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Electronic vaping preferentially target respiratory bronchioles leading to severe bronchiolitis in experimentally-exposed macaques

ABSTRACT: Electronic vaping preferentially target respiratory bronchioles leading to severe bronchiolitis in experimentally-exposed macaques

PROVIDER: PRJNA818290 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18397859.fastq.gz	Fastqsanger.gz
	SRR18397860.fastq.gz	Fastqsanger.gz
	SRR18397861.fastq.gz	Fastqsanger.gz
	SRR18397862.fastq.gz	Fastqsanger.gz

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Electronic vaping preferentially target respiratory bronchioles leading to severe bronchiolitis in experimentally-exposed macaques

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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The impact of vaping on adolescent lung function and nasal epithelial gene expression [RNA-seq]

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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microRNA expression of human periodontal ligament derived stem cell line exposed to 1 microMolar (uM) (-)-nicotine liquid or 1 uM nicotine electronic cigarette vapor extract against untreated control

Project description:Nicotine and cigarette smoking have been previously shown to inhibit the differentiation potential and miRNA expression of human periodontal ligament derived stem cells (PDLSCs). Electronic cigarette (EC) vapor also contains nicotine, as well as other non-nicotine compounds, and, like cigarette smoking, EC vaping results in similar routes of toxic exposure for PDLSCs. The effect of exposure on PDLSC miRNA expression is unknown. To determine these effects, cultured PDLSCs were exposed to media supplemented with 1 uM nicotine EC vapor extract for 72h, during which media was changed every 24h. To produce vapor extract, an EC filled with 36 mg/ml nicotine, 50%/50% (w/v) PG/VG, non-flavored e-liquid (American E-liquid) was vaped using an automated vaping robot programmed with experienced e-cigarette user patterns (i.e. puff volume: 70 ml, duration: 3s, frequency: 20s) and resulting vapor was extracted via a liquid impinger. 1 uM of pure (-)-nicotine liquid (Sigma Aldrich) was used as a positive control. Total miRNA was collected with the mirVana miRNA isolation kit. miRNA concentration and quality was measured by spectrophotometry and expression was analyzed with Affymetrix GeneChip miRNA 4.0 Arrays. Results were normalized against human-positive and negative chip controls using Robust Multi-Array Average Normalization.

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The impact of vaping on adolescent lung function and nasal epithelial gene expression [Genome wide DNA methylation]

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.

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