Fluticasone and ibuprofen do not add to the effect of salmeterol on organic dust-induced airway inflammation and bronchial hyper-responsiveness.

Author(s): Strandberg K, Ek A, Palmberg L, Larsson K

Affiliation(s): Lung and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. karin.strandberg@ki.se

Publication date & source: 2008-07, J Intern Med., 264(1):83-94. Epub 2008 Feb 21.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Exposure in a pig house causes airway inflammation and bronchial hyper-responsiveness which are not influenced by anti-asthma drugs, including a beta(2)-agonist (salmeterol). OBJECTIVES: We hypothesized that a glucocorticoid or a cyclo-oxygenase-inhibitor synergistically interacts with salmeterol offering a protection against dust-induced increased bronchial responsiveness and airway inflammation. As data did not confirm previous results a retrospective analysis of pooled data on dust-induced bronchial hyper-responsiveness from four other studies was performed. DESIGN: Fluticasone or ibuprofen was administered for 1 week and salmeterol or placebo was inhaled 1 h prior to a 3-h exposure in a pig barn in a double-blind, placebo-controlled, cross-over design (2-3 weeks apart) in 12 healthy subjects. Lung function, bronchial responsiveness to methacholine and inflammatory markers were evaluated before and after exposure. Pre- and postexposure bronchial responsiveness in nontreated subjects was retrospectively evaluated from four previous studies. SUBJECTS: Twelve healthy, nonatopic nonsmokers. RESULTS: Salmeterol partially protected against bronchial hyper-responsiveness but did not influence inflammatory markers. Fluticasone and ibuprofen did not add to these effects. The retrospective analysis showed that PD(20)FEV(1) after exposure in a pig barn is almost totally independent of pre-exposure PD(20)FEV(1)-level; all subjects end up at the same low postexposure PD(20)FEV(1). CONCLUSION: Contradictory to our previous results, salmeterol offered partial protection against enhanced bronchial responsiveness induced by exposure in a pig barn. This effect was not modified by fluticasone or ibuprofen. Our data clearly demonstrate that interventions altering bronchial responsiveness must be compared between groups with similar prechallenge bronchial responsiveness or in a cross-over design.