![Illustration of exercise-induced hyperventilation in a teenage girl athlete. This figure describes measurements of pulse oximetry, expiratory flow rate (one-second forced expiratory volume [FEV 1 ]), and her end-tidal carbon dioxide (CO 2 , which correlates with arterial partial pressure of carbon dioxide). Chest tightness begins early, about 4 minutes into the exercise, in association with the decreasing endtidal CO 2 . O 2 Sat, oxygen saturation.](https://www.researchgate.net/profile/Miles-Weinberger/publication/331798852/figure/fig4/AS:753248256405504@1556599787206/Illustration-of-exercise-induced-hyperventilation-in-a-teenage-girl-athlete-This-figure_Q320.jpg)
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PEDIATRIC ANNALS • Vol. 48, No. 3, 2019 e121
SPECIAL ISSUE ARTICLE
Exercise-Induced Dyspnea in Children
and Adolescents: Differential Diagnosis
Rajeev Bhatia, MD; Mutasim Abu-Hasan, MD; and Miles Weinberger, MD
ABSTRACT
Exercise-induced dyspnea in children and adolescents can occur for many reasons. Al-
though asthma is the common cause, failure to prevent exercise-induced asthma by pre-
treatment with a bronchodilator, such as albuterol, indicates that other etiologies should be
considered. Other causes of exercise-induced dyspnea include exercise-induced vocal cord
dysfunction, exercise-induced laryngomalacia, exercise-induced hyperventilation, chest
wall restrictive abnormalities, cardiac causes, and normal physiologic limitation. When exer-
cise-induced dyspnea is not from asthma, cardiopulmonary exercise testing with reproduc-
tion of the patient’s dyspnea is the means to identify the other causes. Cardiopulmonary
exercise testing monitors oxygen use, carbon-dioxide production, end-tidal pCO2 (partial
pressure of carbon dioxide), and electrocardiogram. Additional components to testing are
measurement of blood pH and pCO2 when symptoms are reproduced, and selective flexible
laryngoscopy when upper airway obstruction is observed to specifically identify vocal cord
dysfunction or laryngomalacia. This approach is a highly effective means to identify exer-
cise-induced dyspnea that is not caused by asthma. [Pediatr Ann. 2019;48(3):e121-e127.]
Dyspnea is defined as the per-
ception of shortness of breath,
difficult or labored breathing.
Exercise-induced dyspnea (EID) is
dyspnea that occurs or worsens with
physical activity. As more children and
adolescents are choosing to exercise
regularly, often for an athletic activ-
ity, EID is becoming an increasingly
common reason to see a physician.
The frequency of EID was examined
by Johansson et al.1 in a large survey
of Swedish children age 12 and 13
years. They reported that 14% of the
children had experienced shortness of
breath with exercise in the previous 12
months. Although a history of asthma
was reported in 14.6% of those chil-
dren, only 5.4% of those with asthma
had a history of EID. No history of
asthma was reported in 61% of those
with EID.1 Exercise-induced broncho-
spasm can be demonstrated in most
children with active asthma.2 However,
EID may result from reasons other than
asthma and can be mistaken for asth-
ma.3 This review describes the causes
of EID and provides guidance for the
clinician to identify and treat the prob-
lem in the individual patient.
CAUSES OF EXERCISEINDUCED
DYSPNEA
Exercise-Induced Bronchospasm
and Exercise-Induced Asthma
Exercise-induced bronchospasm
(EIB) involves the transient narrowing
of the airways during or after exercise.
It is a pathophysiological response
that can be measured using lung func-
tion testing. Exercise-induced asthma
(EIA), on the other hand, is a clinical
diagnosis based on demonstration of
EIB in association with EID. Generally,
the patient will have experienced other
symptoms of asthma. The mechanism
of EIB involves airway dehydration
from increased ventilation resulting in
mediator release.4
The presence of EIB can be sup-
pressed with warm, humidified air.
Consequently, EIB is likely to be less
when swimming in warm water. Pre-
ceding exercise with an inhaled bron-
chodilator such as albuterol (salbuta-
mol) can prevent EIB and EIA. EIB can
sometimes be seen in the absence of
Rajeev Bhatia, MD, is a Pediatric Pulmonologist, Akron Children’s Hospital; and an Associate Profes-
sor of Pediatrics, Northeast Ohio Medical University. Mutasim Abu-Hasan, MD, is a Clinical Professor,
Pediatric Pulmonary, University of Florida. Miles Weinberger, MD, is a Professor Emeritus, University of
Iowa; and a Visiting Clinical Professor of Pediatrics, University of California San Diego, Rady Children’s
Hospital.
Address correspondence to Miles Weinberger, MD, 450 Sandalwood Court, Encinitas, CA 92024;
email: miles-weinberger@uiowa.edu.
Disclosure: The authors have no relevant nancial relationships to disclose.
doi:10.3928/19382359-20190219-02
e122 Copyright © SLACK Incorporated
SPECIAL ISSUE ARTICLE
associated dyspnea or in the absence of
other symptoms consistent with asth-
ma.5 If dyspnea does not occur in as-
sociation with EIB, then another cause
for EID may be present.
Estimates of the global prevalence
of EIB in children and adolescents have
been attempted,6 but are confounded
by different methodologies, such as
free running versus treadmill testing,
differences in the environmental tem-
perature and humidity, and differences
in the definition of EIB based on the
percent decrease in FEV1 (forced ex-
piratory volume-one second; decreases
of 10%-15% have been used in various
studies). EIB in the absence of asthma
has been described in elite athletes and
in healthy college athletes.7 There is
evidence that the prevalence of EIB in
athletes is overestimated. Price et al.8
examined asymptomatic athletes using
eucapnic voluntary hyperpnoea, which
is a provocative indirect stimulus test
used to diagnose EIB. Mild broncho-
spasm that met diagnostic criteria for
EIB was common in that population of
asymptomatic athletes, especially when
a 10% decrease in FEV1 was used to
define EIB. The use of 10% increases
sensitivity but decreases specificity by
including the upper range of normal
responses. They concluded that there
is a spectrum of mild airway reactivity
to exercise in that population, which
should not be regarded as pathologic
unless the fall in FEV1 was substantially
greater and associated with symptoms.8
A typical pattern of EIA includes
initial transient bronchodilation fol-
lowed by bronchoconstriction that
peaks within about 5 minutes after ces-
sation of exercise and lasts about 30
minutes in the absence of treatment
(Figure 1). Symptoms include short-
ness of breath, cough, and chest tight-
ness in association with the decrease in
pulmonary function. Some people with
asthma develop severe acute broncho-
spasm and hypoxemia during exercise
(Figure 2).
The mechanism of EIB in athletes
appears to be different when it is not
associated with other clinical manifes-
tations of asthma.4 Rather than being
associated with the intrinsic airway
reactivity of asthma, EIB in athletes
is suggested to be from the irritant ef-
fect of repeated episodes of certain
high-level sports, especially when per-
formed in noxious environments.9 Ex-
amples include swimmers exposed to
chlorine derivatives used to disinfect
swimming pools and hockey players
exposed to emissions from ice-resur-
facing machines.
Treatment of symptomatic EIB is
relatively simple, as a beta-2-agonist
such as albuterol, given prior to exercise
reliably prevents EIB. In the occasional
patient in whom a long-acting beta-2-
agonist is associated with down-
regulation of the beta-2 receptor, alb-
uterol may not prevent EIB.10 Treat-
ment with asthma maintenance therapy,
such as inhaled corticosteroids and
montelukast, can also effectively de-
crease EIB. However, treatment of EIB
with these medications would be more
appropriate in patients with other mani-
festations of persistent asthma.
Exercise-Induced Vocal Cord
Dysfunction
Vocal cord dysfunction (VCD) re-
fers to abnormal functioning of the
vocal cords. There are different phe-
notypes of this disorder.11 It can occur
spontaneously and unpredictably, but it
is the exercise-induced VCD (EIVCD)
phenotype that is addressed in this re-
view. There are two physiologic pat-
terns of VCD. The most common that is
seen with EIVCD is paradoxical vocal
cord movement. The normal movement
of vocal cords is abduction with inspi-
ration so that the vocal cords move out
of the way allowing air to pass unob-
structed, and then relax on expiration.
Paradoxical movement occurs when
the vocal cords adduct on inspiration.
This vocal cord adduction creates ob-
struction to air flow that is shown on a
spirometric tracing as a flattening of the
inspiratory portion of the flow-volume
loop (Figure 3A). Stridor on inspira-
tion and the feeling that the patient can-
not get enough air are the most common
presenting symptoms. If the patient
also has asthma, the dyspnea and in-
spiratory stridor associated with VCD
may be confused with the dyspnea and
expiratory wheezing of the patient’s
underlying asthma.12 Less common but
more serious upper airway obstruction
occurs when the vocal cords stay in ad-
duction during both inspiration and ex-
piration. This results in blunting of both
the inspiratory and expiratory portions
of the flow-volume loop (Figure 3B).
(See Weinberger and Doshi13 for sup-
plemental videos demonstrating both
physiologic types of VCD.)
Prevention of EIVCD has been suc-
cessful by pretreating with an anticho-
linergic aerosol, ipratropium bromide,
which is available as a metered-dose
inhaler. The vocal cords’ adductors
and abductors derive motor innerva-
tion from superior laryngeal and recur-
rent laryngeal nerves, both of which
are branches of the vagus nerve. Vagal
nerve stimulators, used for patients with
intractable seizures, have been shown
to cause VCD as a complication.14
Those reports provide a rationale for
the use of an anticholinergic inhibitor
aerosol as VCD prevention. Although
data from a controlled clinical trial are
not available, six patients in one report
described complete blocking of their
EIVCD by pretreatment with ipratro-
pium bromide.11 One other single case
report has also described efficacy of ip-
PEDIATRIC ANNALS • Vol. 48, No. 3, 2019 e123
SPECIAL ISSUE ARTICLE
ratropium for EIVCD.15 Speech therapy
has been described in detail as a means
for preventing EIVCD, but neither con-
trolled clinical trials nor specific case
outcomes are available.16
Exercise-Induced Laryngomalacia
Laryngomalacia is the term used to
describe collapse of supraglottic struc-
tures, mainly the arytenoids and/or the
epiglottis, during inspiration causing
upper airway obstruction. Laryngoma-
lacia is a common disorder affecting
infants and the most common cause of
the inspiratory sound known as stridor.
Some infants with congenital laryngo-
malacia have been seen to later have
exercise-induced laryngomalacia (EIL)
as adolescents when they begin vigor-
ous athletic activity.17 EIL causes symp-
toms and physiologic abnormalities like
EIVCD but is much less common. Both
cause upper airway obstruction with in-
spiratory stridor. EIL and EIVCD cause
similar spirometric abnormalities when
symptomatic (Figure 3A). Flexible la-
ryngoscopy is the only reliable means
of distinguishing whether vocal cord
closure or invaginating laryngeal struc-
tures are obstructing the inspiratory air-
flow. Some have chosen to lump EIL and
EIVCD with the term exercise-induced
laryngeal obstruction.18 Because the
physiology, anatomy, and treatment of
EIL and EIVCD are different, the spe-
cific disorder, EIL or EIVCD, should be
identified.
Treatment of EIL is supraglottoplas-
ty. The abnormality and the successful
outcome of the corrective procedure
are described and illustrated in several
publications.19
Restrictive Physiological
Abnormalities
Vigorous exercise depends on the in-
crease in ventilation, which is achieved
by increasing tidal volume and respira-
tory rate. Therefore, any disease pro-
cess that limits chest expansion can
limit exercise capacity. Pectus abnor-
malities and scoliosis, even if not af-
fecting normal activities, may influence
maximal exercise by causing restrictive
physiology.20 Abu-Hasan et al.3 defined
respiratory limitation from restrictive
Figure 1. Typical time course of pulmonary function from exercise-induced asthma. The one-second
forced expiratory volume (FEV1) is used as the measure in this example.
Figure 2. A 15-year-old girl with a history of repeated exertion-induced, severe acute life-threatening
episodes from asthma was given a treadmill exercise test. The test was performed at 4 mph with a 10%
grade, and heart rate reaching a value consistent with 85% of maximal aerobic capacity for age. The
peak expiratory flow rate (PEFR) was used to monitor her pulmonary function.
e124 Copyright © SLACK Incorporated
SPECIAL ISSUE ARTICLE
physiology as the etiology for EID if
symptoms were reproduced during car-
diopulmonary stress testing in associa-
tion with a low maximal tidal volume
during exercise and increased respiratory
rate. The patient essentially compensates
for the lower maximal tidal volume dur-
ing exercise by increasing respiratory
rate, a less efficient means of maximiz-
ing ventilation. The result is a limitation
of maximal voluntary ventilation during
exercise.
In our evaluation of 120 sequential
children and adolescents seen for EID and
evaluated with cardiopulmonary exercise
testing, our criteria for restrictive physiol-
ogy were met in 15 patients (11% of the
120).3 These patients often had minor de-
grees of thoracic cage abnormalities (sco-
liosis and pectus deformities) that were
not associated with a decrease in forced
vital capacity or total lung capacity at
rest. In severe cases of pectus excavatum,
exercise limitation can be due to low car-
diac stroke volume and decreased cardiac
output rather than decreased minute ven-
tilation. Pulmonary function, chest dy-
namics, and exercise have been examined
after the Nuss method of surgical repair
for severe pectus excavatum. Although
that procedure results in little change in
either spirometric measures or dynamic
chest wall motion, significant increase
in exercise tolerance has been described.
There is evidence that the improvement
in exercise after pectus repair is related to
improved cardiac function.21
Another group of patients with EID
due to restrictive physiology are those
with obesity. EID in obese children and
adolescents may result from increased
restrictive loading of the chest wall and
abdomen, resulting in exercise limitation
associated with decreased lung volumes
and decreased peak work rate during ex-
ercise. EID from obesity is sometimes
misdiagnosed as being from asthma.22
Exercise-Induced Hyperventilation
Exercise-induced hyperventilation
(EIH) was first reported in some patients
who were initially diagnosed with EIA
but experienced chest discomfort asso-
ciated with hyperventilation in the ab-
sence of bronchospasm or hypoxemia
on exercise testing (Figure 4).23 Hy-
perventilation is identified by increased
ventilation accompanied by a decrease
in pCO2 (partial pressure of carbon di-
oxide) in the absence of bronchospasm
(no significant decrease in any measure
of expiratory flow rate) and not explain-
able as compensation for metabolic aci-
dosis that results from lactic acid gener-
ated with sustained vigorous exercise.
A decrease in end-tidal CO2 early in the
exercise that is associated with chest
discomfort without wheezing is typical
of EIH. Dizziness, a feeling of being
light-headed, and/or tingling in fingers
or toes may be present. Anxiety may
be related to EIH. Interestingly, similar
chest discomfort with decreased pCO2
has been reproduced in adults who have
been exercise tested because of con-
cern for angina but had no accompany-
ing abnormality on electrocardiogram
(ECG) testing.24 Moreover, their symp-
toms could be reproduced with volun-
tary hyperventilation sufficient to lower
their pCO2.25 Thus, chest discomfort
during exercise in a child causes con-
cern that asthma is the cause, whereas
the same symptoms in an adult causes
concern that there is cardiac disease. In
both cases, inappropriate hyperventila-
tion can be the cause.
EIH is a result of increased minute
ventilation early in exercise. Excess
CO2 production and decreasing end-
tidal CO2 will be seen during cardio-
pulmonary exercise testing. Diagnosis
of EIH is made by monitoring end-tidal
CO2 and obtaining a blood gas to mea-
sure pH and pCO2 when symptoms are
reproduced. An elevated pH and low
pCO2 at the time of dyspnea confirm
the diagnosis.
Treatment of EIH consists of expla-
nation, reassurance, and counseling.
Cardiac Causes of EID
Although most instances of cardiac
disease will have been previously iden-
tified prior to seeing a physician for
EID, exercise-induced supraventricu-
lar tachycardia may be quiescent until
a vigorous exercise stress. We saw this
Figure 3. (A) Flow-volume loop in a 15-year-old.
girl with exercise-induced vocal cord dysfunction.
The paradoxical adduction during inspiration
after exercise results in the low post-exercise in-
spiratory flow shown. (B) Flow-volume loops from
another 15-year-old girl with a history of repeat-
ed episodes of sudden-onset severe dyspnea. In
this case, where adduction persists during both
inspiration and expiration, the inspiratory and ex-
piratory flows are both compromised.
PEDIATRIC ANNALS • Vol. 48, No. 3, 2019 e125
SPECIAL ISSUE ARTICLE
during cardiopulmonary exercise test-
ing in an adolescent athlete whose sole
complaint was EID that prevented him
from completing a quarter during bas-
ketball games.3 He experienced no pal-
pitations or other symptoms associated
with the dyspnea. When his EID was
reproduced on a treadmill, it was asso-
ciated with a sudden increase of heart
rate to greater than 200 beats per min-
ute. Return to normal values occurred
suddenly after 20 minutes of rest. The
associated ECG reading was ventricu-
lar tachycardia. Radio frequency cath-
eter ablation subsequently eliminated
the disorder.
Pathological conditions that de-
crease cardiac output will result in ex-
ercise limitation.26 In children, most
exercise limitation from cardiac causes
is due to congenital heart disease where
structural heart defects result in de-
creased cardiac output and/or hypox-
emia. Cyanotic congenital heart disease
cause more significant exercise limita-
tions than noncyanotic heart disease.27
This is likely due to the associated gas
exchange abnormality from shunting
and compromised cardiac output.28 In
addition to congenital heart diseases,
cardiomyopathies in children are also
associated with severe exercise limita-
tion due to depressed cardiac function.29
Exercise limitation due to vascular ab-
normalities, especially atherosclerosis,
are common in adults but rarely present
in children.
Cardiac causes of exercise limitation
in otherwise healthy-appearing people
are suspected when symptoms of chest
pain, chest tightness, presyncope, syn-
cope, and heart palpitation are present
in association with EID. Cardiac abnor-
malities are usually detected and char-
acterized by ECG, cardiac echocardiog-
raphy, and cardiac catheterization. The
value of cardiopulmonary stress test in
these patients is mainly to quantify the
extent to which cardiac or respiratory
disease is limiting exercise.30
Normal Physiologic Limitation
Causing EID
In people without EID, peak exer-
cise is determined mainly by reaching
maximum cardiac output. Increasing
exercise intensity is dependent on the
increase of oxygen supply to the ex-
ercising muscles up to the point when
cardiac output is not sufficient for
their increasing demand. At that point,
which is called anaerobic threshold,
any further exercise activity is achieved
by switching from oxygen-dependent
metabolism (aerobic metabolism) to
oxygen-independent metabolism (an-
aerobic metabolism). Continued exer-
cise beyond anaerobic threshold causes
accumulation of lactic acid.
Although the various causes of EID
discussed above need to be consid-
ered, the most common cause of EID
in children and adolescents referred
to a specialist for evaluation is normal
physiologic limitation.3 This common-
ly occurs in a highly motivated adoles-
cent or preadolescent who exceeds the
anaerobic threshold sufficiently during
exercise that lactic acid production re-
sults in metabolic acidosis, after which
compensatory respiratory alkalosis by
increasing respiration occurs. Respira-
tory drive eventually reaches maximum
output, and yet the acidosis is creating
increased respiratory drive. The patient
then perceives that they are not getting
enough air, which is technically cor-
rect; they cannot physically get more
air, as their ability to respond to the fur-
ther respiratory drive is limited by their
maximal ventilatory capacity. This is
identified in these children during car-
diopulmonary exercise testing. When
symptoms are reproduced, no airway
obstruction is observed, and the blood
pH is acidotic. Essentially, the patient
then has reached the maximum capac-
ity of the cardiovascular system to de-
liver oxygen, and yet the low pH from
the lactic acidosis is creating further re-
spiratory drive beyond the ability to de-
liver. This could occur in a patient with
normal, subnormal, or above-normal
cardiovascular conditioning.3
The treatment for EID caused by
normal physiologic limitation in the
Figure 4. Illustration of exercise-induced hyperventilation in a teenage girl athlete. This figure describes
measurements of pulse oximetry, expiratory flow rate (one-second forced expiratory volume [FEV1]),
and her end-tidal carbon dioxide (CO2, which correlates with arterial partial pressure of carbon dioxide).
Chest tightness begins early, about 4 minutes into the exercise, in association with the decreasing end-
tidal CO2. O2 Sat, oxygen saturation.
e126 Copyright © SLACK Incorporated
SPECIAL ISSUE ARTICLE
absence of any anatomic or physiologic
etiology is reassurance and counseling.
Providing an age-appropriate explana-
tion of exercise physiology is likely
to enable the patient to understand the
cause of their EID and permits coun-
seling and education in conditioning
and pacing during vigorous athletic
activities.
EVALUATION OF THE PATIENT WITH
EID
The evaluation for patients with EID
begins with a detailed history (Table 1),
physical examination, and spirometry.
Patients with an abnormal examina-
tion and/or spirometry should be fur-
ther evaluated for the relevant finding.
In patients with evidence of underlying
asthma and/or symptoms suggestive of
EIB, a trial of short-acting bronchodi-
lator inhaler (SABA) such as albuterol
taken before exercise is reasonable be-
fore pursuing any further testing. Pre-
vention of EID by pretreatment with
albuterol provides evidence of EIB and
a presumption of EIA if other symptoms
suggestive of asthma are present. If there
is minimal or no improvement from a
trial of a SABA or symptoms had been
atypical, alternative diagnoses should be
considered and cardiopulmonary exer-
cise testing (CPET) is needed to identify
other causes of EID.5
CPET is the most effective means
for arriving at a diagnosis once EIA
cannot be demonstrated by blocking
the EID with a SABA. For most cases,
a treadmill is used because it usually
more closely approximates the activity
causing EID in the patient. CPET is a
noninvasive test that provides a global
assessment of the integrative exercise
responses of pulmonary, cardiovascu-
lar, hematopoietic, neuropsychological,
and skeletal muscle systems. Patients
with atypical symptoms of EID and es-
pecially nonresponders to bronchodila-
tors are candidates for CPET that results
in reproduction of the patient’s EID. In
addition to spirometry before and after
exercise to assess EIB, metabolic, re-
spiratory, and cardiac parameters are
continuously recorded during exercise
in CPET. This permits a continuous vi-
sualization of air flow to identify upper
or lower airway obstruction, oxygen uti-
lization, carbon dioxide production, and
heart rate. From these parameters, maxi-
mal oxygen utilization, which reflects
the degree of cardiovascular condition-
ing, can be determined. Suppression of
inspiratory flow identified during CPET
warrants prompt examination of the up-
per airway with a flexible laryngoscope
while the patient is still symptomatic to
identify if the upper airway obstruction
is from the more common EIVCD or the
less common EIL. A blood gas (usually
a finger stick for capillary blood is suf-
ficient) while reproduced symptoms are
present enables examination of pH and
pCO2. A high pH and low pCO2 identi-
fies EIH. The more commonly observed
low pH identifies metabolic acidosis
from muscle lactate production. The
associated low pCO2 demonstrates the
extent to which respiratory effort was
attempting to compensate for the meta-
bolic acidosis by increasing ventilation.
The extent of the data generated re-
quires that the physician be experienced
in interpreting and explaining the results
of the test. It is useful for the physician
interpreting the results of the CPET to
have observed the test in order to assess
the patient’s effort and response. Finally,
the results need to be translated to a level
appropriate for the patient and family.
SUMMARY
EID can occur for many reasons
in children and adolescents. Although
asthma is the most common cause, EIA
is readily diagnosed by demonstrating
elimination of EID and EIB when exer-
cise is preceded by a beta-2 adrenergic
agent such as albuterol, commonly re-
ferred to as a SABA. In the absence of
prevention of EID with a SABA, other
diagnoses including EIVCD, EIL, EIH,
chest wall restrictive abnormalities,
cardiac causes, and normal physiologic
limitation need to be considered. When
EIA is not confirmed by consistent pre-
vention with a SABA, a CPET is essen-
tial to identify the other causes of EID.
REFERENCES
1. Johansson H, Norlander K, Hedenström H,
et al. exercise-induced dyspnea is a prob-
lem among the general adolescent popula-
tion. Respir Med. 2014;108(6):852-858.
doi:10.1016/j.rmed.2014.03.010.
2. Godfrey S, Bar-Yishay E. Exercised-
TABLE 1.
History Taking for
Exercise-Induced dyspnea
Duration
How long
Sports or activities
Competitive or recreational
Symptoms
Shortness of breath, chest tightness,
cough, wheezing, or stridor
Inspiratory, expiratory, or both?
Dizziness/syncope
Tingling in arms/legs
Timing
Gradual vs dramatic onset
During or after exercise and duration
Modifying factors
Seasonal
Outdoor vs. indoor
Family history
Asthma
Allergies
Serious heart disease
Psychosocial history
Academic performance and anxiety
Response to bronchodilators
(if already tried)
PEDIATRIC ANNALS • Vol. 48, No. 3, 2019 e127
SPECIAL ISSUE ARTICLE
induced asthma revisited. Respir Med.
1993;87(5):331-344.
3. Abu-Hasan M, Tannous B, Weinberger M.
Exercise-induced dyspnea in children and
adolescents: if not asthma then what? Ann Al-
lergy Asthma Immunol. 2005;94(3):366-371.
doi:10.1016/S1081-1206(10)60989-1.
4. Anderson SD, Kippelen P. Exercise-induced
bronchoconstriction: pathogenesis. Curr Al-
lergy Asthma Rep. 2005;5(2):116-122.
5. Weinberger M, Abu-Hasan M. Is exercise-
induced bronchoconstriction exercise-
induced asthma? Respir Care.
2016;61(5):713. doi:10.4187/respcare.04767.
6. de Aguiar KB, Anzolin M, Zhang L. Global
prevalence of exercise-induced broncho-
constriction in childhood: a meta-analysis.
Pediatr Pulmonol. 2018;53(4):412-425.
doi:10.1002/ppul.23951.
7. Burnett DM, Burns S, Merritt S, Wick J,
Sharpe M. Prevalence of exercise-induced
bronchoconstriction measured by standard-
ized testing in healthy college athletes. Respir
Care. 2016;61(5):571-576. doi:10.4187/
respcare.04493.
8. Price OJ, Ansley L, Levai IK, et al. Eucap-
nic voluntary hyperpnoea testing in asymp-
tomatic athletes. Am J Respir Crit Care
Med. 2016;193(10):1178-1180. doi:10.1164/
rccm.201510-1967LE.
9. Price OJ, Ansley L, Menzies-Bow A,
Cullinan P, Hull JH. Airway dysfunction
in elite athletes – an occupational lung dis-
ease? Allergy. 2013;68(11):1343-1352.
doi:10.1111/all.12265.
10. Weinberger M, Abu-Hasan M. Life threat-
ening asthma during treatment with salme-
terol. N Engl J Med. 2006;355(8):852-853.
doi:10.1056/NEJMc066282.
11. Doshi D, Weinberger M. Long-term out-
come of vocal cord dysfunction. Ann Al-
lergy Asthma Immunol. 2006;96(6);794-799.
doi:10.1016/S1081-1206(10)61341-5.
12. Christopher KL, Wood RP 2nd, Eckert RC,
Blager FB, Raney RA, Souhrada JF. Vocal-
cord dysfunction presenting as asthma.
N Engl J Med. 1983;308(26):1566-1570.
doi:10.1056/NEJM198306303082605.
13. Weinberger M, Doshi D. Vocal cord dys-
function: a functional cause of respiratory
distress. Breathe (Sheff). 2017;13(1):15-21.
doi:10.1183/20734735.019316.
14. Vassilyadi M, Strawsburg RH. Delayed on-
set of vocal cord paralysis after explantation
of a vagus nerve stimulator in a child. Child
Nerv Syst. 2003;19(4):261-263. doi:10.1007/
s00381-003-0722-4.
15. Schmidt M, Brugger E, Richter W. Stress-
inducible functional laryngospasm: differen-
tial diagnostic considerations for bronchial
asthma [article in German]. Laryngol Rhinol
Otol (Stuttg). 1985;64(9):461-465.
16. Shaffer M, Litts JK, Nauman E, Haines J.
Speech-language pathology as a primary
treatment for exercise-induced laryngeal
obstruction. Immunol Allergy Clin North
Am. 2018;38(2):293-302. doi:10.1016/j.
iac.2018.01.003.
17. Hilland M, Røksund OD, Sandvik L,
Haaland Ø, Halvorsen T, Heimdal JH. Con-
genital laryngomalacia is related to exercise-
induced laryngeal obstruction in adoles-
cence. Arch Dis Child. 2016;101(5):443-448.
doi:10.1136/archdischild-2015-308450.
18. Buchvald F, Phillipsen LD, Hjuler T,
Nielsen KG. Exercise-induced inspira-
tory symptoms in school children. Pedi-
atr Pulmonol. 2016;51(11):1200-1205.
doi:10.1002ppul.23530.
19. Björnsdóttir US, Gudmundsson K, Hjartar-
son H, Bröndbo K, Magnússon B, Juliusson
S. Exercise-induced laryngochalasia: an imi-
tator of exercise-induced bronchospasm. Ann
Allergy Asthma Immunol. 2000;85(5):387-
391. doi:10.1016/S1081-1206(10)62552-5.
20. Redlinger RE, Kelly RE, Nuss D, et al.
Regional chest wall motion dysfunction
in patients with pectus excavatum demon-
strated via optoelectronic plethysmogra-
phy. J Pediatr Surg. 2011;46(6):1172-1176.
doi:10.1016/j.jpedsurg.2011.03.047.
21. Tang M, Nielsen HH, Lesbo M, et al. Im-
proved cardiopulmonary exercise function
after modified Nuss operation for pec-
tus excavatum. Eur J Cardiothorac Surg.
2012;41(5):1063-1067. doi:10.1093/ejcts/
ezr170.
22. Fitzgerald DA. The weighty issue of obesity
in paediatric respiratory medicine. Paedi-
atr Respir Rev. 2017;24:4-7. doi:10.1016/j.
prrv.2017.06.008.
23. Hammo AH, Weinberger M. Exercise in-
duced hyperventilation: a pseudoasthma
syndrome. Ann Allergy Asthma Immu-
nol. 1999;82(6):574-578. doi:10.1016/
S1081-1206(10)63169-9.
24. Chambers JB, Kiff PJ, Gardner WN, Jackson
G, Bass C. Value of measuring end tidal par-
tial pressure of carbon dioxide as an adjunct
to treadmill exercise testing. Br Med J (Clin
Res Ed). 1988;2996(6632):1281-1285.
25. Bass C, Chambers JB, Gardner WN. Hy-
perventilation provocation in patients with
chest pain and a negative treadmill exercise
test. J Psychosom Res. 1991;35(1):83-89.
doi:10.1016/0022-3999(91)90009-D.
26. Shafer KM, Mann N, Hehn R, et al. Relation-
ship between exercise parameters and non-
invasive indices of right ventricular function
in patients with biventricular circulation and
systemic right ventricle. Congenit Heart Dis.
2015;10(5):457-465. doi:10.1111/chd.12248.
27. Kempny A, Dimopoulos K, Uebing A, et
al. Reference values for exercise limitations
among adults with congenital heart disease.
Relation to activities of daily life--single
centre experience and review of published
data. Eur Heart J. 2012;33(11):1386-1396.
doi:10.1093/eurheartj/ehr461.
28. Dimopoulos K, Okonko DO, Diller GP, et al.
Abnormal ventilatory response to exercise in
adults with congenital heart disease relates
to cyanosis and predicts survival. Circula-
tion. 2006;113(24):2796-2802. doi:10.1161/
CIRCULATIONAHA.105.594218.
29. Chen CK, Manlhiot C, Russell JL, Kantor
PF, McCrindle BW, Conway J. The utility of
cardiopulmonary exercise testing for the pre-
diction of outcomes in ambulatory children
with dilated cardiomyopathy. Transplanta-
tion. 2017;101(10):2455-2460. doi:10.1097/
TP.0000000000001672.
30. Miliaresis C, Beker S, Gewitz M. Cardio-
pulmonary stress testing in children and
adults with congenital heart disease. Car-
diol Rev. 2014;22(6):275-278. doi:10.1097/
CRD.0000000000000039.
