Effect of vaping on COVID-19 infection

电子烟对 COVID-19 感染的影响

• 批准号: 10176655
• 负责人: Carl W White
• 金额: $ 18.24万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176655
• 关键词: 2019-nCoV; ACE2; Acetaldehyde; Acrolein; Acute; Acute Lung Injury; Acute Renal Failure with Renal Papillary Necrosis; Address; Adult Respiratory Distress Syndrome; Affect; Aldehydes; American; Angiotensins; Animal Model; Anti-Inflammatory Agents; Asthma; Autopsy; Bacterial Pneumonia; Behavior; Behavioral; Binding; Blood Coagulation Disorders; Blood Vessels; Blood coagulation; COVID-19; COVID-19 pandemic; COVID-19 susceptibility; Camels; Cardiovascular Diseases; Cause of Death; Cell surface; Characteristics; Chemicals; Chronic Obstructive Airway Disease; Colorado; Computer software; Coronavirus; Critical Illness; Devices; Disease; Docking; Dromedaries; Electronic cigarette; Equilibrium; Event; Face; Ferrets; Flavoring; Formaldehyde; Gastrointestinal tract structure; Genetic; Goals; Hamsters; Histopathology; Human; Infection; Institution; K-18 conjugate; Laboratories; Lung; Lung diseases; Mediating; Medical; Mesocricetus auratus; Modeling; Modification; Monitor; Mouse Strains; Multiple Organ Failure; Mus; Nicotine; Nose; Oral cavity; Outcome; Particulate; Pathogenesis; Pathway interactions; Peptides; Pharmacology; Physiological; Pneumonia; Poison; Population; Process; Propylene Glycols; Proteins; Rattus; Renin-Angiotensin System; Research; Respiratory System; Rhabdomyolysis; Robot; Rodent; SARS coronavirus; SARS-CoV-2 infection; SARS-CoV-2 spike protein; Septic Shock; Severe Acute Respiratory Syndrome; Severities; Severity of illness; Site; Smoker; Smoking; Structure; Surface; Thrombosis; Tissues; Touch sensation; Toxicology; Transgenic Mice; United States National Institutes of Health; Universities; Vasoconstrictor Agents; Viral Load result; Viral Pneumonia; Virus; Yin-Yang; airway epithelium; biosafety level 3 facility; cardiovascular endothelium; cigarette smoking; combustible cigarette; computerized; cytokine release syndrome; effective therapy; electronic cigarette use; emerging pathogen; former smoker; infection rate; interest; intestinal epithelium; lung injury; medically underserved population; member; mortality; nonhuman primate; pollutant; programs; receptor; senior faculty; social; thrombotic; vaping; vaping nicotine; vegetable glycerin; virology

PROJECT SUMMARY In the COVID-19 pandemic, >1.5 million Americans have become ill, and over 100,000 have died. So far, medically underserved populations are more than twice as likely to die or develop critical illness relative to their proportion in the population. Current and former smokers are also more likely to develop critical COVID-19 and/or die. The basis for this could be social, behavioral and/or physiological. Recent findings show that smoking and nicotine may change the ‘docking site’ (ACE2) where the virus enters the airway epithelium. This study will explore the effect of vaping and nicotine in hamsters that are susceptible to COVID-19 to see if this changes their lung ACE2 expression and/or worsens their disease due to the SARS-CoV-2 virus. Vaping is a delivery device for the addicting, toxic and vasoactive compound nicotine. E-cigarette use, or dual use of traditional and e-cigarettes, has not been examined in the context of SARS-CoV-2 infection. Specifically, the effects of vaping and nicotine on COVID-19 lung disease severity, viral load, and ACE2/ACE expression at the message, protein and activity levels will be investigated. Thus, this model will be used to clarify the importance of vaping-induced lung injury on ACE2 expression and subsequent SARS2 infection and pathogenesis. To address these questions, we hypothesized that subacute and/or acute nicotine vaping could alter the ACE2/ACE activities and, potentially, lung histopathology in the hamster. Further, we postulated that acute/subacute vaping could increase SARS-CoV-2 infection and/or lung disease severity in the hamster. If true, pharmacologic modification of ACE2/ACE ratio in the vaping and/or nonvaping hamster could diminish SARS-CoV-2 infection severity. Two aims will be undertaken: 1) Define the effects of vaping nicotine on ACE2/ACE and lung histopathology in Syrian hamster, and 2)Define the effect of vaping on SARS-CoV-2 viral load, clearance, and COVID-19 lung disease in model(s) developed in Aim 1 APPROACH: We will use a newly acquired e-cigarette ‘vaping robot’ that is fully computerized and programmable using flexiWare software (inExpose, SCIREQ, Montreal) for nose-only delivery to rodents, and a recently described hamster model for SARS-CoV-2-mediated lung injury. The vaping exposures will be conducted at University of Colorado Anschutz Medical Campus (Denver), and, following brief transport, the COVID-19 model will be done at Colorado State University’s (CSU) BSL3 facility (Ft. Collins, CO). There we will monitor hamsters for up to 7 days, with studies of airway/lung histopathology and ACE2/ACE expression after necropsy. The project involves two laboratories with long-standing research interests: acute lung injury and toxicology, and virology and emerging pathogens, respectively. We will better understand mechanism(s) for worsening COVID-19 in smokers, and potentially new pathways to their more effective treatment.

项目概要 迄今为止，在 COVID-19 大流行中，已有超过 150 万美国人患病，超过 10 万人死亡。 医疗服务不足的人群死亡或罹患危重疾病的可能性是其正常人群的两倍多 当前和以前吸烟者也更有可能患上严重的 COVID-19。 和/或死亡的基础可能是社会、行为和/或生理。 吸烟和尼古丁可能会改变病毒进入气道上皮的“停靠位点”（ACE2）。 研究将探讨电子烟和尼古丁对易感染 COVID-19 的仓鼠的影响，看看是否会产生这种影响 由于 SARS-CoV-2 病毒，Vaping 改变了他们的肺部 ACE2 表达和/或使他们的疾病恶化。 用于成瘾、有毒和血管活性复合电子烟或双重用途的输送装置。 传统香烟和电子香烟尚未在 SARS-CoV-2 感染的背景下进行研究。 电子烟和尼古丁对 COVID-19 肺部疾病严重程度、病毒载量和 ACE2/ACE 表达的影响 因此，该模型将用于阐明信息、蛋白质和活性水平。 电子烟引起的肺损伤对 ACE2 表达和随后的 SARS2 感染的重要性 为了解决这些问题，我们研究了亚急性和/或急性尼古丁电子烟。 可以改变 ACE2/ACE 活性，并可能改变仓鼠的肺组织病理学。 假设急性/亚急性电子烟可能会增加 SARS-CoV-2 感染和/或肺部疾病 仓鼠的严重程度 如果属实，则对电子烟和/或 ACE2/ACE 比率进行药理学修改。 不吸电子烟的仓鼠可以降低 SARS-CoV-2 感染的严重程度，我们将实现两个目标： 1) 定义电子烟尼古丁对叙利亚仓鼠 ACE2/ACE 和肺组织病理学的影响，以及 2) 定义电子烟对 SARS-CoV-2 病毒载量、清除率和 COVID-19 肺部疾病的影响 目标 1 中开发的模型 方法：我们将使用新购买的电子烟“电子烟机器人”，它是完全计算机化的， 使用 FlexiWare 软件（inExpose、SCIIREQ、蒙特利尔）进行编程，仅通过鼻子向啮齿类动物输送药物，并且 最近描述了 SARS-CoV-2 介导的肺损伤的仓鼠模型。 在科罗拉多大学安舒茨医学校区（丹佛）进行，经过短暂的运输后， COVID-19 模型将在科罗拉多州立大学 (CSU) 的 BSL3 设施（科罗拉多州柯林斯堡）完成。 将监测仓鼠长达 7 天，研究气道/肺组织病理学和 ACE2/ACE 表达 该项目涉及两个长期研究兴趣的实验室：急性肺损伤。 我们将分别更好地了解毒理学、病毒学和新出现的病原体。 针对吸烟者中 COVID-19 恶化的情况，以及更有效治疗的潜在新途径。

项目成果

Mesna Improves Outcomes of Sulfur Mustard Inhalation Toxicity in an Acute Rat Model.

美司纳改善急性大鼠模型中硫芥吸入毒性的结果。

• 发表时间: 2024-01-17
• 作者: Nick, Heidi J;Johnson, Carly A;Stewart, Amber R;Christeson, Sarah E;Bloomquist, Leslie A;Appel, Amanda S;Donkor, Abigail B;Veress, Livia A;Logue, Brian A;Bratcher, Preston E;White, Carl W
• 通讯作者: White, Carl W

Analysis of sodium 2-mercaptoethane sulfonate in rat plasma using high performance liquid chromatography tandem-mass spectrometry.

使用高效液相色谱串联质谱法分析大鼠血浆中的 2-巯基乙磺酸钠。

• 发表时间: 2022-01-15
• 作者: Donkor, Abigail B;White, Carl W;Nick, Heidi J;Logue, Brian A
• 通讯作者: Logue, Brian A

Determination of methyl isopropyl hydantoin from rat erythrocytes by gas-chromatography mass-spectrometry to determine methyl isocyanate dose following inhalation exposure.

通过气相色谱质谱法测定大鼠红细胞中的甲基异丙基乙内酰脲，以确定吸入暴露后异氰酸甲酯的剂量。

• 发表时间: 2018-09-01
• 作者: Logue, Brian A;Zhang, Zhiling;Manandhar, Erica;Pay, Adam L;Croutch, Claire R;Peters, Eric;Sosna, William;Rioux, Jacqueline S;Veress, Livia A;White, Carl W
• 通讯作者: White, Carl W

Thioredoxin Prevents Loss of UCP2 in Hyperoxia via MKK4-p38 MAPK-PGC1α Signaling and Limits Oxygen Toxicity.

硫氧还蛋白通过 MKK4-p38 MAPK-PGC1α 信号传导防止高氧中 UCP2 的丢失并限制氧毒性。

• 发表时间: 2022-03
• 影响因子: 6.4
• 作者: Raghavan, Somasundaram;Kundumani;Kumar, Sudhir;White, Carl W;Das, Kumuda C
• 通讯作者: Das, Kumuda C

Acute vaping in a golden Syrian hamster causes inflammatory response transcriptomic changes.

金色叙利亚仓鼠的急性吸电子烟导致炎症反应转录组变化。

• 发表时间: 2022-11-01
• 作者: Hinds, Daniel M;Nick, Heidi J;Vallin, Tessa M;Bloomquist, Leslie A;Christeson, Sarah;Bratcher, Preston E;Cooper, Emily H;Brinton, John T;Bosco;White, Carl W
• 通讯作者: White, Carl W