The impact of vaping aerosol exposure on innate pulmonary defense mechanisms in nonhuman primates

电子烟气溶胶暴露对非人灵长类动物先天肺防御机制的影响

• 批准号: 10428016
• 负责人: Robert Blair
• 金额: $ 20.05万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10428016
• 关键词: 2019-nCoV; Acute; Adolescent; Adolescent and Young Adult; Adoption; Aerosols; Affect; Alveolar; Alveolar Macrophages; Anatomy; Animal Model; Area; Autopsy; Biological Assay; Bronchiolitis; Bronchoalveolar Lavage Fluid; Cells; Centers for Disease Control and Prevention (U.S.); Centers of Research Excellence; Cessation of life; Chad; Clinical; Data; Defense Mechanisms; Defensins; Development Plans; Devices; Diffuse; Disease; Disease Outbreaks; Disease model; Dyspnea; Educational workshop; Ensure; Environment; Enzyme-Linked Immunosorbent Assay; Exposure to; Flow Cytometry; Foundations; Functional disorder; Funding; Funding Agency; Future; Goals; Grant; HIV; Hospitalization; Human; Immune; Immunohistochemistry; Immunology; Individual; Inflammation; Inflammatory; Innate Immune Response; Innate Immune System; Investigation; Lipids; Liquid substance; Lower respiratory tract structure; Lung; Lung immune response; Macaca mulatta; Mentors; Mentorship; Microscopic; Modeling; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; National Institute of Drug Abuse; Onset of illness; Pathogenesis; Pathogenicity; Pathologic; Patients; Phagocytes; Phagocytosis; Phenotype; Physiology; Play; Pneumonia; Policies; Positioning Attribute; Primates; Privatization; Public Health; Pulmonary Inflammation; Pulmonary Pathology; Pulmonary function tests; Reporting; Research; Research Personnel; Resources; Respiratory Disease; Rodent Model; Role; SIV; Saline; Sampling; Study models; System; Terminal Bronchiole; Testing; Tetrahydrocannabinol; Time; Tissues; Toll-like receptors; Training; Trees; Tumor-infiltrating immune cells; United States National Institutes of Health; Vitamin E Acetate; Writing; aerosolized; airway inflammation; base; career; career development; chemokine; comorbidity; cytokine; electronic vape; improved; innate immune function; innate immune mechanisms; interest; liquid nicotine; macrophage; nonhuman primate; novel; pulmonary function; radiological imaging; receptor expression; response; skills; success; surfactant; targeted treatment; vaping; vaping associated lung injury; 2019-nCoV; Acute; Adolescent; Adolescent and Young Adult; Adoption; Aerosols; Affect; Alveolar; Alveolar Macrophages; Anatomy; Animal Model; Area; Autopsy; Biological Assay; Bronchiolitis; Bronchoalveolar Lavage Fluid; Cells; Centers for Disease Control and Prevention (U.S.); Centers of Research Excellence; Cessation of life; Chad; Clinical; Data; Defense Mechanisms; Defensins; Development Plans; Devices; Diffuse; Disease; Disease Outbreaks; Disease model; Dyspnea; Educational workshop; Ensure; Environment; Enzyme-Linked Immunosorbent Assay; Exposure to; Flow Cytometry; Foundations; Functional disorder; Funding; Funding Agency; Future; Goals; Grant; HIV; Hospitalization; Human; Immune; Immunohistochemistry; Immunology; Individual; Inflammation; Inflammatory; Innate Immune Response; Innate Immune System; Investigation; Lipids; Liquid substance; Lower respiratory tract structure; Lung; Lung immune response; Macaca mulatta; Mentors; Mentorship; Microscopic; Modeling; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; National Institute of Drug Abuse; Onset of illness; Pathogenesis; Pathogenicity; Pathologic; Patients; Phagocytes; Phagocytosis; Phenotype; Physiology; Play; Pneumonia; Policies; Positioning Attribute; Primates; Privatization; Public Health; Pulmonary Inflammation; Pulmonary Pathology; Pulmonary function tests; Reporting; Research; Research Personnel; Resources; Respiratory Disease; Rodent Model; Role; SIV; Saline; Sampling; Study models; System; Terminal Bronchiole; Testing; Tetrahydrocannabinol; Time; Tissues; Toll-like receptors; Training; Trees; Tumor-infiltrating immune cells; United States National Institutes of Health; Vitamin E Acetate; Writing; aerosolized; airway inflammation; base; career; career development; chemokine; comorbidity; cytokine; electronic vape; improved; innate immune function; innate immune mechanisms; interest; liquid nicotine; macrophage; nonhuman primate; novel; pulmonary function; radiological imaging; receptor expression; response; skills; success; surfactant; targeted treatment; vaping; vaping associated lung injury

PROJECT SUMMARY Vaping is a serious public health concern that was associated with outbreaks of hospitalizations and deaths in 2019. These outbreaks of electronic vaping associated lung injury (EVALI) coincided with increased use of electronic vaping devices by adolescents and young adults. The rapid disease onset of EVALI and the role of macrophages in its progression, support a role for the innate immune system in the pathogenesis of EVALI. Despite its rising use little is currently known about the effect of vaping on pulmonary immunology and physiology highlighting the need for animal models to better understand its effects. Small animal models have shown pathologic changes following exposure to vaping aerosols; however, they do not recapitulate the pathologic manifestations of EVALI reported in humans necessitating a more translatable animal model to investigate the pathogenesis of EVALI. Nonhuman primates (NHPs) are ideally suited for studying respiratory diseases in humans due to their similarity in both pulmonary anatomy and immunology which provide advantages over other animal models. Here, we aim to utilize a NHP model to investigate the impact of vaping aerosol exposure on innate pulmonary defense mechanisms. We will longitudinally assess pulmonary and innate immune function (immune cell infiltrates, alveolar macrophage phagocytosis, and secretion of cytokines, chemokines, and defense molecules) over a four-week period of daily vaping aerosol exposure. At the end of the study, correlation with pathologic changes will occur through rigorous postmortem examination and sampling of the upper and lower respiratory tract. The data generated from this study will inform on mechanisms by which vaping aerosols effect innate pulmonary defenses, an important area of investigation in this time of highly infectious respiratory diseases. Furthermore, this study will provide preliminary data for future investigations evaluating the contribution of individual constituents within the vaping liquid (nicotine, tetrahydrocannabinol, and vitamin E acetate); and vaping in the context of comorbid conditions (SARS-CoV-2 and HIV/SIV), areas of special interest supported by several funding agencies (NIDA, NHLBI, NIAID). This proposed study and Mentored Career Development Plan will be conducted at the Tulane National Primate Research Center under the guidance of Drs. Ronald Veazey and Chad Roy. The TNPRC has been a national resource and center of excellence for biomedical research using nonhuman primates for over 50 years. The TNPRC has a strong commitment to training and mentorship and provides support (financial and effort-based) to create a rich and diverse training environment for early-stage investigators. The TNPRC fully supports Dr. Blair in his career goal to develop into an independently funded private investigator working with NHP models to study diseases of major public health importance. The dedicated time and additional mentorship provided by this K01 will help Dr. Blair refine his grant writing and project management skills to ensure the success of his future R01 proposals.

项目摘要 烟是一个严重的公共卫生问题，与住院和死亡的爆发有关 2019年。这些电子蒸发相关的肺损伤的暴发（evali）与使用的使用增加相吻合 青少年和年轻人的电子蒸发设备。评估的快速疾病发作和 巨噬细胞在其进展中，支持先天免疫系统在评估发病机理中的作用。 尽管使用量增加了，目前对烟的影响对肺部免疫学和生理学的影响知之甚少。 强调需要动物模型更好地理解其影响。小动物模型已显示 暴露于气溶胶​​的病理变化；但是，它们不会概括病理学 人类报道的评估表现形式需要一个更可翻译的动物模型来研究 评估的发病机理。非人类灵长类动物（NHP）非常适合研究呼吸道疾病 人类由于它们在肺部解剖结构和免疫学方面的相似性，这比其他人具有优势 动物模型。在这里，我们旨在利用NHP模型来研究烟雾气体暴露对 先天肺防御机制。我们将纵向评估肺部和先天免疫功能 （免疫细胞浸润，肺泡巨噬细胞吞噬作用，细胞因子，趋化因子和分泌 防御分子）在每天的每日蒸气气雾剂暴露期间。在研究结束时，相关性 随着病理的变化，将通过严格的验尸检查和上部和 下呼吸道。这项研究产生的数据将告知蒸发气溶胶的机制 影响先天肺防御，这是在高度感染性呼吸的时候进行的重要调查领域 疾病。此外，这项研究将为未来的研究提供初步数据，以评估贡献 烟液（尼古丁，四氢大麻酚和维生素E乙酸）中的个体成分的；和 在合并条件（SARS-COV-2和HIV/SIV）的背景下进行烟，特别感兴趣的领域由 几个资金机构（NIDA，NHLBI，NIAID）。这项拟议的研究和指导的职业发展计划 将在Drs的指导下在图兰国家灵长类动物研究中心进行。罗纳德·韦兹（Ronald Veazey） 和乍得·罗伊。 TNPRC一直是国家资源和生物医学研究卓越中心 使用非人类灵长类动物超过50年。 TNPRC对培训和指导有坚定的承诺 并提供支持（基于财务和努力），以创造早期阶段丰富多样的培训环境 调查人员。 TNPRC完全支持布莱尔博士的职业生涯目标，以发展为独立资助的 使用NHP模型研究的私人研究人员研究了主要公共健康重要性的疾病。专用 该K01提供的时间和其他指导将帮助布莱尔博士完善他的赠款写作和项目 管理技能，以确保他未来的R01提案的成功。