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Background: Established equations to predict peak oxygen uptake (VO 2 max) in healthy subjects are not directly applicable to patient populations, including people with multiple sclerosis (PwMS). PwMS, who commonly exhibit impaired cardiorespiratory and neuromuscular function, often require tailored predictive models. This study aimed at (1) testing the validity, reliability, and accuracy of four widely used formulae, developed in healthy populations, to estimate VO 2 max in mildly to moderately disabled women with MS, and (2) develop adjusted formulae tailored on MS features., Methods: Fifty-one mildly to moderately disabled women (mean age 46, median EDSS 3.5) with relapsing-remitting multiple sclerosis (RRMS) underwent incremental cardiopulmonary exercise testing (CPET) using cycle ergometry. Gas exchanges were analyzed by open-circuit spirometry. Four commonly employed predictive equations (ACSM, Storer's, Uth's, and Myers') were tested for reliability and accuracy against measured VO 2 max. Regressions were performed to identify significant VO 2 max predictors and to introduce adjustments to develop gender-specific equations aimed at estimating cardiorespiratory fitness with varying degrees of exercise involvement., Results: ACSM and Storer's equations underestimated VO 2 max (-6.09 %, Z = -3.22, p = 0.001; and -21.74 %, Z = -5.02, p < 0.001, respectively) whereas Uth's and Myers' equations overestimated it (+20.19 %, Z = -5.92, p < 0.001; and +19.31 %, Z = -6.19, p < 0.001, respectively). Regressions for adjusted equations revealed work rate/bodyweight (WR/BW) (β = 0.867, p < 0.001) for ACSM adjusted; age (β = -0.275, p = 0.004), BW (β = -0.658, p < 0.001) and peak Watts (β = 0.485, p < 0.001) for Storer's adjusted; heart rate ratio (β = 0.512, p < 0.001) for Uth's adjusted, and age (β = -0.492, p < 0.001), BW (β = -0.483, p < 0.001) and EDSS (β = -0.211, p = 0.046) for Myers' adjusted as predictors of VO 2 max., Conclusions: VO 2 max can be validly estimated in women with MS using established formulae, provided that specific adjustments are introduced to account for their signature functional impairments. The models proposed in this study enable reliable assessment of cardiorespiratory fitness with protocols at different levels of exercise involvement, making them practical for clinical and everyday use. This approach supports a translationally driven bench-to-bedside perspective, allowing for patient VO 2 max assessment in virtually all settings., Competing Interests: Declaration of competing interest We certify that no party having a direct interest in the results of the research supporting this article has or will confer a benefit on us or on any organization with which we are associated. All authors declare that they have no conflict of interest. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To improve preoperative risk stratification in lung cancer lobectomy by identifying and comparing optimal thresholds for peak oxygen uptake (VO 2peak ) presented as weight-indexed and percent of predicted values, respectively., Methods: This was a longitudinal cohort study including national registry data on patients scheduled for cancer lobectomy that used available data from preoperative cardiopulmonary exercise testing. The measured VO 2peak was indexed by body mass (mL/kg/min) and also compared with 2 established reference equations (Wasserman-Hansen and Study of Health in Pomerania, respectively). By receiver operating characteristic analysis, a lower 90% specificity and an upper 90% sensitivity threshold were determined for each measure, in relation to the outcome of any major complication or death. For each measure and based on these thresholds, patients were categorized as low risk, intermediate risk, or high risk. The frequency of complications was compared between groups using χ 2 ., Results: The frequency of complications differed significantly between the proposed low-, intermediate-, and high-risk groups when using % predicted Study of Health in Pomerania (5%, 21%, 35%, P = .007) or % predicted Wasserman-Hansen (5%, 25%, 35%, P = .002) but not when using the weight-indexed VO 2peak groups (7%, 23%, 15%, P = .08). Nonsignificant differences were found using the threshold <15 mL/kg/min (P = .34)., Conclusions: This study showed that weight-indexed VO 2peak was of less use as a marker of risk at the lower range of exercise capacity, whereas % predicted VO 2peak was associated with a continuously increasing risk of major complications, also at the lower end of exercise capacity. As identifying subjects at high risk of complications is important, % predicted VO 2peak is therefore preferable., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiopulmonary exercise testing (CPET) is a unique diagnostic tool that assesses the functional capacity of the heart, lungs, and peripheral oxidative system in an integrated manner. However, the clinical utility of CPET for evaluating interstitial lung disease (ILD) remains uncertain. The objective of this study was to determine the predictive value of CPET for mortality in subjects with ILD., Methods: We prospectively enrolled subjects with ILD who underwent CPET at a tertiary medical center in Taiwan and followed up their survival status for 12 months. Mortality prediction was based on comparing CPET parameters between subjects who survived and those who died. We further analyzed CPET parameters that showed significant differences using receiver operating characteristic curves to identify their optimal cutoff values., Results: A total of 106 newly diagnosed subjects with ILD underwent CPET, and the 1-y mortality rate was 7.5%. Six CPET variables were found to be significant predictors of mortality: peak oxygen consumption, oxygen pulse, end-tidal partial pressure of carbon dioxide, heart rate recovery 1 min after CPET, minute ventilation to carbon dioxide output slope, and functional aerobic impairment. We calculated a summed score by adding the number of CPET variables that exceeded their cutoff values. Subjects with a summed score of 6 had a 1-y survival rate of only 25%, whereas subjects with scores of 0-5 had a survival rate of 98%., Conclusions: In conclusion, the summed score represents a useful tool for screening patients with ILD who can undergo a CPET to determine their prognosis., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Purpose of Review: Cardiac amyloidosis (CA) constitutes an important etiology of heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF). Since patients with CA show early exhaustion, we aimed to investigate whether non-exertional variables of cardiopulmonary exercise testing (CPET) provide additional information in comparison to traditional peak oxygen consumption (VO 2peak )., Recent Findings: We retrospectively investigated CPET variables of patients with HFpEF and HFmrEF with (n = 21) and without (n = 21, HF) CA at comparable age and ejection fraction. Exertional and non-exertional CPET variables as well as laboratory and echocardiographic markers were analyzed. The primary outcome was the difference in CPET variables between groups. The secondary outcome was rehospitalization in patients with CA during a follow-up of 24 months. Correlations between CPET, NTproBNP, and echocardiographic variables were calculated to detect patterns of discrimination between the groups. HF patients with CA were inferior to controls in most exertional and non-exertional CPET variables. Patients with CA were hospitalized more often (p = 0.002), and rehospitalization was associated with VE/VCO 2 (p = 0.019), peak oxygen pulse (p = 0.042), the oxygen equivalent at the first ventilatory threshold (p = 0.003), circulatory (p = 0.024), and ventilatory power (p < .001), but not VO 2peak (p = 0.127). Higher performance was correlated with lower E/e' and NTproBNP as well as higher resting heart rate and stroke volume in CA. Patients with CA displayed worse non-exertional CPET performance compared to non-CA HF patients, which was associated with rehospitalization. Differences between correlations of resting echocardiography and CPET variables between groups emphasize different properties of exercise physiology despite comparable ejection fraction., (© 2024. The Author(s).)

Stringer et al. [ J Appl Physiol (1985) 82: 908-912, 1997] developed a method from invasive data to estimate cardiac output during incremental exercise testing based on Fick's principle. The authors proposed that the arterio-mixed venous oxygen content difference increases linearly with percentage of maximal O 2 consumption. We hypothesized an S-shaped pattern in the published data and calculated the inflection point of this curve and of the standard resting oxygen dissociation curve. Using a partial F test, we compared the linear model with a third-order polynomial model, which showed a better fit to the data [ F (2,101) = 9.5, P < 0.001]. This finding was reproduced in a dataset published by Åstrand et al. in 1964 [ F (2, 122) = 10.6, P < 0.001]. The inflection point of the curve coincided with the lactate acidosis threshold [first ventilatory threshold (VT1)] as measured by Stringer et al. (VT1 at 50% and inflection point at 56% [95% CI, 52.9 to 60.7] of maximal O 2 consumption). The inflection point of the standard resting oxygen dissociation curve was calculated at a partial pressure of 21.5 mmHg and a saturation of 36%, matching the "critical capillary Po 2 " concept of Stringer et al. (21.2 mmHg). We conclude that the arterio-mixed venous oxygen content difference increases in an S-shaped manner with percentage of maximal oxygen consumption and that the inflection point of this curve may correspond to VT1 and that of the in vivo oxygen dissociation curve. Further research is needed to confirm these findings and improve the method. NEW & NOTEWORTHY In 1997, Stringer, Hansen, and Wasserman developed a method for estimating cardiac output during incremental exercise testing. They observed that the arterio-mixed venous oxygen content difference increases linearly with the percentage of maximal O 2 consumption. This increase may be better modelled by an S-shaped function, the inflection point of which may be related to the first ventilatory threshold and the inflection point of the oxygen dissociation curve. This finding may help to improve the method.

Background: One metabolic equivalent (MET) is equal to resting oxygen consumption. The average value for one MET in humans is widely quoted as 3.5 mL/kg/min. However, this value was derived from a single male participant at the end of the 19th century and has become canonical. Several small studies have identified varied estimates of one MET from widely varying populations. The ability of a patient to complete 4 MET (or 14 mL/kg/min) is considered an indicator of their fitness to proceed to surgery., Aims: To define a typical value of one MET from a real-world patient population, as well as determine factors that influenced the value., Methods: A database of cardiopulmonary exercise testing (CPET) was interrogated to find a total of 1847 adult patients who had undergone CPET testing in the previous 10 years. From this database, estimates of oxygen consumption (VO 2 ) at rest and at the anaerobic threshold and several other variables were obtained. The influence of age, body mass index (BMI), sex and the use of beta-blockers was tested., Results: The median resting VO 2 at rest was 3.6 mL/kg/min (interquartile range (IQR): 3.0-4.2). Neither sex, age >65 years or the use of beta-blockers produced a significant difference in resting VO 2 , while those with a BMI >25 kg/m 2 had a significantly lower VO 2 at rest (3.4 mL/kg/min vs 4.0 mL/kg/min; P < 0.001)., Conclusions: The estimate of 3.6 mL/kg/min for resting VO 2 presented here is consistent with the previous literature, despite this being the first large study of its kind. This estimate can be safely used for pre-operative risk stratification., (© 2021 Royal Australasian College of Physicians.)

Purpose: Whether the modified shuttle test (MST) achieves maximal effort in children and adolescents with asthma is unclear. The aim was to compare the physiological responses of MST to the cardiopulmonary exercise test (CPET) in pediatric patients with asthma, to observe its convergent validity., Patients and Methods: A cross-sectional study with volunteers with asthma (6-17 years of age) under regular treatment. The MST is an external-paced test, and the participants were allowed to walk/run. CPET was performed on a cycle ergometer to compare with MST. Gas exchange (VO 2 , VCO 2 , and VE) and heart rate (HR) were the outcomes and were continuously assessed in both tests., Results: Forty-seven volunteers were included, normal lung function expiratory forced volume at 1st second/forced vital capacity (FEV 1 /FVC) 88.6 (7.7). VO 2peak was higher at MST (2.0 ± 0.6 L/min) compared to CPET (1.6 ± 0.5 L/min), p < 0.001. Similar results was observed to VE at MST (50 ± 16 L/min) versus VE at CPET (40 ± 13 L/min), and to VCO 2 at MST (2.1 ± 0.8 L/min) versus VCO 2 at CPET (1.7 ± 0.6 L/min), p < 0.001. HR was also higher at MST (94 ± 6%pred) versus CPET (87 ± 8%pred), p = 0.002. VO 2peak in MST correlated to the CPET (r = 0.78, p < 0.001). The ICC of VO 2peak between tests was 0.73 (0.06-0.89), p < 0.001, and VO 2peak Bland-Altman analysis showed a bias of 0.46 L/min., Conclusion: The MST showed a maximal physiologic response in children and adolescents with asthma. It is a valid test and can be used as an alternative to evaluating exercise capacity., (© 2021 Wiley Periodicals LLC.)

Background: This study sought to evaluate the impact of the advancements in clinical care, obtained over the last 20 years, for patients aged 70 and older undergoing liver resection for colorectal liver metastases (CRLM)., Methods: Consecutive patients age 70 or older who underwent liver resection for CRLM at Aintree University Hospital (Liverpool, UK) between May 2008 and May 2015 were compared to a dataset of consecutive patients, meeting the same criteria, between 1990 and 2007. An enhanced recovery programme after surgery (ERAS) combined with cardiopulmonary exercise testing (CPET) was introduced in January 2008., Results: The proportion of patients over 70 years undergoing liver resection for CRLM increased over the study period (6% in 1990, 16.3% in 2000, 26.5% in 2005 and 25.8% in 2007). The patients in the later group were more often treated with neoadjuvant chemotherapy (58 vs 34, p = 0.006) and underwent parenchymal sparing surgery, resulting in fewer major hepatectomies (51 vs 111, p < 0.001) and less perioperative morbidity (49 vs 70, p = 0.043) and mortality (3 vs 9, p = 0.229). Although there was shorter disease free survival (DFS) in the later group (DFS at 1, 3 and 5 years was 52.1%, 31.6%, 29% vs. 71.8%, 49.1%, 44.0%)(p < 0.01), similar overall survival (OS) was achieved (OS at 1, 3 and 5 years was 85.4%, 51.6%, 32.8% vs. 81.7%, 42.1%, 27.3%)(p = 0.21)., Conclusions: This study demonstrates that, with modern management (ERAS, CPET, neoadjuvant chemotherapy and parenchymal sparing surgery), a greater number of patients with CRLM, over the age of seventy, can undergo liver resection, with improved perioperative outcomes., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Background: Many studies have highlighted sex preponderance in idiopathic pulmonary arterial hypertension (IPAH). It is well established that there are differences in exercise capacities in the two sexes but how much of that difference reflects on disease severity or correlates to markers of severity in the two sexes is still not clear. Right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET) have been widely used for assessing functional capacity, prognosis and treatment response in IPAH. We aimed to investigate the 'sex-specific' CPET parameters in relation to hemodynamics in IPAH., Methods: Data were retrieved from 30 males and 53 females [mean ± standard deviation (SD) age: 39.6 ± 17.2 and 37.5 ± 12.0] stable IPAH patients who underwent both RHC and CPET at Shanghai Pulmonary Hospital from 2010 to 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the prognostic value of CPET and hemodynamic parameters., Results: There were no significant differences in clinical variables between men and women. Peak workload, peak oxygen uptake, anaerobic threshold (AT), peak minute ventilation, carbon dioxide output, O 2 pulse and oxygen uptake efficiency slope were significantly higher in men compared with women ( p < 0.05). Several CPET indexes correlated with hemodynamics. Pulmonary vascular resistance (PVR) and cardiac output (CO) were distinctly different between the sexes. Peak end-tidal partial pressure of CO 2 (P ET CO 2 ) was an independent predictor of PVR elevation in all patients and in men. Peak maximum oxygen consumption (VO 2 ) was independently predictive of CO decline in all patients and in men. Only peak O 2 pulse was an independent predictor of increased PVR and decreased CO in women., Conclusions: Even after adjusting for age, body mass index and World Health Organization functional class, different CPET parameters correlated with PVR elevation and CO decline in men and women differently, which could potentially better predict severity in men and women with IPAH.

Purpose: This study assessed the utility of the Children's Effort Rating Table (CERT) and the Eston-Parfitt (EP) Scale in estimating peak oxygen uptake ([Formula: see text]) in children, during cardiopulmonary exercise testing (CPET) on a treadmill., Methods: Fifty healthy children (n = 21 boys; 9.4 ± 0.9 years) completed a continuous, incremental protocol until the attainment of [Formula: see text]. Oxygen uptake ([Formula: see text]) was measured continuously, and ratings of perceived exertion (RPE) were estimated at the end of each exercise stage using the CERT and the EP Scale. Ratings up to- and including RPE 5 and 7, from both the CERT (CERT 5, CERT 7) and EP Scale (EP 5, EP 7), were linearly regressed against the corresponding [Formula: see text], to both maximal RPE (CERT 10, EP 10) and terminal RPE (CERT 9, EP 9)., Results: There were no differences between measured- and predicted [Formula: see text] from CERT 5, CERT 7, EP 5 and EP 7 when extrapolated to either CERT 9 or EP 9 (P > 0.05). Pearson's correlations of r = 0.64-0.86 were observed between measured- and predicted [Formula: see text], for all perceptual ranges investigated. However, only EP 7 provided a small difference when considering the standard error of estimate, suggesting that the prediction of [Formula: see text] from EP 7 would be within 10 % of measured [Formula: see text]., Conclusions: Although robust estimates of [Formula: see text] may be elicited using both the CERT and EP Scale during a single CPET with children, the most accurate estimates of [Formula: see text] occur when extrapolating from EP 7.

Objectives: To determine whether the 6-minute walk test (6MWT) is predictive of peak oxygen consumption (Vo(2)peak) and whether the 6MWT is a clinically applicable alternative to cardiopulmonary exercise testing (CPET) in ambulatory adolescents and young adults with cerebral palsy (CP)., Design: Cross-sectional., Setting: University hospital and rehabilitation centers., Participants: Adolescents and young adults with CP (N=41) classified in Gross Motor Function Classification System (GMFCS) level I or II., Interventions: Not applicable., Main Outcome Measures: The covered distance during 6 minutes was measured with a 6MWT. The Vo(2)peak was obtained with CPET on a cycle ergometer., Results: Univariate linear regression analysis was used to study the relationship between the outcomes of both tests. A multiple linear regression analysis was performed to determine whether Vo(2)peak could be predicted by the 6MWT, sex, body mass, and GMFCS level. A significant relationship (P<.01) was found between the outcomes of the 6MWT and CPET, with an explained variance of 21%. The multiple linear regression analysis showed an explained variance of 58% and a standard error of estimate (SEE) corresponding to 18% of the mean Vo(2)peak., Conclusions: The 6MWT is poorly related to Vo(2)peak in ambulatory adolescents and young adults with CP. Because of a high SEE, the multiple regression model did not allow for prediction of Vo(2)peak from the 6MWT in ambulatory adolescents and young adults with CP., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Insomnia treatment among individuals with comorbid insomnia and obstructive sleep apnea is suboptimal. In a pilot randomized controlled trial, 19 individuals with comorbid insomnia and obstructive sleep apnea were allocated to one of two arms: EX + EX, consisting of two 8-week phases of exercise training (EX), or RE + CBTiEX, encompassing 8 weeks of relaxation training (RE) followed by 8 weeks of combined cognitive-behavioral therapy and exercise (CBTiEX). Outcomes included Insomnia Severity Index (ISI), polysomnography, and cardiorespiratory fitness measures. A mixed-model analysis of variance revealed a Group × Time interaction on peak oxygen consumption change, F(1, 14) = 10.1, p =.007, and EX increased peak oxygen consumption (p =.03, g′ = −0.41) and reduced ISI (p =.001, g′ = 0.82) compared with RE (p =.49, g = 0.16) post-8 weeks. Post-16 weeks, there was a significant Group × Time interaction (p =.014) driven by RE + CBTiEX yielding a larger improvement in ISI (p =.023, g′ = 1.48) than EX + EX (p =.88, g′ < 0.1). Objective sleep was unchanged. This study showed promising effects of regular EX alone and combined with cognitive-behavioral therapy for insomnia on ISI in comorbid insomnia and obstructive sleep apnea. [ABSTRACT FROM AUTHOR]

Purpose: We studied the effect of O2 supplementation on physiological response to exercise in patients with moderate to severe interstitial lung disease (ILD). Methods: Thirteen patients (age 66 ± 10 yr, 7 males) with ILD (total lung capacity, 71% ± 22% predicted; carbon monoxide diffusion capacity, 44%± 16%predicted) and 13 healthy individuals (age 50 ± 17 yr, 7 males) were tested. ILD patients performed symptom-limited cardiopulmonary exercise tests and constant work rate (WR) tests at 80% of the WR at the gas exchange threshold. Tests breathing room air (RA; 21% O2) were compared with tests performed breathing 30% O2. Oxygen uptake (VO2) kinetics were calculated from the constantWRtest results. Results: In the ILDgroup, peakWR, peakVO2, andVO2 at the gas exchange threshold improved significantlywhen breathing 30% O2 compared with RA (mean ± SD, 75 ± 26 vs 66 ± 23 W, 17 ± 4 vs 15 ± 2 mL·kg-1·min-1, and 932 ± 245 vs 854 ± 232 mL·min-1; P = 0.004, P = 0.001, and P = 0.01, respectively). O2 saturation (SpO2%) at peak exercise was higher with 30% O2 (97% ± 4% vs 88% ± 9%, P = 0.002). The time constant (tau) of VO2 kinetics was faster in ILD patients while breathing 30% O2 (41 ± 10 s) compared with RA (52 ± 14 s, P = 0.003). There was a negative linear relation between tau and SpO2% with RA (r = -0.76, P = 0.006) and while breathing 30%O2 (r = -0.68, P = 0.02). Conclusions: Using a clinically applicable level of O2 supplementation (30%) improvedmaximal, aerobic exercise capacity and VO2 kinetics in ILD patients, likely due to increased blood O2 content subsequently increasing the O2 delivery to the working muscles. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a unique diagnostic tool that assesses the functional capacity of the heart, lungs, and peripheral oxidative system in an integrated manner. However, the clinical utility of CPET for evaluating interstitial lung disease (ILD) remains uncertain. The objective of this study was to determine the predictive value of CPET for mortality in subjects with ILD. METHODS: We prospectively enrolled subjects with ILD who underwent CPET at a tertiary medical center in Taiwan and followed up their survival status for 12 months. Mortality prediction was based on comparing CPET parameters between subjects who survived and those who died. We further analyzed CPET parameters that showed significant differences using receiver operating characteristic curves to identify their optimal cutoff values. RESULTS: A total of 106 newly diagnosed subjects with ILD underwent CPET, and the 1-y mortality rate was 7.5%. Six CPET variables were found to be significant predictors of mortality: peak oxygen consumption, oxygen pulse, end-tidal partial pressure of carbon dioxide, heart rate recovery 1 min after CPET, minute ventilation to carbon dioxide output slope, and functional aerobic impairment. We calculated a summed score by adding the number of CPET variables that exceeded their cutoff values. Subjects with a summed score of 6 had a 1-y survival rate of only 25%, whereas subjects with scores of 0-5 had a survival rate of 98%. CONCLUSIONS: In conclusion, the summed score represents a useful tool for screening patients with ILD who can undergo a CPET to determine their prognosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cardiopulmonary exercise testing is an increasingly common test and is considered the accepted standard for assessing exercise capacity. Quantifying variability is important to assess the instrument for quality control purposes. Though guidelines recommend biologic control testing, there are minimal data on how to do it. We sought to describe variability for oxygen consumption (V̇O2 ), carbon dioxide production (V̇CO2 ), and minute ventilation (V̇E) at various work rates under steady-state conditions in multiple subjects over a 1-y period to provide a practical approach to assess and perform biologic control testing. METHODS: We performed a single-center, prospective study with 4 healthy subjects, 2 men and 2 women. Subjects performed constant work rate exercise tests for 6 min each at 25-100 W intervals on a computer-controlled cycle ergometer. Data were averaged over the last 120 s at each work rate to reflect stepwise steady-state conditions. Descriptive statistics, including the mean, median, range, SD, and coefficient of variation (CoV) are reported for each individual across the 4 work rates and all repetitions. As these data were normative, z-scores were utilized, and a value greater than ± 1.96 z-scores was used to define significant test variability. RESULTS: Subjects performed 16-39 biocontrol studies over 1-y. The mean CoV for all subjects in V̇O2 was 6.59%, V̇CO2 was 6.41%, and V̇E was 6.32%. The ± 1.96 z-scores corresponded to a 9.4-18.1% change in V̇O2 , a 9.6-18.1% change in V̇CO2 , and a 9-21.5% change in V̇E across the 4 workloads. CONCLUSIONS: We report long-term variability for steady-state measurement of V̇O2 , V̇CO2 , and V̇E obtained during biocontrol testing. Utilizing ± 1.96 z-scores allows one to determine if a result exceeds expected variability, which may warrant investigation of the instrument.

Physiological response to physical exercise through analysis of cardiopulmonary measurements has been shown to be predictive of a variety of diseases. Nonetheless, the clinical use of exercise testing remains limited because interpretation of test results requires experience and specialized training. Additionally, until this work no methods have identified which dynamic gas exchange or heart rate responses influence an individual's decision to start or stop physical activity. This research examines the use of advanced machine learning methods to predict completion of a test consisting of multiple exercise bouts by a group of healthy children and adolescents. All participants could complete the ten bouts at low or moderate-intensity work rates, however, when the bout work rates were high-intensity, 50% refused to begin the subsequent exercise bout before all ten bouts had been completed (task failure). We explored machine learning strategies to model the relationship between the physiological time series, the participant's anthropometric variables, and the binary outcome variable indicating whether the participant completed the test. The best performing model, a generalized spectral additive model with functional and scalar covariates, achieved 93.6% classification accuracy and an F1 score of 93.5%. Additionally, functional analysis of variance testing showed that participants in the 'failed' and 'success' groups have significantly different functional means in three signals: heart rate, oxygen uptake rate, and carbon dioxide uptake rate. Overall, these results show the capability of functional data analysis with generalized spectral additive models to identify key differences in the exercise-induced responses of participants in multiple bout exercise testing.

A 64‐year‐old obese gentleman attended for further evaluation of ongoing dyspnoea in the context of a previous diagnosis of moderate COPD treated with dual long‐acting bronchodilators. A cardiopulmonary exercise test (CPET) was performed, which demonstrated reduced peak work and oxygen consumption with evidence of dynamic hyperinflation, abnormal gas exchange and ventilatory limitation despite cardiac reserve. The CPET clarified the physiological process underpinning the patient's dyspnoea and limiting the patient's activities. This, in turn, helped the clinician tailor the patient's management plan. [ABSTRACT FROM AUTHOR]

Aerobic, or endurance, exercise is an energy requiring process supported primarily by energy from oxidative adenosine triphosphate synthesis. The consumption of oxygen and production of carbon dioxide in muscle cells are dynamically linked to oxygen uptake (V̇O 2) and carbon dioxide output (V̇CO 2) at the lung by integrated functions of cardiovascular, pulmonary, hematologic, and neurohumoral systems. Maximum oxygen uptake (V̇O 2max) is the standard expression of aerobic capacity and a predictor of outcomes in diverse populations. While commonly limited in young fit individuals by the capacity to deliver oxygen to exercising muscle, (V̇O 2max) may become limited by impairment within any of the multiple systems supporting cellular or atmospheric gas exchange. In the range of available power outputs, endurance exercise can be partitioned into different intensity domains representing distinct metabolic profiles and tolerances for sustained activity. Estimates of both V̇O 2max and the lactate threshold, which marks the upper limit of moderate-intensity exercise, can be determined from measures of gas exchange from respired breath during whole-body exercise. Cardiopulmonary exercise testing (CPET) includes measurement of V̇O 2 and V̇CO 2 along with heart rate and other variables reflecting cardiac and pulmonary responses to exercise. Clinical CPET is conducted for persons with known medical conditions to quantify impairment, contribute to prognostic assessments, and help discriminate among proximal causes of symptoms or limitations for an individual. CPET is also conducted in persons without known disease as part of the diagnostic evaluation of unexplained symptoms. Although CPET quantifies a limited sample of the complex functions and interactions underlying exercise performance, both its specific and global findings are uniquely valuable. Some specific findings can aid in individualized diagnosis and treatment decisions. At the same time, CPET provides a holistic summary of an individual's exercise function, including effects not only of the primary diagnosis, but also of secondary and coexisting conditions. [ABSTRACT FROM AUTHOR]

Background: Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery. Methods: A prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb]) < 130 g.l−1 and iron deficiency/depletion. Patients underwent CPET and tHb-mass measurements before and a minimum of 14 days after receiving intravenous (i.v.) Ferric derisomaltose (Monofer®) at the baseline visit. Comparative analysis of hematological and CPET variables was performed pre and post-iron treatment. Results: Twenty-six subjects were recruited, of whom 6 withdrew prior to study completion. The remaining 20 (9 [45%] male; mean ± SD age 68 ± 10 years) were assessed 25 ± 7 days between baseline and the final visit. Following i.v. iron, increases were seen in [Hb] (mean ± SD) from 109 ± 14 to 116 ± 12 g l−1 (mean rise 6.4% or 7.3 g l−1, p = < 0.0001, 95% CI 4.5–10.1); tHb-mass from 497 ± 134 to 546 ± 139 g (mean rise 9.3% or 49 g, p = < 0.0001, 95% CI 29.4–69.2). Oxygen consumption at anerobic threshold ( V ˙ O2 AT) did not change (9.1 ± 1.7 to 9.8 ± 2.5 ml kg−1 min−1, p = 0.09, 95% CI − 0.13 − 1.3). Peak oxygen consumption ( V ˙ O2 peak) increased from 15.2 ± 4.1 to 16 ± 4.4 ml.kg.−1 min−1, p = 0.02, 95% CI 0.2–1.8) and peak work rate increased from 93 [67–112] watts to 96 [68–122] watts (p = 0.02, 95% CI 1.3–10.8). Conclusion: Preoperative administration of intravenous iron to iron-deficient/deplete anemic patients is associated with increases in [Hb], tHb-mass, peak oxygen consumption, and peak work rate. Further appropriately powered prospective studies are required to ascertain whether improvements in tHb-mass and performance in turn lead to reductions in perioperative morbidity. Trial registration: ClinicalTrials.gov identifier: NCT 033 46213. [ABSTRACT FROM AUTHOR]

Children are the most naturally physically active human beings; reduced physical activity is a cardinal sign of childhood disease, and exercise testing provides mechanistic insights into health and disease that are often hidden when the child is at rest. The physical inactivity epidemic is leading to increased disease risk in children and, eventually, in adults in unprecedented ways. Cardiopulmonary exercise testing (CPET) biomarkers are used to assess disease severity, progress, and response to therapy across an expanding range of childhood diseases and conditions. There is mounting data that fitness in children tracks across the life span and may prove to be an early, modifiable indicator of cardiovascular disease risk later in life. Despite these factors, CPET has failed to fulfill its promise in child health research and clinical practice. A major barrier to more accurate and effective clinical use of CPET in children is that data analytics and testing protocols have failed to keep pace with enabling technologies and computing capacity. As a consequence, biomarkers of fitness and physical activity have yet to be widely incorporated into translational research and clinical practice in child health. In this review, the author re-examines some of the long-held assumptions that mold CPET in children. In particular, the author suggests that current testing strategies that rely predominantly on maximal exercise may, inadvertently, obfuscate novel and clinically useful insights that can be gleaned from more comprehensive data analytics. New pathways to discovery may emanate from the simple recognition that the physiological journey that human beings undertake in response to the challenge of exercise may be far more important than the elusive destination of maximal or peak effort.

Cardiopulmonary exercise testing (CPET) was limited to peak oxygen consumption analysis (VO2peak), and now the ventilation/carbon dioxide production (VE/VCO2) slope is recognized as having independent prognostic value. Unlike VO2peak, the VE/VCO2 slope does not require maximal effort, making it more feasible. There is no consensus on how to measure the VE/VCO2 slope; therefore, we assessed whether different methods affect its value. This is a retrospective study assessing sociodemographic data, left ventricular ejection fraction, CPET parameters, and indications of patients referred for CPET. The VE/VCO2 slope was measured to the first ventilatory threshold (VT1-slope), secondary threshold (VT2-slope), and included all test data (full-slope). Of the 697 CPETs analyzed, 308 reached VT2. All VE/VCO2 slopes increased with age, regardless of test indications. In patients not reaching VT2, the VT1-slope was 32 vs. 36 (p < 0.001) for the full-slope; in those surpassing VT2, the VT1-slope was 29 vs. 33 (p < 0.001) for the VT2-slope and 37 (all p < 0.001) for the full-slope. The mean difference between the submaximal and full-slopes was ±4 units, sufficient to reclassify patients from low to high risk for heart failure or pulmonary hypertension. We conclude that the method used for determining the VE/VCO2 slope greatly influences the result, the significant variations limiting its prognostic value. The calculation method must be standardized to improve its prognostic value. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the benefits of cardio-pulmonary rehabilitation on severe to moderate COVID-19 patients. 25 discharged COVID-19 patients underwent a cardio-pulmonary test (CPET), a spirometry test and a measure of carbon monoxide lung diffusion capacity (DLCO) at the beginning of their rehabilitation program and after 23 ± 5 rehabilitation sessions. This rehabilitation program combined interval training exercises on a bike and resistance exercises for major muscle groups. We then compared their progress in rehabilitation to that obtained with cardiac patients. At the beginning of their rehabilitation program, COVID-19 patients presented a reduced physical capacity with a maximal aerobic capacity (VO2 max) at 71% of predicted value, a maximal workload at 70% of predicted value and an exercise hyperventilation measured by a higher VE/VCO2 slope. Exercise was mainly limited by muscle deconditioning. After rehabilitation, the VO2 max and maximal workload increased in COVID 19 patients by 18% and 26%, respectively. In patients with ischemic heart disease the post-rehabilitation gains in VO2 max and maximal workload were 22% and 25%, respectively. Moreover, exercise hyperventilation decreased by 10% in both groups. On the other hand, the intrinsic pulmonary function of COVID 19 patients improved following natural recovery. In conclusion, even if cardio-pulmonary rehabilitation is probably not the only parameter which explains the partial recovery of moderate to severe COVID-19 patients, it certainly helps to improve their physical capacity and reduce exercise hyperventilation. [ABSTRACT FROM AUTHOR]

Cardiopulmonary exercise testing (CPET) allows for a non-invasive assessment of the integrative response of the pulmonary, cardiovascular, and skeletal muscle system during exercise. Therefore CPET in sports medicine covers a wide spectrum, ranging from diagnosis of disease, preoperative assessment, to athlete monitoring. High standards of reliability and validity are needed to ensure high-quality and diagnostically conclusive CPET data, necessitating a systematic process of quality assurance and control in the daily application of CPET. Therefore, methodological aspects such as CPET equipment principles, calibration, verification, maintenance, preparation, and plausibility checks need to be considered. As inter-technology, inter-device, and inter-unit differences in reliability and validity are reported for automated metabolic analyzers, the choice of the appropriate device should follow the purpose of use and comprehensible data on reliability and validity. › To ensure high-quality measurements, careful calibration, and verification of all sensors, the integrated overall measurement performance, and maintenance of all equipment need to be performed and monitored longitudinally. Further, standardized ambient conditions, with adequate circulation and exchange of room air are essential. As the choice of the ergometer and protocol influences various target values in CPET, appropriateness for the selected diagnostic objective as well as a corresponding standardization is needed. While patients should receive pretest information that clearly outlines the test procedure, the correct attachment of the CPET equipment is of utmost importance. › To detect and correct malfunctions of the metabolic analyzer and equipment, plausibility checks of the outcome measures validity should be performed during the resting, unloaded, loaded, and recovery test phase. A basic plausibility check should include adequate rest values and increases for a given workload rate of minute ventilation (V̇E), oxygen consumption (V̇O2) and respiratory exchange ratio (RER), using rules of thumb by Rühle. Before the final data interpretation is performed, e.g. ventilatory threshold or maximum oxygen consumption (V̇O2max) or V̇O2peak determination, again a plausibility check should be performed and the patient's effort whether or not maximal should be determined. › Consequently, a standard operating procedure for quality assurance and control, including an intuitive data visualization with thresholds for "pass", "fail" or outliers and trends of concerns should be specifically defined, taught, and implemented in each facility. [ABSTRACT FROM AUTHOR]

People with chronic obstructive pulmonary disease (COPD) tend to have abnormally low levels of fat-free mass (FFM), which includes skeletal muscle mass as a central component. The purpose of this systematic review was to synthesise available evidence on the association between FFM and exercise test outcomes in COPD. MEDLINE, Cochrane Library, EMBASE, Web of Science, and Scopus were searched. Studies that evaluated exercise-related outcomes in relation to measures of FFM in COPD were included. Eighty-three studies, containing 18,770 (39% female) COPD participants, were included. Considerable heterogeneity was identified in the ways that FFM and exercise test outcomes were assessed; however, higher levels of FFM were generally associated with greater peak exercise capacity. This association was stronger for some exercise test outcomes (e.g. peak rate of oxygen consumption during incremental cycle exercise testing) than others (e.g. six-minute walking distance). This review identified heterogeneity in the methods used for measuring FFM and exercise capacity. There was, in general, a positive association between FFM and exercise capacity in COPD. There was also an identified lack of studies investigating associations between FFM and temporal physiological and perceptual responses to exercise. This review highlights the significance of FFM as a determinant of exercise capacity in COPD. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2049737. [ABSTRACT FROM AUTHOR]

Background: Physiologic and symptom responses at the ventilatory threshold (Tvent) during incremental cardiopulmonary exercise testing (CPET) can provide important prognostic information.Research Question: This study aimed to develop an updated normative reference set for physiologic and symptom responses at Tvent during cycle CPET (primary aim) and to evaluate previously recommended reference equations from a 1985 study for predicting Tvent responses (secondary aim).Study Design and Methods: Participants were adults 40 to 80 years of age who were free of clinically relevant disease from the Canadian Cohort Obstructive Lung Disease. Rate of oxygen consumption (V˙O2) at Tvent was identified by two independent raters; physiologic and symptom responses corresponding to V˙O2 at Tvent were identified by linear interpolation. Reference ranges (5th-95th percentiles) for responses at Tvent were calculated according to participant sex and age for 29 and eight variables, respectively. Prediction models were developed for nine variables (oxygen pulse, V˙O2, rate of CO2 production, minute ventilation, tidal volume, inspiratory capacity, end-inspiratory lung volume [in liters and as percentage of total lung capacity], and end-expiratory lung volume) using quantile regression, estimating the 5th (lower limit of normal), 50th (normal), and 95th (upper limit of normal) percentiles based on readily available participant characteristics. The two one-sided test of equivalence for paired samples evaluated the measured and 1985-predicted V˙O2 at Tvent for equivalence.Results: Reference ranges and equations were developed based on 96 participants (49% men) with a mean ± SD age of 63 ± 9 years. Mean V˙O2 at Tvent was 50% of measured V˙O2 peak; the normal range was 33% to 66%. The 1985 reference equations overpredicted V˙O2 at Tvent: mean difference in men, -0.17 L/min (95% CI, -0.25 to -0.09 L/min); mean difference in women, -0.19 L/min (95% CI, -0.27 to -0.12 L/min).Interpretation: A contemporary reference set of CPET responses at Tvent from Canadian adults 40 to 80 years of age is presented that differs from the previously recommended and often used reference set from 1985.Trial Registry: ClinicalTrials.gov; No.: NCT00920348; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the application, outcomes, and validity of cardiopulmonary exercise test (CPET) outcomes using a modified Balke protocol on a motor-driven treadmill in fully ambulatory people with multiple sclerosis (MS). Methods: Fully ambulatory people with MS (N 5 20) underwent assessments of disability (Expanded Disability Status Scale, EDSS), walking endurance (6-minute walk distance, 6MWD), and cognition (Symbol Digit Modalities Test, SDMT), and completed a maximal CPET (modified Balke protocol) on a motor-driven treadmill while expired gases were collected with indirect calorimetry. Serious adverse events (AEs) and AEs, defined by National Institutes of Health guidelines, and provision of a maximal effort test using standard criteria for a maximal effort were documented. The physiological outcomes derived from the CPET included oxygen uptake (V.O2), carbon dioxide production, ventilation (VE), respiratory exchange ratio, and heart rate (HR). Other outcomes were calculated using standard guidelines, including V.O2/HR slope and oxygen uptake efficiency slope (V.O2/log10VE). Descriptive statistics were summarized with mean 6 SD and descriptively compared with normative data from apparently healthy individuals using a similar CPET protocol. Spearman's rho rank-order correlations (r) were performed among peak V.O2 and SDMT, 6MWD, and EDSS scores. Results: There were no AEs, and 17 of 20 tests were characterized as yielding a maximal effort and therefore interpretable. V.O2 peak derived from the modified Balke protocol was predictably different in MS (25.8 6 6.3) than normative values for healthy samples men (43.4 6 9.3) and women (35.0 6 7.2). V.O2 peak positively correlated with SDMT (r 5 0.53, P 5 .01) and 6MWD (r 5 0.73, P 5 .0003), and negatively correlated with disability (r520.51, P5.02). Conclusions: Cardiopulmonary exercise test using a modified Balke protocol on a motorized treadmill is safe, feasible, and valid for the measurement of aerobic power in fully ambulatory people with MS. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: Cardiopulmonary exercise testing (CPET) plays an important role in clinical medicine and research. Repeatability of CPET parameters has not been well characterized, but is important to assess variability and determine if there have been meaningful changes in a given CPET parameter. Methods: We recruited 45 healthy subjects and performed two symptom-limited CPET within 30 d using a cycle ergometer. Differences in relevant CPET parameters between CPET-1 and CPET-2 were assessed using a paired t-test. Coefficient of variation (CoV) and Bland-Altman plots are reported. Factors that may be associated with variability were analyzed (sex, age, time of day, fitness level). The coefficient of repeatability was calculated for peak oxygen consumption (...O2) and ...O2 at lactate threshold (LT) to establish a 95% threshold for meaningful change. Results: There were no significant differences between tests in the parameters reported. Specifically, we found overall low CoV in peak ...O2 (4.9%), V...O2@LT (10.4%), peak O2 pulse (4.6%), peak minute ventilation (...E; 7.4%), ...E/... CO2@LT (4.0%), and ...E/...O2@LT (4.8%). The CoV for peak respiratory exchange ratio@LT was significantly affected by diurnal factors; age, sex, and fitness level did not affect variability. The 95% threshold for meaningful change was 0.540 L⋅min-1 in peak ...O2 and 0.520 L⋅min-1 in ...O2@LT. Conclusions: Repeatability of CPET parameters is generally higher than previously reported. There were no significant differences in variability related to sex, age, and fitness level; diurnal factors had a limited effect. The threshold for meaningful change in peak ...O2 and for ...O2@LT should be considered when gauging a response to therapies or training. [ABSTRACT FROM AUTHOR]

Objective: To determine the main reasons for cardiopulmonary exercise test (CPET) referrals in our hospital over the last two years; to evaluate clinical usefulness of CPET. Methods: We included 207 patients between 17 and 76 years of age. For every patient, we measured electrocardigraphy (ECG), arterial blood gases, spirometry, maximal voluntary ventilation (MVV) and diffusing capacity. CPET was then performed; using a treadmill, according to the modified Bruce protocol; then spirometry and diffusing capacity were repeated. Results: The most common reason for sending patients for CPET was dyspnea during exertion (85%), then preoperative assessment of lung cancer patients (11.6%), and preoperative assessment of heart transplant candidates (3.4%). After CPET in a dyspnea group, 33.5% had normal findings, 22.2% had pulmonary limitation, 31.8% had non pulmonary pathology, and 12.5% reached submaximal effort due to subjective problems (poor condition, feeling discomfort) but no objective reasons to stop. From a lung cancer group, 25% were deemed unsuitable surgical candidates, and 14.29% of a heart transplant group was recommended immediate surgery, the remainder needed re-evaluation. Conclusion: Dyspnea of unknown cause is optimally investigated with CPET, allowing us to differentiate between the major causes of limitation (lung, heart, cardiovascular, muscular) and, within each area, the specific causes of limitation. The most common diagnoses after CPET are pulmonary and cardiac diagnoses. CPET helps us to detect concurrent cardiovascular disease at respiratory impaired patients. CPET is the gold standard for evaluation of morbidity and mortality risk of lung cancer surgery and for selection of patients for heart transplant. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Maximum oxygen consumption per min (VO2max) is currently considered the most accurate test for the preoperative risk assessment in patients scheduled for pulmonary resection. Due to its high-technology requirements and cost, VO2max is performed less frequently than is desired. The objective of this investigation is to determine if the measurement of the basal daily ambulatory activity of the patients, with a pedometer, can be used to predict VO2max values. Methods: This is a prospective study on 38 patients referred for scheduled lobectomy or pneumonectomy. Daily basal preoperative activity of the patients was measured 3 weeks before surgery by means of an OMROM HJ-72OIT-E2 pedometer. Before surgery, VO2max (dependent variable) was calculated using a Master Screen CPX module of Jaeger-Vyasis-Healthcare. The following independent variables were studied: age, sex, preoperative forced expiratory volume in 1s percentage (FEV1%) and carbon monoxide diffusing capacity percentage (DLCO%), mean number of steps per day (aerobic and non-aerobic), mean daily time of aerobic activity (in min) and mean daily walked distance (in km). Two linear regression models with bootstrap robust estimation of the standard error of the coefficients were adjusted and the estimated values of VO2max were kept as a new variable for comparison. To avoid collinearity problems, only one of the pedometer records entered the regression model. Results: Data of the series (mean±SD): age 62.8±10.14 years; FEV1% 90.1±21.8; DLCO% 82.8±20.1. After collinearity analysis, mean daily walked distance was chosen as the most representative variable. In the first regression model, ‘Distance’ (p =0.000) was highly correlated to the dependent variable (adjusted R 2: 0.812). The second model improved the predictive value of the first one adding DLCO% to the model. In this model, DLCO% (p =0.000) and ‘Distance’ (p =0.002) were correlated to the dependent variable. The adjusted R 2 of the second lineal model was 0.935. Conclusion: These preliminary data show that a combination of the measured daily ambulatory activity using a pedometer, especially the mean daily walked distance in km, and the DLCO% of the patient could predict the VO2max value. Larger data series are needed for conclusive results. [Copyright &y& Elsevier]

Aim: Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. Methods and results: Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). Conclusion: Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea. [ABSTRACT FROM AUTHOR]