HIV and COPD:Immune mediated mechanisms

HIV 和 COPD：免疫介导机制

基本信息

批准号：
9323504
负责人：
Douglas Kwon
金额：
$ 65.6万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
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 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9323504
关键词：
Alveolitis Anatomy Antioxidants Biological Markers Blood Blood Vessels Bronchoalveolar Lavage Bronchoalveolar Lavage Fluid Bronchoscopy CD8-Positive T-Lymphocytes Cells Chronic Chronic Obstructive Airway Disease Color Control Groups Data Development Disease Echocardiography Environmental air flow Equilibrium Flow Cytometry Gene Chips Gene Expression Gene Expression Profiling HIV HIV Infections High Resolution Computed Tomography Imaging Techniques Imaging technology Immune Immune System Diseases Immune response Immune system Immunology procedure Incidence Individual Infection Injury Institutes Lung Lung diseases Malignant neoplasm of lung Measurement Measures Mediating Molecular Morbidity - disease rate Oxidants Oxidative Stress Pathogenesis Patients Perfusion Phenotype Physiological Physiology Population Positron-Emission Tomography Process Pulmonary Emphysema Pulmonary Hypertension Pulmonary artery structure Pulmonary function tests Respiratory Signs and Symptoms Respiratory physiology Role Saline Sampling Severities T-Cell Activation T-Lymphocyte Vascular remodeling Viral Virus Work X-Ray Computed Tomography airway obstruction antiretroviral therapy cohort defined contribution indexing innovative technologies lung injury metabolomics mortality novel marker novel therapeutics peripheral blood pressure public health relevance

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（由申请人提供）：全世界有超过3000万人患有艾滋病毒。在患有慢性HIV感染的个体中，肺部疾病是发病率和死亡率的主要原因。 HIV感染增加了慢性阻塞性肺疾病（COPD）以及其他肺部疾病的发生率。实际上，在某些研究中，HIV患者的呼吸道症状和/或异常肺功能测试（PFT）的发生率高达60％。众所周知，引起非感染性肺部疾病的机制知之甚少。已经提出，来自HIV的免疫失调是该过程的重要促进者。此外，病毒对肺部细胞的直接作用，氧化细菌，肺部的慢性低度感染以及抗逆转录病毒疗法（ART）的使用可能有助于这些疾病的发病机理。对与HIV相关的肺部疾病涉及的分子机制的更多了解可能有助于鉴定新型的生物标志物，促进预防方法并指导新型疗法的发展。但是，确定慢性HIV感染中COPD的确切发病机理的研究受到限制。为了更好地定义慢性HIV中COPD的分子机制，我们建议使用尖端的成像技术，支气管镜检查和先进的免疫测定法对表型HIV感染的受试者进行广泛的疾病感染受试者，并将这些措施与COPD的发病率和进展相关。我们假设在慢性HIV感染的患者中，对小气道的反复损伤以及肺血管造成了肺血管，从而导致过滤变化和肺血管重塑导致COPD。使用慢性艾滋病毒感染患者的队列，我们将确定气道阻塞的受试者，并将其与具有正常肺功能的受试者进行比较。我们将使用高分辨率计算机断层扫描（HRCT），超声心动图和正电子发射断层扫描（PET）进一步表型受试者。这些成像技术将提供定量的解剖和生理数据，包括对肺和肺血管破坏的极敏感测量，区域肺通风和区域肺灌注。这些数据将与对T细胞活性的评估和支气管肺泡灌洗（BAL）液和外周血中的氧化应激相关。此外，我们将广泛探索具有代谢组和基因表达研究的人群中COPD的其他潜在原因。我们还将通过利用独特的精英HIV控制器来探讨ART在COPD发病机理中的潜在作用。具体目的是：1）确定慢性HIV中T细胞，肺损伤和COPD的慢性激活之间的关系； 2）确定慢性HIV患者肺中氧化应激水平，并定义对肺损伤和COPD的贡献。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

PET Imaging Reveals Early Pulmonary Perfusion Abnormalities in HIV Infection Similar to Smoking.

PET 成像显示 HIV 感染的早期肺灌注异常，与吸烟类似。

DOI：
10.2967/jnumed.120.245977
发表时间：
2021
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
0
作者：
Kohli,Puja;Kelly,VanessaJ;Hibbert,KathrynA;Corleis,Björn;Kone,Mamary;Cho,JosalynL;DeFaria-Yeh,Doreen;Kwon,DouglasS;Medoff,BenjaminD;Harris,RScott;Winkler,Tilo
通讯作者：
Winkler,Tilo

Lung T cells in HIV infection. Driven to exhaustion?

HIV 感染中的肺 T 细胞。