestational products, chiefly during pregnancy. Epigenetic alterations induced by cigarette smoke must be related to perinatal abnormalities. Methods: 219 pregnant women, aged 16 to 34 years, with or without a history of cigarette consumption (1–5/day) during the first trimester of pregnancy and their offspring were studied in this work. A validated dietary questionnaire was used to estimate daily consumptions of macronutrients and micronutrients, including total energy, during pregnancy. As a marker of DNA damage, 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels were determined in plasma of women, before delivery, in umbilical cord blood after delivery, in the new-borns. The proportion of methylated DNA in the placentas (metDNA) was determined by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Results: Non-significant differences were observed between smoking and non-smoking women groups, or between the new-borns groups (p > 0.05). Smoking women showed up higher intakes of vitamins, lipids, proteins, and carbohydrates in comparison with non-smoking women (p < 0.01). 8-OHdG levels correlated among the mothers and new-borns (p = 5.386e-15) and were lower in the smoking binomials in comparison with non-smoking binomials (β = −1.20 to −64). Negative correlations were found between micronutrients and macronutrients but Vitamin C, and 8-OHdG levels of the women (p < 0.01). However, the new-borns 8-OHdG correlated with proteins, vitamin A, and vitamin B12 (p < 0.05). Cigarettes consumed per day correlated to the 8-8HdG levels (Rho = −0.247, p = 0.012), alcohol consumption (Rho = 0.219, p = 0.001), to macronutrients (Rho = 212 to 332, p < 0.01), micronutrients (Rho = 186 to 289, p < 0.01), and to energy (Rho = 0.286, p = 0.001). Finally, metDNA deceased in the smoking women than in the non-smoking women (β = −0.12, p < 0.05), and correlated with the number of cigarettes consumed per day (Rho = −0.229, p = 0.009). Conclusion: Cigarette smoking alters metDNA levels of the placenta, however, their clinical effects come out over years or transgenerationally.

Evaluation of a novel CFTR potentiator in copd ferrets with acquired cftr dysfunction

Rationale.The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been tested in vivo, given limitations to rodent models of COPD. Ferrets exhibit cystic fibrosis-related lung pathology when CFTR is absent and COPD with bronchitis following cigarette smoke exposure.Objectives.To evaluate CFTR dysfunction induced by smoking and test its pharmacologic reversal by a novel CFTR potentiator, GLPG2196, in a ferret model of COPD with chronic bronchitis.Methods.Ferrets were exposed for six months to cigarette smoke to induce COPD and chronic bronchitis and then treated with eneral GLPG2196 once daily for one month. Electrophysiologic measurements of ion transport and CFTR function, assessment of mucociliary function by one-micron optical coherence tomography imaging and particle tracking microrhelogy, microcomputed tomography imaging, histopathological analysis, and quantification of CFTR protein and mRNA expression were used to evaluate mechanistic and pathophysiological changes.Measurements and Main Results.Following cigarette smoke exposure, ferrets exhibited CFTR dysfunction, increased mucus viscosity, delayed mucociliary clearance, airway wall thickening, and airway epithelial hypertrophy. In COPD ferrets, GLPG2196 treatment reversed CFTR dysfunction, increased mucus transport by decreasing mucus viscosity, and reduced brochial wall thickening and airway epithelial hypertrophy.Conclusions.The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathologic features of chronic bronchitis in a COPD ferret model.

MicroRNASeq Target Analysis and Validation by Real-Time PCR in Abdominal Aortic Aneurysm

Background/ Objective: Abdominal aortic aneurysm (AAA) is an epigenetic event characterized by chronic inflammation and degeneration of the aortic wall leading to catastrophic rupture. Cigarette smoke exposure is the greatest environmental risk factor associated with AAA development. MicroRNAs (miRNA) regulate gene expression and may play a role in smoking-induced aortic inflammation. Epigenetic changes could include dysregulation of miRNA, causing post-transcriptional abnormalities pathogenic to AAA. Methods: miRNA was extracted from plasma of 24 AAA patients and 7 risk factor matched (RFM) patients and analyzed by RNA sequencing. We compared previous (PS) and current smokers (CS) within and between both patient cohorts. Differential expression of miRNAs was analyzed by ANOVA (p≤ 0.05). Potential targets of significant differentially expressed miRNAs were predicted using cross-analysis of TargetScan and miRanda databases. Results: Analysis revealed 7 significantly different miRNAs between AAA CS and AAA PS and 6 significantly different miRNAs between RFM CS and RFM PS. Of greatest significance, hsa-miR-223-3p was significantly downregulated as an effect of smoking cessation in AAA PS compared to AAA CS (p=0.000263), while also showing clinically relevant expression levels. Target genes of hsa-miR-223-3p include pro-inflammatory factors IL-6, TNFα, TGFβ, and MCP-1. Speculatively, as tissue levels of miR-223 tend to inversely correlate with plasma levels, we could hypothesize that the observed plasma upregulation of hsa-miR-223-3p in AAA CS contributes to the pro-inflammatory microenvironment of aortic tissue. Conclusion: Cigarette smoke contributes to epigenetic changes impacting factors of immune regulation or inflammation, eventually leading to disease states such as AAA. Inflammatory-related hsa-miR-223-3p is upregulated in AAA CS, suggesting its potential role in the disease course. Implications: Upregulation of hsa-miR-223-3p in AAA CS offers a link between disease state and the number one environmental factor attributed to AAA. This signature miRNA could serve as a biomarker for AAA or as a potential therapy target.

The effect of Etlingera elatior J. flower on the pulmo histology of white rat (Rattus novergicus L.) after cigarette smoke exposure

Cigarette smoking is one of health issues that mainly harmed the lung due to its free radicals. Kecombrang (Etlingera elatior J.) is a medicinal plant known to have a high amount of antioxidant. This study aims to determine the effect of antioxidant in Etlingera elatior J. flower on the improvement of pulmonary histology of male white rats (Rattus novergicus L.) as the secondhand smoke (cigarette exposure). This research was conducted by experimental method with ethanol extract of Etlingera elatior J. flower and pulmonary organ of white male rats as the test materials. There were 25 white male rats that divided into 5 groups (Positive Control, Negative Control, P1: 30 mg/Kg, P2:60 mg/Kg, and P3:90 mg/Kg). The results were statistically analyzed using One Way ANOVA test and Duncan’s test. The results showed a decreased amount of damage at P1, P2 and P3 groups. The statistical analysis showed that Etlingera elatior J. flower extract had a significant effect (p <0.05) on the histological improvement in each group. Group P2 shows the lowest rate of damage that it can be concluded the most effective dose in repairing the damage to rat pulmonary histology due to exposure of cigarette smoke.