Abstract
Release of bronchoactive mediators from mast cells during exercise hyperpnea is a key factor in the pathophysiology of exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effect of a standard, single dose of an inhaled β2-adrenoceptor agonist on mast cell activation in response to dry air hyperpnea in athletes with EIB. Twenty-seven athletes with EIB completed a randomized, double-blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was inhaled 15 min prior to 8 min of eucapnic voluntary hyperpnea (EVH) with dry air. Pre- and postbronchial challenge, urine samples were analyzed by enzyme immunoassay for 11β-prostaglandin F2α (11β-PGF2α). The maximum fall in forced expiratory volume in 1 s of 14 (12-20)% (median and interquartile range) following placebo was attenuated to 7 (5-9)% with the administration of terbutaline (P < 0.001). EVH caused a significant increase in 11β-PGF2α from 41 (27-57) ng/mmol creatinine at baseline to 58 (43-72) ng/mmol creatinine at its peak post-EVH following placebo (P = 0.002). The rise in 11β-PGF2α was inhibited with administration of terbutaline: 39 (28-44) ng/mmol creatinine at baseline vs. 40 (33-58) ng/mmol creatinine at its peak post-EVH (P = 0.118). These data provide novel in vivo evidence of mast cell stabilization following inhalation of a standard dose of terbutaline prior to bronchial provocation with EVH in athletes with EIB.
Highlights
This study provides the first in vivo evidence for a mast cell stabilizing effect of the short-acting inhaled 2-adrenoceptor agonist terbutaline, when administered prophylactically at a clinically recommended dose (0.5 mg) before bronchial provocation with dry air
Evidence of mast cell activation associated with exercise and hyperpnea of dry air is well established by the finding of an increase in urinary excretion of 11-prostaglandin F2␣ (11-PGF2␣), i.e., a main metabolite of prostaglandin (PG) D2, which is produced almost exclusively from mast cells [31, 34, 35, 37, 38, 46]
EXERCISE-INDUCED BRONCHOCONSTRICTION (EIB) was determined by a fall of Ն10% in forced expiratory volume in 1 s (FEV1) following an 8-min eucapnic voluntary hyperpnea (EVH) challenge during a screening visit
Summary
This study provides the first in vivo evidence for a mast cell stabilizing effect of the short-acting inhaled 2-adrenoceptor agonist terbutaline, when administered prophylactically at a clinically recommended dose (0.5 mg) before bronchial provocation with dry air. In 1975 and 1976, Anderson and colleagues [4, 5] reported that 2-adrenoceptor agonists given by inhalation in low doses were superior to tablets (given in much higher doses) in preventing EIB, even though both formulations induced bronchodilatation Those authors proposed that the aerosol had an additional site of action to the smooth muscle and prevented EIB by delivering a concentration of drug sufficient to stabilize mast cells in the airways and inhibit the release of “bronchoconstrictor substances.”. Standard dose of shortacting 2-adrenoceptor agonist—the mainstay treatment for EIB prevention— has a similar stabilizing effect on mast cells during EIB remains to be established
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