Bates R D, Nahata M C
College of Pharmacy, Ohio State University, Columbus 43210, USA.
J Clin Pharm Ther. 1995 Dec;20(6):313-5. doi: 10.1111/j.1365-2710.1995.tb00703.x.
Advances in the treatment and management of respiratory and pancreatic disorders has increased the life expectancy of patients with cystic fibrosis to 28 years (1). Despite the use of potent antibiotics and chest physiotherapy, persistent bacterial infection of the lung is the major cause of morbidity and mortality in these patients (2). This occurs, in part, because of the production of copious amounts of pulmonary secretions. It has been found that these secretions contain high amounts of human DNA (3-8). This high DNA concentration causes two problems. First, it increases the viscosity of sputum. This, in conjunction with reduced mucociliary clearance, decreases the removal of sputum. Second, the DNA binds to aminoglycosides, which decreases their antimicrobial efficacy (9, 10). Until recently there was no effective drug to decrease the viscosity of sputum in patients with cystic fibrosis. Dornase alpha (Pulmozyme) is the first drug to offer a safe and effective method to treat excessive DNA in sputum. In vitro studies demonstrated that rhDNase greatly decreased the viscosity of sputum by decreasing the concentration of DNA in a concentration-dependent manner (11).
呼吸和胰腺疾病治疗与管理方面的进展已将囊性纤维化患者的预期寿命提高到了28岁（1）。尽管使用了强效抗生素和胸部物理治疗，但肺部持续性细菌感染仍是这些患者发病和死亡的主要原因（2）。部分原因在于肺部会产生大量分泌物。已发现这些分泌物含有大量人类DNA（3 - 8）。这种高DNA浓度引发两个问题。首先，它会增加痰液的黏稠度。这与黏液纤毛清除功能降低共同作用，减少了痰液的排出。其次，DNA会与氨基糖苷类药物结合，降低其抗菌效力（9, 10）。直到最近，还没有有效的药物来降低囊性纤维化患者痰液的黏稠度。重组人脱氧核糖核酸酶（普米克令舒）是第一种提供安全有效方法来治疗痰液中过量DNA的药物。体外研究表明，重组人脱氧核糖核酸酶通过以浓度依赖的方式降低DNA浓度，极大地降低了痰液的黏稠度（11）。
