PART 1

CARDIOVASCULAR EVALUATION OF ATHLETES
Recommendations concerning participation in athletics by persons with possible
cardiovascular disorders arise in three contexts: ﬁrst, the eligibility of potential
athletes with a known cardiovascular disorder to participate in athletics; second, theathlete with symptoms that suggest a possible cardiovascular abnormality; ﬁnally,
non-symptomatic, “healthy” young people may be found to have a possible cardiac
abnormality during routine pre-participation examination.
Although the risk of sudden death is small, a few athletes die from cardiovascular disease each year, and the impact of these deaths is great. Persons withsevere aortic stenosis, hypertrophic cardiomyopathy, and some congenital lesions areat increased risk of sudden death during and after exercise. Thus it is the physician’s
responsibility to make participation by these athletes as safe as possible. Also, thepossible effects of exercise on the progression of existing heart disease must berecognised, assessed, and addressed.
A. Diagnostic Techniques

Most valvular and septal defects can be detected and diagnosed by physicalexamination. In order to make an informed opinion regarding sports participation,
however, additional diagnostic tests are usually needed to determine the severityof the problem. The test to assess the severity of the defect is echocardiography,
with electrocardiogram and chest X-ray providing additional measures of heartsize. Other non-invasive tests must be used in speciﬁc situations. For example,
two-dimensional and M-mode echocardiography can be used to assess chambersize, wall thickness, and valve motion. Doppler ﬂow echocardiography is valuable
in quantifying obstruction to ﬂow or regurgitation. Radio-nuclide angiography can
assist in determining coronary circulation and cardiac output.
Exercise electrocardiography may be necessary to determine an individual’s
response to exercise, especially if an arrhythmia or ischemia is suspected. Exercise
testing should be modiﬁed to simulate the athlete’s event or sport. If an intermittent
rhythm or conduction disturbance is suspected, continuous ECG (Holter) monitoring
will be needed.
Finally, cardiac catheterisation may be required to determine the degree of
valvular stenosis, shunting, or pressure gradient.
B. The “Athlete’s Heart Syndrome”

Athletes who participate regularly in athletics often develop changes in theirheart, circulation, and electrocardiogram that may be difﬁcult to distinguish fromthose associated with true cardiac pathology. This complex of changes is often
referred to as the “athlete’s heart syndrome.” It is seen most often in endurance
athletes. The athlete’s heart syndrome is characterised by an increase in para-

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

sympathetic tone, especially vagotonia and consequent bradycardia, as well as avariety of conduction changes. Characteristics of the syndrome may include:
1. Increased left ventricular volume. This is seen as cardiomegaly duringphysical examination and X-ray. It is usually accompanied by a mild
to moderate degree of ventricular wall thickness (hypertrophy).
2. Resting bradycardia
3. Electrocardiographic changes:
a. Left ventricular hypertrophyb. Sinus bradycardia
c. Anterior wall S-T and T wave changes
d. Atrio-ventricular conduction abnormalities:
i. First degree A-V blockii. Wandering pacemakeriii. Second degree A-V block, of Mobitz Type I (Wenckebach)varietye. Bundle branch block:
Partial or complete right bundle branch block (the occurrenceof left bundle branch block is usually indicative of cardiac
pathology).
Athletes whose training includes primarily resistive exercises, such as strength
training (weight lifting) or wrestling show evidence of left ventricular wall hypertrophy, but little or no increase in ventricular volume. However, the ventricular wall
thickness does not exceed 13 mm, but a “gray zone” of 13–15 mm may exist insome large male athletes, and requires evaluation by additional criteria to exclude
the possibility of hypertrophic cardiomyopathy (Figure 14-1). Female athletes havenot been found to have a ventricular wall thickness of more than 13 mm, but those
who train extensively with high intensity resistance exercise have not been studied.
C. Athletes with Known Cardiovascular Disorders

Athletes may exhibit a wide variety of disorders, but most fall into six generalcategories:
1. Congenital Disorders
2. Acquired Valvular Disease
3. Cardiomyopathies and Mitral Valve Prolapse
4. Hypertension
5. Rhythm and Conduction Disturbances
6. Ischemic Heart Disease
A careful, detailed medical history can help the physician determine the natureof a disorder and advise the athlete about participation in strenuous activities.
A thorough discussion of all possible defects in each category is beyond thescope of this brief review, but the high-risk conditions in each category are as
follows:

CHAPTER 14, SPECIAL MEDICAL PROBLEMS“Gray Zone” of
LV Wall Thickness(13–15mm)

Athlete’s
Heart

HCM*

“Gray Zone” of
LV Wall Thickness
UnusualPatterns of LVH †(13–15mm)
LV Cavity < 45mm
LV Cavity
55mm of“Gray>Zone”

LV WallMarkedLAThickness
Enlargement“Gray Zone” of
LV Wall Thickness(13–15mm)(13–15mm)
Athlete’s
HCM*
Bizarre ECG Patterns
Heart
Abnormal LV Filling
Female Gender
Thickness withAthlete’s
Deconditioning

HCM*

Heart

Family History of HCM
UnusualPatternsof LVH†Max.
VO > 45ml/kg/min.

HCM*

2
Athlete’sLV Cavity < 45mm
> 110% predicted ‡Heart

Cavityused> 55mmFigure 14-1. Chart showingLVcriteria
to favour or distinguish hypertrophic cardiomyopathy(HCM) from athlete’s heart Marked
when maximal
left ventricular (LV) wall thickness is within shaded
LA Enlargement
UnusualPatternsof LVH† both diagnoses. *Assumed to begray zone of overlap (i.e., 13Bizarre
to15 mm),
consistentwith
ECG Patterns
the non-obstructive form of HCM(underresting conditions) in this discussion because the
LV Cavity< 45mmAbnormal
LV Fillingpresence of substantial mitralvalvesystolic
anterior motion would conﬁrm the diagnosis
LV Cavity > 55mm
Unusualof LVH † May
of HCMPatterns
in the athlete.
involvea variety of abnormalities, including heterogeneous
FemaleGender
LA Enlargementof left ventricularMarked
hypertrophy(LVH) in which asymmetry is prominent andLVdistribution
Cavity < 45mm
Thickness with Deconditioning
adjacent regions may show greatly
thicknesses with sharp transitions evident
Bizarredifferent
ECG Patterns
LVbetween
Cavity > segments,
55mm
Historyof HCM
as wellFamily
as unusual
patterns
in which the anterior ventricular septum
Abnormal LV Fillingis spared
from the hypertrophic
processandLV
thickening may be in posterior portion ofMarkedLA Enlargement
Max. VO2 > 45 ml/kg/min.
Female Gender
septumoranterolateralor
posterior
free
wall
or
apex. ‡ Assessed with cardiopulmonary>110%
predicted
Bizarre ECG Patterns(metabolic) exercise testing. Thickness= decreased;
ECG=
electrocardiogram; LA = left atrial. Adaptedwith Deconditioning
Abnormal
LV Fillingfrom Maron,
B. J., and D. P. Zipes (2005).
Female Gender

Family History of HCM

Max. VO2 > 45 ml/kg/min.
Thickness with Deconditioning> 110% predicted ‡1. Congenital Heart Disease
Most congenital heart disorders are discovered in childhood, and repair will
Max. VO2 > 45 ml/kg/min.
have been
carried our before participation in sports. Mild defects that do not affect> 110% predicted ‡cardiac function or that have a good long-term prognosis should not affect the ability
to participate in sports. In other cases, the ability to participate in sports will be
determined by the extent of the defect, the success of the repair, and any residual
Family History of HCM

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

effects, such as pulmonary hypertension, chamber hypertrophy, or shunting andarterial desaturation.
2. Acquired Valvular Diseases
a. Aortic Valve Diseasei. Stenosis
Sudden death can occur in individuals with severe stenosis but israre in those with mild degrees of obstruction. Those with mild stenosis
may participate in competitive athletics, but the disorder should be
re-assessed periodically with Doppler echocardiography and possible
catheterisation, as the lesion may progress in severity.
ii. Regurgitation
Individuals with any degree of aortic regurgitation should notparticipate in vigourous exercise.
b. Mitral Valve Disorders
Athletes with mild degrees of stenosis or insufﬁciency, and with normal
left ventricular size and normal sinus rhythm, may participate in all sports.
3. Cardiomyopathies and Mitral Valve Prolapsea. Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden
death in young athletes, whereas coronary artery disease is the most frequentcause in older athletes. HCM is a relatively common genetic abnormality,
occurring in approximately 0.2% (1:500) of the population. It is inheritedas a mendelian autosomal dominant caused by a mutation in one of 12 genes(over 400 mutations have been found), each encoding proteins of the cardiac
sarcomere that have contractile, structural, or regulatory functions. Due to theheterogeneity of the many identiﬁed mutations, there is considerable clinicalvariance in the presentation of this disorder. Genotyping of suspectedindividuals is available, but is time-consuming and expensive.
The clinical presentation of HCM usually does not occur before the lateteens. The diagnosis may be suspected if there is a systolic murmur
associated with outﬂow tract obstruction, but this is not common. Other
indications are a family history of premature sudden death, new symptoms ofchest pain or dyspnea, an arrhythmia, or an abnormal ECG. A major clinicalproblem is one of distinguishing between the cardiac changes seen in highly
trained athletes, and those due to cardiac diseases such as HCM, dilated cardio
myopathy, and arrhythmogenic right ventricular cardiomyopathy (ARVC) .
The ventricular wall thickness in trained athletes seldom exceeds 13 mm.
However, some large male athletes who participate in resistance sports(weightliftng, wrestling) may have a ventricular wall thickness in the 13–
15 mm “gray zone.” Similarly, some endurance athletes may have dilated
left ventricular (LV) chambers that exceed the end-diastolic dimension of

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

60 mm or more, with low-normal LV function. Criteria for distinguishing
between HCM and the “Athlete’s Heart” are listed in Figure 14-1.
Cautions:
Athletes with probable or diagnosed HCM should not participate in mostcompetitive sports. Prior treatment with drugs, surgical interventions, alcohol
septal ablation, an implantable pacemaker or implantable deﬁbrillator, should not
be criteria for allowing sports participation. The stresses of the competitive milieu
present unique challenges for which these interventions may not be able to adapt,or the devices may malfunction. Further, the presence of an automated externaldeﬁbrillator (AED) at sports activities should not be considered as a protection
against sudden death, or as a rationale for allowing participation of athletes with
HCM or other high-risk cardiac disorders.
b. Marfan’s Syndrome
Marfan’s Syndrome is an autosomal dominant disorder of connective
tissue. Over 400 mutations have been found in the gene that encodesﬁbrillin-1 (FBN-1). It has an estimated prevalence of 1:5000–1:10000in the general population.
Those with Marfan’s Syndrome are typically tall and thin, with hyperextensible joints, mitral valve prolapse, aortic valve regurgitation, aortic
dilatation, and a potential for aortic dissection. Dissection can result in
sudden death. The degree of aortic dilation must be assessed by echocardiography. Individuals without aortic root dilation or mitral valve
prolapse may participate in low-intensity activities; a few may engage inactivities with a high dynamic and low static demands (i.e., endurance
activities).
c. Mitral Valve Prolapse (MVP)This common, usually benign lesion affects 2–3% of the general population
and rarely causes sudden death. Contra-indications to exercise include:
i. History of syncopeii. Family history of sudden death due to MVP
iii. Chest pain, worse with exercise
iv. Repetitive ventricular ectopy or supra-ventricular tachycardia,
worse with exercise
v. Moderate to marked mitral valve regurgitation
vi. Associated dilated aorta, with Marfan’s Syndromevii. A prior embolic eventd. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
This is a rare disorder, but it has been associated with sudden death inyoung athletes. It has a broad phenotypic spectrum, and is characterisedby a loss of myocytes in the right ventricular myocardium, with replacement
by fatty or ﬁbro-fatty cells. There is thinning of the ventricular wall, and it isoften associated with myocarditis. Diagnosis is difﬁcult—a family history,

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

ventricular tachyarrhythmias, and T wave inversion in leads V1–V3 arediagnostic clues. These individuals should not participate in competitive
sports.
e. Congenital Long Q-T Syndrome
The diagnosis of this syndrome is complex, as many individuals with thisgenotype may have a normal corrected Q-T interval (QTc), while normal
persons (approximately 25%) may have a Q-T interval of 440 ms, which
previously has been considered as the upper limit of normal. A Q-T intervalof 470 ms in males, and 480 ms in females requires further study. A patientwith the Long Q-T Syndrome (LQTS) and a resting QTc of 500 ms or longer
is considered at risk for severe arrhythmias.
There are at least 150 mutations in 7 cardiac ion-channel genes that are
responsible for 75% of these cases, and a diagnostic test is now available.
Other diagnostic criteria include: family history, T wave abnormalities, andsymptoms such as syncope, in addition to the ﬁnding of a long QTc.
All competitive sports should be prohibited in those who have had an
out-of-hospital cardiac arrest, or a suspected LQTS-precipitated syncopal
episode. Athletes who are genotype-positive/phenotype-negative (i.e.,mutations but no symptoms and a non-diagnostic QTc) may be allowed tocompete. Non-symptomatic patients with a baseline QT (QTc 470 ms inmales, 480 ms in females) should be restricted to mild activities.
f. Other Inherited Arrhythmias
Other inherited arrhythmias include the Brugada Syndrome (J wave in
V1-3, ST segment elevation, and negative T wave), Short Q-T Syndrome(QTc less than 300 ms), and Catecholaminergic Polymorphic Ventricular
Tachycardia (CPVT), which are caused by mutations in various conduction
and receptor systems. All of these may precipitate a sudden fatal arrhythmia
during exercise or with a rise in body temperature, and must disqualify the
subject from participation in vigorous exercise until further studies arecarried out and the extent of the abnormality is determined.
g. Anomalous L. Coronary Artery from the R. Sinus of Valsalva
This rare condition is difﬁcult to diagnose pre-mortem, but can cause
sudden death. After surgical repair, participation is permissible if an
exercise ECG is normal.
4. Hypertension
Secondary causes of hypertension, including coarctation of the aorta andpolycystic renal disease, must be excluded.
Sports participation depends on the extent of organ involvement (left ventricular
hypertrophy, renal, or eye disease) and the ability to control blood pressure withappropriate medications. Calcium channel blockers or angiotension-converting
enzyme inhibitors are the most suitable for those who participate in athletics. Bloodpressure control should be assessed during exercise or immediately post-exercise.

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

5. Arrhythmias/Conduction Disturbances
Arrhythmias are often transient and difﬁcult to diagnose, and are not always
reproduced by exercise. Autonomic “tone,” which is higher in trained athletes,
affects arrhythmia occurrence. Changes in sinus node function and low-grade A-V
conduction delays may result from chronic endurance exercise itself.
a. Ventricular Pre-excitation
This disorder is characterised by a P-R interval of less than 120 ms anda QRS that exceeds 120 ms and has a slurred, slowly rising onset andsecondary ST-T changes. It is often associated with tachy-arryhthmias,i.e., the Wolff-Parkinson-White Syndrome (WPW). The tachycardia is
usually 150–250 beats per minute.
An individual whose accessory pathway has a short refractory period(less than 200 ms) is at risk of very rapid heart rates and sudden death.
Those with a history of palpitations or syncope should be examined to
exclude structural heart diseases, and have 24-hour monitoring and anelectro-physiologic study to determine the properties of the accessory
pathway. Recently, surgery has been used to ablate the accessory pathway.
b. Ventricular Dysrhythmias (PVCs, Ventricular Tachycardia, Ventricular
Flutter)
Individuals whose dysrhythmia is precipitated by exercise, who haveunderlying heart disease, or who have the “Prolonged QT Syndrome”
should not participate in intense exercise.
c. Heart BlockFirst-degree heart block and Mobitz Type I block (Wenckebach) may
occur as a result of endurance training itself. Athletes with these disorders
who have no heart disease and whose block is not worsened by exercise
may compete in sports. Persons with Mobitz Type II block or acquiredcomplete (3rd degree) heart block should be treated with a pacemaker.
Those with congenital complete block, a satisfactory response to exercise,and no dysrhythmias may participate in athletics.
d. Bundle Branch Block
Partial Right Bundle Branch Block (BBB) is common in endurance
athletes. Left Bundle Branch Block is more often associated with structural
heart disease, especially in older patients. Athletes with complete BBB, no
structural defects, and no ventricular dysrhythmias may participate in all
sports.
6. Atherosclerotic Coronary Artery Disease
Atherosclerotic coronary artery disease (CAD) is the commonest cause of
cardiac events in older athletes, especially those over age 35–40. Although exercise
has beneﬁcial effects on the healthy as well as those with diagnosed CAD, vigorous
exercise transiently increases the risk of a cardiac event (myocardial infarction orCHAPTER 14, SPECIAL MEDICAL PROBLEMS

sudden death). Plaque rupture or plaque erosion may be responsible for these events,
even though the coronary arteries may not have been signiﬁcantly narrowed.
Known risk factors such as hypertension, hyperlipidemia, obesity, and a positive
family history, as well as other unknown factors, must be considered in evaluating
the older adult athlete. As older athletes who have exercise-related CAD events may
have less extensive vascular disease than the average, standard risk assessment ismore difﬁcult. Variations in the resting and exercise ECG may make interpretation
difﬁcult. Further, more precise imaging techniques such as computerised tomographic
calcium scoring may identify early atherosclerotic lesions. Coronary calcium
increases substantially with age, so that nearly 50% of males age 40 and older show
measurable calcium in their coronary arteries. Presently, there are no clear guidelines
as to how well coronary calciﬁcation per se can be used as an indicator to govern or
restrict exercise in non-symptomatic individuals. However, progressively increasing
calciﬁcation is associated with rising CAD risk.
The prognosis for patients with known CAD worsens depending on the extent
of disease, left ventricular systolic dysfunction, inducible ischemia, and electricalinstability. Therefore, older persons who contemplate or participate in a competitive
athletics programme should have a maximal exercise test that simulates as closely as
possible the metabolic demands of the training programme and competitive event,even though such testing cannot entirely replicate the actual stresses of training andcompetition. Any evidence of LV dysfunction, ischemia, or electrical instability
should lead to a limitation of physical activity and further cardiovascular evaluation.
D. Athletes with Symptoms Suggestive of Cardiovascular Disorder

Athletes with known heart disease may exhibit symptoms of syncope, faintness,or palpitations, which suggest a cardiac origin. A careful history and physicalexamination are needed to clarify the condition; for example, to differentiate
among vagal fainting, hyperventilation, and true syncope. Careful auscultation may
detect valvular or other congenital defects. Selected non-invasive tests may also benecessary to clarify the problem. A baseline 12-lead ECG and an echocardiogram
can reveal conduction or structural abnormalities. An exercise ECG may beneeded to elicit the underlying problem, and 24-hour monitoring is often used if anarrhythmia is suspected.
Continued participation in sports should depend on the ﬁndings. Restrictions onparticipation may be necessary until the nature of the problem is identiﬁed.
References

1.

2.

Albert, C. M., M. A. Mittleman, C. U. Chae, I. M. Lee, C. H. Hennekens, andJ. E. Manson. Triggering of sudden death from cardiac causes by vigorous
exertion. N. Engl. J. Med. 343:1355-61, 2000.
Bifﬁ A., A. Pelliccia, L. Verdile, et al. Long-term clinical signiﬁcance of
frequent and complex ventricular tachyarrhythmias in trained athletes. J. Am.
Coll. Cardiol. 40: 446-52, 2002.

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

3.

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6.

7.
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Burke, A. P., A. Farb, G. T. Malcom, Y. Liang, J. E. Smialek, and R. Virmani.
Plaque rupture and sudden death related to exertion in men with acute coronary
syndromes. JAMA 281:921-6, 1999.
Cheng Y. J., T. S. Church, T. E. Kimball, et al. Comparison of coronary artery
calcium detection by electron beam tomography in patients with to those without symptomatic coronary heart disease. Am. J. Cardiol. 92:498-503, 2003.
Giri S., P. D. Thompson, F. J. Kiernan, et al. Clinical and angiographic characteristics of exertion-related acute myocardial infarction. JAMA 282:1731-6,
1999.
Greenland, P., L. LaBree, S. P. Azen, T. M. Doherty, and R. C. Detrano.
Coronary artery calcium score combined with Framingham score for risk
prediction in asymptomatic individuals. JAMA 291:210-5, 2004.
Huston, T. P., J. C. Puffer, and W. M. Rodney. The athletic heart syndrome.
New Eng. J. Med. 313(1):24-32, 1985.
Kapetanopoulos, A., J. Kluger, B. J. Maron, and P. O. Thompson. The
congenital long Q-T syndrome and implications for young athletes. Med. Sci.
Sports Exerc. 38(5): 816-825, 2006.
Maron, B. J. Hypertrophic cardiomyopathy: a systematic review. JAMA 287(10):1308-1320, 2002.
Maron, B. J. Sudden death in young athletes. N. Engl. J. Med. 349:1064-1075,
2003.
Maron, B. J., and D. P. Zipes (eds.). 36th Bethesda Conference: Eligibility
recommendations for competitive athletes with cardiovascular abnormalities.
J. Am. Coll. Cardiol. 45(8):1-64, 2005.
Maron, B. J., C. G. Araujo, P. D. Thompson, et al. Recommendations for
preparticipation screening and assessment of cardiovascular disease in masters
athletes: an advisory for health care professionals from the working groups ofthe World Heart Federation, the International Federation of Sports Medicine,and the American Heart Association Committee on Exercise, Cardiac
Rehabilitation, and Prevention. Circulation 103:327-34, 2001.
Maron, B. J., A. Pelliccia, and P. Spirito. Cardiac disease in young trained
athletes: insights into methods for distinguishing athlete’s heart from structural
heart disease, with particular emphasis on hypertrophic cardiomyopathy.
Circulation 91:1596-601, 1995.
Pelliccia, A., and F. M. DiPaolo. Cardiac remodeling in women athletes andimplications for cardiovascular screening. Med. Sci. Sport Exerc. 37(8):14361439, 2005.
Pelliccia, A., F. Culasso , F. M. DiPaoli, and B. J. Maron. Physiologic left
ventricular cavity dilatation in elite athletes. Ann. Int. Med. 130:23-31, 1999.
Pelliccia, A., B. J. Maron, A. Spatare, et al. The upper limit of physiologic
cardio hypertrophy in highly trained elite athletes. New Eng. J. Med.
324(5):295-301, 1991.

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

17. Van Camp, S. P. Sudden death. Clinics in Sports Medicine 11(2):273-289,
1992.

PART 2ASTHMA AND EXERCISE-INDUCED BRONCHOSPASM (EIB)
A. Deﬁnitions

According to the American Thoracic Society, asthma is a clinical lung diseasecharacterised by reversible airway obstruction as a consequence of a wide variety ofstimuli. The term “current asthma” is used when at least one asthmatic episodeoccurred during the last year.
Asthma is characterised by a variety of symptoms, including dyspnoea,
shortness of breath, wheezing, cough, excess mucus, breathlessness, and chest
tightness. The symptoms might be mild or severe; intermittent or continuous; andmore frequent in the morning and at night. Upper or lower airway obstructions arereversible with or without therapy.
The generic deﬁnition can also include bronchial or airway hyperresponsiveness (BHR or AHR), that is, an above-normal airway constriction upon exposure tophysical stimuli or sensitising agents.
A transient airway narrowing occurring in susceptible individuals during or
after exercise is deﬁned as EIB (exercise induced bronchospasm) when observed ina non-asthmatic and non-atopic population; or EIA (exercise induced asthma) when
including asthmatic individuals. Here we will use EIB to also include those with EIA.
Exercise induced asthma or bronchospasm is a transient, reversible, and intermittent narrowing of small and large airways, occurring about 5–15 minutes after
intense exercise (aerobic activity more than anaerobic), performed for 8–10 minutes.
A post-exercise fall in forced expiratory volume in 1 second of >10% is required for
diagnosis. After an attack lasting 20–60 minutes, a complete recovery usually occurs.
In 50% of affected athletes, a refractory phase starts less than 1 hour after initial
exercise; this may last up to 3 hours, with less than half the intensity of exercise
bronchospasm. For this reason, the warm up period might be useful to ensurea refractory phase during competition. Sometimes, 6–8 up to 12 hours after the
exercise, a late phase, less severe state with cough and wheezing is observed in 30%
of subjects with EIB. The aetiology of the refractory period is probably due to thedepletion of local mediators, or increased sympathetic activity.
EIB occurs in 12–15% up to 20–25% of the normal population, increasing
to 35–40% in subjects with allergic rhinitis or hay fever and/or eczema, and up to
90% of those with asthma. The variability of the statistical data depends mainly on
the method used (clinical or laboratory evaluation or epidemiologic questionnaires
based on self reported symptoms or statistics performed in main competitions, based
also on declared use of beta-2 agonists).
Sometimes, EIB is erroneously diagnosed in athletes who have respiratory
stridor during inspiration, typical of vocal cord dysfunction (VCD, statistically up to
5%, by paradoxical narrowing of the vocal cords during inspiration or as describedby patients, while “getting air in”), or with other upper respiratory disorders. Anxiety
and hyperventilation syndrome may mimic asthma or EIB.

CHAPTER 14, SPECIAL MEDICAL PROBLEMSEIB is more prevalent in female athletes, and twice as prevalent in endurance
athletes as in sprinters, jumpers and throwers in track and ﬁeld. Furthermore,evidence exists that top athletes are at an increased risk of developing asthma or EIB
during their career, particularly in endurance events.
High-level exercise performed on a regular basis by previously unaffected elite
athletes, particularly in endurance activities, is liable to increase the incidence ofasthma and airway hyperresponsiveness (AHR).
B. Aetiology

A basic genetic component associated with atopy is presupposed, but many otherfactors are involved and play a signiﬁcant role both in asthma and AHR, particularly
in athletes:
1. Recurrent airways infections or inﬂammations, in which many local cells
and their related mediators are involved (mast cells, macrophages,
eosinophils, neutrophils, etc.). Endurance athletes are particularly susceptible
to upper respiratory tract infection and impaired function of the immune
system after intense repeated training, with decreased activity of lymphocytes, neutrophils, macrophages, and natural killer (NK) cells anddiminution of lymphokines and IgA levels.
2. Drug allergy (aspirin or NSAIDs are common), food allergy, or other allergic
or anaphylactic medical conditions.
3. Environmental exposure to airborne allergens. Prolonged hyperventilation
during intense training increases the possibility of exposure to different
allergens, mainly in seasonal asthmatic patients. These include pollens orother allergens, or irritant pollutants such as cigarette smoke and sulphur
dioxide (SO2), carbon monoxide (CO), nitrous and nitric oxide (NO2,
NO3) in smog, and—very important in track and ﬁeld—also herbicides,
pesticides, insecticides, and fertilisers. Training sessions in contaminatedsituations can cause chronic bronchial inﬂammation triggered by smoke,pollens, irritants, and allergens (IgE production).
4. Cold and dry air inhalation. Hyperventilation, mainly during endurance
efforts, induces a loss of heat and water in the bronchial system: thebronchoconstriction response is due both to the direct effect of “cooling” inbronchial mucosa, and to the “hyperosmolarity” of mucosal ﬂuid, inducing
the release of pro-inﬂammatory mediators (histamine, leukotrienes,
prostaglandins, neutrophil chemotactic factors). In addition, the “rewarming”
after exercise generates a vasodilator effect on the pulmonary capillarysystem with vascular bronchial congestion, increased vascular permeability
and oedema with bronchoconstriction.
5. Parasympathetic hyperactivity is a typical compensatory response to a
prolonged sympathetic stimulation by intense and prolonged training
sessions, which may increase the bronchomotor tone (normally and basicallythe parasympathetic system is dominant over the sympathetic system in theCHAPTER 14, SPECIAL MEDICAL PROBLEMS

bronchial apparatus), and may explain the higher incidence of AHR in
endurance athletes.
C. Diagnosis

1. Self-Reported Symptoms
Self-reported symptoms are not valid to conﬁrm the presence of asthma or EIB.
The misinterpretation of post-exercise fatigue, prolonged recovery time, underperformances, or inadequate training might induce an erroneous diagnosis.
2. History
The history is very important, and permits, as a ﬁrst step, the evaluation anddiscrimination of other possible diseases:
a. Chronic bronchitis, pulmonary ﬁbrosis, lymphoadenopathyb. Seasonal asthmac. Infectious diseases
d. Laryngeal dysfunction; throat or nasal problems; upper airways obstruction;
allergic rhinitis; hypertrophic turbinates; nasal polyps; sinusitis; hay fevere. Cardiac problems with effort dyspnoea
f. Allergic conditions (medicines, food) or anaphylactic reactions
g. Blood disorders (anaemia)h. Thyroid dysfunction
i. Gastro-oesophageal reﬂux
j. Anxiety
3. Basal Screening
Many clinical instruments are useful in basal screening, including:a. Family history of asthma and allergic diseases
b. Personal history of atopy or asthma; use of bronchodilator substances;other, also occasional, allergic disorders
c. Physical and complete examination (lung auscultation is often quite normal)
d. Evaluation of presence or inﬂuence of environmental factors (cigarettesmoke, smog, pollen, animal dander, dust mites, cold or dry air)e. Blood cell count and erythrocyte sedimentation rate (infections)f. Chest radiography (chronic pulmonary diseases, ﬁbrosis, lymphoadenopathy, cardiomegaly)g. Skin allergy tests, IgE and RAST (allergic problems)h. Heart clinic and instrumental evaluation (ECG and/or echocardiogram)
4. Diagnostic Tests
Pulmonary function testing is the next diagnostic step. Note that thepulmonary function tests should be performed on days free from asthma symptoms
and concurrent problems (rhinitis, allergies, sinusitis), without any prior short-acting

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

bronchodilator therapy in the last 8–12 hours, and any long-acting bronchodilator
therapy in the last 12–24 hours. Antileukotrienes should be suspended in the last
48–96 hours prior to the test; cromolyn compounds in the last 12–24 hours; andanti-histamines in the last 48 hours. In addition, inhaled steroids should not be
administered on the day of the test; no caffeine should be taken the morning of thetest; and no vigorous exercise should be performed in the last 4–6 hours prior to thetest, or preferably on the day of the test at all.
Laboratory basal spirometry is good for a simple and standard evaluation (FlowVolume Curve, FVC, FEV1, FEV1/FVC, PEFR, FEF 25–75).
In athletes with solitary EIB, the basal FEV1 will be normal, over 80% ofpredicted normal value, while in asthmatic athletes it will be lower than 80%.
For daily, practical, and on-ﬁeld self-evaluation, athletes can use small andinexpensive peak ﬂow meters.
Exercise challenge tests are commonly performed in the laboratory, using atreadmill, stationary cycle, or rowing equipment; sometimes an exercise test
performed running free and outside, as in natural conditions, is practical but is lesscontrolled in its intensity. However, for athletes, the chance to perform the speciﬁc
ﬁeld test of their sport is optimal for diagnosis. For exercise challenge tests:
a. No warm up is allowed to avoid a direct bronchospasm.
b. The intensity and duration of aerobic exercise should be 80–90% of the
maximum heart rate for 6–10 minutes, preferably without crossing theanaerobic threshold, to avoid the exhaustion of the athlete and the releaseof catecholamines.
c. The inhaled air should have a relative humidity below 50% and an
ambient temperature of 20º–25°C; the use of inhaled cold air during theexercise test increases the sensitivity in diagnosing EIB, without decreasing
speciﬁcity.
d. After the exercise test, spirometric measurements are conducted every
3–5 minutes for 15–30 minutes, and possibly after 4–12 hours in late
responders.
e. A decrease of FEV1 of 10% or more is considered positive for EIB. The
severity of disease is classiﬁed as mild (10–20%), moderate (20–40%),and severe (more than 40%). Reversibility of bronchospasm after aninhaled bronchodilator will conﬁrm the diagnosis.
Pharmacological challenge tests can be used to assess asthma, while being lessspeciﬁc and sensitive for EIB. The methacholine test, which is more sensitive andless speciﬁc, induces bronchoconstriction mainly in the distal bronchi, and increases
airway inﬂation pressure and contraction of the trachealis muscle; histamine causes
airway obstruction by activation of bronchial smooth muscle and mediator receptors.
Both for histamine and methacholine, cut-off levels are deﬁned, in terms ofconcentration or cumulated dose, able to induce a 20% reduction of FEV1 (PC-20 or
PD-20).

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

Osmotic tests include the dry powdered mannitol inhalation challenge and thenebulised hypertonic saline challenge. Increased doses of the stimulating substanceare followed by pulmonary function tests until cut-off levels. Both tests act byaltering the osmolarity of airway surface liquid (ASL) with release of mediatorsfrom sensitised mast cells. The osmotic tests are sensitive and speciﬁc, easy to
perform, and economical.
The eucapnic voluntary hyperventilation (EVH) challenge can, in susceptible
individuals, induce bronchoconstriction with increased ventilation rate by drying the
airway surface liquid and changing the osmolarity of the mucosal surface membranecomponents. In athletes, the respiration rate achieved should be almost 85% of
MVV (maximal ventilation rate), about 35 times FEV1. The test is performed witha dry air mixture containing 4.5% CO2 to ensure eucapnia and protect from the
hypocapnia induced by hyperventilation; this latter, in fact, may cause indistinct
bronchoconstriction both in EIB positive and negative subjects. The inspired air canalso be chilled, although chilling is not necessary.
The bronchodilator test is an indirect but limited method used to detect airway
obstruction by airways reversibility to inhaled short-acting bronchodilators(terbutaline or salbutamol), when the resting FEV1 is below 70% of normal. The
response is variable, and the cut-off criteria for a positive test is 15% FEV1 increaseor, as recently stated by the European Respiratory Society, 12% increase of FEV1
expressed as % predicted.
D. Non-Pharmacologic Treatment

Non-pharmacologic treatment should be the primary focus of the problem, andis based on the following criteria:
1. Education of athletes, coaches, and families is a primary component:
the disorder is frequent and common in the population, and does not
limit performance when adequately treated.
2. Prevention is the main method: avoiding cold or dry air, training indoors,
or covering the mouth and nose with a scarf during winter, or using amask to warm and humidify the air may be helpful.
3. Predominant nasal, more than mouth breathing, may reduce EIB byinhaling more warmed and humidiﬁed air.
4. Exercise conditioning to lower ventilation rate decreases airway
responsiveness.
5. Warming up well before exercise, with repeated short and high intensity
exercises, may induce a refractory period and partially reduce the needfor pre-medication.
6. Avoid training sessions that risk possible exposure to environmental
situations of airborne allergens or irritants.
7. Avoid consumptions of foods with possible allergens, at least in the last
4 hours before an exercise or competition session.

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

8. Reduce training when exacerbation periods of rhinitis, sinusitis, orallergy are present.
9. Stop training during viral respiratory infections or acute bronchial
exacerbations.
E. Pharmacologic Treatment

The treatment of seasonal allergic rhinitis by non-sedating anti-histamines or
local intranasal glucocorticosteroids is an important step in preventing bronchial
hyperreactivity. Generally, the correct use of medications, when needed, will help
the patients to train well and live better, without pharmaceutical addiction and withlimited adverse effects, both of which are possible risks of inhaled beta-2 agonists.
Proper inhalation of the medication will result in a better deposition of thesubstances into the bronchial system: after slow expiration, controlled breathe while
inhaling to total lung volume and holding the breath for 10 seconds will enhance
deposition. A pause of 30 second between the two inhalations will increase thequantity of drug delivered into the lungs.
While describing beta-2 agonists, we will mention only those permitted byinhalation with a previous exemption request:
Short acting beta-2 agonists (salbutamol/albuterol, terbutaline) administered byinhalation 20–30 minutes before exercise have a peak bronchodilator effect within
60 minutes, and maximal duration of 3–4 hours. They are effective in 90% of EIB,
but sometimes they induce tachyphylaxis, worsening asthma, and, with continuous
use, become ineffective in 2–3 years.
Long acting beta-2 agonists (formoterol and salmeterol) need to be administered
well before exercise, because they have their maximal effect in 4 hours and may last
up to 12 hours, permitting the prevention of EIB and asthma attacks in prolonged
exercise sessions and in the night (particularly when used with glucocorticosteroids).
The beta-2 agonists, both short and long acting, work by increasing intracellularconcentration of cyclic adenosine monophosphate (cAMP), which modulates therelaxation of bronchial smooth muscle and inhibits the release of mediators frommast cells. While beta-2 selective, they interact (short acting more than long acting)with alpha- and beta-1 receptors, causing tachycardia, tremors, and palpitations.
Inhaled glucocorticosteroids (beclomethasone dipropionate, budesonide,
ﬂuticasone propionate, ﬂunisolide, momethasone, triamcinolone acetonide, etc.) arepractically long-term drugs. They are not effective on an as-needed basis, but are
useful for chronic asthma, or in EIB if used for at least one month, when the beta-2
agonists are not effective when used individually. They suppress the production ofcytokines, reducing the eosinophils, and prevent inﬂammatory mediators release.
Adverse effects are dysphonia, oral irritation, and candidiasis.
Cromolyn compounds (Cromolyn sodium and Nedocromil sodium) are mastcell stabilisers without bronchodilator effects, which are useful—when inhaled 20
minutes before exercise—in preventing EIB and EIA symptoms in 80% of patients.
They may also prevent the late-phase response of EIB. They can be used many times
a day in the absence of adverse effects, and may be additive when beta-2 agonists

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

are not completely effective. Adverse effects include bad taste, throat irritation,
cough, nausea, vomiting, and abdominal pain.
Antileukotrienes are used for long-term asthma therapy. Montelukast and
Zaﬁrlukast are leukotriene antagonists, while Zileuton is an inhibitor of biosynthesisby 5-lipoxygenase; they are effective in preventing EIA in chronic asthma.
Leukotrienes are products of arachidonic acid metabolism, and increase eosinophil
migration, mucus production, and bronchial oedema, with bronchoconstriction
response 1000 times greater than histamine. The antileukotrienes, normally usedorally for long-term therapy, offer 24-hour protection with very low adverse effects(dyspepsia, nausea).
Inhaled anticholinergics (ipratropium bromide, oxitropium bromide, tiotropium
bromide) are not useful in preventing EIB, and are only used in chronic obstructive
pulmonary diseases and chronic bronchial infections complicated by asthmatic
attacks.
Antihistamines (astemizole, cetirizine, chlorpheniramine, desloratidine,
phexophenadine, terphenadine, etc.) exhibit little effect; they might be useful inallergic asthma only when the disease is combined with allergic rhinitis due to airpollens. The oral dryness and some mild sedative effects are not helpful for athletes.
Further, they are sometimes combined with stimulants not permitted by antidoping
rules. Ketotiphen is a more widely used antihistamine substance; like cromolyncompounds, it acts on mast cells as a stabiliser, with fewer adverse effects.
Antibiotics are used in the presence of infections—sinusitis, rhinitis, bronchitis—that increase bronchial sensitivity.
Methylxanthines (theophylline and aminophylline or theophylline ethylendiamine)work by decreasing the metabolism of cAMP by inhibition of phosphodiesterase;they also have adrenergic effects. They are used systemically (oral or injections),
mainly in chronic asthma and in acute exacerbations, under strict medical control forpossible adverse effects (tachyarrhythmias, hypertension, peptic ulcers, hyperthyroidism, seizure disorders).
Systemic glucocorticosteroids and beta-2 agonists are restricted to more serious
conditions and are administered in emergency situations by medical prescription.
Epinephrine (adrenaline) is administered subcutaneously, under strict medical
control, only in life-threatening emergency situations.
F. Doping Related Issues

Since 1993, the beta-2 agonists have been submitted to restrictions by the IOC
and IAAF, based on their possible effects as anabolic agents (see Chapter 15, Drugs
in Sports/Doping Control). However, a large increase in the number of athletes withdeclared use of beta-2 agonists was reported in high-level competitions and Olympic
Games, perhaps as a consequence of an incomplete or erroneous diagnosis and,sometimes, due to an over-use of and/or acquired tolerance to beta-2 agonists, withan under-use of inhaled glucocorticosteroids.

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

Further, the beta-2 agonists can potentially have positive ergogenic effects onskeletal muscle anabolism, and on aerobic and anaerobic performance. For thisreason the control of their use in accordance with sport rules is becoming morestrict. Also, glucocorticosteroids by inhalation have been subjected since January 1,
2004 to more limited use, and only after application for a therapeutic use exemption(TUE).
In accord with IAAF and World Anti Doping Agency (WADA) rules and IAAF
Procedural Guidelines for doping control:
1. Glucocorticosteroid by inhalation are banned “in” competition, andsubmitted in competition to the “Abbreviated Therapeutic Use
Exemption” application process.
2. Beta-2 agonists by inhalation, are prohibited both “in” and “out” ofcompetition, and are submitted to the “Abbreviated Therapeutic Use
Exemption” application process.
3. Systemic glucocorticosteroids in competition and systemic beta-2 agonists
both in and out of competition are banned, and a “Standard Therapeutic
Use Exemption” application must be applied for before use.
Note that particularly in the case of an abbreviated TUE application to the IAAF
for the use of beta-2 agonists by International Level athletes, and in accord with the
IAAF beta-2 agonists protocol, the medical notiﬁcation justifying the therapeuticnecessity must be accompanied by the athlete’s detailed medical records and by apositive bronchial provocation test with graphic evidence, conforming to the IAAF
speciﬁc protocol (see also Chapter 15, Drugs in Sports/Doping Control).
All of the doping rules are updated yearly by IAAF, in accordance with the yearly
WADA prohibited list. The current list may be found on the websites of WADA
(www.wada-ama.org), IAAF (www.iaaf.org), and IOC www.olympic.org. The list
goes into effect three months after publication.
References

1.

2.
3.
4.

5.

Anderson, S. D., G. J. Argyros, H. Magnussen, and K. Holzer. Provocation byeucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction.
Br. J. Sports Med 35:344-347, 2001.
Anderson, S. D., and K. Holzer. Exercise-induced asthma: is it the rightdiagnosis in elite athletes? J. Allergy Clin. Immunol. 106:419-428, 2000.
Beck, K. C. Control of airway function during and after exercise in asthmatics.
Med. Sci. Sports Exerc. 31:s4-s11, 1999.
Bonini, S., V. Brusasco, K. H. Carlsen, L. Delgado, S. D. Giacco, T. Haahtela,
G. Rasi, and P. B. van Cauwenberge. Diagnosis of asthma and permitted useof inhaled beta-2 agonists in athletes. Allergy 59:33-36, 2004.
Carlsen K. H., G. Engh, and M. Mork. Exercise-induced bronchoconstriction
depends on exercise load. Respir. Med 94:750-755, 2000.

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

6.
7.
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Helenius, I., and T. Haahtel. Allergy and asthma in elite summer sports athletes.
J. Allergy Clin. Immunol. 106:444-452, 2000.
Helenius I., A. Lumme, and T. Haahtela. Asthma, airway inﬂammation andtreatment in elite athletes. Sports Med. 35:565-574, 2005.
Helenius, I., H. O. Tikkanen, and T. Haahtela. Occurrence of exercise induced
bronchospasm in elite runners: dependence on atopy and exposure to cold air
and pollen. Br. J. Sports Med. 32:125-129, 1998.
Hough, D. O., and K. L. Dec. Exercise-induced asthma and anaphylaxis.
Sports Med. 18:162-172, 1994.
Langdeau, J. B., and L. P. Boulet. Prevalence and mechanisms of developmentof asthma and airway hyperresponsiveness in athletes. Sports Med. 31:601-616,
2001.
McFadden, E. R., Jr., and I. A. Gilbert. Exercise-induced asthma. N. Engl. J.
Med. 330:1362-1367, 1994.
Rundell, K. W., and B. A. Spiering. Inspiratory stridor in elite athletes.
Chest 123:468-474, 2003.
Rundell, K. W., and D. M. Jenkinson. Exercise-induced bronchospasm in elite
athletes. Sports Med. 32:583-600, 2002.
Rundell, K. W., J. Im, L. B. Mayers, R. L. Wilber, L. Szmedra, and H. R.
Schmitz. Self-reported symptoms and exercise-induced asthma in the elite
athlete. Med. Sci. Sports Exerc. 33:208-213, 2001.
Rundell, K. W., R. L. Wilber, L. Szmedra, D. M. Jenkinson, L. B. Mayers,
and J. Im. Exercise-induced asthma screening of elite athletes: ﬁelds versus
laboratory exercise challenge. Med. Sci. Sports Exerc. 32:309-316, 2000.
Storms, W. W. Exercise-induced asthma: diagnosis and treatment for therecreational or elite athlete. Med. Sci. Sports Exerc. 31, s33-s38, 1999.
Tan, R. A., and S. L. Spector. Exercise-induced asthma. Sports Med. 25:1-6,
1998.
Weiler, J. M. Why must Olympic athletes prove that they have asthma to bepermitted to take inhaled beta-2 agonists? J. Allergy Clin Immunol 111:36-37,
2003.

PART 3HEADACHES AND EXERCISE-INDUCED ANAPHYLAXISA. Headaches

Headaches may occur with exercise, and are usually benign. However, exerciserelated headache may occasionally signal the presence of an underlying organic
disorder.
1. Benign Exertional Headache
These may occur with exercise, but also with coughing, sneezing, bending, andlifting. No distinct pattern is observed. Pain can occur at any site, and radiate in avariety of patterns.
2. Effort Migraine
Migraine can be precipitated by strenuous exercise, and has an atypical migraine
pattern, with sudden onset, scotoma, photo-sensitivity, nausea, and vomiting, andunilateral headache that is often retro-orbital. It usually lasts 20–60 minutes. Treatment
should initially consist of analgesics, but drugs such as ergotamine tartrate may berequired.
3. Organic Disorders
a. Pheochromocytoma
Pheochromocytoma may appear as a pounding headache of sudden onset,
accompanied by nausea and vomiting. The ﬂushing, sweating, and tremor
typical of this disease may be obscured by exercise. A rise in blood pressure
is often associated with the symptoms, even at rest. Urinary VMA andcatechols are elevated.
b. Vascular Malformations and Tumours
These rarely present with exertional headache. However, persistentheadache, either diffuse or localised, warrants a thorough neurologicalexamination, and possibly an EEG and or CT scan.
B. Exercise-Induced Anaphylaxis

This is an unusual type of physical allergy, but one that can become life-threatening.
1. Manifestations
a. Flushing, sensation of warmthb. Giant urticaria (wheals 10–15 mm diametre)c. Angioedema, respiratory distress, vascular collapse

CHAPTER 14, SPECIAL MEDICAL PROBLEMS

2. History
There is a prior personal or family history in over half of the subjects. The
condition occurs unpredictably, and under variable circumstances associated with
exercise. Prior food allergy may be a factor.
3. Differential Diagnosis
EIA must be distinguished from Cholinergic Urticaria (CU). This latter isuniformly brought on by exposure to heat or exercise, and has punctate urticaria andwheezing, but is not life-threatening.
4. Treatment
Stop exercise at once, and administer epinephrine subcutaneously. Subjects
should be taught to carry and administer their own medication. Exercise with acompanion who is aware of the problem and who can administer the drug.
References

1.
2.
3.

Briner, W. W., Jr. and A. L. Sheffer. Exercise-induced anaphylaxis. Med.Sci.
Sports Exerc. 24:849-850, 1992.
International Olympic Committee Medical Commission. Headaches. In
Sports Medicine Manual, pp. 236-238. Lausanne: IOC, 1990.
Rooke, E. D. 1968. Benign exertional headache. Med. Clin. N. Am. 52:801808, 1968.