This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystic fibrosis (CF) is an autosomal recessive disease characterized by progressive, obstructive pulmonary disease. Approximately one in 2,500 children in the United States each year is born with CF. An estimated 30,000 people in the United States have the disease which designates CF as an orphan disease. The underlying pathology is a defect of the Cystic Fibrosis Transmembrane Conductance Regulator gene, leading to abnormal movement of sodium chloride across respiratory epithelial cell membranes. The resultant abnormally thick mucus interferes with mucociliary clearance of bacteria and other organisms from the airways. Pseudomonas aeruginosa is the most significant bacterial pathogen associated with CF pulmonary disease. Infection with PA is an important event in the natural progression of CF and is associated with increased rates of pulmonary function decline. Across all age groups, 58% of CF patients are infected with PA, and by age 18, nearly 80% of CF patients are infected. Certain strains have been shown to be significant predictors of mortality. Therapy with aerosolized carbenicillin, gentamicin, ticarcillin, tobramycin, and colistin has been studied and/or practiced for many years, 5-17 although only tobramycin solution for inhalation (TOBI ) has FDA licensure for aerosol use. TOBI has been shown to produce substantial improvements in pulmonary function and other clinical parameters in CF patients. Aztreonam is a monobactam antibiotic with an antibacterial spectrum similar to that of the aminoglycoside antibiotics tobramycin and gentamicin. It is currently approved as parenteral therapy for a variety of serious infections. Intravenous aztreonam has been shown to be safe and efficacious for treatment of lower respiratory tract infections in children with CF. Emergence of antibiotic resistance among PA strains is a serious concern within the CF community because uncontrolled PA infections contribute to progressive lung disease. This protocol will test another potential aerosolized agent, inhaled aztreonam lysinate (AI), which could be used with other antibiotics in CF patients
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