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

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。这项研究是一项三臂、多中心、随机、开放对照、平行分组试验，比较布洛芬、塞来昔布或不治疗28天对轻、中度慢性肺病患者诱导痰中炎症标志物的影响。这项研究将测量慢性阻塞性肺疾病患者在使用布洛芬或塞来昔布治疗前(基准期)、治疗期间和(恢复期)治疗前(基准期)、治疗期间和(恢复期)后获得的诱导痰中下呼吸道炎症标志物的变化，并将这些变化与未接受抗炎治疗的慢性阻塞性肺病患者的对照组进行比较。纳入NO治疗组的目的是确定对通过诱导痰(SI)获得的样本进行的测量的可变性，并作为布洛芬和塞来昔布治疗组的对照组。服用布洛芬的受试者每天两次服用20-30毫克/公斤(每天最多3200毫克)。塞来昔布组的受试者每天两次服用体重45公斤的100毫克。在这项研究中测试塞来昔布的基本原理是基于它对COX-2的抑制，COX-2在相当低的血浆浓度下发生，并且应该可以在为本研究选择的临床可接受剂量的上限下实现。为了证实塞来昔布在CF患者中达到了足够的血浆浓度，正在进行塞来昔布的药代动力学研究，作为试验的一部分。在较高浓度的塞来昔布存在未知副作用的情况下，本试验选择儿童最高推荐剂量进行评估。降低气道白细胞计数、中性粒细胞计数、中性粒细胞百分比、活性弹性蛋白酶、IL-8和其他细胞因子(IL-6、TNF-α和IL-1)。将在下呼吸道痰样本中进行测量。年龄至少10岁的受试者可能有资格参加这项研究。诱导痰将在5次研究访问中收集4次。将在开始治疗前(第0天和第14天)收集两个样本，在治疗结束时(第42天)收集一个样本，并在治疗结束后两周(第56天)收集一个样本。在每次检查中，受试者的生命体征、血氧和肺活量将在SI手术前后获得。

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.