Exercise-Induced Bronchoconstriction With or Without Asthma: A Unique Challenge

The numerous health benefits of physical activity are well-established, including improved disease-specific outcomes in individuals with asthma. Studies have demonstrated improvements in symptoms, pulmonary function, exercise capacity, and quality of life, along with reductions in airway inflammation and responsiveness, in patients with asthma who underwent exercise training.¹

However, a large portion of this population is prone to exercise-induced bronchoconstriction (EIB), which typically develops following at least 5 to 8 minutes of high-intensity exercise and resolves within 60 minutes. Research shows that EIB may affect up to 90% of patients with asthma, with the greatest frequency noted in patients with severe or uncontrolled disease, presenting a potential barrier to engagement in regular exercise.¹

Risk Factors and Mechanisms

Findings indicate that the risk of EIB is particularly high with intense and prolonged physical activity, which “may trigger airway symptoms by imposing high demands on the respiratory system and by exposing subjects to increased amounts of inhalant allergens, pollutants, irritants, and adverse environmental conditions,” according to a paper by Bonini and Silvers published in Immunology and Allergy Clinics of North America.¹

Vigorous exercise may also “induce a transient status of immune downregulation with a shift toward a prevalent T-lymphocyte helper-2 response, clinically associated with an increased prevalence of atopy and viral upper respiratory tract infections, both representing relevant risk factors for the onset and worsening of asthma,” according to the researchers.

EIB has also been reported in 5% to 20% of individuals without asthma, especially athletes, children, and patients with rhinitis or recent respiratory infection. The American Academy/College of Allergy Asthma and Immunology has recommended abandoning use of the term “exercise-induced asthma,” and guidelines from the American Thoracic Society recommend differentiating EIB in patients with asthma (EIBa) from EIB in individuals without underlying asthma (EIBwa).¹

EIB in Athletes

In either case, EIB can be especially burdensome for elite athletes and others involved in regular physical activity. Certain sports are associated with especially high rates of EIB, such as long-distance running and cycling, winter sports including cross-country skiing and ice-skating, as well as swimming. For example, studies have reported EIB symptoms in 32% of marathon runners and approximately 55% of cross-country skiers.¹

Environmental factors have been implicated in the high prevalence of EIB in athletes.² In endurance sports, EIB may be partly due to an “increased minute ventilation through the mouth (bypassing the nasal filter) and exposure to allergens and pollutants,” while EIB in winter sports “has been attributed to the high ventilation of cold dry air during training and competition, in combination with the elevated emission of pollutants from fossil-fueled ice resurfacing machines,” Bonini and Silvers explained.¹ In addition, it has been proposed that high rates of asthma and EIB in competitive swimmers may result from “repeated hyperventilation challenges together with the exposure to chlorine-based derivatives” that are used to disinfect swimming pools.

Treatment Strategies

Because of  the dearth of research focused on EIB management in athletes, current recommendations are similar to those proposed in the general population. While short-acting beta agonists (SABAs) represent the first-line treatment for EIB, an estimated 15% to 20% of patients require an alternative or adjunctive therapy to SABAs. In those cases, recent guidelines recommend “stratifying treatment based on the presence or absence of underlying asthma and the frequency of exercise and SABA use.”³

Alternative first-line and adjunctive therapies include inhaled corticosteroids, long-acting beta2-agonists (not to be used as monotherapy), leukotriene receptor agonists, mast-cell stabilizing agents, and short-acting muscarinic antagonists. The investigators emphasized that athletes and their prescribing providers should remain aware of the World Anti-Doping Agency (WADA) regulations, which “can change over time and currently mandate TUEs [therapeutic use exemptions] for multiple classes of medications used in the treatment of EIB and asthma exacerbations.”³

Nonpharmacologic treatment options for EIB have been the focus of emerging research, although there is inadequate evidence to recommend the sole use of nonpharmacologic approaches for EIB.⁴ Various strategies may attenuate EIB or reduce the patient’s perception of exertional dyspnea. In the former category, a pre-exercise warmup consisting of brief intervals of high-intensity or variable intensity exercise led to a 10% reduction in the post-exercise decline of forced expiratory volume in 1 second (FEV₁), according to a 2012 systematic review.⁵ Similar results have been demonstrated with pre-exercise respiratory warm-ups, without compromising subsequent athletic performance.⁴

The investigators noted the importance of avoiding environmental triggers such as training in low-humidity conditions or near high-traffic roadways, and evidence points to the potential benefit of face masks with a heat and moisture exchanger in sports that occur in cold and/or dry settings.^4,6 

Additional research shows promise for the use of omega-3 fatty acids in reducing airway inflammation and bronchoconstriction associated with EIB, and the results of various studies indicate that “caffeine has the potential to reduce EIB severity and improve ventilatory dynamics and respiratory muscle fatigue resilience during exercise.”⁴ Several other studies have linked acute and chronic supplementation of vitamin C to reductions in the post-exercise decline of FEV₁ in EIB.

Most nonpharmacologic research in this area has involved non-athletes, highlighting the need for studies exploring the effects of these therapies in athletes. Research regarding the effects of certain athletic supplements on EIB severity may also be warranted, as animal studies suggest that β-alanine and creatine may reduce and exacerbate EIB severity, respectively.⁴

Along with strategies that attenuate EIB severity, a range of techniques may reduce the perception of exertional dyspnea, including yogic breathing techniques, physiotherapist-supervised breathing training, and respiratory muscle training.⁴ However, further investigation is required to explore the effects of these approaches on EIB both in general and in athletes.

To learn more about updates relevant to EIB, we interviewed J. Tod Olin, MD, MSCS, director of the Exercise and Performance Breathing Center, and associate professor in both the Division of Pediatric Pulmonology and the Division of Pulmonary, Critical Care, and Sleep Medicine at National Jewish Health in Denver, Colorado.

What are some of the latest findings from studies investigating EIB?

In the past 5 years, one of the most important findings related to EIB is that many patients have alternative diagnoses outside of asthma. Specifically, an entity known as exercise-induced laryngeal obstruction (EILO) has been identified as a diagnosis that requires consideration in patients with exertional shortness of breath. [Editor’s note: EILO is “characterized by symptomatic upper airway obstruction at the level of the glottis or supraglottis during exercise in the absence of symptoms or obstruction at rest,” wrote Olin et al in a paper published online in March 2019 in Frontiers in Pediatrics.⁷]

What are believed to be effects of air pollution and climate change on the prevalence and outcomes of EIB?

Air pollution in a general sense can start the immune cascade and make the symptoms of asthma more problematic.⁴ We know that asthma control is worse in patients who live in areas of high pollution.⁴ I am not sure I feel comfortable commenting on climate change because the local effects can be very different depending on which location we are talking about.

What are some of the top diagnostic and treatment challenges pertaining to this condition?

In terms of diagnosis, it can be challenging to mimic real-life circumstances in a hospital setting. Many facilities simply do not have the exercise equipment and safety monitoring necessary to challenge athletes. From a logistics perspective, it is not reasonable to perform hospital-based tests that last as long as the recreational events that patients traditionally engage in.

In terms of treatment challenges, it is important to note that guidelines are based on limited research. Just as it is challenging to diagnose some patients, it is challenging to study EIB for the exact same reasons. It is difficult to create feasible tests that can be performed in a research setting that yield meaningful results, especially in patients who are using traditionally accepted medications.

How can individuals with EIB  remain active?

From an individual perspective, I think there are several important considerations:

• The expectation that patients need to have is that the medical community is obligated to help until patients can achieve their desired state of activity. There are providers who specialize in this area and patients should be encouraged to ask for help.
• The most basic intervention is simply to use 2 puffs of albuterol with a spacer device about 15 minutes prior to exercise.³ There are several other interventions that have been shown to help in isolation.
• Most patients who have EIB probably have asthma at baseline that is triggered by exercise.¹ Acceptance of this reality and control of the baseline asthma will make exercise much easier.
• In patients with good baseline asthma control who continue to have symptoms despite the use of albuterol prior to exercise, clinicians need to think about alternative diagnoses including EILO, which requires completely different treatment.⁷
• Many times, acquisition of a video of characteristic field symptoms can help with diagnosis. Specifically, some alternative diagnoses including EILO can sometimes be identified by video.⁷

References

1. Bonini M, Silvers W. Exercise-induced bronchoconstriction: background, prevalence, and sport considerations. Immunol Allergy Clin North Am. 2018;38(2):205-214.

2. Rundell KW, Smoliga JM, Bougault V. Exercise-induced bronchoconstriction and the air we breathe. Immunol Allergy Clin North Am. 2018;38(2):183-204.

3. Backer V, Mastronarde J. Pharmacologic strategies for exercise-induced bronchospasm with a focus on athletes. Immunol Allergy Clin North Am. 2018;38(2):231-243.

4. Dickinson J, Amirav I, Hostrup M. Nonpharmacologic strategies to manage exercise-induced bronchoconstriction. Immunol Allergy Clin North Am. 2018;38(2):245-258. 

5. Frischhut, C, Kennedy, MD, Niedermeier, M, Faulhaber, M. Effects of a heat and moisture exchanger on respiratory function and symptoms post–cold air exercise. Scand J Med Sci Sports. 2020; 30:591-601.

6. Stickland MK, Rowe BH, Spooner CH, Vandermeer B, Dryden DM. Effect of warm-up exercise on exercise-induced bronchoconstriction. Med Sci Sports Exerc. 2012;44(3):383-391.

7. Olin JT. Exercise-induced laryngeal obstruction: when pediatric exertional dyspnea does not respond to bronchodilators. Front Pediatr. 2019;7:52.