GRAIN DUST, ENDOTOXIN, AND AIRFLOW OBSTRUCTION

谷物灰尘、内毒素和气流阻塞

• 批准号: 2155368
• 负责人: David A Schwartz
• 金额: $ 24.71万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2155368
• 关键词: X ray; agriculture worker; asthma; biomarker; biopsy; bronchoscopy; complement; diagnostic respiratory lavage; dust; endotoxins; fibronectins; grain; histamine; immunologic skin test; inflammation; interleukin 1; interleukin 8; neutrophil; occupational hazard; questionnaires; respiratory airflow disorder; respiratory disorder; spirometry; tumor necrosis factor alpha; tumor necrosis factor beta

The goal of this proposal is to decrease the acute airway response to inhaled grain dust by using biologic and physiologic markers of airway injury to assess the efficacy of specific interventions. Grain dust induced airway disease is a common occupational and environmental form of lung disease. In North America alone, over 5 million agricultural workers are exposed to grain dust each year and between 10 and 20% develop airway disease. The overall hypothesis of this investigation is that endotoxin is the principle component of brain dust responsible for the development of airway inflammation and airflow obstruction. Our preliminary results indicate that the alveolar macrophage and specific cytokines appear to be particularly important in the initial inflammatory response. Our specific aims first investigate the relationship between inhalation of endotoxin and lower respiratory tract inflammation, comparing these results to what we have previously observed following inhalation of grain dust. Next, we study the relationship between endotoxin induced lower respiratory tract inflammation and the development of airflow obstruction, again comparing these results to what we have previously observed for grain dust. Based on our preliminary observations, we have proposed four distinct interventions (biological modification of grain dust, premedication with pentoxifylline, premedication with inhaled cromoglycate, and induction of tolerance to endotoxin); each intervention directed at a specific aspect of the exposure-response relationship. A series of double blinded, crossover intervention trials will be used in this investigation. Subjects will be inhalationally exposed to either buffered saline, grain dust extract, or an endotoxin solution. The physiologic (lung function) and biologic (cell and cell products in the peripheral blood, bronchoalveolar lavage fluid, endobronchial lavage and biopsy, and endobronchial brush biopsy) markers of response to these exposures will be measured and the effect of each specific intervention will be evaluated. Although components of grain dust, other than endotoxin, may lead to the development of grain dust induced asthma and bronchitis, a focused investigation of the role of endotoxin in the development of grain dust induced airway disease will markedly enhance our ability to treat individuals with grain dust induced lung disease and establish the scientific basis for control and prevention of this common occupational and environmental lung disorder.

该提议的目的是减少急性气道响应 使用气道的生物学和生理标记吸入谷物灰尘 伤害以评估特定干预措施的功效。谷物灰尘 诱导气道疾病是一种常见的职业和环境形式 肺部病。仅在北美，超过500万农业工作者 每年暴露于谷物灰尘，10％至20％的气道发生 疾病。这项研究的总体假设是内毒素是 脑尘的主要成分，负责开发 气道炎症和气流阻塞。我们的初步结果 表明肺泡巨噬细胞和特定细胞因子似乎是 在最初的炎症反应中尤为重要。我们的具体 目的首先研究内毒素吸入之间的关系 和下呼吸道炎症，将这些结果与 以前，我们已经观察到谷物灰尘吸入后。接下来，我们 研究内毒素诱导的下呼吸道 炎症和气流阻塞的发展，再次比较 这些结果是我们先前观察到的谷物灰尘的结果。基于 我们的初步观察，我们提出了四种不同的干预措施 （谷物灰尘的生物学修饰，用五氧化脂蛋白进行预处理， 用吸入的cromoglycate进行预处理，并诱导耐受性 内毒素）;每个干预措施都针对 暴露响应关系。一系列双眼的跨界 这项调查将使用干预试验。受试者将是 吸入暴露于缓冲盐水，谷物灰尘提取物或 内毒素溶液。生理（肺功能）和生物学（细胞 和外周血，支气管肺泡灌洗液中的细胞产物， 支气管灌洗和活检，以及支撑式刷子活检）标记 将测量对这些暴露的反应 将评估具体干预措施。虽然谷物的成分 灰尘除了内毒素外，可能导致谷物灰尘的发展 诱发哮喘和支气管炎，重点研究 内毒素在谷物粉尘引起的气道疾病的发展中将 明显增强了我们用谷物灰尘诱导的个人的能力 肺部疾病并建立控制和预防的科学基础 这种常见的职业和环境肺疾病。