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: 8600717
• 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/8600717
• 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. ! PUBLIC HEALTH RELEVANCE: This proposal represents a major step in determining the impact of HAART and immune restoration on the development of COPD and will provide a crucial foundation for future studies of HIV-related chronic lung disease. Given the increasing numbers of aging HIV-infected subjects with prolonged exposure to HIV and HAART, this study will provide important information for care and treatment of these patients.

描述（由申请人提供）：高效抗逆转录病毒疗法（HAART）与心血管并发症和自身免疫性疾病等慢性疾病的风险增加有关。我们最近发现，HAART 的使用与更严重的气道阻塞独立相关。该项目的总体目标是调查以下假设：通过 HAART 进行免疫恢复，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/慢性阻塞性肺疾病增加。我们将通过对匹兹堡大学艾滋病毒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的一部分存档的标本进行分析，来研究HAART启动的效果。研究目的： (1) 检验HAART 启动与气道阻塞和/或肺气肿增加相关的假设。 (2) 检验以下假设：启动 HAART 会诱发“改良免疫恢复综合征”，从而创建一个促炎环境以应对潜在的病原体和/或通过暴露自身抗原。 (3) 检验以下假设：响应肺孢子虫或自身抗原而产生的慢性炎症反应与气道阻塞和/或肺气肿增加相关。职业目标：本研究提案提出了一项综合计划，P.I.将有助于确定HAART和COPD之间的病理生理机制，还将实现以下目标： 1. 通过进行前瞻性纵向研究的经验，扩大候选人进行临床/转化研究的能力； 2. 提高考生统计分析和建模方面的分析能力； 3. 通过密集的教学、会议和研究经验，将候选人转变为艾滋病毒相关肺部疾病领域的领先独立研究者。 ！ 公共卫生相关性：该提案代表了确定 HAART 和免疫恢复对 COPD 发展影响的重要一步，并将为未来 HIV 相关慢性肺病的研究奠定重要基础。鉴于越来越多的老年HIV感染者长期接触HIV和HAART，这项研究将为这些患者的护理和治疗提供重要信息。