A standard, single dose of inhaled terbutaline attenuates hyperpnea-induced bronchoconstriction and mast cell activation in athletes

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.

Keywords: eucapnic voluntary hyperpnea; exercise-induced bronchoconstriction; inhaled β2-agonist; prostaglandin D2.

Fig. 1.

Maximum fall in forced expiratory volume in 1 s (FEV₁) following 8 min of hyperpnea of dry air in athletes with exercise-induced bronchoconstriction pretreated with 0.5 mg terbutaline (closed symbols) or placebo (open symbols). Individual data are shown; box plots represent group median and interquartile range, with whiskers representing the 5th and 95th percentiles. Values under the broken line (10% fall in FEV₁) represent complete bronchoprotection (n = 22, 81%).

Fig. 2.

Median ± interquartile range (Q1–Q3) urinary concentration of 11β-prostaglandin F_2α (11β-PGF_2α) at baseline and 30 and 60 min post-eucapnic voluntary hyperpnea of dry air following pretreatment with 0.5 mg terbutaline (closed circles) or placebo (open circles) in 18 athletes with exercise-induced bronchoconstriction.

Fig. 3.

Urinary concentrations of 11β-PGF_2α at baseline and after eucapnic voluntary hyperpnea (EVH) of dry air (peak value) following pretreatment with 0.5 mg terbutaline (closed circles) or placebo (open circles) in 24 athletes with exercise-induced bronchoconstriction. Individual data are shown; box plots represent group median and interquartile range, with whiskers representing the 5th and 95th percentiles.