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.

项目摘要 在19日期的大流行中，> 150万美国人病了，超过100,000人死亡。迄今为止， 医疗服务不足的人群死亡的可能性是相对于他们的死亡或危重疾病的两倍多 人口比例。当前和以前的吸烟者也更有可能发展关键的Covid-19 和/或死。这可能是社会，行为和/或生理学的基础。最近的发现表明 吸烟和尼古丁可能会改变病毒进入气道上皮的“停靠点”（ACE2）。这 研究将探索在汉仓中烟雾和尼古丁的影响 由于SARS-COV-2病毒，改变其肺ACE2表达和/或使其疾病恶化。烟是一个 用于上瘾，有毒和血管活性复合尼古丁的输送装置。电子烟的使用或双重使用 在SARS-COV-2感染的背景下，尚未检查传统和电子烟。具体来说， Vaping和Nicotine对COVID-19-19肺疾病严重程度，病毒载荷和ACE2/ACE表达的影响 信息，蛋白质和活性水平将进行研究。那就是该模型将用于澄清 烟雾引起的肺损伤对ACE2表达以及随后的SARS2感染的重要性 发病。为了解决这些问题，我们假设亚急性和/或急性尼古丁蒸发 可以改变仓鼠中的ACE2/ACE活动，并可能改变仓鼠的肺组织病理学。此外，我们 假设急性/亚急性蒸发会增加SARS-COV-2感染和/或肺部疾病 仓鼠的严重程度。如果是真的，则在蒸发和/或 无中型仓鼠可能会减少SARS-COV-2感染严重程度。将实现两个目标： 1）定义尼古丁对叙利亚仓鼠中ACE2/ACE和肺组织病理学的影响，以及 2）定义对SARS-COV-2病毒载量，清除率和COVID-19对肺疾病的影响 AIM 1开发的模型 方法：我们将使用已完全计算机化的新获得的电子烟“烟雾机” 可使用Flexiware软件（劣质，Scireq，蒙特利尔）进行编程，用于啮齿动物的鼻子交付 最近描述了SARS-COV-2介导的肺损伤的仓鼠模型。烟的暴露将是 在科罗拉多大学安索兹大学医学校园（丹佛）进行，在短暂交通后 Covid-19模型将在科罗拉多州立大学（CSU）BSL3设施（Ft。Collins，CO）上完成。我们在那里 将对气道/肺组织病理学和ACE2/ACE表达的研究最多监测仓鼠长达7天 尸检后。该项目涉及两个具有长期研究兴趣的实验室：急性肺损伤 和毒理学，病毒学和新兴病原体。我们将更好地了解机制 担心吸烟者中的Covid-19，以及可能获得更有效治疗的新途径。

项目成果

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。

• DOI: 10.1016/j.jchromb.2018.07.004
• 发表时间: 2018
• 期刊: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
• 作者: Logue,BrianA;Zhang,Zhiling;Manandhar,Erica;Pay,AdamL;Croutch,ClaireR;Peters,Eric;Sosna,William;Rioux,JacquelineS;Veress,LiviaA;White,CarlW
• 通讯作者: White,CarlW

Alleviation of methyl isocyanate-induced airway obstruction and mortality by tissue plasminogen activator.

• DOI: 10.1111/nyas.14344
• 发表时间: 2020-11
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Nick HJ;Rioux JS;Veress LA;Bratcher PE;Bloomquist LA;Anantharam P;Croutch CR;Tuttle RS;Peters E;Sosna W;White CW
• 通讯作者: White CW

Verification of chlorine exposure via LC-MS/MS analysis of base hydrolyzed chlorophenols from chlorotyrosine-protein adducts.

通过 LC-MS/MS 分析氯酪氨酸-蛋白质加合物中的碱水解氯酚来验证氯暴露。

• DOI: 10.1016/j.jchromb.2024.124042
• 发表时间: 2024
• 期刊: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
• 作者: Sultana,Sharmin;Christeson,Sarah;Basiouny,Mohamed;Rioux,Jacqueline;Veress,Livia;Logue,BrianA
• 通讯作者: Logue,BrianA

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。

• DOI: 10.1152/ajplung.00162.2022
• 发表时间: 2022
• 期刊: American journal of physiology. Lung cellular and molecular physiology
• 作者: Hinds,DanielM;Nick,HeidiJ;Vallin,TessaM;Bloomquist,LeslieA;Christeson,Sarah;Bratcher,PrestonE;Cooper,EmilyH;Brinton,JohnT;Bosco-Lauth,Angela;White,CarlW
• 通讯作者: White,CarlW

Reply to: Comment on "Bronchiolitis Obliterans and Pulmonary Fibrosis after Sulfur Mustard Inhalation in Rats".

回复：评论《大鼠吸入硫芥后闭塞性细支气管炎和肺纤维化》。

• DOI: 10.1165/rcmb.2018-0119le
• 发表时间: 2018
• 期刊: American journal of respiratory cell and molecular biology
• 影响因子: 6.4
• 作者: McGraw,MatthewD;Veress,LiviaA
• 通讯作者: Veress,LiviaA