Salmeterol does not alter increased bronchial responsiveness caused by organic dust exposure.
BACKGROUND
Exposure in a swine house induces airway inflammation and increases bronchial responsiveness to methacholine in healthy subjects.


OBJECTIVE
The aim was to investigate whether a long-acting beta2-agonist, salmeterol, alters the increased bronchial responsiveness induced in healthy subjects following exposure to organic dust in a swine barn.


METHODS
The study includes three separate parts. In the first part (part 1), healthy subjects inhaled salmeterol (50 microg bid, n = 8) or placebo (n = 8) over 2 weeks. In part 2, healthy subjects inhaled one single dose of salmeterol (100 microg, 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 microg), 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 beta2-adrenoceptor desensitization. We hypothesize that exposure to organic material may alter the airway response to beta2-agonists.
Ek
Alexandra
A
Lung and Allergy Research, Division of Pathology, Institute of Environmental Medicine, Karolinska Institutet, PO Box 287, SE-171 77 Stockholm, Sweden.
Palmberg
Lena
L
Sundblad
Britt-Marie
BM
Larsson
Kjell
K
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004391:Dust; D004781:Environmental Exposure; D005541:Forced Expiratory Volume / Q000187:drug effects; D006799:Housing, Animal; D006801:Humans; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D010919:Placebos; D000068299:Salmeterol Xinafoate; D013552:Swine; D014797:Vital Capacity / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D016085:Bronchoconstrictor Agents; D004391:Dust; D010919:Placebos; D016210:Methacholine Chloride; D000068299:Salmeterol Xinafoate; D000420:Albuterol