Lexmond Anne J, van der Wiel Erica, Hagedoorn Paul, Bult Wouter, Frijlink Henderik W, ten Hacken Nick H T, de Boer Anne H
University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Department of Pulmonary Medicine and Tuberculosis, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Eur J Pharm Biopharm. 2014 Sep;88(1):148-52. doi: 10.1016/j.ejpb.2014.04.008. Epub 2014 Apr 26.
Adenosine is an indirect stimulus to assess bronchial hyperresponsiveness (BHR(2)) in asthma. Bronchial challenge tests are usually performed with nebulised solutions of adenosine 5'-monophosphate (AMP(3)). The nebulised AMP test has several disadvantages, like long administration times and a restrictive maximum concentration that does not result in BHR in all patients. In this study, we investigated the applicability of dry powder adenosine for assessment of BHR in comparison to nebulised AMP. Dry powder adenosine was prepared in doubling doses (0.01-80 mg) derived from the nebulised AMP test with addition of two higher doses. Five asthmatic subjects performed two bronchial challenge tests, one with nebulised AMP following the 2-min tidal breathing method; the second with dry powder adenosine administered with an investigational inhaler and single slow inhalations (inspiratory flow rate 30-40 L/min). All subjects reached a 20% fall in FEV₁(4) with the new adenosine test (PD20(5)) compared to four subjects with the AMP test (PC₂₀(6)). Dry powder adenosine was well tolerated by all subjects and better appreciated than nebulised AMP. In conclusion, this new bronchial challenge test appears to be a safe and convenient alternative to the nebulised AMP test to assess BHR in asthmatic subjects.
腺苷是评估哮喘患者支气管高反应性（BHR(2)）的一种间接刺激物。支气管激发试验通常使用雾化的5'-单磷酸腺苷（AMP(3)）溶液进行。雾化AMP试验有几个缺点，比如给药时间长，且存在一个限制性的最大浓度，并非所有患者都会出现BHR。在本研究中，我们比较了干粉状腺苷与雾化AMP在评估BHR方面的适用性。干粉状腺苷的剂量以雾化AMP试验的剂量翻倍制备（0.01 - 80毫克），并额外增加了两个更高的剂量。五名哮喘患者进行了两次支气管激发试验，一次采用2分钟潮气呼吸法雾化吸入AMP；另一次使用研究性吸入器单次缓慢吸入（吸气流量30 - 40升/分钟）干粉状腺苷。与四名患者在AMP试验中达到FEV₁(4)下降20%（PC₂₀(6)）相比，所有患者在新的腺苷试验（PD20(5)）中均达到了FEV₁下降20%。所有患者对干粉状腺苷耐受性良好，且比雾化AMP更易接受。总之，这种新的支气管激发试验似乎是评估哮喘患者BHR的一种安全、便捷的替代雾化AMP试验的方法。
