Shah P L, Scott S F, Knight R A, Marriott C, Ranasinha C, Hodson M E
Department of Cystic Fibrosis, Royal Brompton Hospital, UK.
Thorax. 1996 Feb;51(2):119-25. doi: 10.1136/thx.51.2.119.
Viscoelastic secretions in cystic fibrosis cause impaired mucus clearance and persistence of bacteria within the lung. The abnormal rheology is partly due to the presence of high molecular weight deoxyribonucleic acid (DNA). Recombinant human DNase I (rhDNase) has been shown to depolymerise DNA and thereby reduce the in vitro viscoelasticity of sputum in patients with cystic fibrosis. A phase II double blind placebo controlled study showed that rhDNase improved pulmonary function in patients with cystic fibrosis. The object of the present study was to evaluate the in vivo effects of rhDNase on sputum rheology and to determine whether these were correlated with changes in pulmonary function.
Patients were randomised to receive either placebo or rhDNase 2.5 mg twice daily for 10 days. Sputum samples were collected in sterile containers during screening and during treatment with the study drug. Pulmonary function and rheological analysis were the primary outcomes evaluated. Other parameters assessed were quantitative sputum bacteriology, sputum DNA concentration, and change in molecular mass of DNA polymers.
The viscoelasticity of the sputum in untreated patients with cystic fibrosis was high and treatment with rhDNase reduced all the rheological parameters measured: dynamic storage modulus (a measure of elasticity), dynamic loss modulus (a measure of viscosity), and log complex modulus (a measure of mucus rigidity). The calculated cough clearance index was also improved following treatment with rhDNase. These rheological parameters showed a correlation with forced expiratory volume in one second (FEV1) which was improved by a mean (SE) of 13.3 (5.6)% on day 10 of treatment with rhDNase compared with a change of 0.2 (3.1)% in the placebo group. There was no change in bacterial colony counts or sputum DNA concentrations following treatment with rhDNase, but a small decrease in high molecular weight DNA was observed.
Patients with cystic fibrosis treated with rhDNase show an improvement in rheological properties and pulmonary function, one of the mechanisms being a reduction in the proportion of high molecular weight DNA.
囊性纤维化患者的粘弹性分泌物会导致黏液清除功能受损以及肺部细菌持续存在。异常的流变学部分归因于高分子量脱氧核糖核酸（DNA）的存在。重组人脱氧核糖核酸酶I（rhDNase）已被证明能使DNA解聚，从而降低囊性纤维化患者痰液的体外粘弹性。一项II期双盲安慰剂对照研究表明，rhDNase可改善囊性纤维化患者的肺功能。本研究的目的是评估rhDNase对痰液流变学的体内影响，并确定这些影响是否与肺功能变化相关。
患者被随机分为两组，分别接受安慰剂或每日两次、每次2.5mg的rhDNase治疗，为期10天。在筛查期间以及使用研究药物治疗期间，将痰液样本收集于无菌容器中。主要评估的结果是肺功能和流变学分析。评估的其他参数包括痰液定量细菌学、痰液DNA浓度以及DNA聚合物分子量的变化。
未经治疗的囊性纤维化患者痰液的粘弹性较高，rhDNase治疗降低了所有测量的流变学参数：动态储能模量（弹性指标）、动态损耗模量（粘度指标）和对数复合模量（黏液硬度指标）。rhDNase治疗后，计算得出的咳嗽清除指数也有所改善。这些流变学参数与一秒用力呼气量（FEV1）相关，与安慰剂组0.2（3.1）%的变化相比，rhDNase治疗第10天时，FEV1平均（标准误）提高了13.3（5.6）%。rhDNase治疗后，细菌菌落计数和痰液DNA浓度没有变化，但观察到高分子量DNA略有减少。
接受rhDNase治疗的囊性纤维化患者的流变学特性和肺功能有所改善，其中一个机制是高分子量DNA比例的降低。
