Suri Ranjan, Marshall Lindsay J, Wallis Colin, Metcalfe Christopher, Bush Andrew, Shute Janis K
MRCPCH, Department of Respiratory Paediatrics, Royal Brompton and Harefield NHS Trust, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK.
Am J Respir Crit Care Med. 2002 Aug 1;166(3):352-5. doi: 10.1164/rccm.2110015.
Recombinant human DNase (rhDNase) is an established treatment in cystic fibrosis (CF), but it may liberate cationic mediators bound to DNA in the airways. An alternative mucolytic therapy is hypertonic saline (HS); however, HS may potentiate neutrophilic inflammation. We compared the effect of rhDNase and HS on cationic proinflammatory mediators in CF sputum. In a randomized, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once-daily 2.5 mg rhDNase, alternate-day 2.5 mg rhDNase, and twice-daily 7% HS. Sputum levels of total interleukin-8 (IL-8), free IL-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase (NE) activity were measured before and after each treatment. The change in mediator levels from baseline with daily rhDNase and HS was not significant; however, with alternate-day rhDNase, there was an increase in free IL-8. When changes in mediator levels with daily rhDNase were compared with alternate-day rhDNase and HS, no significant differences were detected. Only changes in NE activity were associated with changes in lung function. In summary, we were unable to show that rhDNase or HS promote airway inflammation in CF.
重组人脱氧核糖核酸酶(rhDNase)是治疗囊性纤维化(CF)的一种成熟疗法,但它可能会释放气道中与DNA结合的阳离子介质。另一种黏液溶解疗法是高渗盐水(HS);然而,HS可能会增强中性粒细胞炎症。我们比较了rhDNase和HS对CF痰液中阳离子促炎介质的影响。在一项随机交叉试验中,48名CF儿童被连续分配接受为期12周的每日一次2.5毫克rhDNase、隔日一次2.5毫克rhDNase和每日两次7% HS治疗。在每次治疗前后测量痰液中总白细胞介素-8(IL-8)、游离IL-8、髓过氧化物酶、嗜酸性粒细胞阳离子蛋白和中性粒细胞弹性蛋白酶(NE)活性的水平。每日使用rhDNase和HS时,介质水平相对于基线的变化不显著;然而,隔日使用rhDNase时,游离IL-8有所增加。当比较每日使用rhDNase时介质水平的变化与隔日使用rhDNase和HS时的变化时,未发现显著差异。只有NE活性的变化与肺功能的变化相关。总之,我们未能证明rhDNase或HS会促进CF患者的气道炎症。