Physical exertion is one of many non-pharmacological and non-immunological stimuli that can produce episodes of airway obstruction in patients with asthma. Unlike other types of provocations that function only periodically in the lives of patients with the disease, exercise is one of the most common precipitants of acute symptoms encountered in medical practice. Physical activity is the second-leading cause of acute airway constriction and ranks only behind viral upper respiratory tract infections in this regard.

Exercise-induced airway narrowing, exercise-induced asthma (EIA) and exercise-induced bronchospasm (EIB) are synonymous terms and describe a condition in which vigorous physical activity triggers acute airway narrowing in people with heightened bronchial reactivity. The diagnosis is established by demonstrating a measurable fall in some aspect of airway mechanics. By convention, a 15-20% decrement in either the one-second forced expiratory volume (FEV1) or the peak flow is typically employed.

Other indices have been used from time to time to increase sensitivity, eg. specific conductance, flows in the mid-vital capacity, but selectivity invariably diminishes and false-positive diagnoses increase. 

Exercise-induced asthma

Because exercise does not cause asthma per se, the most accurate description is exercise-induced airway narrowing. Long usage, however, has left the term EIA firmly fixed in the lexicon. Researchers focusing on the underlying pathogenesis of this phenomenon have proposed the term, ‘thermally induced asthma.’ EIA is not an isolated disorder or a specific disease but rather part of the overall asthmatic diathesis in which exercise is but one of many stimuli that induce airflow limitation. It is common for physical exertion to be the first clinically apparent precipitant of asthma; however, with time, others also emerge.

If they do not, the care provider should re-examine the diagnosis with a formal challenge. In rare instances, EIA can be the only manifestation of asthma; here, too, the diagnosis should be objectively confirmed since other conditions, such as vocal cord dysfunction, can mimic this illness.

The prevalence of exercise-induced symptoms in asthmatic people has been reported to vary from 40-90%. This wide range results from differences among studies in the intensity of the exercise stress used to produce obstruction, variations in definition, a lack of uniformity in the methods used to detect the response, and failure to standardise the environmental variables that control the magnitude of the obstruction.

Respiratory heat exchange

The initial reaction sequence in the production of airway narrowing with exercise and hyperventilation is linked to the process of respiratory heat exchange and involves a decrease in airway temperature. For a fixed ventilation, humidification of the inspirate reduces the severity of the obstructive response, whereas drying and cooling the air increases bronchial narrowing. Inhaling air preconditioned to body temperature and humidity during hyperpnoea prevents the obstruction from developing. For a given set of inspired conditions, high levels of ventilation result in greater responses than at low levels. Examination of these data from the standpoint of respiratory heat exchange reveals a highly significant quantitative and predictive relationship between the physical amount of heat loss during exercise and the magnitude of the post-exertional obstruction (see Figure 1).

Sport-related asthma

In response to a marked increase in the notification by athletes of use of inhaled ß-2 agonists from 3.7% in Atlanta in 1996 to 5.6% at the 1998 Winter Games in Nagano, and to 5.7% in Sydney 2000, the International Olympic Committee’s (IOC) Medical Commission conducted a symposium on asthma in 2001. Concerned that athletes without asthma may have been using inhaled ß-2 agonists, the symposium recommended that to be granted permission to use inhaled ß2-agonists at future Games, athletes should be required to demonstrate current asthma, EIA, EIB or airway hyper-responsiveness (AHR). The IOC agreed with the recommendation which was made for health and not doping reasons.

Subsequent publications have reviewed the consequences of this decision at the Olympics in 2002¹ and in 2004² and provided an overview of ß-2 agonists at the Olympic Games. In 2003, the International Association of Athletics Federations (IAAF) introduced the same requirements and criteria as the IOC. At a conference in January 2008, the IOC re-examined this topic, a decision in part provoked by the World Anti-Doping Agency (WADA) seeking clarification for the differences in policy between the IOC and WADA with respect to ß-2 agonists.

The conference examined a number of issues including:

• The diagnosis and optimal treatment of asthma, EIB and AHR in elite athletes
• Past experience of ß-2 agonists before and after the need to obtain approval
• Environmental and genetic aspects
• Intense endurance training as a possible cause of asthma/AHR
• The performance of athletes inhaling ß-2 agonists
• The future of ß-2 agonists at Olympic Games.

Benefits and dangers of ß-2 agonists

Athletes with asthma will need a fast-acting bronchodilator. Inhaled ß-2 agonists are the most effective bronchodilators for the relief of asthma symptoms and for pre-treatment of EIB. In addition, long-acting ß-2 agonists are often combined with inhaled corticosteroids to improve asthma control.

Unfortunately, studies show that regular treatment with ß-2 agonists increases the sensitivity of the airways to bronchoconstrictive stimuli including exercise and allergens (see Figure 2).

Athletes who have been using ß-2 agonists regularly or frequently are likely to experience worsening of EIB if they do not take them before exercise. In addition, both the bronchodilator and the bronchoprotective effects of ß-2 agonists diminish after a few days of regular use. Hence athletes using regular or frequent ß-2 agonists will have reduced protection against EIB even if they take them immediately before exercise. They are also likely to have a suboptimal response to rescue ß-2 agonists taken to relieve exercise-induced symptoms. These effects are probably a result of downregulation of ß-2 receptors on airway smooth muscle (ASM) and inflammatory cells such as mast cells induced by chronic exposure to agonist. Although tolerance (or tachyphylaxis) is usually only partial, it may present a management dilemma for athletes who use ß-2 agonists to prevent EIB. Ideally athletes should use ß-2 agonists infrequently, but this may not be appropriate for those who train every day. 

Other than avoiding frequent ß-2 agonist use, there are no known ways to prevent tolerance. It occurs with both long-acting and short-acting ß-2 agonists. Tolerance is neither prevented by inhaled corticosteroid treatment nor overcome by using a higher dose of ß-2 agonist. However, adequate anti-inflammatory treatment may help to reduce  the severity of EIB and thereby reduce the need for additional ß-2 agonist.  

Alternative bronchodilators such as the anticholinergics, eg. ipratropium bromide do not prevent EIB in most patients with asthma. In keeping with standard guidelines, it is not recommended that either long-acting ß-2 agonists or regular/frequent use of short-acting ß-2 agonists is relied on as sole therapy for athletes with asthma.

Environmental aspects

Airway function can be affected by exposure to seasonal and perennial allergens in sensitised individuals, dry/cold air, and poor-quality air containing pollutants such as chlorine derivatives in swimming pools, ozone and oxides of nitrogen, and fine and ultrafine PM derived from combustion. The effects may be greater in subjects with asthma than without asthma. Because of the high minute ventilation during exercise, the effects of these exposures may be more marked in athletes than in non-athletes with the development of non-allergic asthma symptoms and bronchoconstriction during or after exercise. A significant part of variability in reported prevalence of EIB between sports is likely a result of environmental influence. The 30-50% prevalence of AHR in cross-country skiers has been attributed to the high minute ventilations achieved and sustained during training and racing in cold/dry ambient conditions.

Recently, attention has been given to the effect of environmental pollutants on asthma and EIB. The high prevalence of EIB identified in the ice rink athletes has been related to inhalation of exhaust fumes from ice resurfacing equipment during training and competition. Current information suggests other associations of exposure to exhaust emissions with changes in allergy prevalence, asthma exacerbations, and increase in the severity of asthma symptoms and medication usage. A likely mechanism for particulate matter (PM) inhalation-induced bronchoconstriction involves increased production of reactive oxygen species that activate 5-lipoxygenase and increase production of leukotrienes. Pulmonary hypertension has been associated with exposure to fine PM (PM2.5) and may be related to the observed decrease in exercise performance in high-emission pollution air. Bronchoconstriction from inhalation of combustion derived particles has been shown to be strongly associated with leukotrienes in human beings with significant falls in FEV1 after 30 minutes of high-intensity exercise while breathing air with a high concentration of ultrafine PM (PM1).

Training as a cause of asthma

The prevalences of asthma, EIB and AHR are increased in elite athletes. For swimmers, this has been attributed to the frequent recommendation for patients with asthma to engage in this sport. 

However, the proportion of elite swimmers who commence swimming because of asthma compared with those who develop asthma and/or AHR after years of intense training is unknown. Several studies in the past decade have suggested that long-term intense endurance training may promote the development of asthma and AHR. Environmental conditions together with the high ventilation required by the intense effort may contribute to this phenomenon. Exposure to chlorinated pools, cold air, allergens or high levels of pollutants may irritate or sensitise the airways. The mechanical stress of extreme breathing on airway epithelial cells may cause release of mediators. The effects of these mediators may be to initiate or increase inflammatory processes in the airways, leading to airway remodelling, variable airway obstruction and AHR.

The changes in lung function and airway responsiveness may be at least partly reversible after cessation of long-term endurance training. More research is needed on how to prevent or minimise the adverse effects of long-term training on the airways, particularly the effects of environmental exposure on airway structure and function.

Why are athletes with asthma successful at the Olympic Games?

Athletes who notified ß-2 agonist use in Sydney and were approved to inhale ß-2 agonists in Salt Lake City, Athens, and Torino won more individual Olympic medals than their counterparts without asthma at each Games (see Figure 3).

The differences were greater in winter athletes than in summer athletes because a greater percentage of winter competitions can be classed as endurance events. Of the 28 summer sports, six – boxing, wrestling, gymnastics, judo, shooting, and weightlifting – award 42% of all individual medals, and none of these can be classed as an endurance sport. 

This raises the intriguing question whether some endurance athletes develop asthma or AHR after achieving success as an elite athlete. There is some evidence that the age of onset of asthma/AHR is unusually high in endurance winter athletes. In addition, the psychology of having a chronic disease and competing at this level may represent an additional training stimulus for the elite athlete.

Inhaled ß-2 agonists are not considered to enhance endurance performance, although oral salbutamol does increase strength. Every medalist is drug-tested after the event, and oral salbutamol is distinguishable from inhaled, a test introduced before the 2000 Olympics.

Conclusion

Elite endurance athletes may develop respiratory symptoms, AHR, and/or asthma as a consequence of their training. To reduce the risk of developing these conditions, athletes and their medical advisors should address specific aspects such as frequency of intense training, especially under adverse environmental and ambient conditions. Elite athletes with asthma and AHR and their medical advisors must adhere to WADA regulations and should be aware of the high likelihood of developing tolerance/tachyphylaxis to ß-2 agonists with regular use. Nevertheless, the treatment of asthma, EIB, and AHR in elite athletes should follow the currently accepted guidelines for these conditions in non-athletes.

Athletes should continue to be required to demonstrate the presence of asthma and EIB or AHR to be approved to inhale ß-2 agonists at the Olympic Games.