Houghton Catherine M, Woodcock Ashley A, Singh Dave
Medicines Evaluation Unit, North West Lung Research Centre, Wythenshawe Hospital, Manchester, UK.
Br J Clin Pharmacol. 2004 Aug;58(2):134-41. doi: 10.1111/j.1365-2125.2004.02105.x.
Pulmonary function methods which are able to detect small pharmacological effects may be useful for assessing the full dose-response curve of bronchodilatators. We compared the ability of impulse oscillometry (R5, R20, X5, RF), plethysmography (sGaw) and spirometry [forced expiratory volume in 1 s (FEV(1)), maximal mid expiratory flow rate (MMEF)] to measure the dose-response effects of salbutamol in 12 healthy subjects, 12 mild asthmatics (mean FEV(1) 96% predicted) and 12 moderate asthmatics (mean FEV(1) 63% predicted). The techniques were performed twice to assess variability. Then salbutamol 10, 20, 100, 200 and 800 microg was administered. The sensitivity of the methods were compared by determining the lowest dose that caused changes greater than variability. In healthy subjects significant changes (p < or = 0.05) were observed only in FEV(1) (4.1%) and MMEF (14.6%) at 100 microg and sGaw (25.6%) and R20 (8.3%) at 200 microg. In mild asthmatics significant changes were observed in sGaw (15.9%) at 10 microg, X5 (23%), RF (20.3%) and MMEF (15.7%) at 20 microg, R5 (13.9%) and R20 (9.4%) at 100 microg and FEV(1) (7.1%) at 200 microg. All measurements except R20 demonstrated significant changes at 10 micro g in moderate asthmatics. The most sensitive test for assessing bronchodilatation is different in healthy subjects and asthmatics, and varies with severity of airflow obstruction.
能够检测到微小药理效应的肺功能检测方法,可能有助于评估支气管扩张剂的完整剂量-反应曲线。我们比较了脉冲振荡法(R5、R20、X5、RF)、体积描记法(sGaw)和肺量计法[第1秒用力呼气量(FEV(1))、最大呼气中期流速(MMEF)]在12名健康受试者、12名轻度哮喘患者(平均FEV(1)为预测值的96%)和12名中度哮喘患者(平均FEV(1)为预测值的63%)中测量沙丁胺醇剂量-反应效应的能力。这些技术进行了两次以评估变异性。然后给予10、20、100、200和800微克的沙丁胺醇。通过确定引起变化大于变异性的最低剂量来比较这些方法的敏感性。在健康受试者中,仅在100微克时FEV(1)(4.1%)和MMEF(14.6%)以及在200微克时sGaw(25.6%)和R20(8.3%)观察到显著变化(p≤0.05)。在轻度哮喘患者中,在10微克时sGaw(15.9%)、在20微克时X5(23%)、RF(20.3%)和MMEF(15.7%)、在100微克时R5(13.9%)和R20(9.4%)以及在200微克时FEV(1)(7.1%)观察到显著变化。在中度哮喘患者中,除R20外,所有测量在10微克时均显示出显著变化。评估支气管扩张的最敏感检测方法在健康受试者和哮喘患者中不同,并且随气流阻塞的严重程度而变化。