Cane Jennifer L, Mallia-Millanes Brendan, Forrester Douglas L, Knox Alan J, Bolton Charlotte E, Johnson Simon R
a Division of Respiratory Medicine and Nottingham Respiratory Research Unit, School of Medicine , University of Nottingham , Nottingham , United Kingdom.
COPD. 2016;13(1):26-34. doi: 10.3109/15412555.2015.1043522. Epub 2015 Sep 29.
Matrix metalloproteinases (MMPs) are elevated in the airways and blood of COPD patients, contributing to disease pathogenesis and tissue remodelling. However, it is not clear if MMP levels in airways, blood and urine are related or if MMP levels are related to disease severity or presence of exacerbations requiring hospitalisation. Seventy-two patients requiring hospitalisation for COPD exacerbations had serum, urine and sputum MMP-8, -9 and active MMP-9 measured by ELISA and gelatin zymography on day one, five and four weeks later (recovery). Clinical history, spirometry, COPD Assessment Test and MRC dyspnoea score were obtained. Twenty-two stable COPD patients had MMP measurements one week apart. During exacerbations, serum and urine MMP-9 were slightly elevated by 17% and 30% compared with recovery values respectively (p = 0.001 and p = 0.026). MMP-8 was not significantly changed. These MMP levels related to serum neutrophil numbers but not to outcome of exacerbations, disease severity measures or smoking status. In clinically stable patients, serum MMP levels did not vary significantly over 7 days, whereas urine MMPs varied by up to nine fold for MMP-8 (p = 0.003). Sputum, serum and urine contained different MMP species and complexes. Median values for sputum active MMP-9 were significantly different from serum (p = 0.035) and urine (p = 0.024). Serum and urine MMPs are only modestly elevated during exacerbations of COPD and unlikely to be useful biomarkers in this clinical setting. Airway, serum and urine MMP levels are independent of each other in COPD patients. Further, MMP levels are variable between patients and do not reflect airflow obstruction.
基质金属蛋白酶（MMPs）在慢性阻塞性肺疾病（COPD）患者的气道和血液中水平升高，这与疾病的发病机制和组织重塑有关。然而，目前尚不清楚气道、血液和尿液中的MMP水平是否相关，以及MMP水平是否与疾病严重程度或需要住院治疗的急性加重的发生有关。72例因COPD急性加重而需要住院治疗的患者在第1天、第5天和4周后（康复期）通过酶联免疫吸附测定（ELISA）和明胶酶谱法检测血清、尿液和痰液中的MMP-8、-9以及活性MMP-9。同时获取患者的临床病史、肺功能检查、COPD评估测试和医学研究委员会（MRC）呼吸困难评分。22例稳定期COPD患者每隔一周进行一次MMP检测。在急性加重期，血清和尿液中的MMP-9分别比康复期的值略有升高，分别升高了17%和30%（p = 0.001和p = 0.026）。MMP-8没有显著变化。这些MMP水平与血清中性粒细胞数量相关，但与急性加重的结果、疾病严重程度指标或吸烟状况无关。在临床稳定的患者中，血清MMP水平在7天内没有显著变化，而尿液中的MMP-8变化高达9倍（p = 0.003）。痰液、血清和尿液中含有不同的MMP种类和复合物。痰液中活性MMP-9的中位数与血清（p = 0.035）和尿液（p = 0.024）有显著差异。在COPD急性加重期，血清和尿液中的MMP只是略有升高，在这种临床情况下不太可能成为有用的生物标志物。在COPD患者中，气道、血清和尿液中的MMP水平相互独立。此外，患者之间的MMP水平存在差异，且不能反映气流阻塞情况。
