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

• Published in: Journal of applied physiology (1985) Vol. 130; no. 4; pp. 1106 - 1113
• Main Authors: Demey, Lucas, Van Muylem, Alain, Malinovschi, Andrei, Haccuria, Amaryllis, Perez-Bogerd, Silvia, Michils, Alain
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01-04-2021
• Subjects: Adult; Agonists; Albuterol - therapeutic use; Asthma; Asthma - drug therapy; Bronchodilation; Bronchodilator Agents - pharmacology; Bronchodilators; Exhalation; Female; Forced Expiratory Volume; Humans; Inhalation; Kinetics; Male; Middle Aged; Nitric oxide; Nitric Oxide - pharmacology; Respiration; Salbutamol; asthma; ventilation distribution; fractional exhaled nitric oxide; bronchodilation
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00643.2020

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 (FEV
), and the slope (
) of He and SF
phase III (single-breath test) were measured in asthma patients before, and up to 6 h after SABA inhalation (salbutamol 400 µg).
and
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+,
= 9), negative (NO-,
= 11), and no (NO=,
= 10) FENO acute change. In the NO- group, FEV
increased for up to 4 h, whereas FENO,
, and
decreased in the early phase only. In stark contrast, in the NO+ group, FEV
increased in the early phase only whereas the FENO increase and the
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 FEV
.
FEV
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 FEV
.