Harms H K, Matouk E, Tournier G, von der Hardt H, Weller P H, Romano L, Heijerman H G, FitzGerald M X, Richard D, Strandvik B, Kolbe J, Kraemer R, Michalsen H
Kinderspital der Universität München, Germany.
Pediatr Pulmonol. 1998 Sep;26(3):155-61. doi: 10.1002/(sici)1099-0496(199809)26:3<155::aid-ppul1>3.0.co;2-k.
Cystic fibrosis is characterized by the accumulation of thick viscous purulent secretions. Recombinant human deoxyribonuclease I (rhDNase) breaks down extracellular DNA, which contributes to the increased viscosity of sputum. A multinational, open-label study was conducted in 974 cystic fibrosis patients with moderate lung disease [forced vital capacity (FVC) 40-70% of predicted values] to examine the safety and efficacy of aerosolized rhDNase, 2.5 mg, once daily over a period of at least 12 weeks. Patients were assessed under conditions reflecting routine clinical practice. During rhDNase therapy, at least one respiratory tract infection (RTI) requiring intravenous antibiotics was experienced by 29.5% of patients. Forced expiratory volume in 1 second (FEV1) and FVC were significantly improved from baseline by a mean of 10.5% and 7.2%, respectively. Voice alteration and pharyngitis were the most frequent rhDNase-related adverse events, but only 2% of all patients discontinued treatment due to adverse events. The results obtained were similar to a subanalysis of data from the first 3 months of a placebo-controlled U.S. study. The patients in the present study had a similar frequency of RTIs and improvement in pulmonary function, and reported fewer rhDNase-related and cystic fibrosis-related adverse events than patients in the U.S. study. We conclude that administration of rhDNase is safe, well tolerated, and effective under conditions reflecting routine clinical practice in patients with cystic fibrosis and moderate lung disease.
囊性纤维化的特征是浓稠的脓性分泌物积聚。重组人脱氧核糖核酸酶I（rhDNase）可分解细胞外DNA，而细胞外DNA会导致痰液黏稠度增加。一项针对974例中度肺部疾病（用力肺活量[FVC]为预测值的40 - 70%）的囊性纤维化患者开展的多中心、开放标签研究，旨在检验雾化吸入2.5毫克rhDNase、每日一次、至少持续12周的安全性和有效性。在反映常规临床实践的条件下对患者进行评估。在rhDNase治疗期间，29.5%的患者至少经历过一次需要静脉使用抗生素的呼吸道感染（RTI）。第1秒用力呼气容积（FEV1）和FVC较基线水平显著改善，平均分别提高了10.5%和7.2%。声音改变和咽炎是最常见的与rhDNase相关的不良事件，但因不良事件而停药的患者仅占所有患者的2%。所获得的结果与一项美国安慰剂对照研究前3个月数据的亚分析结果相似。本研究中的患者呼吸道感染的频率和肺功能改善情况相似，且与美国研究中的患者相比，报告的与rhDNase相关和与囊性纤维化相关的不良事件更少。我们得出结论，在反映囊性纤维化和中度肺部疾病患者常规临床实践的条件下，使用rhDNase是安全的，耐受性良好且有效。
