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(Chest. 2001;119:370-375.)
© 2001 American College of Chest Physicians

Regular Inhaled Salbutamol*

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

Ruzica Jokic, MD; Veronica A. Swystun, BSc; Beth E. Davis, BSc and Donald W. Cockcroft, MD, FCCP

* From the Division of Respiratory Medicine, Department of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada.

Correspondence to: Donald W. Cockcroft, MD, FCCP, Royal University Hospital, Division of Respiratory Medicine, 103 Hospital Dr, Ellis Hall, Saskatoon, SK S7N 0W8 Canada; e-mail: cockcroft{at}sask.usask.ca

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 µg, 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 µg (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.

Key Words: adenosine 5'-monophosphate • airway hyperresponsiveness • asthma • {beta}2-agonists • bronchoprotection • methacholine • tolerance




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