INDUCED SPUTUM AS A TOOL 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，不一定是研究者所在机构。炎症有助于囊性纤维化（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，但不良反应和其他考虑因素明显限制了其使用。因此，非常需要设计一种用于评价前瞻性抗炎剂的策略，该策略将允许仅选择最有希望的药物用于III期类型试验中的进一步研究。另一个值得关注的事实是，一些制药公司没有开发用于CF的抗炎剂，因为没有早期疗效指标。本研究将评估诱导痰中炎症介质的测量作为这样的策略之一。待检验的假设是，CF患者接受布洛芬和塞来昔布治疗4周后，诱导痰中的中性粒细胞、活性弹性蛋白酶和促炎细胞因子减少。具体目标：为了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患者更广泛临床试验的合适候选药物。这一目标将使用一种抗炎药布洛芬来解决，布洛芬已被证明在CF中具有临床益处。

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 contributes to the progression of cystic fibrosis (CF) lung disease. Anti-inflammatory therapy with alternate-day corticosteroids and twice-daily high-dose ibuprofen in patients with CF has shown clinical benefit, but adverse effects and other considerations have markedly limited their use. Thus, it is highly desirable to design a strategy for evaluation of prospective anti-inflammatory agents that will allow for the selection of only the most promising agents for further study in Phase III type trials. Of additional concern is the fact that some pharmaceutical firms have not pursued development of anti-inflammatory agents for CF because there were no early indicators of efficacy. This study will assess the measurement of inflammatory mediators in induced sputum as one such strategy. The hypothesis to be tested is that ibuprofen and celecoxib will reduce neutrophils, active elastase, and proinflammatory cytokines in induced sputum after 4 weeks of therapy in patients with CF. Specific Aim: To determine whether neutrophils, active elastase, and cytokines measured in sputum induced using hypertonic saline are useful screening tests for determining if a particular agent with known anti-inflammatory properties is a suitable candidate for more extensive clinical trials in patients with CF. This aim will be addressed using one anti-inflammatory agent, ibuprofen, that has been shown to have clinical benefit in CF.