University of Rome Tor Vergata, Department of System Medicine, Rome, Italy.
Respir Med. 2013 Jun;107(6):848-53. doi: 10.1016/j.rmed.2013.02.008. Epub 2013 Mar 11.
Tolerance to both the bronchoprotective effect, and, to a lesser extent, the bronchodilator activity, occurs with all inhaled β2-agonists. Assumed the importance of this topic and the lack of a clinical evaluation specifically designed to assess the impact of chronic administration of indacaterol on the response to salbutamol, we sought to compare the effect of 4-week treatment with indacaterol 150 μg once-daily versus formoterol 12 μg twice-daily on the dose-response curve to inhaled salbutamol (total cumulative dose of 800 μg) in a non-double-blinded, crossover, randomised, and controlled pilot trial that enrolled 20 outpatients with moderate to severe COPD. At the end of 4-week treatments, there was not a statistically significant difference between the two trough FEV1 (p = 0.16), and both indacaterol and formoterol were able to produce a significant (p < 0.001) increase in FEV1 mean differences (L) = indacaterol 0.15 (95% confidence interval (CI) 0.12-0.18); formoterol 0.10, (95% CI 0.08-0.12) 2 h after their inhalation. Salbutamol elicited an evident dose-dependent increase in FEV1 and this occurred also after regular treatment with indacaterol and formoterol with a further mean maximum increase of 0.10L (95% CI 0.05-0.14) and 0.05L (95% CI 0.02-0.08), respectively. The differences between indacaterol and formoterol in FEV1 increases after salbutamol were never statistically significant. The results of this study support the use of salbutamol as rescue medication for rapid relief of bronchospasm in patients suffering from COPD, even when they are under regular treatment with indacaterol.
所有吸入型β2 受体激动剂均会产生对支气管保护作用和(在较小程度上)支气管扩张作用的耐受性。鉴于这个话题的重要性,以及缺乏专门设计的临床评估来评估慢性使用茚达特罗对沙丁胺醇反应的影响,我们试图比较 4 周治疗后,每天一次吸入 150μg 茚达特罗与每天两次吸入 12μg 福莫特罗对吸入沙丁胺醇(总累积剂量 800μg)剂量反应曲线的影响。这是一项非双盲、交叉、随机、对照的初步试验,共纳入 20 例中重度 COPD 门诊患者。在 4 周治疗结束时,两种药物的谷值 FEV1 没有统计学差异(p=0.16),并且茚达特罗和福莫特罗均能显著增加 FEV1 平均值(L),分别为 0.15(95%置信区间(CI)0.12-0.18);福莫特罗 0.10(95% CI 0.08-0.12),吸入后 2 小时。沙丁胺醇引起 FEV1 明显的剂量依赖性增加,即使在常规使用茚达特罗和福莫特罗治疗后也是如此,其平均最大增加分别为 0.10L(95% CI 0.05-0.14)和 0.05L(95% CI 0.02-0.08)。沙丁胺醇后,茚达特罗和福莫特罗在 FEV1 增加方面的差异从未具有统计学意义。这项研究的结果支持使用沙丁胺醇作为快速缓解 COPD 患者支气管痉挛的急救药物,即使他们正在接受茚达特罗的常规治疗。