CLINICAL TRIAL: ANTI-LEUKOTRIENE THERAPY FOR COPD EXACERBATIONS

临床试验：抗白三烯疗法治疗慢性阻塞性肺病恶化

• 批准号: 7718095
• 负责人: STEVEN M SCHARF
• 金额: $ 0.4万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718095
• 关键词: Accounting; Acute; Adrenal Cortex Hormones; Antibiotics; Arachidonate 5-Lipoxygenase; Asthma; Bronchodilator Agents; Caring; Cessation of life; Charge; Chronic Obstructive Airway Disease; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Condition; Cost Savings; Data; Drops; Elevation; Funding; Grant; Health Care Costs; Hospitalization; Hospitals; Inflammation Mediators; Inpatients; Institution; Length of Stay; Leukotriene B4; Leukotriene E4; Leukotrienes; Lipoxygenase Inhibitors; Morbidity - disease rate; Motivation; Oral; Patients; Plasma; Play; Pulmonary Function Test/Forced Expiratory Volume 1; Purpose; Research; Research Personnel; Resources; Risk Factors; Role; Safety; Severities; Source; Sputum; Testing; United States Agency for Healthcare Research and Quality; United States National Institutes of Health; Zileuton; base; day; mortality; neutrophil; novel therapeutics; prednisolone

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. Exacerbations of chronic obstructive pulmonary disease impose a considerable burden with regard to morbidity, mortality, and health care cost. In the year 2000, COPD exacerbations were responsible for 726,000 hospitalizations, and 119,000 deaths in the US. Based on data from the Agency for Healthcare Research and Quality, patients admitted to US hospitals for COPD in 2002 had a mean length of stay of 5.1 days and accounted for $15,400 in charges. Current management of COPD exacerbations includes bronchodilators, corticosteroids, and antibiotics. Because leukotrienes may play an important role in COPD exacerbations, we propose to study whether anti-leukotriene therapy provides additional benefit to usual care in the management of COPD exacerbations requiring inpatient care. The rationale for anti-leukotriene therapy in acute exacerbations of COPD is based on studies of mediators of inflammation in COPD, on clinical trials of anti-leukotriene therapy in COPD, and on a clinical trial of anti-leukotriene therapy in exacerbations of asthma. The motivation for identification of a novel therapeutic approach to COPD exacerbations is that a reduction in hospital length of stay should result in significant cost savings in the management of this common condition. Clinical studies of the role of leukotrienes in COPD exacerbations indicate that leukotriene levels are elevated in acute exacerbations of COPD, that these elevations are associated with the severity of exacerbation, that levels drop with treatment of the exacerbation and that leukotriene B4 (LTB4)contributes significantly to the neutrophil chemotactic activity of sputum. Shindo et al. demonstrated that mean plasma leukotriene E4 (LTE4) levels in patients with COPD are elevated during acute exacerbation before treatment. They also found that LTE4 levels correlated with PaO2 and FEV1 in patients during acute exacerbation before prednisolone treatment, suggesting that elevated LTE4 levels are a risk factor for more severe exacerbations. The purpose of this study is to test the safety and efficacy of oral zileuton (a 5-lipoxygenase inhibitor) in addition to usual care for treatment of acute exacerbations of COPD requiring inpatient care.

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。 慢性阻塞性肺疾病的加重在发病率、死亡率和卫生保健费用方面造成相当大的负担。2000年，COPD急性加重导致美国726，000例住院治疗和119，000例死亡。根据美国卫生保健研究和质量局的数据，2002年因COPD住院的患者平均住院时间为5.1天，费用为15，400美元。目前COPD急性加重的治疗包括支气管扩张剂、皮质类固醇和抗生素。由于白三烯可能在COPD急性加重中发挥重要作用，因此我们建议研究抗白三烯治疗是否为需要住院治疗的COPD急性加重的管理提供常规治疗的额外获益。抗白三烯治疗COPD急性加重的基本原理是基于COPD炎症介质的研究、抗白三烯治疗COPD的临床试验和抗白三烯治疗哮喘急性加重的临床试验。确定COPD急性加重的新治疗方法的动机是缩短住院时间应导致这种常见疾病管理的显着成本节约。关于白三烯在COPD急性加重中的作用的临床研究表明，在COPD急性加重中，白三烯水平升高，这些升高与加重的严重程度相关，水平随着加重的治疗而下降，并且白三烯B4（LTB 4）显著促进痰液的中性粒细胞趋化活性。Shindo等人证明，COPD患者治疗前急性加重期间平均血浆白三烯E4（LTE 4）水平升高。他们还发现，LTE 4水平与泼尼松龙治疗前急性加重期患者的PaO 2和FEV 1相关，这表明LTE 4水平升高是更严重急性加重的风险因素。本研究的目的是测试口服齐留通（一种5-脂氧合酶抑制剂）在常规治疗之外治疗需要住院治疗的COPD急性加重的安全性和有效性。