Electronic Cigarette Vapor Inhalation Adversely Affects Lung Cellular and Physiologic Function and Alters Systemic Inflammatory Pathways
Electronic Cigarette Vapor Inhalation Adversely Affects Lung Cellular and Physiologic Function and Alters Systemic Inflammatory Pathways
批准号:
10220439
负责人:
Laura Elise Crotty Alexander
金额:
$36.65万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-07-28 至 2021-12-31
关键词:
AcuteAcute Lung InjuryAdultAdverse effectsAdvertisementsAffectAmericanBacteremiaBacterial Antibiotic ResistanceBacterial InfectionsBacterial PneumoniaBloodBlood CirculationBlood PressureCardiovascular systemCause of DeathCellsCessation of lifeChemicalsChildChronicChronic DiseaseChronic Obstructive Airway DiseaseCigaretteCigarette SmokerCommunicable DiseasesComplexDataDevelopmentDevicesDiseaseDrug Delivery SystemsElectronic cigaretteEpithelial CellsEventExposure toFibrosisFutureGene ExpressionHeart DiseasesHeart RateHost DefenseHumanImpairmentIn VitroIncidenceIndividualInflammationInflammatoryInflammatory ResponseInhalationInterleukin-6IntravenousKidney FailureLeadLinkLong-Term EffectsLungLung diseasesMalignant NeoplasmsMinorityModelingMusNasopharynxNatural ImmunityOrganPathogenicityPathologicPathway interactionsPatientsPhysiologicalPlasmaPneumoniaPopulationPredispositionPublic HealthPulmonary EmphysemaRaceRecommendationRiskSafetySalesSerumSideSkin TissueSmokeSoft Tissue InfectionsStaphylococcus aureusSystemSystemic diseaseTNF geneTemperatureTestingTight JunctionsTimeTobaccoTobacco smokeToxic effectUp-RegulationVirulenceVirulentWomanWorkaerosolizedairway hyperresponsivenessantimicrobialbronchial epitheliumcarcinogenesiscell typecigarette smokecoronary fibrosiscytokinecytokine release syndromedefense responsee-cigarette aerosolselectronic cigarette useelectronic cigarette userepidemiologic dataexperimental studygram-negative sepsishuman diseasehuman subjectimmunoregulationin vivoinfection riskinflammatory markerintraperitonealinventionkidney fibrosismacrophagemethicillin resistant Staphylococcus aureusmouse modelneutrophilnever smokernicotine usenicotine vapornon-smokerpathogenresponsesmoking cessationsystemic inflammatory responsetheoriestranscriptome sequencingvapingvaporyoung adult
中文摘要
摘要/文摘
英文摘要
SUMMARY/ABSTRACT
COPD is the 3rd leading cause of death and incidence continues to rise. Many people are trying to quit
smoking by using electronic (e)-cigarettes, even though data suggest that e-cigarette use adversely impacts
cessation rates. Patients are switching to or adding on e-cigarette use because advertisements say they are
completely safe. Young adult (18-40) never smokers are vaping e-cigarettes - inhaling vapor containing
nicotine and other chemicals from these drug delivery devices. Our in vivo, ex vivo and in vitro data suggest
significant adverse effects on host defenses, inflammation in the lung and systemically, and bacterial virulence.
Vaping may lead to long-term effects, such as development of COPD, heart disease, and kidney failure, but it
will be decades before epidemiologic data can demonstrate or disprove it.
We propose experiments to evaluate effects of e-cigarette vapor on primary human airway cells of host
defense: macrophages (>90% of airway cells in normal human subjects) and neutrophils (elevated in the
airways of cigarette smokers - the largest population using e-cigarettes). These cells are directly exposed to
inhaled vapor in the airways and are the mainstays of host defense in lung and blood. Comparison to cigarette
smoke is important to answer one of the most urgent questions: Are e-cigarettes safer than conventional
cigarettes? We will determine whether e-cigarette vapor negatively impacts the ability of macrophages and
neutrophils to kill common pathogens and examine whether e-cigarettes dysregulate inflammatory responses,
as both increases and decreases in inflammation are known to cause chronic disease. We will use our
established mouse model of e-cigarette vapor inhalation, such that we may study effects of e-cigarettes in the
setting of common human diseases, such as gram-negative sepsis, acute lung injury, and gram-positive
pneumonia and bacteremia.
Finally, the incidence of invasive disease and death due to antibiotic resistant bacteria is growing
rapidly. In particular, methicillin resistant Staphylococcus aureus (MRSA) is the leading cause of bloodstream,
skin and soft tissue infections. MRSA colonizes the nasopharynx of 20% of the population chronically. We
recently found that MRSA is harder to kill and more virulent after exposure to e-cigarette vapor as well as
conventional tobacco smoke. In this proposal we will: 1. Determine whether e-cigarette vapor promotes
virulence in colonizing S. aureus in vivo by isolating strains from e-cigarette users, cigarette smokers and
controls; and 2. Evaluate e-cigarette effects on both host defense and bacterial virulence in a physiologic
setting (mice colonized with MRSA and concomitantly inhaling e-cigarette vapor) to determine whether
deleterious effects of e-cigarettes on host defenses and bacterial pathogenicity occur in a more complex
setting, as would happen in human airways. These studies may have a major public health impact, laying
groundwork for future studies and for making informed e-cigarette recommendations to the public at large.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:10555145
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项目类别:
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资助金额:$38.31万
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财政年份:2023
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负责人:Laura Elise Crotty Alexander
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依托单位:
Convergence of Vitamin E, THC, Nicotine, Propylene Glycol and Glycerin Effects on Lung Inflammation When Vaped
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批准号:10371746
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项目类别:
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资助金额:$12.17万
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财政年份:2022
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负责人:Laura Elise Crotty Alexander
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依托单位:
Convergence of Vitamin E, THC, Nicotine, Propylene Glycol and Glycerin Effects on Lung Inflammation When Vaped
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批准号:10546469
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项目类别:
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资助金额:$12.12万
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财政年份:2022
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负责人:Laura Elise Crotty Alexander
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依托单位:
Hypoxia inducible factors in pulmonary endothelial cells regulate allergic inflammatory airways disease
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批准号:10292906
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项目类别:
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资助金额:$0.0万
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财政年份:2019
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负责人:Laura Elise Crotty Alexander
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依托单位:
Hypoxia inducible factors in pulmonary endothelial cells regulate allergic inflammatory airways disease
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批准号:10515302
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项目类别:
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资助金额:$0.0万
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财政年份:2019
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负责人:Laura Elise Crotty Alexander
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依托单位:
Hypoxia inducible factors in pulmonary endothelial cells regulate allergic inflammatory airways disease
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批准号:10045518
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项目类别:
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资助金额:$0.0万
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财政年份:2019
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负责人:Laura Elise Crotty Alexander
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依托单位:
Genetic and Pharmacologic Evaluation of the Role of HIF-1a in asthma
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批准号:8305975
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项目类别:
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资助金额:$0.0万
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财政年份:2011
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负责人:Laura Elise Crotty Alexander
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依托单位:
Genetic and Pharmacologic Evaluation of the Role of HIF-1a in asthma
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批准号:8698286
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Laura Elise Crotty Alexander
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依托单位:
Genetic and Pharmacologic Evaluation of the Role of HIF-1a in asthma
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批准号:8143209
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Laura Elise Crotty Alexander
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依托单位:
Genetic and Pharmacologic Evaluation of the Role of HIF-1a in asthma
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批准号:8402123
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Laura Elise Crotty Alexander
-
依托单位:
Genetic and Pharmacologic Evaluation of the Role of HIF-1a in asthma
-
批准号:8795680
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
-
负责人:Laura Elise Crotty Alexander
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依托单位:
海外基金