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

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 具体目标： 主要目的：本研究的总体目标是通过新颖的放射线照相技术和生理测量来表征急性加重缓解期间的小气道功能，并将这些发现与小气道炎症标志物的缓解相关联。哮喘急性发作 (AE) 将通过猫抗原 (Fel d I) 的自然刺激进行实验诱导，已知猫抗原会穿透远端气道。轻度至中度、从未使用过类固醇的哮喘受试者将暴露在猫室中，其中每立方米空气中含有已知浓度的来自居住的活猫的 Fel d I，持续足够长的时间以引起 FEV1 下降 20%。将使用以下措施在基线和猫房挑战后的不同时间评估远端气道反应：1) 新颖的放射线照相技术（对残余容量下获取的肺部高分辨率计算机断层扫描 [HRCT] 图像进行定量分析）2) 生理研究（吸气量 [IC]、等容中期流速 [FEF25-75%，iso] 和脉冲振荡 [IOS] 呼吸 不同频率下的阻力和 IOS 电抗），3）呼出一氧化氮（FENO），包括 FENO 的计算肺泡成分，以及 4）生物免疫标志物（通过支气管镜远端肺刷检获得的远端肺部炎症的免疫标志物）。一旦确定了小气道中放射学、生理学和炎症变化解决的时间进程，将在未来的研究中解决以下次要目标。 次要目标：a) 确定在初次猫房挑战后，在 FEV1 和症状正常化的情况下，未解决的小气道炎症是否在二次猫房挑战后容易出现更明显的恶化； b) 评估接受或未接受针对小气道的抗炎治疗（即使用超细吸入皮质类固醇与粗粒吸入皮质类固醇（ICS））治疗或未治疗的个体的小气道炎症机制的变化； c) 使用本研究中采用的小气道异常的非侵入性测量来开发急性哮喘恶化消退的预测模型，该模型更接近于自然急性哮喘恶化的炎症消退。