EPITHELIAL FUNCTION AND DYSFUNCTION IN CHRONIC SINUSITIS

慢性鼻窦炎的上皮功能和功能障碍

• 批准号: 6373438
• 负责人: Alkis Togias
• 金额: $ 87.79万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373438
• 关键词: cellular pathology; chronic disease /disorder; respiratory epithelium; sinusitis

Chronic rhinosinusitis effects n estimated 15% of the population of the United States, and the prevalence of this disease has been rising over the past decade. Annual direct medical costs are conservatively estimated at $2.4 billion; excluding the costs associated with the almost 200,000 sinus surgeries performed each year. Despite the high incidence of chronic rhinosinusitis, and its major impact on the health care system, little is known regarding the etiology and pathogenesis of this disease. Epithelial hyperplasia and inflammation are consistent and striking features of chronic rhinosinusitis. Indeed, imaging of these mucosal changes by CT or MRI is used to support diagnosis. It remains our central hypothesis that epithelial cell/mucosal dysfunction plays a central role in the pathogenesis of chronic rhinosinusitis. This dysfunction may arise due to an inherent genetic defect(s) environmental influences, or, most likely, a combination of the two. This Program Grant presents an integrated, multi-disciplinary approach to test this central hypothesis. The first project continues to focus on the potential genetic predisposition of some subjects to develop chronic rhinosinusitis. Specifically, a variety of approaches will be used to further test the hypothesis that patients with chronic rhinosinusitis have a higher rte of mutations in the cystic fibrosis transmembrane regulator than the health population. The second project focuses on the role of a specific environmental factor, respiratory viral infection as a trigger factor in altering epithelial cell function in a manner that plays a role in the pathogenesis of chronic rhinosinusitis. The third project has demonstrated that patients with refractory chronic rhinosinusitis demonstrated mucosal hyporesponsiveness to stimuli such as histamine, despite the presence of profound inflammation. Efforts will focus on determining the mechanism underlying this hyporesponsiveness and on evaluating if there is a familial predisposition for mucosal hyporesponsiveness. The three projects will interact by sharing protocols, expertise and patients, as well as through intellectual exchange. All three projects depend absolutely on the CORE for recruitment and characterization of patients and control population, and for critical support services. These studies should include important insights into the pathogenesis of chronic rhinosinusitis and may lead to the development of new approaches for the treatment of this major health problem.

据估计，美国15%的人口患有慢性鼻窦炎，在过去十年中，这种疾病的患病率一直在上升。每年直接医疗费用保守估计为24亿美元；不包括每年近20万例鼻窦手术的相关费用。尽管慢性鼻窦炎的发病率很高，并对卫生保健系统产生了重大影响，但人们对这种疾病的病因和发病机制知之甚少。上皮增生和炎症是慢性鼻窦炎的一贯和显著特征。事实上，这些粘膜改变的CT或MRI成像可用于支持诊断。我们的中心假设仍然是上皮细胞/粘膜功能障碍在慢性鼻窦炎的发病机制中起核心作用。这种功能障碍可能是由于固有的遗传缺陷、环境影响，或者最可能是两者的结合而引起的。该项目提供了一个综合的、多学科的方法来检验这一中心假设。第一个项目继续关注某些受试者发展慢性鼻窦炎的潜在遗传易感性。具体来说，将使用多种方法来进一步验证慢性鼻窦炎患者囊性纤维化跨膜调节因子的突变率高于健康人群的假设。第二个项目的重点是一个特定的环境因素，呼吸道病毒感染作为一个触发因素，在改变上皮细胞功能的方式中发挥作用，在慢性鼻窦炎的发病机制中起作用。第三个项目表明，难治性慢性鼻窦炎患者表现出粘膜对组胺等刺激的低反应性，尽管存在严重的炎症。努力将集中于确定这种低反应性的机制，并评估是否存在黏膜低反应性的家族易感性。这三个项目将通过共享协议、专业知识和患者以及知识交流进行互动。所有三个项目都完全依赖核心中心来招募和确定患者和对照人群的特征，以及提供关键的支持服务。这些研究应该包括对慢性鼻窦炎发病机制的重要见解，并可能导致治疗这一主要健康问题的新方法的发展。