Exercise-Induced Asthma

Exercise-induced asthma (EIA) is a condition of respiratory difficulty that is related to histamine release,[1, 2, 3] triggered by aerobic exercise, and lasts several minutes (see Pathophysiology). Causes include medical conditions, environmental factors, and medications (see Etiology).[4]

Symptoms of EIA may resemble those of allergic asthma, or they may be much more vague and go unrecognized, resulting in probable underreporting of the disease (see Clinical Presentation). The optimal treatment for EIA is to prevent the onset of symptoms, and the basis of treatment is with preexercise short-acting β2 -agonist administration.[1] Long-acting β2 -agonists and mast cell stabilizers, as well as antileukotriene drugs have also been shown to be effective (see Treatment and Management).[8, 9]

With proper interventions, the prognosis is excellent for athletes with asthma. Most symptoms can be prevented, and performance should not be limited by EIA with proper treatment (see Prognosis).

Exercise-induced urticaria, or exercise-induced anaphylaxis, is often presumed to be related to EIA, even though this condition is extremely rare and unrelated (see Diagnostic Considerations).

Go to Asthma, Pediatric Asthma, Exercise-Induced Anaphylaxis, Angioedema, and Urticaria for more information on these topics.

The problem with the functional anatomy in exercise-induced asthma (EIA) occurs distal to the glottis, in the lower airway. Bronchoconstriction is involved that is distinguishable from laryngospasm, which can occur in other exercise-related conditions. One such example is the condition known as vocal cord dysfunction in which there is paradoxical narrowing of the vocal cords during inspiration, resulting in stridor that is often misconstrued as audible wheezing.[10, 11] Normally, the vocal cords open with inspiration. (Go to Vocal Cord Dysfunction for more information on this topic.)

EIA usually affects individuals who participate in sports that include an aerobic component. The condition can be seen in any sport, but EIA is much less common in predominantly anaerobic activities. This is likely due to the role of consistent and repetitive air movement through the airways (seen in aerobic sports), which affect airway humidity and temperature. EIA triggers an unknown biochemical and neurochemical pathway, resulting in the bronchospasm, which manifests as the symptoms of the disease.

Although the exact mechanism of EIA is unknown, there are 2 predominant theories as to how the symptom complex is triggered. One is the airway humidity theory, which suggests that air movement through the airway results in relative drying of the airway. This, in turn, is believed to trigger a cascade of events that results in airway edema secondary to hyperemia and increased perfusion in an attempt to combat the drying. The result is bronchospasm.

The other theory is based on airway cooling and assumes that the air movement in the bronchial tree results in a decreased temperature of the bronchi, which may also trigger a hyperemic response in an effort to heat the airway. Again, the result is a spasm in the bronchi.

Many authors believe there may be a combination of the above 2 theories that takes place, but the biochemical or physical pathways that mediate these responses are unclear. Evidence may even exist to support the idea that the resulting cascades are not the inflammatory pathways to which we attribute allergic asthma.

Likewise, certain sports and their environments predispose individuals with asthma to experience EIA. Sports played in cold and dry environments usually result in more symptom manifestation for athletes with this condition. On the other hand, when the environment is warm and humid, the incidence and severity of EIA decrease.

Also see the figure below.

Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.

The causes of EIA can be divided into the categories of medical, environmental, and drug related. Eliminating some causes can diminish—but may not eliminate—the athlete's symptoms. EIA may also exist without the presence of any of these causes.

Medical conditions

Poorly controlled asthma results in increased patient symptoms with exercise. Maximizing control of the patient's baseline asthma, when present, is critical in the treatment of EIA.[1] In addition, poorly controlled allergic rhinitis also results in increased patient symptoms with exercise, and secretions resulting from hay fever can aggravate both allergic asthma and EIA.

Viral, bacterial, and other forms of upper respiratory infections also aggravate the symptoms of EIA. Controlling the secretions of these illnesses, as with allergic rhinitis, can make the EIA symptoms much more tolerable.

Environmental factors

Excess of pollens or other allergens in the air can exacerbate the allergic and exercise-induced forms of asthma. Pollutants in the air are irritants to the airways and can lower the threshold for symptomatic bronchospasm.

The chemicals used in certain sports for environmental maintenance can predispose individuals to wheezing and worsen EIA symptoms. These chemicals include the following:

• Chlorination in pools

• Insecticides and pesticides used to maintain playing fields

• Fertilizers and herbicides used to maintain playing fields

• Paints and other decorative substances to enhance the appearance of playing fields

Asthmogenic agents

Certain medication classifications and specific drugs can provoke or exacerbate bronchial reactivity in EIA, such as the following:

• β-blockers

• Aspirin

• Nonsteroidal anti-inflammatory drugs (NSAIDs)

• Diuretics

• Zanamivir

EIA affects 12-15% of the population. Ninety percent of asthmatic individuals and 35-45% of people with allergic rhinitis experience EIA, but even when those with rhinitis and allergic asthma are excluded, a 3-10% incidence of EIA is seen in the general population.[3, 12]

EIA seems to be more prevalent in some winter or cold-weather sports.[13] Some studies have demonstrated rates as high as 35% or even 50% in competitive-caliber figure skaters, ice hockey players, and cross-country skiers.[14, 6]

An observational cohort study of 149 pediatric asthma patients found that exercise-induced bronchoconstriction was present in 52.5% of these children.[15]  

The prognosis is excellent for athletes with asthma. With proper interventions, most symptoms can be prevented, and performance should not be limited by EIA if this condition is treated properly. Newly diagnosed young athletes need to be educated that this condition should not be perceived as an insurmountable disability. Using examples of the numerous elite athletes (eg, Jackie Joyner-Kersee [track and field Olympian]; Amy Van Dyken [Olympic swimmer]; Jerome Bettis [former running back for the Pittsburgh Steelers]) with this condition can help young impressionable athletes continue in their endeavors without fear of failure or medical distress.

Patient education is a critical part of the treatment of EIA. Once the diagnosis is made, athletes should be encouraged to continue in their activities with the reassurance that proper treatment can allow for an unhampered performance for most individuals.

In addition to reassurance, it is also important to teach individuals to recognize the signs of an impending attack. Once recognized, individuals should be taught to remove themselves from the aggravating activity and initiate treatment as necessary. This includes education about the proper choice of agents to abort an acute attack (ie, albuterol), but not cromolyn, salmeterol, or an inhaled steroid.

Teaching the proper mechanics of inhalant medication administration is also important, along with, if needed, teaching and demonstrating the proper use of a spacer device to the patient; without the proper mechanics in using such devices, the medication does not reach the area of pathology and does not benefit the athlete.

Education of the coaching staff is also crucial, because coaches need to know that shortness of breath in athletes does not always indicate poor conditioning and that the consequences of ignoring an asthma attack can be serious.

For patient education information, see the Asthma Center, as well as Asthma, Asthma FAQ, and Exercise-Induced Asthma.

Patients with exercise-induced asthma (EIA) usually present complaining of exercise-related respiratory symptoms. This complaint is much more common among children and younger athletes but can be seen at any age.

Symptoms during or following exercise include the following[1, 3, 16] :

• Chest tightness or pain

• Cough

• Shortness of breath

• Wheezing

• Underperformance or poor performance on the field of play

• Fatigue

• Prolonged recovery time

• Gastrointestinal (GI) discomfort

The following factors may cause patients to deny symptoms:

• Peer pressure

• Embarrassment

• Fear of losing position on the team

• Misinterpretation as postexercise fatigue

Factors contributing to EIA consist of the following:

• Cool temperatures

• Low-humidity environment

• Poor air quality

• High pollen counts

• Coincident respiratory infection

• Poor physical conditioning

Exercise factors can include the following:

• Aerobic exercise appears to be much more problematic than anaerobic exercise.

• Duration of aerobic activity greater than 8-10 minutes provokes EIA.

• High-intensity aerobic exercise also provokes EIA.

Weiler et al conducted a systematic review of the literature that evaluated the accuracy of exercise-induced bronchoconstriction (EIB) screening questionnaires that might be adopted for widespread EIB screening in the general population. Results of this review indicated that no existing EIB screening questionnaire had adequate sensitivity and specificity for this purpose.[17]

The patient's physical examination is often unremarkable in the clinical setting; a higher yield is obtained on the field or after an exercise challenge.[5] Exercise challenge, for the purpose of the physical examination, may be informal. For example, the clinician may have the athlete come to the office wearing athletic clothing and run on a treadmill or around the parking lot for 10 minutes, which is then followed by another pulmonary examination.

The physical examination should include the following areas:

• Skin - Note any signs of atopic disease.

• Head, ears, eyes, nose, and throat - Note any evidence of acute infection, chronic infection, and/or allergic/atopic disease.

• Pharynx - Note any mucus, cobblestoning, and/or erythema.

• Nose - Note the presence of enlarged turbinates, erythema, and/or congestion.

• Sinuses - Note the presence of tenderness.

• Lungs - Note the presence of rales, rhonchi, wheezes, and/or a prolonged expiratory phase.

• Heart - Note the presence of murmurs and/or an irregular rhythm.

There is a time interval between sessions of aerobic exercise. This interval includes the refractory and late-phases.

Refractory phase

The refractory phase starts less than 1 hour after the initial aerobic exercise and lasts up to 3 hours. This phase is unpredictable and intermittent and results in as little as one half the degree of bronchospasm as in the first episode. The warm-up period can be used in an attempt to ensure that competition occurs during this refractory phase.

The mechanism is unknown but is believed to involve the following possibilities: depletion of mast cell mediators, release of endogenous catecholamines, and release of endogenous protective prostaglandins.

Late-phase response

This phase occurs 3-9 hours after the initial exercise challenge, and unlike the refractory phase, the late phase manifests as an increase in symptoms, with cough, wheezing, or shortness of breath. This response is much more common in children, usually less severe than the early response, and more likely to occur if severe early exercise-induced bronchospasm (EIB) is present.

The common pitfalls in asthma occur with downplaying of symptoms or patient complaints. Complications of an untreated asthma attack include progression to status asthmaticus, respiratory failure, and even death. More commonly, an anxiety attack can be precipitated secondary to dyspnea.

In general, exercise-induced asthma (EIA) is diagnosed clinically and may not need any further laboratory studies, imaging studies, or other tests and procedures. Laboratory evaluation is reserved for equivocal cases, for treatment failures, and to narrow the differential diagnosis when it seems reasonable. Testing may then be appropriate to differentiate EIA from cardiac conditions, vocal cord and upper airway obstructive conditions, allergic conditions, and psychiatric conditions when these are strongly considered in the differential diagnosis.

Imaging studies are often not indicated in the evaluation of routine EIA, but they may be useful for evaluating other possibilities in the differential diagnosis.

A complete blood cell count and differential can help in the assessment of the likelihood of infection by analysis of the patient's white blood cells and by evaluation of the eosinophil counts (for allergy).

Assessing the immunoglobulin E (IgE) level helps in determining the likelihood of allergic disease. If the diagnosis is uncertain, performing a nasal swab for the presence of eosinophils is helpful in identifying the role of allergic rhinitis.

Skin allergen testing or a radioallergosorbent test (RAST) can be used to help identify specific allergens to promote patient avoidance or immunotherapy, if indicated. Either method has been used extensively in atopic workups. In young children, RAST testing may be preferable, owing to the relative ease of administration, but this is a less specific test, and therefore, skin testing may be preferred in general.

An erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) may help in the evaluation of inflammatory and infectious conditions. Sputum analysis and culture can be used to help identify the presence of infection and treatment options for strains of resistant organisms.

Thyrotropin levels can be used to help evaluate the potential of patient thyroid dysfunction in the likelihood that anxiety is mimicking the symptoms of asthma.

Chest radiography is used to evaluate for signs of chronic lung disease (eg, hyperexpansion, scarring, fibrosis, hilar adenopathy), for congestive heart failure and/or valvular heart disease (eg, chamber enlargement, pulmonary edema, vascular or valvular calcification), and for a foreign body. Lateral neck radiographs/soft-tissue penetration can also evaluate the upper airway for a foreign body or obstruction

Go to Imaging in Asthma for complete information on this topic.

Echocardiography may be used to evaluate for cardiac valvular abnormality or global contractile function, as well as dysrhythmia, cardiomegaly, or other heart disease that may manifest during exercise.

Laryngoscopy can be performed to evaluate for foreign body or other obstruction in the upper airway. Postexercise laryngoscopy can be used to evaluate for vocal cord dysfunction, a condition often mistaken for EIA. Vocal cord dysfunction manifests as stridor with exercise due to paradoxical contraction of the vocal cords with inspiration; this condition can be evaluated via laryngoscopy after an exercise challenge.

Various challenge tests exist that can be used to formalize the diagnosis of EIA. A formal diagnosis is often not critical, clinically, but in recent years, the US Olympic Committee (USOC) has required a positive challenge test to be documented for an athlete to qualify for the use of controlled substances that aid in ameliorating the symptoms of EIA. This requirement has resulted in new studies that have been used to validate some of these assessment tools, whether they are field challenges, treadmill testing, or new techniques such as eucapnic voluntary hyperventilation (EVH).[6, 5, 7] At present, the USOC requires EIA to be diagnosed via EVH in order for preventive and treatment-related medications to be used in competition.

Treadmill exercise challenges with preexercise and postexercise pulmonary functions

This type of testing formalizes an aerobic challenge and provides an objective measure of the degree of bronchospasm that results from the exercise. The results can help the physician to clarify the diagnosis and to enforce the treatment; the results can also be used to evaluate success of the treatment.

Before the exercise challenge, the patient's baseline pulmonary function levels should be obtained (preferably forced expiratory volume in 1 second [FEV1]; forced vital capacity [FVC], or FEV1/FVC; or, less ideally, peak expiratory flow rate [PEFR]). The exercise challenge involves exercising the athlete on a treadmill until his or her heart rate reaches 70-85% of the maximum predicted heart rate. This is maintained for 6-10 minutes, at which time the exercise is stopped. Pulmonary function levels are measured every 2-10 minutes for 15-30 minutes and then compared with the baseline measurements.

Any drop from the baseline that is greater than or equal to 10%, on any postexercise measurement, indicates EIA. Severity of disease can be classified as follows:

• Mild - Decrease of 10-20% from baseline

• Moderate - Decrease of 20-40% from baseline

• Severe - Decrease of greater than 40% from baseline

Informal exercise challenge

An informal exercise challenge can be substituted for the above procedure, but without monitoring the heart rate, the level of work is not reliable.

Pulmonary function testing

Pulmonary function testing can be used to evaluate baseline pulmonary function or allergic asthma and to categorize pulmonary function as obstructive or restrictive disease.

Bronchoprovocation testing

Bronchoprovocation testing, as used with general asthma, methacholine, histamine, or cold air challenges, can be used to assess asthma. However, if the results are positive, they are indicative of asthma in general, not specifically EIA.

A study of 46 children with exercise-induced asthma-like symptoms reported that a combination of the methacholine test, followed by the mannitol test, gives the highest return to identify bronchial hyper-responsiveness in children for the diagnosis of exercise-induced asthma or bronchospasm. The combination of methacholine test and mannitol tests detected bronchial hyper-responsiveness in all of the children in whom bronchial hyper-responsiveness (BHR) was found (93.5% of all the children) compared to the exercise challenge testing which detected BHR in 23.90%, the bronchodilator testing which detected BHR in 21.7%, mannitol testing which detected BHR in 80% and methacholine testing which detected BHR 91%.[19, 20]

Eucapnic voluntary hyperventilation

Eucapnic voluntary hyperventilation (EVH) is a technique believed to be more sensitive and more accurate for diagnosing EIA.[6, 7] Furthermore, EVH can be applied in a laboratory setting and altered to mimic the environmental conditions of the sport in question.

Go to Peak Flow Rate Measurement for complete information on this topic.

The optimal treatment for EIA is to prevent the onset of symptoms. After controlling the patient's underlying and contributing factors (eg, respiratory infection, allergy, allergic asthma), a combination of drugs can be used to prevent EIA.[1] The basis of treatment is with preexercise short-acting β2 -agonist administration.[1] A role also exists for long-acting β2 -agonists and mast cell stabilizers. Antileukotriene drugs have been shown to be effective as well (see Medications).[8, 9]

Although rare, as with any asthma attack, progression of exercise-induced asthma (EIA) can result in status asthmaticus and even death. Treatment for this condition should be provided immediately and the situation taken seriously.

Go to Asthma, Pediatric Asthma, Exercise-Induced Anaphylaxis, Angioedema, and Urticaria for more information on these topics.

Treatment of the athlete who is experiencing an acute attack of EIA is the same as in any asthma attack situation and includes immediately removing the patient from competition or play.

Provide immediate administration of a rapid onset, short-acting β2 -agonist (eg, albuterol); this has the highest therapeutic yield. The usual dose is 2 puffs of albuterol via a metered dose inhaler (MDI). If the patient's response is not satisfactory, transportation to an emergency facility should be initiated, because the EIA attack may escalate. If available, the use of a spacer device can help to transport the medication to the area of greatest need, especially when an athlete is distracted in the midst of competition or anxious from dyspnea and unable to concentrate.

If the initial response to treatment was adequate, patient observation and monitoring need to continue for several hours in case of a relapse. If mild, residual symptoms persist in the patient after relief of the acute symptoms, a repeat administration of albuterol is advisable; the recommended dosing interval is 4 hours.

If the initial treatment fails or is unavailable, or if patient relapse is immediate, immediate transfer of the patient to an acute care facility should occur. Subcutaneous epinephrine can be administered in such life-threatening situations.

On the playing field, consultation is rarely available and is not needed in the acute EIA attack; however, access to the emergency medical system should be readily available.

Sports selection and altering breathing and/or warm-up techniques are measures can also be taken in the treatment of EIA.

Sports selection can be helpful in guiding an athlete toward the performance of sports in environments that are less likely to cause bronchospasm. In addition, if the athlete has a choice, he or she can choose a time or place to exercise where the air is warmer and the humidity is higher. Likewise, a flexible athlete can change sports to be more active in these sorts of environments (eg, changing from running to swimming automatically increases the humidity of the environment). As indicated in Pathophysiology above, focusing on sports with less prolonged aerobic demands (eg, sprinting, weight lifting, baseball, football) is better tolerated by affected athletes.

An example of altering breathing techniques is changing from predominant mouth breathing to nasal breathing, which can result in less bronchospasm with the performance of an activity, because the inhaled air is both warmed and humidified.

The coordination and timing of competition with medication use can also maximize exercise performance with regard to bronchospasm. To minimize the likelihood of bronchospasms, the athlete can time the warm-up so that the competition coincides with a refractory phase (see Phases of EIA above). This is most likely to occur by initiating a 15-30 minute warm-up, followed by a 15-minute rest period, at which time the medication is administered. This entire period should be timed to result in commencement of the competition 15-30 minutes after medication administration.

The severity of an EIA attack varies greatly. Although cases of respiratory arrest and even death have been reported, the usual scenario is of a mild respiratory difficulty during play, which either spontaneously resolves or immediately responds to inhaled albuterol. Oftentimes, the athlete self-medicates and never leaves play or alerts the trainer or doctor.

Although no clear-cut guidelines exist, a player who is removed from play for an asthma attack should be kept out of play until his or her respiration has normalized. This should occur within 5-10 minutes of medication administration. The athlete should be monitored closely for signs of relapse over the next several hours. If the symptoms do not completely resolve with sideline medication, the athlete should not return to play and should be referred for further treatment. Depending on the severity of the patient's symptoms, this may require transportation via ambulance.

American Thoracic Society guidelines for exercise-induced bronchoconstriction

The American Thoracic Society has developed new evidence-based practice guidelines for individuals with exercise-induced bronchoconstriction. These guidelines address its diagnosis, management, and environmental triggers, as well as considerations in elite athletes.[21]

The recommendations in managing exercise-induced bronchoconstriction include the following:

• Preexercise administration of an inhaled short-acting beta-agonist (SABA) (about 15 minutes before exercise)

• Use of a daily inhaled corticosteroid, a daily leukotriene receptor antagonist, or a mast cell stabilizing agent before exercise for patients who continue to exhibit symptoms despite administration of SABA therapy or who require daily or more frequent SABA use

• Interval or combination warm-up exercise before planned exercise for all patients with exercise-induced bronchoconstriction

Daily use of an inhaled long-acting beta-agonist (LABA) or an inhaled corticosteroid is not recommended as monotherapy in patients with symptoms despite SABA therapy or in patients who require daily or more frequent SABA use.[21]

Traditional asthma medications (eg, corticosteroids, theophylline) have less of a role in the treatment of pure exercise-induced asthma (EIA). There is ongoing investigation regarding other agents (eg, heparin, calcium-channel blockers, diuretics).

As discussed earlier, the optimal treatment for exercise-induced asthma (EIA) is to prevent the onset of symptoms. The basis of treatment is with preexercise short-acting β2-agonist administration.[1] Long-acting β2-agonists, mast cell stabilizers, and antileukotriene drugs also have a role.[8, 9]

A study by Stelmach et al found that monotherapy with ciclesonide 320 microgram can be as successful as ciclesonide 160 microgram daily combined with either a leukotriene receptor antagonist or with a long-acting beta-agonist.[22]

In December 2018, FDA approved ProAir Digihaler (albuterol), the first digital and mobile-connected inhaler. The built-in sensors detects when the device is used and measures the strength of the user’s inhalation. The inhaler sends the user’s data to its mobile app companion and their healthcare provider.[23]

Go to Use of Metered Dose Inhalers, Spacers, and Nebulizers for complete information on this topic.

Special Patient Considerations

Although most of the commonly used drugs to treat EIA are in pregnancy category C, these agents are often used for asthma, which is a common condition of pregnancy. Another issue to consider is that many of the agents used for asthma are not indicated for children younger than 2 years; other agents are not indicated for children younger than 6 years. However, these medications have been used successfully for decades in the management of childhood asthma.

Class Summary

These agents are used for prophylactic bronchodilation to prevent the onset of symptoms with exercise and have been shown to have a 90% efficacy.

Albuterol (AccuNeb, Proventil HFA, Ventolin HFA, ProAir HFA, ProAir RespiClick, ProAir Digihaler)

Albuterol is the drug of choice and first-line agent in the treatment of EIA. It is a β2-agonist used to treat bronchospasm that is refractory to epinephrine by relaxing bronchial smooth muscle via action on β2-receptors. This agent has little effect on cardiac muscle contractility.

Levalbuterol (Xopenex, Xopenex HFA)

Levalbuterol is a β-agonist for bronchospasm. It relaxes bronchial smooth muscles by action on β2 receptors, with little effect on cardiac muscle contractility.

Class Summary

Long-acting β-agonists have a greater selectivity for the β2 adrenoreceptors than the short-acting agents. These agents cause bronchial smooth muscle relaxation with little effect on cardiac muscle contractility.

Salmeterol (Serevent)

Salmeterol is FDA approved for the prevention of exercise-induced bronchospasms. This agent can relieve bronchospasms by relaxing the smooth muscles of the bronchioles in conditions that are associated with bronchitis, emphysema, asthma, or bronchiectasis. The effect may also facilitate expectoration. Adverse effects are more likely to occur when this agent is administered at high or more frequent doses than recommended; the incidence of side effects is then higher.

Class Summary

These agents are 70-80% effective in preventing bronchospasm during exercise. An additive effect is noted when used in combination with albuterol.

Cromolyn sodium (NasalCrom)

Cromolyn sodium is a first- or second-line agent in the prevention of EIA but should not be used as rescue therapy for acute bronchospasm. In addition, avoid use of cromolyn sodium with isoproterenol during pregnancy.

Class Summary

These agents provide no bronchodilatory effect but are useful in controlling the underlying inflammation of allergic asthma.

Beclomethasone dipropionate (QVAR Redihaler)

Beclomethasone dipropionate inhibits bronchoconstriction mechanisms and produces direct smooth muscle relaxation. It may decrease number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. As with other agents in this class, beclomethasone dipropionate is also considered a third-line agent.

Ciclesonide (Alvesco)

Ciclesonide is an aerosol inhaled corticosteroid indicated for maintenance treatment of asthma as prophylactic therapy. It is not indicated for relief of acute bronchospasm. Corticosteroids have wide range of effects on multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (eg, histamines, eicosanoids, leukotrienes, cytokines) involved in inflammation. Individual patients experience a variable time to onset and degree of symptom relief.

Fluticasone (Flovent HFA, Flovent Diskus)

Fluticasone inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and decreases the number and activity of inflammatory cells, in turn decreasing airway hyper-responsiveness. It also has vasoconstrictive activity.

Budesonide (Pulmicort Flexhaler)

Budesonide inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and decreases the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It has extremely potent vasoconstrictive and anti-inflammatory activity. It alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing the production of cytokines and other mediators. It also decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.

Class Summary

Xanthine derivatives have been used in allergic asthma for their bronchodilatory and anti-inflammatory properties; however, these agents have multiple side effects. Therefore, monitoring for nontoxic levels is necessary. Traditional asthma medications such as theophylline have less of a role in the treatment of pure exercise-induced asthma.

Theophylline (Theo-24)

Theophylline potentiates exogenous catecholamines and stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which in turn stimulates bronchodilation. However, near-toxic levels (>20 mg/dL) are usually required.

Class Summary

Leukotriene receptor antagonists can be used as adjuncts in cases of incompletely controlled EIA with the use of other agents; however, leukotriene receptor antagonists should be reserved for more frequent and persistent cases of EIA rather than for intermittent cases. Leukotriene receptor antagonists should not to be used alone for the treatment of EIA.

Zafirlukast (Accolate)

Zafirlukast is a third-line agent that is used only as an adjunct. This agent inhibits effects by the leukotriene receptor, which has been associated with asthma, including airway edema, smooth muscle contraction, and cellular activity associated with the symptoms.

Montelukast (Singulair)

Like zafirlukast, montelukast is a third-line agent and is used only as an adjunct. This agent inhibits the leukotriene receptor effects associated with asthma, including airway edema, smooth muscle contraction, and cellular activity associated with the symptoms. In addition, European studies suggest an improvement in gas exchange versus β2-agonist medication.

Class Summary

5-Lipoxygenase inhibitors such as zileuton are indicated for the prophylaxis and long-term treatment of asthma in children and adults.

Zileuton (Zyflo CR)

Zileuton selectively inhibits 5-lipoxygenase and inhibits leukotriene formation, which, in turn, decreases neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, capillary permeability, and smooth muscle contractions. Zileuton is a third-line agent and is used only as an adjunct.

Class Summary

Adrenergic agonists are used in the emergency treatment of life-threatening situations, when β-agonists are unavailable, or treatment with β-agonists has failed.

Epinephrine (Adrenalin, EpiPen, Primatene Mist)

Epinephrine is indicated in the emergency treatment of bronchospasm. This medication has α-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. β-agonist effects of epinephrine include bronchodilation, chronotropic cardiac activity, and positive inotropic effects.