The effect of different work rate increasing rates on cardiopulmonary exercise testing in arm ergometer

Introduction

The cardiopulmonary exercise testing (CPET) is a continuous, objective, quantitative, repeatable, non-invasive and comprehensive clinical technique for evaluating the human body’s multi-system functions that may be used on both normal individuals and patients with diverse medical conditions. In addition to being extensively utilized in clinical practice to assess exercise tolerance, cardiorespiratory fitness, and create training regimens, CPET is essential for the diagnosis, management, and prognosis of various illnesses, including metabolic, respiratory, cardiovascular, and cerebrovascular disorders (1,2).

CPET has predominantly employed two methods: treadmill testing and cycle ergometer. The latter has become the preferred choice due to several advantages, including minimal interference with electrocardiogram (ECG) and blood pressure measurements, reduced likelihood of false positives for dynamic myocardial oxygen supply/demand imbalance, and decreased noise and space requirements. Traditional CPET employs cycle ergometer as a standardized testing tool. Its key variables such as peak oxygen uptake (Peak V˙O2) and anaerobic threshold (AT), which are based on the exercise patterns of large muscle groups in the lower limbs, have become the gold standard for evaluating cardiorespiratory fitness. Peak V˙O2 is recognized as the primary indicator of cardiorespiratory fitness, reflecting the body’s maximum aerobic metabolism and cardiorespiratory reserve capacity; it serves as the gold standard for assessing an individual’s exercise endurance. The AT is the critical point when the skeletal muscle energy supply mode shifts from aerobic metabolism to anaerobic metabolism to compensate for aerobic deficiency during incremental loading exercise, and individualized exercise prescription is often formulated based on the corresponding heart rate (HR), V˙O2, and METs at the time of the AT (3). The respiratory exchange ratio (RER) is a crucial parameter that reflects substrate metabolism and ventilatory compensation. It indicates the percentage of carbohydrate oxidation at sub-extreme intensities and is frequently utilized as a reference criterion for determining maximal effort during the exhaustion phase. In clinical practice, it has been observed that patients with spinal cord injuries, occupational upper limb work populations (e.g., firefighters, rowers), and other specialized groups exhibit significant differences in motor metabolism between the upper and lower limbs, and traditional leg CPET may not accurately reflect the true functional status of these individuals. The introduction of arm ergometry into clinical practice presents a promising direction for CPET, particularly for patients with lower extremity dyskinesia, motor incomplete spinal cord injury patients, and the elderly (4-6). The study of physiological responses to upper limb exercise holds significant applied value, and arm ergometer CPET provides an important means of assessing an individual’s physiologic response to upper limb exercise. Arm ergometer CPET offers similar physiological response data to traditional CPET, collecting a range of indices such as gas exchange parameters centered on oxygen metabolism and full-lead ECG recordings throughout the resting-exercise-recovery process. This dynamic assessment under gradually increasing exercise intensity provides significant insights into the functional capacity of the human body during upper extremity exercise. In the new theory of Holistic Integrative Physiology and Medicine (HIPM) (7-10), it is posited that oxygen metabolism needs the mutual cooperation among respiratory system, blood circulation system and metabolic system, and the coupling between internal and external respiration can be accomplished under the regulation of nerves and body fluids, etc.; while at the same time, energy substances need the digestive system and urinary system to maintain the stability of the internal circulation and the internal environment, and the participation of other physiological systems is also needed. The CPET embodies the core concept of overall regulation, which is realized under the combination of respiration, blood circulation, nerves, metabolism and other systems, and all the peak indexes obtained have important clinical significance. The HIPM theory, articulated by Professor X.G.S., provides a theoretical framework for comprehending the physiological responses observed in human CPET.

Notably, existing studies have shown that test parameters such as crank rate (11,12), type of incremental protocol (13) and work rate increasing rate significantly modulate the sensitivity and specificity of CPET-evoked physiological responses. The work rate increasing rate acts as a temporal gradient controller for load intensity, directly influencing the timing of the AT trigger and the stability of the peak V˙O2. There have been more studies on leg CPET work rate increasing rate protocols, and research concerning arm ergometer work rate increasing rates remains limited. The arm CPET based on hand-cranked arm ergometer can accurately quantify the gas metabolic response and hemodynamic changes of the shoulder girdle muscles during exercise by establishing a standardized upper limb incremental work rate protocol. At the earliest Smith et al. (14) compared two different ramp rates (6 and 12 W/min) during arm crank ergometry (ACE) to investigate the effect of ramp rate on the physiological response to peak physiological responses in subjects. They found that the difference in ramp rate significantly affected peak work rate, carbon dioxide emission (V˙CO2), and RER, but did not influence V˙O2 and HR during ACE. While current arm CPET research has explored arm ergometer protocols with different work rate increasing rates, these protocols have been limited to two-by-two comparisons of limited combinations of incremental rates, and systematic comparisons of cross-gradient protocols have not yet been achieved in a unified experimental framework (14,15). In this study, we achieve a direct comparison of multi-gradient loading protocols for the first time in a uniform subject population by innovatively integrating four incremental rate datasets: slow (5 W/min), medium (20 W/min), fast (35 W/min), and high (50 W/min). To this end, the study includes 14 healthy participants who first complete a traditional leg CPET, followed by sequential arm ergometer tests at rates of 5, 20, 35, and 50 W/min. We observe both similarities and differences in the peak exercise-related indices of arm CPET across different work rate increasing rates, analyzing their effects on the physiological responses of upper limb exercise in healthy participants. Faster work rate increasing rate can reduce test duration, thereby limiting the number of metabolic steady-state phases available for robust AT identification. Confirmation of the AT of the rapid protocol test in this study deserves further attention. When upper limb exercise is involved, varying incremental rates may exert more pronounced modulatory effects on the RER due to reduced muscle recruitment and an inclination towards an earlier onset of ventilatory-metabolic imbalance. However, no systematic exploration has been conducted on the mechanisms by which the work rate increasing rate in arm CPET influences the temporal characteristics of RER, including the maximum RER during recovery. This kind of influence may directly relate to the scientific of the test plan formulation and the establishment of the result interpretation criteria. Furthermore, we will optimize protocol selective strategies to provide high-confidence evidence for determining the optimal intensity-time gradient for upper limb exercise testing. Additionally, since arm exercise predicts clinical outcomes (16), the core indicators of arm and leg CPET were also compared between the 14 participants in this study to explore differences in metabolic mechanisms between limb movements, which offers potential benefits for the precise guidance of exercise rehabilitation. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-531/rc).

Methods

Participants

A total of 14 healthy participants (5 males and 9 females) who were working at Fuwai Hospital and did not have diagnosed illness were recruited for the study in 2023. As shown in Table 1, Basic information of the participants was recorded (age 34.36±7.65 years, body mass 65.93±11.03 kg, height 1.67±0.06 m and BMI 23.66±3.20 kg/m²). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Fuwai Hospital (No. 2023-2236). All the participants provided written informed consent.

CPET equipment and daily calibration

CPET was conducted using the Quark PFT Ergo cardiopulmonary exercise testing system from COSMED S.R.L., Italy. Before each test, the equipment underwent comprehensive calibration procedures, including gas volume calibration, high, medium, and low flow rate calibration, as well as air, oxygen, and carbon dioxide gas calibration. The calibration of gas concentration is performed using a two-point standard gas method, which involves a reference gas (0.00% CO₂ and 21.00% O₂) and a calibration gas (5% CO₂ and 10–15% O₂). Additionally, the metabolic simulator’s low, medium, and high metabolic rates were utilized daily to validate the CPET for measuring errors in V˙O2 and V˙CO2. Validation was deemed successful when the absolute values of all three titers—low, medium, and high—were ≥10%, thereby enhancing and sustaining data accuracy and reliability within the cardiopulmonary exercise laboratory (17). Participants can be tested only after all calibration is passed.

CPET normalized operation

The entire monitoring and recording process followed the standardized operations of the Cardiopulmonary Exercise Laboratory at the University of California at Los Angeles (Harbor-UCLA) Medical Center (18). The protocol involved completing a resting state pulmonary function test followed by a symptom-limited maximal CPET using a continuous work rate increasing rate protocol. The resting pulmonary data involved lung volumes, lung ventilation function and diffusing capacity of the lungs for carbon monoxide. Indicators include forced vital capacity (FVC), first second forced expiratory volume (FEV1), slow vital capacity (SVC), maximal voluntary ventilation (MVV), etc. Data is not reported here as a non-patient population was examined. Participants were fitted with a mouthpiece and a nose clip (or a mask, as an alternative) to ensure no air leaks. They first performed maximal leg CPET for functional evaluation, then followed four maximal arm ergometer CPETs using different work rate increasing rates (5, 20, 35, and 50 W/min) on various days in one week, under the close supervision of the physician. The CPET protocol comprised four stages: a 3-minute resting period, followed by a 3-minute no-load warm-up period, progressive loading of work rate until maximal exercise was reached, and finally, a 5-minute recovery period. The CPET cadence was maintained at approximately 60 rpm. The 3-minute warm-up phase was set at 0 W resistance (60 rpm), generating baseline power outputs of 10 W (arm ergometer) and 20 W (cycle ergometer) through system inertia and limb movement. Indicators such as peak HR, peak RER, and subjective fatigue and exhaustion as assessed by the Borg Rating Scale were integrated with the Max test (19) to ascertain that the participant had performed the CPET to the best of their ability. Throughout the CPET procedure, many kinds of data were continuously monitored and recorded, i.e. 12-lead ECG, oxygen saturation (SaO₂), non-invasive cuff blood pressure measurements, and gas exchange parameters. blood pressure and SaO₂ were not measured in the arm ergometer CPET due to interference.

CPET data processing and interpretation

The raw data of breath-by-breath were segregated from the COSMED cardiopulmonary exercise testing system, split second-by-second, and a 10 s average of all variables was calculated to produce a new 9 plots and data analysis (20,21). The CPET data for every 10 s were plotted carbon dioxide emissions (V˙CO2)-vs-oxygen uptake (V˙O2) graph with V˙O2 as the horizontal coordinate and V˙CO2 as the vertical coordinate, and the AT was measured using Beaver’s V slope method (22). The key variables were analyzed and calculated by averaging the resting stage values (last 120 s), warm-up stage values (last 30 s), AT stage values (10 s), peak exercise stage values (last 30 s), and recovery stage values (last 120 s) (23,24). All graphs and data processing were undertaken using Sigma Plot professional mapping software (version 14).

CPET key observation variables

The key variables include V˙O2, V˙CO2, HR, AT, tidal volume (VT), minute ventilation (V˙E), breathing frequency (Bf), oxygen pulse (V˙O2/HR), work rate, Tlim, RER. The peak oxygen uptake efficiency plateau (OUEP) is a reliable indicator of oxygen uptake efficiency, The lowest ratio of minute ventilation to carbon dioxide output (Lowest V˙E/V˙CO2) and slope of carbon dioxide ventilatory efficiency (V˙E/V˙CO2 Slope) are excellent indicator for assessing the effectiveness of ventilation, The oxygen uptake per unit work rate (ΔV˙O2/ΔWR) indicates the oxygen delivery capacity of peripheral exercising muscles. For leg ergometer CPET, unit values, predicted values, and percentages of predicted values for these key variables were calculated using standardized algorithms published in relevant literature (24). However, there are currently no established formulas for calculating the expected values of the arm ergometer CPET variables. Therefore, analysis of arm ergometer CPET data typically relies on actual measured values as the basis for interpretation and comparison.

Statistical analysis

Measurements that followed a normal distribution were presented as mean ± standard deviation (x¯±SD). Statistical analysis was conducted using SPSS 26.0 statistical software, and graphs were generated using Origin 2021. One-way ANOVA with Tukey’s post hoc test were performed to compare each variable among the four tests with different work rate increasing rates. A paired t-test assessed arm vs. leg differences. Statistical significance was set at P<0.05. Additionally, the linear regression analysis between key variables and work rate increasing rate of arm ergometer CPET were analyzed via Pearson’s correlation coefficient.

Results

Functional evaluation using leg ergometer CPET

All participants completed all trials, and the maximal leg ergometer CPET results indicated that their physiological function was essentially normal, with a peak V˙O2 of 1.96±0.43 L/min, 30.22±6.06 mL/(min·kg), and 92.89%±18.37% of the predicted value, as well as an AT of 1.01±0.12 L/min, 15.82±2.88 mL/(min·kg), and 88.86%±18.83% of the predicted value. As shown in Table 2, the data was consistent with our expectations for this population.

Comparison of peak physiological responses for each work rate protocols

Submaximal responses

The data of the third healthy male participant is provided as an example to demonstrate the dynamic change process (see Figure 1). V˙O2 and V˙CO2 rose during the warm-up phase, but the RER barely changed. During this time, there was an increase in V˙O2 and V˙CO2, a slightly reduced RER, and a continuous rise in RER after the AT. Peak work rate, V˙O2, and V˙CO2 achieved their maximums when the peak movement was reached, but peak RER did not. Work rate was at zero when the recovery stage began, and both V˙O2 and V˙CO2 decreased. In contrast, the RER showed a rapid increase, reaching its maximum in approximately two minutes before gradually decreasing. Tlim decreases significantly as the work rate increasing rate increases. In the 5 W/min protocol, V˙O2 and V˙CO2 increases slowly, the peak occurs at a later point in time. The RER value is more stable without significant fluctuations. V˙O2 increases rapidly and peaks in the shortest Tlim. V˙CO2 reaches its maximum peak swiftly, accompanied by a sharp rise in RER, which subsequently declines rapidly back to baseline during the recovery phase. The group with a work rate increasing rate of 20 W/min was able to complete the work rate increase stage in approximately 5 min, while the lower and higher work rate increasing rate groups lengthened and decreased the Tlim, respectively.

Figure 1 Dynamic change of oxygen uptake (A), carbon dioxide excretion (B), respiratory exchange ratio (C), and work rate (D) of arm ergometer CPET at different work rate increasing rates in participant 3 as a typical example, with arm ergometer CPET at work rate increasing rates of 5 (orange), 20 (red), 35 (blue), and 50 W/min (green), respectively. The 1st and 2nd vertical purple dashed lines in the figure are the end-of-rest and end-of-warm-up segmentation lines, respectively; the 3rd green dashed line, the 4th blue dashed line, the 5th red dashed line, and the 6th black dashed line is the segmentation lines of the exercise and recovery periods for the four work rate increasing rate groups, respectively; the recovery period is 2 minutes of data during recovery. CPET, cardiopulmonary exercise testing.

Maximal responses

The 5, 20, 35 and 50 W/min work rate increasing rates for different arm ergometer CPETs on the same NS obtained similar V˙O2 (1.37±0.31, 1.35±0.32, 1.34±0.31 and 1.33±0.30 L/min, P=0.99), HR (P=0.96), V˙E (P=0.98), VT (P=0.98), Bf (P=0.81) at peak exercise, respectively. There also were similar OUEP (P=0.93), Lowest V˙E/V˙CO2 (P=0.93), V˙E/V˙CO2 Slope (P=0.84) and AT (0.72±0.10, 0.75±0.11, 0.71±0.08, 0.74±0.11, P=0.72), respectively (Table 3, Figure 2). For each individual, the variables of four arm ergometer CPETs may not exhibit significant similarities. The degree of similarity is primarily based on the statistical analysis results of the average values of 14 healthy participants, which do not exhibit significant differences.

Figure 2 Comparison of V˙O2/HR (A), V˙CO2 (B), RER (C), and WR (D) of maximal arm ergometer CPETs performed with work rate increasing rates of 5, 20, 35, 50 W/min at different exercise stages. Error bars represent SEM. *, P<0.05; **, P<0.01 20 W/min group vs. 5 W/min group; ^##, P<0.01 50 W/min group vs. 5 W/min group; ^&, P<0.05; ^&&, P<0.01 35 W/min group vs. 5 W/min group; ^△, P<0.01 50 W/min group vs. 20 W/min group; ^£, P<0.05 35 W/min group vs. 20 W/min group; ^※, P<0.05 50 W/min group vs. 35 W/min group. AT, average value of 10 s data at anaerobic threshold; CPET, cardiopulmonary exercise testing; Peak, average value of last 30 s data at peak exercise; Rec2min, average data value at 2 min of recovery; RER, respiratory exchange ratio; Resting, average value of last 120 s data during resting stage; SEM, standard error of the mean; V˙O2, oxygen uptake; V˙CO2, carbon dioxide emissions; Warm-up, average value of last 30 s data during warm-up stage; WR, work rate.

There was a significant difference in peak work rate among the four protocols of the arm ergometer CPET (P<0.001). The 50 W/min protocol demonstrated the highest peak work rate, followed by the 35 and 20 W/min protocols, while the 5 W/min protocol exhibited the lowest peak work rate. All comparison between work rate increasing rate protocol were significantly different (P=0.001–0.048). Additionally, there were significantly different peak RER (P=0.03) and maximal RER during recovery (P=0.04). The peak RER value in the 5 W/min group was significantly lower than in the 20, 35, and 50 W/min groups (P=0.048, P=0.01, and P=0.008, respectively) but there were no statistically significant differences among the 20 vs. 35 W/min groups (P=0.58), 35 vs. 50 W/min groups (P=0.85) and 20 vs. 50 W/min groups (P=0.46). However, Tlim for the four tested protocols were significantly different (P<0.001). The high incremental rate (50 W/min) protocol resulted in the shortest Tlim, whereas the low incremental rate (5 W/min) protocol led to the longest Tlim. However, no statistically significant difference in Tlim was observed between the 35 W/min and 50 W/min test protocols (P=0.29) (Tables 3,4). In arm ergometer CPET, peak work rate, peak RER, and maximal RER during recovery were positively correlated with work rate increasing rate (R²=0.985, 0.823, 0.939, respectively), while Tlim was negatively correlated with it (R²=0.383) (Figure 3).

Figure 3 Linear correlation analysis of arm ergometer CPET key variables with work rate increasing rate in 14 normal subjects. (A) Correlation of peak work rate versus work rate increasing rate. (B) Correlation of Tlim versus work rate increasing rate. (C) Correlation of peak RER versus work rate increasing rate. (D) Correlation of maximal RER during recovery versus work rate increasing rate. CPET, cardiopulmonary exercise testing; RER, respiratory exchange ratio.

Variables of four arm ergometer CPETs compare with those of leg ergometer CPET

During warm-up, there was only V˙O2 using arm ergometer was slightly lower than that using leg ergometer (all P<0.05, P=0.02–0.03). However, there were no statistically significant differences in other variables, such as HR, V˙E, VT, and Bf (all P>0.05). At midway of exercise, the AT (P<0.001) and OUEP (P=0.02–0.04) using arm ergometer were significantly lower than those using leg ergometer, while lowest (P=0.03–0.04) showed a slightly higher value. Additionally, there was no statistically significant difference in V˙E/V˙CO2 Slope (P=0.12–0.3). At peak exercise, the V˙O2 (P=0.001–0.005), HR (P<0.001), (P=0.001–0.003), VT (P=0.01–0.02) and work rate (P<0.01) values of arm ergometer CPETs were all significantly lower than those of leg ergometer CPET, while the difference in Bf was not statistically significant (P=0.21–0.73). At resting and 2 minutes of recovery, there were no differences in variables between arm and leg ergometer CPET (all P>0.05).

Discussion

Difference and similarity of arm CPET key variables

The 5, 20, 35 and 50 W/min work rate increasing rates for different arm ergometer CPETs on the same healthy participant obtained similar peak V˙O2, peak HR, peak V˙E, peak VT, peak Bf, OUEP, Lowest V˙E/V˙CO2, V˙E/V˙CO2 Slope and AT, respectively. The data suggest that variations in the work rate increasing rate (ranging from 5 to 50 W/min) do not significantly influence variables such as peak V˙O2, AT, etc., achieved during arm ergometer CPET. However, differing work rate increasing rates resulted in significant variations in peak work rate and Tlim. Peak work rate was significantly greater in test protocols characterized by shorter Tlim (50 and 35 W/min) compared to those with medium (20 W/min) and longer Tlim (5 W/min). To the best of our knowledge, this is the first study to extend the arm ergometer CPET work rate increasing rate to 50 W/min and systematically observe the effects of varying work rate levels on peak key metrics through the implementation of multiple loading protocols (slow, medium, and fast). Previous studies have reported that work rate increasing rate schemes do not affect peak HR or peak V˙O2, but they do influence peak work rate and peak RER (14,15,25-27). The changes in key arm ergometer CPET metrics observed in healthy participants in this study are consistent with those found in previous studies.

Peak V˙O2 was not influenced by the work rate increasing rate, indicating that the maximal functional reserve of the cardiorespiratory system may be primarily determined by individual physiological limits rather than the incremental pattern of exercise loads. Peak V˙O2 serves as the most reliable indicator of aerobic metabolism, representing the upper limit of aerobic capacity of the large muscle groups during exercise in the human body. The core determinants of this capacity include maximum cardiac output, the arteriovenous oxygen difference, and the mitochondrial oxidative capacity of skeletal muscle. During extreme exercise in CPET, regardless of the work rate increasing rate, subjects ultimately reach the maximal oxygen supply capacity of the cardiorespiratory system, resulting in stabilization of peak V˙O2. Similarly, peak HR is constrained by the upper limits of autonomic regulation, demonstrating independence from the work rate increasing rate. Although the four groups of participants exhibited high intergroup similarity in key metrics such as peak V˙O2, this finding primarily stemmed from a statistical analysis of the group mean derived from 14 healthy participants, where none of the intergroup differences reached statistical significance. This suggests that individuals may be characterized by physiological variability. In the present study, we observed that a slightly higher peak V˙O2 was achieved during arm CPET at an increasing rate of 5 W/min, while a slightly lower peak V˙O2 was obtained at a rate of 50 W/min. This discrepancy may be attributed to the rapid onset of muscle fatigue resulting from excessively high work rate increasing rates (28), which may hinder the achievement of the highest possible peak V˙O2 within a short duration of force exhaustion. Our analysis indicates that the AT, the point where oxygen delivery cannot keep up with metabolic demand, remains relatively constant regardless of work rate increasing rate. This stability is attributed to the threshold’s strong correlation with daily exercise and cardiovascular function (29). Essentially, the AT primarily serves as a reflection of an individual’s exercise endurance, an aspect that remains unaffected by variations in effort level or work rate increasing rate. Some researchers noted that increasing rates and crank rate simultaneously does not enhance incremental exercise performance but facilitates valid measurements of peak physiological variables within a shorter test duration (30). This suggests that the choice of work rate increasing rate is less critical for these variables of interest; if rapid data acquisition is desired, a higher work rate increasing rate may be selected. To quickly determine peak V˙O2 or AT values in the arm ergometer CPET, we can increase the work rate increasing rate accordingly. Castro et al. (27) found that a rapid 20 W/min protocol was effective in healthy young adults performing arm CPET, achieving the same peak V˙O2 at a higher peak work rate compared to a slower protocol. The present study corroborates these findings by incorporating faster protocols of 35 and 50 W/min, both of which reached similar endpoints at higher peak work rate, but with varying Tlim. There was a significant difference in peak work rate obtained with arm ergometer CPET at four work rate increasing rates and all comparison between increasing rate protocol were significantly different. The differences in peak work rate between groups may arise from an increased activation of the anaerobic energy metabolism system. The shorter test protocol prompted subjects to achieve higher peak work rate more rapidly, which led the neuromuscular system to recruit higher-order motor units earlier, thereby facilitating an earlier transition to anaerobic metabolic pathways (31). Higher work rate increasing rates result in a greater increase in load per unit of time, which leads to earlier activation of the muscle anaerobic metabolic system and a rapid accumulation of lactic acid, thereby shortening Tlim. Additionally, high incremental rates may cause subjects to reach subjective exhaustion earlier than cardiorespiratory failure by accelerating peripheral fatigue. This phenomenon aligns with the theory in HIPM that exercise tolerance is limited by the synergistic effects of multiple systems rather than the function of a single organ. Although peak work rate increased significantly with the incremental rate (about 27% increase in peak work rate in the 50 W/min group compared with the 20 W/min group), peak V˙O2 remained stable, and peak work rate was positively correlated with the work rate increasing rate, which was consistent with the kinetic inertia of V˙O2 (32). The significant differences observed in Peak work rate further reinforce the notion that a consistent protocol should be adhered to when making longitudinal comparisons.

Although no statistical differences were observed between the peak V˙O2 and peak V˙CO2 groups across the four tests in this experiment, higher work rate increasing rates exhibited a slight upward trend in peak V˙CO2 and a slight downward trend in peak V˙O2. Consequently, peak RER was positively correlated with the work rate increasing rate, and the group with a work rate increasing rate of 5 W/min demonstrated a significantly lower peak RER compared to the other three groups. Furthermore, the recovery RER also varied according to the work rate increasing rate. The RER serves as a secondary characteristic in CPET to ascertain whether a maximal physiological endpoint has been achieved. Muscle lactate production experiences a surge when exercise intensity surpasses the AT. The neutralization reaction of lactate with bicarbonate (H++HCO3−→CO2+H2O) results in the rapid release of stored CO₂, accompanied by a compensatory enhancement of respiration to expel excess CO₂, leading to a significant increase in RER. Research (33) indicates that the peak RER value is not solely determined by the real-time CO₂ produced during exercise; it is also significantly influenced by the volume of CO₂ reserves expelled from the body. The total CO₂ released through metabolic activity comprises both a generation component and a reserve release component. Consequently, the peak RER is elevated when there is an abundance of CO₂ stored in tissues, a process accelerated by the circulatory system. Furthermore, RER tends to continue to rise rapidly during the initial phase of the transition from exercise to recovery, as oxygen uptake decreases more swiftly than carbon dioxide excretion following the cessation of exercise. CO₂ undergoes several physiological processes from cellular mitochondrial production to eventual excretion via the lungs, including intercellular fluid diffusion, venous transport, and alveolar exchange. This intricate metabolic clearance pathway produces a spatial and temporal delay effect, resulting in a rapid increase in RER during the initial recovery phase. The low peak RER observed during the low-rate incremental protocol may be attributed to the extended duration of exercise, which facilitates the complete mobilization of the aerobic metabolic system and enhances fat oxidation for energy supply. Conversely, higher work rate increasing rates result in shorter Tlim, compelling the body to depend on anaerobic glycolysis for rapid energy provision. This indicates that as the incremental work rate increases, the rate of CO₂ expulsion from the body near peak exercise also increases, leading to a rapid elevation of the RER. However, no significant differences in peak RER values were found among the 20, 35, and 50 W/min tests. This lack of variation may be due to the limited sample size, which predominantly consisted of females, suggesting that further research is necessary to increase the sample size or to account for age and gender differences. Additionally, the peak RER achievable by an individual is not constant and can be significantly influenced by varying work rate increasing rates. This finding supports previous research (34), indicating that RER should not be utilized as a criterion for terminating a trial.

Comparison of arm and leg ergometer CPET

All participants in this study successfully completed CPET using cycle ergometer and arm ergometer without any adverse events. A comparison of key metrics between the two modes of exercise revealed that V˙O2 during warm-up and the values of V˙O2, HR, V˙E, VT, and work rate at peak exercise in the arm ergometer group were significantly lower than that in the cycle ergometer group, with a mean peak V˙O2 value of approximately 69% of the leg values and an AT of approximately 72% of the leg values. This finding aligns with previous studies (35,36), which typically report arm values as a percentage of leg values at around 70%. We found OUEP using arm ergometer were significantly lower than those using leg ergometer but Lowest V˙E/V˙CO2 showed a slightly higher value, indicating that leg ergometer CPET mobilized more muscles and led to a better ventilation-blood flow match. As a result, compared to leg ergometer CPET, arm ergometer CPET is not frequently utilized in clinical practice to evaluate a patient’s overall cardiopulmonary function. Muscle work during exercise necessitates a complex integration of cardiac, pulmonary, vascular, and peripheral mechanisms. The lower V˙O2 observed during arm movements can be attributed to the specificity of the muscle groups involved in this movement pattern. The primary muscles engaged during arm exercise—namely, the biceps, triceps, and deltoids—are smaller and less conditioned compared to the leg muscles. These arm muscles possess a higher proportion of type II muscle fibers relative to the leg muscles, resulting in a greater O₂ cost compared to the slower type I fibers (37). The elevated HR observed during cycling exercise is due to the lower limbs, which represent the largest muscle group in the body, generating a greater overall metabolic demand during exercise and imposing a more substantial load on the cardiovascular system. In contrast, the activity of smaller muscle groups during upper limb exercise exerts relatively limited stress on the circulatory system (38). It suggests that we need to lower the standard of judgment if we use CPET with an arm ergometer to assess the overall functional status of the subject. Schrieks et al. (39) compared a treadmill with an arm crank ergometer and proposed a regression equation to predict V˙O2 on a treadmill based on physiological variables of the ACE. Additionally, it has been demonstrated that the arm ergometer CPET can serve as an alternative mode of exercise for sedentary adults and holds potential for application in clinical populations to assess cardiorespiratory fitness in individuals with lower extremity mobility limitations (40). Currently, under the guidance of CPET, there are numerous successful cases of chronic disease diagnosis and treatment centered around individualized exercise training utilizing lower limb cycle ergometer (41). Upper limb exercise training effectively engages the muscles of the upper body, enhances blood circulation in this region, and contributes positively to the overall blood flow to the heart and cerebrovascular system. The use of the arm ergometer CPET for cardiopulmonary function testing and rehabilitation training demonstrates a high degree of safety and feasibility, warranting further investigation.

Optimizing the selection of work rate increasing rate

The results of the study indicate that the work rate increasing rate is a significant factor affecting CPET variables. Selecting the appropriate protocol for arm ergometer CPET is crucial for accurately evaluating exercise capacity and individualized precision training. Davis et al. (42) found that the work rate increasing rates ranging from 20 to 50 W/min were more effective in assessing the functional status of subjects during leg ergometer CPET. The theoretical arm ergometer CPET work rate increasing rate was selected at no higher than the leg ergometer CPET because of the limited number of muscle groups activated by arm CPET and more type II muscle fibers in the upper limb muscles, which are relatively weak. A greater work rate increasing rate will lead to a rapid rise in resistance, causing the subject’s muscles to feel strained and resulting in premature fatigue (43). For instance, the 50 W/min test in this study may lead to a shorter Tlim to exhaustion due to faster muscle fatigue. Too high a work rate increasing rate can impede the attainment of steady-state V˙O2 kinetics due to the delayed response of the cardiopulmonary system, potentially leading to an underestimation of the true peak. And the sudden load increase at high work rate may induce a burning sensation in the upper limb muscles or joint discomfort, prompting premature subjective termination by the subject and compromising objectivity. In the tests conducted in this study with all healthy participants, key variables at the 35 and 50 W/min protocols were recorded as feasible by splitting the data collected for each breath second-by-second and calculating a 10 s average. However, due to time constraints, the ultra-rapid testing process impedes effective data collection and analysis. This limitation is particularly concerning for the average healthy participant, which is precisely why ultra-rapid testing is not commonly utilized in clinical practice. High work rate increasing rates are more appropriate for athletes assessing their instantaneous work rate capacity. In comparison to the more rapid increase in resistance observed in the 50 W/min protocol, the 5 W/min test demonstrated a significantly more favorable match between ventilation and perfusion, with an exercise duration ranging from 8 to 15 minutes. This duration is conducive to capturing V˙O2 kinetic homeostasis, including the oxygen deficit recovery curve and the ventilatory threshold. During work rate increments, smaller increases in workload are less easily detected. Consequently, smaller workload increments, such as 1 W per 10 seconds, exert less psychological and physiological impact, thereby delaying fatigue and enabling participants to sustain exercise for extended periods. However, protocols with too low a work rate increasing rate may result in an excessively long Tlim, potentially leading to premature termination due to factors unrelated to cardiorespiratory capacity. These factors may include subjects experiencing dry mouth, localized muscular fatigue, psychological fatigue, or distractions that affect endpoint judgments. Low work rate increasing rate regimens are more suitable for the refined assessment of patients with impaired cardiopulmonary function. If the work rate increasing rate increases too rapidly or insufficiently, or if the peak exercise is reached too soon or too late, the results may miscalculate the patient’s actual maximal exercise capacity. The test duration of the 20 W/min protocol was approximately 4–6 min, effectively reflecting muscle anaerobic reserve with an increase of up to 27% in peak work rate, while ensuring the stability of peak V˙O2 data. The duration of exercise at this rate is slightly shorter than the guidelines set forth by the American Thoracic Society/American College of Chest Physicians (44), recommending 8–12 min as the ideal duration for incline exercise protocols, which is based on data generated from exercise tests performed in a treadmill and bicycle. In contrast, arm exercises that engage smaller muscle masses may lead to premature fatigue before reaching peak V˙O2. Given practical considerations, shorter tests are preferable, provided they can sufficiently induce the physiological load necessary to maximize the subject’s V˙O2. Thus, the 20 W/min protocol is suitable for routine upper limb cardiorespiratory fitness assessments and the development of exercise prescriptions.

Guo et al. (45) studied that adjusting the examination program based on variables obtained from multiple examinations of the same subject is the most reliable method. In this study, we expanded the upper and lower limits of the duration of test protocols (ranging from 1 min 70 s to 15 min 30 s) to evaluate the effects of shorter and longer duration incremental arm ergometer CPET protocols on peak variables. The data from this study showed that the Tlim of participants in the 5 W/min protocol varied between 8 and 15.30 minutes. Specifically, 9 participants exercised for durations ranging from 8 to 12 minutes, while 5 participants engaged in exercise for more than 12 minutes. In the 20 W/min protocol, participants’ Tlim ranged from 2.75 to 5.10 minutes, with all male participants exercising for more than 4 minutes, whereas only two females exceeded 4 minutes. Notably, the Tlim in the 35 and 50 W/min protocols did not exceed 4 minutes. We suggest a more appropriate duration for incremental arm ergometer CPET is between 4 and 8 minutes. This window of time ensures that the subject’s physical strength is not overexerted for too long and allows for the collection and analysis of respiratory, circulatory, and other relevant data. Consequently, our preliminary investigation suggests a suitable work rate increasing rate protocol for arm ergometer CPET would be between 10 and 20 W/min, with an increase of another 5 W/min if the subject is a strong male.

Limitations

The study acknowledges several limitations that could be addressed in future research. First, the sample size of the current study was limited and consisted primarily of a mixed population of healthy men and women; therefore, future research should expand the sample to consider the inclusion of different age, gender, and disease groups. Second, the 20 W/min work rate increasing rate protocol demonstrated better overall performance in healthy individuals. However, the incremental gradients set in this study (5, 20, 35, and 50 W/min, with 15 W/min intervals between adjacent groups) may restrict the sensitivity required to accurately identify the optimal protocol. For instance, the difference from 5 to 20 W/min is considerable (Δ15 W/min), whereas the physiological response of upper limb muscles to load variations may be more nuanced. Thus, it is necessary to implement finer incremental gradients (e.g., 5, 10, 15, and 20 W/min) within the 5–20 W/min range in future studies to elucidate the effects of different work rate increasing rates on key peak variables, Tlim, and other differential impacts, thereby enhancing the optimization of arm ergometer CPET protocols.

Conclusions

In the range of 5–50 W/min, different work rate increasing rates had no significant effect on core functional indices such as peak V˙O2, peak HR, peak V˙E, AT, and V˙E/V˙CO2 Slope of arm ergometer CPET in healthy participants. Therefore, when considering these variables, the choice of work rate increasing rates is not critical. However, the high load protocol resulted in higher peak work rate, peak RER, and shorter Tlim compared to the low load protocol. Thus, higher work rate increasing rate protocols may be preferred when subjects possess strong upper extremity muscles and when peak work rate is a primary index of exercise capacity. It is also important to note that the work rate increasing rate protocol should not be altered arbitrarily when assessing changes in cardiorespiratory fitness or monitoring adaptations to the upper limb training program for the same subject. Considering the appropriateness of the Tlim (4–8 min), a work rate increasing rate in the range of 10–20 W/min is generally advisable for arm CPET in healthy subjects. This rate can be clinically adjusted by 5 W/min based on the severity of the disease, as well as factors such as gender, age, and baseline fitness level. This work enhanced researchers’ understanding of how variations in work rate increasing rate influenced physiological responses and preliminarily optimized the selection of work rate increasing rates for arm ergometer CPET, warranting further investigation.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease for the series “Holistic Integrative Physiology Medicine and Health: from theory to clinical practice”. The article has undergone external peer review.

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-531/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-531/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-531/prf

Funding: This work was supported by National Key Research and Development Program of China (Nos. 2022YFC2010000, 2022YFC2010003, 2022YFC3601000, 2020YFC2009002 and 2020YFC2009006); National Natural Science Foundation of China (No. 81470204); Fuwai Hospital, National Cardiovascular Institute of Chinese Academy of Medical Sciences (No. 2012-YJR02); National Hi-Tech Research and Development Program (863 Program) (No. 2012AA021009); Research on Clinical Characteristics of the Capital (No. Z141107002514084); Research and Outcome Promotion of Clinical Characteristics in the Capital (Project No. Z161100000516127); Foreign Experts Project of State Administration of Foreign Experts (Nos. 2015,2016, T2017025, T2018046 and G2019001660); and Peking Union Medical College Teaching Reform Program (No. 2018E-JG07).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-531/coif). The series “Holistic Integrative Physiology Medicine and Health: from theory to clinical practice” was commissioned by the editorial office without any funding or sponsorship. X.G.S. served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Fuwai Hospital (No. 2023-2236). All the participants provided written informed consent.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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