Asthma, Bronchial Hyperresponsiveness and Sports
Updated: September 2016
Originally Posted: July 2009
|Kai-Håkon Carlsen, MD, PhD
Professor emeritus of Paediatric Respiratory Medicine and Allergology
Medical Faculty, University of Oslo
Professor emeritus of Sports Medicine, Norwegian School of Sport Sciences, Oslo
Voksentoppen, Dept. of Paediatrics, Rikshospitalet University Hospital
Ullveien 14, NO 0791 Oslo
|Luis Delgado, MD, PhD
Professor of Internal Medicine and Allergology
Serviço e Laboratório de Imunologia, Faculdade de Medicina da Universidade do Porto,
Hospital de S.João, Porto
Exercise-induced asthma (EIA) is a concern for children and adolescents with asthma during growth and development. According to most International and National guidelines on treating asthma, one of the main objectives in children is to master EIA. Among elite athletes EIA and bronchial hyperresponsiveness (BHR) have become major problems, interfering with the performance of sports and representing a health risk. Athletes have, in the same manner as ordinary patients, the need for optimal diagnosis and treatment of their asthma. This was fully shown by Becker et al who reported deaths linked to athletic performance over a seven-year period in the USA. Out of 263 deaths, 61 were related to asthma. Only one of the 61 athletes who died had used inhaled steroids1. This underlines the need for optimal asthma treatment and follow-up among competitive athletes.
Due to reports of frequent use of inhaled β2-agonists, the Medical Commission of the International Olympic Committee (IOC-MC) in 1993 introduced restrictions in their use in relationship to sport. These rules have been altered several times and from 2002 with the introduction of applications to obtain approval for the use of the drugs when competing as an international athlete presenting measurements of lung function and bronchial responsiveness. A joint Task Force established by the European Respiratory Society and the European Academy of Allergy and Clinical Immunology reviewed the problems of asthma in athletes and published an overview as well as guidelines for diagnosing and treating asthma in athletes in three publications2-4. The present article focuses on the problems raised by this report in respect to diagnosis, treatment as well as novel research results outlining a hypothesis of why athletes do develop asthma due to their sports activity5.
Also, other allergic diseases represent a problem in elite sports. Especially exercise -induced anaphylaxis, which is a major problem for those affected. In addition, allergic rhinoconjunctivitis and urticaria both physical and allergic types, represent major problems for those affected.
In 1986, in a screening reported by the US Olympic Committee, 67 out of 597 American Olympic Athletes for the Los Angeles 1984 summer Olympic Games suffered from EIA or asthma. These 67 asthmatic athletes won 41 medals during the Olympic Games6. The prevalence of EIA of 11% among the American Olympic athletes from 19847, increased to >20% among the American participants in the 1996 summer Olympic Games in Atlanta8. The asthma prevalence was 45% in cyclist and mountain bikers compared to none in divers and weight-lifters8. Larsson et al reported in 1993 that 23 of 42 elite cross country skiers had a combination of BHR and asthma symptoms compared to only one of 23 referents9. In a questionnaire-based report, Heir and Oseid showed a prevalence of doctor-diagnosed asthma of 14 % in 155 actively competing skiers compared to 5 % in twice matched controls. Moreover, the prevalence of asthma diagnosis increased with increasing age in the actively competing skiers10. This was followed by reports of high prevalence in Norwegian and Swedish skiers11, in competitive figure skaters12,13, in elite cold-weather athletes14 and among participants in the 1998 American Olympic National team for winter sports including gold medalists15. Langdeau and his coworkers reported that 49 out of 100 competitive athletes (in various sports) suffered from BHR to metacholine (49%) compared to 28% of sedentary subjects (28%)16.
Feinstein et al found EIB in nine of 48 male football players17 whereas a positive bronchodilator test (increase in FEV1 ≧ 12%) to inhaled salbutamol was found in 56% of Canadian professional football players18. Helenius and Haahtela reported on several studies of Finnish elite track and field athletes, showing physician-diagnosed asthma in 17% of long-distance runners, 8 % of speed and power athletes and 3 % of controls19. In another study total asthma (current asthma, physician diagnosed asthma or BHR) was found in 23% of the athletes compared to 4% of the controls; current asthma in 14% compared to 2% among controls and positive skin prick test (SPT) in 48% of the athletes compared to 36% among controls20. High prevalence of BHR (48%) to histamine was also found among swimmers21. Maiolo et al reported an asthma prevalence of 15% and atopy in 18% of 1060 Italian competing summer athletes22. Higher prevalence of asthma among endurance athletes as compared to speed and power athletes was reported in a Norwegian study23. Employing the objective criteria for diagnosing asthma and/or bronchial hyperresponsiveness as were given by the IOC Medical Commission, Dickinson reported prevalence among the British participants in the Olympic Games in 2000 and 2004 to be 21.2% and 20.7%, respectively, with a positive bronchial challenge or bronchodilator test24.
How do athletes contract EIA and BHR?
1. Exercise-induced asthma, why?
Two hypotheses attempt to explain the relationship between physical activity and EIA. One relates to cooling of the airways due to the increased ventilation during exercise while the other hypothesis relates to increased water loss from the respiratory tract also caused by increased ventilation during exercise. The airway cooling due to respiratory heat loss from the increased ventilation during exercise is thought to cause smooth muscle contraction due to anticholinergic stimulation through a vagal reflex and vasoconstriction in bronchial vessels followed by a secondary reactive hyperaemia with resulting oedema and airways narrowing25. On the other hand, symptoms may be due to water loss caused by the high ventilation rates of top athletes (up to >280 L/minute) during exercise, with saturation of the inhaled air with water. The resulting increase in osmolarity of the extracellular fluid of the respiratory mucosa is thought to cause extravasation of water from the intracellular to the extracellular space initiating cells to release mediator resulting in increased airways inflammation and bronchial constriction26. The use of inhaled mannitol as a tool to diagnose bronchial hyperresponsiveness further confirms this hypothesis27.
2. Why do competitive athletes develop EIA and BHR?
That high intensive exercise may cause an increase in BHR was first demonstrated in Norwegian competitive swimmers after swimming exercises of 3000 meters28 and then in young ski athletes during the competitive season10. Heavy endurance training, especially when performed in an unfavorable environment, presents stress to the mucosal membrane of the airways. This was elegantly shown by Sue Chu and coworkers in bronchial biopsies from heavily training young skiers without asthma, but with increased airways responsiveness to cold air29,30, describing increased airways inflammation with lymphoid aggregates and increased tenascin expression (the thickness of the tenascin-specific immunoreactivity band in the basement membrane) in the skiers. These findings were recently reproduced by Bougault et al in elite competitive swimmers31. Signs of epithelial damage was also found in Alaskan dogs after a winter race of several days32 and experimentally in exercising mice as compared to sedentary mice33. Also in runners, respiratory epithelial damage with apoptosis of epithelial cells were found after repeated half-marathon races34. Inflammatory changes were found in induced sputum of competitive swimmers21. Thus, respiratory epithelial damage, as a result of repeated heavy physical endurance training over prolonged periods of time, may initiate and contribute to airways inflammation and the development of athlete’s asthma.
3. The environment
An unfavorable environment in which repeated competitions and training sessions take place is thought to be an important contribution to the development of asthma and BHR among top athletes, as in cross country skiers exposed to cold air9,35,36, competitive swimmers exposed to organic chlorine products from the water in indoor pools21 and figure skaters and ice hockey players in ice rinks with increased levels of ultrafine particles originating from the ice polishing machines13,37,38. Larsson showed that cold air inhalation increased the number of inflammatory cells in broncho-alveolar lavage35. In children, Bernard and co-workers reported that time spent in swimming pools during early childhood are related to the development of asthma and signs of lung involvement by increased serum levels of surfactant proteins39 and reduced levels of Clara cell protein40. It has also been shown that respiratory tract infections increase bronchial responsiveness in actively training athletes41. Thus, the combination of heavy repeated exercise with an unfavorable environmental milieu is probably important for the development of asthma among top athletes. On top of this comes the effect of respiratory infections.
4. Parasympathetic (cholinergic) stimulation
The increased ventilation during exercise causes a cooling of the airways as the inspired air is warmed to 37℃42. The cooling of the airways causes parasympathetic stimulation that contributes to bronchoconstriction and increased cholinergic inflammation.43 Endurance training has been shown to cause increased parasympathetic tonus and parasympathetic modulation, as measured by heart rate variation related to physical fitness.44
It is thought that the combination of repeated respiratory epithelial damage during endurance training and competitions, increasing airways inflammation together with exposure to possible environmental pollution and respiratory infections during sports performance are all factors leading to increased bronchial hyperresponsiveness and respiratory symptoms in the endurance athlete. As also endurance training has been shown to increase parasympathetic tonus45, this may contribute to bronchoconstriction and increased bronchial hyperresponsiveness. The combination of these multiple factors partly related to training effect and partly to environmental exposure during sports performance may explain the increased developing of asthma among endurance athletes.5
The diagnosis of asthma is clinical and should be based on the history of symptoms, physical examination for the presence of bronchial obstruction and variability in lung function spontaneously, or due to bronchodilators (Table 1)46. The main symptoms of asthma are recurring episodes of bronchial obstruction. The term 'current asthma' is used when at least one episode of asthma has occurred during the last year. The competing athlete frequently reports the presence of respiratory symptoms in relationship to exercise, but the diagnosis of asthma or exercise-induced asthma (EIA) may be difficult due to the variability and non-specificity of symptoms14,47. Recently two different phenotypes of asthma in athletes, diagnosed according to the criteria of the IOC, MC and WADA, were identified by latent class analysis in elite Portuguese and Norwegian athletes and classified as atopic asthma and sports asthma48. An exact clinical history, examination with lung function measurements before and after inhalation of a ß2-agonist or another bronchodilator (requiring an increase in FEV1 of 12%), before and after a standardized exercise test such as a treadmill run and/or a cold-air inhalation test and measurement of BHR by metacholine inhalation, are parts of the diagnostic process. One important part of the diagnostic process is the follow-up of patients to evaluate the treatment effect. The eucapnic voluntary hyperpnoea test is, by many, recommended as both sensitive and specific although it is debated if a cut off should be 10 or 15% 49,50.
Table 1. Diagnostic methods recommended by the Medical Commission (MC) of the International Olympic Committee (IOC) and by the World Anti-Doping Association (WADA) for diagnosing asthma in athletes participating in Olympic Games and international sports. A clinical history in combination with a positive bronchodilator response or a positive response to EIA test or another test of bronchial responsiveness is recommended.
|Diagnostic procedure||Results as recommended|
|Clinical history of respiratory symptoms and clinical examination||Positive clinical history|
|Lung function (Spirometry or maximum expiratory flow volume loops).
Reversibility to inhaled bronchodilator
|Increase in FEV1 after inhaled bronchodilator|
|Exercise induced bronchoconstriction by standardised exercise test||FEV1 decrease of 10% from before to after standardized exercise challenge|
|Bronchial hyperresponsiveness to metacholine (histamine presently not allowed by IOC-MC))||PD20 < 2 μmol, PC20 < 4 mg/ml.
Other values when on inhaled steroids.
|Eucapnic voluntary hyperpnoea test||Reduction in FEV1 of 10%, alternatively 15% or more.|
|Mannitol inhalation test
|Reduction in FEV1 of 15% or more.
Determination of PD15 of mannitol
|Exercise field test||Reduction in FEV1 of 10% or more|
EIA may be diagnosed in different ways; running provokes exercise-induced bronchoconstriction more easily than cycling and swimming51,52. A heavy exercise load is recommended. At the University of Oslo, a motor driven treadmill with an inclination of 5.5% is employed, rapidly increasing speed until a steady heart rate of approximately 90-95% of calculated maximum is reached and maintained for 4-6 minutes. The widespread use of inhaled steroids necessitates this level of exercise53. Maximum heart rate is calculated approximately by taking 220 minus the age of the patient, and can be measured electronically or by electrocardiogram. The running is performed at a room temperature of approximately 20℃ and a relative humidity of approximately 40 %. Lung function is measured by FEV1 before running, immediately after stopping, then 3, 6, 10, 15 and 20 minutes after running. A fall of 10 % in FEV1 is taken as a positive sign of EIA. When adding an extra stimulus to the exercise test, as by combining running on a treadmill with the inhalation of dry cold air of -20°C, the sensitivity of the test is markedly increased while simultaneously maintaining a high degree of specificity54. Other tests used for the diagnosis of exercise-induced bronchoconstriction and BHR are eucapnic voluntary hyperpnoea50 and mannitol bronchial provocation, determining the inhaled dose causing a 15% decrease in FEV1 27.
There are several differential diagnoses to EIA, including exercise-induced laryngeal obstruction (EILO)55 and hyperventilation during exercise. These conditions should be borne in mind, as many such patients have been given unnecessary drugs for treatment of asthma, including both inhaled steroids and β2-agonists, which will have no effect upon the exercise-induced laryngeal stridor. EILO is more common among top trained female athletes during adolescence. Marked inspiratory stridor during maximal exercise with a flattening of the maximal inspiratory flow volume curve56 is typical of EILO. In contrast with EIA, the dyspnea occurs after exercise and is expiratory due to the lower airways obstruction. EILO may be of glottic or supraglottic type. The diagnosis of this condition may be made by continuous laryngoscopic exercise test (CLE)57. Other differential diagnoses to EIB include exercise-induced arterial hypoxemia58 and swimming induced pulmonary edema59 (Table 2).
|EIA||Symptoms occurring shortly after (sometimes during) physical exercise.
If observed: Expiratory dyspnoea, expiratory rhonchi and other signs of bronchial obstruction. Gradual improvement either spontaneously or after inhaled bronchodilator
|Exercise induced laryngeal obstruction (EILO)||Symptoms occurring during maximum exertion. Symptoms disappear after stopping exercise (unless hyperventilating)
If observed: Inspiratory stridor, audible inspiratory sounds from laryngeal area. No signs of bronchial obstruction. No effect of pretreatment with inhaled bronchodilator. Glottic or supraglottic type
|Poor physical fitness||Related to expectations
High heart rate after low-grade exercise load
|Other chronic lung diseases||Reduced baseline lung function may reduce physical performance due to limitations in airflow and lung volumes|
|Other general disease||Chronic heart diseases and others|
|Exercise induced arterial hypoxemia (EIAH)||Occurs in well-trained athletes with high max. VO2
Primarily due to diffusion limitations and ventilation-perfusion inequality. Incomplete diffusion in the healthy lung may be due to a rapid red blood cell transit time through the pulmonary capillary
|Swimming induced pulmonary edema (SIPE)||Often hemoptysis after heavy swimming exercise, reduced diffusion capacity|
Despite the epidemiological evidence about increased prevalence of EIA and BHR in top athletes, the frequent use of asthma drugs caused concern about possible improvement of performance by asthma drugs and especially so by inhaled 2-agonists. Thus, already by 1993, the Medical Commission of the International Olympic Committee (IOC-MC) had introduced restrictions to the use of asthma drugs in sports. Among the β2-agonists only salbutamol and terbutaline were allowed for use in sports, and only by the inhaled route. Only athletes with a confirmed diagnosis of asthma were allowed to use these drugs. Later regulations have been changed several times. Shortly before the Salt Lake City Winter Olympic Games in 2002, the IOC-MC introduced new rules for the use of inhaled β2-agonists and inhaled steroids during the games60. Applications had to be submitted beforehand, and results of laboratory tests such as exercise tests, bronchial provocation tests with metacholine, eucapnic hyperpnoea tests or documented reversibility to inhaled 2-agonists had to be submitted to obtain approval for the use of asthma drugs60. It was recommended that after appropriate objective diagnosis, the treatment of the athlete with asthma or other respiratory problems should follow the common guidelines, taking into consideration the rules set up by the doping authorities (WADA and for the Olympic Games; IOC-MC).
Asthma is the most common chronic disease reported among Olympic participants.61 For the Beijing Summer Olympic Games, 813 applications were made for the use of inhaled β2-agonists, and 781 of these were approved. Of the 781 athletes with approval for the use of inhaled β2-agonists, 711 also used inhaled steroids. Inhaled steroids alone were used by 121 additional athletes (From Report of the Independent observers, XXIX Beijing Olympic Games)
As the regulations for the use of asthma drugs among athletes have been repeatedly changed, the physician treating asthmatic athletes and children and adolescents with asthma should keep updated on the present regulations. This may be done by going to the website of the World Antidoping Association (WADA) https://www.wada-ama.org. On this website, a guide for team physicians on treating asthma in athletes may be found. The rules for asthma drugs were last changed from 2012. Presently, all inhaled corticosteroids are allowed for use in sports, also inhaled ipratropium bromide and montelukast. All β2 –agonists are prohibited except inhaled salbutamol, salmeterol, and formoterol. For salbutamol, a maximum dose of 1.6 mg inhaled over 24 hours is given, for formoterol a maximum dose of 64 μg over 24 hours are given, and for salmeterol, the dose should follow the manufacturer’s recommendation. The concentration of salbutamol and formoterol will be controlled in the urinary sample if the athlete is taken out for a doping test. If the physician finds a reason to prescribe salbutamol inhaled by nebulization, an application for Therapeutic Use Exemption (TUE) should be made.
Physicians caring for athletes should know the rules for doping given by WADA and check for the latest updates. New updates are given each year being effective usually from 1st of January. The athletes should also be made aware of that they should know the regulations themselves, as it is their own responsibility not to use prohibited drugs.
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