ACUTE-, LATE- AND RESOLUTION PHASE OF THE ASTHMATIC RESPONSE IN THE SMALL AIR

小空气中哮喘反应的急性期、晚期期和消退期

• 批准号: 7718007
• 负责人: DONALD P TASHKIN
• 金额: $ 0.11万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718007
• 关键词: Acute; Address; Adrenal Cortex Hormones; Air; Alveolar; Anti-Inflammatory Agents; Anti-inflammatory; Antigens; Asthma; Breathing; Computer Retrieval of Information on Scientific Projects Database; Distal; Exhalation; Felis catus; Frequencies; Funding; Future; Grant; Immunologic Markers; Individual; Inflammatory; Inspiratory Capacity; Institution; Invasive; Life; Lung; Lung Inflammation; Measures; Nitric Oxide; Phase; Physiological; Pulmonary Function Test/Forced Expiratory Volume 1; Rate; Research; Research Personnel; Residual volume; Resistance; Resolution; Resources; Source; Steroids; Symptoms; Techniques; Time; United States National Institutes of Health; airway inflammation; computerized; lung imaging; novel; predictive modeling; respiratory; response; Acute; Address; Adrenal Cortex Hormones; Air; Alveolar; Anti-Inflammatory Agents; Anti-inflammatory; Antigens; Asthma; Breathing; Computer Retrieval of Information on Scientific Projects Database; Distal; Exhalation; Felis catus; Frequencies; Funding; Future; Grant; Immunologic Markers; Individual; Inflammatory; Inspiratory Capacity; Institution; Invasive; Life; Lung; Lung Inflammation; Measures; Nitric Oxide; Phase; Physiological; Pulmonary Function Test/Forced Expiratory Volume 1; Rate; Research; Research Personnel; Residual volume; Resistance; Resolution; Resources; Source; Steroids; Symptoms; Techniques; Time; United States National Institutes of Health; airway inflammation; computerized; lung imaging; novel; predictive modeling; respiratory; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SPECIFIC AIMS: Primary Objective: The overall objective of this study is to characterize small airways function during the resolution of an acute exacerbation by novel radiographic techniques and physiologic measures and correlate those findings with the resolution of small airways inflammatory markers. The asthma exacerbation (AE) will be experimentally induced by a naturalistic challenge with cat antigen (Fel d I), which is known to penetrate the distal airways. Mild to moderate, steroid na¿ve asthmatic subjects will be exposed in a cat room, containing a known concentration of Fel d I per m3 of air from resident, live cats, for a sufficient period of time to provoke a 20% decline in FEV1. Distal airways response will be assessed at baseline and at various times following a cat room challenge using the following measures: 1) novel radiographic techniques (quantitative analysis of high-resolution computerized tomographic [HRCT] images of the lung acquired at residual volume) 2) physiologic studies (inspiratory capacity [IC], isovolume mid flow rate [FEF25-75%, iso], and impulse oscillation [IOS] respiratory resistance at different frequencies and IOS reactance), 3) exhaled nitric oxide (FENO), including the computed alveolar component of FENO, and 4) bioimmunologic markers (immunologic markers of distal lung inflammation obtained via bronchoscopic distal lung brushings). Once the time course to resolution of the radiographic, physiologic and inflammatory changes in the small airways is ascertained, the following secondary objectives will be addressed in future studies. Secondary Objectives: a) establish if unresolved small airways inflammation, after an initial cat room challenge, in the setting of normalized FEV1 and symptoms, predisposes to a more pronounced exacerbation after a secondary cat room challenge; b) evaluate alterations in mechanisms of small airways inflammation in individuals treated or not treated with anti-inflammatory therapy targeted to the small airways, i.e., with an extra-fine vs. a coarse inhaled corticosteroid (ICS); and c) to use the non-invasive measures of small airways abnormalities employed in this study to develop a predictive model for resolution of acute asthma exacerbations which more closely parallels the inflammatory resolution of natural acute asthma exacerbations.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 具体目的： 主要目的：这项研究的总体目标是通过新颖的放射线学技术和生理测量方法来表征小气道功能，并将这些发现与小型气道炎症标记的分辨率相关联。哮喘恶化（AE）将通过猫抗原（Fel D I）的自然主义挑战在实验中引起，该挑战已知可以穿透远端气道。轻度到现代的类固醇哮喘患者将在猫室中暴露在猫室中，其中包含来自居民的每M3空气，活猫的已知浓度，在足够的时间内激起FEV1下降20％。 Distal airways response will be assessed at baseline and at various times following a cat room challenge using the following measures: 1) novel radiographic techniques (quantitative analysis of high-resolution computerized tomographic [HRCT] images of the lung acquired at residual volume) 2) physiological studies (inspiratory capacity [IC], isovolume mid flow rate [FEF25-75%, iso], and impulse oscillation [IOS] respiratory 3）在不同频率和iOS电抗中的电阻），3）耗尽的一氧化物（FENO），包括FENO的计算肺泡成分，以及4）生物免疫学标记物（通过支气管镜盘盘肺肺刷获得的乳腺肺部乳腺肺部感染的免疫学标记物）。一旦确定了射线照相，生理和炎症变化的时间过程，将在以后的研究中解决以下次要目标。 次要目标：a）确定在初始猫室挑战之后未解决的小气道感染，在归一化FEV1和症状的情况下，在次要猫室挑战之后，易于更明显的加重； b）评估小气道感染机制的改变，在接受针对小气道的抗炎疗法治疗或未治疗的个体中，即用额外的固定性皮质类固醇（ICS）进行了针对小气道的抗炎疗法； c）使用本研究中携带的小气道异常的非侵入性测量，以开发一种预测模型，以解决急性哮喘病变的分辨率，这更紧密地与天然急性哮喘恶化的炎症分辨率相似。