IMMUNE MECHANISMS OF MIDDLE EAR DISEASE

中耳疾病的免疫机制

• 批准号: 3128600
• 负责人: Philip Fireman
• 金额: $ 12.61万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-08-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3128600
• 关键词: airborne allergen; antihistamines; child (0-11); ear disorder chemotherapy; histamine; human subject; immune adherence reaction; immunoglobulins; immunopathology diagnosis; immunopharmacology; leukotrienes; methacholine; otitis media; prostaglandins; respiratory hypersensitivity; respiratory pharmacology; rhinitis; seasons

The objectives of this research are to define those immune mechanisms including allergy which have been suggested but not established as important in the pathogenesis of otitis media with effusion (OME). OME is a multifactorial syndrome in which infection and eustachian tube obstruction (ETO) are the best documented pathogenetic mechanisms. A provocative intranasal antigen (pollen) challenge which induces ETO in adults with allergic rhinitis has been shown to be a reproducible, reversible immune response which is antigen dose dependent and related to IgE antibody. This research plan will study immune and non-immune factors which may sustain and prolong ETO and explore potential relationships for antigen induced ETO and upper respiratory infections. Since OME is a disease primarily of children, this research plan will begin to extend these observations from adults to children with allergic rhinitis and OME. Immune reactions, including allergy, release and generate mediators in tissues and secretions of inflammation. This research will study whether intranasal provocative challenge with these mediators including histamine, prostaglandins and leukotrienes as well as methacholine will induce ETO. New technology including a sonometric method of measuring ETO along with a computer assisted rhinomanometer with capabilities of performing both active and passive, anterior and posterior rhinometry will be utilized. In addition, the presence of these mediators will be studied in middle ear fluids, and nasal secretions of patients with OME and allergic rhinitis and correlated with presence of Ig isotypes, bacteria cultures and clinical course. Since certain questions concerning the development of ETO and OME require invasive techniques and are not suitable in man, a monkey animal model of antigen induced ETO has been developed. Histamine intranasal challenge has also induced ETO in the monkey, especially in younger animals and the role of histamine, methacholine, prostaglandins and leukotrienes in the pathogenesis of ETO and OME will be examined in this model. Age related differences will be explored at each aspect of the experimental design. By understanding the role of immune reactions, especially allergy, in the pathogenesis of ETO and OME, this research should provide the basis for future studies to establish better diagnosis and therapy of this most common pediatric illness.

本研究的目标是定义这些免疫机制 包括已被建议但尚未确定为 在渗出性中耳炎（OME）的发病机制中起重要作用。 OME为 一种多因素综合征，其中感染和咽鼓管 梗阻（ETO）是最好的记录发病机制。 一 激发性鼻内抗原（花粉）激发，诱导ETO， 患有过敏性鼻炎的成年人已被证明是可重复的， 可逆的免疫应答，其是抗原剂量依赖性的，并且与 IgE抗体。 这项研究计划将研究免疫和非免疫因素 这可能会维持和延长ETO，并探索潜在的关系， 抗原诱导的ETO和上呼吸道感染。 由于OME是一个 疾病主要是儿童，这项研究计划将开始扩大 这些观察结果从成人到儿童过敏性鼻炎和OME。 免疫反应，包括过敏，释放和产生介质， 炎症组织和分泌物。 这项研究将研究是否 用这些介质鼻内激发攻击， 三尖杉酯碱和白三烯以及乙酰甲胆碱将诱导ETO。 新技术，包括测量ETO的声测法，沿着 计算机辅助气压计，具有执行 将使用主动和被动、前部和后部的曲率测量法。 在 此外，将研究这些介质在中耳中的存在 OME和过敏性鼻炎患者的液体和鼻分泌物， 与IG同种型的存在、细菌培养和临床 当然了 由于有关ETO和OME发展的某些问题 需要侵入性技术，不适合人类，猴子动物 建立了抗原诱导的ETO模型。 鼻内组胺 攻毒也在猴中诱导ETO，尤其是在年幼动物中 以及组胺、乙酰甲胆碱、三尖杉酯碱和白三烯在 ETO和OME的发病机制将在该模型中进行检查。 年龄 相关的差异将在实验的各个方面进行探讨 设计 通过了解免疫反应的作用，特别是过敏， 在ETO和OME的发病机制中，本研究应为 为未来的研究，以建立更好的诊断和治疗这一最 常见的儿科疾病