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.
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