一项关于囊性纤维化中基质金属蛋白酶（MMP）-9的观察性研究。

An observational study of matrix metalloproteinase (MMP)-9 in cystic fibrosis.

作者信息

Devereux Graham, Steele Sandra, Jagelman Timothy, Fielding Shona, Muirhead Robert, Brady Jeff, Grierson Christal, Brooker Richard, Winter John, Fardon Tom, McCormick Jonathan, Huang Jeffrey T J, Miller Douglas

机构信息

Section of Population Health, University of Aberdeen, Aberdeen AB25 2ZG, UK; Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK.

Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, UK.

出版信息

J Cyst Fibros. 2014 Sep;13(5):557-63. doi: 10.1016/j.jcf.2014.01.010. Epub 2014 Feb 11.

DOI:10.1016/j.jcf.2014.01.010

PMID:24525080

Abstract

BACKGROUND

In cystic fibrosis (CF), cross-sectional studies have reported sputum matrix metalloproteinase (MMP)-9 to be elevated and negatively correlated with FEV1. This longitudinal study examined the association between MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) to prognostic parameters in CF.

METHOD

A cross-sectional survey of CF and control subjects; CF patients were followed up for a median of 49 months. MMP-9 and TIMP-1 and TIMP-2 were quantified in sputum and plasma.

RESULTS

Seventy-three patients with CF, median age 22 years, and 40 controls were recruited. Fifty-three of these CF patients were followed up. Prospectively, in CF subjects, plasma MMP-9 activity was adversely associated with FEV1 (β -1.15 (95% CI -2.10, -0.20), p = 0.019) and rate of FEV1 decline, and plasma TIMP-1 was adversely associated with mortality: hazard ratio 3.66 (1.91-7.04), p < 0.001.

CONCLUSIONS

These associations further justify investigation of MMP-9 and TIMP-1 as biomarkers for short- to medium-term FEV1 decline and mortality in patients with CF.

摘要

背景

在囊性纤维化（CF）中，横断面研究报告痰液基质金属蛋白酶（MMP）-9升高且与第一秒用力呼气容积（FEV1）呈负相关。这项纵向研究调查了MMP-9和金属蛋白酶组织抑制剂（TIMPs）与CF患者预后参数之间的关联。

方法

对CF患者和对照者进行横断面调查；对CF患者进行了中位时间为49个月的随访。对痰液和血浆中的MMP-9、TIMP-1和TIMP-2进行定量分析。

结果

招募了73例CF患者（中位年龄22岁）和40名对照者。其中53例CF患者接受了随访。前瞻性研究发现，在CF患者中，血浆MMP-9活性与FEV1（β -1.15（95%可信区间-2.10，-0.20），p = 0.019）及FEV1下降速率呈负相关，血浆TIMP-1与死亡率呈负相关：风险比3.66（1.91 - 7.04），p < 0.001。