Tag: peak oxygen consumption

Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores

Abstract:

Purpose: Myalgic encephalomyelitis, commonly referred to as chronic fatigue syndrome (ME/CFS), is a severe, disabling chronic disease and an objective assessment of prognosis is crucial to evaluate the efficacy of future drugs. Attempts are ongoing to find a biomarker to objectively assess the health status of (ME/CFS), patients. This study therefore aims to demonstrate that oxygen consumption is a biomarker of ME/CFS provides a method to classify patients diagnosed with ME/CFS based on their responses to the Short Form-36 (SF-36) questionnaire, which can predict oxygen consumption using cardiopulmonary exercise testing (CPET).

Methods: Two datasets were used in the study. The first contained SF-36 responses from 2,347 validated records of ME/CFS diagnosed participants, and an unsupervised machine learning model was developed to cluster the data. The second dataset was used as a validation set and included the cardiopulmonary exercise test (CPET) results of 239 participants diagnosed with ME/CFS. Participants from this dataset were grouped by peak oxygen consumption according to Weber’s classification. The SF-36 questionnaire was correctly completed by only 92 patients, who were clustered using the machine learning model. Two categorical variables were then entered into a contingency table: the cluster with values {0,1} and Weber classification {A, B, C, D} were assigned. Finally, the Chi-square test of independence was used to assess the statistical significance of the relationship between the two parameters.

Findings: The results indicate that the Weber classification is directly linked to the score on the SF-36 questionnaire. Furthermore, the 36-response matrix in the machine learning model was shown to give more reliable results than the subscale matrix (p – value < 0.05) for classifying patients with ME/CFS.

Implications: Low oxygen consumption on CPET can be considered a biomarker in patients with ME/CFS. Our analysis showed a close relationship between the cluster based on their SF-36 questionnaire score and the Weber classification, which was based on peak oxygen consumption during CPET. The dataset for the training model comprised raw responses from the SF-36 questionnaire, which is proven to better preserve the original information, thus improving the quality of the model.

Source: Lacasa M, Launois P, Prados F, Alegre J, Casas-Roma J. Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores. Clin Ther. 2023 Oct 4:S0149-2918(23)00352-1. doi: 10.1016/j.clinthera.2023.09.007. Epub ahead of print. PMID: 37802746. https://www.clinicaltherapeutics.com/article/S0149-2918(23)00352-1/fulltext (Full text)

Validity of 2-Day Cardiopulmonary Exercise Testing in Male Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Introduction: Among the main characteristics of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are effort intolerance along with a prolonged recovery from exercise and post-exertional exacerbation of ME/CFS symptoms. The gold standard for measuring the severity of physical activity intolerance is cardiopulmonary exercise testing (CPET). Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients. A consecutive day CPET protocol has shown a difference on day 2 in ME/CFS patients in contrast to sedentary controls. Because of the low number of male ME/CFS patients in the published literature, and because of a possible gender difference in the clinical phenotype, the aim of this study was to examine whether the response to a 2-day CPET protocol in a larger sample of male ME/CFS patients was similar to that observed in females.

Methods: From 77 male patients, 25 male ME/CFS patients fulfilled the criteria of a 2-day CPET protocol for analysis. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were made at maximal (peak) and ventilatory threshold (VT) intensities. Data were analysed using a paired t-test.

Results: Baseline characteristics of the group were as follows. Mean age was 44 (12) years, mean BMI was 27.1 (4.4) kg/m2. Median disease duration was 10 years (IQR 7 – 13). Heart rate, systolic and diastolic blood pressure at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between <0.005 and <0.0001). All patients experienced a deterioration of performance on CPET2 as measured by the predicted and actual VO2 and workload at peak exercise and ventilatory threshold.

Conclusion: This study confirms that male ME/CFS patients have a reduction in exercise capacity in response to a consecutive day CPET. These results are similar to published results in female ME/CFS populations.

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Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and meta-analysis

Abstract:

Background: Repeated maximal exercise separated by 24 hours may be useful in identifying possible objective markers in people with ME/CFS that are not present in healthy controls.

Aim: We aimed to synthesise studies in which the test-to-retest (24 hours) changes in VO2 and work rate have been compared between people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and controls.

Methods: Seven databases (CINAHL, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus and MEDLINE) were searched. Included studies were observational studies that assessed adults over the age of 18 years with a clinical diagnosis of ME/CFS compared to healthy controls. The methodological quality of included studies was assessed using the Systematic Appraisal of Quality for Observational Research critical appraisal framework. Data from included studies were synthesised using a random effects meta-analysis.

Results: The pooled mean decrease in peak work rate (five studies), measured at retest, was greater in ME/CFS by −8.55 (95% CI −15.38 to –1.72) W. The pooled mean decrease in work rate at anaerobic threshold (four studies) measured at retest was greater in ME/CFS by −21 (95%CI −38 to −4, tau = 9.8) W. The likelihood that a future study in a similar setting would report a difference in work rate at anaerobic threshold which would exceed a minimal clinically important difference (10 W) is 78% (95% CI 40%–91%).

Conclusion: Synthesised data indicate that people with ME/CFS demonstrate a clinically significant test–retest reduction in work rate at the anaerobic threshold when compared to apparently healthy controls.

Source: John Derek Franklin & Michael Graham (2022) Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review and meta-analysis, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2108628  https://www.tandfonline.com/doi/full/10.1080/21641846.2022.2108628 (Full text)

Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study

Abstract:

Background: Fatigue is the most prevalent and debilitating long COVID symptom, however risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long COVID fatigue and explored its possible pathophysiology.

Methods: Nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long COVID fatigue.

Results: Total of 141 individuals were included. Mean age was 47 (SD 13) years; 115 (82%) were recovering from mild COVID-19. Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long COVID fatigue. They had significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness and long COVID symptoms, and of physical limitation in daily activities. Individuals with fatigue had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53), p=0.038] and oxygen consumption per Kg [27.69 (7.52) vs 30.71 (7.52), p=0.036] at peak exercise. The two independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (odds ratio [OR] 0.79 per 10 beats/minute, 95% confidence interval [CI] 0.65-0.96, p=0.019); and long COVID memory impairment (OR 3.76, 95% CI 1.57-9.01, p=0.003).

Conclusions: Long COVID fatigue may be related to autonomic dysfunction, impaired cognition and decreased mood. This may suggest a limbic-vagal pathophysiology. Clinical Trial registration: NCT04851561.

Source: Margalit I, Yelin D, Sagi M, Rahat MM, Sheena L, Mizrahi N, Gordin Y, Agmon H, Epstein NK, Atamna A, Tishler O, Daitch V, Babich T, Abecasis D, Yarom Y, Kazum S, Shitenberg D, Baltaxe E, Elkana O, Shapira-Lichter I, Leibovici L, Yahav D. Risk factors and multidimensional assessment of long COVID fatigue: a nested case-control study. Clin Infect Dis. 2022 Apr 11:ciac283. doi: 10.1093/cid/ciac283. Epub ahead of print. PMID: 35403679.  https://pubmed.ncbi.nlm.nih.gov/35403679/

Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post–Coronavirus Disease

Abstract:

Objectives: The authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Background: Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom.

Methods: The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO2), slope of minute ventilation to CO2 production (VE/VCO2 slope), and end tidal pressure of CO2 (PetCO2) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing.

Results: Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO2 averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO2). VE/VCO2 slope was 30 ± 7. PetCO2 at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO2 <80% predicted. All patients with peak VO2 <80% had a circulatory limitation to exercise. Fifteen of 17 patients with normal peak VO2 had ventilatory abnormalities including peak respiratory rate >55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO2 (n = 17), and/or hypocapnia PetCO2 <35 (n = 25). Nineteen patients (46%) met criteria for ME/CFS.

Conclusions: Circulatory impairment, abnormal ventilatory pattern, and ME/CFS are common in patients with PASC. The dysfunctional breathing, resting hypocapnia, and ME/CFS may contribute to symptoms. CPET is a valuable tool to assess these patients.

Source: Mancini DM, Brunjes DL, Lala A, Trivieri MG, Contreras JP, Natelson BH. Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease. JACC Heart Fail. 2021 Dec;9(12):927-937. doi: 10.1016/j.jchf.2021.10.002. PMID: 34857177; PMCID: PMC8629098. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629098/ (Full text)

Persistent Exertional Intolerance After COVID-19

Abstract:

Background: Some patients with COVID-19 who have recovered from the acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that often is unexplained by conventional investigative studies.

Research question: What is the pathophysiologic mechanism of exercise intolerance that underlies the post-COVID-19 long-haul syndrome after COVID-19 in patients without cardiopulmonary disease?

Study design and methods: This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 patients who recovered from COVID-19 and were without cardiopulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results with those from 10 age- and sex-matched control participants. These data then were used to define potential reasons for exertional limitation in the cohort of patients who had recovered from COVID-19.

Results: The patients who had recovered from COVID-19 exhibited markedly reduced peak exercise aerobic capacity (oxygen consumption [VO2]) compared with control participants (70 ± 11% predicted vs 131 ± 45% predicted; P < .0001). This reduction in peak VO2 was associated with impaired systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen content difference to arterial oxygen content ratio) compared with control participants (0.49 ± 0.1 vs 0.78 ± 0.1; P < .0001), despite a preserved peak cardiac index (7.8 ± 3.1 L/min vs 8.4±2.3 L/min; P > .05). Additionally, patients who had recovered from COVID-19 demonstrated greater ventilatory inefficiency (ie, abnormal ventilatory efficiency [VE/VCO2] slope: 35 ± 5 vs 27 ± 5; P = .01) compared with control participants without an increase in dead space ventilation.

Interpretation: Patients who have recovered from COVID-19 without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit, along with an exaggerated hyperventilatory response during exercise.

Source: Singh I, Joseph P, Heerdt PM, Cullinan M, Lutchmansingh DD, Gulati M, Possick JD, Systrom DM, Waxman AB. Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing. Chest. 2021 Aug 11:S0012-3692(21)03635-7. doi: 10.1016/j.chest.2021.08.010. Epub ahead of print. PMID: 34389297; PMCID: PMC8354807. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354807/  (Full text)

Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol

Abstract:

(1) Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS )patients, using the gold standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls. No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfill the ME/CFS criteria in a male population and hypothesized a different pattern of response would be present during the 2nd day CPET.

(2) Methods: We compared 25 male patients with ICF who had completed a 2-day CPET protocol to an age-/gender-matched group of 26 male ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities.

(3) Results: Baseline characteristics for both groups were similar for age, body mass index (BMI), body surface area, (BSA), and disease duration. A significant difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs. zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001). ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload.

(4) Conclusion: This study confirms that male ME/CFS patients have a reduction in exercise capacity in response to a second-day CPET. These results are similar to published results in male ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls.

Source: van Campen CLMC, Visser FC. Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol. Healthcare (Basel). 2021 Jun 5;9(6):683. doi: 10.3390/healthcare9060683. PMID: 34198946. https://pubmed.ncbi.nlm.nih.gov/34198946/

Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol

Abstract:

Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients, using the golden standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls. No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfil the ME/CFS criteria in a male population and hypothesized a different pattern of response would be present during the 2nd day CPET.

Methods: Fifty-one female patients with ICF completed a 2-day CPET protocol and were compared to an age/sex-matched group of 50 female ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities.

Results: Baseline characteristics for both groups were similar for age, BMI, BSA, and disease duration. A significance difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001). ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload.

Conclusion: This study confirms that female ME/CFS patients have a reduction in exercise capacity in response to a second day CPET. These results are similar to published results in female ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls.

Source: van Campen CLMC, Visser FC. Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol. Healthcare (Basel). 2021 Jun 5;9(6):682. doi: 10.3390/healthcare9060682. PMID: 34198913. https://pubmed.ncbi.nlm.nih.gov/34198913/

Validation of the Severity of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Other Measures than History: Activity Bracelet, Cardiopulmonary Exercise Testing and a Validated Activity Questionnaire: SF-36

Abstract:

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe and disabling chronic disease. Grading patient’s symptom and disease severity for comparison and therapeutic decision-making is necessary. Clinical grading that depends on patient self-report is subject to inter-individual variability. Having more objective measures to grade and confirm clinical grading would be desirable. Therefore, the aim of this study was to validate the clinical severity grading that has been proposed by the authors of the ME International Consensus Criteria (ICC) using more standardized measures like questionnaires, and objective measures such as physical activity tracking and cardiopulmonary exercise testing.

Methods and results: The clinical database of a subspecialty ME/CFS clinic was searched for patients who had completed the SF 36 questionnaire, worn a SensewearTM armband for five days, and undergone a cardiopulmonary exercise test. Only patients who completed all three investigations within 3 months from each other—to improve the likelihood of stable disease—were included in the analysis. Two-hundred-eighty-nine patients were analyzed: 121 were graded as mild, 98 as moderate and 70 as having severe disease. The mean (SD) physical activity subscale of the SF-36 was 70 (11) for mild, 43 (8) for moderate and 15 (10) for severe ME/CFS patients. The mean (SD) number of steps per day was 8235 (1004) for mild, 5195 (1231) for moderate and 2031 (824) for severe disease. The mean (SD) percent predicted oxygen consumption at the ventilatory threshold was 47 (11)% for mild, 38 (7)% for moderate and 30 (7)% for severe disease. The percent peak oxygen consumption was 90 (14)% for mild, 64 (8)% for moderate and 48 (9)% for severe disease. All comparisons were p < 0.0001.

Conclusion: This study confirms the validity of the ICC severity grading. Grading assigned by clinicians on the basis of patient self-report created groups that differed significantly on measures of activity using the SF-36 physical function subscale and objective measures of steps per day and exercise capacity. There was variability in function within severity grading groups, so grading based on self-report can be strengthened by the use of these supplementary measures.

Source: van Campen, C.L.M.C.; Rowe, P.C.; Visser, F.C. Validation of the Severity of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Other Measures than History: Activity Bracelet, Cardiopulmonary Exercise Testing and a Validated Activity Questionnaire: SF-36. Healthcare 2020, 8, 273 https://www.mdpi.com/2227-9032/8/3/273/htm (Full text)

Physical Activity Measures in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Correlations Between Peak Oxygen Consumption, the Physical Functioning Scale of the SF-36 Questionnaire, and the Number of Steps From an Activity Meter

Abstract:

Background: Most studies to assess effort intolerance in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have used questionnaires. Few studies have compared questionnaires with objective measures like an actometer or an exercise test. This study compared three measures of physical activity in ME/CFS patients: the physical functioning scale (PFS) of the SF-36, the number of steps/day (Steps) using an actometer, and the %peak VO2 of a cardiopulmonary stress test.

Methods: Female ME/CFS patients were selected from a clinical database if the three types of measurements were available, and the interval between measurements was ≤ 3 months. Data from the three measures were compared by linear regression.

Results: In 99 female patients the three different measures were linearly, significantly, and positively correlated (PFS vs Steps, PFS vs %peak VO2 and Steps vs %peak VO2: all P < 0.001). Subgroup analysis showed that the relations between the three measures were not different in patients with versus without fibromyalgia and with versus without a maximal exercise effort (RER ≥ 1.1). In 20 patients re-evaluated for symptom worsening, the mean of all three measures was significantly lower (P < 0.0001), strengthening the observation of the relations between them. Despite the close correlation, we observed a large variation between the three measures in individual patients.

Conclusions: Given the large variation in ME/CFS patients, the use of only one type of measurement is inadequate. Integrating the three modalities may be useful for patient care by detecting overt discrepancies in activity and may inform studies that compare methods of improving exercise capacity.

Source: van Campen CMC, Rowe PC, Verheugt FWA, Visser FC. Physical activity measures in patients with myalgic encephalomyelitis/chronic fatigue syndrome: correlations between peak oxygen consumption, the physical functioning scale of the SF-36 questionnaire, and the number of steps from an activity meter. J Transl Med. 2020;18(1):228. Published 2020 Jun 8. doi:10.1186/s12967-020-02397-7 https://pubmed.ncbi.nlm.nih.gov/32513266/