Mucus clearance and lung function in cystic fibrosis with hypertonic saline
Mucus clearance and lung function in cystic fibrosis with hypertonic saline
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DOI：
10.1056/nejmoa043891
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发表时间：
2006-01-19
影响因子：
158.5
通讯作者：
Boucher, RC
中科院分区：
文献类型：
--
作者：
Donaldson, SH;Bennett, WD;Boucher, RC
背景：囊性纤维化患者呼吸道表面液量的异常动态平衡被认为是粘液清除和呼吸道防御的缺陷。方法：24例囊性纤维化患者随机分为阿米洛利和阿米洛利两组，分别给予高渗盐水(7%氯化钠5ml)雾化吸入，每日4次，每次4次。结果：长期吸入高渗盐水而不用阿米洛利(即安慰剂)可使1h黏液清除率持续(大于或等于8h)高于阿米洛利组(14.0+/-2.0vs.7.0+/-1.5%，P=0.02)，24小时黏液清除率高于基础水平。此外，吸入高渗盐水和安慰剂改善了基准期和治疗期之间一秒用力呼气量(FEV(Sub1))(平均差值为6.62%；95%可信区间为1.6至11.7；P=0.02)，而高渗盐水和阿米洛利并未改善FEV(Sub1)(平均差值为2.9%；95%可信区间为-2.2至8.0；P=0.23)。在接受高渗盐水和安慰剂治疗的患者中，用力肺活量(FVC)、用力呼气流量(FEF)在25%到75%之间(FEF(低于2575))和呼吸症状也得到了显著改善，而残气量占总肺活量的比例(RV：TLC)在两组中都没有变化。两组肺功能变化比较，差异无统计学意义。体外数据表明，持续的呼吸道表面水化是粘液清除持续改善的原因，而阿米洛利抑制渗透驱动的水传输是临床益处丧失的原因。结论：在囊性纤维化患者中，吸入高渗盐水可持续加速粘液清除并改善肺功能。这种治疗可能会保护肺部免受降低粘液清除和产生肺部疾病的侮辱。
BACKGROUND:Abnormal homeostasis of the volume of airway surface liquid in patients with cystic fibrosis is thought to produce defects in mucus clearance and airway defense. Through osmotic forces, hypertonic saline may increase the volume of airway surface liquid, restore mucus clearance, and improve lung function.METHODS:A total of 24 patients with cystic fibrosis were randomly assigned to receive treatment with inhaled hypertonic saline (5 ml of 7 percent sodium chloride) four times daily with or without pretreatment with amiloride. Mucus clearance and lung function were measured during 14-day baseline and treatment periods.RESULTS:Long-term inhalation of hypertonic saline without pretreatment with amiloride (i.e., with placebo pretreatment) resulted in a sustained (greater/equal 8 hours) increase in 1-hour rates of mucus clearance, as compared with those with amiloride pretreatment (14.0+/-2.0 vs. 7.0+/-1.5 percent, respectively; P=0.02) and increased 24-hour rates of mucus clearance over baseline. Furthermore, inhalation of hypertonic saline with placebo improved the forced expiratory volume in one second (FEV(sub 1)) between the baseline period and the treatment period (mean difference, 6.62 percent; 95 percent confidence interval, 1.6 to 11.7; P=0.02), whereas hypertonic saline with amiloride did not improve FEV(sub 1) (mean difference, 2.9 percent; 95 percent confidence interval, -2.2 to 8.0; P=0.23). Forced vital capacity (FVC), the forced expiratory flow between 25 and 75 percent of FVC (FEF(sub 25-75)), and respiratory symptoms also significantly improved in patients treated with hypertonic saline and placebo, whereas the residual volume as a proportion of total lung capacity (RV:TLC) did not change in either group. A comparison of the changes in lung function in the two groups showed no significant difference. In vitro data suggested that sustained hydration of airway surfaces was responsible for the sustained improvement in mucus clearance, whereas inhibition of osmotically driven water transport by amiloride accounted for the observed loss of clinical benefit.CONCLUSIONS:In patients with cystic fibrosis, inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function. This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease.