哮喘联盟

   摘要 
   Olodaterol是一种每日使用1次的长效（超过24h）β2-肾上腺素能受体激动剂类支气管扩张剂。但这些患者中普遍存在高胆碱能作用降低β2-肾上腺素能受体激动剂的作用，这为olodaterol和长效抗胆碱药噻托溴铵成为一日一次的联合治疗提供了合理性。在豚鼠模型中，我们评估了olodaterol单用及与噻托溴铵联用后气道对组胺反应的保护作用，而气道对组胺的反应部分由胆碱反射机制引起。
   此外，在急性过敏性哮喘豚鼠模型中，我们检测了这些支气管扩张剂对过敏原引起的早期(EAR)和晚期哮喘(LAR)反应、组胺引起气道高反应性(AHR)及气道炎症的协同效应。研究发现与噻托溴铵联用，可以协同性增强和延长olodaterol对组胺引起的支气管狭窄的保护作用。此外，olodaterol可以协同性增强噻托溴铵对过敏原引起的EAR后气道高反应性的逆转和保护作用。Olodaterol和噻托溴铵都能有效的抑制过敏原引起的EAR和LAR，且两者合用能使EAR和LAR得到完全抑制。特别是，这些效果与气道炎症细胞浸润无关。
   总之，这些研究结果表明Olodaterol和噻托溴铵联用能高效抑制过敏原引起的哮喘反应和AHR。
 

（苏楠 审校）
J Pharmacol Exp Ther. 2013 Dec 4. [Epub ahead of print]

Bronchoprotection by olodaterol is synergistically enhanced by tiotropium in a guinea pig model of allergic asthma.

Smit M, Zuidhof AB, Bos SI, Maarsingh H, Gosens R, Zaagsma J, Meurs H.

ABSTRACT
The novel once-daily β2-agonist bronchodilator drug olodaterol has recently been shown to be effective in patients with allergic asthma for over 24 h. An increased cholinergic tone common to these patients may decrease the effectiveness of β2-agonists. This could provide a rationale for combination therapy with olodaterol and the long acting anticholinergic tiotropium, to aim for a once-daily treatment regime. In guinea pigs, we evaluated the protective effects of olodaterol, alone and in combination with tiotropium, on airway responsiveness to histamine, which is partially mediated by a cholinergic reflex mechanism. In addition, using a guinea pig model of acute allegic asthma, we examined the cooperative effects of these bronchodilators on allergen-induced early (EAR) and late (LAR) asthmatic reactions, airway hyperresponsiveness (AHR) to histamine and airway inflammation. It was demonstrated that the protective effect of olodaterol against histamine-induced bronchoconstriction was synergistically enhanced and prolonged in the presence of tiotropium. In addition, tiotropium synergistically augmented both the reversal of and the protection against the allergen-induced AHR after the EAR by olodaterol. Olodaterol and tiotropium were highly effective in inhibiting the magnitude of the allergen-induced EAR and LAR and both reactions were fully inhibited by the combination of these drugs. Remarkably, these effects were not associated with an effect on inflammatory cell infiltration in the airways. In conclusion, the results indicate that combination therapy with olodaterol and tiotropium may be highly effective in the treatment of allergen-induced asthmatic reactions and AHR.

J Pharmacol Exp Ther. 2013 Dec 4. [Epub ahead of prin