Challenges in Diagnosing EIA & EIB
The differential diagnosis of EIA should include other respiratory or cardiac conditions that can cause exertional dyspnea, such as exercise-induced vocal-cord dysfunction, gastroesophageal reflux disease (GERD), exercise-induced hyperventilation, being 'out of shape' and exercise-induced anaphylaxis.[1–3] Patients with seasonal symptoms or whose symptoms worsen at certain times of the year should also be evaluated for allergen sensitivities by skin-prick testing. In patients with chronic asthma, EIA may be a manifestation of poor asthma control, so overall control should be assessed along with an evaluation of comorbid conditions and how to optimize controller therapy.
Is it EIA or EIB?
All patients with suspected asthma (including suspected EIA) should be evaluated by their medical history and a physical examination, which should include examination of the ears, nose, throat and chest, and lung function tests performed before and after administration of a short-acting bronchodilator. EIA is distinguished by asthma symptoms (e.g., cough, wheezing, chest tightness, shortness of breath and/or excess mucus) after exercising for 6–8 mins. Symptoms may or may not resolve in patients who continue to exercise.[1,3] Whenever possible, self-reported symptoms of EIA should be confirmed with a positive challenge test (see later) to avoid false-positive and false-negative diagnoses. An algorithm for diagnosing suspected EIA and EIB is shown in Figure 1. The patient with EIB usually has normal pulmonary function tests (PFTs); whereas the patient with EIA usually presents with a less than normal forced expiratory volume in 1 s (FEV1) and at least 12% reversibility following bronchodilator inhalation. Consultation with a respiratory specialist should be considered if the diagnosis is unclear.
Algorithm for diagnosing suspected EIA and EIB in a patient who presents with respiratory symptoms and/or nonspecific symptoms with exercise and/or physical activity.
*Currently in review by the US FDA, although not yet approved.
EIA: Exercise-induced asthma; EIB: Exercise-induced bronchospasm; FEV1: Forced expiratory volume in 1 s; ICS: Inhaled corticosteroid; SABA: Short-acting β2-agonist.
Adapted from [1-3,7].
For patients with asthma, the expression of EIA is affected by:
The baseline level of asthma control (e.g., a patient with poorly controlled asthma might have symptoms from climbing the stairs at home);
Comorbid conditions (e.g., rhinitis) that may alter the air-conditioning ability of the upper respiratory tract, thereby enhancing the likelihood of exercise-related symptoms;
The timing of symptoms is important but may vary. Recreational athletes and children playing hard or exercising during physical education class may complain of asthma symptoms that begin shortly (6–8 min) after strenuous activity. In other cases, particularly with prolonged activity, symptoms may not appear until after exercising. Some patients describe 'running through' their asthma – in other words, they compensate by reducing the intensity of the activity until symptoms subside, after which they then increase the intensity of their exercise. These patients often have symptoms after stopping the activity.
Most patients recognize the association between their asthma symptoms and exercise or physical activity. School-age children need to be questioned about specific symptoms that occur in school – on the playground, in gym class and during any sports activities.[2,3] All patients with asthma should be asked about symptoms that occur or increase during intermittent sports activities (e.g., racquetball and tennis) and with activity in cold, dry air. Patients with both EIA and EIB, including competitive athletes, may present with nonspecific or atypical symptoms, such as poor performance or poor conditioning, 'feeling out of shape' and fatigue ( Box 2 ). One of the most common nonspecific symptoms is a dry cough after exercising that can last for up to a day.
Which Tests Support the Diagnosis?
Pulmonary Function Testing. Pulmonary function testing by spirometry at rest and postexercise should be used to confirm the diagnosis of EIA. Peak flow meters are not recommended owing to device variability, but may be useful for an individual patient to monitor his or her EIA once diagnosed.
As shown in Figure 1, patients with EIB have normal resting spirometry, with changes in pulmonary function (of ≥ 10%) evident after exercising; patients with EIA usually have abnormalities at rest as well as with exercise.[7,11] While an empiric trial of pre-exercise medication with an inhaled short-acting β2 agonist (SABA) or cromolyn sodium is commonly used to confirm the diagnosis of EIA, it is not recommended nor supported by any data, and may result in an inaccurate or missed diagnosis.
Persistent asthma is usually indicated by reduced FEV1 and/or at least 12% reversibility following inhalation of a short-acting bronchodilator. For these patients, who have mild persistent asthma and who have exercise-induced exacerbations of symptoms, a treatment trial that includes daily anti-inflammatory medication (inhaled steroid or montelukast) in addition to pre-exercise medication (as described previously) can help confirm the diagnosis. Follow-up is recommended after 3 weeks to allow the controller medication time to take effect.
For either empiric trial, further diagnostic evaluation is necessary if there is no obvious clinical improvement (Figure 1).
Challenge Tests.Exercise Challenge. Exercise challenge is the most frequently used test, although it is not the preferred test by the International Olympic Committee (IOC) Medical Commission owing to its variability and lack of specificity. It is a direct way to confirm a diagnosis of EIA or EIB, and may be particularly useful when the clinic does not have the appropriate equipment for other types of challenge test.[6,7]
The best type of exercise challenge is a sports-specific challenge or 'field test', with spirometry before and after exercise. This is often not possible, and testing for EIA usually involves standard treadmill, cycle ergometer, free-running, or step-testing in the office or in a pulmonary laboratory.[1,3] Schools often use free-running as a simple method of screening for asthma.
The intensity of the exercise is critical to performing an appropriate challenge test. According to the EIA Work Group, an exercise challenge should be of sufficient intensity to raise the patient's heart rate to 90% maximum for at least 2–4 min. A positive challenge is defined as one that produces at least a 10% reduction in FEV1 from baseline values and symptoms that correlate with the drop in FEV1. Ideally, temperature and humidity should be controlled; but this will not be possible for free-running or sports-specific challenges. High temperature and humidity may produce negative results. Under these conditions, if one test is negative, then a different challenge test should be carried out. All challenge tests should include a flow/volume curve to evaluate for vocal cord dysfunction, which can mimic EIA.
Inhalation Challenges. Indirect and direct inhalation challenges are also useful for confirming the diagnosis of EIA or EIB ( Table 1 ). Direct challenges induce airway smooth muscle contraction but are not very specific; indirect challenges are more accurate, since they cause the release of endogenous mediators that subsequently result in bronchoconstriction.[7,12,13] The most common indirect challenges utilize eucapnic voluntary hyperventilation (EVH; formerly referred to as isocapnic hyperventilation) or hyperosmolar aerosols; the IOC Medical Commission recommends either EVH or hyperosmolar challenge with mannitol dry powder to screen Olympic athletes. Methacholine challenge is the most frequently used direct challenge test, but this is also the least specific test. Tests using other agents are available, but are not accepted by the IOC Medical Commission and will not be discussed here.
Eucapnic Voluntary Hyperventilation. Eucapnic voluntary hyperventilation uses hyperventilation as a trigger of EIA and correlates well with EIA in trained athletes.[6,7,12–14] The subject breathes rapidly (between 22 and 30 times FEV1 in l/min) for 6 min while breathing dry air with 5% CO2 at between 20 and 25°C.[6,7] Although EVH is not difficult to set up, few respiratory physicians or pulmonary laboratories have the specialized equipment necessary to perform the test (Figure 2).
Specialized equipment necessary for performing eucapnic voluntary hyperventilation.
FEV1: Forced expiratory volume in 1 s.
Photo courtesy of the author.
Mannitol. Mannitol powder delivered from capsules using a dry powder inhaler is an osmotic challenge test that is can be used as a surrogate for exercise challenge and EVH in elite athletes. Spirometry is performed before and after mannitol inhalation, and the postchallenge cumulative reduction in FEV1 correlates with the severity of the exercise-induced response. Mannitol is currently used for EIA (and EIB) screening of athletes in Australia, Europe and Korea, but is not yet approved by the US FDA. This challenge has several advantages over other indirect and direct challenges: it is easy to administer, can be performed quickly and does not require specialized equipment.[13,14] When approved in the USA, it should become a commonly used test due to its simplicity, safety and established diagnostic value.[1,6,14]
Hyperosmolar (4.5%) Saline. Hyperosmolar (4.5%) saline aerosol inhalation can be used as a surrogate test for exercise challenge and EVH, simulating the effects of evaporative water loss on the airways. The hyperosmolar saline is delivered by a large-volume ultrasonic nebulizer, making this test less expensive and less complicated than EVH. It has been shown to identify EIA in individuals with asthma, but with less accuracy than either EVH or mannitol.[12,13]
Methacholine. Methacholine is the direct stimulus that is currently most often used to evaluate athletes because it is easily available in most pulmonary laboratories. It is not, however, a preferred test according to the IOC. Most guidelines recommend a provoking concentration to cause a 20% reduction in FEV1 (PC20) of less than or equal to 1 mg/ml to identify clinically recognized asthma. However, methacholine responsiveness can vary depending on testing conditions, even in the same individual, and results are not always reflective of EIA.[7,15]
Expert Rev Clin Immunol. 2009;5(3) © 2009
Cite this: Challenges in the Management of Exercise-induced Asthma - Medscape - May 01, 2009.