A proposal to account for the stimulus, the mechanism, and the mediators released in exercise-induced bronchoconstriction

Exercise induced bronchoconstriction (EIB) describes the transient narrowing of the airways that follows vigorous exercise. It commonly occurs in children and adults who have asthma and in elite athletes. The primary stimulus is proposed to be loss of water, by evaporation, from the airway surface due to conditioning inspired air. The mechanism, whereby this evaporative loss of water provokes contraction of the bronchial smooth muscle, is thought to be an increase in osmolarity of the airway surface liquid. The increase in osmolarity causes mast cells to release histamines, prostaglandins, and leukotrienes. It is these mediators that contract smooth muscle causing the airways to narrow

Urinary CC16 after challenge with dry air hyperpnoea and mannitol in recreational summer athletes

Airway epithelial injury is regarded as a key contributing factor to the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. The concentration of the pneumoprotein club cell (Clara cell) CC16 in urine has been found to be a non-invasive marker for hyperpnoea-induced airway epithelial perturbation. Exercise-hyperpnoea induces mechanical, thermal and osmotic stress to the airways. We investigated whether osmotic stress alone causes airway epithelial perturbation in athletes with suspected EIB. Twenty-four recreational summer sports athletes who reported respiratory symptoms on exertion performed a standard eucapnic voluntary hyperpnoea test with dry air and a mannitol test (osmotic challenge) on separate days. Median urinary CC16 increased from 120 to 310 ρg μmol creatinine-1 after dry air hyperpnoea (P = 0.002) and from 90 to 191 ρg μmol creatinine-1 after mannitol (P = 0.021). There was no difference in urinary CC16 concentration between athletes who did or did not bronchoconstrict after dry air hyperpnoea or mannitol. We conclude that, in recreational summer sports athletes with respiratory symptoms, osmotic stress per se to the airway epithelium induces a rise in urinary excretion of CC16. This suggests that hyperosmolarity of the airway surface lining perturbs the airway epithelium in symptomatic athletes.The study was independently supported financially by the World Anti Doping Agency (WADA). Pharmaxis Ltd. provided the mannitol kits free of charge and approved submission of the manuscript for publication

Effect of creatine supplementation on the airways of youth elite soccer players

Introduction Owing to its well-established ergogenic potential, creatine is a highly popular food supplement in sports. As an oral supplement, creatine is considered safe and ethical. However, no data exist on the safety of creatine on lung function in athletes. The aim of this project was to evaluate the effects of a standard course of creatine on the airways of youth elite athletes. Methods Nineteen elite soccer players, 16-21 yr old, completed a stratified, randomized, double-blind, placebo-controlled, parallel-group trial. The creatine group (n = 9) ingested 0.3 g·kg-1⋅d-1 of creatine monohydrate (CM) for 1 wk (loading phase) and 5 g·d-1 for 7 wk (maintenance phase), and the placebo group (n = 10) received the same dosages of maltodextrin. Airway inflammation (assessed by exhaled nitric oxide, FENO) and airway responsiveness (to dry air hyperpnoea) were measured pre- and postsupplementation. Results Mild, unfavorable changes in FENO were noticed by trend over the supplementation period in the CM group only (P = 0.056 for interaction, η2 = 0.199), with a mean group change of 9 ± 13 ppb in the CM group versus -5 ± 16 ppb in the placebo group (P = 0.056, d = 0.695). Further, the maximum fall in forced expiratory volume in 1 s after dry air hyperpnoea was larger by trend postsupplementation in the CM group compared with the placebo group: 9.7% ± 7.5% vs 4.4% ± 1.4%, respectively (P = 0.070, d = 0.975). These adverse effects were more pronounced when atopic players only (n = 15) were considered. Conclusion On the basis of the observed trends and medium to large effect sizes, we cannot exclude that creatine supplementation has an adverse effect on the airways of elite athletes, particularly in those with allergic sensitization. Further safety profiling of the ergogenic food supplement is warranted

Respiratory health of elite athletes – preventing airway injury: a critical review

Elite athletes, particularly those engaged in endurance sports and those exposed chronically to airborne pollutants/irritants or allergens, are at increased risk for upper and lower airway dysfunction. Airway epithelial injury may be caused by dehydration and physical stress applied to the airways during severe exercise hyperpnoea and/or by inhalation of noxious agents. This is thought to initiate an inflammatory cascade/repair process that, ultimately, could lead to airway hyperresponsiveness (AHR) and asthma in susceptible athletes. The authors review the evidence relating to prevention or reduction of the risk of AHR/asthma development. Appropriate measures should be implemented when athletes exercise strenuously in an attempt to attenuate the dehydration stress and reduce the exposure to noxious airborne agents. Environmental interventions are the most important. Non-pharmacological strategies can assist, but currently, pharmacological measures have not been demonstrated to be effective. Whether early prevention of airway injury in elite athletes can prevent or reduce progression to AHR/asthma remains to be established

Fractional exhaled nitric oxide in the assessment of exercise- induced bronchoconstriction: A multicenter retrospective analysis of UK- based athletes

Introduction: Exercise-induced bronchoconstriction (EIB) is not only highly prevalent in people with asthma, but can also occur independently, particularly in athletes. Fractional exhaled nitric oxide (FeNO) is an indirect biomarker of type 2 airway inflammation that has an established role in the assessment and management of asthma. The aim was to evaluate the value of FeNO in the assessment of EIB in athletes. Method: Multicenter retrospective analysis. In total, 488 athletes (male: 76%) performed baseline FeNO, and spirometry pre- and post-indirect bronchial provocation via eucapnic voluntary hyperpnea (EVH). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for established FeNO thresholds—that is, intermediate (≥25ppb) and high FeNO (≥40ppb and≥50ppb)—and were evaluated against objective evidence of EIB (≥10% fall in FEV1). The diagnostic accuracy of FeNO was calculated using receiver operating characteristics area under the curve (ROC-AUC). Results: Thirty-nine percent of the athletes had a post-EVH fall in FEV1 consistent with EIB. FeNO values ≥25ppb, ≥40ppb, and≥50ppb were observed in 42%, 23%, and 17% of the cohort, respectively. The sensitivity of FeNO ≥25ppb was 55%, which decreased to 37% and 27% at ≥40ppb and≥50ppb, respectively. The specificity of FeNO ≥25ppb, ≥40ppb, and≥50ppb was 66%, 86%, and 89%, respectively. The ROC-AUC for FeNO was 0.656. Conclusions: FeNO ≥40ppb provides good specificity, that is, the ability to rulein a diagnosis of EIB. However, due to the poor sensitivity and predictive values, FeNO should not be employed as a replacement for indirect bronchial provocation in athletes

Misdiagnosis of exercise-induced bronchoconstriction in professional soccer players

Background Physicians typically rely heavily on self-reported symptoms to make a diagnosis of exercise-induced bronchoconstriction (EIB). However, in elite sport, respiratory symptoms have poor diagnostic value. In 2009, following a change in international sports regulations, all elite athletes suspected of asthma and/or EIB were required to undergo pulmonary function testing (PFT) to permit the use of inhaled β2-agonists. The aim of this study was to examine the diagnostic accuracy of physician diagnosis of asthma/EIB in English professional soccer players. Methods Sixty-five players with a physician diagnosis of asthma/EIB were referred for pulmonary function assessment. Medication usage and respiratory symptoms were recorded by questionnaire. A bronchial provocation test with dry air was conducted in 42 players and a mannitol challenge in 18 players. Five players with abnormal resting spirometry performed a bronchodilator test. Results Of the 65 players assessed, 57 (88%) indicated regular use of asthma medication. Respiratory symptoms during exercise were reported by 57 (88%) players. Only 33 (51%) of the players tested had a positive bronchodilator or bronchial provocation test. Neither symptoms nor the use of inhaled corticosteroids were predictive of pulmonary function tests’ outcome. Conclusion A high proportion of English professional soccer players medicated for asthma/EIB (a third with reliever therapy only) do not present reversible airway obstruction or airway hyperresponsiveness to indirect stimuli. This underlines the importance of objective PFT to support a symptoms-based diagnosis of asthma/EIB in athletes