Costello C M, O'Connor C M, Finlay G A, Shiels P, FitzGerald M X, Hayes J P
Department of Medicine and Therapeutics, University College Dublin, Ireland.
Thorax. 1996 Jun;51(6):619-23. doi: 10.1136/thx.51.6.619.
DNA released by degenerating inflammatory neutrophils contributes to mucous plugging of airways in patients with cystic fibrosis. Neutrophil elastase, a major effector of tissue destruction in the lungs of patients with cystic fibrosis, is a highly cationic molecule which is bound and inhibited by negatively charged polyanions such as mucin and DNA in purulent sputum. Thus, the solubilisation of DNA in the airways by aerosolised recombinant DNase may remove a source of neutrophil elastase inhibition, effectively increasing elastase load. The aim of this study was to assess the effect of rhDNase therapy on neutrophil elastase load in patients with cystic fibrosis.
Blood and sputum were collected from 15 patients with cystic fibrosis before initiation of nebulised DNase therapy and at 12 weeks following therapy. The long term effects of continuous rhDNase administration were evaluated at 52 weeks for 11 of these patients. Plasma was analysed for neutrophil elastase, interleukin (IL)-8 and neutrophil elastase in complex with alpha 1-protease inhibitor (alpha 1PI). Sputum was assessed for neutrophil elastase, IL-8, and active elastase. At each visit spirometric measurements were carried out.
Sputum elastase activity decreased at 12 weeks and was maintained at 52 weeks when a decline in total plasma elastase was also observed. Although, as expected, there was a correlation between plasma levels of total elastase and neutrophil elastase/alpha 1PI complex, the decrease in the levels of the complex at 52 weeks did not reach statistical significance.
This study indicates that prolonged daily administration of rhDNase results in a reduction in elastase load in patients with cystic fibrosis.
变性炎症中性粒细胞释放的DNA导致囊性纤维化患者气道黏液堵塞。中性粒细胞弹性蛋白酶是囊性纤维化患者肺部组织破坏的主要效应分子，是一种高度阳离子化的分子，可被脓性痰液中带负电荷的多聚阴离子如黏蛋白和DNA结合并抑制。因此，雾化重组脱氧核糖核酸酶使气道中的DNA溶解，可能会消除中性粒细胞弹性蛋白酶抑制源，有效增加弹性蛋白酶负荷。本研究旨在评估重组人脱氧核糖核酸酶治疗对囊性纤维化患者中性粒细胞弹性蛋白酶负荷的影响。
在雾化脱氧核糖核酸酶治疗开始前及治疗12周后，从15例囊性纤维化患者采集血液和痰液。对其中11例患者在52周时评估持续给予重组人脱氧核糖核酸酶的长期效果。分析血浆中的中性粒细胞弹性蛋白酶、白细胞介素（IL）-8以及与α1-蛋白酶抑制剂（α1PI）结合的中性粒细胞弹性蛋白酶。评估痰液中的中性粒细胞弹性蛋白酶、IL-8和活性弹性蛋白酶。每次就诊时进行肺功能测量。
痰液弹性蛋白酶活性在12周时下降，并在52周时维持，此时血浆总弹性蛋白酶也出现下降。虽然正如预期，血浆总弹性蛋白酶水平与中性粒细胞弹性蛋白酶/α1PI复合物之间存在相关性，但52周时该复合物水平的下降未达到统计学意义。
本研究表明，长期每日给予重组人脱氧核糖核酸酶可降低囊性纤维化患者的弹性蛋白酶负荷。
