Novel Strategies Targeting Acute Exacerbation of COPD

描述(由申请人提供)：这项提案的总体目标是测试三种旨在减少COPD急性加重的频率和/或严重程度的新疗法。 我们描述了两个随机的安慰剂对照试验。第一个将确定长期服用N-乙酰半胱氨酸(一种降低粘液粘度的硫醇化合物，还具有抗氧化、抗炎和细胞保护作用)或克拉霉素(一种兼具抗炎和抗生素作用的大环内酯类抗生素)是否会降低COPD恶化的频率和严重程度。第二项研究将确定，通过氦氧(氦和氧的混合物)而不是空气驱动的雾化器给药，是否会更快地逆转生理异常，并减少住院时间，这与COPD的严重急性加重有关，这是由于氦氧密度较低减少了湍流，从而增加了支气管扩张剂在更远端呼吸道的沉积。作为一个次目标，我们还建议使用一些生物标志物(即呼气空气中的腺苷水平、痰中的白介素6和8的水平、白介素6和8的水平、表面活性蛋白D、血管内皮生长因子、纤维蛋白原、C反应肽、第VIII因子的活性和血液中的von Willebrand因子抗原)来识别和表征那些更有可能发生急性加重的患者。同时，这些信息还将提供有关COPD恶化的病理生物学信息。

DESCRIPTION (provided by applicant): The overall objective of this proposal is to test three novel treatments aimed at reducing the frequency and/or the severity of acute exacerbations of COPD. We describe two randomized placebo-controlled trials. The first will determine whether long-term administration of N-acetyl cysteine (a thiol compound that decreases mucus viscosity and also has anti-oxidant, anti-inflammatory and cytoprotective effects), or clarithromycin (a macrolide antibiotic having both anti-inflammatory and antibiotic effects) will reduce the frequency and severity of COPD exacerbations. The second will determine whether administering bronchodilators via nebulizers that are powered with heliox (a mixture of helium and oxygen), as opposed to air, will more rapidly reverse the physiologic abnormalities, and reduce the length of hospital stay, associated with severe acute exacerbations of COPD as a result of the lower density of heliox reducing turbulent flow, thereby increasing bronchodilator deposition in more distal airways. As a sub goal we also propose to use a number of biomarkers (i.e., levels of adenosine in exhaled air, levels of interleukins 6 and 8 in sputum, levels of interleukins 6 and 8, surfactant protein D, vascular endothelial growth factor, fibrinogen, C-reactive peptide, Factor VIII activity, and von Willebrand's factor antigen in blood), to identify and characterize those patients who are more likely to have acute exacerbations. This information will, at the same time, also provide information regarding the pathobiology of COPD exacerbations.