Salbutamol tolerance to bronchoprotection: course of onset

Abstract

BackgroundRegular use of inhaled β-agonist leads to tolerance to its bronchoprotective effect. This occurs within 12 hours with salmeterol and has been documented at 1 week for salbutamol. The course of onset after introduction of salbutamol has not been investigated. ObjectiveTo determine the course of onset of tolerance to the bronchoprotective effect of salbutamol against methacholine. MethodsThirteen individuals with mild asthma completed a randomized, double-blind, placebo-controlled, cross-over study. Each treatment period consisted of 7 twice-daily doses (2 puffs of 100 μg of salbutamol or placebo). Methacholine challenges were conducted 24 hours apart on 4 consecutive days, 10 minutes after the first, third, fifth, and seventh doses. The 2 treatment periods were separated by at least 14 days. ResultsMethacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) values during the 4 days of placebo treatment did not significantly differ (analysis of variance P = .79). A single dose of salbutamol shifted the methacholine PC20 approximately 5-fold from a geometric mean of 2.1 mg/mL to a geometric mean of 10.7 mg/mL. Maximal bronchoprotection after the active treatment occurred on day 2 after the third dose, which was significantly higher than on day 1 after the first dose (P = .04). After the fifth dose the methacholine PC20 was trending downward, and on day 4 the bronchoprotective effect of salbutamol had significantly decreased from its peak protection (P = .001). ConclusionThe detrimental effects on bronchoprotection after regular use of salbutamol manifest after 5 doses and are significantly reduced from peak protection after 7 doses. Trial Registrationclinicaltrials.gov Identifier: NCT01338311