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: 2517274
• 负责人: David Proud
• 金额: $ 79.23万
• 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 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517274
• 关键词: cellular pathology; chronic disease /disorder; respiratory epithelium; sinusitis

Over 31 million Americans describe chronic sinusitis as a major health problem. Despite its high prevalence and the fact that millions of dollars are spent on treatment, there have been essentially no definitive studies of the etiology, pathogenesis and therapy of this condition. Epithelial inflammation and hyperplasia are a consistent and striking feature of chronic sinusitis. Epithelial thickening, in fact, represents the abnormality, imaged by CT and MRI scans, that is used to support the diagnosis. We hypothesize that certain individuals have a predisposition to developing sinusitis and that, in these patients, environmental influences, such as viruses, allergens and pollution, can act as precipitating factors. These environmental factors can induce epithelial alterations that trigger inflammation and subsequently decrease mucociliary transport. Stasis of mucus in the sinuses could then facilitate bacterial infections, which may further influence the epithelium. If this cycle is not disrupted, the epithelium develops metaplastic changes and the underlying mucosa proliferates, developing a self-perpetuating cycle that manifests clinically as chronic sinusitis and that is no longer dependent on the bacteria or the anatomy. Thus, we hypothesize that, while alterations in epithelial function may be induced by several different mechanisms, it is the corruption of normal epithelial function that is the final common pathway that leads to the chronic manifestations of the disease. In this program project, we developed a multidisciplinary approach to examine this hypothesis. Surgeons, pediatricians, pulmonologists, infectious disease specialists and allergists have combined with basic scientists. Their efforts focus on the role of the epithelium in patients with the most persistent forms of chronic sinusitis. In particular, we plan to examine four aspects: 1) inherent genetic defects in epithelial function, 2) viral infection as a precipitating factor in altering epithelial cell function, 3) functional alterations in epithelial ion transport and mucus secretion and 4) the interaction of allergic and neurogenic inflammation on nasal and sinus mucosa in vivo. The interactions between investigators should provide novel information about pathogenesis and lead to new management strategies.

超过3100万美国人将慢性鼻窦炎描述为主要的健康问题 问题. 尽管其发病率很高， 美元花在治疗上，基本上没有明确的 病因、发病机制和治疗的研究。 上皮炎症和增生是一个一致的和惊人的 慢性鼻窦炎的症状 上皮增厚，事实上，代表了 通过CT和MRI扫描成像的异常，用于支持 诊断. 我们假设某些人有 发展鼻窦炎，在这些患者中， 影响，如病毒，过敏原和污染，可以作为 诱发因素 这些环境因素可以诱导上皮细胞 引发炎症并随后降低 粘液纤毛运输 鼻窦中的粘液淤积 促进细菌感染，这可能进一步影响 上皮 如果这个周期不被破坏， 化生改变和下面的粘膜增生，发展成 自我延续的周期，临床表现为慢性鼻窦炎， 不再依赖于细菌或解剖结构。 因此我们 假设，虽然上皮功能的改变可以被诱导， 通过几种不同的机制，它是正常上皮细胞的腐败， 功能，这是最终的共同途径，导致慢性 疾病的表现。 在这个项目中，我们开发了一种多学科的方法， 检验这个假设。 外科医生，儿科医生，肺科医生， 传染病专家和过敏症专家结合了基本的 科学家 他们的努力集中在上皮细胞在患者中的作用 患有最顽固的慢性鼻窦炎 我们尤其 计划检查四个方面：1）上皮细胞的固有遗传缺陷 功能，2）病毒感染作为改变的诱发因素 上皮细胞功能，3）上皮细胞离子功能改变 运输和粘液分泌和4）过敏和 鼻和鼻窦粘膜的神经源性炎症。 的 研究者之间的互动应提供有关以下方面的新信息： 发病机制，并导致新的管理策略。