Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA; Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA.
Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA; Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA.
J Cyst Fibros. 2015 Nov;14(6):720-6. doi: 10.1016/j.jcf.2015.03.007. Epub 2015 Apr 11.
High-dose ibuprofen (HDI) is a clinically beneficial anti-inflammatory regimen that may be a useful reagent to study induced sputum inflammatory marker changes over short study periods appropriate for early-phase CF clinical trials.
We conducted a 28-day, open-label, randomized, controlled trial among 72 clinically stable CF subjects (FEV1≥40% predicted) randomized to HDI or routine care that assessed IL-6, IL-8, TNF-α, IL-1-β, free neutrophil elastase, and white cell counts with differentials change from baseline in induced sputum.
IL-6 was the only biomarker with significant within-group change: 0.13 log10 pg/mL mean reduction among ibuprofen-treated subjects (p=0.04); and no change in the control group. IL-6 change between groups was statistically significant (p=0.024). No other inflammatory biomarker differences were observed between groups after 28 days.
Although we studied only one agent, HDI, these results suggest that one month may be inadequate to assess anti-inflammatory candidates using markers from induced sputum.
高剂量布洛芬（HDI）是一种具有临床益处的抗炎方案，可能是一种有用的试剂，可用于研究在适合早期 CF 临床试验的短期研究期间诱导痰炎症标志物的变化。
我们对 72 名临床稳定的 CF 受试者（FEV1≥40%预计值）进行了为期 28 天的开放性、随机、对照试验，这些受试者随机分为 HDI 或常规治疗组，评估诱导痰中白细胞介素 6（IL-6）、白细胞介素 8（IL-8）、肿瘤坏死因子-α（TNF-α）、白细胞介素 1-β（IL-1-β）、游离中性粒细胞弹性蛋白酶和白细胞分类计数的基线变化。
IL-6 是唯一具有显著组内变化的生物标志物：布洛芬治疗组的平均降低 0.13 log10 pg/mL（p=0.04）；对照组没有变化。两组之间的 IL-6 变化具有统计学意义（p=0.024）。28 天后，两组之间没有观察到其他炎症生物标志物的差异。
尽管我们仅研究了一种药物，即 HDI，但这些结果表明，使用诱导痰中的标志物评估抗炎候选药物可能需要一个月的时间。
