Association between pulmonary function and sputum biomarkers in cystic fibrosis
Association between pulmonary function and sputum biomarkers in cystic fibrosis
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DOI：
10.1164/rccm.200609-1354oc
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发表时间：
2007-04-15
影响因子：
24.7
通讯作者：
Ramsey, Bonnie W.
中科院分区：
文献类型：
--
作者：
Mayer-Hamblett, Nicole;Aitken, Moira L.;Ramsey, Bonnie W.
原理：感染和炎症的痰生物标记物是能够量化囊性纤维化(CF)肺部疾病的复杂病理生理学的非侵入性方法。目的：我们从4个多中心研究中构建了一个大型数据库，以量化痰生物标志物与FEV1之间的关联强度。方法：从33个中心的269名参与者(年龄9-54岁)获得FEV1(预测范围为25-120%)和痰生物标志物的定量数据，包括游离中性粒细胞弹性蛋白酶、IL-8、中性粒细胞、铜绿假单胞菌和金黄色葡萄球菌。进行横断面和纵向统计分析，以评估标记物和FEV1之间的关联，包括使用多变量分析。3结果：弹性蛋白酶与FEV1呈负相关(r=-0.35，95%可信区间[CI]：-0.46，-0.22)。平均而言，弹性酶测量相差0.5log的CF患者的FEV相差-7.3%(95%CI：-9.7，-4.6)。中性粒细胞计数与IL-8也呈负相关。在多变量回归中，弹性淀粉酶和中性粒细胞计数能够解释FEV1的大部分变化。弹性酶进一步证明与FEV有显著的纵向关联，特别是FEV下降-2.9%，弹性酶每增加1个对数，FEV下降2.9%(95%CI：-5.0，-0.9)。虽然与FEV1相关，但细菌密度不能解释患者内部和患者之间FEV的临床意义差异。结论：这些数据支持痰生物标志物在不同CIF人群中作为疾病严重程度相关者的作用。
Rationale: Sputum biomarkers of infection and inflammation are noninvasive measures that enable quantification of the complex pathophysiology of cystic fibrosis (CF) lung disease. Validation of these biomarkers as correlates of disease severity is a key step for their application.Objectives: We constructed a large database from four multicenter studies to quantify the strength of association between expectorated sputum biomarkers and FEV1,Methods: FEV1 (range, 25-120% predicted) and quantitative data on expectorated sputum biomarkers including free neutrophil elastase, IL-8, neutrophils, Pseudomonas aeruginosa, and Staphylococcus aureus were obtained from 269 participants (ages, 9-54 years) from 33 centers. Cross-sectional and longitudinal statistical analyses were performed to estimate associations between the markers and FEV1, including the use of multivariable analyses. \ Results: Elastase was negatively correlated with FEV1 (correlation [r] - -0.35; 95% confidence interval [Cl]: -0.46, -0.22). On average, patients with CF who differed in their elastase measurements by 0.5 log differed in their FEV, values by -7.3% (95% Cl: -9.7, -4.6). Neutrophil counts and IL-8 were also each negatively correlated. In a multivariable regression, elastase and neutrophil counts were able to explain the majority of variation in FEV1. Elastase was further shown to have a significant longitudinal association with FEV, specifically a -2.9% decline in FEV, (95% Cl: -5.0, -0.9) per 1-log increase in elastase. Although correlated with FEV1, bacterial densities were unable to explain clinically meaningful differences in FEV, within and across patients.Conclusions: These data support the role of sputum biomarkers as correlates of disease severity in a diverse CIF population.