Usmani Omar S, Biddiscombe Martyn F, Nightingale Julia A, Underwood S Richard, Barnes Peter J
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, United Kingdom.
J Appl Physiol (1985). 2003 Nov;95(5):2106-12. doi: 10.1152/japplphysiol.00525.2003. Epub 2003 Aug 1.
Aerosol particle size influences airway drug deposition. Current inhaler devices are inefficient, delivering a heterodisperse distribution of drug particle sizes where, at best, 20% reaches the lungs. Monodisperse aerosols are the appropriate research tools to investigate basic aerosol science concepts within the human airways. We hypothesized that engineering such aerosols of albuterol would identify the ideal bronchodilator particle size, thereby optimizing inhaled therapeutic drug delivery. Eighteen stable mildly to moderately asthmatic patients [mean forced expiratory volume in 1 s (FEV1) 74.3% of predicted] participated in a randomized, double-blind, crossover study design. A spinning-top aerosol generator was used to produce monodisperse albuterol aerosols that were 1.5, 3, and 6 microm in size, and also a placebo, which were inhaled at cumulative doses of 10, 20, 40, and 100 microg. Lung function changes and tolerability effects were determined. The larger particles, 6 and 3 microm, were significantly more potent bronchodilators than the 1.5-microm and placebo aerosols for FEV1 and for the forced expiratory flow between exhalation of 25 and 75% of forced vital capacity. A 20-microg dose of the 6- and 3-microm aerosols produced FEV1 bronchodilation comparable to that produced by 200 microg from a metered-dose inhaler. No adverse effects were observed in heart rate and plasma potassium. The data suggest that in mildly to moderately asthmatic patients there is more than one optimal beta2-agonist bronchodilator particle size and that these are larger particles in the higher part of the respirable range. Aerosols delivered in monodisperse form can enable large reductions of the inhaled dose without loss of clinical efficacy.
气溶胶粒径会影响气道药物沉积。目前的吸入器装置效率低下，所输送的药物粒径分布不均一，其中最多只有20%能到达肺部。单分散气溶胶是研究人类气道内基本气溶胶科学概念的合适研究工具。我们假设，通过工程手段制备沙丁胺醇单分散气溶胶将能确定理想的支气管扩张剂粒径，从而优化吸入治疗药物的递送。18名稳定的轻度至中度哮喘患者[1秒用力呼气容积（FEV1）平均为预测值的74.3%]参与了一项随机、双盲、交叉研究设计。使用旋转顶部气溶胶发生器制备粒径为1.5、3和6微米的单分散沙丁胺醇气溶胶，以及一种安慰剂，以10、20、40和100微克的累积剂量吸入。测定肺功能变化和耐受性影响。对于FEV1以及用力肺活量呼气25%至75%之间的用力呼气流量，6微米和3微米的较大颗粒作为支气管扩张剂的效力明显高于1.5微米的颗粒和气溶胶安慰剂。20微克剂量的6微米和3微米气溶胶产生的FEV1支气管扩张作用与定量吸入器200微克产生的相当。未观察到心率和血浆钾的不良反应。数据表明，在轻度至中度哮喘患者中，存在不止一种最佳的β2受体激动剂支气管扩张剂粒径，且这些粒径在可吸入范围的较高部分，是较大的颗粒。以单分散形式递送的气溶胶可在不损失临床疗效的情况下大幅减少吸入剂量。
