Tag: exercise

Lung diffusing capacities for nitric oxide and carbon monoxide at rest and post-walking in long COVID

Abstract:

Background: Approximately one-third of long coronavirus disease 2019 (long COVID) patients report breathlessness and fatigue even during activities of daily living. We hypothesised that abnormalities of combined diffusing capacity of the lung for nitric oxide (D LNO) and carbon monoxide (D LCO) at rest or after mild exercise are associated with breathlessness in patients with long COVID.

Methods: Single-breath combined D LNO and D LCO were measured at rest and immediately after a short bout of treadmill exercise simulating ordinary walking in 32 Caucasian patients with long COVID and dyspnoea at rest. 20 subjects served as a control group.

Results: At rest, combined D LNO, D LCO and alveolar volume (V A) were significantly lower in long COVID than in controls, with D LNO and D LCO being below the limits of normal in 69% and 41% of cases, respectively. Mean values of D LNO/V A and D LCO/V A in long COVID patients were less than controls, yet, in only 22% and 12% of long COVID patients were the values of D LNO/V A and D LCO/V A below the limits of normal. After treadmill exercise, D LNO, D LNO/D LCO, V A and heart rate increased significantly without differences between groups. D LNO remained below the limit of normal in 47% of long COVID patients.

Conclusion: These data suggest localised discrete loss of lung units in approximately half of long COVID patients, not completely explained by loss of V A or of alveolar-capillary recruitment during exercise.

Source: Barisione G, Brusasco V. Lung diffusing capacities for nitric oxide and carbon monoxide at rest and post-walking in long COVID. ERJ Open Res. 2023 Apr 17;9(2):00363-2022. doi: 10.1183/23120541.00363-2022. PMID: 37070120; PMCID: PMC9638122. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638122/ (Full text)

Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

To assess biobehavioral sex differences in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) utilizing a low burden exercise protocol, 22 females and 15 males with ME/CFS and 14 healthy controls underwent two six-min walk tests.

Fifteen daily assessments were scheduled for fatigue and function ratings and heart monitoring. Six-min walk tests were conducted on days 8 and 9. The ME/CFS group showed high self-report fatigue and impaired physical function, whereas healthy controls did not show fatigue or function abnormalities.

In patients, no significant post-exercise changes were found for heart rate variability (HRV); however, heart rate decreased in ME/CFS males from Day 14 to Day 15 (p = 0.046). Female patients showed increased fatigue (p = 0.006) after the initial walk test, but a downward slope (p = 0.008) in fatigue following the second walk test. Male patients showed a decrease in self-report work limitation in the days after exercise (p = 0.046). The healthy control group evidenced a decrease in HRV after the walk tests from Day 9-14 (p = 0.038).

This pilot study did not confirm hypotheses that females as compared to males would show slower exercise recovery on autonomic or self-report (e.g. fatigue) measures. A more exertion-sensitive test may be required to document prolonged post-exertional abnormalities in ME/CFS.

Trial registration: NCT NCT03331419.

Source: Friedberg F, Adamowicz JL, Bruckenthal P, Milazzo M, Ramjan S, Zhang X, Yang J. Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep. 2023 Apr 3;13(1):5442. doi: 10.1038/s41598-023-32581-w. PMID: 37012343. https://www.nature.com/articles/s41598-023-32581-w (Full text)

Two symptoms can accurately identify post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Post-exertional malaise (PEM) is the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) yet its diverse manifestations make it difficult to recognize. Brief instruments for detecting PEM are critical for clinical and scientific progress.

Objective: To develop a clinical prediction rule for PEM.

Method: 49 ME/CFS and 10 healthy, sedentary subjects recruited from the community completed two maximal cardiopulmonary exercise tests (CPETs) separated by 24 hours.

At five different times, subjects reported symptoms which were then classified into 19 categories. The frequency of symptom reports between groups at each time point was compared using Fisher’s exact test.

Receiver operating characteristics (ROC) analysis with area under the curve calculation was used to determine the number of different types of symptom reports that were sufficient to differentiate between ME/CFS and sedentary groups. The optimal number of symptoms was determined where sensitivity and specificity of the types of symptom reports were balanced.

Results: At all timepoints, a maximum of two symptoms was optimal to determine differences between groups. Only one symptom was necessary to optimally differentiate between groups at one week following the second CPET. Fatigue, cognitive dysfunction, lack of positive feelings/mood and decrease in function were consistent predictors of ME/CFS group membership across timepoints.

Conclusion: Inquiring about post-exertional cognitive dysfunction, decline in function, and lack of positive feelings/mood may help identify PEM quickly and accurately. These findings should be validated with a larger sample of patients.

Source: Davenport, Todd E; Chu, Lily; Stevens, Staci R; Stevens, Jared; Snell, Christopher R; Van Ness, J. Mark. Two symptoms can accurately identify post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome. Work. 1 Jan. 2023 : 1 – 15. https://content.iospress.com/articles/work/wor220554 (Full text)

Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study

Abstract:

Symptoms of long COVID-19 syndrome (long COVID-19) are reported by 80% of convalescents up to several months after contracting the coronavirus-19 disease (COVID-19). The study aimed to assess the frequency and correlations of long COVID symptoms with sex, disease severity, time since the onset of the disease, and exercise capacity in a population of Polish convalescents hospitalized as a part of a rehabilitation program after COVID-19.

The retrospective analysis was carried out based on medical records concerning reported symptoms, comorbidities, exercise capacity, fatigue and dyspnea on Borg’s scale, arterial oxygen saturation (SpO2), spirometric parameters, chest X-rays/computed tomography scans, systolic pulmonary artery pressure, and left ventricular ejection fraction. The study involved 471 patients aged 63.83 ± 9.93 years who had been hospitalized 191.32 ± 75.69 days from the onset of COVID-19, of which 269 (57.1%) were women. The most common symptoms were fatigue (99.57%), dyspnea (99.36%), and myalgia (97.03%). Women reported more symptoms than men (p < 0.001) and rated their fatigue as more severe (p = 0.021). Patients with depressed moods reported more physical symptoms than others (p < 0.001).

Most long COVID symptoms, including dyspnea, fatigue, and depressive symptoms, were found with the same frequency in patients 12-24 weeks and >24 weeks after recovery (p = 0.874, p = 0.400, and p = 0.320, respectively), regardless of acute COVID-19 severity (p = 0.240, p = 0.826, and p = 0.108, respectively). Dyspnea severity correlated with forced vital capacity (FVC) (r = -0.153, p = 0.005), and forced expiratory volume in one second (FEV1) (r = -0.142, p = 0.008). Fatigue severity correlated with impaired FVC and FEV1 (both r = -0.162, p = 0.003). Fatigue and dyspnea inversely correlated with the distance in a six-minute walk test (r = -0.497, p < 0.001, and r = -0.327, p < 0.001).

In conclusion, in our cohort, long COVID symptoms are more common in women. Dyspnea/fatigue and depressive symptoms do not tend to subside after an average six-month recovery period. The intensity of perceived fatigue may be exaggerated by the coexistence of neuropsychiatric disorders. Increased fatigue and dyspnea correlate with impaired spirometric parameters and significantly affects convalescents’ exercise capacity.

Source: Paradowska-Nowakowska E, Łoboda D, Gołba KS, Sarecka-Hujar B. Long COVID-19 Syndrome Severity According to Sex, Time from the Onset of the Disease, and Exercise Capacity-The Results of a Cross-Sectional Study. Life (Basel). 2023 Feb 11;13(2):508. doi: 10.3390/life13020508. PMID: 36836865; PMCID: PMC9961608. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961608/ (Full text)

Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown etiology or effective treatments. Post-exertional malaise (PEM) is a key symptom that distinguishes ME/CFS patients. Investigating changes in the urine metabolome between ME/CFS patients and healthy subjects following exertion may help us understand PEM.
The aim of this pilot study was to comprehensively characterize the urine metabolomes of eight female healthy sedentary control subjects and ten female ME/CFS patients in response to a maximal cardiopulmonary exercise test (CPET). Each subject provided urine samples at baseline and 24 h post-exercise. A total of 1403 metabolites were detected via LC-MS/MS by Metabolon® including amino acids, carbohydrates, lipids, nucleotides, cofactors and vitamins, xenobiotics, and unknown compounds.
Using a linear mixed effects model, pathway enrichment analysis, topology analysis, and correlations between urine and plasma metabolite levels, significant differences were discovered between controls and ME/CFS patients in many lipid (steroids, acyl carnitines and acyl glycines) and amino acid subpathways (cysteine, methionine, SAM, and taurine; leucine, isoleucine, and valine; polyamine; tryptophan; and urea cycle, arginine and proline).
Our most unanticipated discovery is the lack of changes in the urine metabolome of ME/CFS patients during recovery while significant changes are induced in controls after CPET, potentially demonstrating the lack of adaptation to a severe stress in ME/CFS patients.
Source: Glass KA, Germain A, Huang YV, Hanson MR. Urine Metabolomics Exposes Anomalous Recovery after Maximal Exertion in Female ME/CFS Patients. International Journal of Molecular Sciences. 2023; 24(4):3685. https://doi.org/10.3390/ijms24043685 https://www.mdpi.com/1422-0067/24/4/3685 (Full text available as PDF file)

Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls.

Methods: Six female patients with ME/CFS and six age, BMI and sex matched controls underwent 23Na-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content.

Results: Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R2 = 0.3832).

Conclusion: Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.

Source: Petter E, Scheibenbogen C, Linz P, Stehning C, Wirth K, Kuehne T, Kelm M. Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Transl Med. 2022 Dec 9;20(1):580. doi: 10.1186/s12967-022-03616-z. PMID: 36494667. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03616-z (Full text)

Impaired pulmonary and muscle function during moderate exercise in female patients recovered from SARS-CoV-2

Abstract:

This study aimed to assess pulmonary and muscle dysfunction by analyzing the slow component of oxygen uptake (VO2SC), and mechanical and ventilatory efficiency in adult women recovered from the severe acute respiratory syndrome coronavirus type II (SARS-CoV-2) during a constant load test. 32 women (N = 17 patients with SARS-CoV-2; N = 15 control group) performed two cardiopulmonary exercise tests (CPX) on a cycle ergometer.

In the first test, the participants performed incremental CPX until extenuation. In the second test the participants performed a 10-min CPX at a constant load intensity (watts) corresponding to the first ventilatory threshold. There was a 48-72 h rest period between the two tests. There was a significant increase in the VO2SC in the patients recovered from SARS-CoV-2 (160.4 ± 60 mL min-1) in comparison with the healthy participants (59.6 ± 65 mL min-1) (P < 0.001).

Mechanical efficiency significantly decreased in patients recovered from SARS-CoV-2 compared to the control group (P = 0.04). Ventilatory inefficiency significantly increased in the patients recovered from SARS-CoV-2 compared with the control group (P < 0.001). Adult women recovered from SARS-CoV-2 infection have important pulmonary and muscular dysfunction and fatigue which contributes to increasing the VO2SC and reducing mechanical and ventilatory efficiency during mild-moderate exercise at a constant load.

Source: Pleguezuelos E, Del Carmen A, Moreno E, Ortega P, Robles A, Serra-Prat M, Miravitlles M, Yebenes JC, Garnacho-Castaño MV. Impaired pulmonary and muscle function during moderate exercise in female patients recovered from SARS-CoV-2. Sci Rep. 2022 Dec 4;12(1):20943. doi: 10.1038/s41598-022-24941-9. PMID: 36464697.  https://www.nature.com/articles/s41598-022-24941-9 (Full text)

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation

Summary:

ME/CFS is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we used single-cell RNA-seq (scRNA-seq) to examine immune cells in cohorts of patients and controls. Post-exertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. Thus, to detect changes coincident with PEM, we also performed scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients displayed dysregulation of classical monocytes suggestive of inappropriate differentiation and migration to tissue. We were able to identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlated with metrics of disease severity. Comparing the transcriptome at baseline and post-exercise challenge, we discovered patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation following exercise.

Highlights ME/CFS is a debilitating disease with unknown causes. Here, we provide, for the first time, an extensive single cell resolution dataset detailing the gene expression programs of circulating immune cells of ME/CFS cases at baseline and after symptom provocation. We were able to detect robust dysregulation in certain immune cells from patients, with dysregulation of classical monocytes manifesting the strongest signal. Indeed, the fraction of aberrant monocytes in ME/CFS patients correlated with the degree of disease severity. Surprisingly, platelet transcriptomes were also altered in ME/CFS, and they were the only component of the immune system that showed large-scale changes following symptom provocation.

Source: Faraz Ahmed, Luyen Tien Vu, Hongya Zhu, David Shing Huk Iu, Elizabeth A. Fogarty, Yeonui Kwak, Weizhong Chen, Carl J. Franconi, Paul R. Munn, Susan M. Levine, Jared Stevens, Xiangling Mao, Dikoma C. Shungu, Geoffrey E. Moore, Betsy A. Keller, Maureen R. Hanson, Jennifer K. Grenier, Andrew Grimson. Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation. bioRxiv 2022.10.13.512091; doi: https://doi.org/10.1101/2022.10.13.512091 https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(23)00602-X (Full text)

What Primary Care Practitioners Need to Know about the New NICE Guideline for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults

Abstract:

The new NICE guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), published in October 2021, makes significant changes in treatment recommendations. It acknowledges the complexity of this chronic medical condition, which always impacts quality of life and can be profoundly disabling, recognising the prejudice and stigma that people with ME/CFS often experience in the absence of any specific diagnostic test.

The guideline outlines steps for accurate diagnosis, recognising post-exertional malaise as a core symptom; importantly, ME/CFS can now be diagnosed after just 3 months in a bid to improve long-term health outcomes. It recommends the need for individual, tailored management by a multi-disciplinary team, ensuring that the wellbeing of the individual is paramount. The guideline makes clear that any programme based on fixed incremental increases in physical activity or exercise, for example graded exercise therapy (GET), should not be offered as a treatment for ME/CFS and emphasises that cognitive behavioural therapy (CBT) should only be offered as a supportive intervention.

Because of the rigorous methodology required by NICE Committee review and the inclusion of the testimony of people with lived experience as committee members, this guideline will influence the future diagnosis and management of ME/CFS in the UK and beyond.

Source:  Kingdon, C.C.; Lowe, A.; Shepherd, C.; Nacul, L. What Primary Care Practitioners Need to Know about the New NICE Guideline for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults . Preprints 2022, 2022110016 (doi: 10.20944/preprints202211.0016.v1).  https://www.preprints.org/manuscript/202211.0016/v1 (Full text available as PDF file)

Bias in Exercise Trials for ME/CFS: the Importance of Objective Outcomes and Long-term Follow-up

Sharpe and colleagues recommend that patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) be offered cognitive behavior therapy (CBT) and graded exercise therapy (GET)1, advice that contrasts with recent NICE guidance on ME/CFS.2 The authors argue that “there are many randomized trials indicating the safety and efficacy of these treatments.”1

All of these trials, however, were nonblinded and relied on subjective symptom questionnaires as their main outcomes, a combination that creates a high risk of response bias. Treatment manuals used in these trials included explicit encouragements to raise patients’ expectations of GET and CBT. One patient booklet, for example, informed patients: “You will experience a snowballing effect as increasing fitness leads to increasing confidence in your ability. You will have conquered CFS by your own effort and you will be back in control of your body again.”3 These encouragements were not provided to participants in the control group and might have influenced how patients rated their health. In contrast to what Sharpe and colleagues claim, measuring the expectations of patients before the trial begins, does not address how therapists might have influenced symptom reporting during the trial.

There are further arguments that suggest these trials might have measured response bias rather than improvements in health. There were, for example, no clinically significant differences on objective outcome measures that are less prone to response bias such as employment figures, activity levels, or fitness tests.3 In addition, at long-term follow-up, the control group seemed to perform just as well as participants who received GET or CBT. This could not be explained by additional treatment received after the trial ended.4 These findings are difficult to interpret if patients did indeed rehabilitate successfully following GET or CBT. It is unfortunate that the authors, who were primary researchers in many of these trials, do not address these concerns.

Lastly, Sharpe and colleagues argue that “harm reported from patient community surveys reflects poorly implemented therapy.”1 Patient surveys, however, indicate that ME/CFS patients report harm of GET even if prescribed by a specialist or physiotherapist.5 The authors have previously been challenged for misrepresenting the findings of these surveys.5 Post-exertional malaise or a marked worsening of symptoms when patients exceed their energy limit, is a characteristic feature of ME/CFS.2 There are therefore reasonable safety concerns about treatments such as GET and CBT that try to push patients to exceed their limits.

Read the full article HERE.

Source: Tack, M. Bias in Exercise Trials for ME/CFS: the Importance of Objective Outcomes and Long-term Follow-up. J GEN INTERN MED 37, 3193 (2022). https://doi.org/10.1007/s11606-022-07704-0  (Full text)