IMMUNE MECHANISMS OF MIDDLE EAR DISEASE

中耳疾病的免疫机制

• 批准号: 2633434
• 负责人: Philip Fireman
• 金额: $ 28.2万
• 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 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2633434
• 关键词: basophils; chemotaxis; clinical research; disease /disorder etiology; enzyme activity; histamine; human subject; hypersensitivity; immunology; middle ear; natural killer cells; neutrophil; otitis media; phagocytosis; respiratory infections; respiratory syncytial virus; rhinitis; superoxide dismutase

DESCRIPTION: Otitis media is a very common disease of children frequently diagnosed during upper respiratory infection. Surveys suggest that chronic otitis media is more common in children with allergies. The applicant's studies of twins from birth have reportedly found positive allergy skin tests in 50% of twins with chronic otitis media with effusion contrasted with 20% of twins with no ear disease (p<0.02). Past studies in allergic patients by this investigator and his group showed that nasal inflammation provoked by intranasal allergen challenge or natural pollen exposure is associated with eustachian tube obstruction, a risk factor for otitis media. Other studies by this group demonstrated that experimental upper respiratory infection in adult subjects using rhinovirus and influenza virus caused eustachian tube obstruction, abnormal middle ear pressures and otitis media. These viral upper respiratory infections also caused changes in bacterial flora of the nasopharynx, altered neutrophil function and depressed certain aspects of immune function. In addition, increased IgE responses of these subjects were found during and after the viral upper respiratory infections suggesting that a unique response of allergic subjects to virus infections may contribute to their higher incidence of otitis media. This work described in the present proposal is intended to further define various aspects of the interactions between allergy and virus infection and evaluate mechanisms which contribute to otitis media. Plans are also described to study respiratory syncytial virus (RSV) experimental infection and evaluate mechanisms which contribute to otitis media. This collaborative research effort by immunologists, otolaryngologists, microbiologists, physiologists and molecular biologists will better define the role of viral infection and allergy in the pathogenesis of otitis media and should result in improved management of this disease. The specific aims of the investigators in the current proposal are: (1) To extend the virus challenge models to include infection with RSV by: (a) defining the response of the nose, ET, and ME of AR and non-AR subjects to experimental RSV infection; (b) evaluating the potential of RSV to cause OM in adult volunteers; (c) determining the effects of RSV infection on host immune function, inflammatory mediator elaboration and nasopharyngeal bacterial carriage; and (d) evaluating the potential of RSV to prime the responses of the nose, ET, ME, and lungs to secondary challenges with inflammatory stimuli. (2) To evaluate suggested mechanisms of OM pathogenesis during experimental viral URI by (a) determining if poor ET function predisposes to OM; (b) assaying the effusions recovered from subjects with experimental OM for the presence of viruses and bacteria; (c) documenting the changes in nasopharyngeal flora during these infections; and (d) further characterizing the effects of virus infection on host defenses. (3) To evaluate the hypothesis that the presence of nasal allergy is a significant risk factor for the development of OM secondary to viral URIs by (a) comparing the responses of AR and non-AR subjects to viral infection; (b) determining if the response of AR subjects is primed by preexisting and concurrent allergen exposure to a perennial allergen; and (c) determining if a viral URI exacerbates the symptoms and pathophysiologies provoked by nasal challenge with a perennial allergen.

描述：中耳炎是儿童常见病、多发病。 在上呼吸道感染期间确诊。调查表明，慢性 中耳炎在有过敏症状的儿童中更为常见。申请人的 据报道，对双胞胎出生后的研究发现阳性过敏皮肤 50%的双生子慢性中耳炎渗出性中耳炎的对比试验 有20%的双胞胎没有耳部疾病(p&lt；0.02)。过敏性疾病的过去研究 这位研究人员和他的团队的患者表明，鼻部炎症 由鼻内过敏原挑战或自然花粉暴露引起的 与咽鼓管阻塞相关，这是中耳炎的危险因素。 该小组的其他研究表明，实验性上呼吸道 使用鼻病毒和流感病毒引起的成年人感染 咽鼓管阻塞、中耳压力异常和中耳炎。 这些病毒上呼吸道感染也引起了细菌的变化 鼻咽部菌群，改变中性粒细胞功能，抑制某些 免疫功能的各个方面。此外，这些细胞的免疫球蛋白E反应增强 受试者在病毒上呼吸道感染期间和之后被发现 这表明过敏受试者对病毒感染的独特反应 可能是他们中耳炎发病率较高的原因之一。这部作品 本提案中所描述的目的是进一步定义各种 变态反应与病毒感染相互作用的研究进展及评价 导致中耳炎的机制。 还描述了研究呼吸道合胞病毒(Rsv)的计划。 实验性感染和评估导致中耳炎的机制 媒体。这是免疫学家的合作研究成果， 耳鼻咽喉科医生、微生物学家、生理学家和分子生物学家 将更好地定义病毒感染和过敏在 中耳炎的发病机制，应改善治疗 这种病。 目前提案中调查人员的具体目标是：(1) 将病毒挑战模型扩展到包括RSV感染：(A) 确定AR和非AR受试者的鼻子、ET和ME对 实验性呼吸道合胞病毒感染；(B)评价呼吸道合胞病毒引起OM的可能性 成年志愿者；(C)确定呼吸道合胞病毒感染对宿主的影响 免疫功能、炎症介质的合成与鼻咽部 细菌携带；以及(D)评估呼吸道合胞病毒对启动 鼻、ET、ME和肺对二次挑战的反应 炎性刺激。 (2)评价实验性OM发病机制。 病毒URI通过(A)确定糟糕的ET功能是否易患OM；(B) 检测实验性OM受试者的渗出液 病毒和细菌的存在；(C)记录 这些感染期间的鼻咽菌群；和(D)进一步的特征 病毒感染对宿主防御的影响。(3)评估 假设鼻部过敏是一个重要的危险因素 通过(A)比较病毒性URI继发性OM的发生 AR和非AR受试者对病毒感染的反应；(B)确定 AR受试者的反应是由预先存在和同时存在的过敏原启动的 接触常年过敏原；以及(C)确定病毒URI 加重由鼻腔刺激引起的症状和病理生理 常年性过敏原。