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


OBJECTIVE
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.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Strandberg
K
K
Lung and Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. karin.strandberg@ki.se
Ek
A
A
Palmberg
L
L
Larsson
K
K
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000382:Agricultural Workers' Diseases / Q000188:drug therapy; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001985:Bronchial Provocation Tests / Q000379:methods; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004347:Drug Interactions; D004391:Dust; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D012189:Retrospective Studies; D000068299:Salmeterol Xinafoate; D013552:Swine; D014797:Vital Capacity / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001993:Bronchodilator Agents; D004391:Dust; D016210:Methacholine Chloride; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D007052:Ibuprofen