ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS

过敏性支气管肺曲霉病

• 批准号: 3818343
• 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/3818343
• 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.

人们认识到，肺是一种免疫器官。 过敏性巨肺曲霉病(ABPA)可能是一种非常 肺免疫系统如何反应的重要模型。这个 拟议的调查将包括对支气管肺泡的分析 已知的ABPA和疑似ABPA受试者的灌洗(BAL)，将 扩展目前可用的免疫分析方法以研究ABPA的某些方面 和囊性纤维化(CF)，并将尝试开发新的检测方法 这可能为深入了解ABPA的免疫发病机制提供依据。 计划进行调查，以解释肺损伤的机制 以确定ABPA的预后因素，指导强的松 更准确的治疗，并在更早的时候确认诊断 疑似案件。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的升高，并不是所有的都与Af有关， 2)血清Ig E-Af、Ig G-Af升高；3)沉淀 抗Af抗体，4)外周血嗜碱性粒细胞高反应性 对Af和其他真菌，以及5)致敏淋巴细胞。 通过以下途径逐步早期诊断ABPA是可能的 免疫分析。需要检验的主要假设是，当地的 发生的免疫反应(抗体、免疫复合体、细胞) ABPA会导致肺损伤，导致近端支气管扩张， 闭塞性细支气管炎，或混合间质肺泡内 ABPA中的病变。接下来的逻辑问题是：1)可以 肺泡灌洗液和外周血对肺的解释机制分析 损坏？2)当地抗体生产的测量许可吗？ 对可疑病例进行ABPA的早期诊断或作为指导 对已确定的强的松治疗 病人？ ABPA在慢性阻塞性肺疾病患者评估中的假说 慢性阻塞性肺疾病是当ABPA合并慢性阻塞性肺疾病时，进行性肺破坏 是由于对定居的生物的强烈免疫反应造成的 支气管炎。一个关键的问题可能是是否有 粘液同型抗体(IgE、Ig G、Ig A)水平升高 ABPA和ABPA患者血清中产铜绿假单胞菌 Cf与单纯cf患者的血清比较。