REGULAR INHALED SALBUTAMOL AND AIRWAY RESPONSIVENESS TO ALLERGEN

Regular inhaled beta2 agonist causes tolerance to the acute protective effect of beta2 agonist against bronchoconstriction induced by chemic al stimuli such as AMP, histamine, and methacholine. We examined a mor e clinically relevant stimulus, inhaled allergen, in a double-blind, c ross-over, random-order trial in 13 mild atopic asthmatics, who had no t used beta1 agonist for at least 4 weeks. We compared regular inhaled salbutamol (200 mug four times daily for 2 weeks) with placebo (2 wee ks) for effects on bronchodilator response, baseline methacholine, and allergen airway responsiveness, and on the acute protective effect of salbutamol against both stimuli. Baseline forced expiratory volume in 1 s (FEV1), bronchodilator response, and methacholine responsiveness were the same during both treatment periods. After regular salbutamol, the allergen PC20 (provocation concentration producing a 20% FEV1 dec rease) fell by 0.91 (SD 0.66) (p = 0.0009) doubling doses, and the pro tective effects of salbutamol on methacholine and allergen were both s ignificantly reduced (p = 0.026 and 0.025, respectively). Taking into account the reduced baseline allergen PC20, the post-salbutamol allerg en PC20 was almost 2 doubling doses (1.94 [1.43], p < 0.01) lower duri ng salbutamol treatment. Thus, 2 weeks of regular inhaled salbutamol i ncreased airway responsiveness to allergen but not to methacholine, an d caused tolerance to the protective effect of salbutamol on bronchoco nstriction induced by both stimuli. These effects of inhaled beta2 ago nist provide further evidence to support detrimental effects of their regular use.