Knowles M R, Church N L, Waltner W E, Yankaskas J R, Gilligan P, King M, Edwards L J, Helms R W, Boucher R C
Division of Pulmonary Diseases, University of North Carolina, Chapel Hill 27599-7020.
N Engl J Med. 1990 Apr 26;322(17):1189-94. doi: 10.1056/NEJM199004263221704.
Excessive active absorption of sodium is a unique abnormality of the airway epithelium in patients with cystic fibrosis. This defect is associated with thickened mucus and poor clearance of airway secretions and may contribute to the pulmonary disease in these patients. To study whether the inhibition of excessive absorption of sodium might affect the course of lung disease in cystic fibrosis, we performed a double-blind, crossover trial comparing aerosolized amiloride (5 mmol per liter; 3.5 ml four times daily), a sodium-channel blocker, with vehicle alone. Fourteen of the 18 adult patients initially enrolled in the study completed the one-year trial (25 weeks for each treatment). The mean (+/- SEM) loss of forced vital capacity (FVC) was reduced from 3.39 +/- 1.13 ml per day during treatment with vehicle alone to 1.44 +/- 0.67 ml per day during treatment with amiloride (P less than 0.04). A measured index of sputum viscosity and elasticity was abnormal during treatment with vehicle alone and improved during treatment with amiloride. Calculated indexes of mucociliary and cough clearance also improved during amiloride treatment. No systemic, respiratory, or subjective toxic effects of amiloride were noted. We conclude from this preliminary study that aerosolized amiloride can be safely administered to adults with cystic fibrosis. The slowing of the loss of FVC and the improvement in sputum viscosity and elasticity suggest a beneficial clinical effect. Aerosolized amiloride deserves further evaluation in the treatment of lung disease in patients with cystic fibrosis.
钠的过度主动重吸收是囊性纤维化患者气道上皮细胞的一种独特异常。这种缺陷与黏液增厚和气道分泌物清除不良有关，可能导致这些患者的肺部疾病。为了研究抑制钠的过度重吸收是否会影响囊性纤维化患者的肺部疾病进程，我们进行了一项双盲交叉试验，比较雾化的氨氯吡咪（5 mmol/升；3.5 ml，每日4次）（一种钠通道阻滞剂）与单纯赋形剂。最初纳入该研究的18名成年患者中有14名完成了为期一年的试验（每种治疗25周）。用力肺活量（FVC）的平均（±标准误）下降幅度从单纯使用赋形剂治疗期间的每天3.39±1.13 ml降至使用氨氯吡咪治疗期间的每天1.44±0.67 ml（P<0.04）。单独使用赋形剂治疗期间，痰液黏度和弹性的测量指标异常，而使用氨氯吡咪治疗期间有所改善。氨氯吡咪治疗期间，黏液纤毛清除和咳嗽清除的计算指标也有所改善。未观察到氨氯吡咪的全身、呼吸或主观毒性作用。我们从这项初步研究得出结论，雾化氨氯吡咪可安全地给予成年囊性纤维化患者。FVC下降速度减慢以及痰液黏度和弹性改善提示有有益的临床效果。雾化氨氯吡咪在囊性纤维化患者肺部疾病治疗中值得进一步评估。
