Phase II studies of gamma tocopherol as an intervention for environmental asthma
γ-生育酚作为环境性哮喘干预措施的 II 期研究
基本信息
- 批准号:9057036
- 负责人:
- 金额:$ 87.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-12 至 2018-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAir PollutantsAir PollutionAllergensAllergicAnimalsAnti-Inflammatory AgentsAnti-inflammatoryAntioxidantsArachidonate 5-LipoxygenaseAsthmaBasophilsBiologicalBiological MarkersBreathingCellsChronicCytokine SignalingDNADataDehydrationDevelopmentDoseDouble-Blind MethodEndotoxinsEnrollmentEosinophiliaEotaxinEpidemiologic StudiesEpithelial CellsExhalationExtrinsic asthmaGene ProteinsGenesGenotypeGlutathioneGoalsHealthHomozygoteHourHumanIgEInflammationInflammatoryInflammatory ResponseInterleukin-13InterventionLOX geneLipidsLipopolysaccharidesLungLung diseasesMAPK3 geneMediatingMediator of activation proteinModelingMorbidity - disease rateMucinsMucociliary ClearanceMucous body substanceNeutrophiliaNitrogenNutritionalOxidantsOxygenOzoneParticipantParticulatePathologicPeripheral Blood Mononuclear CellPeroxonitritePhasePhosphorylationPlacebo ControlPlasmaPopulationPreparationProductionProstaglandin-Endoperoxide SynthaseProtein IsoformsProteinsProtocols documentationPublic HealthReactive Oxygen SpeciesRecruitment ActivityReportingRespiratory SystemRespiratory tract structureRiskRisk FactorsRodentRodent ModelRoleSamplingSerumSignal TransductionSourceSputumStressSupplementationTestingTherapeuticTissuesTobacco smokeTocopherolsUnited StatesVariantVitamin Eairway inflammationasthmaticbiomass smokecostcost effectivecytokinedesignefficacy testingenvironmental interventioneosinophileosinophilic inflammationgamma-Tocopherolgranulocytehealthy volunteerinjured airwaymonocyteneutrophilnovelphase 2 studyphase 3 studyplacebo controlled studypollutantpreventrandomized placebo controlled trialresponsetargeted treatmentvolunteer
项目摘要
DESCRIPTION (provided by applicant): Allergic asthma (AA) is the most commonly encountered respiratory disease in the United States and is a leading cause of morbidity worldwide The goals of this project are to undertake phase IIa studies of a gamma tocopherol enriched mixed tocopherol (γT-mT) preparation on chronic eosinophilic inflammation and acute increases in neutrophilic inflammation in allergic asthmatics (AAs) associated with LPS and O3 challenge. Endotoxin (lipopolysaccharide or LPS) is a component of coarse and fine mode PM, bioaerosols, tobacco and biomass smoke. Ozone (O3) is the most commonly encountered ambient air pollutant in the US. Epidemiological studies have shown that both LPS and O3 are important asthma triggers. In challenge studies of AAs, we have shown that LPS and O3 induces influx of neutrophils (PMNs) and eosinophils in AAs as well as augmenting response to inhaled allergens. O3 is also an oxidant, and both O3 and LPS increase radical production by airway cells, with both nutritional and genetically defined antioxidant deficiencies (such as the GSTM1 null genotype) being associated with increased risk for pollutant-induced asthma exacerbation. In challenge studies, we have reported that LPS and O3 PMN responses are increased in GSTM1 null volunteers. Gamma tocopherol has known antioxidant and anti-inflammatory actions. We have shown that γT prevents allergen, O3 and LPS-induced respiratory tract inflammation in rodents. Our phase I human studies with γT-mT established a dose which maintains γT and its anti-inflammatory metabolites, decreases monocyte responses to LPS and IgE-mediated basophil response to allergen. Data from our initial double-blinded, placebo controlled phase IIa study in healthy volunteers demonstrates that γT-mT inhibits LPS-induced granulocyte influx. Successful completion of this phase IIa study in AAs will guide development of a phase III efficacy study of this low cost nutriceutical intervention for preventio of pollutant-induced asthma exacerbations.
描述(由申请人提供):过敏性哮喘(AA)是美国最常见的呼吸系统疾病,也是全球发病率的主要原因。该项目的目标是进行伽马生育酚强化混合生育酚(γT-MT)制剂的IIa期研究,以治疗与脂多糖和臭氧激发相关的过敏性哮喘患者的慢性嗜酸性炎症和中性粒细胞炎症的急性增加。内毒素(脂多糖或内毒素)是粗细模式PM、生物气溶胶、烟草和生物质烟雾的一种成分。臭氧(臭氧)是美国最常见的环境空气污染物。流行病学研究表明,内毒素和臭氧都是重要的哮喘诱因。在对AAS的攻击性研究中,我们发现,内毒素和臭氧可诱导AAS内中性粒细胞(PMN)和嗜酸性粒细胞的内流,并增强对吸入性变应原的反应。臭氧也是一种氧化剂,臭氧和脂多糖都会增加呼吸道细胞的自由基产生,营养和基因定义的抗氧化剂缺陷(如GSTM1零基因)都与污染物诱导的哮喘恶化的风险增加有关。在挑战研究中,我们已经报道了在GSTM1缺失的志愿者中,内毒素和臭氧的PMN反应增加。生育酚具有已知的抗氧化和抗炎作用。我们已经证明,γT可以预防过敏原、臭氧和脂多糖诱导的啮齿动物呼吸道炎症。我们对γT-Mt进行的I期人体试验确定了维持γT及其抗炎代谢物、降低单核细胞对内毒素的反应和IgE介导的嗜碱性细胞对变应原的反应的剂量。我们最初在健康志愿者中进行的双盲、安慰剂对照IIa期研究的数据表明,γT-mt可以抑制脂多糖诱导的粒细胞内流。在AAs中成功完成这项IIa期研究将指导开展这一低成本营养干预措施预防污染物引起的哮喘加重的III期疗效研究。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
David B. Peden其他文献
Impact of Aeroallergen Sensitization on Asthma Control in African-American Teens with Persistent Asthma
空气过敏原敏化对患有持续性哮喘的非洲裔美国青少年哮喘控制的影响
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
A. Burbank;S. Grabich;Krista Todorich;Marcia Frye;C. Loughlin;Kelly Duncan;C. Robinette;K. Mills;David B. Peden;David Diaz;Michelle L. Hernandez - 通讯作者:
Michelle L. Hernandez
Airway cells from atopic asthmatic patients exposed to ozone display an enhanced innate immune gene profile
- DOI:
10.1016/j.jaci.2011.11.007 - 发表时间:
2012-01-01 - 期刊:
- 影响因子:
- 作者:
Michelle Hernandez;Willie June Brickey;Neil E. Alexis;Rebecca C. Fry;Julia E. Rager;Baiming Zhou;Jenny P.Y. Ting;Haibo Zhou;David B. Peden - 通讯作者:
David B. Peden
Effect of prednisone on woodsmoke-induced sputum inflammation in healthy volunteers: A randomized, placebo-controlled pilot study
- DOI:
10.1016/j.jacig.2024.100347 - 发表时间:
2025-02-01 - 期刊:
- 影响因子:
- 作者:
Terry L. Noah;Neil E. Alexis;William D. Bennett;Michelle L. Hernandez;Allison J. Burbank;Haolin Li;Haibo Zhou;Ilona Jaspers;David B. Peden - 通讯作者:
David B. Peden
Global change, climate change, and asthma in children: Direct and indirect effects - A WAO Pediatric Asthma Committee Report
全球变化、气候变化与儿童哮喘:直接和间接影响——世界过敏组织儿科哮喘委员会报告
- DOI:
10.1016/j.waojou.2024.100988 - 发表时间:
2024-11-01 - 期刊:
- 影响因子:4.300
- 作者:
Peter N. Le Souëf;Yuichi Adachi;Eleni Anastasiou;Ignacio J. Ansotegui;Héctor A. Badellino;Tina Banzon;Cesar Pozo Beltrán;Gennaro D'Amato;Zeinab A. El-Sayed;Rene Maximiliano Gómez;Elham Hossny;Ömer Kalayci;Mário Morais-Almeida;Antonio Nieto-Garcia;David B. Peden;Wanda Phipatanakul;Jiu-Yao Wang;I-Jen Wan;Gary Wong;Paraskevi Xepapadaki;Nikolaos G. Papadopoulos - 通讯作者:
Nikolaos G. Papadopoulos
David B. Peden的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('David B. Peden', 18)}}的其他基金
Research Training in Allergy and Clinical Immunology
过敏和临床免疫学研究培训
- 批准号:
10493540 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别:
Research Training in Allergy and Clinical Immunology
过敏和临床免疫学研究培训
- 批准号:
10686797 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别:
Project 4: Treatment of mucostasis and airways obstruction in asthma with a novel mucolytic
项目 4:用新型粘液溶解剂治疗哮喘粘膜淤积和气道阻塞
- 批准号:
10001602 - 财政年份:2017
- 资助金额:
$ 87.73万 - 项目类别:
Project 4: Treatment of mucostasis and airways obstruction in asthma with a novel mucolytic
项目 4:用新型粘液溶解剂治疗哮喘粘膜淤积和气道阻塞
- 批准号:
9356821 - 财政年份:2017
- 资助金额:
$ 87.73万 - 项目类别:
Gamma tocopherol chemoprevention of wood smoke PM2.5-induced airway inflammation
γ-生育酚化学预防木烟PM2.5引起的气道炎症
- 批准号:
9222012 - 财政年份:2016
- 资助金额:
$ 87.73万 - 项目类别:
Gamma tocopherol chemoprevention of wood smoke PM2.5-induced airway inflammation
γ-生育酚化学预防木烟PM2.5引起的气道炎症
- 批准号:
9883794 - 财政年份:2016
- 资助金额:
$ 87.73万 - 项目类别:
Gamma tocopherol chemoprevention of wood smoke PM2.5-induced airway inflammation
γ-生育酚化学预防木烟PM2.5引起的气道炎症
- 批准号:
9055845 - 财政年份:2016
- 资助金额:
$ 87.73万 - 项目类别:
Phase II studies of gamma tocopherol as an intervention for environmental asthma
γ-生育酚作为环境性哮喘干预措施的 II 期研究
- 批准号:
9269215 - 财政年份:2013
- 资助金额:
$ 87.73万 - 项目类别:
Phase II studies of gamma tocopherol as an intervention for environmental asthma
γ-生育酚作为环境性哮喘干预措施的 II 期研究
- 批准号:
8598698 - 财政年份:2013
- 资助金额:
$ 87.73万 - 项目类别:
Phase II studies of gamma tocopherol as an intervention for environmental asthma
γ-生育酚作为环境性哮喘干预措施的 II 期研究
- 批准号:
8733697 - 财政年份:2013
- 资助金额:
$ 87.73万 - 项目类别:
相似海外基金
How are plants responding to damage by oxidizing air pollutants?
植物如何应对氧化空气污染物造成的损害?
- 批准号:
DP230100296 - 财政年份:2023
- 资助金额:
$ 87.73万 - 项目类别:
Discovery Projects
Unified assessment of health effects of multiple air pollutants inducing reactive oxygen species production
统一评估多种引起活性氧产生的空气污染物的健康影响
- 批准号:
22KJ0372 - 财政年份:2023
- 资助金额:
$ 87.73万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Air pollutants, heat exposure, and kidney health: A longitudinal study in women in Central America
空气污染物、热暴露和肾脏健康:针对中美洲女性的纵向研究
- 批准号:
10583301 - 财政年份:2023
- 资助金额:
$ 87.73万 - 项目类别:
Prenatal Traffic-Related Air Pollutants, Placental Epitranscriptomics, and Child Cognition
产前交通相关空气污染物、胎盘表观转录组学和儿童认知
- 批准号:
10366988 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别:
Analysis of the protective effect of metallothioneins against lung injury caused by air pollutants.
金属硫蛋白对空气污染物所致肺损伤的保护作用分析
- 批准号:
22K06588 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Disrupting Noxious Synergies of Indoor Air Pollutants and their Impact in Childhood Health and Wellbeing, using Advanced Intelligent Multisensing and Green Interventions
利用先进的智能多传感和绿色干预措施,破坏室内空气污染物的有害协同作用及其对儿童健康和福祉的影响
- 批准号:
10051924 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别:
EU-Funded
Development and/or evaluation of emission factors for Odour, air pollutants, greenhouse gas emissions and air quality impact assessment for industrial and municipal sources in cold region
寒冷地区工业和市政源恶臭、空气污染物、温室气体排放排放因子的制定和/或评价以及空气质量影响评价
- 批准号:
RGPIN-2019-07299 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别:
Discovery Grants Program - Individual
Exposure to Ambient Air Pollutants, Circulating microRNAs, and Hepatic Fat Fraction Among Young Adults
年轻人接触环境空气污染物、循环 microRNA 和肝脂肪分数
- 批准号:
10537895 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别:
Novel Approaches for Improving Inflammation Resolution Following Chronic Exposure to Air Pollutants
改善长期接触空气污染物后炎症消退的新方法
- 批准号:
10348421 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别:
Prenatal Traffic-Related Air Pollutants, Placental Epitranscriptomics, and Child Cognition
产前交通相关空气污染物、胎盘表观转录组学和儿童认知
- 批准号:
10589926 - 财政年份:2022
- 资助金额:
$ 87.73万 - 项目类别: