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: 2672429
• 负责人: David Proud
• 金额: $ 81.36万
• 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/2672429
• 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视为主要健康问题 问题。 尽管其患病率很高并且事实上有数以百万计的人 美元用于治疗，基本上没有明确的 研究这种情况的病因、发病机制和治疗。 上皮炎症和增生是一致且引人注目的 慢性鼻窦炎的特点。 上皮增厚，实际上代表 通过 CT 和 MRI 扫描成像的异常情况，用于支持 诊断。 我们假设某些人有这样的倾向 发展为鼻窦炎，并且在这些患者中，环境因素 病毒、过敏原和污染等影响可以起到 诱发因素。 这些环境因素可诱发上皮细胞 引发炎症并随后减少的改变 粘液纤毛运输。 鼻窦内粘液的淤滞可能会导致 促进细菌感染，这可能进一步影响 上皮。 如果这个循环不被破坏，上皮就会发育 化生变化和下面的粘膜增殖，形成 自我延续的循环，临床上表现为慢性鼻窦炎和 这不再依赖于细菌或解剖结构。 因此，我们 假设，虽然可能诱导上皮功能的改变 通过几种不同的机制，它是正常上皮细胞的腐败 功能是导致慢性疾病的最终共同途径 疾病的表现。 在这个项目中，我们开发了一种多学科方法 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。 他们的工作重点是上皮细胞在患者中的作用 患有最持久的慢性鼻窦炎。 特别是，我们 计划检查四个方面：1）上皮细胞固有的遗传缺陷 功能，2）病毒感染作为改变的诱发因素 上皮细胞功能，3) 上皮离子功能改变 运输和粘液分泌以及4）过敏和过敏的相互作用 体内鼻和鼻窦粘膜的神经源性炎症。 这 研究者之间的互动应提供有关以下方面的新颖信息： 发病机制并导致新的管理策略。