Effect of nebulised recombinant DNase on neutrophil elastase load in cystic fibrosis
Effect of nebulised recombinant DNase on neutrophil elastase load in cystic fibrosis
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DOI：
10.1136/thx.51.6.619
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发表时间：
1996-06-01
期刊：
影响因子：
10
通讯作者：
Hayes, JP
中科院分区：
文献类型：
--
作者：
Costello, CM;OConnor, CM;Hayes, JP
背景-退行性炎性中性粒细胞释放的DNA有助于囊性纤维化患者呼吸道的粘液堵塞。中性粒细胞弹性蛋白酶是囊性纤维化患者肺组织破坏的主要效应因子，是一种高度阳离子的分子，它被化脓性痰中的粘蛋白和DNA等带负电荷的多阴离子结合并抑制。因此，雾化重组DNA酶对DNA在呼吸道中的增溶作用可以消除中性粒细胞弹性蛋白酶抑制的一个来源，有效地增加弹性酶负荷。本研究的目的是评价重组人DNA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。方法：15例囊性纤维化患者在雾化DNA酶治疗前和治疗后12周分别采集血液和痰标本。其中11例患者在52周时评估了持续应用重组人DNA酶的远期疗效。测定血浆中性粒细胞弹性蛋白酶、白细胞介素8和中性粒细胞弹性蛋白酶与α(1)-蛋白水解酶抑制剂(α(1)PI)的复合体。痰中检测中性粒细胞弹性蛋白酶、IL-8和活性弹性蛋白酶。结果：痰弹性蛋白酶活性在12周时下降，并在52周时保持不变，同时观察到血浆总弹性酶的下降。尽管如预期，血浆总弹力酶水平与中性粒细胞弹力酶/α(1)PI复合体之间存在相关性，但52周时该复合体水平的下降没有达到统计学意义。结论--本研究表明，长期每日服用重组人DNA酶可降低囊性纤维化患者的弹力酶负荷。
Background - 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.Methods - 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(1)PI). Sputum was assessed for neutrophil elastase, IL-8, and active elastase. At each visit spirometric measurements were carried out.Results - 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(1)PI complex, the decrease in the levels of the complex at 52 weeks did not reach statistical significance.Conclusions - This study indicates that prolonged daily administration of rhDNase results in a reduction in elastase load in patients with cystic fibrosis.