The impact of vaping on adolescent lung function and nasal epithelial gene expression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1002332 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25420600_1.fastq.gz | Fastqsanger.gz | |||
| SRR25420600_2.fastq.gz | Fastqsanger.gz | |||
| SRR25420601_1.fastq.gz | Fastqsanger.gz | |||
| SRR25420601_2.fastq.gz | Fastqsanger.gz | |||
| SRR25420602_1.fastq.gz | Fastqsanger.gz |
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Project description:Electronic cigarette use (vaping) among adolescents is a pressing public health issue. We aimed to investigate the impact of vape use on lung function and nasal epithelial gene expression in adolescents. We hypothesized that vaping results in abnormal lung function and differential expression of inflammatory genes in the nasal epithelium of adolescent vape users in comparison to non-vape users. We assessed airflow obstruction with impulse oscillometry (IOS) and collected nasal epithelial brush samples for genome-wide gene expression and targeted DNA methylation analyses in middle and high school students in Colorado. Written informed consent was obtained from participants and Institutional Review Board approval was obtained. Vape users [mean age (standard deviation): 14.8 (1.4) years] reported vaping within the past 6 months while non-vape users [14.8 (1.4)] years did not report any vape use in the past 6 months. Mean airway resistance identified by the IOS R5 measure revealed that vape users (n=13) had higher values than non-vape users (n=37) [p=0.026]. Of 16,860 nasal epithelial genes tested, 7,136 were significantly differentially expressed between vape and non-vape users (false discovery rate (FDR) <0.05), after covariate adjustment. Enrichment analyses identified overexpression of inflammatory response genes and underexpression of ciliogenesis genes in vape users compared to non-vape users. DNA methylation analysis revealed that REXO1 (FDR=0.01) and CERK (FDR=0.06) were differentially methylated among vape users compared to non-vape users. Vaping during adolescence may increase airway resistance and dysresgulation of nasal epithelial genes, including genes involved in airway inflammation and ciliary function.
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Project description:Genome wide DNA methylation profiling of nasal-epithelial swabs collected from vaping and non-vaping (within 6 months) adolescents from Denver, Aurora, and Pueblo, CO . The Illumina Infinium Human Methylation 850K beadchip profiling microarray was used to obtain DNA methylation profiles across approximately 868,000 CpGs. Samples included 11 swabs from adolescents who had vaped in the last 6 months, and 37 who had not.
2024-07-05 | GSE240130 | GEO
Project description:The impact of vaping on adolescent lung function and nasal epithelial gene expression [RNA-seq]
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Project description:The impact of vaping on adolescent lung function and nasal epithelial gene expression [Genome wide DNA methylation]
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Project description:This SuperSeries is composed of the SubSeries listed below.
2024-07-05 | GSE240132 | GEO
Project description:Electronic cigarette use has increased dramatically over the past three years, despite numerous reports of acute lung injury and even death. In this report we provide evidence from a nonhuman primate model for Electronic Vapor-Induced Lung Injury (EVALI), demonstrating significant lung pathology from electronic vaping (EV). Here we characterized the particle size and pathogenic effects induced by EV exposure of nonhuman primates using the commercial nicotine JUUL® pod modular devices. Vaping aerosols appear to preferentially and exclusively target the bronchioles while bypassing larger bronchi. We demonstrate a significantly smaller particle size, generated by the EV device relative to combustion product aerosols produced by conventional cigarettes. Histopathologically, vaping aerosols appear to preferentially and exclusively target the bronchioles while bypassing larger bronchi which is consistent with a significanlty smaller particle size compared to cigarette smoke. Our immunohistochemical and RNAseq studies provide further evidence for severe small airway inflammation and dysregulation of gene expression within immune cells derived from bronchial lavage, respectively. Our findings raise major concerns regarding the safety of e-cigarettes, and provide a mechanism for the preferential induction of lung injury by EV. Our results, in a species whose lung architecture is the closest possible approximation of that of a human adolescent, suggest the danger of the EV device itself and resultant small particulate aerosols produced, preferentially entering and damaging a highly susceptible part of the respiratory system.
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Project description:In vitro toxicology approaches have evolved, from a focus on the molecular changes within a cell to understanding of toxicity-related mechanisms that simulate the in vivo environment. The recent development of three dimensional (3-D) organotypic nasal epithelial culture models offer a physiologically robust system for studying the effects of exposure through inhalation. Exposure to cigarette smoke (CS) is associated with nasal inflammation; thus the nasal epithelium is relevant for evaluating the pathophysiological impact of CS exposure. The present study investigated further the relevancy and application of in vitro human 3-D nasal epithelial culture models for toxicological assessment of inhalation exposure. The biological impact was assessed following exposure to aerosol generated from a candidate modified risk tobacco product (MRTP), the Tobacco Heating System (THS) 2.2, as compared with smoke generated from reference cigarette 3R4F using an in vitro human 3-D nasal epithelial cultures. A series of experimental repetitions where multiple doses of the aerosol and smoke were applied, were conducted to obtain reproducible measurements and reliable observations to understand the cellular/molecular changes that occur following exposure. Aligned with the 3Rs Strategy and the Vision-and-Strategy of the Toxicity Testing in the 21st Century, this study implemented a systems toxicology approach and found that for all tested concentrations, the impact of 3R4F smoke was considerably greater than that of THS2.2 aerosol in terms of cytotoxicity levels, alterations in the tissue morphology, secretion of pro-inflammatory mediators, impaired ciliary function, and increased perturbed transcriptomes and miRNA expression profiles. In addition, to evaluate further the possible adverse effects of THS2.2 aerosol, a dose range assessment was conducted. A broader range of THS2.2 concentrations were exposed to the nasal cultures. Various dilutions of THS2.2 were applied to the cultures using the Vitrocell® 24/48 exposure system, corresponding to the concentrations of nicotine between 0.15 mg/L and 1.79 mg/L.
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Project description:Purpose: to determine the cardiac complications of vaping in adult (3 month old) and juvenile (3 week old) FVB mice. Methods: mice were exposed to filtered air or vape with or without nicotine for 4 hrs/day, 5 days/week for a total of 3 months time. RNA-seq. was conducted on RNA isolated from the left ventricle of mice from each group.
2021-12-25 | GSE183614 | GEO
Project description:The nasal epithelium represents the first line of defense against inhaled pathogens, allergens, and irritants and plays a key role in the pathogenesis of a spectrum of acute and chronic airways diseases. Despite age-dependent clinical phenotypes triggered by these noxious stimuli, little is known about how ageing affects the structure and function of the airway epithelium that is crucial for lung homeostasis and host defense. The aim of this study was therefore to determine age-related differences in structural and functional properties of primary nasal epithelial cultures from healthy children and non-smoking elderly people. To achieve this goal, highly differentiated nasal epithelial cultures were established from nasal brushes at air-liquid-interface and used to study epithelial cell type composition, mucin (MUC5AC and MUC5B) expression and ion transport properties. Further, we determined age-dependent molecular signatures using global proteomic analysis. We found lower numeric densities of ciliated cells and higher levels of MUC5AC expression in cultures from children vs. elderly people. Bioelectric studies showed no differences in basal ion transport properties, ENaC-mediated sodium absorption or CFTR-mediated chloride transport, but detected decreased calcium-activated TMEM16A-mediated chloride secretory responses in cultures from children vs. elderly people. Proteome analysis identified distinct age-dependent molecular signatures associated with ciliation and mucin biosynthesis, as well as other pathways implicated in ageing. Our data identified intrinsic, age-related differences in structure and function of the nasal epithelium and provide a basis for further studies on the role of these findings in age-dependent airways disease phenotypes observed with a spectrum of respiratory infections and other noxious stimuli.
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Project description:To investigate how SMAD4 mutations associated with Myhre syndrome impact SMAD4 protein levels, activation and physiological functions in patient derived nasal epithelial cells. We derived primary nasal basal stem cells from inferior turbinate brushings of healthy subjects and Myhre syndrome patients (SMAD4-Ile500Val, Arg496Cys, Ile500Thr). After ALI differentiation, RNA was collected from healthy nasal basal epithelial cells and Myhre syndrome-epithelial cells to perform mRNA Deep sequencing. We then performed gene expression profiling analysis using data obtained from RNA-seq.
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