Mayer-Hamblett Nicole, Aitken Moira L, Accurso Frank J, Kronmal Richard A, Konstan Michael W, Burns Jane L, Sagel Scott D, Ramsey Bonnie W
Department of Pediatrics, University of Washington, 4800 Sand Point Way N.E., Box 5371, Seattle, WA 98105-0371, USA.
Am J Respir Crit Care Med. 2007 Apr 15;175(8):822-8. doi: 10.1164/rccm.200609-1354OC. Epub 2007 Jan 18.
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.
We constructed a large database from four multicenter studies to quantify the strength of association between expectorated sputum biomarkers and FEV(1.)
FEV(1) (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 FEV(1), including the use of multivariable analyses.
Elastase was negatively correlated with FEV(1) (correlation [r] = -0.35; 95% confidence interval [CI]: -0.46, -0.22). On average, patients with CF who differed in their elastase measurements by 0.5 log differed in their FEV(1) values by -7.3% (95% CI: -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 FEV(1). Elastase was further shown to have a significant longitudinal association with FEV(1), specifically a -2.9% decline in FEV(1) (95% CI: -5.0, -0.9) per 1-log increase in elastase. Although correlated with FEV(1), bacterial densities were unable to explain clinically meaningful differences in FEV(1) within and across patients.
These data support the role of sputum biomarkers as correlates of disease severity in a diverse CF population.
痰液中感染和炎症的生物标志物是一种非侵入性检测手段，能够对囊性纤维化（CF）肺部疾病复杂的病理生理学进行量化。验证这些生物标志物与疾病严重程度的相关性是其应用的关键步骤。
我们通过四项多中心研究构建了一个大型数据库，以量化咳出痰液生物标志物与第一秒用力呼气容积（FEV₁）之间的关联强度。
从33个中心的269名参与者（年龄9 - 54岁）获取FEV₁（范围为预测值的25% - 120%）以及咳出痰液生物标志物的定量数据，包括游离中性粒细胞弹性蛋白酶、白细胞介素 - 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估计这些标志物与FEV₁之间的关联，包括使用多变量分析。
弹性蛋白酶与FEV₁呈负相关（相关性[r] = -0.35；95%置信区间[CI]：-0.46，-0.22）。平均而言，CF患者中弹性蛋白酶测量值相差0.5对数时，其FEV₁值相差 -7.3%（95% CI：-9.7，-4.6）。中性粒细胞计数和白细胞介素 - 8也均呈负相关。在多变量回归中，弹性蛋白酶和中性粒细胞计数能够解释FEV₁的大部分变异。进一步表明弹性蛋白酶与FEV₁存在显著的纵向关联，具体而言，弹性蛋白酶每增加1对数，FEV₁下降 -2.9%（95% CI：-5.0，-0.9）。尽管细菌密度与FEV₁相关，但无法解释患者内部和患者之间FEV₁的临床有意义差异？
这些数据支持痰液生物标志物在不同CF人群中作为疾病严重程度相关指标的作用。
