MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters.

MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters.
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DOI:
10.1186/1465-9921-15-5
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发表时间:
2014-01-21
影响因子:
5.8
通讯作者:
Weiden MD
Weiden MD
中科院分区:
医学2区
文献类型:
--
作者:
Nolan A;Kwon S;Cho SJ;Naveed B;Comfort AL;Prezant DJ;Rom WN;Weiden MD

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2001年9月11日以后,大多数FDNY工人出现持续性肺功能下降,但部分工人恢复。我们假设,暴露后不久血清中的蛋白酶/抗蛋白酶平衡预测随后的恢复。我们进行了一项巢式病例对照研究,测量2002年3月之前抽取的血清中的生物标志物,并随后在2008年3月之前重复肺功能测定一秒用力呼气量(FEV 1)。检测血清基质金属蛋白酶(MMP-1、2、3、7、8、9、12和13)和金属蛋白酶组织抑制剂(TIMP-1、2、3、4)。代表性子队列定义了分析物分布,高于第75百分位数的浓度定义了生物标志物表达升高。FEV 1比定义的气道损伤阻力平均值高一个标准差。对9/11前FEV 1、BMI、年龄和暴露强度进行Logistic回归校正,模拟生物标志物表达升高与高于平均值的FEV 1之间的相关性。2001年9月11日以后,病例组和对照组的FEV 1下降了10%。病例随后恢复到暴露前FEV 1的99%,而对照组持续下降。TIMP-1和MMP-2升高使耐药几率增加5.4和4.2倍,而MMP-1升高使耐药几率降低0.27倍。耐药病例显示愈合,恢复到暴露前值的99%。高TIMP-1和MMP-2预测愈合。MMP/TIMP平衡反映了WTC暴露后气道损伤和修复的独立途径。
After 9/11/2001, most FDNY workers had persistent lung function decline but some exposed workers recovered. We hypothesized that the protease/anti-protease balance in serum soon after exposure predicts subsequent recovery. We performed a nested case–control study measuring biomarkers in serum drawn before 3/2002 and subsequent forced expiratory volume at one second (FEV1) on repeat spirometry before 3/2008. Serum was assayed for matrix metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte distribution and a concentration above 75th percentile defined elevated biomarker expression. An FEV1 one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV1, BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV1. FEV1 in cases and controls declined 10% of after 9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV1 while decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold. Resistant cases displayed healing, returning to 99% of pre-exposure values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects independent pathways to airway injury and repair after WTC exposure.
DOI: 10.1056/nejmoa0904006
发表时间: 2009-12-31
期刊: The New England journal of medicine
影响因子: --
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