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.

令人信服的新数据表明电子烟对肺部有毒。事实上，目前已有 700 多个 电子烟使用者因急性肺损伤而住院的病例。对这种伤害的原因知之甚少并且 虽然许多住院的电子烟用户表示他们使用了稀释在维生素 E 油中的 THC，但许多人并没有这样做。我们 之前从健康的不吸烟者、吸烟者或电子烟使用者那里收集了血清、唾液和痰液。我们也 进行了研究支气管镜检查并收集支气管肺泡灌洗液（BALF）。从这些样本中， 我们的小组发现了支气管和分泌蛋白质组的独特变化。我们还发现电子烟增加了 已知会导致肺气肿和支气管扩张的肺蛋白酶水平。我们的初步数据表明 电子烟使用者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， 更大的 M1/促炎表型和基因表达的显着下调。此外，我们的新 数据表明，电子烟使用者的巨噬细胞细胞内空泡数量增多，这可能是由于 通过脂质积累。由于我们看到电子烟使用者的肺部样本发生了广泛而显着的变化，尽管 它们是“健康的”，我们建议它们是理想的生物库数据集，可用于评估健康程度 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 保密证书，我们还了解任何潜在的药物用途。我们最近开发了检测方法 检测电子烟使用者 BALF 和痰液中的尼古丁，我们还建议开发我们的分析技术，以便 检测这些样本中的 THC 及其代谢物，我们将关联肺巨噬细胞/脂质的任何变化 与肺尼古丁和 THC 水平有关。为了实现这些目标，我们提出以下具体目标： 目标 1. 确定 BAL、痰生物库样本中表面活性蛋白的浓度 以及非吸烟者、吸烟者和电子烟使用者的唾液。 目标 2. 进行脂质组学并用油红 O 染色肺泡巨噬细胞以寻找改变的脂质 电子烟使用者巨噬细胞和气道分泌物中的含量。 目标 3. 对非吸烟者的 BAL、痰液和唾液生物库样本进行代谢组学分析， 吸烟者和电子烟使用者。 这些研究将使用来自 CTP 资助的研究 (P50 HL120100) 的生物库肺部样本。我们相信，这 该提案响应了 FDA 的以下关注领域：（i）检查各种健康结果 烟草产品类型，不包括香烟； (ii) 检查对健康的长期和短期影响 从可燃烟草过渡到不可燃烟草，以及从不可燃烟草过渡到可燃烟草， 使用生物标志物和/或健康结果； (iii) 将生物标志物表达谱与自我报告的使用情况进行比较 烟草产品，并分析与可能告知风险的暴露生物标志物相关的措施 与年龄、性别和种族/民族的烟草暴露相关的死亡率/发病率。