AN ASSESSMENT OF INDUCED SPUTUM AS A TOOL TO EVALUATE ANTI-INFLAMMATORY AGENT

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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. This study is a three-arm, multicenter, randomized, open-label, controlled, parallel-group trial comparing the effects of 28 days of ibuprofen, celecoxib, or no treatment on inflammatory markers in induced sputum obtained from subjects with mild to moderate CF lung disease. The study will measure changes in markers of lower airway inflammation in samples of induced sputum obtained before (Baseline Period), during (Treatment Period), and after (Recovery Period) treatment with ibuprofen or celecoxib in subjects with CF, and compare these changes with those observed in a control group of CF subjects who receive no anti-inflammatory treatment. The purpose for including the no treatment group is to define the variability of measurements performed on samples obtained by sputum induction (SI) and to serve as a control group for the ibuprofen and celecoxib treatment arms. Subjects in this ibuprofen arm will receive 20-30 mg/kg twice daily (maximum 3200 mg/day). Subjects in the celecoxib arm will receive 100 mg for weight 45 kg twice daily. The rationale for testing celecoxib in this study is based on its inhibition of COX-2, which occurs at fairly low plasma concentrations, and should be achievable with the upper limits of clinically acceptable doses chosen for this study. To confirm that adequate plasma concentrations of celecoxib were achieved in CF patients, pharmacokinetic studies of celecoxib are being obtained as part of this trial. In the vent that there is some unknown side effect of celecoxib at higher concentrations, the highest recommended dose in children was chosen for evaluation in this trial. Lower airway white cell count, PMN count, percentage of PMNs, active elastase, IL-8 and other cytokines (IL-6,TNF-., and IL-1.) will be measured in lower airway sputum samples. Subjects who are at least 10 years of age may be eligible for enrollment in the study. Induced sputum will be collected on 4 of 5 study visits. Two specimens will be collected prior to initiating therapy (Days 0 and 14), one specimen will be collected at the end of therapy (Day 42), and one specimen will be collected two weeks after therapy has stopped (Day 56). At each visit, the subject's vital signs, oximetry, and spirometry will be obtained before and after the SI procedure.