Puchelle E, Zahm J M, de Bentzmann S, Grosskopf C, Shak S, Mougel D, Polu J M
Unité INSERM 314, Université de Reims, France.
Eur Respir J. 1996 Apr;9(4):765-9. doi: 10.1183/09031936.96.09040769.
Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce in vitro the viscosity and to improve the transport capacity of purulent respiratory mucus in cystic fibrosis. During episodes of exacerbation of chronic bronchitis, the patients generally expectorate purulent mucus. Purulence of mucus is associated with an increased deoxyriboneucleic acid (DNA) concentration. We analyzed in vitro the potential effect of rhDNase on chronic bronchitis mucus transport by the ciliary activity (frog palate model) and by simulated cough (cough machine model), as well as the effect on mucus viscosity (controlled stress rheometer) and surface properties (contact angle). Purulent sputa collected from patients with chronic bronchitis (n = 15) during an episode of exacerbation were incubated for 30 min at 37 degrees C with either rhDNase at two different concentrations (final concentration 2 or 4 micrograms.mL-1) or placebo. The median mucociliary transport rate was significantly improved by rhDNase from 0.68 with placebo to 0.79 and 0.83 with 2 and 4 micrograms.mL-1 of rhDNase, respectively. A significant improvement in mucus cough transport was also induced by rhDNase from 25.5 mm with placebo to 27.0 mm with either 2 or 4 micrograms.mL-1 rhDNase. These improvements in mucus transport capacity were associated with alterations in the physical properties of the mucus. The mucus median control viscosity (511.4 Pa.s) and median contact angle (0.85 rd) significantly decreased to 112.5 Pa.s and 0.74 rd, respectively, in the presence of 4 micrograms.mL-1 of rhDNase. These findings demonstrate that recombinant deoxyribonuclease may exert a beneficial effect on mucus clearance in vitro by altering the viscosity and surface properties of the purulent chronic bronchitic sputum samples.
重组人脱氧核糖核酸酶（rhDNase）已被证明在体外可降低囊性纤维化患者脓性呼吸道黏液的黏度，并提高其运输能力。在慢性支气管炎急性加重期，患者通常咳出脓性黏液。黏液的脓性与脱氧核糖核酸（DNA）浓度升高有关。我们通过纤毛活动（蛙腭模型）和模拟咳嗽（咳嗽机模型）在体外分析了rhDNase对慢性支气管炎黏液运输的潜在影响，以及对黏液黏度（控制应力流变仪）和表面特性（接触角）的影响。从15例慢性支气管炎急性加重期患者收集的脓性痰液，在37℃下分别与两种不同浓度（终浓度2或4μg/mL）的rhDNase或安慰剂孵育30分钟。rhDNase使黏液纤毛运输速率中位数显著提高，安慰剂组为0.68，rhDNase 2μg/mL和4μg/mL组分别为0.79和0.83。rhDNase还使黏液咳嗽运输显著改善，安慰剂组为25.5mm，rhDNase 2μg/mL或4μg/mL组为27.0mm。这些黏液运输能力的改善与黏液物理性质的改变有关。在存在4μg/mL rhDNase的情况下，黏液的控制黏度中位数（511.4Pa·s）和接触角中位数（0.85弧度）分别显著降至至112.5Pa·s和0.74弧度。这些发现表明，重组脱氧核糖核酸酶可能通过改变脓性慢性支气管炎痰液样本的黏度和表面特性，在体外对黏液清除发挥有益作用。
