Medication Summary
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.
Beta2-Adrenergic Agonists, Short-Acting
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.
Beta2-Adrenergic Agonists, Long-Acting
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.
Mast Cell Stabilizers
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.
Inhaled Corticosteroids
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.
Xanthine Derivatives
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.
Leukotriene Receptor Antagonist
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.
5-lipoxygenase Inhibitor
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.
Adrenergic Agents
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.
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Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.
