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(Chest. 2005;128:3038-3047.)
© 2005 American College of Chest Physicians

Salmeterol Does Not Alter Increased Bronchial Responsiveness Caused by Organic Dust Exposure*

Alexandra Ek, PhD; Lena Palmberg, MD, PhD; Britt-Marie Sundblad, PhD and Kjell Larsson, MD, PhD

* From Lung and Allergy Research (Drs. Palmberg, Sundblad, and Larsson), Division of Physiology, Institute of Environmental Medicine, Karolinska Institutet; and National Institute for Working Life (Dr. Ek), Stockholm, Sweden.

Correspondence to: Lena Palmberg, MD, PhD, Lung and Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, PO Box 287, SE-171 77 Stockholm, Sweden; e-mail: Lena.Palmberg{at}imm.ki.se

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 ß2-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 ß2-adrenoceptor desensitization. We hypothesize that exposure to organic material may alter the airway response to ß2-agonists.

Key Words: airway inflammation • ß2-agonist • bronchial responsiveness • methacholine • organic dust • salmeterol






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