Objective: Regular treatment with inhaledβ
2-agonists increases airway responsiveness consistently
to indirect bronchoconstrictors (allergen, exercise, hypertonic saline
solution, etc) and inconsistently to direct bronchoconstrictors
(histamine, methacholine). Studies demonstrating tolerance toβ
2-agonist bronchoprotection against the indirect
bronchoconstrictor adenosine 5′-monophosphate (AMP) have not examined
changes in baseline AMP responsiveness. This study assessed the effect
of regular salbutamol on AMP and methacholine responsiveness and on
tolerance to bronchoprotection.
randomized, crossover study.
hospital bronchoprovocation laboratory.
Fourteen atopic asthmatic subjects with FEV1 > 65%
predicted, and methacholine provocative concentration causing a 20%
fall in FEV1 (PC20) < 8 mg/mL.
Interventions: Salbutamol, 100 μg, and placebo inhalers,
two puffs qid, each for 10 days.
Methacholine PC20 and AMP PC20 measured 12
h after blinded inhaler after each treatment period. Methacholine
PC20 and AMP PC20 repeated 10 min after
salbutamol, 200 μg (eight subjects).
There was no difference between placebo and salbutamol treatment
in geometric mean methacholine PC20 (0.85 mg/mL vs 0.82
mg/mL, p = 0.86) or AMP PC20 (22 mg/mL vs 17.4 mg/mL,
p = 0.21; n = 14). The acute bronchoprotective effect of salbutamol
was greater vs AMP than vs methacholine (5.1 doubling concentrations vs
3.5 doubling concentrations, p = 0.06) and loss of protective effect
of salbutamol (mean ± SD) was greater vs AMP than vs methacholine
(2.4 ± 0.33 doubling concentration loss vs 0.8 ± 0.21 doubling
concentration loss, p = 0.008; n = 8).
Regular salbutamol (mean ± SD) treatment did not enhance airway
responsiveness to either the indirect bronchoconstrictor AMP or the
direct bronchoconstrictor methacholine. Compared to its effect on
methacholine, salbutamol had a greater acute protective effect vs AMP
and produced greater loss of protection vs AMP when used