Study of Asthma and Nasal Steroids Trial-An ancillary mechanistic study

哮喘和鼻类固醇试验的研究-辅助机制研究

• 批准号: 8111232
• 负责人: Christian Bime
• 金额: $ 5.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-16 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111232
• 关键词: Allergens; Allergic; Ancillary Study; Asthma; Blood; Blood Circulation; Bronchodilator Agents; Bronchoscopy; Cells; Chronic; Chronic Rhinitis; Chronic Sinusitis; Clinical; Clinical Trials; Comorbidity; Data; Development; Disease; Enrollment; Eotaxin; Event; Exhalation; Family; Forced expiratory volume function; Frequencies; Future; Goals; Hyperactive behavior; Hypersensitivity; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interleukin-5; Juniper; Lead; Lung; Measurement; Measures; Mediator of activation protein; Nasal Lavage Fluid; Nitric Oxide; Nose; Outcome; Pathology; Patients; Phase; Placebos; Play; Proteins; Pulmonary Function Test/Forced Expiratory Volume 1; Respiratory physiology; Serum; Severities; Small inducible cytokine A24; Steroids; Stimulus; Suggestion; Symptoms; Therapeutic Intervention; Tissues; Work; bone; cell type; chemokine; cytokine; eosinophil; eosinophilic inflammation; human CCL26 protein; improved; inflammatory marker; member; public health relevance; pulmonary function; randomized trial; respiratory; response; trafficking

DESCRIPTION (provided by applicant): Chronic sinonasal disease is associated with more severe asthma and contributes to poor asthma control. One possible mechanism for a proposed interaction between upper and lower airways includes a systemic `inflammatory response. The suggestion is that stimulus in one part of the airway leads to systemic release of cytokines and chemokines responsible for eosinophil trafficking to the respiratory tissues and thus inflammatory response occurs in other parts of the airway as well. The eotaxins are the key chemokines responsible for trafficking of eosinophils to the tissues. Eosinophilic cationic protein is the main marker of eosinophil activation in tissues. We are proposing to conduct an ancillary mechanistic study among the first 190 patients enrolled for the STAN trial to establish whether six months of intranasal steroids in poorly controlled allergic asthmatics with chronic sinonasal disease will lead to reduction in local nasal and systemic inflammatory mediators - eotaxins and ECP. We will also assess if decreasing levels of eotaxin and ECP levels correlate with improved asthma control. The ongoing Asthma Clinical Trials Center (ACRC) Study of Asthma and Nasal Steroids (STAN) trial will determine if six months of intranasal steroids compared to placebo will improve asthma control in 380 patients with poorly controlled asthma and chronic sinonasal disease. This ancillary study is important because it will provide answers relating to the possible mechanisms of interaction between disease in the upper and lower airways. If changes in serum and nasal lavage fluid levels correlate with improved asthma control, then we would have more targets for future therapeutic interventions. PUBLIC HEALTH RELEVANCE: We are proposing to perform an ancillary study as part of a large multicenter randomized trial, the Study of Asthma and Nasal Steroids (STAN). The objective of our ancillary study is to determine if treating patients with poorly controlled asthma who have chronic rhinitis, chronic sinusitis or both with intranasal mometasone will lead to a reduction in the levels of nasal lavage fluid and blood markers that are associated with mobilizing and activation of specific allergy associated inflammatory cells called eosinophils. We will also determine if there is improvement in asthma control as measured by severity and frequency of symptoms and also by measurement of lung function. Finally we will determine if reduction in levels of these blood and nasal lavage fluid markers correlate with improvement in asthma control.

描述（由申请人提供）：慢性鼻窦疾病与更严重的哮喘有关，并导致哮喘控制不良。上和下气道之间提议相互作用的一种可能机制包括系统性的炎症反应。建议是，气道一部分的刺激导致细胞因子和趋化因子的全身释放，导致嗜酸性粒细胞运输到呼吸道组织，因此在气道的其他部分也会发生炎症反应。 eotaxins是负责将嗜酸性粒细胞运输到组织的关键趋化因子。嗜酸性阳离子阳离子蛋白是组织中嗜酸性粒细胞活化的主要标记。我们提议在参加Stan试验的前190名患者中进行一项辅助机理研究，以确定患有慢性辛纳纳纳索疾病的控制不良的过敏性哮喘患者中六个月的鼻内类固醇是否会导致局部鼻腔和全身性炎症性介体的减少 - Eotaxins -Eotaxins和ECP。我们还将评估降低息脂素和ECP水平是否与改善哮喘控制相关。与安慰剂相比，正在进行的哮喘和鼻固醇（Stan）试验的哮喘临床试验中心（ACRC）研究将确定六个月的鼻内类固醇是否会改善380例控制哮喘和慢性鼻窦病较差的患者的哮喘。这项辅助研究很重要，因为它将提供与上下气道中疾病之间可能相互作用机制有关的答案。如果血清和鼻腔灌洗液水平的变化与改善的哮喘控制相关，那么我们将为将来的治疗干预措施提供更多目标。 公共卫生相关性：我们提议作为大型多中心随机试验的一部分进行辅助研究，即对哮喘和鼻固醇（Stan）的研究。我们辅助研究的目的是确定治疗患有慢性炎，慢性鼻窦炎的哮喘患者是否会导致鼻腔内蒙马松的患者是否会导致鼻腔灌洗液和血液标志物的水平降低，这些水平与动员和激活的特定eLlergy相关炎性细胞相关的血液标记水平降低。我们还将确定通过症状的严重程度和频率以及通过测量肺功能来衡量的哮喘控制是否有所改善。最后，我们将确定这些血液和鼻腔灌洗液标记水平的降低是否与哮喘控制的改善相关。