INTRODUCTION Biomarkers of inflammation in blood and sputum can play a critical role in anti-inflammatory drug development in cystic fibrosis (CF). The objectives of this analysis were to examine relationships between airway and systemic measurements of inflammation, associations between inflammatory biomarkers and FEV1, differences in airway and systemic inflammation by baseline covariates, reproducibility of serum biomarkers, and to assess the effects of freezing and delayed processing on sputum analyte measurements. METHODS We analyzed baseline and serial concentrations of inflammatory markers in blood and induced sputum collected from individuals with CF ages 10 years and older who participated in a multicenter clinical trial. RESULTS Among circulating biomarkers, serum high sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) correlated most strongly with each other (rs = 0.85). Comparing sputum-based inflammation measurements, sputum neutrophil elastase and myeloperoxidase (MPO) were the most highly correlated (rs = 0.88). Markers most strongly correlated with ppFEV1 were serum hsCRP (rs = -0.55), SAA (rs =-0.58), and sputum neutrophil elastase (rs = -0.53). Within-subject standard deviation was consistently lower than between-subject standard deviation for all serum biomarkers. Serum calprotectin and MPO had the highest ratio of between-to-within subject variability. Freezing and delayed sputum processing were not associated with significant differences in measurements of sputum neutrophil elastase, IL-1β, or MPO. CONCLUSIONS Among the biomarkers analyzed, serum hsCRP and sputum neutrophil elastase are promising candidates to include in CF anti-inflammatory clinical trials to avoid redundancy, minimize variation, and serve as correlates of lung disease severity and change.

中文翻译：

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评估用于囊性纤维化药物开发的气道和循环炎症生物标志物

引言 血液和痰中炎症的生物标志物在囊性纤维化 (CF) 的抗炎药物开发中起着关键作用。该分析的目的是检查气道和全身炎症测量值之间的关系、炎症生物标志物和 FEV1 之间的关联、气道和全身炎症的基线协变量差异、血清生物标志物的可重复性，并评估冷冻和延迟处理对痰分析物测量。方法 我们分析了从参加多中心临床试验的 10 岁及以上 CF 患者收集的血液和诱导痰中炎症标志物的基线和系列浓度。结果 在循环生物标志物中，血清高敏 C 反应蛋白 (hsCRP) 和血清淀粉样蛋白 A (SAA) 之间的相关性最强 (rs = 0.85)。比较基于痰的炎症测量，痰中性粒细胞弹性蛋白酶和髓过氧化物酶 (MPO) 的相关性最高 (rs = 0.88)。与 ppFEV1 相关性最强的标志物是血清 hsCRP (rs = -0.55)、SAA (rs =-0.58) 和痰中性粒细胞弹性蛋白酶 (rs = -0.53)。所有血清生物标志物的受试者内标准偏差始终低于受试者之间的标准偏差。血清钙卫蛋白和 MPO 的受试者间变异性比率最高。冷冻和延迟痰液处理与痰中性粒细胞弹性蛋白酶、IL-1β 或 MPO 测量值的显着差异无关。结论 在分析的生物标志物中，