INDUCED SPUTUM TO EVALUATE ANTI-INFLAMMATORY AGENTS IN CF PATIENTS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定是研究者机构。炎症明显有助于囊性纤维化（CF）肺病的进展。在CF患者中，隔日皮质类固醇和每日两次高剂量布洛芬的抗炎治疗已显示出临床益处。然而，这种疗法可能不会改善肺功能，因为它减缓了肺功能下降的速度。这对测试新抗炎药的试验设计造成了一定的限制，特别是当它涉及到疗效结果参数的选择时。假设布洛芬和塞来昔布治疗CF患者4周后，将减少诱导痰中的中性粒细胞、活性弹性蛋白酶和促炎细胞因子。本研究的具体目的是确定使用高渗盐水诱导的痰液中测量的中性粒细胞、活性弹性蛋白酶和细胞因子是否是有用的筛选试验，用于确定具有已知抗炎特性的特定药物是否是CF受试者进一步临床试验的合适候选药物。这一目标将通过使用一种抗炎药布洛芬和一种抗炎药塞来昔布来实现，布洛芬已被证明在CF中具有临床获益，塞来昔布有可能在CF中具有临床获益。将纳入“无治疗”组作为对照组。

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.