title: Effect of terbutaline on hyperpnoea-induced bronchoconstriction and urinary club cell protein 16 in athletes.
abstract: Repeated injury of the airway epithelium caused by hyperpnoea of poorly conditioned air has been proposed as a key factor in the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. In animals, the short-acting β2-agonist terbutaline has been shown to reduce dry airflow-induced bronchoconstriction and the associated shedding of airway epithelial cells. Our aim was to test the efficacy of inhaled terbutaline in attenuating hyperpnoea-induced bronchoconstriction and airway epithelial injury in athletes. Twenty-seven athletes with EIB participated in a randomized, double-blind, placebo-controlled, crossover study. Athletes completed an 8-min eucapnic voluntary hyperpnoea (EVH) test with dry air on two separate days 15 min after inhaling 0.5 mg terbutaline or a matching placebo. Forced expiratory volume in 1 s (FEV1) and urinary concentration of the club cell (Clara cell) protein 16 (CC16, a marker of airway epithelial perturbation) were measured before and up to 60 min after EVH. The maximum fall in FEV1 of 17 ± 8% (SD) on placebo was reduced to 8 ± 5% following terbutaline (P < 0.001). Terbutaline gave bronchoprotection (i.e., post-EVH FEV1 fall <10%) to 22 (81%) athletes. EVH caused an increase in urinary excretion of CC16 in both conditions (P < 0.001), and terbutaline significantly reduced this rise (pre- to postchallenge CC16 increase 416 ± 495 pg/μmol creatinine after placebo vs. 315 ± 523 pg/μmol creatinine after terbutaline, P = 0.016). These results suggest that the inhalation of a single therapeutic dose of terbutaline offers significant protection against hyperpnoea-induced bronchoconstriction and attenuates acute airway epithelial perturbation in athletes.
authors.affiliation: Centre for Sports Medicine and Human Performance, Brunel University, Uxbridge, United Kingdom;
authors.forename: A J
authors.initials: AJ
authors.lastname: Simpson
authors.forename: E
authors.initials: E
authors.lastname: Tufvesson
authors.forename: S D
authors.initials: SD
authors.lastname: Anderson
authors.forename: L M
authors.initials: LM
authors.lastname: Romer
authors.forename: L
authors.initials: L
authors.lastname: Bjermer
authors.forename: P
authors.initials: P
authors.lastname: Kippelen
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001250:Asthma, Exercise-Induced / Q000503:physiopathology / Q000517:prevention & control* / Q000652:urine; D056352:Athletes; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004739:England; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006985:Hyperventilation / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D012123:Pulmonary Ventilation; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D013726:Terbutaline / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014598:Uteroglobin / Q000652:urine*; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; C556389:SCGB1A1 protein, human; D014598:Uteroglobin; D013726:Terbutaline
keywords: Clara cell; epithelial injury; exercise-induced bronchoconstriction; inhaled β2-agonist