Department of Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas 75390-8558, TX, USA.
Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA, USA.
J Cyst Fibros. 2021 Jan;20(1):50-56. doi: 10.1016/j.jcf.2020.06.017. Epub 2020 Jul 1.
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 FEV, 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.
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.
Among circulating biomarkers, serum high sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) correlated most strongly with each other (r = 0.85). Comparing sputum-based inflammation measurements, sputum neutrophil elastase and myeloperoxidase (MPO) were the most highly correlated (r = 0.88). Markers most strongly correlated with ppFEV were serum hsCRP (r = -0.55), SAA (r =-0.58), and sputum neutrophil elastase (r = -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.
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.
血液和痰液中的炎症生物标志物在囊性纤维化（CF）的抗炎药物开发中可发挥关键作用。本分析的目的是检查气道和全身炎症测量之间的关系，炎症生物标志物与 FEV 之间的关联，基线协变量的气道和全身炎症差异，血清生物标志物的可重复性，并评估冷冻和延迟处理对痰液分析物测量的影响。
我们分析了来自参加多中心临床试验的年龄在 10 岁及以上 CF 患者的基线和连续血液和诱导痰液中炎症标志物的浓度。
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）彼此之间相关性最强（r = 0.85）。比较基于痰液的炎症测量，痰液中性粒细胞弹性蛋白酶和髓过氧化物酶（MPO）相关性最强（r = 0.88）。与 ppFEV 相关性最强的标志物是血清 hsCRP（r =-0.55），SAA（r =-0.58）和痰液中性粒细胞弹性蛋白酶（r =-0.53）。所有血清生物标志物的个体内标准差始终低于个体间标准差。血清钙卫蛋白和 MPO 的个体间与个体内变异性比最高。冷冻和痰液处理延迟与痰液中性粒细胞弹性蛋白酶，IL-1β或 MPO 测量无显著差异。
在分析的生物标志物中，血清 hsCRP 和痰液中性粒细胞弹性蛋白酶是有希望被纳入 CF 抗炎临床试验的候选物，以避免冗余，减少变异性，并作为肺疾病严重程度和变化的相关指标。
