INTERACTION OF INHALED BETA(2) AGONIST AND INHALED CORTICOSTEROID ON AIRWAY RESPONSIVENESS TO ALLERGEN AND METHACHOLINE

Regular treatment with salbutamol increases airway responsiveness to allergen but not to methacholine and produces tolerance to the bronchoprotective effect of salbutamol. The current study addresses the effect of inhaled corticosteroid on these aspects of regular beta(2) agonist use. A group of 13 atopic asthmatic subjects free from all asthma medications and remote from allergen exposure were studied. We used a double-blind, random-order, crossover study to compare four 1-wk treatment periods with greater than or equal to 1 wk washout: placebo, salbutamol, 200 mu g four times per day, budesonide, 400 mu g four times per day, and the combination of salbutamol and budesonide. We measured the methacholine PC20 and the methacholine dose shift produced acutely by 200 mu g salbutamol after 7 d and the allergen PC15 after 8 d treatment. Blinded medications were withheld for 8 to 10 h before measurements. The methacholine PC20 was not affected by regular salbutamol but increased significantly (p < 0.014) after both budesonide-containing regimens. Neither the dose shift nor its significant reduction by regularly used beta(2) agonist were influenced by the inhaled corticosteroid. The four allergen PC15 values were significantly different from each other. Compared with placebo, the allergen PC15 was 0.6 doubling doses lower after salbutamol (p = 0.021) and 1.3 doubling doses higher after budesonide (p < 0.001); the allergen PC15 was reduced by 0.53 doubling doses from this new baseline (p = 0.039) when salbutamol and budesonide were used together. In conclusion, the inhaled corticosteroid, budesonide, caused a slight improvement in methacholine PC20 and a larger improvement in allergen PC15 but did not prevent the tolerance to the bronchoprotective effect of salbutamol, nor did it protect against the increased airway responsiveness to allergen seen after regular salbutamol use.