IDIOPATHIC PULMONARY FIBROSIS--PATHOGENESIS AND STAGING

特发性肺纤维化——发病机制和分期

• 批准号: 3858937
• 负责人: TALMADGE E KING
• 金额: --
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3858937
• 关键词: T lymphocyte; allergic pneumonitis; alveolar macrophages; bactericidal immunity; biopsy; cellular pathology; diagnostic respiratory lavage; disease /disorder classification; extracellular matrix; fibroblasts; histopathology; human subject; human therapy evaluation; immunocytochemistry; immunoregulation; inflammation; interferons; lung alveolus; lung disorder; lung imaging /visualization /scanning; monocyte; noninvasive diagnosis; pathologic process; phagocytosis; phospholipids; platelet derived growth factor; prognosis; pulmonary fibrosis /granuloma; pulmonary surfactants; respiratory disorder chemotherapy; transforming growth factors; vascular endothelium permeability

Idiopathic pulmonary fibrosis is a disease of unknown etiology characterized pathologically by a chronic inflammatory process that precedes and likely controls the alterations in connective tissue matrix that eventually destroys the normal lung architecture. The mechanisms involved in this process are not known but a complex cell-cell interactive sequence, involving principally neutrophils, lymphocytes, macrophages and fibroblast is believed to be responsible. The long-term objectives of this project are to determine what alterations in cellular composition, function and trafficking occurs in the lung parenchyma of patients with idiopathic pulmonary fibrosis and to relate these alterations to the disease stage, prognosis, and therapeutic responsiveness. Our specific aims are to: (1) correlate noninvasive methods, primarily bronchoalveolar lavage and a new lung scanning technique, Inulin- labelled neutrophils (or monocytes), with clinical and morphological parameters to determine if (and how) these methods are to be used in diagnosis, staging and predicting therapeutic response; (2) to utilize functional assays and immunohistochemical techniques to characterize the cells and extracellular matrix of the lung parenchyma and to correlate these findings with those obtained by BAL and with the clinical parameter. We expect that these investigations will answer several questions: What are the features of IPF that determine disease activity and therapeutic responsiveness? Is lavage analysis a sensitive and specific method for the detection of these features in all patients with IPF? How can lavage be used most effectively, especially its relationship to other measures of disease activity such as immune complexes? Is the inflammatory response in the lavage "in phase" with that found in the lung parenchyma? Can the extent and severity of the disease be measured/assessed by semiquantitative routine histologic methods or does it require morphometric techniques?

特发性肺纤维化是一种未知病因的疾病 通过慢性炎症过程在病理上表征 这是之前并可能控制结缔组织的变化 最终破坏正常肺的组织基质 建筑学。 此过程中涉及的机制不是 已知但复杂的细胞 - 细胞交互序列，涉及 主要是中性粒细胞，淋巴细胞，巨噬细胞和成纤维细胞 被认为是负责任的。 该项目的长期目标是确定什么 细胞组成，功能和运输的改变 发生在特发性患者的肺实质中 肺纤维化并将这些改变与疾病联系起来 阶段，预后和治疗反应能力。 我们的具体 目的是：（1）关联无创方法，主要是 支气管肺泡灌洗和一种新的肺扫描技术，inulin- 标记的嗜中性粒细胞（或单核细胞），具有临床和 形态学参数以确定是否（以及如何） 方法应用于诊断，分期和预测 治疗反应； （2）利用功能分析和 免疫组织化学技术以表征细胞和 肺实质的细胞外基质并相关 这些发现与BAL和临床获得的发现 范围。 我们希望这些调查会回答几个 问题：确定疾病的IPF的特征是什么 活动和治疗反应？ 是灌洗分析 检测这些特征的敏感和特定方法 在所有患有IPF的患者中？ 如何最多使用灌洗 有效，尤其是其与其他措施的关系 疾病活动，例如免疫复合物？ 是炎症 与肺中发现的灌洗型“相”的反应 实质？ 疾病的程度和严重程度可以 通过半定量常规组织学方法进行测量/评估 还是需要形态计量技术？