Armstrong Hilary F, Podolanczuk Anna J, Barr R Graham, Oelsner Elizabeth C, Kawut Steven M, Hoffman Eric A, Tracy Russell, Kaminski Naftali, McClelland Robyn L, Lederer David J
1 Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York.
2 Department of Medicine, Columbia University Medical Center, New York, New York.
Am J Respir Crit Care Med. 2017 Nov 15;196(10):1311-1317. doi: 10.1164/rccm.201701-0254OC.
Matrix metalloproteinase-7 (MMP-7) has been implicated in interstitial lung disease pathobiology and proposed as a diagnostic and prognostic biomarker of idiopathic pulmonary fibrosis.
To test associations between serum MMP-7 and lung function, respiratory symptoms, interstitial lung abnormalities (ILA), and all-cause mortality in community-dwelling adults sampled without regard to respiratory symptoms or disease.
We measured serum MMP-7 in 1,227 participants in MESA (Multi-Ethnic Study of Atherosclerosis) at baseline. The 5-year outcome data were available for spirometry (n = 697), cough (n = 722), and dyspnea (n = 1,050). The 10-year outcome data were available for ILA (n = 561) and mortality (n = 1,227). We used linear, logistic, and Cox regression to control for potential confounders.
The mean (±SD) serum MMP-7 level was 4.3 (±2.5) ng/ml (range, 1.2-24.1 ng/ml). In adjusted models, each natural log unit increment in serum MMP-7 was associated with a 3.7% absolute decrement in FVC% (95% confidence interval [CI] = 0.9-6.6%), a 1.6-fold increased odds of exertional dyspnea (95% CI = 1.3-1.9), a 1.5-fold increased odds of ILAs (95% CI = 1.1-2.1), and a 2.2-fold increased all-cause mortality rate (95% CI = 1.9-2.5). The associations with ILA and mortality tended to be stronger among never-smokers (P values for interaction 0.06 and 0.01, respectively).
Serum MMP-7 levels may be a quantitative biomarker of subclinical extracellular matrix remodeling in the lungs of community-dwelling adults, which may facilitate investigation of subclinical interstitial lung disease.
基质金属蛋白酶-7（MMP-7）与间质性肺疾病的病理生物学有关，并被提议作为特发性肺纤维化的诊断和预后生物标志物。
在不考虑呼吸道症状或疾病的情况下，对社区居住的成年人进行抽样，以测试血清MMP-7与肺功能、呼吸道症状、间质性肺异常（ILA）和全因死亡率之间的关联。
我们在基线时测量了动脉粥样硬化多民族研究（MESA）中1227名参与者的血清MMP-7。可获得5年的肺活量测定结果数据（n = 697）、咳嗽结果数据（n = 722）和呼吸困难结果数据（n = 1050）。可获得10年的ILA结果数据（n = 561）和死亡率结果数据（n = 1227）。我们使用线性、逻辑和Cox回归来控制潜在的混杂因素。
血清MMP-7的平均（±标准差）水平为4.3（±2.5）ng/ml（范围为1.2 - 24.1 ng/ml）。在调整后的模型中，血清MMP-7每增加一个自然对数单位，FVC%就会绝对下降3.7%（95%置信区间[CI] = 0.9 - 6.6%），运动性呼吸困难的几率增加1.6倍（95% CI = 1.3 - 1.9），ILA的几率增加1.5倍（95% CI = 1.1 - 2.1），全因死亡率增加2.2倍（95% CI = 1.9 - 2.5）。从不吸烟者中，MMP-7与ILA和死亡率之间的关联往往更强（交互作用的P值分别为0.06和0.01）。
血清MMP-7水平可能是社区居住成年人肺部亚临床细胞外基质重塑的定量生物标志物，这可能有助于亚临床间质性肺疾病的研究。
