Effect of anti-asthmatic drugs on the response to inhaled endotoxin.
BACKGROUND
Endotoxin is a pro-inflammatory agent contaminating the dust that has been associated with the risk to develop pulmonary diseases. There is no data on the protective efficacy of anti-asthmatic drugs on the response induced by inhaled endotoxin in human.


METHODS
Twelve mildly asthmatic subjects were submitted weekly to bronchial challenge tests with 20 microg endotoxin. The response was evaluated by the changes in FEV1, blood cells count, neutrophils activation (measured with the luminol-enhanced chemiluminescence) and blood concentration in the acute phase proteins, C-reactive protein (CRP) and haptoglobin. In a double-blind randomized cross-over placebo-controlled design, a single dose each of 500 microg beclomethasone dipropionate, 200 microg salbutamol, and 50 microg salmeterol were administered 30 minutes before the endotoxin challenge test.


RESULTS
The 20-microg endotoxin challenge test induced a significant decrease in FEV1 and luminol-enhanced chemiluminescence (P < .001 and <.05, respectively). There was an increase in the blood neutrophils count (P < .05), in CRP (P < .02) and in haptoglobin (P < .03) concentrations. Pretreatment with beclomethasone dipropionate did not have any significant effect on the response to inhaled endotoxin. Salbutamol and salmeterol completely prevent the FEV1 decline due to their potent bronchodilatation activity. Salmeterol and salbutamol did not have any significant effect on the blood inflammation induced by endotoxin inhalation.


CONCLUSIONS
The bronchodilating properties of beta2-agonists prevent the lung function response to inhaled endotoxin. When given in a single dose, an inhaled corticosteroid does not have protective activity on the endotoxin-induced blood inflammation.
Michel
O
O
Clinic of Allergology and Respiratory Diseases, Saint-Pierre University Hospital, Brussels, Belgium. omichel@ulb.ac.be
Olbrecht
J
J
Moulard
D
D
Sergysels
R
R
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004731:Endotoxins / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000276:immunology*; D008297:Male; D000068299:Salmeterol Xinafoate
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D004731:Endotoxins; D000068299:Salmeterol Xinafoate; D000420:Albuterol