Exercise Induced Asthma

Exercise-induced asthma (EIA) is described in asthmatics, elite athletes, and the general population alike. Difficulties reconciling the variety of presentations complicate our understanding of the disease process and prevalence.

Exercise-induced bronchospasm (EIB) can be measured during and after exercise in susceptible individuals, but whether this signifies exercise-induced asthma is unclear. Exercise can cause an inflammatory response in the airway that appears to be dose dependent and exaggerated by breathing cold dry air.

Classical understanding of the pathogenesis of exercise-induced asthma suggests that drying of the airway mucosa leading to an osmotic gradient across the epithelium and basement membrane combined with cooling of the bronchial wall triggers bronchospasm in exercise-induced asthma.

Modern investigation suggests that airway surface stress can be communicated to the bronchial wall by chemical signals arising from the epithelium. Managing a patient with exercise-induced asthma requires careful investigation to ensure the correct diagnosis and consideration of alternative disease processes should be made.

Pharmacological intervention can both treat and limit the extent of exercise-induced bronchospasm, but behavioral modifications can also be introduced. Finally, clinicians managing exercise-induced asthma should be aware of the conflicts that arise when regular asthma medications are used by patients engaging in competitive sport.


Increased airway resistance triggered by vigorous exercise is variously called exercise-induced asthma (EIA) or exercise-induced bronchospasm (EIB). Although a consensus exists on the criteria for making a diagnosis of EIB, the range of circumstances in which it has been recognized mean a precise clinical definition of EIA is difficult to achieve. EIB has been described in asthmatics and those with no history of asthma and subjects ranging from school children to elite athletes. It is not clear whether the disease is the same in all cases. While it may be more accurate to reserve the term EIA for exercise-induced, symptomatic bronchial narrowing occurring in previously diagnosed asthma we will use the term broadly to describe asthmatic symptoms or physiological changes consistent with asthma developing during or immediately after exercise.


Exercise-induced asthma is common in known asthmatic subjects and exercise has been recognized as a trigger for ‘asthma’ since the seventeenth century. At least 90% of asthma sufferers will experience a fall in forced expiratory volume (FEV1) or peak flow during or shortly after an appropriate exercise challenge. Some authorities believe that all asthmatics will have demonstrable bronchospasm following sufficient exercise challenge. In atopic patients who suffer only from allergic rhinitis prevalence drops to 40%. Studies of other groups are complicated by the definition of exercise-induced asthma used. For example, comparing the prevalence of exercise-induced bronchospasm, hypersensitivity to methacholine, and self-reported symptoms of exercise-induced asthma consistently identify different groups within a given population. Most of the prevalence data provided are therefore relatively generalized.

Exercise-induced bronchospasm is a useful model for clinical asthma and it has been used as a screening tool. These cohorts are frequently drawn from populations engaged in regular exercise so may not represent a truly unselected population. Based on these studies the prevalence of exercise-induced asthma in the general adult population is estimated at between 6% and 13% and this varies geographically with higher levels in the UK and Australia and lower levels in developing countries. In cohorts of normal school children challenged with exercise then tested by spirometry up to 12% are shown to have exercise-induced asthma. The identification of exercise-induced bronchial narrowing is often a surprise to both child and adult subjects, who may not have been aware of any such problem. A poor perception of airflow restriction is generally recognized in asthma but also casts some doubt on the definition of EIA based on spirometry alone. It is not known if otherwise normal subjects who experience a fall in FEV1 with exercise will benefit from asthma therapy or will go on to develop clinical asthma later in life.

Failure to recognize potentially reversible exercise-induced asthma may not be a trivial matter. Children who suffer distressing symptoms will tend to avoid exercise leading to possible psychosocial and neurological development problems. Similarly, the importance of correct identification of EIA is highlighted by studies demonstrating lower self-esteem scores in children who perceive themselves to be socially disadvantaged by asthma.

A surprisingly high prevalence of exercise-induced asthma is reported in both recreational and elite athletes. Anecdotally, this association has been explained by the focus of some asthmatic children on ventilatory control and on athletic pursuit to achieve this. Whatever the cause, around 23% of recreational athletes report asthma induced by exercise while within the elite ranks prevalence rates of between 16% in summer outdoor events and 50% in winter events such as cross-country skiing or ice skating are reported. While asthmatics frequently state that swimming tends to cause less bronchospasm than other sports, a particularly high prevalence of EIA has been observed in elite swimmers in whom up to 79% have been reported to have demonstrable bronchial hyperresponsiveness to methacholine and 33% have asthma.

The prevalence of exercise-induced asthma reported in elite athletes has raised concern among sporting governing bodies regarding the potential for inappropriate use of performance enhancing medications. As a result a considerable body of research has focused on EIA developing in elite athletes. However, elite athletes are subject to a variety of additional possible triggers of exercise-induced bronchospasm including the stress of competition. Thus, whether this research is equally applicable to recreational athletes or nonathletic sufferers from EIA is not known.

Therefore, it appears that exercise-induced asthma, defined by a fall in FEV1, occurs in a relatively high proportion of the general population. This prevalence is increased by underlying atopy, asthma, and athletic pursuit, particularly outdoor winter endurance events. Accurate assessments of prevalence are hampered by difficulty in definition stemming from the range of possible criteria for diagnosis and the variety of presenting complaints, which will be outlined later. Further difficulties stem from poor perception and variable self-reporting. This difficulty in precise definition has also limited understanding of the pathology underlying exercise-induced asthma.



The normal respiratory responses to exercise result in an increase in ventilation of up to 200 l min1. In order to facilitate the increased airflow, mild bronchodilation occurs early during an exercise event and this can be measured using spirometry. Classically, EIA was described as taking place after the exercise challenge was completed, but it is clear that airway narrowing can occur during exercise lasting more than 12 min and in the postexercise period. The ‘stop–start’ nature of some sporting events means that symptoms developing during exercise are entirely consistent with a diagnosis of EIA. Avariable period of protection from further exercise-induced bronchial narrowing known as the refractory period is well described. A refractory period may last from 30 min to 2 h and may be due in part to the bronchodilator properties of prostaglandin E2 (PGE2).

The cause of exercise-induced asthma and the refractory period are not fully understood; however, considerable evidence points to a cellular response to increased ventilation triggering an inflammatory reaction in the airway. EIA may therefore be considered as a subset of chronic asthma in which exercise is the trigger to inflammation. While this hypothesis is attractive, a variety of studies have produced conflicting data regarding the inflammatory character of EIA.

The three-stage model proposed by R Gotshall serves as a useful framework to consider the pathogenesis of exercise-induced asthma. In this model an exercise challenge serves as a trigger sensed in the airway that ultimately signals to the cells of the airway controlling caliber. Hyperventilation alone can cause bronchoconstriction in human and canine subjects and has been identified as the key element of exercise that triggers EIA. How this trigger leads to bronchoconstriction is a matter of controversy.

Airway Cooling and Hyperosmolarity

In 1864, H H Slater noted that cold air triggered asthma and offered pulmonary vascular congestion as a possible explanation. This theory has been developed by McFadden and others. Airway cooling in response to inspired cold air may trigger vasoconstriction of the bronchial vasculature. Subsequent reflex vasodilation and hyperemia with extravasated fluid leading to mucosal edema could lead to airway narrowing. Although attractive, this theory fails to acknowledge the capacity of the upper airways to warm inspired air such that it is unlikely that cold air is delivered to medium-sized airways, the main site of narrowing in asthma. However, cooling of the airways could take place if evaporation of mucosal water exceeded the replacement capacity of the airway.

Exercise is associated with mouth breathing, which bypasses the humidifying effect of the nasal mucosa, and dry air has been shown to increase the capacity of an exercise challenge to trigger exercise-induced bronchospasm. Evaporation of water from the upper airways might take place as a result of a large increase in ventilation of relatively dry air. This would cause an increase in the osmolarity of the airway mucosa. This concept of airway hyperosmolarity has been developed by Anderson and colleagues and has become popular in current literature. Inhaling hyperosmolar mannitol or saline solutions can trigger bronchospasm in the absence of an exercise stimulus. It has been difficult to separate the specific elements of these two processes and it may be that both are partly responsible for the effect of hyperventilation on the airway in exercise-induced asthma. Since cold air holds less moisture than warm air, this may add to the drying of the airway.

Alternative mechanisms for transducing the proasthmatic stimulus to a bronchoconstrictive response can be postulated. These include stretching of the airway wall cells and altered pressure dynamics of the airway lumen. Ultimately, a signal to alter the diameter of the airway lumen is generated that results in a fall in FEV1. The nature of this signal is also controversial but biochemical mediators associated with inflammation offer a possible explanation.

Inflammation in exercise-induced asthma

It has become clear that an inflammatory process in the airway leads to bronchial hyperresponsiveness and chronic asthma. Exacerbations of asthma can be caused by a variety of inflammatory triggers such as allergen exposure or viral infection. While less intuitive it seems possible that EIA may also have an inflammatory basis. 

Biological markers of inflammation A variety of studies have demonstrated elevated inflammatory cells in the airway lumen and bronchial wall from athletes engaged in a wide spectrum of athletic pursuits. These cells include eosinophils, T lymphocytes, macrophages, and mast cells all of which are recognized as key cellular elements of the asthmatic inflammatory response. Changes in airway inflammatory cell number correlate with changes in bronchial reactivity and some groups have demonstrated that the degree of bronchospasm in response to exercise challenge more closely reflects the level of airway eosinophilia than the prechallenge methacholine sensitivity. Bronchial biopsies taken from resting cross-country skiers demonstrated increased inflammatory cells in the bronchial wall compared to nonathlete controls. Regular exercise may therefore lead to a persistent airway inflammation beyond the acute effects of exercise challenge. Cell-based studies appear to support the role of exercise as a trigger for airway inflammation.

The study of winter athletes described above demonstrated that airway wall inflammation occurred even in the absence of symptomatic exercise-induced bronchospasm. This suggests that airway inflammation is not sufficient to cause exercise-induced asthma and that exercise per se can induce inflammation in normal subjects. Unfortunately, none of these studies offer an explanation for why some athletes are susceptible to the inflammatory effects of exercise while others are not.

Inflammatory cells in the airway are presumed to cause bronchial hyperresponsiveness by the production of chemical mediators of inflammation. A variety of such mediators have been studied in asthma and EIA. Early studies investigating the role of the mast cell stabilizers such as nedcromil and sodium cromoglycate identified histamine as a likely trigger for exercise-induced asthma although this has been challenged recently. The role of other chemical mediators of inflammation including cysteinyl leukotrienes (LTD4 and LTC4) and prostaglandins (PGD2 and PGF2) have been supported by the discovery of increased levels in postexercise plasma and urine and by the effects of specific antagonists.

The role of inflammatory cells and their products in the development of exercise-induced asthma is supported by studies demonstrating the capacity of exercise to increase their availability to airway cells. However, not all investigators have found increased levels of proasthmatic mediators in response to exercise, and the presence of a particular agent does not imply a causal link. Further evidence is available from interventions aimed at reducing airway inflammation.

Do Anti-Inflammatory Therapies Prevent Exercise-induced Ashma?

Inhaled corticosteroids (ICs) are the most widely used airway-delivered anti-inflammatory agents. Among well-controlled asthmatic subjects who use regular ICs to abolish normal symptoms 50% will still experience EIB on testing. This suggests that EIA is relatively resistant to standard doses of inhaled corticosteroid therapy. This hypothesis is supported by early studies demonstrating only a 50% reduction in exercise-induced fall of FEV1 when ICs were introduced. When a short-acting b-adrenergic receptor agonist was added to the IC therapy, this further reduced EIB by 30%, hinting that increased airway resistance in exercise-induced asthma is a complex phenomenon.

The introduction of modern anti-inflammatories has reinforced the theory that exercise-induced asthma is an inflammation- mediated phenomenon. Leukotrienes and in particular LTD4 are regarded as among the most potent proasthmatic inflammatory mediators. Leukotriene receptor antagonists (LTRAs) inhibit the effect of these mediators at their specific receptors. The introduction of LTRAs to common practice suggested that they might have efficacy in treating exercise-induced asthma, a suggestion supported by subsequent examination. LTRA therapy provides a dose-dependent protection from exercise-induced bronchospasm and shortens the time to recovery of FEV1. In contrast antihistamine therapy does not appear to add any further protection over LTRA medication.

Several lines of evidence support the role of inflammatory processes in exercise induced asthma. Exercise can trigger and maintain airway inflammation that is associated with bronchial hyperresponsiveness. Intervention studies show that combating inflammation can improve exercise induced asthma. What is unclear, however, is what predisposes an individual to develop exercise-induced airway inflammation and why otherwise potent antiinflammatory agents are only partially effective in preventing exercise-induced asthma despite improved control in underlying asthma.

Finally, various chemical triggers of asthma have been investigated for their ability to trigger or enhance bronchoconstriction on exercise challenge. Of these adenosine, the product of ATP breakdown, seems worthy of further investigation. Exercise increases circulating adenosine levels suggesting that any proasthmatic activity of this chemical could then be enhanced by exercise. A correlation between the fall in FEV1 following exercise challenge in asthmatic subjects and plasma adenosine levels has been reported. Adenosine is believed to trigger inflammatory cell degranulation, and in the context of asthma this may enhance a mild asthmatic response making it considerably more severe. Such studies may ultimately explain why exercise can be the only trigger for symptomatic exercise-induced asthma in otherwise nonasthmatic subjects.

Integrating the Two Pathogenic Theories

It can be concluded that exercise-induced hyperventilation can trigger physical changes in the airway that are subsequently transduced to an inflammatory signal in the bronchial wall, which can be assumed to lead to bronchoconstriction and possibly chronic inflammation in susceptible people. Can physical changes at the surface of the airway communicate to the bronchial wall to cause inflammation and bronchial hypersensitivity? Evidence for pathways communicating signals between different airway compartments has been accumulating over the last decade, offering possible mechanisms to complete the model. As yet these pathways are untested in the context of exercise-induced asthma but do offer intriguing possibilities.

It is becoming clear that airway epithelial stress can cause the release of inflammatory mediators that promote airway inflammation. Recent research supports the development of an integrated epithelium– mesenchyme complex (the epithelial mesenchymal trophic unit) reminiscent of the embryonic lung. Epithelial monolayers in vitro can trigger inflammatory signals in fibroblasts and smooth muscle cells of the airway supporting such a communication. Inflammatory cells found superficially in the airway, such as eosinophils, can be activated by osmolar stress and release mediators capable of eliciting an asthmatic response offering a more direct line of communication. Thus, drying and cooling of surface epithelium could in theory at least trigger generalized airway inflammation as seen in chronic asthma. The hyperemia following airway rewarming would support an inflammatory process by supplying exudates and inflammatory cells.

Clinical Presentation

Symptoms associated with exercise can arise from a variety of sources including the lungs, heart, and gastrointestinal tract. A careful history can help to identify the most likely source, but exercise induced asthma may present with classical symptoms such as dyspnea, wheeze, and cough or with more obscure symptoms making the diagnosis difficult. Complaints such as headache, abdominal pain, chest pain, cramps, and severe fatigue may all respond to treatment for exercise-induced asthma. Symptoms may develop early during an exercise event or following its completion. The association with exercise should alert the clinician to the possibility of EIA although the complaint may seem unrelated to the lungs. Frequently patients believe they are simply ‘out of condition’ and even well-controlled asthmatics may not associate their exercise-induced symptoms with asthma. EIA can be the only manifestation of hyperresponsive airways so the absence of a formal diagnosis of asthma does not exclude the possibility of exercise-induced asthma.

Differential Diagnosis

Since the diagnosis of exercise-induced asthma is not always straightforward to make a high index of clinical suspicion, it should be combined with an open mind regarding the variety of other potential sources of symptoms. In particular, true vocal cord dysfunction can be difficult to distinguish from EIA when symptoms predominantly present with exercise. A list of alternative diagnoses for exercise-induced dyspnea is presented (Table 4). It is not yet clear if patients who have demonstrable exercise-induced bronchoconstriction but no symptoms will benefit from pharmacological treatment.

Examination of the lungs of a subject with exerciseinduced dyspnea will usually be normal in the context of asthma or lone exercise-induced bronchospasm. The presence of wheeze or hyperinflation might point to chronic airflow obstruction that has gone unrecognized. A full examination might point to an alternative diagnosis as listed. Again quiescent asthma or lone exercise-induced bronchospasm will usually be associated with normal pulmonary function tests while abnormalities may point to alternative pulmonary diagnoses or chronic airflow obstruction.


The need for further investigation will be directed by the clinical findings but may fall into two groups. In the first a pragmatic trial of pharmacological intervention prior to a predictable exercise trigger of symptoms can be the most useful and easiest test. In some cases, however, detailed pulmonary function in response to exercise is desirable either to monitor treatment, to make a difficult diagnosis, or if the presence of exercise-induced asthma would limit the performance of essential life-saving work (American Thoracic Society (ATS) Guideline). Other uses for detailed exercise testing include the diagnosis of asthma in elite athletes for drug monitoring or performance testing.

In a pragmatic trial a patient should be prescribed either a preventative or a reliever inhaled therapy and advised to use this prior to or during exercise that would normally trigger the reported symptoms. Antiinflammatory drugs such as inhaled corticosteroids or cromoglycate have been shown to have some preventative efficacy in this setting. b2-adrenergic agonists have been shown to relieve exercise-induced bronchoconstriction but their efficacy is reduced in exercise-induced bronchospasm. Patients should be able to record the effect of treatment on symptoms or on peak flow with a small degree of training.

Where it is desirable to direct investigations towards a specific diagnosis of exercise-induced asthma, a variety of alternative procedures, ranging from exercise provocation to bronchial challenge, are available. Various procedures have been described that are capable of triggering airway narrowing in asthma consistent with a diagnosis of execise-induced asthma. The principal element of all these tests is to raise minute ventilation as occurs with exercise. It is possible to trigger bronchial narrowing by hyperventilation and this has been recommended as a surrogate for more formal exercise challenge. More exercise specific tests have been developed for both field and laboratory. While testing in the field has the advantage of replicating the conditions that normally trigger asthma in the subject, the equipment required to make useful measurements has to be portable. This has led to the development of protocols designed to measure pulmonary responses to exercise under laboratory conditions that replicate the essential features of outdoor activity. Guidelines recommending the best practice for performing these tests are available, the essential features of which are summarized below.

Patient Instructions

Subjects should avoid bronchoprotective or bronchoreliever medication for 48 h and have eaten only a light meal. Antihistamines and caffeine should also be avoided. Exercise should be kept to a minimum prior to the test, as around 50% of exercise-induced asthma sufferers will experience a refractory period of up to 4 h after vigorous exercise. Any medical or orthopedic contraindications to exercise should be considered and the ability of the patient to fulfill the physiological requirements should be ensured.


Exercise can be performed on an electronic treadmill or stationary bicycle as both methods have been validated. The desired level of exercise is based on 80–90% of maximal heart rate (based on an HR 220 – age) or 50–60% of maximal voluntary ventilation. The degree of exercise required to achieve this level of exercise response will vary considerably among subjects and it is advised that a period of rapid progressive increase in workload is used to achieve these targets and then maintained for at least 4 min. The total exercise time for adults should be around 6– 8min. During the exercise, heart rate and where possible minute ventilation should be measured to ensure that an adequate stimulus to the airway is being achieved.

Climatic Considerations

Outdoor exercises are generally better than indoor exercises at triggering bronchospasm. This is believed to be due to lower humidity and temperature and cool dry air is known to trigger asthma in exercise sensitive subjects better than indoor room air. Maintaining the ambient temperature at 20–251C and relative humidity at 50% is satisfactory. Exercise should be performed with a nose clip to prevent nasal humidification of inspired air.

Severe responses to exercise have been described in susceptible people and it is advisable to have medical supervision available to monitor patients’ responses and administer bronchodilator therapies as required.


FEV1 is the most useful and convenient measurement to make in the laboratory. Where an alternative diagnosis is suspected full flow-volume loops can offer additional information, while peak expiratory flow might be used if field testing is performed. FEV1 should be measured before exercise and following the exercise challenge. Intervals of 5, 10, 15, 20, and 30 min are recommended by the ATS; however, additional measurements can be taken and should be in the event of severe symptoms of bronchial obstruction. Changes in FEV1 can then be observed by plotting percent resting FEV1 against time.

What constitutes a ‘positive’ exercise test is controversial due to the variety of techniques described for measurement. Most authorities consider a fall of more than 10% of resting FEV1 as abnormal especially as the ‘normal’ response to exercise is bronchodilation. Some groups require a greater than 15% fall in FEV1 to diagnose EIA and this appears to be the most frequently quoted value. Plotting the FEV1 against time allows an area under the graph calculation to be made that improves the reliability of the test.

Alternative Testing Procedures

Other techniques to mimic the airway response to exercise have been described. These are generally thought to be more convenient than full exercise challenge, but are necessarily less specific. Osmotic drying of the airway has been achieved by inhalation of mannitol and this method has received some attention from testers from the field of elite sport. Eucapnic hyperventilation achieves a ventilation rate that mimics that achieved by exercise and has also been used as an outpatient measure of the airway responses.


Patients should be encouraged to manage their symptoms rather than stop the exercise activity that triggers it. Occasionally, altering the exercise environment is helpful, for example, changing to indoor from outdoor activity. Some elite athletes have learned to manage their asthma by introducing a targeted warm up to trigger a mild episode of exercise induced asthma and the resultant refractory period elite may allow the completion of the competitive element of the activity. Sporting authorities restrict the use of most inhaled therapeutic agents for asthma. It is sensible for athletes and their coaches to be aware of these restrictions, which can be accessed easily. A range of websites for agencies involved in regulating drugs in sport is given at the end of this article.


Exercise induced asthma may be a specific disease entity in some circumstances or may be the only manifestation of latent asthma. It is common in asthma sufferers and in athletes of all capabilities. The basis for the development and persistence of exercise triggered airway pathology is not fully understood but probably reflects the ability of hyperventilation to trigger airway inflammation. Diagnosis can be complicated by the variety of presentations and detailed investigations are sometimes required. Asthma management is not always successful at controlling symptoms and behavioral changes may have to be made to achieve control of the disease. 

Further Reading

Anderson SD and Brannan JD (2002) Exercise-induced asthma: is there still a case for histamine? Journal of Allergy and Clinical Immunology 109(5): 771–773.

Anderson SD and Daviskas E (2000) The mechanism of exerciseinduced asthma is. Journal of Allergy and Clinical Immunology 106(3): 453–459.

Gotshall RW (2002) Exercise-induced bronchoconstriction. Drugs 62(12): 1725–1739.

Milgrom H (2004) Exercise-induced asthma: ways to wise exercise. Current Opinion in Allergy and Clinical Immunology 4: 147–153.

Seale JP (2003) Science and physicianly practice: are they compatible? Clinical and Experimental Pharmacology and Physiology 30(11): 833–835.

Storms WW (2003) Review of exercise-induced asthma. Medicine and Science in Sports and Exercise 35(9): 1464–1470.

Tan RA and Spector SL (2002) Exercise-induced asthma: diagnosis and management. Annals of Allergy, Asthma, and Immunology 89(3): 226–235.

Relevant Websites

http://www.olympic.org – Home page of the International Olympic Movement, offering insight into the role of antidoping authorities in elite sport. It includes useful links to national Olympic committees detailing specific national guidelines for athletes.

http://www.wada-ama.org Homepage of the world antidoping authority. Including details of the use of prescribed proscribed therapeutics in sport.

http://www.asthma.org.uk Asthma UK link to exercise induced asthma with tips for patients and some general information regarding school and preschool sporting activities for asthma sufferers.