Background: Exposure in a swine house induces airway inflammation and increases bronchial responsiveness to methacholine in healthy subjects.
Study objectives: The aim was to investigate whether a long-acting β2-agonist, salmeterol, alters the increased bronchial responsiveness induced in healthy subjects following exposure to organic dust in a swine barn.
Design and subjects: The study includes three separate parts. In the first part (part 1), healthy subjects inhaled salmeterol (50 μg bid, n = 8) or placebo (n = 8) over 2 weeks. In part 2, healthy subjects inhaled one single dose of salmeterol (100 μg, n = 6) or placebo (n = 6) 1 h prior to exposure in a swine barn, which was followed by a bronchial methacholine challenge. In part 3, eight healthy individuals inhaled placebo or salmeterol (100 μg), 2 h or 8 h prior to a bronchial methacholine provocation, without being exposed in the swine barn.
Results: Exposure caused an increase of bronchial responsiveness to methacholine by 3.2 doubling concentration steps (25 to 75th percentiles, 2.8 to 4.1) and 2.6 doubling concentration steps (25 to 75th percentiles, 1.4 to 3.7) in the placebo and salmeterol groups (2 weeks), respectively, with no significant differences between the groups (p = 0.3; part 1). Similar results were obtained when salmeterol was administered as a single dose (part 2) prior to exposure. However, salmeterol significantly attenuated the bronchial responsiveness to methacholine by 1.2 doubling concentration steps (0.8 to 1.7) 8 h after inhalation (part 3).
Conclusions: Salmeterol inhalation did not protect against the increased bronchial responsiveness induced in healthy subjects following exposure to organic dust when administered for 2 weeks or as a single dose prior to exposure. This lack of protection cannot be explained by homologous β2-adrenoceptor desensitization. We hypothesize that exposure to organic material may alter the airway response to β2-agonists.