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: 6281959
• 负责人: David Proud
• 金额: $ 5.69万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281959
• 关键词: chronic disease /disorder; clinical research; disease /disorder etiology; genetic susceptibility; human subject; ion transport; mucus; pathologic process; respiratory epithelium; respiratory hypersensitivity; respiratory virus; sinusitis; virus infection mechanism

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 consistent and striking features of chronic sinusitis. In fact, epithelial thickening, imaged by CT and MRI scans, is the supporting diagnostic abnormality. The hypothesis is that environmental influences such as viruses, allergens and pollutions can act as precipitating factors in individuals with predispostion to sinusitis. These envrionmental factors induce epithelial alterations triggering inflammation and subsequently decrease mucociliary transport. Stasis of mucus in the sinuses facilitates bacterial infection, which may then 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 which 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 fundtion that is the final common pathway leading to the chronic manifestations of the diasease. In this study, we have developed a multidisciplinary approach to examine this hypothesis. Surgeons, pediatricians, pulmonologists and allergists have combined with basic scientists to focus their efforts on the role of the epithelium in 378 patients with the most persistent forms of chronic sinusitis. In particular, we wil examine four aspects: 1) inherent genetic defects in epithelial function, 2) viral infections as a precipitating factor in epithelial function, 3) functional alterations in epithelial ion transport and mucus secretion, and 4) the interaction of allergic and neurogenic inflammation in nasal and sinus mucosa in vivo. The interactions among invetsigators from diverse disciplines 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一种主要健康 有问题。尽管它的高流行率和数百万人 美元都花在了治疗上，基本上还没有确定的 对这种情况的病因、发病机制和治疗方法的研究。 上皮炎症和增生是一致和显著的 慢性鼻窦炎的特点。事实上，上皮细胞增厚，由 CT和MRI扫描，是辅助诊断的异常。假说 是环境影响，如病毒、过敏原和污染 可作为易感人群的诱发因素 鼻窦炎。这些环境因素导致上皮细胞的改变。 引发炎症，随后减少粘液纤毛运输。 鼻窦内粘液的淤积有助于细菌感染，这可能 然后进一步影响上皮细胞。如果这个循环没有被打乱， 上皮发生化生改变和下面的粘膜 扩散，形成一个自我永续的循环，表现为 临床上表现为慢性鼻窦炎，不再依赖于 细菌或解剖结构。因此，我们假设，当 上皮功能可能由几种不同的机制诱导：它是 正常的上皮细胞功能的破坏是最终常见的 导致疾病慢性表现的途径。在这 研究，我们开发了一种多学科的方法来检查这一点 假设。外科医生、儿科医生、肺科医生和过敏症专家 与基础科学家结合起来，集中力量发挥作用 378例慢性阻塞性肺疾病最顽固型患者的上皮细胞 鼻窦炎。特别是，我们将检查四个方面：1)固有 上皮功能的遗传缺陷，2)病毒感染作为一种 上皮功能中的沉淀因子，3)功能改变 上皮离子转运和粘液分泌，以及4)相互作用 鼻和鼻窦粘膜的变态反应性和神经源性炎症。 来自不同学科的调查者之间的互动应该 提供关于发病机制的新信息，并导致新的管理 战略。