Hypertonic Aerosols Hydrate Airways Longer and Reduce Acidification Risk with Nonpermeating Cation and Permeating Anion Salts.

IF 2 4区 医学 Q3 RESPIRATORY SYSTEM Journal of Aerosol Medicine and Pulmonary Drug Delivery Pub Date : 2024-04-01 Epub Date: 2024-02-14 DOI:10.1089/jamp.2023.0039
Ana Flavia Zuim, Aurélie Edwards, Dennis Ausiello, Deen Bhatta, David A Edwards
{"title":"Hypertonic Aerosols Hydrate Airways Longer and Reduce Acidification Risk with Nonpermeating Cation and Permeating Anion Salts.","authors":"Ana Flavia Zuim, Aurélie Edwards, Dennis Ausiello, Deen Bhatta, David A Edwards","doi":"10.1089/jamp.2023.0039","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Background:</i></b> 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. <b><i>Methods:</i></b> In a double-blinded, placebo-controlled clinical study, phonation threshold pressure (PTP) was measured prenasal and postnasal inhalation of hypertonic aerosols of NaCl, KCl, CaCl<sub>2</sub>, and MgCl<sub>2</sub> 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. <b><i>Results:</i></b> PTP decreased by 9%-22% relative to baseline (<i>p</i> < 0.05) for all salts within the first 30 minutes postadministration, indicating effective laryngeal hydration. Only MgCl<sub>2</sub> 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 MgCl<sub>2</sub>, 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 (CaCl<sub>2</sub> and MgCl<sub>2</sub>), this acid-trigger signature does not exist. <b><i>Conclusions:</i></b> 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.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"64-76"},"PeriodicalIF":2.0000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jamp.2023.0039","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/14 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0

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.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
非渗透性阳离子盐和渗透性阴离子盐的高渗气溶胶可使呼吸道长时间保持水合状态并降低酸化风险。
背景:高渗气溶胶似乎能促进或抑制脱水引起的上呼吸道功能障碍,而这取决于气溶胶的成分。我们试图在一项介入性人体临床研究中通过实验来探索这种成分依赖性,并通过对上气道离子和水分运输的数值分析从理论上探索这种依赖性。研究方法在一项双盲、安慰剂对照的临床研究中,在七名受试者鼻前和鼻后吸入 NaCl、KCl、CaCl2 和 MgCl2 的高渗气溶胶时测量了发音阈压(PTP)。使用先前在文献中描述的数学模型对这些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。结果显示PTP 相对于基线下降了 9%-22%(p 2),90 分钟后 PTP 下降(给药后 2 小时比基线低 21%)。通过数值分析,我们确定沉积后 15 分钟内的气道水容量由渗透压决定,而 30 分钟后,二价阳离子盐(如 MgCl2)通过缓慢的二价阳离子旁细胞清除,能更好地保持气道表面液体(ASL)容量。随着 ASL 高度的升高,CFTR 氯化通量也随之下降,这似乎是渗透性阳离子(氯化钠)和非渗透性阴离子(甘露醇)气溶胶沉积的特征。对于缺乏渗透性阳离子而包括渗透性阴离子(CaCl2 和 MgCl2)的高渗气溶胶,则不存在这种酸触发特征。结论:无渗透性阳离子和渗透性阴离子的高渗气溶胶似乎能更长时间地为上呼吸道补充水分,不仅不会引起咳嗽和支气管收缩等喉部功能障碍,反而会减轻这种症状。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
6.70
自引率
2.90%
发文量
34
审稿时长
>12 weeks
期刊介绍: Journal of Aerosol Medicine and Pulmonary Drug Delivery is the only peer-reviewed journal delivering innovative, authoritative coverage of the health effects of inhaled aerosols and delivery of drugs through the pulmonary system. The Journal is a forum for leading experts, addressing novel topics such as aerosolized chemotherapy, aerosolized vaccines, methods to determine toxicities, and delivery of aerosolized drugs in the intubated patient. Journal of Aerosol Medicine and Pulmonary Drug Delivery coverage includes: Pulmonary drug delivery Airway reactivity and asthma treatment Inhalation of particles and gases in the respiratory tract Toxic effects of inhaled agents Aerosols as tools for studying basic physiologic phenomena.
期刊最新文献
In Vitro Comparison of Inspiration-Synchronized and Continuous Vibrating Mesh Nebulizer During Adult Invasive Mechanical Ventilation. Prospects of Inhalable Formulations of Conventionally Administered Repurposed Drugs for Adjunctive Treatment of Drug-Resistant Tuberculosis: Supporting Evidence from Clinical Trials and Cohort Studies. Scale-Up and Postapproval Changes in Orally Inhaled Drug Products: Scientific and Regulatory Considerations. Assessing Human Lung Pharmacokinetics Using Exhaled Breath Particles. Demographic and Asthma-Related Characteristics of Asthmatics Using Pressurized Metered Dose Inhalers and Dry Powder Inhalers.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1