Robichaud Annette, Fereydoonzad Liah, Schuessler Thomas F
SCIREQ Scientific Respiratory Equipment, Inc., Montreal, Quebec, Canada
SCIREQ Scientific Respiratory Equipment, Inc., Montreal, Quebec, Canada.
Am J Physiol Lung Cell Mol Physiol. 2015 Apr 15;308(8):L837-46. doi: 10.1152/ajplung.00343.2014. Epub 2015 Jan 30.
Airway hyperresponsiveness often constitutes a primary outcome in respiratory studies in mice. The procedure commonly employs aerosolized challenges, and results are typically reported in terms of bronchoconstrictor concentrations loaded into the nebulizer. Yet, because protocols frequently differ across studies, especially in terms of aerosol generation and delivery, direct study comparisons are difficult. We hypothesized that protocol variations could lead to differences in aerosol delivery efficiency and, consequently, in the dose delivered to the subject, as well as in the response. Thirteen nebulization patterns containing common protocol variations (nebulization time, duty cycle, particle size spectrum, air humidity, and/or ventilation profile) and using increasing concentrations of methacholine and broadband forced oscillations (flexiVent, SCIREQ, Montreal, Qc, Canada) were created, characterized, and studied in anesthetized naïve A/J mice. A delivered dose estimate calculated from nebulizer-, ventilator-, and subject-specific characteristics was introduced and used to account for protocol variations. Results showed that nebulization protocol variations significantly affected the fraction of aerosol reaching the subject site and the delivered dose, as well as methacholine reactivity and sensitivity in mice. From the protocol variants studied, addition of a slow deep ventilation profile during nebulization was identified as a key factor for optimization of the technique. The study also highlighted sensitivity differences within the lung, as well as the possibility that airway responses could be selectively enhanced by adequate control of nebulizer and ventilator settings. Reporting results in terms of delivered doses represents an important standardizing element for assessment of airway hyperresponsiveness in mice.
气道高反应性通常是小鼠呼吸研究的主要结果。该实验通常采用雾化激发，结果通常以雾化器中加载的支气管收缩剂浓度来报告。然而，由于不同研究的实验方案经常不同，特别是在气溶胶生成和输送方面，因此很难进行直接的研究比较。我们推测，实验方案的差异可能导致气溶胶输送效率的差异，进而导致输送给实验对象的剂量以及反应的差异。我们创建了13种包含常见实验方案差异（雾化时间、占空比、粒径谱、空气湿度和/或通气模式）的雾化模式，并使用递增浓度的乙酰甲胆碱和宽带强迫振荡（flexiVent，SCIREQ，加拿大蒙特利尔），在未接触过实验的麻醉A/J小鼠中进行了表征和研究。引入了根据雾化器、呼吸机和实验对象的特定特征计算得出的输送剂量估计值，并用于解释实验方案的差异。结果表明，雾化实验方案的差异显著影响到达实验对象部位的气溶胶比例和输送剂量，以及小鼠的乙酰甲胆碱反应性和敏感性。在所研究的实验方案变体中，雾化期间添加缓慢的深度通气模式被确定为优化该技术的关键因素。该研究还强调了肺内的敏感性差异，以及通过适当控制雾化器和呼吸机设置可以选择性增强气道反应的可能性。以输送剂量来报告结果是评估小鼠气道高反应性的一个重要标准化因素。
