INDUCED SPUTUM TO EVALUATE ANTI-INFLAMMATORY AGENTS IN CF PATIENTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。炎症显然促进了囊性纤维化(CF)肺部疾病的进展。交替使用糖皮质激素和每天两次大剂量布洛芬的抗炎治疗已显示出临床疗效。然而，这种疗法可能没有改善肺功能那么多，因为它减缓了肺功能下降的速度。这对测试新型抗炎药的试验设计造成了一定的限制，特别是当它与疗效结果参数的选择有关时。假说是布洛芬和塞来昔布在治疗4周后会减少CF患者诱导痰中的中性粒细胞、活性弹性蛋白酶和促炎细胞因子。这项研究的具体目的是确定使用高渗盐水诱导的痰中中性粒细胞、活性弹性蛋白酶和细胞因子是否为有用的筛查试验，以确定具有已知抗炎特性的特定药物是否适合于在CF受试者中进行进一步的临床试验。这一目标将通过一种抗炎药布洛芬和一种抗炎药塞来昔布来实现，布洛芬已被证明对CF具有临床益处，塞来昔布可能对CF具有临床益处。另设“不接受治疗”的手臂作为对照组。

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.