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 disorder, which lacks a curative therapy, has a median survival of 30 years1, and affects approximately 25,000 individuals in the United States. CF is caused by mutations in a single gene on chromosome 7 that encodes the CF transmembrane conductance regulator (CFTR), a membrane protein that has multiple functions involving fluid balance across epithelial cells2. The primary cause of morbidity and mortality in patients with CF is progressive obstructive pulmonary disease, associated with chronic Pseudomonas aeruginosa (Pa) endobronchial bacterial infection and an intense neutrophilic inflammatory response. Currently available intravenous anti-pseudomonal antibiotics transiently improve lung function and clinical status3, but they do not eradicate Pa. Between 1994 and 1997, a tobramycin solution for inhalation (TOBI ) was developed as a new chronic therapy to treat Pa endobronchial infection in patients with CF. The rationale for development of this inhaled therapy was to deliver a high antibiotic concentration directly to the site of infection with limited systemic absorption to minimize toxicity4. Recent studies in infants and toddlers with CF have shown that Pa lower airway infections may occur in the first 3 years of life 7,8,9, frequently prior to the onset of symptoms. A recent report from a cohort study of CF patients followed from birth to age 7 showed that early acquisition of Pa was associated with increased morbidity and mortality. Therefore, there is a growing interest in investigating anti-pseudomonal therapies in very young children, with the long-term goal of delaying or preventing irreversible lung disease. This is a multicenter open label single arm study of tobramycin solution for inhalation (TOBI ) in young children from 6 months to 6 years of age who have CF. The patients who have a positive culture of Pa in the lower airway at the time of a baseline BAL will be treated for 28 days with a twice a day inhalation of 300 milligrams of preservative free tobramycin, 60 mg/ml with a Pari LC Plus nebulizer with facemask powered by a Pulmo-Aide compressor. There will be a follow-up bronchoscopy with additional monitoring for a total of six months. Patients with lower airway cultures negative for Pa at the baseline BAL will be followed for a total of six months to monitor oropharyngeal cultures, serology and clinical parameters.
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