Pulmonary Issues in the Athlete/Exercise Induced Bronchoconstriction

Disease/ Disorder:

Definition

Exercise-induced bronchoconstriction (EIB) is defined as the transient airway narrowing that occurs following exercise without regards to the presence or absence of asthma.^1,2 While the term “exercise-induced asthma” (EIA) has been used, the term is misleading as exercise is not an independent risk factor for asthma, but, instead, a trigger for bronchoconstriction in some asthmatics.¹ EIB may be present in patients with or without underlying asthma and can affect athletes of all levels.^{3, 11}

​​Etiology

EIB occurs following high-intensity exercise when high minute ventilation dehydrates the airways and ultimately results in the release of inflammatory mediators.⁴ This occurs more frequently in cold/dry environmental conditions.^4,5 The sustained high-level ventilation reached during exercise and the water content of inspired air are the two most important factors of EIB.⁵

Epidemiology including risk factors and primary prevention

The prevalence of EIB is 5%-20% of the general population and is likely underestimated due to lack of gold standard for diagnosis, while the prevalence in asthmatics is 40-90%³. EIB affects athletes of any level with studies showing higher rates (30%-70%) in Olympic/elite athletes.⁵ Those participating in indoor (i.e. ice hockey, swimming), endurance, and winter sports are more susceptible, and high-intensity training may contribute to the development of EIB.⁵ Environmental exposures such as cold air, dry air, ambient ozone, airborne particulate matter, gases associated with ice rink resurfacing equipment, and elevated levels of trichloramines in indoor pools are also thought to contribute to EIB.⁵ Poorly controlled chronic asthma, oral breathing, personal/family history of cardiovascular disease, allergic rhinitis, sinusitis, atopy and urbanization are additional risk factors.^1,5

Patho-anatomy/physiology

The mechanism of EIB is likely multifactorial and not entirely understood, with several theories existing to explain the pathophysiology¹². The osmotic theory is the most universally accepted. It infers that large volumes of cool, dry air inhaled during exercise lead to changes in the osmolarity of the airway surfaces.^2,3 A hyperosmolar environment results, triggering a mast cell-mediated release of mediators (i.e. histamine, leukotrienes, prostaglandins) from inflammatory cells, which cause bronchial smooth muscle constriction and edema.¹ Uncontrolled underlying airway inflammation may exacerbate this response.^1,2 These osmotic and mechanical stresses due to repeated heavy ventilation may also contribute to airway remodeling in the long-term through effects on epithelial cells. Over time this process alters smooth muscle contractile properties, leading to increased bronchial hyper-responsiveness .^1,2,12 The re-warming hypothesis has some supporting evidence, but is mostly overlooked for the above hypertonicity mechanism.¹

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Symptoms of EIB usually occur during or after exercise, but may only occur in specific environments (i.e. ice rinks or swimming pools), or at a certain intensity or duration.⁵ In the acute phase, athletes may experience coughing, shortness of breath (SOB), chest tightness, and wheezing, or subtle symptoms such as fatigue, headache, dizziness, or impaired performance.² Peak onset occurs within a 10-15 of exercise and lasts 30-90 minutes.³ Recovery is spontaneous with FEV1 returning to 95% baseline in 30-90 minutes.⁵ Patients can be refractory to another exercise stimulus for up to four hours and some can develop symptoms 4-8 hours after exercise, known as a late-phase response.^5,13 Airway hyperresponsiveness may improve or normalize (weeks to years) if athletes refrain from competitive participation.^2,6

Specific secondary or associated conditions and complications

Co-existing conditions, or conditions that may mimic EIB, include asthma, upper-airway cough syndrome, chronic eosinophilic bronchitis, allergies, rhinitis, gastroesophageal reflux (GERD), exercise induced laryngeal obstruction (EILO), central airway obstruction, exercise-induced anaphylaxis, restrictive lung disease, swimming-induced pulmonary edema, and environmental exposures. EILO, is a frequent imitator of EIB, but does not respond to bronchodilators, symptoms resolve upon exercise cessation, and leads to persistent dyspnea.⁷ Additionally, SOB may be caused conditions other than airway dysfunction including anemia, infectious diseases, cardiovascular disease, and musculoskeletal conditions.⁷ Potential complications of misdiagnosis include persistent or worsening symptoms, impaired performance, discontinuation of a sport, hypoxemia, and, in extreme cases, death.⁷

Essentials of Assessment

History

The history should include when symptoms occur, initial onset, duration, frequency, and severity. Inquire if the patient has difficulty breathing, coughing, excessive mucous production, or chest tightness associated with exercise, that gradually improves upon stopping. Distinguishing inspiratory stridor with or without expiratory wheezing from inspiratory stridor alone is important, especially to help discern EIB from EILO¹⁴. Atypical symptoms may include fatigue, feeling out of shape or unable to keep up with peers, and abdominal discomfort. History of prior injury to the head/neck/chest, family/personal history of cardiopulmonary conditions, prior hospitalizations and current/past treatment are relevant.

Physical examination

A comprehensive physical should include examinations of the head, ear, nose, and throat (HEENT), chest, cardiopulmonary, extremity, and skin systems. HEENT exam should look for any signs of allergic rhinitis, sinusitis, or otitis. Examination of the chest (and back) should look for any structural deformities (such as pectus excavatum) or spinal scoliosis. On cardiopulmonary exam, auscultate for cardiac murmurs, wheezing, rales, or rhonchi and palpate pulse to detect arrhythmias. Examine skin and extremities for signs of eczema, cyanosis, digital clubbing, or edema.

Functional assessment

The impact of EIB on athletic performance has not been well established.⁸EIB may hypothetically impair performance due to exercise airflow limitations, increased work/oxygen cost of respiratory muscles, dyspnea/perception of effort, and ventilation/perfusion mismatch.⁸ Follow-up with patients once a treatment plan has been implemented to ensure compliance with treatment, assess that co-morbidities are adequately addressed, and to monitor for ongoing dyspnea, fatigue, or underperformance.⁷ From a psychological perspective, recent studies have described the negative emotional burden associated with EIB and EIA. This has been particularly seen in the adolescent population with reports of lower quality of life (QoL) and more mood symptoms including anxiety, depression, and frustration.^11,15-17

Laboratory studies

Symptoms of EIB are non-specific and have a poor predictive value.⁵ Serial lung function measurements, using forced expiratory volume in one second (FEV₁), objectively determine the presence and severity of EIB.⁵ Indirect challenges (exercise challenge or surrogate testing) are more sensitive than direct challenge (i.e., methacholine). During an exercise challenge test, spirometry measures FEV₁ pre-exercise and at 5, 10, 15, and 30-minute intervals post-exercise.⁵ An athlete should reach >90% of maximum heart rate at 2 minutes and maintain this level for another 6 minutes during the exercise. Airway response is the percent fall in FEV₁ from baseline, and a diagnosis of EIB is established with a 10-15% decrease in FEV₁.⁵ Pre-exercise studies should be normal in those with EIB without underlying asthma, so normal spirometry at rest does not rule out EIB.⁵ Regarding severity, a decrease in FEV₁ of 10-< 25% is mild, 25-<50% is moderate, and ³50% is severe.

Imaging

Imaging is not routinely required for diagnosis. However, a chest x-ray or computed tomography of the chest may be performed to rule out suspected structural abnormalities (such as pectus excavatum or scoliosis), injury, or intra-cardiopulmonary process (such as cardiomegaly, pleural effusion, or pneumonia).

Supplemental assessment tools

Bronchial provocative tests are necessary to confirm the diagnosis of EIB, especially for athletes participating in high-level competition or those who fail to respond appropriately to treatment.² Other than a sports-specific exercise challenge performed during the provoking activity, various surrogates exist. These include the eucapnic voluntary hyperpnea (EVH) challenge (greatest sensitivity for EIB), hyperosmolar tests with mannitol or saline, and methacholine inhalation.^2,3,5 These surrogate tests are not entirely sensitive nor specific, but they can all identify airway hyperesponsivness.⁵ For the EVH test, dry air (5% carbon dioxide) is hyperventilated for 6 minutes at room temperature, with a decline of ³10% of the pre-test FEV1 being diagnostic.¹¹ Furthermore, some athletes may test positive to only one test and so more than one type of challenge may be necessary to establish diagnosis.² When EILO is suspected, laryngoscopy is the test of choice.⁷

Early prediction of outcomes

There are no well-established early predictors of outcome in EIB. In general, symptoms of EIB are mild to moderate in severity, causing some impairment on athletic performance without significant respiratory distress.⁵ Airway hyperresponsiveness may even normalize a few weeks after stopping intense training.² In patients with asthma, EIB is thought to be a marker of poor asthma control.¹

Environmental

Rates of EIB are higher in urban populations secondary to increased air pollution (i.e. ozone and particulate matter from combustion engines).¹ Exposure to cold/dry air is thought to contribute to bronchoconstriction, as EIB is more common in colder seasons and winter sports, such as ice skaters and Nordic skiers.^1,5 Elevated levels of chloramines in swimming pools are thought to be responsible for the increased prevalence seen in swimmers (11-29%).⁵ Those with longer duration of exposure (>100 hours of pool exposure) have a higher EIB prevalence and cessation of swimming can decrease EIB incidence.¹⁹

Social role and social support system

A team approach should be utilized in optimizing and preventing EIB. Sports medicine physicians, pulmonologists, coaches, teachers, and families should work together with the athlete and be aware of the available treatment options and methods to decrease episode frequency, while maintaining exercise fitness.

Professional Issues

Symptom-based diagnosis of EIB lacks sensitivity and specificity, so diagnosis requires objective measures of lung function, especially for the elite athlete.⁹ Once the diagnosis is confirmed, goals of treatment are to maintain symptom control, prevent exacerbations, optimize pulmonary function, and allow patients to exercise safely.² For patients who fail to respond appropriately to treatment, it is important to consider co-existing conditions that may be present. In the event of respiratory distress or hypoxemia despite treatment, emergent medical attention is warranted.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Management recommendations are still largely based on expert opinion, however the American Thoracic Society (ATS) recently published evidence-based guidelines for the diagnosis and treatment of EIB. The quality of evidence used to determine these guidelines ranges from low to high. Furthermore, the majority of studies are on patients with both EIB and asthma, and limited data exists on athletes with EIB only.³ For patients with chronic, persistent asthma, their treatment should be in accordance with the National Asthma Education and Prevention Program guidelines.

At different disease stages

Prevention should start with education on inhaler technique and methods to avoid environmental triggers (i.e. exercise outside in low-traffic hours, avoid exercising near high allergen-exposed areas).² A 10-15 minute warm-up consisting of variable high-intensity activity (i.e. wind sprints) is recommended as it may induce a 2-hour “refractory period.”^2,5 Breathing through a loose fitting scarf or mask may benefit those exercising in cold/dry conditions by promoting humidification.³ Improving nasal breathing techniques may help warm the inhaled air during exercise as opposed to oral breathing. For pharmacological prophylaxis, short-acting beta₂-agonists (SABAs) such as albuterol are first-line treatment and should be used 5-20 minutes prior to exercise.^2,5 Daily use of beta₂-agonists, however, may lead to tolerance.^2,5 When combined with pre-exercise warm-ups, SABAs display a protective effect compared to warm-ups or SABA alone in those with asthma and EIB.¹⁸

Maintenance therapy involving low-dose inhaled corticosteroids (ICS) such as budenoside or fluticasone or alternatively, leukotriene receptor antagonist (LTRA) such as montelukast is initiated in patients who need their rescue inhaler more than twice per week (including prophylactic doses), or if symptoms limit exercise tolerance.^2,5 If symptoms are still poorly controlled, a LTRA or long-acting beta₂-agonists (LABA) such as salmeterol may be added to the ICS.⁵ However, daily use of LABAs with ICS is not advised for EIB except in the setting of moderate to severe persistent asthma.¹⁴ Co-existing conditions should be identified and treated. For example, antihistamines may be an appropriate addition in patients with allergies and EIB who have symptoms despite using a SABA.⁵

For rescue therapy, a SABA should be available on demand.

Coordination of care

For high-level athletes, the care team should be familiar with the World Anti-Doping Agency’s (WADA) policies on which medications require a therapeutic use exemption (TUE). TUE applications should be submitted at least 30 days prior to participating in an event. As of January 2022, all beta-2 agonists except inhaled albuterol, vilanterol, formoterol, and salmeterol are prohibited and require a TUE.¹⁰ Inhaled corticosteroids are currently permitted, however the use of systemic corticosteroids (i.e., via oral, intravenous, intramuscular, or rectal routes) are prohibited.¹⁰

Patient & family education

Educate patients on environmental factors, inhaler technique, when to use medications, and how to recognize and respond to worsening symptoms. Patients should be provided with an action plan for acute exacerbations.² Asthmatic patients should also be educated that exercise is not detrimental to their health and encouraged to participate in regular exercise and aerobic conditioning.^1,3

Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally-based

Monitoring response to treatment can be completed subjectively or objectively. Subjective monitoring can be done in regards to symptom control and exercise tolerance, as knowing how frequently an athlete uses their rescue inhaler can help to guide treatment adjustment.³ For athletes who persistently experience EIB, medical adjustment may be needed.³ When objective outcomes are required, formal exercise testing in a sport/environment specific field-based exercise challenge is preferred.^3,9

Translation into Practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice

The practice pearls for handling EIB include the following:

1. Communicate with the coaches, parents, and certified athletic trainer.
2. Educate patients on when and how to take their medication, and on the importance of always carrying their rescue inhaler with them.
3. Athletes and their care team should check the WADA website (www.wada-ama.org/en) to stay updated on current regulations.
4. Know the process and deadline for filing a TUE application; it usually needs to be submitted 30 days prior to the event.​​
5. Most athletes can be managed on a low-dose ICS or a LTRA with occasional use of a SABA, however regular use of a SABA may lead to tolerance.

Cutting Edge/ Emerging and Unique Concepts and Practice

The role of nutrition in managing or preventing EIB has been suggested, but there is limited evidence in the literature to support these claims. While there is no obvious risk to trying dietary modification in interested patients, there is insufficient evidence to recommend the use of fish oil, low salt diet, vitamins (C and E), or antioxidants as treatment.⁵ The ATS currently recommends against the use of dietary supplementation with lycopene in patients with EIB.⁵ In respect to better understanding pathogenesis, new cytokine and genetic markers are being investigated to assess their contributions to the development of EIB. Several genetic alterations have been discovered which may protect or predispose athletes to EIB, but further studies are needed to better delineate the role of genetic susceptibility in EIB.¹²

Gaps in the Evidence-Based Knowledge

The majority of guidelines are based on studies in patients with both EIB and asthma, and limited data exists on athletes with EIB as their only diagnosis of airway hyperresponsiveness.³ Optimal treatments may be different in those with EIB and underlying asthma versus those with EIB alone.^2,5 Additionally, the method used to detect EIB can greatly affect the estimates of prevalence as routine diagnostic strategies may not be appropriate for elite athletes.⁹ For this reason, sport-specific protocols performed in provocative environments need to be established.⁸ The role and benefit of screening for EIB in the general population and among athletes is also still unknown.⁵ Lastly, further studies are still needed to determine the impact of EIB on athletic performance and whether initiating treatment in an asymptomatic individual with a positive eucapnic voluntary hyperpnea challenge will have any benefit on health and performance.^6,8

References

1. Craig TJ, Dispenza MC. Benefits of exercise in asthma. Ann Allergy Asthma Immunol. 2013;110(3):133-140 e132.
2. Boulet LP, O’Byrne PM. Asthma and exercise-induced bronchoconstriction in athletes. N Engl J Med. 2015;372(7):641-648.
3. O’Byrne PM. Exercise-induced bronchoconstriction. In:UpToDate. Hollingsworth, H (Ed), UpToDate, Waltham, MA, 2016.
4. Smoliga JM, Weiss P, Rundell KW. Exercise induced bronchoconstriction in adults: evidence based diagnosis and management. BMJ. 2016;352:h6951.
5. Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013;187(9):1016-1027.
6. Levai IK, Hull JH, Loosemore M, Greenwell J, Whyte G, Dickinson JW. Environmental influence on the prevalence and pattern of airway dysfunction in elite athletes. Respirology. 2016.
7. Smoliga JM, Mohseni ZS, Berwager JD, Hegedus EJ. Common causes of dyspnoea in athletes: a practical approach for diagnosis and management. Breathe (Sheff). 2016;12(2):e22-37.
8. Price OJ, Hull JH, Backer V, Hostrup M, Ansley L. The impact of exercise-induced bronchoconstriction on athletic performance: a systematic review. Sports Med. 2014;44(12):1749-1761.
9. Rundell KW, Slee JB. Exercise and other indirect challenges to demonstrate asthma or exercise-induced bronchoconstriction in athletes. J Allergy Clin Immunol. 2008;122(2):238-246; quiz 247-238.
10. World Anti-Doping Agency. http://www.wada-ama.org/. Accessed March 2, 2022.
11. Aggarwal B, Mulgirigama A, Berend N. Exercise-induced bronchoconstriction: prevalence, pathophysiology, patient impact, diagnosis and management. NPJ Prim Care Respir Med. 2018;28(1):31. Published 2018 Aug 14. doi:10.1038/s41533-018-0098-2
12. Couto M, Kurowski M, Moreira A, Bullens DMA, Carlsen KH, Delgado L, Kowalski ML, Seys SF. Mechanisms of exercise-induced bronchoconstriction in athletes: Current perspectives and future challenges. Allergy. 2018 Jan;73(1):8-16. doi: 10.1111/all.13224. Epub 2017 Jul 12. PMID: 28599081.
13. Molis MA, Molis WE. Exercise-induced bronchospasm. Sports Health. 2010;2(4):311-317. doi:10.1177/1941738110373735
14. Weiler JM, Brannan JD, Randolph CC, Hallstrand TS, Parsons J, Silvers W, Storms W, Zeiger J, Bernstein DI, Blessing-Moore J, Greenhawt M, Khan D, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Schuller DE, Tilles SA, Wallace D. Exercise-induced bronchoconstriction update-2016. J Allergy Clin Immunol. 2016 Nov;138(5):1292-1295.e36. doi: 10.1016/j.jaci.2016.05.029. Epub 2016 Sep 21. PMID: 27665489.
15. Parsons JP, et al. Impact of exercise-related respiratory symptoms in adults with asthma: Exercise-Induced Bronchospasm Landmark National Survey. Allergy Asthma Proc. 2011;32:431–437. doi: 10.2500/aap.2011.32.3501.
16. Kojima N, et al. Exercise-induced asthma is associated with impaired quality of life among children with asthma in Japan. Allergol. Int. 2009;58:187–192. doi: 10.2332/allergolint.08-OA-0034.
17. Johansson H, et al. The relationship between exercise induced bronchial obstruction and health related quality of life in female and male adolescents from a general population. BMC Pulm. Med. 2016;16:63. doi: 10.1186/s12890-016-0226-0.
18. Mickleborough TDL, M. R, Turner LA. Comparative effects of a high-intensity interval warm-up and salbutamol on the bronchoconstrictor response to exercise in asthmatic athletes. Int. J. Sports Med. 2007;28:456–462. doi: 10.1055/s-2006-924583.
19. Bernard A, Nickmilder M, Voisin C, Sardella A. Impact of chlorinated swimming pool attendance on the respiratory health of adolescents. Pediatrics. 2009 Oct;124(4):1110-8. doi: 10.1542/peds.2009-0032. Epub 2009 Sep 14. PMID: 19752078.

Original Version of the Topic

Richard G. Chang, MD, MPH, Joseph E. Herrera, DO. Pulmonary issues in the athlete / exercise induced asthma. 4/05/2013

Previous Revision(s) of the Topic

Richard G. Chang, MD, MPH, Caitlin Cicone, DO, and Brian Pekkerman, DO. Pulmonary issues in the athlete / exercise induced asthma. 4/4/2017

Author Disclosure

Kevin Ozment, MD
Nothing to Disclose

Richard G. Chang, MD, MPH
Nothing to Disclose