Regular inhaled salbutamol -: Effect on airway responsiveness to methacholine and adenosine 5′-monophosphate and tolerance to bronchoprotection

Objective: Regular treatment with inhaled beta (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 to beta (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. Design: Double-blind, randomized, crossover study. Setting: University hospital bronchoprovocation laboratory. Patients: 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 <mu>g, and placebo inhalers, mo puffs qid, each for 10 days. Measurements: Methacholine PC20 and AMP PC20 measured 12 h after blinded inhaler after each (eight subjects). Results: 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), Conclusion: 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 regularly.