Clinical Features

  • Definition: Exercise-induced bronchoconstriction (EIB) is defined as the transient narrowing of the lower airways (10-15% decrease in FEV1) that occurs after vigorous exercise.
  • Mechanism: Vigorous exercise results in hyperpnea > drying of the airways > airway cooling/dehydration > increased airway surface osmolarity > degranulation of airway mast cells > bronchoconstriction and inflammation
  • EIB usually requires a decrease in FEV1 after exercise of 10-15% of the pre-exercise value.
  • Observed in patients with or without asthma (including those with a negative methacholine challenge), and may be the first sign of developing asthma
  • Healthy individuals usually have an increase in FEV1 after exercise
  • In approximately 50% with EIB, there is an interval of refractory period lasting ~1-3 hours after an episode of EIB during which additional exercise results in little or no bronchoconstriction. This may also occur after strenuous exercise at a level that does not provoke EIB.


Symptoms

  • Cough, wheeze, chest pain primarily in children or chest tightness, shortness of breath, dyspnea
  • Excessive mucous production
  • Feeling out of shape when the patient is actually in good physical condition



Differential Diagnosis (Twarog)

  • In a study of 117 children with isolated exercise-induced symptoms refractory to albuterol, 63% had normal physiologic exercise limitation (i.e. severe exertional dyspnea and chest discomfort from lactic acidosis), 13% had restrictive abnormalities, 11% VCD, 9% EIB, 2% exercise-induced laryngomalacia, 1 patient with arrhythmia (exercise-induced SVT) and 1 with hyperventilation
  • Vocal cord abnormalities (exercise-induced laryngeal dysfunction, EILD)
    • VCD
      • More common in competitive young female athletes, respiratory sounds (including wheezing or stridor) prominent with inspiration and may peak and/or occur during exercise (rather than following exercise), respond poorly to EIB treatment
      • Flattening of the inspiratory phase of the flow-volume loop, vocal cords will at times demonstrate aberrant vocal-cord movement or posterior notch. May coexist with asthma and some feel that GER can contribute. Management includes speech therapy and inhaled anticholinergics may be effective. Spontaneous resolution common. Sometimes discussion of the diagnosis itself is helpful in resolving symptoms.
    • Less common:
      • Exercise-induced laryngeal prolapse, arytenoid collapse
      • Exercise-induced laryngomalacia - often the cause of inspiratory respiratory sounds in young infants and children, may occur even in adults, effectively treated with laser laryngoplasty
  • Exercise-induced dyspnea - dyspnea with vigorous exercise, may be related to hyperventilation resulting in hypocapnea without bronchoconstriction. Etiology is poorly understood.
  • Underlying pulmonary pathophysiology (other than asthma) - including obstructive lung disease and restrictive abnormalities secondary to skeletal defects, obesity, diaphragmatic paralysis, and interstitial fibrosis
    • Chest structural abnormalities (e.g. pectus excavatum and scoliosis), may result in decreased exercise tolerance.
    • Alpha-1 antitrypsin deficiency may result in early-onset fixed airway obstruction and exertional dyspnea.
  • Exercise-induced anaphylaxis (EIA) - differentiated from EIB by presence of pruritus, urticaria, upper airway congestion, GI symptoms. May be associated with foods or occur independently. Wheat allergens, NSAID use frequently associated with food-dependent EIA.
  • Cardiovascular - cardiac-associated dyspnea due to arrhythmias, cardiomyopathy, etc. requiring cardiology referral.
  • Structural abnormalities (e.g. vascular rings, congenital tracheobronchial stenosis) - suggested by decreased peak flow rates and fixed obstruction on inspiratory and expiratory flow-volume loops
  • Deconditioning - a common cause of exercise-induced dyspnea in childhood, is poor conditioning
  • GERD - controversial, many individuals with GERD are diagnosed with EIB, but the relationship is unclear
  • Psychological factors - factors other than VCD may contribute to symptoms and should be kept in mind




Diagnosis


ACAAI/AAAAI Practice Parameter Algorithm (2010)

EIB_algorithm.png



ATS Practice Parameter 2012

ATS EIB PP algo.png




Exercise Challenge Procedure (ATS)

  • Contraindications
    • Absolute
      • Severe airflow limitation (FEV1 <50% predicted or <1 L)
      • Heart attack or stroke in last 3 mo
      • Uncontrolled hypertension, systolic BP >200, or diastolic BP <100
      • Known aortic aneurysm
      • Unstable cardiac ischemia
      • Malignant arrhythmias (for patients over 60, a 12-lead EKG obtained within the past year should be available)
    • Relative:
      • Moderate airflow limitation (FEV1 <60% predicted or <1.5 L)
      • Inability to perform acceptable-quality spirometry
      • Pregnancy Nursing mothers
      • Current use of cholinesterase inhibitor medication (for myasthenia gravis)
  • Patient preparation
    • Antihistamines withheld for 48 hours
    • Vigorous exercise avoided >4 hours before testing, as prior exercise has been found to exert a protective effect. The interval between repeat testing must also be at least 4 h.
  • Monitoring
    • Spirometry
      • Baseline before exercise
      • 1-3, 5, 10, 15, 20, and 30 min after exercise
        • Olympic committee recommends first post-exercise spirometry at 3 minutes to decrease influence of muscle fatigue. Also, severe EIB can sometimes be present at the cessation of exercise.
        • If the FEV1 has returned from its nadir to baseline level (or greater), spirometry may be terminated at 20 min post-exercise.
      • If vocal cord dysfunction or other possible causes of central airway obstruction are suspected, full inspiratory and expiratory flow–volume loops should be obtained
    • Heart rate
    • Pulse ox
  • Exercise
    • Treadmill with adjustable incline, exercise bike with adjustable brake (indoors), or field challenge (usually outdoors)
    • Duration: 6-8 min (6 min for children <12, 8 min for older children/adults)
    • Intensity: target heart rate 80-90% of max heart rate for at least 4-6 minutes, with heart rate gradually increased to target during first 2-3 min.
      • The intensity of the exercise should be such that the person cannot exercise much beyond 6-8 min. If they can, it is unlikely that the workload was sufficiently hard to elicit EIB
      • Max heart rate formulas
        • HRmax = 220 - age
        • HRmax = 208 - 0.7 x age
    • Environment:
      • Standardized lab-based challenges have been performed at 68-77°F (20-25°C) with humidity <50%
      • Outdoor field challenge conditions may vary
    • End exercise when target HR maintained for at least 4 min (usually requires 6-8 min total exercise).
  • Interpretation
    • Post-exercise FEV1 values are compared with pre-exercise FEV1 values to calculate % change
    • A 10% decrease in FEV1 at any 2 consecutive time points within 30 min of stopping exercise may be considered diagnostic of EIB
      • There is no absolute standard cutoff post-exercise decrease in FEV1. Lowering the cutoff (e.g. 6% instead of 10%) will increase likelihood of false-positives, raising the cutoff will increase false-negatives.
      • Some suggest 6-10% decrease for lab-based challenge, 15% for field challenge
  • Complications
    • Beta2-agonist may be administered at any time if the patient experiences appreciable dyspnea, or if the FEV1 has not recovered to within 10% of baseline when the patient is ready to leave.


Asthma and Scuba Diving (Lang)

  • At this time, the decision for an asthmatic to proceed with scuba as a recreational activity should be made by the patient in concert with his/her asthma provider on an individualized basis, informing the patient of the potential for harm and associated theoretical risks (see below) and inviting the patient to voice his/her values and preferences.
  • Asthmatics who scuba dive are theoretically at an increased risk for the following:
    • Arterial gas embolism
    • Barotrauma
    • Bronchospasm triggered by:
      • exposure to cold ambient aquatic temperatures
      • inspiring dry, compressed air
      • physical exertion
      • apprehension that may occur in inexperienced divers.
  • Due to these risks, many believe that scuba diving is contraindicated in asthmatic persons. Epidemiologic studies have not convincingly demonstrated that a greater risk for complication exists among asthmatics, however, these surveys may have a selection bias.
  • Recent guidelines have recommended that patients with well-controlled asthma (i.e., asymptomatic, normal spirometry, with negative exercise or bronchoprovocation (e.g., mannitol) challenge should be permitted to engage in scuba diving; however, more data may be needed to make an evidence-based decisions.





Treatment


Pharmacologic

Drug
EIB Prevention Dose
Properties
Comment
Indicated by FDA for EIB
Albuterol HFA MDI
4 years old: 2 puffs 15-30 min pre-exercise
Duration: 2-4 hours
  • Most effective drugs for short-term prophylaxis and treatment of EIB
  • Daily use (alone or with ICS) may lead to tolerance with reduction in duration and/or magnitude of prophylaxis against EIB and decreased response to SABA if EIB occurs.
  • Tolerance may not develop when use of these drugs is limited to an interval of 48-72 hours (~3 times/week)
  • Indicated for children 4 years old
Salmeterol DPI (Serevent Diskus)
4 years old: 1 inhalation (50 mcg) 15-30 min pre-exercise
Onset: 15-30 min
Duration: 12 hours
  • Most effective drugs for short-term prophylaxis and treatment of EIB
  • LABAs used alone up to 3 times/week do not appear to be associated with tolerance
  • Indicated for children 4 years old
  • Starts preventing EIB ~30 min after dose
Formoterol DPI
(Foradil Aerolizer)
5 years old: 1 inhalation (12 mcg) 15 min pre-exercise
Onset: 5 min
Duration: 12 hours
  • Most effective drugs for short-term prophylaxis and treatment of EIB
  • LABAs used alone up to 3 times/week do not appear to be associated with tolerance
  • Indicated for children 5 years old
  • Starts preventing EIB ~15 min after dose
Montelukast (Singulair)
For EIB:
≥15 years: 10 mg tablet ≥2 hours pre-exercise

For asthma:
  • 1-5 years: 4 mg oral granules packet QD
  • 2-5 years: 4 mg chewable tablet QD
  • 6-14 years: 5 mg chewable tablet QD
  • ≥15 years: 10 mg tablet QD
Onset: 1-2 hours
Duration: 12-24 hours (waning with time)
  • Not as effective as SABA or LABA, providing less complete prophylaxis and "no use to reverse airway obstruction when it occurs"
  • Indicated for adolescents 15 years old
Less effective and/or not well-established
ICS
Varies, usually in combination product with LABA

  • May decrease the frequency and severity of EIB, but its use does not necessarily eliminate the need for additional acute therapy with beta2-agonists or other agents
  • Does not decrease tolerance to beta-agonists when used in combination
Ipratropium bromide HFA MDI (Atrovent)
For asthma:
2 puffs Q6 hours PRN

  • Limited data demonstrate inconsistent effect on EIB, but some patients may respond
  • Limited data demonstrates effectiveness for exercise-induced VCD
  • Weinberger: use prior to exercise for exercise-induced VCD
Loratadine
Desloratadine
?Fexofenadine


  • Loratadine, desloratadine, terfenadine (fexofenadine pro-drug) with some studies for EIB, inconsistent results
  • Common practice to use antihistamines for allergic rhinitis in the hope that there will be some effect on EIB
Note: Cromolyn sodium and nedocromil sodium (not available in US) inhaled shortly before exercise attenuate EIB but have a short duration of action. They do not have a bronchodilator activity. They may be effective alone or as added therapy with other drugs for EIB.


Nonpharmacologic therapy

  • Pre-exercise warm-up may reduce severity of EIB
    • Warm-up should be done at 60% to 80% max heart rate (220 minus patient's age) to provide partial attenuation of EIB; this refractory period may last typically from 1-3 hours and occasionally 4 hours.
    • Use with drug therapy, not alone
  • Dietary changes
    • Reduction of sodium intake - low sodium diet maintained for 1-2 weeks decreases EIB, but long-term effectiveness not known
    • Ingestion of fish oil - dietary omega-3 polyunsaturated fatty acids may reduce EIB
    • Vitamin C supplementation - 2 weeks of supplementation has been shown to improve pulmonary function, asthma symptom scores, eNO, and urinary LTs in asthmatic patients with EIB


References