Edu0096-2012 287.296

2Immunology Department, Faculty Hospitalar Sa˜o Joa˜o, EPE, Systems, Faculty of Medicine,University of Porto, Porto, Portugal Diagnosis and treatment ofasthma in athletes A. Moreira has receivedfees for providing [ To increase awareness in physicians for a prevalent but manageable health problem [ To describe the strategies to diagnose asthma in athletes and the most common practioners and takespart on the scientific [ To improve physicians’ confidence in dealing with international guidelines and Regular physical activity is recommended for with the 2012 Olympic Games approaching, it all individuals, but asthmatic athletes face seemed appropriate to review some answers special challenges in managing their disorder while practicing sport. In athletes, a diagnosis of asthma is crucial because of potential this condition. Our aim is to demystify, in implications not only on their general health, an educational perspective, this subject, and but also on their competing performance.
improve the physician’s confidence in dealing heterogeneity in asthma expression [1], as wellas variability in clinical, physiological and pathologic parameters [2]. In addition, multi-ple asthma phenotypes exhibiting differences in clinical response to treatment exist, whichposes additional difficulties in the manage- Well known by Aretaeus since the year 100 ment of these patients [3]. Also, careful AD [5], asthma induced by sport is not always consideration of available therapies is required in order to avoid adverse effects on athletic performance and also to comply with World Anti-Doping Agency (WADA) regulations.
plexes, frustrates and distresses both patients and their physicians [4]. In this context, and Diagnosis and treatment of asthma in athletes asthma occurring after intensive physical exercise [6]. The reduction in lung function taken to ensure that sport does not affect the (forced expiratory volume in 1 second; FEV1) health or welfare of the participants, as stated occurring after a standardised exercise test is called exercise-induced bronchoconstriction understand the imperative focus that should be posed in the diagnosis of asthma.
identified as major risk factors for asthma inathletes [4]. In this perspective, two different clinical phenotypes of asthma in athleteshave been recently suggested by HAAHTELAet al. [7]: 1) those who have had asthma from The clinical presentation of EIA includes early childhood, often accompanied by aller- wheezing, cough, shortness of breath and/or gic sensitisation; and 2) another distinct chest tightness, generally occurring within 5 to 30 min after intense exercise (and sometimes the sporting career, through repeated heavy during) [1, 11]. Gradual spontaneous improve- training and competitions, presenting with ment is common after finishing exercise.
Physical examination can often reveal expira- hyperventilation test and a variable associa- tory dyspnoea, expiratory wheezing or rhonchi tion with atopic markers and eosinophilic and other signs of bronchial obstruction, such ciated with allergic rhinitis can be part of the clinical presentation as allergic rhinitis affects a high percentage of elite competitive athletes.
A significant increased prevalence of hayfever In athletes, asthma diagnosis is particularly relevant because of potential implications on competition performance and training, as endurance athletes. Therefore, sneezing, ante- airway narrowing during exercise could com- rior rhinorrhoea and bilateral nasal obstruc- promise ventilatory capacity and efficiency.
tion, as well as ocular symptoms such as teary, burning and itching eyes, should be addressed [14]. Other symptoms include significant loss Olympic athletes [8]. It is also well known that it of smell (hyposmia or anosmia), snoring, post- is more frequent than in the general popula- nasal drip or chronic cough, and itching ears, tion, as well as more prevalent in elite athletes nose and throat. Besides, physicians should be (particularly those who participate in endur- aware of the fact that in athletes the clinical presentation of rhinitis is frequently more than in recreational athletes [4, 6].
subtle and might include poor-quality sleep, Additionally, asthma has been highlighted fatigue, reduced exercise performance and as a significant risk factor for unexplained death difficulty to recover after more demanding in young and healthy subjects [9], and a high proportion of asthma-related deaths have been But it should be noted that in athletes symp- reported in athletes associated with a sporting toms have been shown to be poor predictors event [10]. Moreover, there is a subgroup of of asthma [15]. Asthma-like symptoms in elite athletes who are asymptomatic but present athletes are not necessarily associated with with objective evidence of EIB [11], which raises classic features of asthma. Athletes may not the question of its potential under diagnosis suffer from the obvious symptoms like regular and the resulting under performance.
asthmatic patients do, but rather suffer from cough [15] or some nonspecific complaints, such as poor performance or ‘‘feeling out of results in chronic sustained inflammation shape’’, abdominal pain, headaches, muscle associated with persistent epithelial damage, which contributes to airway remodelling and fibrotic changes, progressive lung function letes, this poses several issues unique to this decline over time and fixed obstruction [12].
Diagnosis and treatment of asthma in athletes training with the extremely high level of asthma include: previous appointments with physical fitness and maximum oxygen uptake their physician; parental history of asthma; reached makes it difficult to discriminate between physiological and pathological limita- admissions for acute asthma exacerbations or oral corticosteroids treatment; detailed some athletes will not reveal their symptoms description of both daytime and night-time due to fear that their asthma disclosure will symptoms; triggering factors; and medication.
be detrimental, whereas, on the other side, athletes without asthma may try to secure asth- regarding cases of athletes with known asthma ma treatments in an attempt to gain a compe- but who, due to a well-controlled status, record titive advantage [1], although several studies a negative result in the bronchial provocation have proved that anti-asthmatic drugs do not test(s). In this case, the negative result should enhance performance in healthy subjects [17] not be interpreted as a misdiagnosis but as this is still a general misbelief. Therefore, objec- an improvement in relation to a well-designed tive evidence of asthma should always be part of the assessment in these subjects.
not that simple. Baseline spirometry is poorlypredictive of asthma in competitive athletes.
Often they record lung function values higherthan the general population; they may appear Other clinical entities can produce symptoms to be within the ‘‘normal’’ range, although, in similar to those related to asthma [19, 20] and reality, show a pulmonary deficit on the basis might, therefore, lead to an incorrect diag- of what is expected for an athlete [4, 18].
nosis and unsuccessful treatments (table 2).
Exercise-induced dyspnoea, in particular, is associated with many disease processes andit is interesting to note that it is in fact an suffer from EIB [19]. Wheezing or stridorcan also be caused by other airway abnorm- Due to the heterogeneity in asthma expres- question. In one instance, most of the elite athletes referred for respiratory problems do multidimensional including variability in clin- not suffer from asthma or EIB [21]. Also, it is ical, physiological and pathological para- meters. Also, and in relation to the the above one condition may coexist in a given subject.
mentioned facts related to clinical presenta- Furthermore, in the particular case of ath- tion and symptoms in athletes, it is recom- letes, their underlying high cardiorespiratory mended in this special population to obtain fitness makes the diagnostic process even more complex, as a variety of both common diagnosis by either a positive bronchodilator and rare alternative diagnoses must be con- or bronchoprovocation test. Diagnostic tests and positivity criteria are presented in table 1.
Therefore, its evaluation requires a combina- diagnoses is exercise-induced inspiratory stri- tion of patient’s history, clinical examination dor or vocal cord dysfunction. Obstruction of and judgment, as well as adequate tests in a the upper airway can cause symptoms such as shortness of breath, increased inspiratory effort, stridor and wheeze, and in many sub- rent atopic disorders should be addressed jects it is only presented during exercise [19].
and skin-prick tests or specific immunoglo- bulin E (in case skin-prick tests could not be relatively small cross-sectional area of the laryngeal orifice, which may be even further reduced by the negative pressure created on inspiration during heavy exercise, and the when evaluating an athlete with suspected paradoxical movement (adduction instead of Diagnosis and treatment of asthma in athletes Table 1 Diagnosis methods and positivity criteria set by the International OlympicCommittee to document exercise-induced bronchoconstriction in athletes [1, 4, 6] taking ICSPC20 f16 mg?mL-1 or PD20f1,600 mg (cumulative dose) orf800 mg (noncumulative dose) inthose taking ICS for at least 1 month inhalation at 85% of predictedmaximum voluntary ventilation mannitol inducing FEV1 decreasefrom baseline o15% (PD15M) FEV1: forced expiratory volume in 1 s; ICS: inhaled corticosteroids.
normal abduction) of the vocal cords during Upper respiratory tract infections are also inspiration [6, 19]. This condition is frequent- very common in elite athletes, giving rise to ly associated with psychologically stressful respiratory complaints over prolonged peri- events such as competitions. Its prevalence ods of time that are often related to competi- has been reported to be higher in elite athletes tion seasons or heavy training blocks [23].
than in the general population, and it affects Another differential diagnosis relates to 5% of those referred for routine evaluation for poor physical fitness. The increase in respira- asthma and/or EIB [22]. Differential diagnosis tory drive and work may be interpreted as is important as asthma treatment will have pathologic by subjects who find that it limits definitively no effect. However, it should be their ability to perform to their expectations noticed that about half of athletes can present [19]. Deconditioned subjects have a lower lactate/ventilatory threshold, accumulating Besides vocal cord dysfunction, exertional lactate and increasing minute ventilation inspiratory stridor may be caused by foreign body aspiration, poor-performance, psycho- lactate build-up results in exercise-associated genic stridor, infectious croup, laryngomala- increases in ventilation and ultimately hypo- cia, subglottic stenosis and exercise-induced capnia. An athlete who has become decondi- anaphylaxis, although these diagnoses are tioned during the ‘‘off season’’ may interpret an increase in respiratory drive with lesser Diagnosis and treatment of asthma in athletes Diagnosis and treatment of asthma in athletes as a prevention strategy as they protect for up to 12 h after a single inhalation. However, Other chronic disorders that are possible only formoterol acts as fast as short-acting differential diagnoses related to asthma in b2-agonists. Therefore, formoterol or a short- athletes are presented in table 2. Heart dis- acting b2-agonist, but not salmeterol, should eases and other respiratory disorders should also be considered. Obesity, which may repre- Nevertheless, it is important to note that sent a differential diagnosis to EIA in the there may be potential adverse events with common asthmatic patient, is rare in athletes.
the use of these agents, and healthcareproviders should be aware of these concerns [1]. Inhaled b2-agonists may mask worseningairway inflammation. Also, EIB is frequently not completely abolished, as exemplified instudy with a maximum reduction in FEV1 post-exercise of 18–19% after inhaling salme- both symptoms and inflammation, with mini- terol compared with 30% after placebo [27].
mal or absent adverse effects of the medica- In addition, tachyphylaxis occurs with regular tion, allowing full participation in physical use of inhaled b2-agonists, reducing their protective effect [1, 17]. Additionally, some There is no evidence supporting different concerns regarding cardiovascular side-effects treatment for EIA/EIB in athletes and non- in patients who uptake long-acting inhaled b2- athletes. However, when choosing treatment agonists on a regular basis have been high- for a specific athletic population compared lighted [28, 29]. Despite some controversy and the lack of large, well-designed, controlled, prospective studies evaluating these risks, account. For the top athlete it is important while this question remains unresolved this not only to control symptoms of asthma and possibility should be taken into consideration prevent progression, but it becomes equally when treating athletes and other patients with imperative to reduce its impact on sporting inhaled b2-agonists [30, 31]. Furthermore, an performance, often practiced under extraor- increased risk of serious adverse events with dinary circumstances. Therefore, the possibi- regular salmeterol has recently been shown, lity of a side-effect (e.g. systemic effects of together with an increase in risk of asthma- inhaled treatments or sedation of some H1- related mortality in patients not using inhaled antihistamines) from a prescribed treatment corticosteroids [32]. Besides, it has been should also be carefully considered [17].
potentiate downregulation of bronchoprotec- frequently needed to fully control EIA/EIB in tion in response to b2-agonists [33]. Therefore, athletes, and comprise two categories: con- long-acting b2-agonists should never be used troller (anti-inflammatory) and reliever (pre- regularly without an inhaled steroid, and so medication before exercise and treatment of should be reserved for a further step-up [26].
ipratropium bromide may also be tried before general population are applicable to athletes exercise or competition; it has been sug- [26], including a ‘‘step-up’’ approach if worsen- ing of EIA symptoms occur, as it may be a sign particularly well and with a higher reversibility of inadequate control of underlying asthma [4].
to this drug than to inhaled b2-agonists [13] sent, as-needed reliever medication is suitable.
Short-acting b2-agonists, such as salbutamol ticosteroids should be started if symptoms or terbutaline, are effective in reversing persist, if bronchial hyperesponsiveness and EIA/EIB. Their efficacy is optimal approxi- inflammation are present, or if bronchodila- tion therapy is required on a regular basis. Due within a few hours. Therefore, they are also to tachyphylaxis associated with inhaled b2- used before exercise for prevention. Short- agonists, the use of controller medication will acting b2-agonists are more commonly used, avoid their daily use, optimising their rescue or but long-acting b2-agonists are also effective preventive effects when most needed.
Diagnosis and treatment of asthma in athletes Table 3 Most frequent asthma and rhinitis medications and the 2012 World Anti-DopingAgency (WADA) rules [24] over 24 h; the presence in urine ofsalbutamol .1,000 ng?mL-1 orformoterol .30 ng?mL-1 is presumed notto be an intended therapeutic use of thesubstance and will be considered as anadverse analytical finding Therapeutic use exemption approvalrequired Second-generation H1-antihistaminesshould be preferred to avoid somnolence prohibited when its concentration inurine is .10 mg?mL-1Pseudo-ephedrine is prohibited when itsconcentration in urine is .150 mg?mL-1 #: depends on appropriate patient selection (evidence of specific immunoglobulin E to clinical relevant allergens),choice of allergen and correct dosage, pending a risk/benefit evaluation. It should be performed by, or under theclose supervision of, trained physicians. There is no contraindication to perform allergen immunotherapy inathletes, with the precaution to avoid physical exercise just after receiving the injection [25].
Inhaled corticosteroids have side-effects showed in children on low-to-moderate doses that should be taken into account mainly in of inhaled budesonide [35]. Despite the con- relation to sports. Although uncommon, adre- troversial results concerning growth retardation nal suppression is of particular concern. In in children and adolescents induced by inhaled healthy males inhaling fluticasone proprionate corticosteroids, this possibility should be also 440 mg twice daily it has been found that taken into account. Although rare, reduction in exercise significantly increased circulating levels bone mineral density should be considered, of fluticasone, as well as inducing a decrease in cortisol and adrenocorticotropin. The systemic practicing endurance sports, as female mara- effects of this topical treatment were demon- strated by an increase in peripheral blood leu- particular risk for osteoporosis [17].
kocytes and neutrophils, as well as interleukin-6 levels [34]. Adrenal suppression has also been protective strategy. Although, it should be Diagnosis and treatment of asthma in athletes noted that in athletes only a few studies have been performed to assess the effect of mon- telukast and they have presented some diver- rhinitis enhances the severity of asthma.
gent results. One study found no effect on Controlling rhinitis could, therefore, improve asthma control. Also, reduced nasal conges- meters [36], another study found evidence of tion should improve sleep and thereby im- EIB protection in some but not all athletes prove quality of life and, most likely, athletic performance [4]. Intranasal corticosteroids for physical performance was observed [38]. It nasal congestion are a good options [14]. Oral is probable, therefore, that these drugs are H1-antihistamines are one of the first-line effective in some athletes with EIB, but not in therapeutic options for allergic rhinitis as they attenuate the itching, sneezing and rhinor- Unlike with b2-agonists, tachyphylaxis for rhea; however, they might affect vigilance and anti-leukotrienes and inhaled corticosteroids reaction time in athletes. Therefore, second- generation non-sedating H1-antihistamines If control is not achieved, the next step should be preferred. Anti-leukotrienes benefit will comprise the increase of inhaled corti- costeroids dosage and/or the addition of a long-acting b2-agonist to corticosteroids.
respect to WADA rules related to medication Even with the potential for tachyphylaxis or use in sports. It is the athlete’s responsibility partial loss of efficacy, regular use of long- to know the rules and to abide by them.
acting b2-agonists (formoterol or salmeterol) However, as these guidelines often change, in a combined strategy does have a role in the changes [13], the physicians treating subjects receiving formoterol or salmeterol, in addi- who are active in sports should also be up to tion to budesonide or fluticasone, achieved asthma control 10 days earlier, as defined by toms, and improved quality of life, including exercise and decreased exacerbations [1]. To prescribe a combination of both molecules in the same device may be of interest as a Prophylaxis of EIA includes not only premedi- cation but also some interventions beyond pharmacotherapy which should be considered.
In difficult to control EIA/EIB, combining These include allergen/irritant avoidance (when inhaled corticosteroids, oral anti-leukotrienes possible) and immunotherapy in patients with specific allergies. A mask that facilitates warm- If treatment fails, the diagnosis should be ing of inhaled air for exercise in cold air, and also warm-up and cool-down exercises [4] may For severe exacerbations oral corticoster- be helpful to prevent or minimise EIB. A warm- oids might be necessary for short periods, up of 10–15 min, including calisthenics with although submission of a therapeutic use ex- stretching exercises with an objective of reach- emption to WADA will be then required [24].
ing 50–60% of maximum heart rate, should be mast cell stabilisers such as cromolyn or Comorbidities such as infections, gastro- oesophageal reflux and sinusitis should be modest attenuating effects on EI-broncho- promptly addressed. Exposure to pollutants constriction, but side-effects generally rele- and tobacco smoke must be avoided. In light gate these treatment classes to the side lines of the pathophysiology, hydration should be [1]. Anticholinergics have been considered as third-line treatments and are rarely required or suggested, but recent data renewed the cool dry air to be humidified and warmed, interest for this drug with some endurance which reinforces the importance of rhinitis athletes presenting higher reversibility to inhaled ipratropium bromide than to inhaled b2-agonists [13] (unpublished data).
tion should arise for patients with EIA/EIB, Diagnosis and treatment of asthma in athletes and take all necessary actions so that asthma sport based on its low asthmogenic potential [1].
is not a limitation to reach a podium and world Olympic athletes with asthma have consis- tently outperformed their peers [8], proving that with a careful diagnosis, adequate treat- We would like to acknowledge K-H. Carlsen ment and efficient preventive measures, they are able to perform at their very best. It is the Dept of Paediatris, Rikshospitalet, both Oslo, physicians’ obligation to recognise the disease Norway) for critical review of the manuscript.
o10% from baselineafter eucapnicvoluntary hyperpnoea N In athletes, asthma diagnosis is crucial because it is a prevalent condition with potential implications not only on their general health, but also on their competing performance.
N Self-reported symptoms of asthma and baseline spirometry tests are poor diagnostic predictors in athletes’ asthma and either a positive bronchodilator or bronchial provocation challenges are required.
N Treatment of underlying asthma and rhinitis should follow available guidelines and, for those engaged in competition, physicians must also keep up-to-date on the latest doping regulations both from the IOC and WADA.
N If asthma treatment is not successful, reconsider the possible differential diagnoses.
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