MACROLIDES TO PREVENT EXACERBATIONS OF ASTHMA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 哮喘和慢性阻塞性肺疾病（COPD）是两种最常见的阻塞性肺疾病。 慢性气道炎症和呼吸道症状的发作性恶化和气流阻塞（加重）发生在哮喘和COPD中。 尽管在这些呼吸系统疾病的治疗开发方面取得了重大进展，但哮喘和COPD急性加重很常见，并导致大量发病率和死亡率。 此外，因哮喘或COPD急性加重住院的患者在出院回家后发生近致死性和致死性再加重的风险较高。 这些观察结果强调了对预防哮喘和COPD急性加重的新型疗法的需求。 大环内酯类抗生素的作用（例如，阿奇霉素、克拉霉素、红霉素）在治疗细菌感染中的作用已得到充分证实。 最近的临床前证据也表明，大环内酯类药物可能具有独特的抗炎特性，甚至抗病毒特性。 这些令人兴奋的观察结果导致了评估哮喘和COPD患者使用大环内酯类药物维持治疗的研究。 在临床稳定的哮喘或COPD中进行的小型研究表明，大环内酯类药物维持治疗（例如，使用6周），当添加到常规护理中时，可以减轻气道炎症，减轻呼吸道症状，并改善肺功能。 然而，尚无研究评价在哮喘或COPD急性加重期间开始大环内酯类药物维持治疗的潜在获益。 我们假设，对哮喘或COPD急性加重住院患者开始大环内酯类药物维持治疗，在常规医疗护理的基础上，将加速气流阻塞、呼吸道症状和生活质量的改善，并降低出院回家后再次加重的风险。 本初步研究的目的是评估研究方案的可行性（招募、保留和对研究程序和药物的依从性），以及收集有关细菌或病毒感染所致急性加重比例的初步数据，并估计临床重要结局（呼吸道症状、生活质量、气流阻塞、气道炎症和再加重率）的潜在效应量。 为了实现这些目标，我们建议在约翰霍普金斯医院或约翰霍普金斯Bayview医学中心因哮喘或COPD急性加重住院的成人中进行一项为期48周的随机、双盲、安慰剂对照交叉临床试验（24周阿奇霉素，24周安慰剂）。

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. Asthma and chronic obstructive pulmonary disease (COPD) are the two most common obstructive lung diseases. Chronic airway inflammation and episodic worsening of respiratory symptoms and airflow obstruction (exacerbations) occur in asthma and COPD. Despite major advances in the development of therapies for these respiratory disorders, asthma and COPD exacerbations are common and result in substantial morbidity and mortality. Moreover, patients hospitalized for asthma or COPD exacerbations are at high risk for near fatal and fatal re-exacerbations after discharge home. These observations highlight the need for novel therapies to prevent asthma and COPD exacerbations. The role of macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin) in treating bacterial infections is well established. Recent pre-clinical evidence also suggests that macrolides may posses distinct anti-inflammatory properties and even anti-viral properties. These exciting observations have led to research evaluating the use of maintenance therapy with macrolides in patients with asthma and COPD. Small studies in clinically stable asthma or COPD suggest that maintenance macrolide therapy (e.g., use for 6 weeks), when added to usual care, may attenuate airway inflammation, reduce respiratory symptoms, and improve lung function. However, there are no studies that have evaluated the potential benefits of initiating maintenance macrolide therapy during asthma or COPD exacerbations. We hypothesize that initiating maintenance macrolide therapy in hospitalized patients with asthma or COPD exacerbations will, when added to usual medical care, accelerate the improvement in airflow obstruction, respiratory symptoms, and quality of life and reduce the risk of re-exacerbations after discharge home. The objective of this pilot study is to evaluate the feasibility of the study protocol (recruitment, retention, and adherence to study procedures and medications), as well as collect preliminary data about the proportion of exacerbations due to bacterial or viral infections and estimate potential effect sizes for clinically important outcomes (respiratory symptoms, quality of life, airflow obstruction, airway inflammation, and rate of re-exacerbations). To achieve these objectives, we propose a 48 week randomized, double-blind, placebo-controlled crossover clinical trial (24 weeks azithromycin, 24 weeks placebo) in adults hospitalized for asthma or COPD exacerbations to the Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center.