Cystic Fibrosis Research and Treatment Center/Marsico Lung Institute, Chapel Hill, NC, USA.
Division of Pulmonary and Critical Care Medicine, Dept of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Eur Respir J. 2018 May 17;51(5). doi: 10.1183/13993003.02652-2017. Print 2018 May.
Inhaled hypertonic saline (HS) is an effective therapy for muco-obstructive lung diseases. However, the mechanism of action and principles pertinent to HS administration remain unclear.An system aerosolised HS to epithelial cells at rates comparable to conditions. Airway surface liquid (ASL) volume and cell height responses were measured by confocal microscopy under normal and hyperconcentrated mucus states.Aerosolised HS produced a rapid increase in ASL height and decrease in cell height. Added ASL volume was quickly reabsorbed following termination of nebulisation, although cell height did not recover within the same time frame. ASL volume responses to repeated HS administrations were blunted, but could be restored by a hypotonic saline bolus interposed between HS administrations. HS-induced ASL hydration was prolonged with hyperconcentrated mucus on the airway surface, with more modest reductions in cell volume.Aerosolised HS produced osmotically induced increases in ASL height that were limited by active sodium absorption and cell volume-induced reductions in cell water permeability. Mucus on airway surfaces prolonged the effect of HS mucus-dependent osmotic forces, suggesting that the duration of action of HS is increased in patients with hyperconcentrated mucus.
吸入高渗盐水(HS)是治疗黏液阻塞性肺部疾病的有效方法。然而,HS 给药的作用机制和原则尚不清楚。该系统以与生理条件相当的速率将 HS 气溶胶化为上皮细胞。通过共聚焦显微镜在正常和高浓度黏液状态下测量气道表面液(ASL)体积和细胞高度反应。雾化 HS 可迅速增加 ASL 高度并降低细胞高度。尽管在相同的时间范围内细胞高度没有恢复,但在雾化结束时,添加的 ASL 体积很快被吸收。重复 HS 给药的 ASL 体积反应减弱,但通过在 HS 给药之间插入低渗盐水冲击可以恢复。气道表面上的高浓度黏液会延长 HS 诱导的 ASL 水合作用,使细胞体积减少幅度较小。雾化 HS 产生渗透压诱导的 ASL 高度增加,受主动钠吸收和细胞体积诱导的细胞水通透性降低的限制。气道表面上的黏液延长了 HS 的作用,这表明高浓度黏液患者 HS 的作用持续时间延长。