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: 2073797
• 负责人: David Proud
• 金额: $ 75万
• 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/2073797
• 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 对该病的病因、发病机制和治疗进行研究。 上皮炎症和增生是一致的和引人注目的 慢性鼻窦炎的特点。事实上，上皮增厚代表着 通过CT和MRI扫描成像的异常，用于支持 诊断。我们假设某些人有易感性 发展成鼻窦炎，在这些患者中，环境 病毒、过敏原和污染等影响可以起到 诱发因素。这些环境因素可以诱导上皮细胞 引发炎症并随后减少的改变 粘液纤毛运输。鼻窦内粘液的淤积可以 促进细菌感染，这可能进一步影响 上皮组织。如果这个循环没有被打乱，上皮就会发育。 化生改变和下面的粘膜增殖，发展成 自持性循环，临床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 假设虽然上皮功能的改变可能会导致 通过几种不同的机制，它是正常上皮的腐败 功能，这是最终的共同途径，导致慢性 这种疾病的表现。 在这个项目中，我们开发了一种多学科的方法来 检验这一假设。外科医生，儿科医生，肺科医生， 传染病专家和过敏症专科医生已经将基础 科学家们。他们的努力集中在上皮细胞在患者身上的作用上。 患有最顽固的慢性鼻窦炎。特别是，我们 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因 上皮细胞功能，3)上皮细胞功能改变 运输和粘液分泌；4)过敏和粘液分泌的相互作用 活体鼻窦粘膜神经源性炎症。这个 调查人员之间的互动应该提供关于以下方面的新信息 并引出新的治疗策略。