Do E-Cigarette Users Airways Have an Altered Lipid Content?

电子烟使用者的呼吸道脂质含量是否发生改变？

• 批准号: 10220134
• 负责人: ROBERT TARRAN
• 金额: $ 23.33万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220134
• 关键词: Acute Lung Injury; Alveolar Macrophages; Area; Behavior; Biological Assay; Biological Markers; Bronchiectasis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cell secretion; Certificate of Confidentiality; Chemicals; Cigarette; Cotinine; Data; Data Set; Diagnosis; Down-Regulation; Drug usage; Electronic cigarette; Ethnic Origin; Foamy Macrophage; Funding; Gene Expression; Goals; Health; Heterogeneity; Histological Techniques; Hospitalization; Individual; Inflammatory; Injury; Intracellular Accumulation of Lipids; Lipid-Laden Macrophage; Lipids; Lung; Mass Spectrum Analysis; Measures; Morbidity - disease rate; Nicotine; Oils; Outcome; Pathogenicity; Patient Self-Report; Peptide Hydrolases; Phagocytosis; Pharmaceutical Preparations; Phenotype; Proteins; Proteome; Public Health; Pulmonary Emphysema; Race; Recording of previous events; Research; Risk; Saliva; Sampling; Serum; Smoker; Smoking; Sputum; Stains; THC exposure; Techniques; Tobacco smoking behavior; Tobacco use; United States National Institutes of Health; Vacuole; Vitamin E; Western Blotting; biobank; cigarette smoke; cohort; combustible tobacco; electronic cigarette use; electronic cigarette user; exposure to cigarette smoke; extracellular; interest; lipid metabolism; lipidomics; lung injury; macrophage; marijuana use; metabolomics; mortality; never smoker; nicotine exposure; non-smoker; sex; smoking cessation; surfactant; tobacco exposure; tobacco products; tobacco smokers; tool; vaper; vaping

Compelling new data suggests that e-cigarettes are toxic to the lungs. Indeed, there have now been over 700 hospitalization cases due to acute lung injury in vapers. The cause(s) of this injury are poorly understood and whilst many hospitalized vapers said that they have used THC diluted in Vitamin E oil, many did not. We previously collected serum, saliva and sputum from healthy never-smokers, tobacco smokers or vapers. We also performed research bronchoscopies and collected bronchoalveolar lavage fluid (BALF). From these samples, our group found unique changes to the bronchial and secreted proteomes. We also found that vaping increased levels of lung proteases that are known to cause emphysema and bronchiectasis. Our preliminary data indicate that vapers’ macrophages are phenotypically different to non-smokers’ and smokers’ macrophages, have a greater M1/pro-inflammatory phenotype and significant downregulation of gene expression. Moreover, our new data indicate that vapers’ macrophages have increased numbers of intracellular vacuoles, which may be caused by lipid accumulation. Since we see extensive and significant changes in the vaper’s lung samples, even though they are “healthy”, we propose that they are an ideal biobanked data set that can be used to assess the extent to which altered lung lipid content and lipid-laden/foamy macrophages exist. Importantly, since we obtained an NIH certificate of confidentiality, we also know about any potential drug use. We have recently developed assays to detect nicotine in vapers’ BALF and sputum and we also propose to develop our analytic techniques in order to detect THC and its metabolites in these samples, and we will correlate any changes in lung macrophages/lipids with lung nicotine and THC levels. To achieve these goals, we propose the following specific aims: Aim 1. To determine the concentrations of surfactant proteins in biobanked samples of BAL, sputum and saliva from non-smokers, smokers and vapers. Aim 2. To perform lipidomics and stain alveolar macrophages with Oil Red O to look for altered lipid content in vaper’s macrophages and airway secretions. Aim 3. To perform metabolomics on biobanked samples of BAL, sputum and saliva from non-smokers, smokers and vapers. These studies will use biobanked lung samples from a CTP-funded study (P50 HL120100). We believe that this proposal is responsive to the following FDA areas of interest: (i)Examine health outcomes from various tobacco product types, not to include cigarettes; (ii) Examine the long- and short-term health effects of transitioning from combustible to non-combustible tobacco, and from non-combustible to combustible tobacco, using biomarker and/or health outcomes; (iii) Compare biomarker expression profiles with self-reported use of tobacco products, and analyze measures associated with biomarkers of exposure that may inform risk associated with tobacco exposure for mortality/morbidity by age, sex, and race/ethnicity.

引人入胜的新数据表明，电子烟对肺有毒。确实，现在已经有700多个 由于蒸气中的急性肺损伤，住院病例。这种伤害的原因知之甚少， 许多住院的蒸气说，他们使用的是在维生素E油中稀释的THC，但许多人没有。我们 先前从健康的永不吸烟者，吸烟者或蒸气中收集的血清，唾液和痰。我们也是 进行了研究支气管镜检查并收集了支气管肺泡灌洗液（BALF）。从这些样品中， 我们的小组发现了支气管和分泌蛋白质组的独特变化。我们还发现烟气增加了 已知会导致肺气肿和支气管张的肺蛋白酶水平。我们指示的初步数据 vapers的巨噬细胞在表型上与非吸烟者和吸烟者的巨噬细胞不同，有一个 更大的M1/促炎表型和基因表达的显着下调。而且，我们的新人 数据表明蒸气巨噬细胞的细胞内液泡数量增加，这可能是引起的 通过脂质积累。由于我们看到Vaper的肺样本发生了很大变化，尽管 它们是“健康的”，我们建议它们是理想的生物群体数据集，可用于评估程度 存在改变的肺脂质含量和富含脂质/泡沫的巨噬细胞。重要的是，由于我们获得了 NIH信任证书，我们还知道任何潜在的药物使用。我们最近开发了测定 在Vapers的Balf和Putum中检测尼古丁，我们还建议开发我们的分析技术 在这些样品中检测THC及其代谢物，我们将相关 肺尼古丁和THC水平。为了实现这些目标，我们提出以下具体目标： 目标1。确定BAL，痰液生物群样品中生存蛋白的浓度 和非吸烟者，吸烟者和蒸气的唾液。 目标2。用油红O进行脂质组学和染色肺泡巨噬细胞以寻找改变的脂质 在Vaper的巨噬细胞和气道分泌物中的内容。 AIM 3。对非吸烟者的BAL，痰和唾液的生物群样品进行代谢组学， 吸烟者和蒸气。 这些研究将使用来自CTP资助的研究（P50 HL120100）的生物群体样品。我们相信这个 提案对以下FDA感兴趣的领域有反应：（i）检查各种健康状况 烟草产品类型，不包括公民； （ii）检查长期和短期健康影响 从混合到不燃烧的烟草，从不耐燃料的烟草过渡， 使用生物标志物和/或健康结果； （iii）将生物标志物表达曲线与自我报告的使用进行比较 烟草产品，并分析与暴露生物标志物相关的措施，这些措施可能会为风险提供依据 与年龄，性别和种族/种族的死亡率/发病率有关的烟草暴露有关。

项目成果

Early Studies of Respiratory Disease Associations with Nicotine and Tobacco Use.

• DOI: 10.1093/ntr/ntaa200
• 发表时间: 2020-12-15
• 期刊: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
• 作者: Stanton CA;Tarran R;Mermelstein R
• 通讯作者: Mermelstein R