Exploring the sites and kinetics of bronchodilator response to β-2 agonists in asthma

We previously documented, in patients with asthma, three different profiles of bronchodilation induced by short-acting β-2 mimetics (SABA), characterized by dilation up to central, preacinar, and intra-acinar airways assessed by ventilation distribution tests and associated with no change, increase, and decrease of fractional exhaled nitric oxide concentration (FENO), respectively. To investigate the dynamics of these profiles over the entire SABA action period, assuming that bronchodilation of proximal and peripheral airways could exhibit varying kinetics due to differences in the distribution of β-2 receptors in both the central and peripheral human airways. FENO, forced expired volume in one second (FEV₁), and the slope (S) of He and SF₆ phase III (single-breath test) were measured in asthma patients before, and up to 6 h after SABA inhalation (salbutamol 400 µg). S_He and S_SF6 decrease reflects pre- and intra-acinar obstruction relief, respectively. Thirty patients with asthma (12F/18M, aged 45 ± 18 yr) 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 4 h, 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 whereas the FENO increase and the S_He decrease lasted for up to 4 h. This study documents various profiles of SABA-induced bronchodilation in patients with asthma, 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.NEW & NOTEWORTHY FEV₁ increase usually observed after the inhalation of short-acting β2-agonists in asthma patients tends to involve peripheral airways. This study shows that the heterogeneity of responses to short-acting β2-agonists in asthma not only involves distinct sites of bronchodilation, but also distinct sequences between these sites. This indicates that a detailed understanding of the bronchodilator effect of β2-agonists in asthma should not be limited to studying its early impact on FEV₁.