Background: Regular 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.
Objective: To determine the course of onset of tolerance to the bronchoprotective effect of salbutamol against methacholine.
Methods: Thirteen 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.
Results: Methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC(20)) 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 PC(20) 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 PC(20) was trending downward, and on day 4 the bronchoprotective effect of salbutamol had significantly decreased from its peak protection (P = .001).
Conclusion: The detrimental effects on bronchoprotection after regular use of salbutamol manifest after 5 doses and are significantly reduced from peak protection after 7 doses.
Trial Registration: clinicaltrials.gov Identifier: NCT01338311.
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