Abstract：
Background: Hyperosmolar aerosols appear to promote or suppress upper airway dysfunction caused by dehydration in a composition-dependent manner. We sought to explore this composition dependence experimentally, in an interventional human clinical study, and theoretically, by numerical analysis of upper airway ion and water transport. Methods: In a double-blinded, placebo-controlled clinical study, phonation threshold pressure (PTP) was measured prenasal and postnasal inhalation of hypertonic aerosols of NaCl, KCl, CaCl2, and MgCl2 in seven human subjects. Numerical analysis of water and solute exchanges in the upper airways following deposition of these same aerosols was performed using a mathematical model previously described in the literature. Results: PTP decreased by 9%-22% relative to baseline (p < 0.05) for all salts within the first 30 minutes postadministration, indicating effective laryngeal hydration. Only MgCl2 reduced PTP beyond 90 minutes (21% below baseline at 2 hours postadministration). By numerical analysis, we determined that, while airway water volume up to 15 minutes postdeposition is dictated by osmolarity, after 30 minutes, divalent cation salts, such as MgCl2, better retain airway surface liquid (ASL) volume by slow paracellular clearance of the divalent cation. Fall of CFTR chloride flux with rise in ASL height, a promoter of airway acidification, appears to be a signature of permeating cation (NaCl) and nonpermeating anion (mannitol) aerosol deposition. For hypertonic aerosols that lack permeating cation and include permeating anion (CaCl2 and MgCl2), this acid-trigger signature does not exist. Conclusions: Nonpermeating cation and permeating anion hypertonic aerosols appear to hydrate upper airways longer and, rather than provoke, may reduce laryngeal dysfunction such as cough and bronchoconstriction.
摘要：
背景：高渗性气雾剂似乎以成分依赖性方式促进或抑制由脱水引起的上呼吸道功能障碍。我们试图通过实验探索这种成分依赖性，在一项介入人体临床研究中，理论上,通过数值分析上气道离子和水的运输。方法：在双盲中，安慰剂对照临床研究，测量鼻前和鼻后吸入NaCl高渗气溶胶的发声阈值压力（PTP），KCl,七个人类受试者中的CaCl2和MgCl2。使用文献中先前描述的数学模型，对这些相同气溶胶沉积后上呼吸道中的水和溶质交换进行了数值分析。结果：在给药后的前30分钟内，所有盐的PTP相对于基线降低了9％-22％（p<0.05），表明有效的喉部水合作用。仅MgCl2将PTP降低超过90分钟(施用后2小时低于基线21%)。通过数值分析,我们决定，虽然沉积后15分钟内的气道水体积是由渗透压决定的，30分钟后,二价阳离子盐，例如MgCl2,通过缓慢的细胞旁清除二价阳离子更好地保留气道表面液体(ASL)的体积。CFTR氯化物通量随ASL高度上升而下降，气道酸化的促进剂，似乎是渗透阳离子（NaCl）和非渗透阴离子（甘露醇）气溶胶沉积的标志。对于缺乏渗透性阳离子并包括渗透性阴离子（CaCl2和MgCl2）的高渗气溶胶，此酸触发签名不存在。结论：非渗透性阳离子和渗透性阴离子高渗气溶胶似乎可以延长上呼吸道的水合时间，而不是挑衅，可以减少喉功能障碍，如咳嗽和支气管收缩。
