INDUCED SPUTUM TO EVALUATE ANTI-INFLAMMATORY AGENTS IN CF PATIENTS

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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. Inflammation clearly contributes to the progression of cystic fibrosis (CF) lung disease. Anti-inflammatory therapy with alternative-day corticosteroids and twice-daily high-dose ibuprofen in patients with CF has shown clinical benefit. However, this therapy probably does not improve lung function as much as it slows the rate of decline in lung function. This poses certain constraints on the design of trials to test new anti-inflammatory agents, especially as it pertains to selection of efficacy outcome parameters. The hypothesis is that ibuprofen and celecoxib will reduce neutrophils, active elastase, and pro-inflammatory cytokines in induced sputum after 4 weeks of therapy in patients with CF. The specific aim of this study is to determine whether neutrophils, active elastase, and cytokines measured in sputum induced by using hypertonic saline are useful screening tests for determining if a particular agent with known anti-inflammatory properties is a suitable candidate for further clinical trials in CF subjects. This aim will be addressed using one anti-inflammatory agent, ibuprofen, that has been shown to have clinical benefit in CF, and one anti-inflammatory agent, celecoxib, that has potential to have clinical benefit in CF. A "no treatment" arm will be included as the control group.