HAART-mediated Immune Restoration in Chronic Obstructive Pulmonary Disease

HAART 介导的慢性阻塞性肺疾病的免疫恢复

• 批准号: 8403968
• 负责人: MARJORIE Patricia GEORGE
• 金额: $ 13.11万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-18 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8403968
• 关键词: Acquired Immunodeficiency Syndrome; Age; Aging; Antibodies; Antibody Formation; Antinuclear Antibodies; Archives; Autoantigens; Autoimmune Diseases; Autoimmune Responses; Biological Assay; CD4 Lymphocyte Count; Carbon Monoxide; Cardiovascular Diseases; Cardiovascular system; Caring; Chest; Chronic; Chronic Obstructive Airway Disease; Chronic lung disease; Clinic; Clinical; Cohort Studies; Collaborations; Control Groups; Controlled Study; Data; Development; Diffuse; Disease; Dyslipidemias; Elastin; Enrollment; Environment; Enzyme-Linked Immunosorbent Assay; Event; Exposure to; Foundations; Future; Goals; HIV; HIV Infections; HIV Seropositivity; Health; Highly Active Antiretroviral Therapy; Immune; Immune response; Indirect Immunofluorescence; Individual; Inflammation; Inflammatory; Inflammatory Response; Lead; Length; Life; Linear Regressions; Link; Literature; Logistic Regressions; Longitudinal Studies; Lung; Lung diseases; Measures; Mediating; Medical; Modeling; Multivariate Analysis; Obstruction; Outpatients; Pathogenesis; Patients; Persons; Play; Pneumocystis; Population; Pulmonary Emphysema; Pulmonary function tests; Recovery; Research; Research Personnel; Research Proposals; Risk; Risk Factors; Role; Sampling; Schedule; Serum; Smoking History; Specimen; Spirometry; Sputum; Stimulus; Syndrome; Techniques; Testing; Time; To autoantigen; Universities; Woman; X-Ray Computed Tomography; airway obstruction; autoimmune thyroid disease; career; cohort; experience; improved; pathogen; prospective; public health relevance; response; restoration; symposium; therapy duration; tobacco exposure; translational study

DESCRIPTION (provided by applicant): Highly active antiretroviral therapy (HAART) has been linked to increased risk of chronic medical conditions, from cardiovascular complications to autoimmune diseases. We have recently found that use of HAART is independently associated with worse airway obstruction. The overall goal of this project is to investigate the hypothesis that immune restoration through HAART leads to increased airway obstruction/chronic obstructive pulmonary disease via propagation of a chronic inflammatory response to pulmonary pathogens and/or autoantigens. We will study the effects of HAART initiation through a prospective longitudinal study of HIV outpatients at the University of Pittsburgh, as well as through an analysis of specimens archived as part of the Multicenter AIDS Cohort Study and the Women's Interagency Study. Research Aims: (1) To test the hypothesis that HAART initiation is associated with increased airway obstruction and/or emphysema. (2) To test the hypothesis that initiating HAART induces a "modified immune restoration syndrome," creating a pro-inflammatory environment in response to an underlying pathogen and/or through unmasking of autoantigens. (3) To test the hypothesis that development of a chronic inflammatory response, either in response to Pneumocystis or autoantigens, is associated with increased airway obstruction and/or emphysema. Career Goals: This research proposal presents a comprehensive plan by which the P.I. will help determine pathophysiologic mechanisms connecting HAART and COPD and will also achieve the following: 1. Broaden the candidate's ability to perform clinical/translational studies through the experience of conducting a prospective longitudinal study; 2. Increase the candidate's analytical techniques in statistical analysis and modeling; and 3. Transform the candidate into a leading independent investigator in HIV-associated pulmonary disease through intensive didactics, conferences, and research experience. !

描述（由申请人提供）：高效抗逆转录病毒疗法（HAART）与慢性疾病风险增加有关，从心血管并发症到自身免疫性疾病。我们最近发现HAART的使用与气道阻塞恶化独立相关。本项目的总体目标是研究通过HAART的免疫恢复通过传播对肺部病原体和/或自身抗原的慢性炎症反应导致气道阻塞/慢性阻塞性肺病增加的假设。我们将通过对匹兹堡大学HIV门诊患者的前瞻性纵向研究，以及对作为多中心艾滋病队列研究和妇女机构间研究一部分存档的标本进行分析，研究HAART启动的影响。研究目的：（1）验证HAART启动与气道阻塞和/或肺气肿增加相关的假设。(2)为了检验启动HAART诱导“改良免疫恢复综合征”的假设，即响应潜在病原体和/或通过暴露自身抗原产生促炎环境。(3)检验肺孢子虫或自身抗原引起的慢性炎症反应与气道阻塞和/或肺气肿增加相关的假设。职业目标：本研究建议提出了一个全面的计划，其中P.I.将有助于确定连接HAART和COPD的病理生理机制，并将实现以下目标：1.通过进行前瞻性纵向研究的经验，拓宽候选人进行临床/转化研究的能力; 2.提高考生在统计分析和建模方面的分析技巧; 3.通过密集的教学，会议和研究经验，将候选人转变为HIV相关肺部疾病的领先独立研究者。!