Lötvall Jan
Department of Respiratory Medicine & Allergology, Göteborg University, Göteborg, Sweden.
Curr Med Res Opin. 2004 Nov;20(11):1711-27. doi: 10.1185/030079904X3104.
The introduction of combination products, for the coadministration of an inhaled corticosteroid (ICS) with a long-acting beta2-agonist in a single inhaler, has greatly simplified asthma therapy. The two combination inhalers currently available, Symbicort (budesonide/formoterol in a single inhaler) and Seretide (salmeterol/fluticasone), comply with Step 3 of international guidelines that recommend the addition of a long-acting beta2-agonist to ICS in patients who are inadequately controlled on ICS alone. Importantly, combination inhalers ensure that patients cannot neglect their ICS maintenance therapy in favour of the long-acting beta2-agonist--which may improve adherence and overall asthma control. In vitro experiments suggest that ICS and long-acting beta2-agonists may interact beneficially when they are administered via one inhaler. The efficacy and tolerability of budesonide/formoterol and salmeterol/fluticasone have been demonstrated. There are currently two approaches for treating asthma using combination therapy--fixed and adjustable dosing. Fixed dosing with budesonide/formoterol or salmeterol/fluticasone provides effective asthma control in line with guideline goals. However, given the inherent variability of asthma, there is increasing evidence that adjusting the dose of ICS according to fluctuations in symptoms is beneficial. Findings from a series of studies comparing fixed and adjustable symptom-guided dosing regimens demonstrate that adjustable dosing may improve asthma control at an overall lower steroid dose. Ultimately, if adjustable dosing proves to be an effective treatment option, it may be possible to use budesonide/formoterol for both maintenance therapy and symptom relief, thereby overcoming the need for a separate reliever inhaler. This is because formoterol has a more rapid onset and greater dose-related effects than salmeterol in salmeterol/fluticasone. Given that all patients are different, with different disease severities and treatment preferences, both fixed and adjustable dosing strategies are likely to be important in the long-term management of asthma. It is possible that different treatment options will be used for different patients, depending on their disease severity, personality and ability to adhere to therapy.
联合制剂的推出，即将吸入性糖皮质激素（ICS）与长效β2受体激动剂共同置于单一吸入器中，极大地简化了哮喘治疗。目前市面上的两种联合吸入器，信必可都保（布地奈德/福莫特罗单一吸入器）和舒利迭（沙美特罗/氟替卡松），符合国际指南的第3步，该步骤建议在仅使用ICS控制不佳的患者中，加用长效β2受体激动剂。重要的是，联合吸入器可确保患者不会为了长效β2受体激动剂而忽视ICS维持治疗，这可能会提高依从性并改善整体哮喘控制。体外实验表明，当通过同一吸入器给药时，ICS和长效β2受体激动剂可能会产生有益的相互作用。布地奈德/福莫特罗和沙美特罗/氟替卡松的疗效和耐受性已得到证实。目前使用联合疗法治疗哮喘有两种方法——固定剂量和调整剂量。布地奈德/福莫特罗或沙美特罗/氟替卡松的固定剂量可根据指南目标有效控制哮喘。然而，鉴于哮喘存在内在变异性，越来越多的证据表明，根据症状波动调整ICS剂量是有益的。一系列比较固定剂量和症状引导调整剂量方案的研究结果表明，调整剂量可能以总体较低的类固醇剂量改善哮喘控制。最终，如果调整剂量被证明是一种有效的治疗选择，那么可能可以使用布地奈德/福莫特罗进行维持治疗和缓解症状，从而无需单独使用缓解药物吸入器。这是因为在沙美特罗/氟替卡松中，福莫特罗比沙美特罗起效更快且剂量相关效应更大。鉴于所有患者都各不相同，疾病严重程度和治疗偏好各异，固定剂量和调整剂量策略在哮喘的长期管理中可能都很重要。根据患者的疾病严重程度、个性和坚持治疗的能力，可能会对不同患者使用不同的治疗选择。
