Viral Induced Asthma Exacerbations

病毒引起的哮喘加重

• 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
• 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

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加重 (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，并开始确定宿主的遗传易感性可能调节这些过程的因素。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。

项目成果

Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C.

新鉴定的人鼻病毒 C 的分子建模、器官培养和反向遗传学。

• 发表时间: 2011-05
• 影响因子: 82.9
• 作者: Bochkov, Yury A;Palmenberg, Ann C;Lee, Wai;Rathe, Jennifer A;Amineva, Svetlana P;Sun, Xin;Pasic, Thomas R;Jarjour, Nizar N;Liggett, Stephen B;Gern, James E
• 通讯作者: Gern, James E

Lower airway rhinovirus burden and the seasonal risk of asthma exacerbation.

降低气道鼻病毒负担和哮喘恶化的季节性风险。

• 发表时间: 2011-11-01
• 影响因子: 24.7
• 作者: Denlinger, Loren C;Sorkness, Ron L;Lee, Wai;Evans, Michael D;Wolff, Michele J;Mathur, Sameer K;Crisafi, Gina M;Gaworski, Katie L;Pappas, Tressa E;Vrtis, Rose F;Kelly, Elizabeth A;Gern, James E;Jarjour, Nizar N
• 通讯作者: Jarjour, Nizar N

Semiautomated Ventilation Defect Quantification in Exercise-induced Bronchoconstriction Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: A Repeatability Study.

使用超极化 Helium-3 磁共振成像对运动引起的支气管收缩进行半自动通气缺陷定量：重复性研究。

• 发表时间: 2016
• 影响因子: 4.8
• 作者: Zha, Wei;Niles, David J;Kruger, Stanley J;Dardzinski, Bernard J;Cadman, Robert V;Mummy, David G;Nagle, Scott K;Fain, Sean B
• 通讯作者: Fain, Sean B