HIV and COPD:Immune mediated mechanisms
HIV 和 COPD:免疫介导机制
基本信息
- 批准号:8639121
- 负责人:
- 金额:$ 62.45万
- 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:2013-09-26 至 2018-07-31
- 项目状态:已结题
- 来源:
- 关键词:AlveolitisAnatomyAntioxidantsBiological AssayBiological MarkersBloodBlood VesselsBronchoalveolar LavageBronchoalveolar Lavage FluidBronchoscopyCD8B1 geneCellsChronicChronic Obstructive Airway DiseaseColorControl GroupsDataDevelopmentDiseaseEchocardiographyEnvironmental air flowEquilibriumFlow CytometryGene ExpressionGene Expression ProfilingHIVHIV InfectionsHigh Resolution Computed TomographyImaging TechniquesImaging technologyImmuneImmune responseImmune systemIncidenceIndividualInfectionInjuryInstitutesLifeLungLung diseasesMalignant neoplasm of lungMeasurementMeasuresMediatingMolecularMorbidity - disease rateOxidantsOxidative StressPathogenesisPatientsPerfusionPhenotypePhysiologicalPhysiologyPopulationPositron-Emission TomographyProcessPulmonary EmphysemaPulmonary HypertensionPulmonary artery structurePulmonary function testsRespiratory physiologyRoleSalineSamplingSeveritiesSymptomsT-Cell ActivationT-LymphocyteVascular remodelingViralVirusWorkairway obstructionantiretroviral therapycohortdefined contributionindexinginnovative technologieslung injurymetabolomicsmortalitynovelperipheral bloodpressurepublic health relevancerespiratory
项目摘要
DESCRIPTION (provided by applicant): More than 30 million people worldwide are living with HIV. In individuals with chronic HIV infection, lung disease is a major cause of morbidity and mortality. HIV infection increases the incidence of chronic obstructive pulmonary disease (COPD), as well as other lung diseases. In fact, the incidence of respiratory symptoms and/or abnormal pulmonary function tests (PFTs) in people with HIV is as high as 60% in some studies. The mechanisms causing non-infectious pulmonary disease in HIV are poorly understood. It has been suggested that immune dysregulation from HIV is an important contributor to the process. In addition, direct effects of the virus on lung cells, oxidative stres, chronic low-grade infection of the lung, and antiretroviral therapy (ART) use may contribute to the pathogenesis of these disorders. An increased understanding of the molecular mechanisms involved in HIV-associated lung disease may help identify novel biomarkers, facilitate preventative approaches, and guide the development of novel therapies. However, studies to determine the exact pathogenesis of COPD in chronic HIV infection have been limited. To better define the molecular mechanisms of COPD in chronic HIV, we propose to extensively phenotype HIV infected subjects using cutting-edge imaging technologies, bronchoscopy, and advanced immune assays, and correlate these measures to the incidence and progression of COPD. We hypothesize that in patients with chronic HIV infection, repeated injury to the small airways and the pulmonary vasculature result in emphysematous changes and pulmonary vascular remodeling leading to COPD. Using a cohort of patients with chronic HIV infection, we will identify subjects with airway obstruction and compare them to subjects with normal lung function. We will further phenotype subjects using high resolution computed tomography (HRCT), echocardiography, and positron emission tomography (PET) with 13N2-saline. These imaging techniques will provide quantitative anatomic and physiologic data, including extremely sensitive measurements of lung and pulmonary vascular destruction, regional lung ventilation, and regional lung perfusion. These data will be correlated with assessment of T cell activity and oxidative stress in bronchoalveolar lavage (BAL) fluid and peripheral blood. In addition, we will broadly explore other potential causes for COPD in this population with metabolomic, and gene expression studies. We will also explore the potential role of ART in COPD pathogenesis by utilizing a unique cohort of elite HIV controllers. The specific aims are: 1) To determine the relationship between chronic activation of T cells, lung injury and COPD in chronic HIV; 2) To determine levels of oxidative stress in the lung of patients with chronic HIV and define the contribution to lung injury and COPD.
描述(申请人提供):全球有3000多万艾滋病毒携带者。在慢性艾滋病毒感染者中,肺部疾病是发病率和死亡率的主要原因。艾滋病毒感染会增加慢性阻塞性肺疾病(COPD)以及其他肺部疾病的发病率。事实上,在一些研究中,艾滋病毒携带者出现呼吸道症状和/或肺功能测试(PFT)异常的发生率高达60%。艾滋病毒引起非传染性肺部疾病的机制还知之甚少。有人认为,艾滋病毒的免疫失调是这一过程的重要贡献者。此外,病毒对肺细胞的直接作用、氧化应激、慢性低度肺部感染和抗逆转录病毒疗法(ART)的使用可能有助于这些疾病的发病。加深对HIV相关肺部疾病分子机制的了解可能有助于识别新的生物标记物,促进预防方法,并指导新疗法的开发。然而,确定慢性阻塞性肺疾病在慢性HIV感染中的确切发病机制的研究一直有限。为了更好地确定慢性HIV中COPD的分子机制,我们建议使用尖端成像技术、支气管镜检查和先进的免疫分析方法对HIV感染者进行广泛的表型分析,并将这些措施与COPD的发生和进展联系起来。我们推测,在慢性HIV感染的患者中,小气道和肺血管的反复损伤导致肺气肿改变和肺血管重构,从而导致COPD。利用一组慢性HIV感染患者,我们将确定患有呼吸道阻塞的受试者,并将他们与肺功能正常的受试者进行比较。我们将使用高分辨率计算机断层扫描(HRCT)、超声心动图和13N-生理盐水正电子发射断层扫描(PET)对受试者进行进一步的表型研究。这些成像技术将提供定量的解剖学和生理学数据,包括对肺和肺血管破坏、区域肺通气量和区域肺血流灌注的极其敏感的测量。这些数据将与支气管肺泡灌洗液(BAL)液和外周血中T细胞活性和氧化应激的评估相关。此外,我们将通过代谢学和基因表达研究,广泛探索该人群中COPD的其他潜在原因。我们还将利用一个独特的精英HIV控制者队列,探索ART在COPD发病机制中的潜在作用。其具体目的是:1)确定慢性HIV患者T细胞的慢性激活、肺损伤与COPD的关系;2)测定慢性HIV患者肺内氧化应激水平,明确其在肺损伤和COPD中的作用。
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)
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Douglas Kwon其他文献
Douglas Kwon的其他文献
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{{ truncateString('Douglas Kwon', 18)}}的其他基金
Immunometabolic regulation of CD8+ T cell mediated intestinal epithelial cell death in people with HIV (PWH)
HIV 感染者 (PWH) 中 CD8 T 细胞介导的肠上皮细胞死亡的免疫代谢调节
- 批准号:
10528704 - 财政年份:2022
- 资助金额:
$ 62.45万 - 项目类别:
Immunometabolic regulation of CD8+ T cell mediated intestinal epithelial cell death in people with HIV (PWH)
HIV 感染者 (PWH) 中 CD8 T 细胞介导的肠上皮细胞死亡的免疫代谢调节
- 批准号:
10674959 - 财政年份:2022
- 资助金额:
$ 62.45万 - 项目类别:
Multi-omics characterization of HIV-associated changes in the gut microbiome and host mucosal immunity
HIV相关肠道微生物组和宿主粘膜免疫变化的多组学表征
- 批准号:
10242686 - 财政年份:2018
- 资助金额:
$ 62.45万 - 项目类别:
Multi-omics characterization of HIV-associated changes in the gut microbiome and host mucosal immunity
HIV相关肠道微生物组和宿主粘膜免疫变化的多组学表征
- 批准号:
9695789 - 财政年份:2018
- 资助金额:
$ 62.45万 - 项目类别:
Multi-omics characterization of HIV-associated changes in the gut microbiome and host mucosal immunity
HIV相关肠道微生物组和宿主粘膜免疫变化的多组学表征
- 批准号:
10466926 - 财政年份:2018
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Inflammation and the vaginal metagenome in HIV acquisition
炎症和艾滋病毒感染中的阴道宏基因组
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9012013 - 财政年份:2014
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$ 62.45万 - 项目类别:
The enteric microbiome in treated and progressive HIV infection
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- 批准号:
8731684 - 财政年份:2014
- 资助金额:
$ 62.45万 - 项目类别:
Inflammation and the vaginal metagenome in HIV acquisition
炎症和艾滋病毒感染中的阴道宏基因组
- 批准号:
8820884 - 财政年份:2014
- 资助金额:
$ 62.45万 - 项目类别:
The enteric microbiome in treated and progressive HIV infection
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9135396 - 财政年份:2014
- 资助金额:
$ 62.45万 - 项目类别:
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