Exercise testing in children and adolescents: Principles and clinical application

INTRODUCTION — Aerobic exercise testing in children and adolescents will be discussed here.

Related topics include:

●(See "Physical activity and exercise in patients with congenital heart disease", section on 'Exercise testing'.)

●(See "Exercise ECG testing: Performing the test and interpreting the ECG results".)

●(See "Cardiopulmonary exercise testing in cardiovascular disease".)

●(See "Selecting the optimal cardiac stress test".)

●(See "Cardiopulmonary exercise testing in the evaluation of unexplained dyspnea".)

EXERCISE TESTING BASICS

Purpose of testing — Incremental aerobic exercise tests are performed in children and adolescents for a variety of reasons (table 1) [1,2]. (See 'Clinical applications' below.)

The primary aim is to provide information about the patient's physical working capacity. The information gained from an aerobic exercise test is helpful in determining:

●Whether a patient can perform daily activities within his or her functional capacity

●Whether a patient is responding appropriately to an exercise intervention program

●Whether chronic disease progression is affecting the patient's physical capacity

Contraindications — Exercise testing can be performed safely in most children. Absolute contraindications to exercise testing include:

●Patients with acute myocardial or pericardial inflammatory disease

●Patients with severe right or left ventricular outflow tract obstruction in whom surgical intervention is indicated

With the exception of these conditions, there are few other absolute or relative contraindications to exercise testing within the pediatric patient population, and decisions regarding whether to perform testing should be based upon the child's specific risk. Patients with symptoms of exercise intolerance and those with underlying cardiac or pulmonary conditions can be categorized as lower or higher risk for adverse events during testing, using the risk stratification schema put forth by the American Heart Association, which is summarized in the table (table 2) [1].

In many cases, the benefits of evaluating the child in a controlled environment before allowing him or her unrestricted activity outweigh procedure-related risks. The procedure should be performed in an environment with appropriate safety equipment and personnel. A clinician should be available in case of unforeseen complications [1]. (See 'Equipment' below.)

Criteria for stopping the test — Exercise testing should be terminated if any of the following occur [1]:

●Diagnostic findings have been established and further testing would not yield any additional information

●Monitoring equipment fails

●Signs or symptoms indicate that further testing may compromise the patient's well-being

Indications for terminating pediatric exercise testing before reaching maximal voluntary capacity level are summarized in the table (table 3) [1].

Limitations in young children — In young children, exercise testing can be challenging due to poor cooperation with the test protocol. In addition, interpretation of exercise testing results in young children (<7 years) is challenging because normative reference values are largely lacking [3], though there are some reference values for four- and five-year-old children using the Bruce treadmill protocol [4].

The responsibility of the technologist and interpreting clinician when exercise testing is performed in younger children requires a careful balance of kindness, the ability to encourage and exhort the child to a maximal and consistent effort, and the ability to discern the quality of the overall performance. Behaviorally mediated submaximal performance will lead to inaccurate diagnostic implications.

There is no consensus regarding the age at which formal exercise testing is generally feasible, and there is great variability among different children at the same age and even in the same child on separate occasions. In our experience, most children can cooperate with exercise testing beginning at around the age of five to six years. A cycle protocol may be easier to administer and may increase the likelihood that the child completes the test. We have used the McMaster cycle protocol in children as young as six years; however, normative values are lacking. The Bruce treadmill protocol has also been used in young children [4].

Equipment — A clinical pediatric exercise testing unit should include, at minimum, the following equipment [1,2]:

●Treadmill

●Cycle ergometer

●Indirect calorimeter

●Electrocardiographic equipment

●Spirometer

●Pediatric resuscitation cart (including defibrillator)

●Pulse oximeter

●Doppler flow detectors

Motorized treadmills and cycle ergometers are the most common exercise modalities used in aerobic exercise testing (figure 1). The treadmill is used in children who are old enough to follow the required safety precautions. Treadmill running provides a more accurate indication of cardiorespiratory fitness because it uses greater and more diverse muscle mass than the cycle ergometer, which relies primarily on the quadriceps muscle group. When using the cycle, acute leg fatigue may limit performance slightly before the true cardiorespiratory limit has been reached. Thus, the values for peak aerobic capacity measured on a cycle ergometer are typically 5 to 10 percent lower than those obtained during treadmill testing [5].

Nonetheless, the cycle ergometer is a viable testing option, particularly if the child's medical condition or cognitive abilities preclude treadmill testing. Certain physiologic measurements, such as electrocardiogram and blood pressure, are easier to assess and of better quality using a cycle ergometer. The cycle is the preferred exercise testing modality if serial blood samples, blood pressure measurements at high workloads, or arterial oxygen (O₂) saturation measurements are to be obtained.

Indirect calorimetry units (or metabolic systems) with a computer interface have become more portable (and affordable) over the years. All metabolic systems measure the volume and the fractional concentrations of O₂ and carbon dioxide (CO₂) in expired air. More expensive units also can measure lung volume, arterial O₂ saturation, and cardiac output (via indirect methods). The internal computer calculates the variables of interest, including the volume of O₂ consumed (VO₂), volume of CO₂ produced (VCO₂), minute ventilation (VE), tidal volume, and respiratory rate. Depending upon the type of metabolic system, measurements can be made on a breath-by-breath basis, or every 20 to 30 seconds.

Protocols — A detailed discussion of exercise testing protocols is beyond the scope of this review but is available in reference [1]. As a general rule, the exercise test should begin at a low workload so that the child becomes accustomed to the exercise and surroundings. In some cases, the child may need to practice before beginning the test. Exercise testing protocols may be continuous or discontinuous. When comparing results of two tests performed on an individual patient (eg, pre- and postexercise training), it is important to perform both tests using the same protocol and exercise modality.

Continuous — Test protocols are usually continuous (ie, without rest periods) and have either ramped or incremental stages.

●Ramped protocols begin at a given speed or power output and increase in intensity throughout the following minute; a metabolic steady state is never achieved during testing. Ramped protocols are preferred when the clinician is primarily interested in subtle metabolic or respiratory responses, such as ventilatory threshold, that occur with increasing exercise intensity up to a maximal level.

●Incremental protocols increase the workload at the end of stages that typically last between one to three minutes, depending upon the information being collected. Stages are usually longer if it is important to determine the child's steady state response to a given submaximal workload in addition to his or her maximal exercise values. Incremental protocols permit more time for the clinician to obtain submaximal blood pressure and blood lactate measurements.

Total test time for both ramped and incremental protocols should average between 9 and 14 minutes. Longer tests, particularly in young children, may result in acute leg fatigue and volitional exhaustion before a true maximum VO₂ is achieved.

Discontinuous — In discontinuous exercise protocols, children are permitted to rest between stages. As an example, each exercise stage might last two to three minutes, with one to two minutes of rest in between. Discontinuous protocols may be preferred when more invasive measures, such as fingerstick or venous blood sampling (eg, for glucose and/or lactate analysis), are required or when blood pressure must be measured soon after high workloads. Discontinuous protocols also may be more appropriate for children who are unfit and have low exercise tolerance.

Treadmill — When a motorized treadmill is used, exercise usually begins with a walk at a slow pace of approximately 2 miles per hour. The workload becomes more challenging as a result of increasing speed (usually 0.5 to 1 miles per hour per stage), treadmill elevation (usually 2 to 3 percent per stage), or both. Depending upon the patient's ability, later test stages may involve running. For children who are physically fit, peak VO₂ estimates obtained with running protocols may be somewhat higher than those obtained from walking tests [6]. This occurs because acute leg fatigue may precede true maximum cardiorespiratory effort during an extended walking protocol that involves long steps up a steep hill. Walking protocols may be more appropriate for overweight or unfit children.

Cycle — For cycle tests, the pedal speed should be set at a comfortable rate for the child, usually between 50 to 90 revolutions per minute. The initial power output is typically set at approximately 25 watts and increases by increments of 12.5 to 25 watts per stage, depending upon the age and fitness level of the child. Greater increments may be used if the patient is extremely fit.

MEASUREMENTS OF AEROBIC CAPACITY

Physiologic principles — Aerobic capacity is the maximum volume of oxygen (O₂) consumed (VO₂max) by the body during an exercise challenge. VO₂max is considered to be the best overall measure of the cardiorespiratory fitness of a healthy individual [7].

The physiologic components that make up VO₂ are illustrated by the following rearrangement of the classic Fick equation (figure 2):

Where (CaO₂ – CvO₂) is the difference in O₂ content between arterial and mixed venous blood

Thus, the VO₂max can be affected by both central (cardiac output) and peripheral (CaO₂ and CvO₂) factors. Maximum cardiac output is limited by HR and SV, which are affected by age, cardiac structure, and cardiac function. The peripheral factors that limit VO₂max include aerobic enzyme activity, mitochondrial density, hemoglobin concentration, and capillary density in the exercising musculature. These factors are affected by normal biology, heredity, body size, and illness. Acute or chronic disease usually results in lower-than-normal VO₂max. In contrast, heredity or chronic aerobic exercise training can increase VO₂max to above-normal levels.

The unit of measure for VO₂max in the Fick equation is mL/min. However, it is common practice to divide this value by the body weight (in kg) of the individual who is being tested, resulting in a value that is expressed in mL/kg per min. This is done because most daily activities, and many sports and exercises, are "weightbearing" (ie, the child must move his or her body weight against gravity). The adjustment for weight permits the clinician to compare the individual patient's VO₂max with normal or population-specific values.

Maximum effort — VO₂max is considered to be the best overall measure of the cardiorespiratory fitness of a healthy individual [7]. However, many children are unable or unwilling to achieve a "true" VO₂max during exercise testing. Thus, the term "VO₂peak" is often used rather than "VO₂max" when measuring O₂ consumption during exercise in children [7,8]. "VO₂peak" refers to a measure of endurance performance without implying that maximal O₂ uptake was achieved. Whether a child is able to provide a maximal effort during exercise testing is dependent upon the child's age, developmental status, cognitive ability, motivation, and disease state. To obtain a "true" VO₂max, the patient must exercise to volitional exhaustion that is limited by O₂ delivery to, and extraction in, the working muscles, and many children (particularly young children) are unwilling and/or unable to do so.

When VO₂ is lower than expected for a particular patient, the clinician must decide whether the patient put forth maximal or at least near-maximal effort. This is particularly true in patients who are being tested for fatigue. The following criteria can be used to help determine whether a maximal or at least near-maximal effort has been given:

●VO₂ plateau

●HR maximum (HRmax)

●Respiratory exchange ratio maximum (RERmax)

VO2 plateau — The VO₂ plateau occurs when a patient continues to exercise after his/her VO₂max has been reached, even though the exercise intensity continues to increase (figure 3) [9,10]. Exercise is able to continue through the contribution of anaerobic metabolism.

The VO₂ plateau is often considered the "gold standard" criterion for VO₂max and has been used as such since the mid-1950s [8]. Unfortunately, however, a plateau does not always occur when testing children, even if they are healthy and exercising to maximal effort [1,7,8].

Heart rate maximum — The achievement of HRmax is another criterion for maximal effort. In adults, HRmax decreases as a function of age and can be predicted by various equations [11,12]. HRmax in adults is usually predicted as follows [11] (see "Exercise physiology"):

The average HRmax in children and adolescents is considered to be 200 bpm, with a wide range of individual values [3]. In our experience, the average HRmax of young adolescents is 197 bpm, with a range of 181 to 231 bpm. This is similar to the findings of other investigators. HRmax may vary by 5 to 10 bpm within an individual child performing different protocols. Most researchers accept an exercise test to be a maximal effort if the child's HRmax is greater than 95 percent of predicted HRmax (ie, HR ≥190 bpm).

Respiratory exchange ratio maximum — The respiratory exchange ratio maximum (RERmax) is another criterion that is used to evaluate the maximum effort. The RERmax is calculated as the ratio of the volume of carbon dioxide (CO₂) produced (VCO₂) to the VO₂.

When an individual is in a metabolic steady state, the RER (or respiratory quotient) ranges from 0.70 at rest to close to 1.00 during vigorous exercise, primarily because of fat and carbohydrate metabolism, respectively. At maximal workloads, the ratio increases (usually to above 1.00) because of respiratory compensation for the metabolic acidosis of exercise. In addition, children may have an unusually high RER during the pre-exercise period. This is usually caused by anxiety, which results in increased respiratory rate and depth of breathing. The RER returns to a normal value once the exercise begins.

In one study, the average RERmax among 453 girls who underwent maximal treadmill testing was 1.15±0.09; only 4 percent had RERmax below 1.00 [13]. Many experts consider an RERmax value >1.00, combined with an adequate HRmax and/or VO₂ plateau, sufficient evidence of a maximal effort in children.

Normal capacity — Reviews of "normal" VO₂peak during childhood and adolescence have been published [5,14]. In boys, VO₂peak appears to be fairly constant throughout childhood and adolescence, with reported values averaging between 50 to 55 mL/kg per min. In contrast, in girls, VO₂peak is highest in early childhood at approximately 50 mL/kg per min and declines steadily throughout adolescence by approximately 1 mL/kg per min per year. It is not well understood if this is mainly the result of onset of puberty, decline in physical activity, or both.

Although VO₂peak decreases or plateaus with increasing age, the time to volitional exhaustion typically increases. This is because exercise economies (ie, the VO₂ used per kg of body weight at a given workload) usually increase with age and growth, decreasing the amount of energy required to perform a given exercise task.

It is important to choose the correct standard when comparing aerobic capacity with the norm. As an example, a 12-year-old girl who has breathlessness and lightheadedness during soccer practice may have a normal VO₂peak compared with other 12-year-old females but a low VO₂peak compared with other 12-year-old female soccer players.

Submaximal capacity — Very few activities require a sustained maximal aerobic effort. However, many activities, sports, and other endurance exercises require extended work at a high submaximal level. Thus, for research on aerobic fitness in children, we suggest that VO₂peak and submaximal VO₂ (or VO₂ at a given workload) be used as outcome measures.

The ability for a child to perform at a high percentage of his or her VO₂max is usually estimated by calculating either the lactate or ventilatory thresholds.

Lactate threshold — At low to moderate exercise intensity, lactate production and clearance are matched and blood lactate does not increase significantly. However, as exercise intensity increases, production exceeds clearance and lactate concentration increases exponentially. The lactate threshold occurs just before the exponential rise (figure 4). The closer this threshold comes to VO₂max, the greater an individual's potential for high-level endurance performance. Many coaches believe aerobic training should occur at an intensity level just prior to the point where the onset of the lactate threshold occurs in order for an athlete to derive maximum benefit from a workout.

It is possible to increase the lactate threshold by performing vigorous aerobic training that might result in little change in VO₂max (figure 5). Although the effect of aerobic training on lactate threshold has been studied thoroughly in adults, few investigators have examined this issue in children [15,16].

Most experts agree that lactate threshold protocols should be incremental, with at least three- to four-minute stages. [17]. For logistic reasons, unless a discontinuous protocol is used, cycle exercise is preferred over treadmill. The clinician should find the most suitable protocol for his or her laboratory and perform all tests in the same manner. This will increase the internal validity of the measurements. (See 'Protocols' above.)

Blood lactate values can be obtained from simple fingerstick samples. However, some clinicians would prefer not to perform any invasive measure that is not absolutely necessary on a child. They may prefer to use the ventilatory threshold to estimate submaximal performance.

Ventilatory threshold — The ventilatory threshold is the intensity at which ventilation during exercise begins to rise in excess of VO₂. It is best demonstrated by plotting VE/VO₂ and VE/VCO₂ on the same graph, where VE is the minute ventilation (ie, the volume of gas expired in L/min), VO₂ is the volume of O₂ consumed (L/min), and VCO₂ is the volume of CO₂ produced (L/min). The ventilatory threshold is the point just before VE/VO₂ begins to rise without a similar rise in VE/VCO₂ (figure 6).

Given the subtleties associated with respiratory changes during exercise, the best ventilatory threshold results usually are obtained when using ramped protocols. Either the treadmill or the cycle may be used. The clinician should find the most suitable protocol for his or her laboratory and perform all tests in the same manner. This will increase the internal validity of the measurements.

The use of the ventilatory threshold to measure the ability of a child to perform at a high percentage of his or her VO₂max is controversial [18]. However, some investigators believe that it provides information similar to that gained from the lactate threshold [18]. The advantage to the ventilatory threshold is that it is noninvasive. The main disadvantage is that respiration may be affected by many factors during exercise in addition to metabolism. Thus, the ventilatory threshold is usually considered to be less reliable than the lactate threshold measure.

Training effects — In previously sedentary adults, aerobic exercise training increases VO₂max by approximately 20 percent on average [19]. However, studies of the effect of training on VO₂max in normal healthy children have inconsistent results [20-22].

It appears that exercise training has a limited effect on VO₂max in children [23]. Some authors contend this is because of insufficient training regimens [23,24]. In one meta-analysis of the effects of exercise training on VO₂max in prepubescent and peripubescent children, including studies with both cross-sectional and pretest-posttest designs, the reported changes in VO₂max in children were small to moderate [20]. Nonetheless, the average effect size indicated a difference in VO₂max between trained and untrained athletes, though possible sources of confounding data were identified in the cross-sectional studies (eg, subject self-selection). Analysis of the subset of studies with pretest-posttest designs indicated that on average, training resulted in a 2 mL/kg per minute increase in VO₂max and was not affected by the sufficiency of the training protocol [20]. These results support the "trigger hypothesis" that the trainability of children is low until after puberty [25].

On the other hand, cross-sectional studies have shown that child and adolescent athletes have significantly higher VO₂max values compared with their less athletic peers [26,27]. Values of 60 to 70 mL/kg per min are not unusual in endurance-trained child and adolescent runners [26].

In one study, VO₂max, SV, cardiac output, left ventricular dimensions, arterial pressure, and systemic vascular resistance were compared between prepubertal trained and untrained children [27]. VO₂max was greater among the trained children (58.5±4.4 versus 45.9±6.7 mL/kg per min). Cardiac output during exercise and at rest was also higher in the trained children. The increased cardiac output was explained by increased SV since HR at rest and during exercise were similar between groups. In addition, diastolic and systolic left ventricular dimensions and the pattern of systemic vascular resistance were similar for both groups. These findings suggest that the higher maximal SV in the trained children results from factors that influence resting SV (eg, cardiac hypertrophy, augmented myocardium relaxation properties, expanded blood volume), indicating that genetics may play a role in the determination of VO₂max values.

The most convincing evidence of a genetic influence was provided in a comparison of VO₂ variability between monozygotic and dizygotic twin pairs [28]. Monozygous twins had much less variability in VO₂max than dizygous twins and non-twin brothers. The authors concluded heredity was responsible for between 25 to 50 percent of the variance in the boys' VO₂max values.

In contrast with its moderate impact on children's VO₂max, exercise training may have a greater effect on submaximal exercise performance. (See 'Submaximal capacity' above.)

FUNCTIONAL AEROBIC IMPAIRMENT — Functional aerobic impairment (FAI) is the difference between an individual's actual and expected aerobic capacity (based on age, sex, and activity level). FAI occurs as the result of muscle wasting or atrophy secondary to deconditioning and may result in debilitating fatigue.

It is important to consider FAI and debilitating fatigue when performing exercise testing in patients with clinical conditions associated with muscle wasting or atrophy (eg, Down syndrome, neuromuscular disease) because FAI and debilitating fatigue can contribute to decreased capacity for physical activity. Consideration of FAI and debilitating fatigue permits exercise recommendations to be appropriately tailored to the individual patient, which may result in improved comfort during exercise and increased adherence to the exercise program.

CLINICAL APPLICATIONS — The indications for and the issues related to exercise testing in children and adolescents with chronic medical conditions are presented below.

Children with the conditions discussed below often have reduced aerobic capacity (ie, lower peak oxygen [O₂] consumption [VO₂peak]) compared with healthy children, indicating decreased cardiorespiratory fitness. However, it is important to remember that many children with these conditions are sedentary, either because of inability to exercise or advice from doctors and/or parents/caregivers who encourage inactivity [29]. In most cases, physical activity can be prescribed for children with these conditions and will result in increased fitness and/or decreased symptoms. (See "Physical activity and strength training in children and adolescents: An overview", section on 'Benefits of regular physical activity'.)

Exercise-induced bronchoconstriction — Exercise-induced bronchoconstriction (EIB) affects up to 80 percent of individuals who have asthma [30]. In addition, approximately 8 to 10 percent of children with no apparent history of asthma have EIB [31-33]. (See "Exercise-induced bronchoconstriction".)

Exercise testing is a useful tool in the diagnosis of EIB and for evaluating the exercise capacity and cardiopulmonary response to exercise in the child with asthma [31]. Children with EIB commonly present with postexercise coughing and chest pain; wheezing and dyspnea also may be present. Exercise testing can help to differentiate EIB from other causes of exercise-induced dyspnea in children and may be particularly helpful in those who have no other signs or symptoms of asthma and who do not respond to pretreatment with bronchodilators [34,35]. Other causes of exercise-induced dyspnea may include normal physiologic exercise limitation, restrictive abnormalities, and vocal cord dysfunction.

The standard exercise protocol for children with EIB is motorized treadmill running at 80 to 90 percent of the child's age-predicted maximal heart rate (HRmax) for six to eight minutes. In the Michigan State University laboratory, this is typically accomplished by setting the treadmill speed at approximately 6 miles per hour, with a 5 to 6 percent elevation. A positive test is one in which the child's postexercise forced expiratory volume in one second (FEV₁) decreases more than 15 percent from pre-exercise level [31].

In children and adolescents who have EIB, the development of bronchoconstriction during exercise and the presence of preexisting obstruction can profoundly alter exercise test performance and the ventilatory responses to exercise. In one study comparing 11 children with EIB and normal controls, children with EIB had lower VO₂peak (34.5±3.5 versus 44.5±10 mL/kg per min) [36]. In contrast with children without EIB, respiratory mechanics and lung capacity in children with EIB may limit aerobic performance and they may quit the exercise test before achieving a true HRmax. Thus, the HRmax criterion is not a good indicator of effort intensity in children with EIB. (See 'Maximum effort' above.)

Cystic fibrosis — Children, adolescents, and young adults with cystic fibrosis (CF) who exercise regularly may recover more quickly from acute illnesses compared with those who are sedentary. Regular exercise is thought to improve mucus clearance and is encouraged for all patients with CF, as discussed separately. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Exercise'.)

Many pediatric CF centers routinely perform exercise testing in patients with CF [37]. An incremental cycle protocol is often used, where power output begins at 0 watts for one minute and increases by 10 to 20 watts each minute thereafter. Because of the inherent pulmonary limitations, the time to "exhaustion" will be significantly shorter for CF patients than for healthy children [31]. The steep ramp test, an alternative cycle ergometer test that measures peak work rate and does not require the use of respiratory gas analysis, has also been studied in patients with CF and, in one series, was found to correlate well with VO₂peak measurements obtained using standard cardiopulmonary exercise tests [38].

In one study of 36 children with CF who were between 6 and 19 years of age, mean VO₂peak values were more than one standard deviation below the mean for healthy children (31.6±6.1 mL/kg per min) [39]. Similar to patients with EIB, those with CF typically reach a pulmonary limitation to their exercise performance before achieving their HRmax.

Exercise testing appears to be a good prognostic tool for children with CF because it correlates with functional status (perhaps simply because it is a marker for less severe illness), as illustrated below [40]:

●In one cohort study, 109 CF patients age 7 to 35 years underwent pulmonary function and exercise testing and then were followed for eight years [40]. Survival rates were greatest among patients with the highest levels of aerobic fitness (83, 51, and 28 percent among those with VO₂peak ≥82 percent, 59 to 81 percent, and ≤58 percent of predicted, respectively). Patients with higher levels of aerobic fitness were more than three times as likely to survive than those with lower levels of aerobic fitness after adjustment for other risk factors.

●In a review of annual spirometric and exercise testing data from 58 children (aged 11 to 15 years) with moderate CF lung disease, those who retained carbon dioxide (CO₂) at baseline had a more rapid decline in FEV₁ than those who did not (overall decline in percent predicted FEV₁ of -14.8 versus -6.7 percent) [41]. Pulmonary function testing in children, including spirometry, is discussed in detail separately. (See "Overview of pulmonary function testing in children".)

Exercise training in patients with CF may be associated with a small but significant improvement in clinically relevant endpoints, including spirometric changes over time, nutritional status, and overall quality of life. Several studies have indicated improvement or delayed worsening in various pulmonary function indices with exercise training [42-46]. As an example, in a randomized controlled trial, 65 children with CF were randomly assigned to exercise (a minimum of 20 minutes of aerobic exercise at an HR of approximately 150 beats per minute [bpm] three times per week) or control groups (usual physical activity) [45]. Exercise was associated with a small but significant decrease in the rate of pulmonary function decline. Further research is warranted to determine whether improving aerobic fitness through exercise programs will result in a better prognosis.

Idiopathic pulmonary arterial hypertension — Idiopathic pulmonary arterial hypertension is considered by some to be a contraindication to maximal exercise testing in children, and it is not performed at the author's institution. However, careful exercise testing may be safely performed in even the most severely affected patients in centers that routinely care for these patients [47,48].

Exercise testing may be used to assess functional capacity and to identify high-risk patients as well as patients who are most likely to benefit from vasodilator treatment [48]. Either cycle or treadmill (walking) protocols can be used, depending upon the patient's confidence and ability. In one small study of 16 patients, two subjects who attained exercise capacity >75 percent of predicted benefited from vasodilator treatment, whereas three subjects with exercise capacity <10 percent of predicted died at or soon after cardiac catheterization [47].

Submaximal exercise testing also may be a valuable tool for assessing the prognosis and treatment of children with idiopathic pulmonary arterial hypertension [49]. In many clinics, the six-minute walk test is given in lieu of maximal testing [50]. (See "Pulmonary hypertension in children: Classification, evaluation, and diagnosis".)

Growth hormone deficiency — Physical exercise is a well-known stimulus to growth hormone (GH) secretion. Clinicians have begun to explore the use of clinical exercise testing as an adjunct to and, in some cases, a replacement for pharmacologic stimulus of GH secretion to aid in the diagnosis of GH deficiency in children with short stature [51]. The use of exercise testing is advantageous because it uses a physiologic stimulus and has minimal side effects [52]. (See "Diagnosis of growth hormone deficiency in children", section on 'Growth hormone stimulation tests'.)

Exercise protocols used to evaluate GH deficiency in children with short stature have not been standardized. In one study, a submaximal cycle protocol was used to test for GH secretion [53]. Although the protocol was as effective as L-DOPA/propranolol for stimulating GH response, it was time-consuming because additional testing was required to obtain the child's VO₂peak. In another study, a treadmill protocol to volitional exhaustion was used to stimulate GH secretion in 77 children with short stature, 47 children with normal growth, and 30 children with GH deficiency [52]. The results were compared with those obtained with standard pharmacologic stimulation. The children had VO₂peak values similar to normal-height children of the same age (46.1±1 mL/kg per min). Compared with pharmacologic testing, the treadmill exhaustion test had sensitivity of 90 percent for detecting GH deficiency but specificity of only 11 percent. The authors recommend against the use of the treadmill exhaustion test as a screening tool for GH insufficiency.

HIV infection — Debilitating fatigue, mediated by cardiorespiratory insufficiency, is one of the chief complaints of individuals infected with HIV. Exercise test results may be used to compare the patient's fitness level with the energy requirements for activities of daily living [54]. (See "Pediatric HIV infection: Classification, clinical manifestations, and outcome".)

Children and adolescents with HIV infection are at risk for HIV-related or pharmacologically mediated skeletal muscle dysfunction, which may result in functional aerobic impairment (FAI; ie, VO₂peak <73 percent of minimal predicted physiologic values). (See 'Functional aerobic impairment' above.)

In one study of 17 untrained, sedentary adolescents with HIV infection, VO₂peak values were approximately 50 percent lower than the average for healthy teenagers (27.7±11.6 mL/kg per min for boys and 21.4±6.2 mL/kg per min for girls) [54].

Cancer survivors — Exercise testing in childhood cancer patients can be used to detect cardiopulmonary abnormalities associated with radiation and/or chemotherapy that are not evident at rest, which may include [55] (see "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity"):

●Decreased cardiac contractility

●Conduction disturbances

●Inability to increase O₂ uptake because of decreased chest wall motility and/or pulmonary fibrosis

●Musculoskeletal weakness

In one study comparing 30 children and adolescents who were treated for cancer and an age-matched control group, most cancer patients were able to attain the predicted HRmax but failed to increase left ventricular ejection fraction during exercise [55]. Pulmonary limitation appeared to be minimal. Cancer patients averaged only 80 percent of the exercise capacity of the controls. Whether putting childhood cancer patients on an exercise training program, as is recommended by some researchers, affects exercise capacity is not known, because long-term outcome data are lacking [55].

In a larger study, 84 survivors of childhood cancer (7 to 21 years of age) and 779 healthy controls underwent treadmill exercise testing at a mean age of 7.7 years after diagnosis [56]. The cancer survivors had been treated with anthracyclines or chest irradiation but had normal left ventricular systolic function at rest. Exercise responses were similar between groups, with the exception of slightly decreased VO₂peak in boys <13 years old. This finding was attributed to decreased physical fitness since the other exercise parameters were similar.

Congenital diaphragmatic hernia — In patients who have undergone repair of congenital diaphragmatic hernia (CDH) during the neonatal period, respiratory impairment may result from lung hypoplasia and hypoperfusion on the involved side. Exercise testing may help determine whether these conditions affect VO₂ during stressful activities, such as competitive sports [57]. (See "Congenital diaphragmatic hernia in the neonate", section on 'Long-term complications'.)

One study compared 15 children who had surgically repaired CDH and 15 active healthy control children [57]. Compared with healthy controls, children with CDH had decreased VO₂peak, particularly if they were sedentary. The authors speculated that physical inactivity, rather than ventilatory dysfunction, was responsible for low aerobic capacity in the sedentary children.

Down syndrome — Because of their musculoskeletal disabilities, children, adolescents, and young adults with Down syndrome may have FAI (ie, VO₂peak <73 percent of expected), which could lower their aerobic capacity. Exercise testing may be warranted to determine the child's ability to perform physical activities and sports and to determine whether FAI is present [58]. (See 'Functional aerobic impairment' above and "Down syndrome: Clinical features and diagnosis".)

In one study of clinical and functional status, 37 children with Down syndrome were evaluated and compared with control children [58]. Compared with controls, subjects with Down syndrome had a low exercise tolerance and achieved only 61±12 percent of predicted values for age and sex. Only 3 of 37 subjects had exercise tolerance within the reference range of 80 to 100 percent of normal values; 27 had VO₂peak 50 to 80 percent of predicted, and 7 had VO₂peak <50 percent of predicted. Reduced exercise tolerance in these patients may be caused by physical inactivity, obesity, or pathogenic skeletal muscle dysfunction.

Another study evaluated VO₂peak in youth with Down syndrome (n = 80) compared with children with intellectual disability (but not Down syndrome; n = 59) and controls (n = 74) [59]. The children with Down syndrome achieved the lowest VO₂peak (26.5 mL/kg per min) compared with those with intellectual disabilities (38.9 mL/kg per min) and controls (44.4 mL/kg per min). This study also looked at the impact of obesity on VO₂peak and found that Down syndrome had the greatest impact on VO₂peak, regardless of weight status.

Arthritis — Children and adolescents who have arthritis of any type may be less physically active than their healthy peers. Reasons for inactivity include chronic joint pain and stiffness, reduced strength [60], synovitis, and/or joint deformity [61]. Muscle strength and endurance may be affected by these problems, causing FAI (ie, VO₂peak <73 percent of expected). Exercise testing can be used to determine the extent, if any, of FAI. A non-weightbearing cycle protocol is recommended for exercise testing of children and adolescents who have arthritis [61].

Children and adolescents who have arthritis appear to have decreased aerobic capacity for a variety of reasons. In one comparison study of aerobic capacity and workload completed by children with juvenile idiopathic arthritis (JIA; formerly juvenile rheumatoid arthritis) and healthy children during cycle ergometer exercise, children with JIA had a significantly lower VO₂peak (33 versus 46.9 mL/kg per min) [61]. No direct relationship was found between functional aerobic capacity and disease severity in the affected children. The authors speculated that the lower VO₂peak values in children with JIA appear to be caused by either mechanical inefficiency or hypoactivity. Another author attributes the low aerobic capacities associated with conditions such as JIA to the sedentary lifestyle caused by the disease [29].

In another study, children with JIA had significantly lower VO₂peak compared with healthy controls (34.6 versus 49.1 mL/kg per min) [62]. Differences were also found among JIA subgroups, with the polyarticular rheumatoid factor positive-onset subgroup having the highest FAI. Longitudinal studies are needed to help determine the causal pathways. (See "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis".)

Neuromuscular disease — In children who have neuromuscular disease, exercise performance is usually limited by decreased muscle function rather than cardiorespiratory capacity. Exercise testing of these patients can provide a quantitative assessment of the child's condition, the improvement in economy of locomotion after surgical treatment, and the potential effects of exercise stress [63].

Children with neuromuscular disease usually have lower VO₂peak than healthy children because of sedentary behavior. In one study that evaluated aerobic capacity in 19 adolescents with spastic cerebral palsy, VO₂peak values were 20 to 40 percent lower in patients with cerebral palsy compared with healthy controls [64].

In addition to lower VO₂peak, the metabolic cost for physical activity is greater in children with neuromuscular disease than in their healthy counterparts [63]. Exercise training can reduce the metabolic inefficiency, although VO₂peak values may not increase significantly [63].

Chronic fatigue syndrome — Chronic fatigue syndrome, also known as myalgic encephalomyelitis/chronic fatigue syndrome, is a complicated and controversial disease characterized by unexplained, persistent, and relapsing fatigue. A single etiology has not been elucidated [65]. Deconditioning from a sedentary lifestyle is an important component of the maintenance of the chronic fatigue [66]. (See "Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome".)

Similar to children who suffer from other disorders of neuromuscular function, exercise testing may be indicated to compare the patient's physical tolerance with the energy costs of activities of daily living.

Submaximal and maximal exercise testing can be performed, as tolerated, in patients with chronic fatigue [67,68]. The exercise capacity in individuals with chronic fatigue syndrome is at the low end of the normal range and is limited by reduced central drive and deconditioning [66,69]. Functional capacity and fatigue have been shown to improve with exercise [66]. (See "Treatment of myalgic encephalomyelitis/chronic fatigue syndrome".)

Congenital heart disease — Exercise testing in patients with congenital heart disease is discussed separately. (See "Physical activity and exercise in patients with congenital heart disease", section on 'Exercise testing'.)

SUMMARY AND RECOMMENDATIONS

●Aim of exercise testing – The primary aim is to provide information about the patient's physical working capacity. The information gained from an aerobic exercise test is helpful in determining (table 1) (see 'Purpose of testing' above):

•Whether a patient can perform daily activities within their functional capacity

•Whether a patient is responding appropriately to an exercise intervention program

•Whether chronic disease progression is affecting the patient's physical capacity

●Contraindications – Exercise testing can be performed safely in most children. Absolute contraindications to exercise testing include acute myocardial or pericardial inflammatory disease and severe outflow tract obstruction requiring surgical intervention. Additional relative contraindications are summarized in the table (table 2). (See 'Purpose of testing' above and 'Contraindications' above.)

●Reasons to stop the test – Exercise testing should be terminated if any of the following occur (table 3) (see 'Criteria for stopping the test' above):

•Diagnostic findings have been established and further testing would not yield any additional information

•Monitoring equipment fails

•Signs or symptoms indicate that further testing may compromise the patient's well-being

●Equipment – Motorized treadmills and cycle ergometers are the most common exercise modalities used in aerobic exercise testing (figure 1). Treadmill running generally provides a more accurate indication of cardiorespiratory fitness and is used for exercise testing in children who are old enough to follow the required safety precautions. The cycle ergometer is another viable testing option, particularly if the child's medical condition or cognitive abilities preclude treadmill testing. Certain physiologic measurements, such as electrocardiogram and blood pressure, are easier to assess and of better quality using a cycle ergometer. (See 'Equipment' above.)

●Maximum effort – Aerobic capacity is the maximum volume of oxygen (O₂) consumed (VO₂max) by the body during an exercise challenge. VO₂max is considered to be the best overall measure of cardiorespiratory fitness. Whether a child is able to provide a maximal effort during exercise testing is dependent upon the child's age, developmental status, cognitive ability, motivation, and disease state. Because many children (particularly young children) are unable or unwilling to attain a true VO₂max during exercise testing, many experts use the term "VO₂peak," which refers to a measure of endurance performance without implying that maximal O₂ uptake was achieved. (See 'Maximum effort' above.)

●Normal capacity – In boys, VO₂peak appears to be fairly constant throughout childhood and adolescence, with reported values averaging between 50 to 55 mL/kg per min. In girls, VO₂peak is highest in early childhood at approximately 50 mL/kg per min and declines steadily throughout adolescence by approximately 1 mL/kg per min per year. (See 'Normal capacity' above.)

●Clinical applications – Exercise testing may be helpful in the diagnosis or prognosis of chronic medical conditions, including (see 'Clinical applications' above):

•Exercise-induced bronchoconstriction (EIB) (see 'Exercise-induced bronchoconstriction' above)

•Cystic fibrosis (CF) (see 'Cystic fibrosis' above)

•Growth hormone (GH) deficiency (see 'Growth hormone deficiency' above)

•HIV infection (see 'HIV infection' above)

•Cancer survivors (see 'Cancer survivors' above)

•Congenital diaphragmatic hernia (CDH) (see 'Congenital diaphragmatic hernia' above)

•Down syndrome (see 'Down syndrome' above)

•Arthritis (see 'Arthritis' above)

•Neuromuscular disease (see 'Neuromuscular disease' above)

•Chronic fatigue syndrome (see 'Chronic fatigue syndrome' above)

•Congenital heart disease (see "Physical activity and exercise in patients with congenital heart disease", section on 'Exercise testing')