AEROSOLIZED TYLOXAPOL IN THE AIRWAYS DISEASE OF CYSTIC FIBROSIS

厚的、顽强的、化脓性支气管分泌物的产生是囊性纤维化的标志。这些分泌物难以清除，阻塞气道，并通过阻塞气道内的炎症过程极大地促进阻塞性肺疾病的进展。这种停滞延长了囊性纤维化患者气道暴露于与炎症反应相关的有害消化酶和氧化自由基的时间。囊性纤维化患者分泌物的厚度部分是由于来自退行性炎症细胞，特别是中性粒细胞细胞核的DNA的存在。另一个导致痰液坚韧的因素是由一种叫做肌动蛋白的蛋白质组成的交联蛋白丝网络的存在。一种能够“稀释”囊性纤维化患者气道分泌物的有效且廉价的药物将是非常有用的，本研究正在测试泰洛沙波尔可以达到这一目的的假设。泰洛沙波尔是一种非常有效的粘液溶解剂（粘液稀释剂），用于囊性纤维化分泌物在试管中测试。泰洛沙波尔也是一种强大的抗氧化剂，能够清除囊性纤维化患者气道中大量产生的有害自由基。最后，泰洛沙波尔是囊性纤维化患者气道分泌物中激活的清道夫细胞产生炎症分子的有效抑制剂。这三种活性的结合在任何单一的、有效的、廉价的药物中都找不到。本研究旨在开发将雾化泰洛沙泊送入气道的必要方法，并研究泰洛沙泊在正常受试者中使用的安全性。然后计划进行一项研究，以测试雾化泰洛沙波尔对囊性纤维化患者的有效性。

The production of thick, tenacious, purulent bronchial secretions is the hallmark of cystic fibrosis. These secretions are difficult to clear, obstruct the airway, and contribute greatly to the progression of obstructive lung disease by stagnating the inflammatory process within airways. This stagnation prolongs the exposure of the airway in patients with cystic fibrosis to harmful digestive enzymes and oxidizing radicals associated with the inflammatory response. The thickness of the secretions in patients with cystic fibrosis are due, in part, to the presence of DNA from the nuclei of degenerating inflammatory cells, particularly neutrophils. Another factor contributing to the tenacity of sputum is the presence of a network of cross-linked protein filaments made up of a protein called actin. An effective and inexpensive agent capable of "thinning" the airway secretions of patients with cystic fibrosis would be extremely useful, and this study is testing the hypothesis that tyloxapol can achieve this end. Tyloxapol is a dramatically effective mucolytic (mucous thinner) for cystic fibrosis secretions when tested in a test tube. Tyloxapol is also a powerful antioxidant, capable of scavenging injurious radicals produced in abundance in the airway of patients with cystic fibrosis. Finally, tyloxapol is a potent inhibitor of the production of inflammatory molecules by activated scavenger cells found in the airway secretions in patients with cystic fibrosis. The combination of these three activities is not found in any single, effective, inexpensive drug. This study is designed to develop the methods necessary to deliver aerosolized tyloxapol to the airway and to study the safety of the use of tyloxapol in normal subjects. A study is then planned to test the effectiveness of aerosolized tyloxapol in patients with cystic fibrosis.