用于识别硬化性肺病或特发性肺纤维化中的间质性肺病并预测肺功能下降的生物标志物。
Biomarkers to identify ILD and predict lung function decline in scleroderma lung disease or idiopathic pulmonary fibrosis.
作者信息
Kennedy Barry, Branagan Peter, Moloney Fiachra, Haroon Muhammad, O'Connell Oisin J, O'Connor Terence M, O'Regan Kevin, Harney Sinead, Henry Michael T
机构信息
Department of Respiratory Medicine, Mercy University Hospital, Cork, Ireland..
出版信息
Sarcoidosis Vasc Diffuse Lung Dis. 2015 Sep 14;32(3):228-36.
BACKGROUND
SSc-ILD and IPF demonstrate significant morbidity and mortality. Predicting disease progression is challenging in both diseases.
OBJECTIVES
We sought a serum biomarker that could identify patients with SSc-ILD or IPF and prospectively predict short-term decline in lung function in these patients.
METHODS
10 healthy controls, 5 SSc w/o ILD, 6 SSc-ILD and 13 IPF patients underwent venesection. An array of cytokines including KL-6, SP-D and MMP7 were measured. PFTs were obtained at baseline and six months. Cytokine measurements were correlated with PFTs.
RESULTS
KL-6 in IPF patients (633 ng/ml, IQR 492-1675) was significantly elevated compared to controls (198 ng/ml, IQR 52-360, p<0.01) and SSc w/o ILD patients (192 ng/ml, IQR 0-524, p<0.05); KL-6 in SSc-ILD patients (836 ng/ml, IQR 431-1303) was significantly higher than in controls (p<0.05). SP-D was significantly higher in IPF patients (542 ng/ml, IQR 305-577) compared to controls (137 ng/ml, IQR 97-284, p<0.01) or to SSc w/o ILD patients (169 ng/ml, IQR 137-219, p<0.05). In comparison with controls (0.0 ng/ml, IQR 0.0-0.6), MMP7 was significantly higher in both IPF patients (2.85 ng/ml, IQR 1.5-3.6, p<0.05) and SSc-ILD patients (5.41 ng/ml, IQR 2.6-7.2, p<0.001). Using a cut-off level of 459ng/ml for KL-6 and of 1.28 ng/ml for MMP7, 18 out of 19 patients with ILD had a serum value of either KL-6 or MMP7 above these thresholds. For all ILD patients, baseline serum SP-D correlated with ΔFVC %pred over six months (r=-0.63, p=0.005, 95% CI -0.85 to -0.24).
CONCLUSIONS
Combining KL-6 with MMP7 may be a useful screening tool for patients at risk of ILD. SP-D may predict short-term decline in lung function.
背景
系统性硬化症相关间质性肺病（SSc-ILD）和特发性肺纤维化（IPF）具有较高的发病率和死亡率。预测这两种疾病的病情进展具有挑战性。
目的
我们寻找一种血清生物标志物，能够识别SSc-ILD或IPF患者，并前瞻性预测这些患者肺功能的短期下降。
方法
10名健康对照者、5名无ILD的SSc患者、6名SSc-ILD患者和13名IPF患者接受静脉采血。检测了一系列细胞因子，包括KL-6、表面活性蛋白D（SP-D）和基质金属蛋白酶7（MMP7）。在基线和六个月时进行肺功能测试（PFTs）。细胞因子检测结果与PFTs进行相关性分析。
结果
IPF患者的KL-6（633 ng/ml，四分位间距492 - 1675）显著高于对照组（198 ng/ml，四分位间距52 - 360，p<0.01）和无ILD的SSc患者（192 ng/ml，四分位间距0 - 524，p<0.05）；SSc-ILD患者的KL-6（836 ng/ml，四分位间距431 - 1303）显著高于对照组（p<0.05）。与对照组（137 ng/ml，四分位间距97 - 284，p<0.01）或无ILD的SSc患者（169 ng/ml，四分位间距137 - 219，p<0.05）相比，IPF患者的SP-D显著更高（542 ng/ml，四分位间距305 - 577）。与对照组（0.0 ng/ml，四分位间距0.0 - 0.6）相比，MMP7在IPF患者（2.85 ng/ml，四分位间距1.5 - 3.6，p<0.05）和SSc-ILD患者（5.41 ng/ml，四分位间距2.6 - 7.2，p<0.001）中均显著更高。使用KL-6的截断值为459ng/ml和MMP7的截断值为1.28 ng/ml，19名ILD患者中有18名患者的血清KL-6或MMP7值高于这些阈值。对于所有ILD患者，基线血清SP-D与六个月内的预计用力肺活量变化百分比（ΔFVC %pred）相关（r = -0.63，p = 0.005，95%可信区间 -0.85至 -0.24）。
结论
将KL-6与MMP7联合使用可能是ILD风险患者的一种有用筛查工具。SP-D可能预测肺功能的短期下降。
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