Malcolm Sue-Chu

Asthma and the elite athlete: Summary of the International Olympic Committee's Consensus Conference, Lausanne, Switzerland, january 22-24, 2008

Respiratory symptoms cannot be relied on to make a diagnosis of asthma and/or airways hyperresponsiveness (AHR) in elite athletes. For this reason, the diagnosis should be confirmed with bronchial provocation tests. Asthma management in elite athletes should follow established treatment guidelines (eg, Global Initiative for Asthma) and should include education, an individually tailored treatment plan, minimization of aggravating environmental factors, and appropriate drug therapy that must meet the requirements of the World Anti-Doping Agency. Asthma control can usually be achieved with inhaled corticosteroids and inhaled beta(2)-agonists to minimize exercise-induced bronchoconstriction and to treat intermittent symptoms. The rapid development of tachyphylaxis to beta(2)-agonists after regular daily use poses a dilemma for athletes. Long-term intense endurance training, particularly in unfavorable environmental conditions, appears to be associated with an increased risk of developing asthma and AHR in elite athletes. Globally, the prevalence of asthma, exercise-induced bronchoconstriction, and AHR in Olympic athletes reflects the known prevalence of asthma symptoms in each country. The policy of requiring Olympic athletes to demonstrate the presence of asthma, exercise-induced bronchoconstriction, or AHR to be approved to inhale beta(2)-agonists will continue.

Prevalence of asthma in young cross-country skiers in central Scandinavia: differences between Norway and Sweden

An increased prevalence of asthma in cross-country skiers has been reported previously. This study was conducted in order to evaluate the prevalence of asthma among young, elite cross-country skiers in Trøndelag, Norway and Jämtland, Sweden. These two regions in central Scandinavia have different climates during the winter season, with a coastal type in Trøndelag while Jämtland is characterized by a colder, drier, inland type of climate. The study population consisted of 171 skiers (118 from Norway, 53 from Sweden). The investigation included an asthma questionnaire, spirometry and methacholine provocation testing. The prevalence of self-reported asthma-related symptoms was 46% in Norway and 51% in Sweden. The prevalence of bronchial hyper-responsiveness (BHR) was significantly different between the two regions. In Norway, 14% of the skiers were hyper-responsive to methacholine compared to 43% in Sweden (P < 0.001). Moreover, the estimated prevalence of clinically diagnosed asthma was 12% in Norway and 42% in Sweden (P < 0.001). The self-reported frequency of respiratory allergy was higher in Sweden (32%) than in Norway (11%). However, on an individual basis, self-reported allergy did not predict occurrence of asthma or BHR. In conclusion, there is a high prevalence of BHR and asthma among young, elite cross-country skiers in central Scandinavia, especially in Sweden. Cross-country skiing may be a risk factor for the development of asthma. Longitudinal studies of cross-country skiers, and studies to acquire further knowledge of the mechanisms involved in the development of asthma are indicated.

Placebo-Controlled Study of Inhaled Budesonide on Indices of Airway Inflammation in Bronchoalveolar Lavage Fluid and Bronchial Biopsies in Cross-Country Skiers

Background: Asthma-like symptoms, methacholine hyperresponsiveness, use of inhaled steroids, airway inflammation, and increased tenascin expression in the reticular basement membrane have been reported in competitive cross-country skiers. Objective: To investigate the effect of inhaled budesonide, 400 μg twice daily, on indices of airway inflammation in ‘ski asthma’, defined as asthma-like symptoms within the previous year and bronchial hyperresponsiveness to methacholine. Methods: A randomised double-blind placebo-controlled parallel-group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male) competitive cross-country skiers (mean age 18 (16–20) years for a mean (range) treatment period of 22 (10–32) weeks over the competitive season. Results: No changes were seen regarding cellular inflammation in the bronchial mucosa or tenascin expression. In the BAL fluid, both groups had a significant decrease in activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no differences across the groups. Within the budesonide group, there was a decrease in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV1. Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation test was negative in 15 subjects, and remained positive in 5 subjects in each group. The improvement in bronchial responsiveness occurred in both groups and was not accompanied by a decrease in cellular inflammation. Conclusions: We were unable to show any clear beneficial effect of budesonide in ‘ski asthma’. As changes in training intensity probably accounted for the spontaneous improvement in bronchial responsiveness, more attention should be directed at reducing environmental stress to the airways than at attempting pharmacological modulation of induced inflammatory changes.

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.

Effect of cold exposure (-15 degrees C) and salbutamol treatment on physical performance in elite nonasthmatic cross-country skiers

Abstract The effects of whole-body exposure to ambient temperatures of −15°C and 23°C on selected performance-related physiological variables were investigated in elite nonasthmatic cross-country skiers. At an ambient temperature of −15°C we also studied the effects of the selective β2-adrenergic agonist Salbutamol (0.4 mg × 3) which was administered 10 min before the exercise test. Eight male cross-country skiers with known maximal oxygen uptakes (V˙O2max) of more than 70 ml · kg−1 · min−1 participated in the study. Oxygen uptake (V˙O2), heart rate (fc), blood lactate concentration ([La−]b) and time to exhaustion were measured during controlled submaximal and maximal running on a treadmill in a climatic chamber. Lung function measured as forced expiratory volume in 1 s (FEV1) was recorded immediately before the warm-up period and at the conclusion of the exercise protocol. Submaximal V˙O2 and [La−]b at the two highest submaximal exercise intensities were significantly higher at −15°C than at 23°C. Time to exhaustion was significantly shorter in the cold environment. However, no differences in V˙O2max or fc were observed. Our results would suggest that exercise stress is higher at submaximal exercise intensities in a cold environment and support the contention that aerobic capacity is not altered by cold exposure. Furthermore, we found that after Salbutamol inhalation FEV1 was significantly higher than after placebo administration. However, the inhaled β2-agonist Salbutamol did not influence submaximal and maximal V˙O2, fc, [La−]b or time to exhaustion in the elite, nonasthmatic cross-country skiers we studied. Thus, these results did not demonstrate any ergogenic effect of the β2-agonist used.

Effect of inspired air conditions on exercise-induced bronchoconstriction and urinary CC16 levels in athletes.

Injury to the airway epithelium has been proposed as a key susceptibility factor for exercise-induced bronchoconstriction (EIB). Our goals were to establish whether airway epithelial cell injury occurs during EIB in athletes and whether inhalation of warm humid air inhibits this injury. Twenty-one young male athletes (10 with a history of EIB) performed two 8-min exercise tests near maximal aerobic capacity in cold dry (4°C, 37% relative humidity) and warm humid (25°C, 94% relative humidity) air on separate days. Postexercise changes in urinary CC16 were used as a biomarker of airway epithelial cell perturbation and injury. Bronchoconstriction occurred in eight athletes in the cold dry environment and was completely blocked by inhalation of warm humid air [maximal fall in forced expiratory volume in 1 s = 18.1 ± 2.1% (SD) in cold dry air and 1.7 ± 0.8% in warm humid air, P < 0.01]. Exercise caused an increase in urinary excretion of CC16 in all subjects (P < 0.001), but this rise in CC16 was blunted following inhalation of warm humid air [median CC16 increase pre- to postchallenge = 1.91 and 0.35 ng/μmol in cold dry and warm humid air, respectively, in athletes with EIB (P = 0.017) and 1.68 and 0.48 ng/μmol in cold dry and warm humid air, respectively, in athletes without EIB (P = 0.002)]. The results indicate that exercise hyperpnea transiently disrupts the airway epithelium of all athletes (not only in those with EIB) and that inhalation of warm moist air limits airway epithelial cell perturbation and injury.

Hyperpnea-induced bronchoconstriction and urinary CC16 levels in athletes.

PURPOSE Exercise-induced bronchoconstriction (EIB) is a common condition in both individuals with asthma and otherwise healthy elite athletes. Although excessive water loss by peripheral airways during hyperpnea is regarded as the initial trigger for EIB, the cascade of events that follows remains unclear. Our goal was to establish whether transient disruption of the airway epithelial barrier occurs after a short period of hyperpnea of dry air in athletes with EIB. METHODS Urinary concentration of the pneumoprotein Clara cell (CC16) was used as an assumed biomarker of lung epithelial cell damage or dysfunction. Samples were collected at baseline and for 90 min after an 8-min eucapnic voluntary hyperpnea (EVH) test in 50 female individuals (28 athletes and 22 untrained). RESULTS Nineteen subjects (10 athletes) demonstrated a sustained bronchoconstriction after EVH (mean±SE forced expiratory volume in the first second (FEV1) fall from baseline=23.4%±2.6%). The remaining subjects had a negative challenge result with an FEV1 fall of 5.9%±0.6%. An increase (P<0.001) in urinary CC16 concentration was noticed after EVH in all but one subject, with no group difference (median CC16 increase before to after challenge: athletes EVH 0.083 ng·μmol, athletes EVH 0.223 ng·μmol, untrained EVH 0.074 ng·μmol, untrained EVH 0.571 ng·μmol; P>0.05). CONCLUSIONS Urinary levels of CC16 are increased after EVH in all individuals (trained and untrained, with and without EIB) suggestive of dehydration-induced perturbation of the distal respiratory epithelium during episodes of hyperventilation.

Winter sports athletes: long-term effects of cold air exposure

Athletes such as skaters and skiers inhale large volumes of cold air during exercise and shift from nasal to mouth breathing. Endurance athletes, like cross-country skiers, perform at 80% or more of their maximal oxygen consumption and have minute ventilations in excess of 100 l/min. Cold air is always dry, and endurance exercise results in loss of water and heat from the lower respiratory tract. In addition, athletes can be exposed to indoor and outdoor pollutants during the competitive season and during all-year training. Hyperpnoea with cold dry air represents a significant environmental stress to the airways. Winter athletes have a high prevalence of respiratory symptoms and airway hyper-responsiveness to methacholine and hyperpnoea. The acute effects of exercise in cold air are neutrophil influx as demonstrated in lavage fluid and airway epithelial damage as demonstrated by bronchoscopy. Upregulation of pro-inflammatory cytokines has been observed in horses. Chronic endurance training damages the epithelium of the small airways in mice. Airway inflammation has been observed on bronchoscopy of cross-country skiers and in dogs after a 1100-mile endurance race in Alaska. Neutrophilic and lymphocytic inflammation with remodelling is present in bronchial biopsies from skiers. Repeated peripheral airway hyperpnoea with dry air causes inflammation and remodelling in dogs. As it is currently unknown if these airway changes are reversible upon cessation of exposure, preventive measures to diminish exposure of the lower airways to cold air should be instituted by all winter sports athletes.

Salmeterol and physical performance at ‐15°C in hghly trained nonasthmatic cross‐country skiers

The aim of this double‐blind. placebo‐controlled, cross‐over study was to investigate possible improvement in physical performance at an ambient temperature of −15°C by an inhaled dose of 50 μg salmeterol in 8 highly trained nonasthmatic cross‐country skiers. FEV1 was measured before, during and after the treadmill exercise protocol, which consisted of a warm‐up run. runs of 10 min at 90%, and 5 min at 80%VO2max, followed by a timed run to exhaustion. Despite a significant improvement in FEV1, salmeterol did not have a beneficial effect on heart rate, blood lactate concentration, respiratory exchange ratio, oxygen uptake or minute ventilation during the exercise protocol. Running time to exhaustion was not significantly different from placebo. This lack of enhancement of exercise performance in healthy endurance athletes further supports the recent approval of salmeterol for prophylactic use by asthmatic athletes during training and competition.

A study of the association between exercise-induced wheeze and exercise versus methacholine-induced bronchoconstriction in adolescents

Among asthmatics, exercise‐induced wheeze (EIW) is a frequent symptom, and 40–77% of asthmatics demonstrate exercise‐induced bronchoconstriction (EIB). In the North‐Trøndelag population‐based survey of 8,571 adolescents (YOUNG‐HUNT), 26% reported wheeze during the previous 12 months (current wheeze). Of those subjects, 50% reported EIW. The aim of the present study was to investigate the association between EIW and EIB in randomly selected adolescents with EIW as the only or predominant asthma‐like symptom, and to relate our findings to results from methacholine bronchoprovocation tests (MT) and measurements of exhaled nitric oxide (ENO). Sixty‐three subjects with current wheeze induced by exercise, but not by allergen exposure, were investigated using a treadmill exercise test (ET) and measurements of ENO. Fifty‐eight subjects completed a MT on a separate study day. EIB was defined as a fall of ≥ 10% in the forced expiratory volume in 1 second (FEV1) after exercise (ΔFEV1%ex). Twenty‐one subjects (33%) had EIB and 33 (57%) had a positive MT. The degree of reported dyspnea during the ET was not correlated to the ΔFEV1%ex. The correlation between EIB and methacholine‐induced bronchoconstriction (MIB) was poor, and the ΔFEV1%ex was more pronounced in smokers than in non‐smokers. Moreover, ENO was not increased in subjects with positive vs. negative ET. Hence, EIW, when reported as the only or predominant asthma‐like symptom, was linked to EIB in only one‐third of the patients. We conclude that EIW is a poor predictor of EIB in epidemiological studies. The poor correlation between EIB and MIB indicates that these two tests measure different mechanisms of bronchial hyper‐responsiveness.