Exercise-induced
bronchoconstriction
–
current update and implications for
treating athletes
Demitri Constantinou, MB BCh, BSc (Med) Hons,
FFIMS
Centre for Exercise Science and Sports Medicine and
FIFA Medical Centre of Excellence, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg, South Africa
ABSTRACT
Exercise-induced bronchoconstriction (EIB) is the
occurence of transient airway narrowing that occurs
during or after exercise. A number of pathophysiological theories exist for the condition, from physiological to inhaled air quality and nutrition, all with immune mediation. Detailed history and clinical evaluation are required to make the diagnosis, substantiated by investigations of lung function establishing
minimum airway hyperresponsiveness or bronchodilator response. Chronic management involves the
prevention of acute attacks, which includes inhaled
glucocorticosteroids and either long- and/or shortacting bronchodilators (beta2-agonists), and the use
of non-pharmacological agents and methods. Acute
asthma can be life-threatening and there are established guidelines on how to manage this. Prescribing
and treating should bear in mind the current anti-doping regulations of the World Anti-Doping Agency.
Exercise-induced bronchoconstriction (EIB) is the occurence of transient airway narrowing that occurs during or after exercise, and which is reversible by inhalation of a beta2-agonist in an individual with asthma.1,2
Other reversible airway obstructive patterns relate to
asthma in the traditional sense, and may or may not be
brought on by exercise.
A number of pathophysiological theories have prevailed
in the mechanism of EIB, which include the direct effect of cold air causing bronchospasm, cooling and rewarming, mechanical stimulation of the airways due
to the increased ventilation of exercise, evaporation of
water and cooling in the airways, increased osmolality
and degranulation of mast cells.1
More recently, it appears that other influences play a
role, including the physical characteristics of inhaled air,
the content of inhaled air, immune influences, neurohumoral influences and dietary influences.2,3 Regardless of the triggering event, mediators of EIB include
histamine, acetylcholine, prostaglandins and leukotrienes. Thus the inflammatory markers exist in EIB as
they do in asthma. These mediators form the milieu for
hyperresponsive airways, which are triggered in EIB by
one or more of the abovementioned influences.4
Further, a complex of immune conditions as they relate
to exercise emerges, which includes the conditions that
are recognised as exercise-induced bronchoconstriction, exercise-induced rhinitis, exercise-induced urticaria and exercise-induced anaphylaxis.5 These conditions
are reviewed elsewhere in this edition of the journal.
It has been estimated that asthma occurs in 10-50% of
the athlete population. Among those athletes, around
90% will have EIB. Not only do athletes appear to have
increased levels of allergic and atopic conditions, but
when compared to athletes without atopic signs, they
have a higher incidence of EIB.6,7
In the clinical approach to EIB a detailed history and clinical examination are required. Specific questionnaires
have also been developed which may assist in focusing on the atopic aspect of the history.8 Symptoms of
asthma and EIB commonly include cough and breathlessness, but may also include wheezing, tightness
of the chest, excess mucus production, fatigue, poor
performance, poor recovery from exercise, and chest
pain during exercise. Specific investigations are important to confirm EIB, yet up to 44% of general practitioners would have erroneously selected peak expiratory
flow rate as the investigation of choice to confirm the
diagnosis, rather than FEV1.3,9 It is well recognised that
objective testing with correct application of technique is
required to diagnose EIB.10
MAKING THE DIAGNOSIS
The symptoms reported by an athlete are the first point
of reference from which an attending physician needs
to work. Further questions and details should be ascertained to direct the way forward in either excluding or
confirming the diagnosis. A diary of symptoms and peak
flow recordings would provide additional helpful information, and may be requested by the attending physician. Previous investigations should also be included in
the assessment, e.g. relevant skin tests (radioallergosorbent test (RAST)), serum IgE, total eosinophil count
in peripheral blood, sputum eosinophils, spirometry reports and any previous bronchial provocation tests that
may have been conducted at any age.11,12 Contributing
factors must be evaluated and also managed, bearing in
mind there may be co-pathologies present, e.g. sinusitis or gastro-oesophageal reflux disorder (GORD).
Despite this, there is an element of error in laboratory
testing. A study by Rundell and Slee13 studied laboratory versus field-based challenge tests in 23 cold-weather
athletes. In the history 50% reported symptoms yet
had normal airway function. Further, 50% of athletes
with no symptoms had lung-function abnormalities.
Therefore, if it is assumed that the testing is a reliable
means of determining functional parameters of the airways and a possible diagnosis, self-reporting is not reliable. Also, such results will be inaccurate where there
are inadequate testing conditions and sub-threshold
exercise stress.
Several flow charts have been developed and are useful
to assist a clinician to constructively, and with a specific
plan, approach an athlete who may have asthma or EIB
(Figs 1 and 2).
Bronchodilator test
The accepted threshold to confirm a clinical suspicion
of EIB is by demonstrating a 12% increase in FEV1 from
Correspondence: Prof D Constantinou, Centre for Exercise Science and Sports Medicine and FIFA Medical Centre of Excellence,
School of Therapeutic Sciences, University of the Witwatersrand, Wits 2025. Tel +27-11-717-3372, fax +27-11-717-3379, e-mail:
[email protected]
64
Current Allergy & Clinical Immunology, June 2010 Vol 23, No. 2
Respiratory symptoms of recurrent breathlessness,
cough, wheezing, chest tightness, phlegm production
Normal expiratory flows
Baseline airway obstruction
FEV1 <80%, FEV1/FVC <0.7
Administer inhaled
salbutamol 200-400 μg
No significant
change
Look for
another
cause of
symptoms
Confirm variable airway hyperresponsiveness by either
• ≥10% fall in FEV1 after exercise or eucapnic voluntary hyperpnoea
(EVH); OR
• ≥15% fall in FEV1 after hyperosmolar (saline or mannitol) challenges;
OR
• ≥20% fall in FEV1 after methacholine test – PC20 <4 mg/mL
(steroid-naive)
Provocation test
negative
Post-BD FEV1
12% or more
•
•
•
•
•
•
•
Asthma
confirmed
Provocation
test positive
Identify potential triggers/inducers of asthma and comorbid conditions
Initiate patient education (refer to an asthma educator whenever possible)
Determine environmental control measures to be prioritised
Assess current asthma medication needs (to achieve asthma control)
Initiate treatment according to current guidelines
Design and review an action plan for the management of exacerbations
Inhibit exercise-induced bronchoconstriction (optimise asthma control, pre-exercise
warm-up, preventive medication)
For the elite athlete: consider WADA
recommendations for the use of asthma medication
(in order to provide TUEs required)
Ensure regular follow-up and verify regularly asthma control, comorbidities, environmental exposures, inhaler technique, benefits and
side-effects of therapies, educational needs
Fig. 1. Flow chart for assessing asthma (Fitch et al.2).
either baseline or from predicted value, in response to
a short-acting bronchodilator.14 The predicted value is
that which is standardised for an individual based on
age, gender, weight, height and race. The baseline is
for that individual, implying that medical records of
adequately conducted tests need to be on record and
available. All testing must be done with care, using the
correct technique and reliable equipment that is clean
and calibrated. The technician or physician must be familiar with its function and be able to coach the athlete
in the correct technique and procedure to obtain optimum effort from the athlete. The inhaler use must also
be correct, and if a metered dose inhaler (MDI) is used
for the test, then a spacer device is advised to ensure
adequate active ingredient deposition in the airways.
A bronchodilator test may be negative in a number of
circumstances, such as when the athlete is adequately
treated and controlled at the time of testing, or there
is no asthma or EIB. A washout period is required for
those athletes on treatment, to negate the former reason. The recommended washout to accurately evaluate
these tests is 8 hours for short-acting beta2-agonists
and 24 hours prior to the testing for long-acting beta2agonists and inhaled glucocorticosteroids.12
Bronchial provocation tests (BPTs)9,15,16
Should a bronchodilator test not demonstrate the reversal of bronchoconstriction and the attending physician
still suspects the presence of asthma or EIB, he/she
may want to demonstrate that there is hyperresponsiveness in the athlete’s airways. This is done using a
BPT. These are one of a number of tests performed to
trigger bronchoconstriction in sensitive airways.
The BPTs are either direct or indirect tests, aimed at
provoking bronchoconstriction by the inhalation of cold,
dry air, various aerosols or by doing exercise to provoke
a bronchoconstriction response.
Direct tests
These include inhalation of metacholine as an aerosol
challenge test. Histamine is the mediator with this test.
With these challenge tests, there is direct stimulation
of the smooth muscle in the airways, which leads to the
bronchoconstriction. This process is therefore independent of inflammation.
Indirect tests
These tests include exercise challenge tests (performed
either as field- or laboratory-based tests), eucapnic voluntary hyperpnoea (EVH) (involving hyperventilation,
and considered positive if there is a fall in FEV1 of at
least 10%), and the inhalation of hyperosmolar aerosols
(e.g. hypertonic saline aerosol challenge using 4.5%)
and mannitol inhalation.
The indirect aerosol challenge tests cause inflammatory
cells to release mediators, and as compared with the
direct tests are therefore based on inflammatory cell
responses, which then stimulate bronchoconstriction.
These tests are more effective as a stimulus, and are
also useful for monitoring therapy.
Conducting the tests
Exercise test
The workload in the test is important. In a randomised
controlled clinical trial, Carlsen et al.17 in a study of asthmatic children concluded that exercise work load is essential for the interpretation of EIB and that standardisation of the test is required. Vilozni et al.18 also concluded
that the time to maximal bronchoconstriction is age dependent in children and adolescents, and implied that
the schedule of postexercise measurements should be
appropriately interpreted.
Standardisation of exercise testing
Field-based tests are considered the best environments
for testing, as they emulate the conditions that athletes
are usually exposed to most accurately.3,15,16 Therefore
laboratory-based tests are next best, but are often performed in clinical settings. Clinicians should consider
repeating the test in the field if a lab-based test is inconclusive or produces borderline results.
Current Allergy & Clinical Immunology, June 2010 Vol 23, No. 2
65
Athlete
History
Physical examination
• General, BP, pulse,
temperature
• Respiratory system
• ENT
SUSPECT EIB or asthma
Resting PFT
FEV1
FEV1 normal
FEV1 < 85% predicted
No Hx of URTI
Treat asthma
First line Mx
• β2 agonists
• Glucocorticosteroids
• Other agents
Exercise challenge
? provocation test
Recent URTI
Short trial inhaled
glucococorticosteroid
FEV1 > 15%
Re-evaluate PFT
Improvement
No improvement
Re-evaluate PFT
No improvement
Step 2 treatment
Increase drug dose
Refer to pulmonologist
Improvement
EIB management
•Non-pharmacological
•Pharmacological
•β2 agonists
•cromolyn
• leukotriene antagonists
Monitoring
Improvement
FEV1 normal
No improvement
Monitoring:
• Diary
• FEV1
Consider vocal cord
dysfunction, exercise
hyperventilation, GO
reflux
Combination therapy
Refer to pulmonologist
EIB = exercise-induced bronchoconstriction; ENT = ear nose and throat; FEV1 = forced expiratory volume in one second; PFT = pulmonary function tests; Hx = history; Mx = management; URTI = upper respiratory tract infection; GO = gastro-oesophageal.
Fig. 2. Flow chart for assessing exercise-induced bronchospasm (Constantinou & Derman11).
Once the patient has been briefed on the process, and
the equipment checked and calibrated, pre-spirometry
measurements are conducted. The environmental temperature should be between 20°C and 25°C with a relative humidity of around 50%. An 8-minute exercise test
(running or cycling) is conducted. The intensity of exercise should be such that 90% of predicted maximum
heart rate (220 minus age) should be reached within
2 minutes of the start of exercise. Ideally the athlete
should have a mask, mouthpiece and nose clip in situ.
Postexercise spirometry tests are conducted at 5, 10,
15 and 30 minutes. There should be at least 2 reproducible manoeuvres evident on the readings, within a 3%
variation to be considered adequate. Postexercise challenge tests for EIB are considered positive if there is at
least a 10% drop in FEV1 at any timepoint.
The typical change seen in the FEV1 in response to an
8-minute exercise challenge test in EIB-positive individuals is shown in Figure 3.
Eucapnic voluntary hyperventilation test
This test can be regarded as a surrogate for the exercise challenge test. It is usually conducted by academic
66
pulmonary function laboratories, and thus not commonly performed. The athlete must ventilate 22-30 times
and the FEV1 is measured for 6 minutes while he/she is
breathing dry air containing 5% carbon dioxide. The test
duration, temperature and ventilation speeds are such
that they simulate the conditions of the sport. This test
can be unpleasant for the athlete, with side-effects of
headache and nausea commonly occurring. A minimum
10% fall of FEV1 is considered a positive test.3,12
Mannitol inhalation test
Mannitol powder is delivered by a dry powder inhaler
into the airways. A 15% fall in FEV1 after challenge is
considered a confirmatory test.3,12
Hypertonic saline
A solution of 4.5% saline simulates water loss in the airways, delivered as a tidal volume as a wet aerosol which
is generated by a large nebuliser. A minimum of 15%
fall of FEV1 is considered confirmatory for asthma.3,12
Metacholine
This test appears to be better for cold and dry environ-
Current Allergy & Clinical Immunology, June 2010 Vol 23, No. 2
Management of these conditions includes speech
therapy, possibly psychological intervention and retraining of diaphragmatic breathing. This may require techniques such as mindfulness-based stress reduction,
biofeedback techniques and pharmacology with proton pump inhibitors. Further, GORD can in itself cause
symptoms similar to EIB in addition to contributing to
vocal cord dysfunction and should be treated with appropriate medication and dietary intervention.
5
0
-5
Post-exercise
-10
Exercise
-15
MANAGEMENT OF EIB9,20
-20
-25
-30
-8
0
5
10
15
Time (min)
20
30
Fig. 3. Typical EIB response with exercise test (Rundell
& Slee13)
ments. A 20% fall of FEV1 with PC20<4 mg/ml in a
steroid-naïve patient/athlete is considered a confirmatory test.3,12
Other
Other agents including carbachol, histamine, and adenosine are not tests currently accepted by the International Olympic Committee and the World Anti-Doping
Agency (WADA).
DIFFERENTIAL DIAGNOSIS19
Any athlete who presents with symptoms of asthma
or EIB should have the diagnosis confirmed, and other
pathologies excluded. Some of the simulators of EIB
include physiological limitation (normal VO2max or peak
exercise variable), deconditioning (reduced VO2max or
peak exercise variable), obesity (reduced expiratory reserve volume and total lung capacity), anxiety and hyperventilation syndrome (also known as panic attack –
with supratentorial overinterpretation of receptor input,
and might be associated with carpopedal spasm, tetany
and seizures), cardiac abnormalities (mild pulmonary
oedema, hypertrophic cardiomyopathy, cardiac arrhythmias, vascular abnormalities of the thoracic aorta, pulmonary arteriovenous malformations and other causes
of hypoxia), pulmonary abnormalities and myopathy.
Vocal cord abnormalities
This is a specific condition that should be mentioned,
as it is not unusually misdiagnosed as asthma and EIB.
There is a higher incidence of this in young females as
compared to males. It possibly occurs more frequently than thought, as a result of the diagnosis not being
made, rather than its rarity. There is obstruction of upper airways producing shortness of breath, increased
inspiratory effort, stridor and wheezing, which may be
dynamic and present only during exercise. In this condition there is paradoxical movement of the vocal cords.
It is estimated to occur in 5-15% of all athletes investigated for EIB. The clinical picture includes inspiratory
wheezing and throat tightness. It is more common in
people with GORD and those with ‘type A’ personalities.
Special investigations that can assist in confirming the
diagnosis of vocal cord dysfunction include lung function tests (which show variable blunting of the inspiratory loop of the flow volume), and fibreoptic rhinolaryngoscopy which reveals paradoxical movement of the
vocal cords. The latter may have to be performed before and after exercise to confirm the condition.
Inflammation is the underlying pathology, and should be
managed with inhaled corticosteroids, which should adequately reverse the inflammation within 6-8 weeks. In
addition allergic rhinitis should be addressed and most
if not all these patients should use intranasal glucocorticosteroids. Education on the nature of the condition is
a very important aspect of management, and should be
directed not only at the patient, but also their parents,
coaches and peers. The educational aspect should include an understanding of the condition, factors that
may influence it (e.g. aeroallergens, nonsteroidal anti-inflammatory drugs (NSAIDS)), how to try to avoid acute
attacks, management of attacks, how to use inhalers
and spacer devices correctly and using the refractory
period (see below).
Pharmacological management9,11,12
The pharmacological management of asthma is twofold – to reduce and prevent the incidence of symptoms
and bronchoconstriction, and to assist the reversal of
bronchoconstriction should it occur.
Inhalers
Pre-exercise medication is used to prevent the induction of bronchospasm by the impending exercise bout
(Table I). This includes inhaled glucocorticosteroids
used daily to reduce inflammation; and inhaled beta2agonists. Airway inflammation can be present in athletes with EIB, who would be considered as patients
with exercise-induced asthma. In these patients inhaled
corticosteroids could be a treatment option, although
the efficacy of these products has not yet been demonstrated in patients with EIB without underlying asthma.1 The beta-agonists are either short-acting (e.g. salbutamol) or long-acting (e.g. salmeterol). The long-acting
type may have some anti-inflammatory effect and can
be used on a daily basis for that reason and to maintain bronchodilation. Their onset of action is rapid, as
for short-acting agonists, but duration can be up to 12
hours. In case of EIB without underlying inflammation
(exercise-induced asthma), they can be used as monotherapy.21 Short-acting beta-agonists should not have to
be used more than a few times a month for rescue, but
can also be used pre-exercise (20 minutes).
Mast-cell stabiliser inhalers include nedocromil sodium
and sodium cromoglycate/cromolyn sodium. These appear to be less effective than beta-agonists. They are
however useful where beta-agonist side-effects (palpitations, insomnia, tremors) are problematic. They may
also be used in combination with beta-agonists when
those are not as effective as desired. Unlike beta2agonists they can be used repeatedly and frequently in
a day.
Anticholinergic inhaler treatments, both short- and longacting, are not as effective in EIB as they are in chronic
obstructive pulmonary disease.
Oral and intranasal medication
Leukotriene modifiers are often used in chronic asthma
sufferers, as leukotrienes can cause smooth-muscle
Current Allergy & Clinical Immunology, June 2010 Vol 23, No. 2
67
Table I. Pre-exercise medication for EIB (after Constantinou & Derman11)
Medication
Mode
Recommended dose
Onset of action
Duration of effects
(hours)
Beta2-agonists
Salbutamol
Metered dose inhaler (MDI), dry powder device 2 puffs 15 minutes
before exercise for
adults and children ≥age 4
Within 5 minutes
3-6 hours
Terbutaline sulfate MDI, dry powder device 2 puffs every 4-6
hours for adults and
children ≥12 years
5-30 minutes
3-6 hours
Salmeterol MDI, dry powder device
2 puffs ≥30-60 minutes
before exercise or
12 hourly
Within 20 minutes
12 hours
Formoterol
MDI, dry powder device
2 puffs ≥30-60 minutes
before exercise or
12 hourly
Within 15 minutes
12 hours
2 puffs within 60 minutes of exercise
for adults and children
≥age 5
–
2 hours
May take up to 1
week of use for
full effect
2 hours
Mast cell stabilisers
Cromolyn sodium MDI
Nedocromil sodium MDI
2 puffs qid for adults and children ≥ age 6
Long-term medication for EIB
Inhaled corticosteroids
Beclomethasone MDI
diproprionate ≥age 12, 2 puffs
(84 μg) tid or qid;
age 6-12, 1 or 2 puffs
(42- 84 μg) tid or qid
-2 days
–
Budesonide MDI
Adults 1-2 puffs bid, children ≥6 years
1 puff bid
24 hours
–
Fluticasone
MDI
propionate ≥12 yrs, 2 puffs
bid (88 - 440 μg)
24 hours
–
Triamcinolone MDI
acetonide Adults 2 puffs (200
μg) tid or qid; children
age 6-12, 1 or 2 puffs
(100 - 200 μg) tid or qid
1 week
–
Montelukast
Tablet
10 mg daily for those ≥ age 15; 5 mg daily
for children age 6-14
3 - 4 hours
Up to 24 hours
Zafirlukast
Tablet 20 mg bid for adults and children ≥ age 12
30 minutes
12 hours
Leukotriene modifiers
contraction. They are convenient, being oral formulations, and have few side-effects. They are long-acting
and may be useful in EIB when the symptoms are mild,
but often need to be used as adjunct therapy to optimise control. There is a variable response, with a significant number of non-responders (up to 50%).22
In children leukotriene-modifying drugs may be useful
as a long-term treatment option, but do not appear to
reduce the protective effect on EIB over time.20
Theophylline is an oral treatment, and not very useful
for EIB.
Oral antihistamines are not specifically indicated for
asthma, but may be useful as adjunct treatment in those
68
athletes who have atopic conditions. A randomised,
double-blind, placebo-controlled study in patients with
exercise-induced bronchospam looked at FEV1 and
treadmill exercise. Using 10 mg of oral loratidine once
daily for 3 days the researchers showed that loratadine
reduced but did not prevent EIB in children.23
Intranasal corticosteroids (and/or antihistamine) are also
important adjunct treatments for those with asthma/
EIB as well as chronic or seasonal rhinitis.
In relation to pharmacological treatment of EIB, it may
be that a combination of therapies is required to achieve
optimum control.
Current Allergy & Clinical Immunology, June 2010 Vol 23, No. 2
Table II. Non-pharmacological management of EIB
Management
Mode of action
Maintaining aerobic fitnessCan exercise at lower
ventilator rate for given
workload
Adequate warm-up / pre-competition
exercise
To induce refractory
period
Avoid exercise in excessively cold and /or dry air
Reduced responsiveness
of airways
Avoid exercise/
intense exercise when related symptoms present
Rhinitis, sinusitis, allergies
indicate hyperresponsive
state in airways
Adequate warming down
Avoids rebound warming
and reduces airway
oedema
Change of exercise / sport
With severe symptoms,
changing activities to
sports less likely to
induce EIB
Wearing of face mask
Reduces inhalation of
pollutants and irritants
Avoiding known allergens
or irritants
Prevents allergic reactivity
Non-pharmacological management of EIB
A number of approaches can be tried to reduce the incidence of symptoms of EIB (Table II). One such useful
modality is making use of the refractory period; some
authors have demonstrated that individuals with asthma and EIB will be refractory to an exercise task performed within about 2 hours of an exercise warm-up.
The refractory period could be induced by a release of
prostaglandins and other mediators and mechanisms
in this period. This is not consistent and some authors
have not been able to demonstrate a refractory period
in winter athletes with EIB.13
Nutritional factors are gaining more attention for their
influence on EIB,24,25 and some that may be practically
applied include a low-salt diet, supplementation with
high-dose vitamin C, high-dose omega oils, caffeine
(which is a methyl xanthine with bronchodilator properties), and some which may be less accessible such as
qigong yangsheng.
Experimental modalities include the use of inhaled heparin, inhaled furosemide and oral calcium channel blockers, which are currently not of practical clinical value.
MONITORING ATHLETES
After athletes have been on a trial of active medication,
they should be reassessed for the efficacy of their management by means of symptom diary monitoring and
home peak expiratory flow readings, repeat exercise
testing and spirometry .
If after a trial of management athletes show no or only
a minor response to treatment, or when the diagnosis
is in doubt, they should be evaluated for vocal cord dysfunction, exercise-induced hyperventilation, or chronic
gastro-oesophageal reflux.
ACUTE ASTHMA
The differential diagnosis of acute asthma includes upper airway obstruction with glottic dysfunction, acute
left ventricular failure with pulmonary oedema, pulmo-
nary embolism, endobronchial disease, chronic bronchitis, eosinophilic pneumonia, carcinoid syndrome and
vasculitis.
Management of acute asthma26
At the field side most important is the use of a beta2agonist (e.g. salbutamol 5 mg) via a nebuliser if it is
available. If no nebuliser is available, salbutamol inhalation of 10-20 puffs, using a spacer device is advised. A
spacer device can be made by using a water or cooldrink plastic bottle if one is not available. The technique
is to inhale one puff and allow for 4 breaths between
puffs. Corticosteroids are given as tablets or injected
intravenously, or even intramuscularly, for their action
against the inflammation, which will be effective in the
medium to longer term.
It is advisable that all athletes with asthma carry shortacting beta-adrenergic inhalers with them at all times,
irrespective of their regular management.
Physicians should exercise caution with prescribing antiinflammatory medications and beta-adrenergic blockers, which can cause bronchoconstriction.
Asthma and doping
It is debatable whether beta2-agonists increase sports
performance, but they are subject to certain anti-doping
rules and regulations.17
WADA publishes a list annually of substances that are
prohibited in all or specific sports, based on any two or
all of three criteria.14 These are: (i) medical or scientific
evidence, pharmacological effect or experience that the
substance or method, alone or in combination with other substances/methods, has the potential to enhance
or enhances sport performance; (ii) medical or scientific
evidence, pharmacological effect or experience that the
use of the substance or method represents an actual
or potential health risk to the athlete; (iii) WADA’s determination that the use of the substance or method
violates the spirit of sport (described in the introduction
to the Code).
The prohibited list is divided into different substance
groups and includes prohibited methods (www.wadaama.org).
Prohibition applies not only to finding these substances,
their metabolites or markers in an athlete’s body fluid,
but also a number of other violations.
Therapeutic Use Exemption (TUE)
WADA publishes an International Standard for Therapeutic Use Exemption.27 This is a globally standardised
policy and relates to the allowing of substances, for legitimate medical reasons that are otherwise prohibited
in sport according to WADA. There is also a category of
reporting certain substances via a Declaration of Use
(DoU) to a sporting code’s relevant authority. The 2010
standard allows for a DoU to be lodged for 2 bronchodilators (salbutamol and salmeterol) and for all inhaled
corticosteroids via non-systemic routes. All other bronchodilators and glucocorticosteroids that an athlete and
his attending physician want to use must be subjected
to a TUE process. For acute asthma attacks an athlete’s
health should not be put at threat by withholding treatment in an emergency; corticosteroids, other drugs
and intravenous infusions should be used. Retroactive
TUEs can be approved for emergency treatment in
such cases.
The TUE process follows strict routes via international
standards and a TUE committee (TUEC) that will use
a number of criteria to determine whether the use of
a prohibited substance can be approved for use with
a TUE. To assist in the diagnosis of asthma and allow
Current Allergy & Clinical Immunology, June 2010 Vol 23, No. 2
69
for granting a TUE, WADA has published a document
entitled Medical Information to Support the Decisions
of TUECs: Asthma.12 This guides the TUEC in medical
best practice, making the diagnosis and the recommended management.
12.WADA. World Anti-Doping Program Version 1.4. (2009, June 14).
Medical Information to Support the Decisions of TUECs: Asthma.
Declaration of conflict of interest
15.Cockcroft D, Davis B. Direct and indirect challenges in the clinical
assessment of asthma. Ann Allergy Asthma Immunol 2009; 103:
363-370.
The author declares no conflict of interest.
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to the diagnosis and management of suspected exercise-induced
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10.Millward D, Paul S, Brown M, et al. The diagnosis of asthma and
exercise-induced bronchospasm in division I athletes. Clin J Sport
Med 2009; 19: 482-486.
11.Constantinou D, Derman EW. Exercise-induced asthma. CME 2004;
22 (3): 126-132.
13.Rundell KW, Slee JB. Exercise and other indirect challenges to
demonstrate asthma or exercise-induced bronchoconstriction in
athletes. J Allergy Clin Immunol 2008; 122: 238-246.
14.WADA. World Anti-Doping Code. Montreal: WADA, 2009.
16.Cockcroft DW, Davis BE. Diagnostic and therapeutic value of airway
challenges in asthma. Current Allergy and Asthma Reports 2009; 9:
247-253.
17.Carlsen KH, Anderson SD, Bjermer L, et al. Treatment of exerciseinduced asthma, respiratory and allergic disorders in sports and the
relationship to doping: Part II of the report from the Joint Task Force
of European Respiratory Society (ERS) and European Academy of
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Product News
The importance of LCPUFAs for brain function
Breast milk is the ‘gold standard’ in infant feeding,
both in composition and in the physiological effects
closely tied to its composition. It is established as a
perfect food for term infants and is confirmed as the
best sole source of nutrition for the vast majority of
infants for approximately the first 6 months of life.
Breast milk contains the two most abundant longchain polyunsaturated fatty acids (LCPUFAs), docosahexaenoic acid (DHA) and arachidonic acid (ARA),
which have a functional and structural role in infant
development. LCPUFA levels vary widely depending
on maternal diet, ranging from 0.05% to 1% DHA
and from 0.1% to 0.9%ARA in women who consume
western diets. These LCPUFAs are accreted mainly
in the last trimester, when brain and visual maturation
is at its peak, to about 2 years of age.1
The availability of LCPUFAs in the infant diet may
have long-lasting effects on brain function. Numerous studies have found positive correlations between
blood DHA levels and improvements in cognitive or
visual function outcomes of breastfed and formulafed infants.2
The visual system (retina and brain) continues to
mature throughout the first year of life and the importance of providing an appropriate supply of DHA
and ARA is relevant throughout infancy, as both fatty
acids continue to accumulate rapidly in brain grey
matter through at least the first 2 years of life.1
The role of DHA in visual development is of key interest
because of the uniquely high concentration of DHA in
photoreceptor cell membranes of the retina. Since the
retina and brain are both tissues derived embryologically from neuroectoderm, measuring functional out-
comes in the visual system provides a readily accessible index to neurodevelopmental milestones.3
On January 22, 2009 the Panel on Dietetic Products,
Nutrition and Allergies of the European Food Safety
Authority (EFSA) concluded that the scientific evidence they reviewed supported the claim that ‘DHA
contributes to visual development of infants.’ They
further specified that, in order to bear this claim, an
infant formula should contain at least 0.3% fatty acids from DHA. On March 13, 2009, EFSA delivered
an opinion on DHA and ARA and brain development
in which DHA level and ARA: DHA ratios of 1:1, in formulas were linked to potential neurodevelopmental
effects of supplementation.2
The Nestlé NAN range contains DHA and ARA.
REFERENCES
1.Hoffman DR, Boettcher JA, Diersen-Schade DA. Toward optimizing vision
and cognition in term infants by dietary docosahexaenoic and arachidonic
acid supplementation: A review of randomized controlled trials. Prostaglandins, Leukotrienes and Essential Fatty Acids 2009, 81: 151–158.
2.Morale SE, Hoffman DR, Castaneda YS, et al. Duration of long-chain polyunsaturated fatty acids availability in the diet and visual acuity. Early Human
Development 2005; 81: 197-203
3.Auestad N, Scott DT, Janowsky JS, et al. Visual, cognitive, and language assessments at 39 months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age. Pediatrics 2003;
112:e177-e183