IMMUNE MECHANISMS OF MIDDLE EAR DISEASE

中耳疾病的免疫机制

• 批准号: 3128602
• 负责人: Philip Fireman
• 金额: $ 20.88万
• 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 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3128602
• 关键词: Macaca; acute disease /disorder; airborne allergen; antihistamines; basophils; chronic disease /disorder; disease /disorder prevention /control; ear disorder chemotherapy; ear disorder diagnosis; eosinophil; histamine; histamine release; human subject; human therapy evaluation; immunoglobulins; immunopathology; immunopathology diagnosis; immunopharmacology; inflammation; mast cell; medical complication; neurotoxins; neutrophil; nonhuman therapy evaluation; otitis media; pediatrics; prostaglandins; relapse /recurrence; respiratory hypersensitivity; respiratory virus; rhinitis

The goals of this research are to define the etiologies and pathogeneses of otitis media with effusion. Our past studies have documented several pathogenic pathways whereby nasal inflammation provoked by allergy or viral infection are manifest as eustachian tube obstruction, a recognized cause of otitis media with effusion. The purpose of this ongoing research is to define the role and interaction of allergy and viral infection in promoting nasal congestion, tubal obstruction and middle ear pathophysiology. These relationships will be explored with an emphasis on amplification, modulation and prolongation of primary responses. Specifically, we will utilize human models for challenges with inflammatory mediators, allergens and viruses, and animal models of IgE hypersensitivity to: 1) define the role of inflammatory mediators in causing tubal obstruction and middle ear disease; 2) document the potential of allergen and viral priming and late allergic reactions to enhance and sustain the nasal and middle ear pathophysiologies; and 3) determine if allergic rhinitis subjects are hyperresponsive to upper respiratory virus infection. Age related response differences between children and adults will be further defined. Children who are indentified in prospective studies as "otitis prone" will be evaluated for immune defects to explain their recurrent ear infections. Middle ear effusions (MEE) from children with acute and chronic OME will be assayed for histamine, prostaglandins, tryptase and eosinophil derived major basic protein and neurotoxin. Enhanced basophil histamine release and production of histamine releasing factors will be explored as possible predisposing factors in these children. This collaborative research effort by clinical immunologists, otolaryngologists, microbiologists, physiologists and biochemists will better define the role of allergy and viral infection in the pathogenesis of OME and should result in improved diagnosis and management of this most common pediatric disease.

本研究的目的是确定的病因和发病机制， 渗出性中耳炎 我们过去的研究记录了几个 过敏或病毒引起的鼻腔炎症的致病途径 感染表现为咽鼓管阻塞，这是公认原因 分泌性中耳炎 这项研究的目的是 明确过敏和病毒感染在促进 鼻充血、输卵管阻塞和中耳病理生理。 这些 关系将探讨与放大的重点， 调节和延长主要反应。 具体来说，我们将 利用人类模型进行炎症介质、过敏原的挑战 和病毒，以及IgE超敏反应的动物模型，以：1）定义 炎症介质在输卵管阻塞和中耳炎中的作用 疾病; 2）记录过敏原和病毒引发的可能性， 过敏反应，以提高和维持鼻和中耳 病理生理学;和3）确定过敏性鼻炎受试者是否 对上呼吸道病毒感染有过敏反应。 年龄相关反应 将进一步界定儿童和成人之间的差异。 儿童 在前瞻性研究中被确定为“易患耳炎”的人， 评估免疫缺陷来解释他们反复的耳部感染。 急性和慢性OME儿童的中耳积液（中耳积液）将在 测定组胺、类胰蛋白酶和嗜酸性粒细胞衍生物 主要碱性蛋白和神经毒素。 嗜碱性粒细胞组胺释放增强 并尽可能探索组胺释放因子的产生 这些孩子的诱发因素 这项合作研究成果 临床免疫学家，耳鼻喉科医生，微生物学家， 生理学家和生物化学家将更好地定义过敏的作用， 病毒感染在OME的发病机制，并应导致改善 诊断和管理这种最常见的儿科疾病。