Impact of smoking and its cessation on systemic and airway immune activation
吸烟及其戒烟对全身和气道免疫激活的影响
基本信息
- 批准号:9332352
- 负责人:
- 金额:$ 79.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-15 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAddressAffectAlveolar MacrophagesAmbulatory Care FacilitiesAttenuatedAutomobile DrivingBacterial PneumoniaBiologicalBloodCardiovascular DiseasesCellsCessation of lifeCharacteristicsChronicChronic Obstructive Airway DiseaseClinicalClinical ResearchCollaborationsCross-Sectional StudiesDNADNA DamageDNA Sequence AlterationDataDevelopmentDiseaseEpithelialEpithelial CellsFunctional disorderFutureGene ExpressionGene Expression AlterationGeneral PopulationGenesGenetic TranscriptionHIVHIV InfectionsHealthHigh PrevalenceImmuneImmune System DiseasesImmune System and Related DisordersImmunologicsImmunologyIndividualInflammationInflammation MediatorsInflammatoryInjuryInterruptionInterventionIntervention StudiesLeadLinkLiteratureLungLung InflammationLung diseasesMalignant NeoplasmsMalignant neoplasm of lungMeasuresMediatingMolecular ProfilingMorbidity - disease rateNatureOxidative StressParticipantPathogenesisPathologicPathologic ProcessesPathway interactionsPatientsPersonsPhenotypePlayPopulationProductionPublic HealthPulmonary EmphysemaPulmonary PathologyReactive Oxygen SpeciesRecoveryRecruitment ActivityResearchResearch InfrastructureResidual stateResourcesRespiratory SystemRespiratory tract structureRiskRisk FactorsRoleSamplingSignal TransductionSiteSmokeSmokerSmokingSmoking Cessation InterventionSmoking HistoryTestingTimeTissuesTranscription AlterationViremiaage relatedantiretroviral therapyarmcigarette smokingcytokinehealth disparityimmune activationinflammatory milieulung developmentmicrobialmonocytemortalitynever smokernon-smokerprogramspublic health prioritiesresponsesample collectionsmoking cessationsmoking prevalencetherapeutic developmenttherapeutic targettherapy developmenttranscriptometranslational approachvirology
项目摘要
PROJECT SUMMARY
The exceedingly high rate of smoking and its substantial contribution to morbidity and mortality in the HIV-
infected population despite effective ART makes smoking a major health risk in the HIV-infected population.
The mechanism by which smoking exerts synergistic effects on HIV-induced immune dysfunction remains
unclear. Our central hypothesis is that the persistent HIV-induced immune dysfunction leaves the lung
exceeding vulnerable to further insults by smoking. Smoking further drives immune-mediate pathways, such as
increase in oxidative stress and inflammation, to cause further local tissue destruction. The lung pathology can
result in activation of latently infected alveolar macrophages in the lung to produce low level HIV viremia, and
perpetuates this pro-inflammatory environment. Additionally, the chronic oxidative imbalance can cause not
only local tissue damage but cellular DNA damage, which results in epithelial gene expression alterations. Aim
1 seeks to identify in a cross-sectional study of ART-treated HIV smokers chronic immune effects of smoking
by evaluating for differences in cytokine profile and immune cell phenotype and ROS production of cells
isolated in the airways and blood from HIV-infected never smokers. The relationships of these local and
systemic immune perturbations with airway epithelial gene transcriptome and evidence of residual viremia will
be evaluated to identify biological pathways by which smoking interacts with HIV immune dysfunction. In Aim
2 to further test the hypothesis we propose a proof-of-concept smoking cessation clinical study to assess the
degree and nature of reversibility of lung damage among HIV smokers who achieve smoking cessation
compared to those who continue to smoke. In this single site study, we will employ an intensive smoking
cessation program to help study participants who are recruited from a large urban HIV-infected outpatient clinic
where a unique integrated clinical research infrastructure is in place, achieve smoking cessation. Longitudinally
samples will be collected pre-cessation and post-cessation from those who are able to achieve 10-week
cessation from the lung and blood. We will evaluate the change in level of inflammation, immune activation and
oxidative stress, and determine if these immune-mediate pathways are related to changes in HIV residual
viremia and epithelial gene expression in the lung. Lastly, leveraging existing resources, we will compare these
finding to those in uninfected smokers from banked samples collected already by our collaborator. This
smoking cessation study in HIV-infected patients will be the first of its kind, with longitudinal specimen
collection from both the lung and blood compartments, and utilizing translational approaches through
collaborations with experts in virology, immunology, gene transcription and health disparity research.
Understanding the relative contribution and pathways by which smoking interacts with immune activation and
inflammation characteristic of chronic HIV disease will help guide development of therapeutic interventions to
halt or reverse these pathological processes and ensuing clinical disease.
项目摘要
吸烟率极高及其对艾滋病毒感染者发病率和死亡率的重大影响,
尽管抗逆转录病毒疗法有效,但由于吸烟对艾滋病毒感染人群的健康构成重大风险。
吸烟对艾滋病毒诱导的免疫功能障碍产生协同作用的机制仍然存在
不清楚我们的中心假设是,持续的艾滋病毒诱导的免疫功能障碍离开了肺部
非常容易受到吸烟的进一步侮辱。吸烟进一步驱动免疫介导的途径,如
氧化应激和炎症增加,导致进一步的局部组织破坏。肺部病理学可以
导致肺中潜伏感染的肺泡巨噬细胞活化,产生低水平的HIV病毒血症,和
使这种促炎环境得以延续。此外,慢性氧化失衡可能导致
仅局部组织损伤,但细胞DNA损伤,这导致上皮基因表达改变。目的
1试图在ART治疗的HIV吸烟者的横断面研究中确定吸烟的慢性免疫效应
通过评估细胞因子谱和免疫细胞表型以及细胞的ROS产生的差异,
从不吸烟的艾滋病毒感染者的呼吸道和血液中分离出来。这些地方和
气道上皮基因转录组的系统性免疫紊乱和残留病毒血症的证据将
评估以确定吸烟与HIV免疫功能障碍相互作用的生物学途径。在Aim中
2为了进一步验证这一假设,我们提出了一项概念验证戒烟临床研究,以评估
实现戒烟的HIV吸烟者肺损伤可逆性的程度和性质
与那些继续吸烟的人相比。在这项单中心研究中,我们将采用密集吸烟
一项戒烟计划,帮助从一家大型城市HIV感染者门诊招募的研究参与者
在一个独特的综合临床研究基础设施到位,实现戒烟。纵向
将在戒烟前和戒烟后从能够达到10周的患者中收集样本
从肺和血液停止。我们将评估炎症水平、免疫激活和
氧化应激,并确定这些免疫介导的途径是否与HIV残留量的变化有关。
病毒血症和肺上皮基因表达。最后,利用现有资源,我们将比较
与我们的合作者已经收集的库存样本中未感染吸烟者的结果相比。这
艾滋病病毒感染者戒烟研究将是第一次,纵向标本
从肺和血室收集,并利用平移方法,
与病毒学、免疫学、基因转录和健康差异研究方面的专家合作。
了解吸烟与免疫激活相互作用的相对贡献和途径,
慢性HIV疾病的炎症特征将有助于指导治疗干预措施的发展,
停止或逆转这些病理过程和随后的临床疾病。
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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Nina H. Lin其他文献
Nina H. Lin的其他文献
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{{ truncateString('Nina H. Lin', 18)}}的其他基金
The effects of opioid use on HIV-1 reservoir dynamics
阿片类药物的使用对 HIV-1 病毒库动态的影响
- 批准号:
9762069 - 财政年份:2018
- 资助金额:
$ 79.24万 - 项目类别:
Impact of smoking and its cessation on systemic and airway immune activation
吸烟及其戒烟对全身和气道免疫激活的影响
- 批准号:
9203581 - 财政年份:2016
- 资助金额:
$ 79.24万 - 项目类别:
Impact of smoking and its cessation on systemic and airway immune activation
吸烟及其戒烟对全身和气道免疫激活的影响
- 批准号:
10187537 - 财政年份:2016
- 资助金额:
$ 79.24万 - 项目类别:
Impact of smoking and its cessation on systemic and airway immune activation
吸烟及其戒烟对全身和气道免疫激活的影响
- 批准号:
9529613 - 财政年份:2016
- 资助金额:
$ 79.24万 - 项目类别:
Analysis of properties of HIV-1 subtype C envelope glycoprotein
HIV-1 C亚型包膜糖蛋白的特性分析
- 批准号:
8260473 - 财政年份:2011
- 资助金额:
$ 79.24万 - 项目类别:
Analysis of properties of HIV-1 subtype C envelope glycoprotein
HIV-1 C亚型包膜糖蛋白的特性分析
- 批准号:
8826674 - 财政年份:2011
- 资助金额:
$ 79.24万 - 项目类别:
Analysis of properties of HIV-1 subtype C envelope glycoprotein
HIV-1 C亚型包膜糖蛋白的特性分析
- 批准号:
8641308 - 财政年份:2011
- 资助金额:
$ 79.24万 - 项目类别:
Analysis of properties of HIV-1 subtype C envelope glycoprotein
HIV-1 C亚型包膜糖蛋白的特性分析
- 批准号:
8448272 - 财政年份:2011
- 资助金额:
$ 79.24万 - 项目类别:
Analysis of properties of HIV-1 subtype C envelope glycoprotein
HIV-1 C亚型包膜糖蛋白的特性分析
- 批准号:
8210076 - 财政年份:2011
- 资助金额:
$ 79.24万 - 项目类别:
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