Effect on Airway Responsiveness to Methacholine and Adenosine 5*-Monophosphate and Tolerance to Bronchoprotection

Objective: Regular treatment with inhaled b2-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 b2-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 mg, and placebo inhalers, two puffs qid, each for 10 days. Measurements: 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 mg (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 5 0.86) or AMP PC20 (22 mg/mL vs 17.4 mg/mL, p 5 0.21; n 5 14). The acute bronchoprotective effect of salbutamol was greater vs AMP than vs methacholine (5.1 doubling concentrations vs 3.5 doubling concentrations, p 5 0.06) and loss of protective effect of salbutamol (mean 6 SD) was greater vs AMP than vs methacholine (2.4 6 0.33 doubling concentration loss vs 0.8 6 0.21 doubling concentration loss, p 5 0.008; n 5 8). Conclusion: Regular salbutamol (mean 6 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. (CHEST 2001; 119:370‐375)