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

描述（由申请人提供）：慢性鼻窦疾病与更严重的哮喘相关，并导致哮喘控制不良。上呼吸道和下呼吸道之间的相互作用的一种可能机制包括全身性“炎症反应”。这表明气道一部分的刺激导致细胞因子和趋化因子的全身释放，这些细胞因子和趋化因子负责嗜酸性粒细胞运输到呼吸组织，因此气道的其他部分也发生炎症反应。嗜酸性粒细胞趋化因子是负责将嗜酸性粒细胞运输到组织的关键趋化因子。嗜酸性阳离子蛋白是组织中嗜酸性粒细胞活化的主要标志物。我们建议在入选STAN试验的前190例患者中进行一项辅助机制研究，以确定在控制不佳的慢性鼻窦疾病过敏性哮喘患者中使用6个月的鼻内类固醇是否会导致局部鼻腔和全身炎症介质-嗜酸性粒细胞趋化因子和ECP的减少。我们还将评估嗜酸性粒细胞趋化因子和ECP水平的降低是否与哮喘控制改善相关。正在进行的哮喘临床试验中心（ACRC）哮喘和鼻用类固醇（STAN）研究试验将确定与安慰剂相比，6个月的鼻内类固醇是否会改善380名哮喘控制不良和慢性鼻窦疾病患者的哮喘控制。这项辅助研究很重要，因为它将提供有关上下呼吸道疾病相互作用的可能机制的答案。如果血清和鼻腔灌洗液水平的变化与哮喘控制的改善相关，那么我们将有更多的目标用于未来的治疗干预。 公共卫生相关性：我们建议进行一项辅助研究，作为一项大型多中心随机试验的一部分，哮喘和鼻用类固醇研究（STAN）。我们的辅助研究的目的是确定用鼻内莫米松治疗患有慢性鼻炎、慢性鼻窦炎或两者兼有的哮喘控制不佳的患者是否会导致鼻灌洗液和血液标志物水平的降低，这些标志物与动员和激活称为嗜酸性粒细胞的特异性过敏相关炎性细胞有关。我们还将通过症状的严重程度和频率以及肺功能的测量来确定哮喘控制是否有所改善。最后，我们将确定这些血液和鼻灌洗液标记物水平的降低是否与哮喘控制的改善相关。

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.