Novel Strategies Targeting Acute Exacerbation of COPD

描述（由申请方提供）：本提案的总体目标是测试三种旨在降低COPD急性加重频率和/或严重程度的新型治疗方法。 我们描述了两个随机安慰剂对照试验。 第一项将确定长期给予N-乙酰半胱氨酸（一种硫醇化合物，可降低粘液粘度，并具有抗氧化、抗炎和细胞保护作用）或克拉霉素（一种大环内酯类抗生素，具有抗炎和抗生素作用）是否会降低COPD急性加重的频率和严重程度。 第二项将确定通过氦氧混合气（氦氧混合气）驱动的雾化器（与空气相反）给予支气管扩张剂是否会更快地逆转生理异常，并缩短住院时间，这与COPD严重急性加重相关，因为氦氧混合气密度较低，减少湍流，从而增加支气管扩张剂在更远端气道中的沉积。作为一个子目标，我们还建议使用许多生物标志物（即，呼气中腺苷水平、痰中白细胞介素6和8水平、白细胞介素6和8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、因子VIII活性和血液中血管性血友病因子抗原），以鉴定和表征更可能患有急性加重的患者。 同时，该信息还将提供关于COPD急性加重的病理生物学的信息。

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.