Middleton P G, Geddes D M, Alton E W
Ion Transport Laboratory, Royal Brompton National Heart and Lung Institute, London.
Thorax. 1993 Aug;48(8):812-6. doi: 10.1136/thx.48.8.812.
Mucociliary clearance is an important component of pulmonary defence. Maximum clearance is thought to depend on an optimal depth of the sol layer, allowing the most efficient interaction between the cilia and the overlying mucus layer. Sodium absorption, the major ion transport in human airways, is thought to be important in the regulation of the depth of the sol layer. In the airways of patients with cystic fibrosis sodium absorption is increased and mucociliary clearance decreased. Amiloride, a sodium channel blocker, has been shown to improve pulmonary mucociliary clearance in patients with cystic fibrosis. However, its effects on nasal mucociliary clearance in either normal subjects or those with cystic fibrosis are unknown. A study was therefore performed to investigate whether nebulised amiloride improves nasal mucociliary clearance in normal or cystic fibrosis subjects.
Nasal mucociliary clearance was measured by the saccharin clearance technique in 12 normal subjects and 12 with cystic fibrosis. For the control study measurements were made on two consecutive days and the mean time for each subject averaged. For the drug study measurements were also made on two consecutive days, after administration of nasally nebulised amiloride or placebo (saline) in a double blind manner. Nasal potential difference was measured in eight patients with cystic fibrosis after the administration of amiloride or placebo to assess the efficacy of deposition and duration of action.
Baseline values of mucociliary clearance were significantly faster in the normal subjects than in those with cystic fibrosis. In both groups mucociliary clearance was increased after both saline and amiloride, with no significant difference between either treatment. As previously reported, baseline nasal potential difference was significantly more negative in the subjects with cystic fibrosis. Amiloride significantly reduced the potential difference for at least 60 minutes in these subjects.
Nebulised saline significantly improves nasal mucociliary clearance in both normal subjects and those with cystic fibrosis. Amiloride did not appear to exert any additional effects in either group of subjects, despite evidence of its efficacy of deposition.
黏液纤毛清除功能是肺部防御的重要组成部分。最大清除效率被认为取决于溶胶层的最佳深度,以便纤毛与覆盖其上的黏液层之间实现最有效的相互作用。钠吸收是人类气道中的主要离子转运方式,被认为在溶胶层深度的调节中起重要作用。在囊性纤维化患者的气道中,钠吸收增加而黏液纤毛清除功能下降。氨氯吡脒,一种钠通道阻滞剂,已被证明可改善囊性纤维化患者的肺部黏液纤毛清除功能。然而,其对正常受试者或囊性纤维化患者鼻黏液纤毛清除功能的影响尚不清楚。因此进行了一项研究,以调查雾化吸入氨氯吡脒是否能改善正常或囊性纤维化受试者的鼻黏液纤毛清除功能。
采用糖精清除技术测量12名正常受试者和12名囊性纤维化患者的鼻黏液纤毛清除功能。在对照研究中,连续两天进行测量,并计算每个受试者的平均时间。在药物研究中,同样连续两天进行测量,以双盲方式给予雾化吸入的氨氯吡脒或安慰剂(生理盐水)后进行。在8名囊性纤维化患者中,给予氨氯吡脒或安慰剂后测量鼻电位差,以评估沉积效果和作用持续时间。
正常受试者的黏液纤毛清除功能基线值明显快于囊性纤维化患者。在两组中,生理盐水和氨氯吡脒给药后黏液纤毛清除功能均有所增加,两种治疗之间无显著差异。如先前报道,囊性纤维化受试者的基线鼻电位差明显更负。氨氯吡脒使这些受试者的电位差至少在60分钟内显著降低。
雾化吸入生理盐水可显著改善正常受试者和囊性纤维化患者的鼻黏液纤毛清除功能。尽管有证据表明氨氯吡脒有沉积效果,但在两组受试者中它似乎均未产生任何额外作用。