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首页> 外文期刊>American journal of respiratory and critical care medicine >Sputum Biomarkers of Inflammation and Lung Function Decline in Children with Cystic Fibrosis
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Sputum Biomarkers of Inflammation and Lung Function Decline in Children with Cystic Fibrosis

机译:囊性纤维化患儿炎症和肺功能下降的痰液生物标志物

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摘要

Rationale: Progressive lung function decline is a defining feature of cystic fibrosis (CF). Because airway inflammation plays a central role in CF lung disease, inflammatory biomarkers that can be used to monitor disease activity would be valuable. Objectives: Examine longitudinal relationships between sputum biomarkers and lung function. Methods: In this prospective,' longitudinal cohort study, sputum induction was performed annually over 3 years in 35 children with CF. Sputum was assayed for mediators related to proteolysis and a panel of inflammatory cytokines. Measurements and Main Results: Sputum neutrophil elastase, tissue inhibitor of metalloproteinase-1, and TNF-α increased over time, whereas neutrophil elastase antiprotease complexes (NEAPCs) and secretory leukoprotease inhibitor (SLPI) significantly decreased over time. Higher detectable baseline neutrophil elastase was associated with more rapid lung function decline. Similar results for neutrophil elastase were observed in a validation cohort. When categorizing subjects as "rapid" or "slow" decliners, logistic regression demonstrated that the initial measurement of neutrophil elastase had the highest individual predictive value for subsequent lung function decline, whereas neutrophil elastase, IL-8, and IL-6 had the highest combined predictive value. Lung function decline was associated with increases in neutrophil counts, neutrophil elastase, and IL l|l and declines in NEAPCs and SLPI. Conclusions: In children with CF, a single determination of sputum biomarkers, particularly neutrophil elastase, has predictive value for subsequent lung function decline, and longitudinal changes in sputum inflammatory biomarkers are related to lung function changes. Based on our results, sputum neutrophil elastase was the most informative biomarker to monitor disease activity.
机译:理由:进行性肺功能下降是囊性纤维化(CF)的定义特征。由于气道炎症在CF肺疾病中起着核心作用,因此可用于监测疾病活动的炎症生物标志物将很有价值。目的:检查痰液生物标志物与肺功能之间的纵向关系。方法:在这项前瞻性纵向队列研究中,对35例CF患儿在3年内每年进行痰诱导。测定痰中与蛋白水解有关的介质和一组炎性细胞因子。测量和主要结果:痰中性粒细胞弹性蛋白酶,金属蛋白酶-1的组织抑制剂和TNF-α随时间增加,而中性粒细胞弹性蛋白酶抗蛋白酶复合物(NEAPC)和分泌性白蛋白蛋白酶抑制剂(SLPI)随时间显着减少。可检测的基线中性粒细胞弹性蛋白酶越高,肺功能下降越快。在验证队列中,嗜中性粒细胞弹性蛋白酶的结果相似。当将受试者归类为“快速”或“缓慢”下降者时,逻辑回归表明,中性粒细胞弹性蛋白酶的初始测量值对随后的肺功能下降具有最高的个体预测价值,而中性粒细胞弹性蛋白酶,IL-8和IL-6的预测值最高。综合预测值。肺功能下降与中性粒细胞计数,中性粒细胞弹性蛋白酶和IL_1的增加以及NEAPC和SLPI的下降有关。结论:在CF儿童中,单次测定痰中的生物标志物,特别是嗜中性粒细胞弹性蛋白酶,对随后的肺功能下降具有预测价值,而痰中炎症生物标志物的纵向变化与肺功能变化有关。根据我们的结果,痰中性粒细胞弹性蛋白酶是监测疾病活动的最有用的生物标记。

著录项

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  • 作者单位

    Department of Pediatrics,Children's Hospital Colorado, 13123 E. 16th Avenue, B-395, Aurora, CO 80045;

    Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado;

    Department of Pediatrics, Children's Hospital Colorado and University of Colorado Denver School of Medicine, Aurora, Colorado;

    Pediatric Clinical Translational Research Center Core Laboratory, Children's Hospital Colorado, University of Colorado Denver, Aurora, Colorado;

    Department of Pediatrics, Children's Hospital Colorado and University of Colorado Denver School of Medicine, Aurora, Colorado;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cystic fibrosis; pulmonary function; sputum; inflammation; neutrophil elastase;

    机译:囊性纤维化;肺功能痰;炎;中性粒细胞弹性蛋白酶;

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