Matrix metalloproteinase-9 predicts pulmonary status declines in α1-antitrypsin deficiency.
Matrix metalloproteinase-9 predicts pulmonary status declines in α1-antitrypsin deficiency.
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DOI：
10.1186/1465-9921-12-35
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发表时间：
2011-03-23
影响因子：
5.8
通讯作者：
Blanc PD
中科院分区：
文献类型：
--
作者：
Omachi TA;Eisner MD;Rames A;Markovtsova L;Blanc PD
基质金属蛋白酶-9 (MMP-9) 可能在肺气肿的进展中发挥重要作用，但关于 MMP-9 的纵向临床研究很少，包括肺部状况和 COPD 恶化结果。我们利用一项针对 α1-抗胰蛋白酶缺乏症 (AATD) 和肺气肿患者的临床试验的安慰剂组 (n = 126) 数据来检查一年观察期内血浆 MMP-9 水平、肺部状况和 COPD 恶化之间的联系。在 12 个月内定期评估肺功能、计算机断层扫描肺密度、增量穿梭步行试验 (ISWT) 和 COPD 加重情况。前瞻性分析使用广义估计方程来合并 MMP-9 和所有终点的重复纵向测量，并控制年龄、性别、种族、白细胞计数和烟草史。二次分析还在预测模型中纳入了高度敏感的 C 反应蛋白水平。基线时，较高的血浆 MMP-9 水平与较低的 FEV1 (p = 0.03)、FVC (p < 0.001)、一氧化碳转移因子 (p = 0.03)、静息氧饱和度 (p = 0.02) 和 ISWT 步行距离 (p = 0.02) 呈横断面相关，但与放射学肺密度或总肺容量 (TLC) 无关。在纵向分析中，MMP-9 预测转移因子 (p = 0.04) 和氧饱和度 (p < 0.001) 进一步下降。 MMP-9 还预测随访期间肺密度恶化 (p = 0.003)、TLC 增加 (p = 0.02) 以及 COPD 恶化更频繁 (p = 0.003)。额外控制 hs-CRP 水平并没有实质性改变 MMP-9 与这些结果之间的纵向关联。血浆 MMP-9 水平升高通常预示肺部状况下降，包括转移因子和肺密度恶化以及 AATD 相关肺气肿中慢性阻塞性肺病 (COPD) 加重。
Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes. We utilized data from the placebo arm (n = 126) of a clinical trial of patients with alpha1-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models. At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV1 (p = 0.03), FVC (p < 0.001), carbon monoxide transfer factor (p = 0.03), resting oxygen saturation (p = 0.02), and ISWT distance walked (p = 0.02) but were not associated with radiographic lung density or total lung capacity (TLC). In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p = 0.04) and oxygen saturation (p < 0.001). MMP-9 also predicted worsening lung density (p = 0.003), increasing TLC (p = 0.02), and more frequent COPD exacerbations over follow-up (p = 0.003). Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes. Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.
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影响因子：
10
作者：
Dawkins, PA;Dowson, LJ;Stockley, RA
通讯作者：
Stockley, RA
影响因子：
10
作者：
Man, S. F. P.;Connett, J. E.;Sin, D. D.
通讯作者：
Sin, D. D.
影响因子：
5
作者：
Hanley, JA;Negassa, A;Forrester, JE
通讯作者：
Forrester, JE
影响因子：
4.3
作者：
Higashimoto, Yuji;Iwata, Takuya;Tohda, Yuji
通讯作者：
Tohda, Yuji
DOI：
10.1164/ajrccm.154.1.8680679
发表时间：
1996-07-01
影响因子：
24.7
作者：
Gevenois, PA;DeVuyst, P;Yernault, JC
通讯作者：
Yernault, JC