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Viral Induced Asthma Exacerbations

病毒引起的哮喘加重

基本信息

批准号：
7824755
负责人：
NIZAR N JARJOUR
金额：
$ 0.89万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2009-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7824755
关键词：
Antiviral Agents Antiviral Response Asthma Biology Biopsy Biopsy Specimen Bronchial Lavages Bronchoalveolar Lavage Cells Common Cold Common Cold Virus Computers Data Development Disease Environmental Irritants Epithelial Figs - dietary Functional disorder Generations Genetic Helium Hypersensitivity Image Individual Infection Inflammatory Inflammatory Response Knowledge Location Lung Magnetic Resonance Imaging Mediator of activation protein Molecular Morbidity - disease rate Mucous body substance Neutrophil Activation Neutrophil Infiltration Obstruction Outcome Pathogenesis Patients Physiological Physiology Play Positron-Emission Tomography Predisposition Process Resolution Respiratory physiology Rhinovirus Role Severities Smoke Sputum Structure Symptoms Testing Upper Respiratory Infections Viral Viral Respiratory Tract Infection Virus X-Ray Computed Tomography airway inflammation airway obstruction base imaging modality improved injured airway mortality novel respiratory response tomography

项目摘要

DESCRIPTION (provided by applicant): Viral respiratory tract infections are an important cause of asthma exacerbations. Rhinoviruses (RV) are the most common type detected in these patients. We have evidence that RV infect the lower airway, and stimulate the generation of proinflammatory mediators leading to recruitment of neutrophils which then cause airway injury including epithelial damage and increased mucus secretion. These changes result in airway obstruction, hyper-responsiveness and increased asthma symptoms. Since asthma exacerbations develop only in a subset of asthma patients who suffer a viral respiratory tract infection, host susceptibility factors including decreased generation of antiviral factors or increased release of proinflammatory mediators have been suspected to play a role in the pathogenesis of these attacks. We therefore, hypothesize that virus-induced asthma exacerbation (VIAX) with RV infections are the result of enhanced neutrophil recruitment and activation in the lower airway with subsequent intraluminal airway obstruction and airway parenchymal uncoupling. We further propose that this enhanced neutrophilic inflammatory response is seen in a subset of asthma patients with altered antiviral responses and increased generation of proinflammatory responses to RV. To test this hypothesis we will determine the physiological consequences of VIAX on lung function including intraluminal bronchial obstruction and airway-parenchymal uncoupling. We will also use radiological imaging with CT scans, 3He-MRI, and 18FDG PET to determine the functional and structural changes in the lung during VIAX and to determine the relationship of these changes to observed pulmonary physiology. Finally we will determine the mechanisms of lower airway inflammation associated with the VIAX by analysis of sputum and bronchial lavage cells and mucosal biopsies, determine the relationship of these virus-induced effects to airflow obstruction and lung structure, and begin to determine the genetic host susceptibility factors that may regulate these processes. From these observations, we will be able to better define the mechanisms of VIAX and hopefully help develop improved treatment.

描述（由申请人提供）：病毒性呼吸道感染是哮喘加重的重要原因。鼻病毒（RV）是这些患者中最常见的病毒类型。我们有证据表明，RV 感染下呼吸道，并刺激促炎介质的产生，导致中性粒细胞募集，从而导致气道损伤，包括上皮损伤和粘液分泌增加。这些变化导致气道阻塞、高反应性和哮喘症状加重。由于哮喘恶化仅发生在遭受病毒性呼吸道感染的哮喘患者中，因此宿主易感因素（包括抗病毒因子产生减少或促炎介质释放增加）被怀疑在这些发作的发病机制中发挥作用。因此，我们假设 RV 感染引起的病毒性哮喘急性发作 (VIAX) 是下气道中性粒细胞募集和激活增强以及随后的管腔内气道阻塞和气道实质解偶联的结果。我们进一步提出，这种增强的中性粒细胞炎症反应可见于抗病毒反应改变和对 RV 的促炎症反应产生增加的哮喘患者亚群中。为了检验这一假设，我们将确定 VIAX 对肺功能的生理影响，包括管腔内支气管阻塞和气道实质解偶联。我们还将使用 CT 扫描、3He-MRI 和 18FDG PET 放射成像来确定 VIAX 期间肺部的功能和结构变化，并确定这些变化与观察到的肺部生理学的关系。最后，我们将通过分析痰液和支气管灌洗细胞以及粘膜活检来确定与 VIAX 相关的下气道炎症机制，确定这些病毒诱导的效应与气流阻塞和肺结构的关系，并开始确定可能调节这些过程的遗传宿主易感性因素。根据这些观察结果，我们将能够更好地定义 VIAX 的机制，并希望有助于开发改进的治疗方法。