ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS

过敏性支气管肺曲霉病

• 批准号: 3809780
• 负责人: PAUL A GREENBERGER
• 金额: --
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3809780
• 关键词: Aspergillus; B lymphocyte; Pseudomonas aeruginosa; T lymphocyte; antibody formation; aspergillosis; asthma; basophils; bronchiectasis; cell population study; cystic fibrosis; diagnosis design /evaluation; diagnostic respiratory lavage; emphysema; enzyme linked immunosorbent assay; histamine release; human subject; human therapy evaluation; immunoglobulin A; immunoglobulin E; immunoglobulin G; immunopharmacology; prednisone; respiratory disorder diagnosis; respiratory hypersensitivity

It is recognized that the lung functions as an immunologic organ. Allergic Mronchopulmonary Aspergillosis (ABPA) may serve as a very important model of how the pulmonary immune system responds. The proposed investigations will include analysis of bronchoalveolar lavage (BAL) from known ABPA and suspected ABPA subjects, will extend currently available immunoassays to study aspects of ABPA and cystic fibrosis (CF), and will attempt to develop new assays that may provide insight into the immunopathogenesis of ABPA. Investigations are planned to explain mechanisms of lung damage in ABPA, to identify prognostic factors in ABPA, to guide prednisone therapy more precisely, and to confirm a diagnosis earlier in suspect cases. The pathogenesis of ABPA is unclear but is likely related to the array of immunologic abnormalities including 1) elevation of total serum IgE, not all of which is directed to Af, 2) elevated serum IgE-Af IgG-AF, and IgA-Af, 3) precipitating antibodies to Af, 4) hyperreactivity of peripheral blood basophils to Af and other fungi, and 5) sensitized lymphocytes. Progressively earlier diagnosis of ABPA is possible through immunoassays. The main hypothesis to be tested is that the local immune response (antibodies, immune complexes, cells) occurring in ABPA results in lung injury which produces proximal bronchiectasis, bronchiolitis obliterans, or mixed interstitial intraalveolar lesions in ABPA. Logical questions that follow are: 1) can analysis of BAL and peripheral blood explain mechanisms of lung damage? and 2) does measurement of local antibody production permit an earlier diagnosis of ABPA in suspect cases or serve as a guide to prednisone therapy in established patients? The hypothesis regarding the evaluation of ABPA in patients with CF is that when ABPA complicates CF, progressive lung destruction results from an intense immune response to organisms that colonize the bronchi. A critical question may be whether there are increased levels of isotypic antibodies (IgE, IgG, IgA) to mucoid producing Pseudomonas aeruginosa in sera of patients with ABPA and CF compared to sera of patients ?with CF alone.

肺被认为是一种免疫器官。 过敏性支气管肺炎（ABPA）可能是一种非常 肺免疫系统如何反应的重要模型。 的 建议的研究将包括支气管肺泡 已知ABPA和疑似ABPA受试者的灌洗（BAL）将 扩展目前可用的免疫测定，以研究ABPA的各个方面 和囊性纤维化（CF），并将尝试开发新的检测方法， 这可能会提供深入了解ABPA的免疫发病机制。 研究计划解释肺损伤的机制， ABPA，识别ABPA中的预后因素，以指导泼尼松 更准确地治疗，并在更早的时间内确认诊断。 可疑案件。 ABPA的发病机制尚不清楚，但很可能 与一系列免疫异常有关，包括1） 血清总IgE升高，并非所有IgE均针对Af， 2)血清IgE-Af IgG-AF和IgA-Af升高，3）沉淀 Af抗体，4）外周血嗜碱性粒细胞的高反应性 致敏淋巴细胞。 ABPA的早期诊断是可能的， 免疫测定。 要检验的主要假设是， 免疫反应（抗体，免疫复合物，细胞）发生在 ABPA导致肺损伤，其产生近端支气管扩张， 闭塞性细支气管炎，或混合性间质性肺泡内炎 ABPA病变。 逻辑问题如下：1）可以 BAL和外周血分析解释肺的机制 损害？和2）当地抗体生产的测量是否允许 在可疑病例中早期诊断ABPA或作为指导 泼尼松治疗， 病人？ 关于ABPA在以下患者中的评价的假设 CF是当ABPA并发CF时，进行性肺破坏 是由对殖民生物的强烈免疫反应引起的 支气管 一个关键问题可能是是否有 抗粘液素同种型抗体（IgE、IgG、伊加）水平升高 在ABPA患者血清中产生铜绿假单胞菌， CF与患者血清相比？单独使用CF。