Exercise-Induced Bronchoconstriction: Diagnosis and Management

MICHAEL A. KRAFCZYK; CHAD A. ASPLUND

MICHAEL A. KRAFCZYK, MD, AND CHAD A. ASPLUND, MD

Am Fam Physician. 2011;84(4):427-434

Patient information: See related handout on exercise-induced wheezing, written by the authors of this article.

Author disclosure: No relevant financial affiliations to disclose.

Exercise-induced bronchoconstriction describes the narrowing of the airway that occurs with exercise. More than 10 percent of the general population and up to 90 percent of persons previously diagnosed with asthma have exercise-induced bronchoconstriction. Common symptoms include coughing, wheezing, and chest tightness with exercise; however, many athletes will present with nonspecific symptoms, such as fatigue and impaired performance. Spirometry should be performed initially to evaluate for underlying chronic asthma, although results are often normal. An empiric trial of short-acting beta₂ agonists or additional bronchial provocation testing may be necessary to confirm the diagnosis. Nonpharmacologic treatment options include avoiding known triggers, choosing sports with low minute ventilation, warming up before exercising, and wearing a heat exchange mask in cold weather. Short-acting beta₂ agonists are recommended first-line agents for pharmacologic treatment, although leukotriene receptor antagonists or inhaled corticosteroids with or without long-acting beta₂ agonists may be needed in refractory cases. If symptoms persist despite treatment, alternative diagnoses such as cardiac or other pulmonary etiologies, vocal cord dysfunction, or anxiety should be considered.

Exercise-induced bronchoconstriction (EIB) is a common problem in physically active persons. EIB is defined as transient, reversible bronchoconstriction that happens during or after strenuous exercise. It can occur in persons with or without underlying asthma.¹ Bronchoconstriction that is triggered by exercise in persons with underlying asthma is considered exercise-induced asthma. This article discusses the diagnosis and management of EIB in persons without underlying asthma. The National Asthma Education and Prevention Program also provides guidelines for the diagnosis and management of asthma.² SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation	Evidence rating	References	Comments
Self-reported symptoms alone should not be used to diagnose EIB.	C	^6–8	—
The exercise challenge test can accurately diagnose EIB.	C	⁹	Varying results because of differences in how the test is performed
Warming up before exercise may reduce the degree of EIB.	B	², ¹⁴	—
Wearing a heat exchange mask over the mouth and nose during cold-weather exercise may reduce symptoms of EIB.	B	², ¹⁶	—
Inhaled short-acting beta₂ agonist use before exercise can attenuate symptoms of EIB.	A	², ¹⁴, ²¹	—
Using inhaled corticosteroids as controller therapy is an effective management strategy for EIB in patients with underlying asthma.	A	², ¹⁴, ²⁵	—
Leukotriene receptor antagonist therapy can effectively manage EIB.	A	¹⁴, ²⁶, ²⁹	—

EIB = exercise-induced bronchoconstriction.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.xml.

Epidemiology and Etiology

EIB is more common in persons who participate in endurance sports and sports that require high minute ventilation. More than 10 percent of the general population and up to 90 percent of persons previously diagnosed with asthma have EIB.³ The prevalence of EIB in athletes ranges from 11 to 50 percent, although it approaches 90 percent in athletes with asthma.³ EIB also commonly occurs in cold-weather athletes and has been found to be present in approximately 50 percent of Olympic cross-country skiers.⁴

In persons without asthma, the rapid breathing of cold, dry air over a prolonged period is an ideal setting for EIB. When a person finishes exercising, the airway responds with vasodilation to warm the airway, resulting in water loss and engorgement of the airways. This process causes bronchoconstriction and the release of proinflammatory mediators. Another possible etiology may be environmental irritants, such as chlorine gas in a swimming pool or gases from ice-resurfacing equipment. Persons with EIB and underlying asthma usually experience exacerbation of underlying inflammation and airway hyperactivity caused by any of these mechanisms or by poorly controlled chronic asthma.⁵

Diagnosis

SYMPTOMS

Typical symptoms of EIB include wheezing, shortness of breath, dyspnea, cough, or chest tightness during or after exercise. These symptoms usually occur during strenuous exercise and peak about five to 10 minutes after exercise. Atypical symptoms include fatigue, feeling out of shape, feeling unable to keep up with peers, and abdominal discomfort. Self-reported symptoms have been shown to be poor predictors of EIB because other conditions, such as vocal cord dysfunction, can cause similar symptoms.^6–8 Therefore, symptoms alone should not be used to diagnose EIB.

The physical examination in patients with EIB is often unremarkable. If patients are evaluated when symptomatic, the most common findings are tachypnea and wheezing during end expiration.

TESTING

In patients with possible EIB, spirometry should be performed to rule out underlying asthma² (Figure 1). Normal resting spirometry results are common in patients with EIB. If spirometry reveals an obstruction, additional testing before and after albuterol use is recommended. Obstruction with reversibility is indicative of underlying chronic persistent asthma.

If the patient is not an elite athlete, the next step is to prescribe an empiric trial of a short-acting beta₂ agonist. Only athletes who participate in high-level competition will need documentation of objective testing to use banned asthma medication. Follow-up, usually after one to two weeks, is necessary to determine whether treatment is successful. If the patient's response to treatment is inadequate, additional testing is warranted.

For elite athletes or for persons with EIB that does not respond to a trial of a short-acting beta₂ agonist, bronchial provocation tests can be used to identify provoked decreases in forced expiratory volume in one second (FEV₁). There are two main types of bronchial provocation tests: direct and indirect. Most pulmonary function laboratories can perform direct challenges, such as methacholine challenge. Some are also equipped to perform indirect challenges, such as an exercise challenge test, which can accurately diagnose EIB.⁹ In addition, indirect challenges can be performed with a handheld spirometer at the location in which the athlete develops symptoms. Direct challenges have a lower sensitivity than indirect challenges¹⁰; therefore, indirect challenge is the preferred diagnostic test for EIB. Examples of indirect testing are listed in Table 1.⁹ If bronchial provocation testing results are normal, other diagnoses should be considered (Table 2¹¹ ).

Test	Description	Advantages	Disadvantages
Eucapnic voluntary hyperpnea test	Patient hyperventilates a mixture of cold, dry air	Sensitive and specific Less laboratory space and equipment needed	Need to control inspired gases and humidity Need to monitor minute ventilation Relatively expensive Not readily available
Eucapnic voluntary hyperpnea test	Spirometry performed before and after hyperventilation
Field-based exercise challenge	Usually performed in the environment that causes symptoms	Sensitive and specific for cold-weather athletes Readily available Minimal equipment Inexpensive	Not standardized Unable to control environment
Field-based exercise challenge	Spirometry performed before and after exercise		Not standardized Unable to control environment
Hypertonic saline test	Patient is given nebulized hypertonic saline	Sensitive and specific Less laboratory space and equipment needed	Not as reliable if patient is already being treated with inhaled corticosteroid
Hypertonic saline test	Spirometry performed before and after nebulization
Laboratory-based exercise challenge	Usually performed on a treadmill or stationary bike	ensitive and specific Standardized	Need to control inspired gases and humidity Need to monitor heart rate and minute ventilation Relatively expensive
Laboratory-based exercise challenge	Spirometry performed before and after exercise	ensitive and specific Standardized

Management

EIB can affect many aspects of a patient's life, regardless of the severity of symptoms. The main goal of treatment is to allow patients to exercise safely. Secondary goals should include keeping athletes of all levels active and helping competitive athletes maximize performance. Asthma symptoms in association with exercise have been shown to reduce health-related quality of life scores in adolescents.¹² One report found that among asthma-related deaths during exercise, many athletes had only mild asthma.¹³

NONPHARMACOLOGIC TREATMENT

Several nonpharmacologic options exist for managing EIB. Basic measures include avoiding known triggers (allergen and environmental) and choosing sports with low minute ventilation (short bursts of exercise), such as football, baseball, wrestling, or sprinting. Although nonpharmacologic treatment options can be effective, all athletes with EIB need to have a short-acting beta₂ agonist available.

Preexercise Warm-up. There is some evidence that a preexercise interval warm-up may attenuate the bronchoconstriction associated with EIB by inducing a refractory period.^2,14 However, this has not been shown to be helpful in elite cold-weather athletes.¹⁵

Heat Exchange Mask. Heat exchange masks are designed to limit cold air exposure during exercise in athletes with EIB. They typically can be found in running stores or online. Using a mask has not been shown to be as effective as pretreatment albuterol in the prevention of bronchoconstriction.^2,16 One of the main limitations of a heat exchange mask is that it may not be practical during competition.

Nutrition. A review of the literature suggests that restricting dietary sodium intake for one to two weeks may reduce bronchoconstriction after exercise in patients with asthma and EIB; however, long-term studies are lacking.¹⁷ Additionally, a small, double-blind crossover study showed that high-dose omega-3 fish oil supplementation for three weeks reduced the use of bronchodilators in the treatment group. The limitations of this study included the small size and no mention of adverse effects from the high dosage of omega-3 fish oil.¹⁸

PHARMACOLOGIC TREATMENT

Medication is the mainstay of treatment for persons with EIB (Table 3^19,20 ). Although pharmacologic treatment has been well studied, more research is needed to differentiate between optimal treatment of persons who have EIB with underlying asthma and those who have EIB without asthma.

Medication	Dosage	Onset of action	Duration	Comments	Cost of generic (brand)*
Short-acting beta₂agonists
Albuterol	90 mcg per spray; two puffs 15 minutes before exercise and as needed	Five to seven minutes	Three to six hours	First-line prevention of acute asthma	90 mcg per actuation, 17-g inhaler: $29 to $58 (NA) †
Levalbuterol (Xopenex HFA)	45 mcg per spray; two puffs 15 minutes before exercise and as needed	Five to 10 minutes	Three to six hours	First-line prevention of acute asthma; similar to albuterol in safety and effectiveness, but more expensive	Box of 24
						1.25 mg per 3 mL vials: NA ($123)
						0.63 mg per 3 mL vials: NA ($136)
						0.31 mg per 3 mL vials: NA ($121)
Pirbuterol (Maxair)	200 mcg per spray; one or two puffs 15 minutes before exercise and as needed	Five minutes	Five hours	First-line prevention of acute asthma; not available as generic; more expensive than albuterol	200 mcg per actuation, 14-g inhaler: NA ($146)
Long-acting beta₂agonists
Formoterol (Foradil Aerolizer); combination budesonide/formoterol (Symbicort)	Aerolizer: 12 mcg per capsule; one spray twice per day	One to three minutes	12 hours	Second-line prevention of chronic asthma in conjunction with inhaled corticosteroid	Aerosol: 60 12-mcg capsules: NA ($176)
	Metered-dose inhaler: 4.5 mcg per spray; two puffs twice per day				Inhaler
						80/4.5 mcg per actuation aerosol, 10.2-g inhaler: NA ($196)
						160/4.5 mcg per actuation aerosol, 10.2-g inhaler: NA ($230)
Salmeterol (Serevent Diskus); combination fluticasone/salmeterol (Advair Diskus or HFA)	Diskus: 50 mcg per blister; one puff twice per day	30 to 48 minutes	12 hours	Second-line prevention of chronic asthma in conjunction with inhaled corticosteroid	Serevent Diskus (60 doses)
						50 mcg per dose powder inhaler: NA ($178)
					Advair Diskus (60 doses)
						100/50 mcg per dose aerosol: NA ($186)
						250/50 mcg per dose aerosol: NA ($216)
						500/50 mcg per dose aerosol: NA ($286)
	HFA: 21 mcg per puff; two puffs twice per day				Advair HFA
						45/21 mcg per actuation aerosol, 12-g inhaler: NA ($198)
						115/21 mcg per actuation aerosol, 12-g inhaler: NA ($231)
						230/21 mcg per actuation aerosol, 12-g inhaler: NA ($296)
Mast cell stabilizers
Cromolyn (nebulizer solution)	20 mg per 2 mL; 20 mg taken 10 to 60 minutes before exercise or 20 mg four times per day	Less than one week	Unknown	Second-line prevention of chronic asthma	120 vials: 20 mg per 2 mL: $190 (NA)
Inhaled corticosteroids
Beclomethasone (QVAR)	40 or 80 mcg per spray; one to four puffs twice per day	One week	Variable	Second-line prevention of chronic asthma	40 mcg per actuation, 8.7-g inhaler: NA ($110)
Beclomethasone (QVAR)	40 or 80 mcg per spray; one to four puffs twice per day	One week	Variable	Second-line prevention of chronic asthma	80 mcg per actuation, 8.7-g inhaler: NA ($132)
Budesonide (Pulmicort Flexhaler)	90 or 180 mcg per spray; two puffs twice per day	One week	Variable	Second-line prevention of chronic asthma	90 mcg per actuation aerosol inhaler: NA ($122)
Budesonide (Pulmicort Flexhaler)	90 or 180 mcg per spray; two puffs twice per day	One week	Variable	Second-line prevention of chronic asthma	180 mcg per actuation aerosol inhaler: NA ($160)
Ciclesonide (Alvesco)	80 or 160 mcg per spray; one or two puffs twice per day	One week	Variable	Second-line prevention of chronic asthma	80 mcg per actuation aerosol, 6.1-g inhaler: NA ($166)
Ciclesonide (Alvesco)	80 or 160 mcg per spray; one or two puffs twice per day	One week	Variable	Second-line prevention of chronic asthma	160 mcg per actuation aerosol, 6.1-g inhaler: NA ($167)
Flunisolide	250 mcg per spray; one or two puffs twice per day	One week	Variable	Second-line prevention of chronic asthma	250 mcg per actuation aerosol, 7-g inhaler: NA ($98)
Fluticasone (Flovent Diskus or HFA)	Diskus: 50, 100, or 250 mcg per blister; one or two puffs twice per day	One week	Variable	Second-line prevention of chronic asthma	Diskus (60 doses)
						50 mcg per blister aerosol inhaler: NA ($115)
						100 mcg per blister aerosol inhaler: NA ($116)
						250 mcg per blister aerosol inhaler: NA ($155)
	HFA: 44, 110, or 220 mcg per spray; two puffs twice per day				HFA
						44 mcg per actuation aerosol, 10.6-g inhaler: NA ($120)
						110 mcg per actuation aerosol, 12-g inhaler: NA ($153)
						220 mcg per actuation aerosol, 12-g inhaler: NA ($247)
Mometasone (Asmanex)	110 or 220 mcg per spray; one or two puffs, divided, once or twice per day	One week	Variable	Second-line prevention of chronic asthma	60 metered doses
Mometasone (Asmanex)		One week	Variable	Second-line prevention of chronic asthma		220 mcg per inhalation aerosol, 0.24-g inhaler: NA ($168)
Leukotriene receptor antagonists
Montelukast (Singulair)	Six to 14 years of age: 5 mg per day or two hours before exercise 15 years and older: 10 mg per day or two hours before exercise	Two hours	24 hours	Second-line prevention of chronic asthma and allergic rhinitis	30 5-mg tablets: NA ($157)
Montelukast (Singulair)		Two hours	24 hours		30 10-mg tablets: NA ($152)
Zafirlukast (Accolate)	Five to 11 years of age: 10 mg twice per day, one hour before or two hours after meal 12 years and older: 20 mg twice per day, one hour before or two hours after meal	Unknown	12 hours	Second-line prevention of chronic asthma	60 10-mg tablets: NA ($90)
Zafirlukast (Accolate)		Unknown	12 hours	Second-line prevention of chronic asthma	60 20-mg tablets: NA ($90)
Zileuton, extended-release (Zyflo CR)	Older than 12 years: 1,200 mg twice per day	Two hours	12 hours	Second-line prevention of chronic asthma	120 600-mg tablets: NA ($610)
Anticholinergics
Ipratropium (Atrovent HFA)	17 mcg per spray: two to four puffs, 15 to 30 minutes before exercise and as needed	15 minutes	Two to four hours	Third-line prevention of acute asthma	17 mcg per actuation aerosol, 12.9-g inhaler: NA ($172)

Beta₂Agonists. There are two types of inhaled beta₂ agonists: short-acting and long-acting. Short-acting beta₂ agonists are recommended first-line treatment in the management of EIB, preventively and for acute symptoms.^2,14,21 They should be used 15 minutes before exercise, typically have a peak action of 15 to 60 minutes, and last approximately three hours. There is growing concern about the development of tachyphylaxis with daily use of short-acting beta₂ agonists; therefore, they should be used only before more strenuous workouts or before competition.⁵ Although long-acting beta₂ agonists have been shown to be effective in persons with EIB,² the U.S. Food and Drug Administration has recommended that they not be used in persons with asthma unless there is concomitant use of a controller medication, such as inhaled corticosteroids.²² Concurrent use of inhaled corticosteroids and long-acting beta₂ agonists has been shown to be effective and superior to use of inhaled corticosteroids alone in managing EIB.²³

Mast Cell Stabilizers. Mast cell stabilizers have been shown to be more effective than anticholinergics but less effective than short-acting beta₂ agonists for managing EIB.²⁴ Mast cell stabilizers should be used 15 to 20 minutes before exercise. Metered-dose inhalers have been discontinued because they are difficult to manufacture without chlorofluorocarbon propellants; however, cromolyn is still available as a nebulized solution.

Inhaled Corticosteroids. Inhaled corticosteroids are considered controller medications and are the mainstay of treatment in patients with persistent asthma.^2,14 A meta-analysis showed that use of inhaled corticosteroids for four weeks or more reduced the percentage decrease in FEV₁ after exercise.²⁵ There is a paucity of studies comparing inhaled corticosteroids with other treatments for EIB.

Leukotriene Receptor Antagonists. Leukotriene receptor antagonists have been shown to have a persistent benefit against EIB.^14,26 Montelukast (Singulair) has an onset of action within two hours and continued EIB preventive benefit up to 24 hours after a single oral dose.²⁷ Compared with salmeterol (Serevent), montelukast is equally effective at preventing EIB at two hours and at eight and one-half hours, but montelukast is more effective at 24 hours.²¹ Short-acting beta₂ agonists have been shown to be more effective than montelukast in the prevention of EIB.²⁸ Use of montelukast has not been shown to cause tachyphylaxis.²⁹

Other Agents. Ipratropium (Atrovent) is an anticholinergic that provides some protection against EIB but is not as effective as short-acting beta₂ agonists or leukotriene receptor antagonists.¹⁴ Inhaled heparin³⁰ and furosemide³¹ (Lasix) have been shown to be effective for treating EIB, but only small sample sizes have been used in studies.

A Practical Approach to the Patient

Chronic, persistent asthma should be treated according to the National Asthma Education and Prevention Program guidelines.² In athletes with confirmed EIB, a reasonable approach is to start with a short-acting beta₂ agonist before exercise (Figure 1). If regular dosing of a short-acting beta₂ agonist is needed, or if EIB is not controlled with short-acting beta₂ agonists, a second-line agent (e.g., leukotriene receptor antagonist, mast cell stabilizer, inhaled corticosteroid with or without a long-acting beta₂ agonist) can be added. Inhaled corticosteroids and leukotriene receptor antagonists are the preferred agents in persons with underlying asthma. Leukotriene receptor antagonists are preferred in persons with allergic rhinitis. When prescribing medications to high-level athletes (e.g., those who participate in the National Collegiate Athletic Association or the Olympics), physicians should be aware of which medicines require a waiver (Table 4^32,33 ). Patients should be reassessed periodically; if a satisfactory response is not achieved, the diagnosis of EIB should be reconsidered. Table 4.NCAA and USOC Restricted Medications

Medication class	NCAA	USOC
Anticholinergics	Not prohibited	Not prohibited
Inhaled beta₂ agonists	Permitted only by prescription	Salmeterol (Serevent) and albuterol: athletes must declare use
Inhaled beta₂ agonists	Permitted only by prescription	All other inhaled beta₂ agonists: therapeutic use exemption is needed
Inhaled corticosteroids	Not prohibited	Declaration of use required in competition
Leukotriene receptor antagonists	Not prohibited	Not prohibited
Mast cell stabilizers	Not prohibited	Not prohibited

NCAA = National Collegiate Athletic Association; USOC = United States Olympic Committee.

Information from references ³² and ³³ .

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