Background We previously documented, in asthma patients, three different profiles of bronchodilation induced by short acting β-2 mimetics (SABA), characterized by dilation up to central, pre-acinar and intra-acinar airways assessed by ventilation distribution tests and associated with no change, increase and decrease of fractional exhaled nitric oxide (FENO) respectively. Aim To investigate the dynamics of these profiles over the entire SABA action period, assuming that airways bronchodilation could exhibit varying kinetics due to differences in the distribution of β-2 receptors in both the central and peripheral human airways. Methods FENO, FEV₁, and the slope (S) of He and SF₆ phase III (single-breath test) were measured in asthma patients before, and up to six hours after SABA inhalation (salbutamol 400µg). S_He and S_SF6 decrease reflects pre- and intra-acinar obstruction relief respectively. Results 30 asthma patients (12F/18M, age: 45±18 years) were divided into groups with positive (NO+, n=9), negative (NO-, n=11) and no (NO=, n=10) FENO acute change. In the NO- group, FEV₁ increased for up to four hours, whereas FENO, S_He and S_F6 decreased in the early phase only. In stark contrast, in the NO+ group, FEV₁ increased in the early phase only while the FENO increase and the S_He decrease lasted for up to four hours. Conclusion This study documents various profiles of SABA-induced bronchodilation in asthma patients, differing both by sites and dynamics of the bronchodilator process. So, detailed understanding of the bronchodilator effect of β2-agonists in asthma should not solely be limited to studying their impact on FEV₁.

中文翻译：

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探索支气管扩张剂对 β-2 激动剂在哮喘中的反应位点和动力学

背景 我们之前在哮喘患者中记录了由短效 β-2 模拟物 (SABA) 诱导的三种不同的支气管扩张特征，其特征是扩张至中央、腺泡前和腺泡内气道，通过通气分布测试评估并与无呼出气一氧化氮分数（FENO）的变化、增加和减少。目的 研究这些曲线在整个 SABA 作用期间的动力学，假设气道支气管扩张可能由于人类中枢和外周气道中 β-2 受体分布的差异而表现出不同的动力学。方法 FENO、FEV ₁以及 He 和 SF _{6的斜率 (S)}在哮喘患者吸入 SABA（沙丁胺醇 400 µg）之前和之后长达 6 小时测量 III 期（单次呼吸试验）。S _He和 S _SF6降低分别反映了腺泡前和腺泡内阻塞的缓解。结果 30例哮喘患者（12F/18M，年龄：45±18岁）分为阳性（NO+，n=9）、阴性（NO-，n=11）和无（NO=，n=10）FENO组剧烈变化。在 NO 组中，FEV ₁增加长达 4 小时，而 FENO、S _He和 S _F6仅在早期下降。与此形成鲜明对比的是，在 NO+ 组中，FEV ₁仅在早期增加，而 FENO 增加，S _He下降持续长达四个小时。结论 本研究记录了哮喘患者中 SABA 诱导的支气管扩张的各种特征，这些特征因支气管扩张过程的部位和动力学而异。因此，详细了解 β2 激动剂在哮喘中的支气管扩张作用不应仅仅局限于研究它们对 FEV ₁的影响。