VO₂ is the primary indicator of aerobic metabolic capacity. It reflects the interaction between pulmonary ventilation, cardiovascular transport, and peripheral utilization of oxygen in the working muscles and is considered the “gold standard” for assessing the aerobic capacity of the individual. VO₂ increases linearly with workload increase until the maximal value (VO₂max) is reached.^[10] In children, reaching a clearly defined VO₂ plateau is not always possible. Therefore, the term “peak oxygen consumption” (VO₂peak) is used, which denotes the highest value of VO₂ reached during the test.^[5] VO₂peak is an acceptable and clinically applicable indicator in the pediatric population, provided that the test is performed with a sufficiently high intensity.^[11] The difficulties in reaching true maximal exercise in children also necessitate the introduction of submaximal assessment parameters that are valid even in the absence of maximal effort.^[10]

Ventilatory thresholds are key metabolic points during exercise that mark the characteristic changes in the metabolic processes for energy production required for muscle contraction. The first ventilatory threshold (VT1), also called the anaerobic threshold (AT), reflects the beginning of additional CO₂ production, which is an expression of the increasing reliance on anaerobic metabolic pathways. This is accompanied by the incipient development of metabolic acidosis. The second ventilatory threshold (VT2), called by Wasserman the respiratory compensation point (RCP), marks the moment of a disproportionate increase in ventilation relative to CO₂ production and is associated with the exhaustion of the compensatory mechanisms for maintaining normal acid-base balance.^[12]

In children, ventilatory thresholds often occur at a relatively higher percentage of VO₂peak compared to adults. This is thought to be related to developmental differences in muscle metabolism, including low glycolytic enzyme activity, reduced lactate production, and a greater reliance on oxidative pathways during exercise.^[5] As a result, children often demonstrate a more gradual transition from purely aerobic to mixed (aerobic and anaerobic) energy production.

The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide production to oxygen consumption (VCO₂/VO₂), reflects substrate utilization during exercise. At rest and during low-intensity exercise, RER values are typically below 1.0, indicating predominant fat oxidation. With increasing exercise intensity and greater reliance on carbohydrate metabolism, RER rises and may exceed 1.0 due to additional CO₂ production from buffering of exercise-induced metabolic acidosis.

In pediatric populations, peak RER values during maximal exercise are often lower than those observed in adults.^[5] This might be related to differences in metabolic characteristics, including lower glycolytic capacity, earlier peripheral fatigue, or motivational factors. Consequently, the adult maximality criterion of RER >1.10–1.11 may not always be appropriate in children. Some studies suggest that RER values around 1.00–1.05 may already indicate near-maximal effort when accompanied by other markers such as high HR, VO₂ plateau, or signs of fatigue.^[7,13] Therefore, RER in children should be interpreted in the context of other indicators assessing the overall exercise performance.

The relationship between minute ventilation (VE) and carbon dioxide production (VCO₂) is referred to as ventilatory efficiency (VE/VCO₂). The ventilatory efficiency slope is typically calculated using linear regression of VE against VCO₂ from the onset of exercise until VT2/RCP^[10](Fig. 1). It is one of the most stable and clinically relevant indicators in CPET, as it reflects the extent to which ventilation can ensure the elimination of CO₂ during increment exercise.^[14]

In children, developmental characteristics including higher RR, smaller Vt, and different lung mechanics can affect the absolute values of the VE/VCO₂ slope. Therefore, the use of age-, sex- and height-specific reference values is essential. The ventilatory efficiency slope is informative even at submaximal effort, which makes it a suitable parameter for assessment in individuals who cannot achieve maximum exercise.^[10]

Oxygen uptake efficiency (OUE) reveals the relationship between VO₂ and VE during incremental physical activity. This metric is based on the logarithmic relationship between the two parameters, which is graphically expressed by a regression slope, known as the oxygen uptake efficiency slope (OUES).^[15] (Equation 1. Logarithmic relationship between ventilation and oxygen consumption during physical exertion; Fig. 2) This metric reflects the ability of an individual to increase VO₂ by increasing ventilation and is considered an integral marker of cardiorespiratory efficiency.^[15]

VO₂ = a × log₁₀VE + b (Equ. 1)

A significant advantage of oxygen uptake efficiency slope is its relative independence from the test duration and the achievement of maximum effort.^[15] As such, OUES can be reliably calculated even in submaximal effort.

In children, OUES gains additional significance since the normal values of most CPET parameters are significantly influenced by age and body composition. The use of OUES, especially when calculated to body surface area, allows for better comparability between different age groups. This makes it a valuable tool for assessing cardiorespiratory function in both healthy and diseased children.^[16,17]

When conducting pediatric CPET, careful consideration must be given to both equipment and exercise protocol selection. The child’s height is important when choosing the correct ergometer. Most manufacturers of cycle ergometers require a minimum patient height of 120 cm. Bearing in mind that according to the World Health Organization (WHO), the average height of a preschool-aged child (5 years old) is 111 cm for boys and 109 cm for girls^[22], this makes the use of cycle ergometry highly limited and in some cases practically impossible. Therefore, CPET is often performed on a treadmill or requires specialized pediatric ergometer equipment adapted for younger ages.^[13] All equipment needs to be consistent with the children’s anatomical characteristics. A range of mask sizes should be available to choose from, depending on the child’s age and head circumference. Too large a mask may lead to gas leakage and hinder gas analysis, whereas using too small of a size could be uncomfortable for the child and be the reason for a premature cessation of the test.^[11]

Protocol selection needs to consider the child’s age, height, weight, motor coordination, and level of physical training. Ramp protocols provide a more gradual workload increase, which may allow for a more precise determination of the ventilatory thresholds. However, step protocols may be preferable in cases when steady-state measurements are required or when evaluating submaximal responses.^[10]

Protocol design may influence key parameters such as ventilatory efficiency and oxygen uptake kinetics, highlighting the need for standardization in pediatric CPET protocols. Standardized treadmill protocols may prove too difficult and lengthy for very young children. In such cases, the use of modified protocols, such as the modified Bruce treadmill protocol for children^[23] or the Dubowy protocol^[24] is encouraged. If using the ramp protocol, the workload intensity should be adjusted to the child’s abilities and age so that an optimal test duration of 8 – 12 minutes is achieved.^[25] Using excessively steep ramp increments may lead to premature muscular fatigue before cardiovascular or pulmonary limitation is reached, whereas overly shallow increments may prolong the test and lead to loss of motivation. Workload increments should typically be calculated based on predicted VO₂peak or estimated maximum workload, ensuring a progressive but tolerable increase of the intensity.^[10]

Maintaining attention and following the examiner’s instructions for a prolonged period of time is often challenging for very young kids. Most treadmill step protocols (Bruce) utilize 3-minute steps in order to allow for adaptation and the achievement of a steady state.^[26] This can present a problem due to the relative monotony of the test. Moreover, the unfamiliarity of the laboratory settings, as well as the equipment (mask, electrodes, etc.), can be a source of discomfort or fear. In such cases, the role of the parent is particularly important, as they can predispose the child with encouraging words and prevent them from giving up the test too early.^[11]

Assessment of physical fitness in children is an important component of pediatric health evaluation, since cardiorespiratory fitness is strongly associated with health outcomes later in life.^[29] Traditionally, physical fitness in kids can be evaluated through field tests, such as shuttle runs or timed running protocols, which provide an indirect estimate of aerobic capacity.^[1]CPET is the gold standard for aerobic fitness assessment, and it can be used to evaluate the functional capacity of healthy children and young athletes, allowing for a more detailed characterization of the physiological adaptations to exercise. Additionally, CPET can provide information regarding the predominant metabolic profile of the child and thus help guide orientation towards a sport with predominantly aerobic or anaerobic requirements.

Obesity is a condition associated with the accumulation of excessive adipose tissue and high body mass index (BMI). Childhood obesity proves difficult to manage and leads to numerous complications, including reduced exercise capacity. Obese children have a shorter CPET duration and reach lower values of VO₂peak, as well as report higher levels of subjective symptoms of exertion.^[17] They reach higher levels of VE, RR, and dead space ventilation (VD/VT) – an expression of the difficult adaptation to the workload increase, as well as lower ventilatory efficiency.^[30] This in turn, leads to the faster onset of fatigue and earlier test termination.

CPET can be used both as a means for assessment, and for monitoring obese children during weight loss regimens and assessing their progress regarding functional parameters, as well as program compliance.^[31] The test provides useful information for the child’s individual functional capacity so that the training regimen can be tailored towards the patients’ specific abilities.

CPET proves useful in assessing the functional status of children with asthma, cystic fibrosis (CF), exercise-induced bronchoconstriction (EIB), or dyspnea of unknown origin. In the presence of functional airway obstruction, CPET can objectify the degree of airflow limitation during exercise.‌^[32] Furthermore, it can play a role as an indirect provocation factor during bronchoprovocation testing.^[33]

Multiple studies have shown kids with bronchial asthma to have a lower exercise capacity, including lower VO₂peak, lower ventilatory efficiency, and lower breathing reserve (BR) compared to healthy controls. There is a positive correlation between lower VO₂peak values, poor ventilatory efficiency, and higher BMI in kids.^[17,34]

CPET can be implemented as a prognostic tool in children with chronic respiratory conditions. In case of CF, VO₂peak decline over time has been associated with a worsened functional state of the patient, which can be used as an indicator for the inclusion of more intensive pulmonary rehabilitation.^[35,36] Some attempts at developing prognostic models for mortality in children with CF based on CPET parameters have been made. The forced expiratory volume for 1 second (FEV₁) and the VE/VCO₂ slope have been found to be highly predictive of mortality.^[37,38] In this context, CPET can be used as a tool for identifying high-risk patients. In children with pulmonary hypertension (PH), VO₂peak and the VE/VCO₂ slope values correlate with the severity of the condition and can be implemented as non-invasive markers for assessing the pulmonary status.^[38]

Studies show that in kids with congenital heart defects, aerobic capacity (measured via VO₂peak) decreases four times faster compared to healthy controls.^[39] Male gender, higher baseline VO₂peak, high BMI, and multiple surgical interventions were found to be predictors for a greater decline. CPET has been used to assess health-related quality of life (HR-OoL) in children and adolescents with congenital heart defects. There is a significant correlation between VO₂peak and physical well-being scores from the Kidscreen questionnaire used for assessing HR-OoL, confirming VO₂peak as a reliable indicator of physical well-being in pediatric patients.^[40] The AT also correlates with physical well-being and decreases with the increase of the severity of heart disease, suggesting a potential use as a clinical marker.