Metaproterenol Responsiveness After Methacholine- and Histamine-Induced Bronchoconstriction

¹ From the Department of Medicine, University of Basel, Switzerland
² From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Miami School of Medicine at Mount Sinai Medical Center, Miami Beach, Fla.

We investigated whether the bronchodilator response to a β-adrenergic agonist is influenced by the mechanism of induced bronchoconstriction. Normal subjects and asymptomatic asthmatics inhaled a dry aerosol (mass median aerodynamic diameter, 1.5 µm) with increasing concentrations of methacholine or histamine to produce a 35% decrease in specific airway conductance (SGaw), followed by a single inhalation of a metaproterenol aerosol. By studying normal subjects and asthmatics, we were able to compare metaproterenol responsiveness after widely divergent doses of the bronchoprovocative agents but the same degree of bronchoconstriction. Airway deposition of methacholine, histamine, and metaproterenol was measured using a quinine fluorescence technique. Mean baseline SGaw, metaproterenol responsiveness, and metaproterenol mass deposited were similar in normal subjects and asthmatics. Likewise, mean SGaw after completion of methacholine and histamine challenge, and the subsequently deposited metaproterenol mass were similar in the two groups. After methacholine challenge (mean±SD provocative drug mass causing a 35% decrease in SGaw, PM₃₅: 8.94±5.96 µmol in normal subjects and 0.30±0.29 µmol in asthmatics), metaproterenol increased mean SGaw by 89±33% in normal subjects and by 190±55% in asthmatics (p<0.05, two-way analysis of variance). After histamine challenge (PM₃₅, 2.92±2.49 µmol in normal subjects and 0.17±0.29 µmol in asthmatics), metaproterenol increased mean SGaw by 111±38% in normal subjects and 113±69% in asthmatics (p=not significant). Thus, for the same degree of bronchoconstriction, metaproterenol responsiveness was influenced by the dose of methacholine but not the dose of histamine. The differential metaproterenol response could be related to a functional antagonism between muscarinic and β-adrenergic agonists.

Key Words: airway hyperresponsiveness • functional antagonism • histamine • methacholine • sympathomimetic agents

Submitted on November 6, 1995
Accepted on April 18, 1996

This article has been cited by other articles:

				E. DEROM, L. BORGSTROM, J. VAN SCHOOR, A.-B. LOFROOS, and R. PAUWELS Lung Deposition and Protective Effect of Terbutaline Delivered from Pressurized Metered-Dose Inhalers and the Turbuhaler in Asthmatic Individuals Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1398 - 1402. [Abstract] [Full Text] [PDF]