Zayas Gustavo, Valle Juan C, Alonso Mauricio, Alfaro Henry, Vega Daniel, Bonilla Gloria, Reyes Miguel, King Malcolm
University of Alberta Pulmonary Research Group, Edmonton, Canada.
BMC Pulm Med. 2007 Aug 13;7:11. doi: 10.1186/1471-2466-7-11.
Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action.
To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an ex-vivo model and then to an in-vivo large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes.
Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways.
The ex-vivo frog palate and the in-vivo mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial phase of developing the concept of mucomodulation: Can we modulate the physical characteristics of the respiratory secretions to reduce aerosolization without affecting normal mucociliary clearance function, or even better improving it?
已设计了多种策略和设备，用于在提供护理时保护医护人员免受传染性呼吸道疾病的感染。在调节呼吸道分泌物的物理特性以尽量减少促进空气传播疾病传播的气溶胶形成时，一个基本前提是原型药物对呼吸道第一道防线——通过纤毛作用清除黏液——没有不良影响。
为了评估和证明我们的黏液调节剂（XLs）的主要作用机制，我们构建了从基础实验室研究到体外模型再到体内大型动物模型的证据。我们将无分泌亢进的麻醉犬暴露于不同剂量浓度的雾化XL“B”、XL“D”和XL“S”中。我们评估了：心肺模式、气管黏液清除、气道通畅性和黏液黏弹性变化。
将蛙腭黏液暴露于XLs中不会影响纤毛作用对黏液的清除。给予XLs后犬保持正常的心肺模式。麻醉犬的气管黏液纤毛清除显示平均持续增加40%。气管黏液的丝化增加，气道内没有黏液潴留。
本研究中使用的体外蛙腭模型和体内哺乳动物模型似乎是合适的，且相互补充，以更好地评估我们的黏液调节剂对黏液纤毛清除防御机制的作用。在这两种上皮模型中，黏液纤毛装置的生理功能均未受到负面影响。黏液调节剂交联的气道黏液可从完整的气道和正常运作的呼吸系统中更好地清除，这可能是由于与纤毛的相互作用增强或气流依赖机制。本研究获得的数据使我们能够确保符合在黏液调节概念开发初始阶段确立的基本要求标准：我们能否调节呼吸道分泌物的物理特性以减少气溶胶形成，同时不影响正常的黏液纤毛清除功能，甚至更好地改善它？
