Identifying Exercise-Induced Bronchospasm
Treatment Hinges on Distinguishing It From Chronic Asthma
Christian L. Hermansen, MD; Jeffrey T. Kirchner, DO
THE PHYSICIAN AND SPORTSMEDICINE - VOL 33 - NO. 12 - DECEMBER 2022
In Brief: Exercise-induced bronchospasm (EIB) is an often-undiagnosed but common problem affecting both recreational and elite athletes. Although exercise can trigger exacerbation of chronic asthma, EIB should not be confused with the chronic inflammatory disease. In this article, Drs Hermansen and Kirchner review the incidence, diagnosis, and treatment of EIB and explain how to distinguish EIB from chronic asthma.
EIB is defined as the transient constriction of the airways as a consequence of vigorous exertion. It occurs in about 12% to 15% of the US general population.1 Of patients with chronic asthma, 70% to 90% have an exercise component to their disease.2,3 As many as 40% of patients with allergic rhinitis also have EIB. However, between 5% and 10% of patients with EIB have no concomitant respiratory or allergic disease.2
Olympians have been studied to quantify the incidence of EIB among elite athletes. About 11% of US Olympians who participated in the 1984 Olympic Summer Games met the criteria for EIB.4 These athletes won 41 medals, a testament to EIB's prevalent but controllable nature. Of the US Olympians who participated in the 1998 Olympic Winter Games, 17% admitted the need for medication for their exercise-induced symptoms.5 The incidence of EIB in a recent study involving US Army recruits6 was about 7%, but it had no effect on physical performance during basic training.
The etiology of EIB remains controversial. Two theories, the osmotic hypothesis and the thermal hypothesis, represent the current thinking about the cause of EIB.
The osmotic hypothesis is predicated on the theory that dehydration of the airways causes bronchospasm.3,7 Inspired air is humidified during the act of respiration, which results in water loss in the bronchial tree. Thus, the airway surface liquid evaporates, causing some degree of hyperosmolarity. By mechanisms not fully understood, this state of dehydration and hyperosmolarity triggers the release of cytokines and the degranulation of mast cells. These changes cause bronchospasm and shortness of breath in susceptible patients.
The thermal hypothesis of EIB involves a combination of temperature and vascular changes that cause bronchospasm.7 The inspired air is cool relative to the temperature in the bronchial tree. As the respiration rate increases during exercise, airway temperature gradually decreases. Exercise also causes increased blood flow to the pulmonary vascular beds for adequate oxygen exchange. The influx of warm blood translates to a reactive hyperemia and hyperthermia. The increased blood flow causes airway edema, leading to narrowed airway spaces and resultant pulmonary symptoms.
The pathophysiologic features of chronic asthma are bronchoconstriction, mucus secretion, and inflammation. Abnormal interaction between TH2 lymphocytes seems to instigate the inflammatory pathway in chronic asthma.8 Similar effects have not been specifically demonstrated in EIB. Unfortunately, most studies designed to detect markers of inflammation in EIB have evaluated patients with mild asthma and have had few patients enrolled. Jarjour and Calhoun9 demonstrated an absence of mast cell activation and inflammation in patients with mild stable asthma. After exercise challenge, there was no increase in histamine level or white blood cell count on bronchoalveolar lavage. Karjalainen and coinvestigators10 studied elite cross-country skiers and found that 33% had bronchospasm in response to methacholine chloride. However, no correlation between bronchial responsiveness and inflammation seen on bronchoalveolar lavage was noted. Clearly, the mechanism of EIB and its physiologic distinction from chronic asthma have not been adequately elucidated.
The Exercise Component
Certain activities have a higher propensity to trigger bronchospasm, which is referred to as the asthmogenic potential. Marathon running, basketball, soccer, and ice hockey require significant aerobic exercise that can induce respiratory symptoms. Therefore, these sports have a high asthmogenic potential. Conversely, golf, weight lifting, and the martial arts have a low asthmogenic potential.2 Water sports have an intermediate effect; in some patients, the warm, wet environment does not cause symptoms, but the chlorine in the water produces irritation leading to bronchospasm.11 Realistically, any activity can lead to symptoms, and susceptible patients must be educated about this possibility.
Varied exercise regimens do not change the likelihood of recurrent bronchospastic exacerbation. A Cochrane review12 revealed no significant improvement in peak flow measurement, spirometry readings, or the number of episodes of wheeze in patients with EIB who engaged in various aerobic training regimens. Matsumoto and associates13 showed that a swimming regimen improved aerobic capacity in patients with EIB but did not change histamine responsiveness, indicating a continued likelihood of EIB exacerbation. However, exercise is still recommended because of its cardiovascular benefits.14
Stages of EIB
EIB occurs in three distinct phases that have clinical and therapeutic ramifications.2 The first phase consists of the most severe bronchospasm. Symptoms peak 5 to 10 minutes after exercise begins and last for 30 to 60 minutes. If symptoms are not severe enough to treat, this phase spontaneously resolves after adequate rest.
The second phase, the refractory period, refers to the interval in which little or no bronchospasm occurs. It begins 30 minutes to 4 hours after exercise is initiated and is due to the release of adrenaline and norepinephrine, which act locally as bronchodilators. Concurrently, the depletion of mast cell contents results in diminished bronchoconstriction. About 50% of patients with EIB experience a refractory period and can capitalize on it to allow continued physical activity.
The final phase of EIB involves symptoms similar to those experienced in the first phase, but they are less severe. Symptoms recur 12 to 16 hours after exercise is finished and usually remit within 24 hours.
EIB presents in various ways, and patients report both obvious and vague complaints (table 1). Symptom onset usually occurs 5 to 10 minutes after the start of exercise but may take longer in a conditioned athlete.15 Chest pain rarely indicates cardiac disease in children. In a study by Wiens and colleagues,16 up to 72% of children with chest pain met the criteria for EIB. Adults present with wheezing and dyspnea more often than do children. Determination of functional limitations from symptoms is important for diagnosis and for treatment efficacy. A patient's inability to keep up with his or her peers is an important detail in history taking in pediatric and adolescent athletes.
EIB has multiple triggers that can lead to poor symptom control or frank bronchospastic exacerbation. Cold, dry air classically induces symptoms. Patients may note worsening bronchospasm during viral illness. Because allergic rhinitis and EIB are associated, inhaled seasonal allergens also play a role.2 Other irritants include dust, automobile exhaust, and chlorine. The most problematic irritant is tobacco smoke; all patients with EIB should be strongly encouraged not to smoke.
An old adage states, "All that wheezes is not asthma." Krieger17 provides a review of reasons for wheezing other than asthma. Similarly, symptoms seemingly related to exercise may not be due to EIB. Other diagnostic considerations include vocal cord dysfunction, gastroesophageal reflux disease (GERD), and panic disorder.15 Vocal cord dysfunction can mimic asthma with such complaints as "difficulty getting in air," dysphonia, and an uncomfortable throat tightness. Patients with GERD may have shortness of breath as a result of micro-aspiration of stomach contents into the respiratory tree. These patients also experience frequent belching, dyspepsia, and a metallic or foul taste in the mouth. Panic attacks and frequent anxiety before athletic events are characteristic of panic disorder.
As with any diagnosis, detailed history taking and physical examination are crucial. Determination of which activities trigger which symptoms is necessary for the initial consideration of EIB. Physical examination may reveal signs of allergic rhinitis, such as postnasal drip, turbinate discoloration, and infraorbital ecchymosis. Wheezing found on lung examination at rest may indicate chronic asthma.
If EIB is suspected, the diagnosis can be confirmed by measurement of peak expiratory flow or with spirometry.1,15 In the physician's office, patients can undergo an exercise challenge on a treadmill, attaining 85% to 95% of maximum heart rate. Peak flow and spirometry values are recorded before and after physical activity. (Patients should not take an antihistamine or bronchodilator for 48 hours before testing.) A documented reduction in peak flow of 15% or more is diagnostic of EIB.15 A reversal of peak flow reduction after bronchodilator use can confirm the diagnosis.3
Other methods of documenting potential for bronchospasm include a respiratory challenge with methacholine, histamine, or cold air. These methods often are restricted to a hospital or advanced outpatient setting. An easier but less exact method is to have patients record their peak flows at home with a peak flow meter before and after vigorous exercise. Empirical treatment with a fast-acting bronchodilator that induces subsequent improvement of symptoms also can aid in cost-effective diagnosis.3
EIB Versus Chronic Asthma
Controversy remains as to whether patients with EIB actually have chronic asthma with strictly an exercise component. The current literature on EIB and chronic asthma adds to the confusion. Many authors still use the term exercise-induced asthma, although this usage is discouraged.18 By definition, asthma has broncho-spastic and inflammatory components, yet patients with EIB alone do not have the inflammatory element. Furthermore, many studies on the treatment of EIB have included patients with chronic asthma whose symptoms worsen with exercise. This inclusion makes it difficult to determine whether certain therapies are efficacious in patients without true asthma.
Specific differences between EIB and chronic asthma exist.15 Patients with EIB usually have normal lung examinations at rest. Peak flow and spirometry values also are normal at rest. Patients with EIB experience symptoms at a particular level of exertion and need medication only before exercise, which also suggests a lack of inflammation and only transient bronchoconstriction. Patients with chronic uncontrolled asthma typically wheeze while at rest and have abnormal peak flow and spirometry values at rest. These patients generally require long-term therapy plus additional medication before exercise. It is important to note that there is no evidence that patients with EIB eventually have chronic asthma.
There are various pharmacologic and nonpharmacologic treatment options for EIB (table 2). A general principle in pharmacologic therapy is to use the shortest-acting drug and to introduce longer-acting therapies when it does not control symptoms.15
The hallmark of pharmacologic treatment for EIB is short-acting bronchodilators such as beta-agonists.1,15 Many patients prefer these medications, such as albuterol, because they require administration only before exercise to control symptoms. Two to four puffs taken 15 minutes before exercise provide about 4 hours of relief. Side effects of beta-agonists include palpitations, tachycardia, and tremors, but these usually are mild. Tolerance to beta-agonists can develop if they are used often and in the long term.
Mast cell stabilizers are sometimes used as second-line therapy for EIB. These agents work by preventing leukocyte degranulation and resultant histamine release. Examples of such drugs include cromolyn sodium (Intal) and nedocromil sodium (Tilade). Patients take the medication 15 to 60 minutes before exercise, and its benefits last about 4 hours. A recent Cochrane review of nedocromil sodium use to prevent EIB19 showed it improved forced expiratory volume in 1 second (FEV1) by an average of 16% and shortened the duration of EIB symptoms to less than 10 minutes.
Longer-acting beta-agonists are another option for patients with EIB. Salmeterol (Serevent) has been shown to significantly improve FEV1.20,21 When these medications are taken 30 minutes before activity, they can provide relief for up to 12 hours, making them good treatment options for athletes whose exertion is prolonged.19 However, long-term use seems to shorten the duration of action.21,22
Other adjunctive medicines, such as antihistamines, can help treat EIB by assisting with the allergic component of the disease. Cetirizine hydrochloride (Zyrtec) may be particularly helpful, because recent studies have shown it decreases airway resistance over time and improves lung ventilatory function.23
If symptoms refractory to the previously mentioned medications persist, underlying inflammation from chronic asthma should be considered. A number of anti-inflammatory asthma medications have been studied in the setting of exercise. Regular use of an inhaled corticosteroid can reduce exercise-induced symptoms by as much as 50%.24 Leukotriene inhibitors also have been shown to be beneficial during exercise. Montelukast sodium (Singulair) and zafirlukast (Accolate) improve FEV1 by about 10%, and the effects can last for 24 hours.20,25
In the Field
Physicians should have a plan for managing athletes with EIB during competitive events. These athletes should have a fast-acting bronchodilator with them at all times15 and can use a beta-agonist inhaler before activity. Also, they can perform warm-up exercises, such as wind sprints, at submaximal intensity in an effort to induce an early phase of EIB.15,18,26 After EIB enters the refractory period, participation can begin.
A fast-acting inhaler may be used for rescue therapy if symptoms recur or worsen. In addition to the two inhaled puffs taken before exercise, another dose of two puffs can be used. If an athlete's symptoms persist and further treatment is needed, the inhaler can be used again, but activity should be stopped. The physician should closely monitor the athlete's respiratory status. Despite providing optimal care, the physician may be in the unenviable position of removing the athlete from competition.
Controversy continues about the terminology, causes, and treatment of respiratory symptoms related to exercise. Despite this controversy, EIB is a common disease that can be easily diagnosed and treated by the primary care physician. Patient education is a crucial part of the treatment regimen.
Exercise may not alter the likelihood of future exacerbations, but it should be encouraged nonetheless. As demonstrated by the success of Olympic competitors with EIB, any athlete—from the recreational to the elite—can fully participate in exercise when his or her condition is properly recognized and treated.
Dr Hermansen was formerly a senior resident, department of family and community medicine, Lancaster General Hospital, Lancaster, Pennsylvania. He is now staff physician, Elmer Family Practice, Elmer, New Jersey. Dr Kirchner is associate director, department of family and community medicine, Lancaster General Hospital.
Address correspondence to Christian L. Hermansen, MD, Elmer Family Practice, PO Box 577, Suite 4101, Elmer, NJ 08318. E-mail: [email protected]. Disclosure information: Drs Hermansen and Kirchner disclose no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.