OPPORTUNITIES FOR THE USE OF AEROSOLIZED ALPHA(1)-ANTITRYPSIN FOR THETREATMENT OF CYSTIC-FIBROSIS

Cystic fibrosis (CF), the most common lethal genetic disease affecting the white population, owes its morbidity and mortality primarily to t he devastating effects of chronic inflammation and infection within th e pulmonary airways. It has become increasingly recognized that the ho st's response to Pseudomonas species and Staphylococcus aureus infecti on plays a paramount role in CF lung destruction and eventual developm ent of respiratory insufficiency, A massive pulmonary influx of neutro phils, and accompanying excessive levels of neutrophil elastase (NE), can be detected in the bronchoalveolar fluid of even very young childr en with CF, The excess of NE adversely affects the CF airways by enhan cing mucus secretion, directly injuring airway tissues, exacerbating t he inflammatory process by attracting more neutrophils, and derailing opsonization and elimination of bacterial pathogens, particularly Pseu domonas aeruginosa. Neutralization of excess NE by delivering suppleme ntal alpha(1)-antitrypsin to the airways via aerosolization represents an exciting new potential therapy for CF lung disease.