Molecular Choreography of Acute Exercise.

Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

Exercise testing unmasks exaggerated blood pressure independent of fibrinolytic response in Black but not White postmenopausal females.

Exercise testing unmasks more exaggerated systolic blood pressure responses (SBP) in Black compared with White male adults. Such responses, if translatable to females, may detect racial disparities particularly relevant during menopause. Given the endothelial involvement in BP regulation and as a source of fibrinolytic markers, it follows that fibrinolytic and BP response to exercise could be linked. Thus, we examined BP and fibrinolytic responses to exercise testing in Black and White postmenopausal females. Postmenopausal females (Black = 40; White = 41; 51-70 yr) performed maximal treadmill exercise. BP and blood draws were conducted before and immediately after exercise. Plasma samples, using minimal stasis, were analyzed for tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) activity and antigen, respectively. Resting SBP and fibrinolytic potential were similar between races. Black females exhibited greater increases in SBP during exercise [change (d)=75, 95% CI: 64-86 mmHg, P < 0.001] than White females (d = 60, 95% CI: 48-71 mmHg, P < 0.001). Black compared with White females had smaller changes in tPA (d = 3.27, 95% CI: 2.28-4.27 IU/mL, P < 0.001 vs. d = 5.55, 95% CI: 4.58-6.53, P < 0.001) and PAI-1 (d = -2.89, 95% CI: -4.39 to -1.40 IU/mL, P < 0.001 vs. d = -5.08, 95% CI: -6.59 to -3.61, P < 0.001) activities after exercise. SBP exercise-induced changes were not associated with tPA (r = -0.10, P = 0.42) or PAI-1 (r = 0.13, P = 0.30), without any influence of race (P > 0.05). Our findings show that maximal exercise unmasks risk factors for cardiovascular disease in Black postmenopausal females.NEW & NOTEWORTHY Exaggerated SBP responses to exercise testing are more frequent in Black than in White male adults. Such responses, if translatable to females, may detect early racial disparities arriving during menopause. Because the endothelium regulates BP and fibrinolytic responses, these could be linked during exercise. At peak exercise, Black but not White postmenopausal females had more exaggerated SPB responses regardless of reduced fibrinolytic potential. Maximal exercise unmasked risk factors for cardiovascular disease in Black postmenopausal females.

Biventricular responses to exercise and their relation to cardiorespiratory fitness in pediatric pulmonary hypertension.

Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardio-pulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age 13.4 ±2.9 years. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ±25 mmHg at rest to 130 ±40 mmHg at peak exercise (p<0.001), while RV fractional area change (RV-FAC) and RV free wall longitudinal strain (RVFW-Sl) worsened (35.2% vs 27%, p=0.09 and -16.6% vs -14.6%, p=0.1, respectively). At low and moderate intensity exercise, RVsp was positively associated with stroke volume and O2 pulse (p<0.1). At high intensity exercise RV-FAC, RVFW-Sl and left ventricular longitudinal strain were positively associated with oxygen uptake and O2 pulse (p<0.1), while stroke volume decreased towards peak (p=0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV-PA uncoupling, worsening of inter-ventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population.

Reference Values for Cardiorespiratory Fitness in Patients Aged 6 to 18 Years.

OBJECTIVE: To develop reference values for cardiorespiratory fitness, as quantified by peak oxygen uptake (VO2peak) and treadmill time, in patients aged 6 through 18 years referred for cardiopulmonary exercise testing (CPET). STUDY DESIGN: We reviewed a clinical pediatric CPET database for fitness data in children aged 6-18 years with no underlying heart disease. CPET was obtained via the Bruce protocol utilizing objectively confirmed maximal effort via respiratory exchange ratio. Fitness data (VO2peak and treadmill test duration) were analyzed to determine age- and sex-specific reference values for this pediatric cohort. RESULTS: Data from 2025 pediatric CPETs (53.2% female) were included in the analyses. VO2peak increased with age in males, but not females. Treadmill test duration increased with age in both males and females. Fitness was generally higher in males when compared with females in the same age groups. CONCLUSIONS: Our study provides extensive reference values for both VO2peak and total treadmill test time via the Bruce protocol for a pediatric population without known cardiac disease. Furthermore, the inclusion of objectively confirmed maximal exercise effort increases confidence in these findings compared with prior studies in this area. Clinicians performing CPET in pediatric populations can utilize these reference values to characterize test results according to representative peer data.

Exercise-Induced Pulmonary Hypertension in Long-Term Survivors of Congenital Diaphragmatic Hernia.

OBJECTIVE: To determine the prevalence of exercise-induced pulmonary hypertension (PH) among long-survivors of congenital diaphragmatic hernia repair. STUDY DESIGN: This is a single-center, retrospective cohort study of CDH survivors who underwent exercise stress echocardiography (ESE) at Boston Children's Hospital from January 2006 to June 2020. PH severity was assessed by echocardiogram at baseline and after exercise. Patients were categorized by right ventricular systolic pressure (RVSP) after exercise: Group 1 - no or mild PH; and Group 2 - moderate or severe PH (RVSP ≥ 60 mmHg or ≥ ½ systemic blood pressure). RESULTS: Eighty-four patients with CDH underwent 173 ESE with median age 8.1 (4.8 - 19.1) years at first ESE. Sixty-four patients were classified as Group 1, 11 as Group 2, and 9 had indeterminate RVSP with ESE. Moderate to severe PH after exercise was found in 8 (10%) patients with no or mild PH at rest. Exercise-induced PH was associated with larger CDH defect size, patch repair, use of ECMO, supplemental oxygen at discharge, and higher WHO functional class. Higher VE/VCO2 slope, lower peak oxygen saturation, and lower percent predicted FEV1, and FEV1/FVC ratio were associated with Group 2 classification. ESE changed management in 9/11 Group 2 patients. PH was confirmed in all 5 Group 2 patients undergoing cardiac catheterization after ESE. CONCLUSIONS: Among long-term CDH survivors, 10% had moderate-severe exercise-induced PH on ESE, indicating ongoing pulmonary vascular abnormalities. Further studies are needed to optimally define PH screening and treatment for patients with repaired CDH.

The Child Opportunity Index 2.0 and Disparities in Pediatric Cardiorespiratory Fitness.

OBJECTIVE: To evaluate the effect of neighborhood-level characteristics on cardiorespiratory fitness (CRF) via peak oxygen consumption (VO2peak) for healthy pediatric patients. STUDY DESIGN: The institutional cardiopulmonary exercise testing (CPET) database was analyzed retrospectively. All patients aged ≤ 18 years without a diagnosis of cardiac disease and with a maximal effort CPET were included. Patients were divided into three self-identified racial categories: White, Black, and Latinx. The Child Opportunity Index (COI) 2.0 was used to analyze social determinants of health. CRF was evaluated based on COI quintiles and race. Assessment of the effect of COI on racial disparities in CRF was performed using ANCOVA. RESULTS: A total of 1753 CPETs met inclusion criteria. The mean VO2peak was 42.1 ± 9.8 mL/kg/min. The VO2peak increased from 39.1 ± 9.6 mL/kg/min for patients in the very low opportunity cohort to 43.9 ± 9.4 mL/kg/min for patients in the very high opportunity cohort. White patients had higher percent predicted VO2peak compared with both Black and Latinx patients (P < .01 for both comparisons). The racial differences in CRF were no longer significant when adjusting for COI. CONCLUSION: In a large pediatric cohort, COI was associated with CRF. Racial disparities in CRF are reduced when accounting for modifiable risk factors.

Blood pressure response during exercise testing in individuals with and without hypertension: The value of the recovery phase.

BACKGROUND: Hypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE. METHODS: 800 patients aged 17-90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre-existent hypertension. RESULTS: Of the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (ß [95% CI] 8.0 [4.9-11.1]) and diastolic (2.4 [0.4-4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2-9.4]) and diastolic BP (4.5 [1.9-7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1-7.5]) and fully adjusted (5.5 [1.1-10.0]) models. There was no difference in maximum diastolic BP between groups. CONCLUSION: In this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase.

A Comprehensive Assessment of the Chinese Version of the Duke Activity Status Index in Patients with Cardiovascular Diseases.

Background: Exercise capacity serves as a direct representation of cardiac function. The Duke Activity Status Index (DASI), a self-administered 12-item questionnaire, covers aspects of daily living, household tasks, sexual function, and physical activity. Although widely used to evaluate exercise capacity, its validation in Chinese cardiovascular disease (CVD) patients has not been thoroughly explored. Considering the significant cultural and lifestyle differences between China and Western countries, which may influence Chinese patients' comprehension and responses to DASI, our objective is to culturally adapt DASI for Chinese patients with CVD to ensure its precision in assessing exercise capacity. Methods: The cultural adaptation of the original DASI questionnaire into Chinese followed a rigorous process to ensure its validity, reliability, and sensitivity to Chinese CVD patients. The study included 107 outpatients diagnosed with CVD who completed the DASI and cardiopulmonary exercise testing (CPET). Cronbach's alpha, Spearman correlation, and factor analysis were utilized to test reliability and validity. Receiver operating characteristic (ROC) curve analysis was employed to assess the prognostic utility of the DASI. Results: Participants had a mean DASI score of 39.40 ± 10.75 and a peak oxygen uptake (Peak VO 2 ) of 19.53 ± 5.89 mL/min/kg. The Chinese version of the DASI exhibited satisfactory reliability and validity in CVD patients, with a Chronbach's alpha coefficient of 0.706. The DASI score demonstrated a moderate correlation with Peak VO 2 measured by CPET (r = 0.67, p < 0.001). Factor analysis yielded three factors, accounting for 56.76% of the total variance, with factor 1 contributing to 26.38% of the variance. ROC curve analysis demonstrated that the DASI exhibited discriminative utility in the identification of patients with improved long-term prognosis (p < 0.001). The ROC curve had an area of 0.788 [95% confidence interval (CI) = 0.704-0.871]. The DASI score ≥ 36.85 served as the optimal threshold for enhanced long-term prognosis, exhibiting a sensitivity of 0.80 and a specificity of 0.69. Conclusions: The culturally adapted DASI questionnaire is a straightforward and efficient tool for reasonably evaluating exercise capacity in Chinese CVD patients.

Maximal Exercise Tolerance, Objective Trunk Strength, and Mobility Measurements in Axial Spondyloarthritis.

OBJECTIVE: Although exercise therapy is safe, effective, and recommended as a nonpharmacological treatment for axial spondyloarthritis (axSpA), there is a lack of guidelines regarding type and dosage. Insufficient knowledge about physical and physiological variables makes designing effective exercise programs challenging. Therefore, the goal of this study was to simultaneously assess trunk strength, spinal mobility, and the cardiorespiratory fitness of patients with axSpA. METHODS: In a cross-sectional study, 58 patients with axSpA (mean age 40.8 yrs, 50% male, mean symptom duration 10.3 yrs) performed maximal cervical and trunk mobility and isometric strength tests in all planes (using David Back Concept devices) and a maximal cardiopulmonary bicycle exercise test (n = 25). Mobility and strength data were compared to healthy reference data. Cut-off values for clinical cardiopulmonary exercise testing interpretation were used to judge normality. Patients were compared based on radiographic involvement and symptom duration. RESULTS: Both strength (P ≤ 0.02) and mobility (P ≤ 0.001) were significantly lower for the patients with axSpA compared to the reference. Strength deficits were comparable between the radiographic and nonradiographic groups (P > 0.05, except trunk extension [P = 0.03]), whereas mobility showed higher deficits in the radiographic group (cervical extension [P = 0.02] and rotation [P = 0.01], and trunk extension [P = 0.03] and rotation [P = 0.03]), regardless of symptom duration. Similarly, symptom duration positively affected oxygen pulse (P = 0.03), relative anaerobic threshold (P = 0.02), and aerobic capacity (P = 0.02). CONCLUSION: In patients with axSpA, strength is more affected than mobility when compared to healthy controls. Likewise, mainly the metabolic component of aerobic capacity is impaired, affecting cardiopulmonary fitness. These findings indicate that future personalized exercise programs in patients with axSpA should incorporate exercises for cardiopulmonary fitness next to strength and mobility training.

Assessment of health-related quality of life in patients with Chagas cardiomyopathy using Minnesota living with heart failure questionnaire: A validation study.

OBJECTIVE: Chagas cardiomyopathy (ChC) is the most severe clinical form of Chagas disease and, in association with psychosocial factors, can compromise the health-related quality of life (HRQoL) of affected patients. To date, there is no specific instrument to assess the HRQoL of these patients, and the Minnesota Living with Heart Failure Questionnaire (MLwHFQ), specific for heart failure, is being used both in research and current clinical practice. Therefore, we aimed to verify the validity of the MLwHFQ in the assessment of HRQoL of patients with ChC. METHODS: Fifty patients with ChC (50.6 ± 10.1 years, NYHA I-III) were evaluated. The MLwHFQ, Short-Form of Health Survey (SF-36), Beck Depression Inventory (BDI), and Human Activity Profile (HAP) were applied. All patients underwent echocardiography and Cardiopulmonary Exercise Testing (CPET). RESULTS: The MLwHFQ score correlated with almost all SF-36 domains (with r-value ranging from -0.38 to -0.69), except pain (p = 0.118). The MLwHFQ score also correlated with the BDI score (r = 0.748; p < 0.001), HAP score (r = -0.558; p = 0.001), peak oxygen uptake (r = -0.352; p = 0.01), and left ventricular ejection fraction (r = -0.329; p = 0.021). There was no significant difference in the score found on the MLwHFQ among NYHA classes (p = 0.101), as well as between patients with systolic dysfunction (n = 30) and preserved cardiac function (n = 20) (p = 0.058). Similarly, there was no significant difference in the score found on the physical (p = 0.423) and mental (p = 0.858) components of SF-36 between patients with systolic dysfunction and preserved cardiac function (p = 0.271 and p = 0.609, respectively). There was also no difference in the mental component of SF-36 among NYHA classes (p = 0.673). However, the HRQoL using the physical component of SF-36 was worse in advanced NYHA classes (p = 0.014). CONCLUSION: MLwHF correlated with most SF-36 HRQoL domains, depressive symptoms, physical activity, and systolic function and seems to be valid in assessing the HRQoL of ChC patients.

Maximal cardiopulmonary exercise testing in glioblastoma patients undergoing chemotherapy: assessment of feasibility, safety, and physical fitness status.

PURPOSE: Maximal cardiopulmonary exercise testing (max. CPET) provides the most accurate measurement of cardiorespiratory fitness. However, glioblastoma (GBM) patients often undergo less intensive tests, e.g., 6-min walk test or self-rating scales. This study aims to demonstrate feasibility and safety of max. CPET in GBM patients, concurrently evaluating their physical fitness status. METHODS: Newly diagnosed GBM patients undergoing adjuvant chemotherapy were offered participation in an exercise program. At baseline, max. CPET assessed cardiorespiratory fitness including peak oxygen consumption (VO2peak), peak workload, and physical work capacity (PWC) at 75% of age-adjusted maximal heart rate (HR). Criteria for peak workload were predefined based on threshold values in HR, respiratory quotient, respiratory equivalent, lactate, and rate of perceived effort. Data were compared to normative values. Adverse events were categorized according to standardized international criteria. Further, self-reported exercise data pre- and post-diagnosis were gathered. RESULTS: All 36 patients (median-aged 60; 21 men) met the predefined criteria for peak workload. Mean absolute VO2peak was 1750 ± 529 ml/min, peak workload averaged 130 ± 43 W, and mean PWC was 0.99 ± 0.38 W/kg BW, all clinically meaningful lower than age- and sex-predicted normative values (87%, 79%, 90%, resp.). Only once (3%) a minor, transient side effect occurred (post-test dizziness, no intervention needed). Self-reported exercise decreased from 15.8 MET-h/week pre-diagnosis to 7.2 MET-h/week post-diagnosis. CONCLUSION: Max. CPET in this well-defined population proved feasible and safe. GBM patients exhibit reduced cardiorespiratory fitness, indicating the need for tailored exercise to enhance health and quality of life. CPET could be essential in establishing precise exercise guidelines.

Effect of body mass index on exercise capacity following pediatric heart transplantation.

BACKGROUND: Obesity and impaired exercise tolerance following heart transplantation increase the risk of post-transplant morbidity and mortality. The aim of this study was to evaluate the effect of body mass index on markers of exercise capacity in pediatric heart transplant recipients and compare this effect with a healthy pediatric cohort. METHODS: A retrospective analysis of cardiopulmonary exercise test data between 2004 and 2022 was performed. All patients exercised on a treadmill using the Bruce protocol. Inclusion criteria included patients aged 6-21 years, history of heart transplantation (transplant cohort) or no cardiac diagnosis (control cohort) at the time of testing, and a maximal effort test. Patients were further stratified within these two cohorts as underweight, normal, overweight, and obese based on body mass index groups. Two-way analyses of variance were performed with diagnosis and body mass index category as the independent variables. RESULTS: A total of 250 exercise tests following heart transplant and 1963 exercise tests of healthy patients were included. Heart transplant patients across all body mass index groups had higher resting heart rate and lower maximal heart rate, heart rate recovery at 1 min, exercise duration, and peak aerobic capacity (VO2peak). Heart transplant patients in the normal and overweight body mass index categories had higher VO2peak and exercise duration when compared to underweight and obese patients. CONCLUSION: Underweight status and obesity are strongly associated with lower VO2peak and exercise duration in heart transplant patients. Normal and overweight heart transplant patients had the best markers of exercise capacity.

Ventilatory efficiency as a prognostic factor for postoperative complications in patients undergoing elective major surgery: a systematic review.

BACKGROUND: Major surgery is associated with high complication rates. Several risk scores exist to assess individual patient risk before surgery but have limited precision. Novel prognostic factors can be included as additional building blocks in existing prediction models. A candidate prognostic factor, measured by cardiopulmonary exercise testing, is ventilatory efficiency (VE/VCO2). The aim of this systematic review was to summarise evidence regarding VE/VCO2 as a prognostic factor for postoperative complications in patients undergoing major surgery. METHODS: A medical library specialist developed the search strategy. No database-provided limits, considering study types, languages, publication years, or any other formal criteria were applied to any of the sources. Two reviewers assessed eligibility of each record and rated risk of bias in included studies. RESULTS: From 10,082 screened records, 65 studies were identified as eligible. We extracted adjusted associations from 32 studies and unadjusted from 33 studies. Risk of bias was a concern in the domains 'study confounding' and 'statistical analysis'. VE/VCO2 was reported as a prognostic factor for short-term complications after thoracic and abdominal surgery. VE/VCO2 was also reported as a prognostic factor for mid- to long-term mortality. Data-driven covariable selection was applied in 31 studies. Eighteen studies excluded VE/VCO2 from the final multivariable regression owing to data-driven model-building approaches. CONCLUSIONS: This systematic review identifies VE/VCO2 as a predictor for short-term complications after thoracic and abdominal surgery. However, the available data do not allow conclusions about clinical decision-making. Future studies should select covariables for adjustment a priori based on external knowledge. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022369944).

Cardiopulmonary function in paediatric post-COVID-19: a controlled clinical trial.

Recently, the importance of post-COVID-19 in children has been recognized in surveys and retrospective chart analysis. However, objective data in the form of cardiopulmonary exercise test as performed in adults suffering from this condition are still lacking. This study aimed to investigate the cardiopulmonary effects of post-COVID-19 on children and adolescents. In this cross-sectional study (the FASCINATE study), children fulfilling the criteria of post-COVID-19 and an age- and sex-matched control group underwent cardiopulmonary exercise testing on a treadmill and completed a questionnaire with regard to physical activity before, during and after the infection with SARS-CoV-2. We were able to recruit 20 children suffering from post-COVID-19 (mean age 12.8 ± 2.4 years, 60% females) and 28 control children (mean age 11.7 ± 3.5 years, 50% females). All participants completed a maximal treadmill test with a significantly lower V ˙ O 2 peak in the post-COVID-19 group (37.4 ± 8.8 ml/kg/min vs. 43.0 ± 6.7 ml/kg/min. p = 0.019). This significance did not persist when comparing the achieved percentage of predicted V ˙ O 2 peak . There were no significant differences for oxygen pulse, heart rate, minute ventilation or breathing frequency.   Conclusion: This is the first study to investigate post-COVID-19 in children using the cardiopulmonary exercise test. Although there was a significantly reduced V ˙ O 2 peak in the post-COVID-19 group, this was not true for the percent of predicted values. No pathological findings with respect to cardiac or pulmonary functions could be discerned. Deconditioning was the most plausible cause for the experienced symptoms.    Trial registration: clinicaltrials.gov, NCT054445531, Low-field Magnetic Resonance Imaging in Pediatric Post Covid-19-Full Text View-ClinicalTrials.gov. What is Known: • The persistence of symptoms after an infection with SARS-CoV 2, so-called post-COVID-19 exists also in children. • So far little research has been conducted to analyze this entity in the pediatric population. What is New: • This is the first study proving a significantly lower cardiopulmonary function in pediatric patients suffering from post-COVID-19 symptoms. • The cardiac and pulmonary function appear similar between children suffering from post-COVID-19 and those who don't, but the peripheral muscles seem affected.

Accuracy of respiratory gas variables, substrate, and energy use from 15 CPET systems during simulated and human exercise.

PURPOSE: Various systems are available for cardiopulmonary exercise testing (CPET), but their accuracy remains largely unexplored. We evaluate the accuracy of 15 popular CPET systems to assess respiratory variables, substrate use, and energy expenditure during simulated exercise. Cross-comparisons were also performed during human cycling experiments (i.e., verification of simulation findings), and between-session reliability was assessed for a subset of systems. METHODS: A metabolic simulator was used to simulate breath-by-breath gas exchange, and the values measured by each system (minute ventilation [V̇E], breathing frequency [BF], oxygen uptake [V̇O2 ], carbon dioxide production [V̇CO2 ], respiratory exchange ratio [RER], energy from carbs and fats, and total energy expenditure) were compared to the simulated values to assess the accuracy. The following manufacturers (system) were assessed: COSMED (Quark CPET, K5), Cortex (MetaLyzer 3B, MetaMax 3B), Vyaire (Vyntus CPX, Oxycon Pro), Maastricht Instruments (Omnical), MGC Diagnostics (Ergocard Clinical, Ergocard Pro, Ultima), Ganshorn/Schiller (PowerCube Ergo), Geratherm (Ergostik), VO2master (VO2masterPro), PNOE (PNOE), and Calibre Biometrics (Calibre). RESULTS: Absolute percentage errors during the simulations ranged from 1.15%-44.3% for V̇E, 1.05-3.79% for BF, 1.10%-13.3% for V̇O2 , 1.07%-18.3% for V̇CO2 , 0.62%-14.8% for RER, 5.52%-99.0% for Kcal from carbs, 5.13%-133% for Kcal from fats, and 0.59%-12.1% for total energy expenditure. Between-session variation ranged from 0.86%-21.0% for V̇O2 and 1.14%-20.2% for V̇CO2 , respectively. CONCLUSION: The error of respiratory gas variables, substrate, and energy use differed substantially between systems, with only a few systems demonstrating a consistent acceptable error. We extensively discuss the implications of our findings for clinicians, researchers and other CPET users.

Reference values for leg effort during incremental cycle ergometry in non-trained healthy men and women, aged 19-85.

Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex- and age-adjusted frame of reference to judge symptom's normalcy across progressively higher exercise intensities during incremental exercise. Two-hundred and seventy-five non-trained subjects (130 men) aged 19-85 prospectively underwent incremental cycle ergometry. After establishing centiles-based norms for Borg leg effort scores (0-10 category-ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom's severity individually. Peak O2 uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort-work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, "heavy" (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th ("mild"), >50th to <75th ("moderate"), ≥75th to <95th ("severe"), and ≥ 95th ("very severe") (p < 0.05). Although most subjects reporting peak scores <5 were in "mild" range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0-10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom's normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations.

The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study.

BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. CONCLUSION: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.

Defining the role of exertional hypoxemia and pulmonary vasoconstriction on lung function decline, morbidity, and mortality in patients with chronic obstructive lung disease - the PROSA study: rationale and study design.

BACKGROUND: Chronic obstructive lung disease (COPD) has diverse molecular pathomechanisms and clinical courses which, however, are not fully mirrored by current therapy. Intermittent hypoxemia is a driver of lung function decline and poor outcome, e.g., in patients with concomitant obstructive sleep apnea. Transient hypoxemia during physical exercise has been suggested to act in a similar manner. The PROSA study is designed to prospectively assess whether the clinical course of COPD patients with or without exertional desaturation differs, and to address potential pathophysiological mechanisms and biomarkers. METHODS: 148 COPD patients (GOLD stage 2-3, groups B or C) will undergo exercise testing with continuous pulse oximetry. They will be followed for 36 months by spirometry, echocardiography, endothelial function testing, and biomarker analyses. Exercise testing will be performed by comparing the 6-min walk test (6MWT), bicycle ergometry, and a 15-sec breath-hold test. Exertional desaturation will be defined as SpO2 < 90% or delta-SpO2 ≥ 4% during the 6MWT. The primary endpoint will be the rate of decline of FEV1(LLN) between COPD patients with and without exertional desaturation. DISCUSSION: The PROSA Study is an investigator-initiated prospective study that was designed to prove or dismiss the hypothesis that COPD patients with exertional desaturation have a significantly more rapid rate of decline of lung function as compared to non-desaturators. A 20% difference in the primary endpoint was considered clinically significant; it can be detected with a power of 90%. If the primary endpoint will be met, exercise testing with continuous pulse oximetry can be used as a ubiquitously available, easy screening tool to prospectively assess the risk of rapid lung function decline in COPD patients at an early disease stage. This will allow to introduce personalized, risk-adapted therapy to improve COPD outcome in the long run. PROSA is exclusively funded by public funds provided by the European Research Council through an ERC Advanced Grant. Patient recruitment is ongoing; the PROSA results are expected to be available in 2028. TRIAL REGISTRATION: The PROSA Study has been prospectively registered at clinicaltrials.gov (register no. NCT06265623, dated 09.02.2024).

Validity and reliability of linear encoder muscle power testing in persons with Parkinson's disease.

OBJECTIVE: To investigate the construct validity ON medication and the reliability both ON and OFF medication of linear encoder muscle power testing in persons with Parkinson's disease (pwPD). DESIGN: A study using baseline data from one randomized controlled trial (study 1) and one cohort study (study 2). SETTING: University exercise lab. PARTICIPANTS: Study 1: 35 healthy controls and 70 pwPD. Study 2: 20 pwPD. INTERVENTION: Study 1: baseline data. Study 2: 4 chair rise tests (2 ON and 2 OFF medication), in a randomized order, separated by 4 to 16 days. MAIN MEASURES: Linear encoder data were collected from a chair rise test. Known groups validity and convergent validity (i.e., construct validity) were assessed by comparing peak power between pwPD and healthy controls and associations between peak power and functional performance (i.e., 6-Min Walk Test, Timed Up and Go Test, Six-Spot Step Test), respectively. Reliability was assessed as day-to-day variation and by intraclass correlation coefficients. RESULTS: Peak power was comparable between pwPD and healthy controls (-7.2%, p = 0.17), but lower in moderately impaired pwPD compared to mildly impaired pwPD (-27%, p < 0.01) and healthy controls (-23%, p < 0.01). Moderate to strong associations were observed between peak power and functional performance (r2 = 0.44-0.51). Day-to-day variation ON and OFF medication were 1.0 and 1.3 W/kg, respectively, while intraclass correlation coefficients were 0.95 (0.87;0.98) and 0.93 (0.82;0.97), respectively. CONCLUSION: Linear encoder muscle power testing shows inconsistent known groups validity, acceptable convergent validity ON medication, and excellent day-to-day reliability ON and OFF medication in pwPD.

Lack of effect of an in-line filter on cardiopulmonary exercise testing variables in healthy subjects.

PURPOSE: Pathogen transmission during cardio-pulmonary exercise testing (CPET) is caused by carrier aerosols generated during respiration. METHODS: Ten healthy volunteers (age range: 34 ± 15; 4 females) were recruited to see if the physiological reactions to ramp-incremental CPET on a cycle ergometer were affected using an in-line filter placed between the mouthpiece and the flow sensor. The tests were in random order with or without an in-line bacterial/viral spirometer filter. The work rate aligned, time interpolated 10 s bin data were compared throughout the exercise period. RESULTS: From rest to peak exercise, filter use increased only minute ventilation ([Formula: see text]E) (Δ[Formula: see text]E = 1.56 ± 0.70 L/min, P < 0.001) and tidal volume (VT) (ΔVT = 0.10 ± 0.11 L, P = 0.014). Over the entire test, the slope of the residuals for [Formula: see text]CO2 was positive (0.035 ± 0.041 (ΔL/L), P = 0.027). During a ramp-incremental CPET in healthy subjects, an in-line filter increased [Formula: see text]E and VT but not metabolic rate. CONCLUSION: In conclusion, using an in-line filter is feasible, does not affect appreciably the physiological variables, and may mitigate risk of aerosol dispersion during CPET.