Tag: aerobic capacity

Exercise capacity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) treated with long-term pyridostigmine

Abstract:

Background: The pathophysiology underlying exertional intolerance in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains poorly understood. Previously, a single-dose of 60 mg pyridostigmine, a reversible acetylcholinesterase inhibitor, was found to acutely improve aerobic capacity (Joseph, P. et al. Chest 2022; 162:1116–26).

Aims: To build upon these prior findings, this study aimed to evaluate the long-term effect (>1 month) of pyridostigmine treatment on exercise intolerance in ME/CFS.

Methods: Between 2017-2022, patients who met the National Academy of Medicine criteria for ME/CFS, and had a minimum of two clinical, constant load, submaximal exercise tests (Shape Medical System, MN) were evaluated. Patients who began pyridostigmine after their baseline test were considered the treatment group. Measurements were taken at baseline (T0) and most recent follow-up (T1).

Results: At the follow-up evaluation (690 ± 547 days), the treatment group (n=37, dose range: 24-360mg/d) demonstrated a significant increase in oxygen uptake efficiency slope (OUES) (T0: 1.82 ± 0.56, T1: 1.98 ± 0.53; p=0.044) and pulmonary vascular capacitance (PVCAP) (T0: 486.19 ± 169.89 ml*mmHg, T1: 540.03 ± 170.59 ml*mmHg; p=0.040). These differences were not observed in the control group (n=16) OUES (T0: 1.62 ± 0.40, T1: 1.77 ± 0.47; p=0.268) and PVCAP (T0: 446.94 ± 144.80 ml*mmHg, T1: 465.81 ± 124.34 ml*mmHg; p=0.590).

Conclusion: Long-term treatment with pyridostigmine improved aerobic capacity in ME/CFS as demonstrated by an increase in OUES, mediated by improvements in central hemodynamics (PVCAP).

Source: Johanna Squires, Sarra Al-Zayer, David Systrom. Exercise capacity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) treated with long-term pyridostigmine. European Respiratory Journal Sep 2023, 62 (suppl 67) PA4639; DOI: 10.1183/13993003.congress-2023.PA4639 https://erj.ersjournals.com/content/62/suppl_67/PA4639

Proteomic profiling demonstrates inflammatory and endotheliopathy signatures associated with impaired cardiopulmonary exercise hemodynamic profile in Post Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome

Abstract:

Approximately 50% of patients who recover from the acute SARS-CoV-2 experience Post Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome. The pathophysiological hallmark of PASC is characterized by impaired system oxygen extraction (EO2) on invasive cardiopulmonary exercise test (iCPET). However, the mechanistic insights into impaired EO2 remain unclear.

We studied 21 consecutive iCPET in PASC patients with unexplained exertional intolerance. PASC patients were dichotomized into mildly reduced (EO2peak-mild) and severely reduced (EO2peak-severe) EO2 groups according to the median peak EO2 value. Proteomic profiling was performed on mixed venous blood plasma obtained at peak exercise during iCPET.

PASC patients as a group exhibited depressed peak exercise aerobic capacity (peak VO2; 85 ± 18 vs. 131 ± 45% predicted; p = 0.0002) with normal systemic oxygen delivery, DO2 (37 ± 9 vs. 42 ± 15 mL/kg/min; p = 0.43) and reduced EO2 (0.4 ± 0.1 vs. 0.8 ± 0.1; p < 0.0001). PASC patients with EO2peak-mild exhibited greater DO2 compared to those with EO2peak-severe [42.9 (34.2-41.2) vs. 32.1 (26.8-38.0) mL/kg/min; p = 0.01]. The proteins with increased expression in the EO2peak-severe group were involved in inflammatory and fibrotic processes. In the EO2peak-mild group, proteins associated with oxidative phosphorylation and glycogen metabolism were elevated.

In PASC patients with impaired EO2, there exist a spectrum of PASC phenotype related to differential aberrant protein expression and cardio-pulmonary physiologic response. PASC patients with EO2peak-severe exhibit a maladaptive physiologic and proteomic signature consistent with persistent inflammatory state and endothelial dysfunction, while in the EO2peak-mild group, there is enhanced expression of proteins involved in oxidative phosphorylation-mediated ATP synthesis along with an enhanced cardiopulmonary physiological response.

Source: Singh I, Leitner BP, Wang Y, Zhang H, Joseph P, Lutchmansingh DD, Gulati M, Possick JD, Damsky W, Hwa J, Heerdt PM, Chun HJ. Proteomic profiling demonstrates inflammatory and endotheliopathy signatures associated with impaired cardiopulmonary exercise hemodynamic profile in Post Acute Sequelae of SARS-CoV-2 infection (PASC) syndrome. Pulm Circ. 2023 Apr 1;13(2):e12220. doi: 10.1002/pul2.12220. PMID: 37091121; PMCID: PMC10113513. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113513/ (Full text)

Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study

Abstract:

Background: Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear.

Purpose: To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness.

Methods: As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent ([Formula: see text], [Formula: see text]), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges’ g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20-100% peak [Formula: see text]). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak [Formula: see text] (~1 ml/kg/min-1).

Results: Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20-100% peak [Formula: see text]) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for [Formula: see text], [Formula: see text] and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency, [Formula: see text], [Formula: see text], and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g., [Formula: see text]) were generally reflective of those seen throughout exercise (i.e., 20-100%).

Conclusion: Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.

Source: Cook DB, VanRiper S, Dougherty RJ, Lindheimer JB, Falvo MJ, Chen Y, Lin JS, Unger ER; MCAM Study Group. Cardiopulmonary, metabolic, and perceptual responses during exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Multi-site Clinical Assessment of ME/CFS (MCAM) sub-study. PLoS One. 2022 Mar 15;17(3):e0265315. doi: 10.1371/journal.pone.0265315. PMID: 35290404; PMCID: PMC8923458. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923458/  (Full text)

Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine if self-reported levels of physical activity and fatigue are related to peak oxygen uptake (VO(2peak)) and whether these relationships differ among the patient groups (rheumatoid arthritis [RA], polymyositis [PM], and chronic fatigue syndrome [CFS]).

DESIGN: Correlational investigation.

SETTING: Two ambulatory research clinics at the National Institutes of Health, Clinical Center, Bethesda, MD.

PARTICIPANTS: There were 9 patients with PM, 10 with RA, and 10 with CFS. All patients met case criteria for their respective diagnoses. METHODS/MAIN OUTCOME MEASUREMENTS: VO(2peak) during bicycle ergometry and self-reported fatigability, fatigue, and physical activity. VO(2peak) was used as the criterion measurement of physiological fatigue with which the self-reported variables were compared.

RESULTS: The Pearson r revealed that self-reported physical activity correlated with VO(2peak) (r = 61, P = .01). However, fatigability and fatigue did not correlate with VO(2peak). Linear regression analysis was performed to assess the effects of diagnosis group, self-reported activity level or fatigue, and their interaction. A trend in the data showed a distinctive relationship between fatigue/fatigability within the 3 groups. In addition, when controlling for group status, self-reported activity predicted aerobic capacity as measured by VO(2peak).

CONCLUSIONS: This study confirms that patients with chronic, but stable RA, PM, or CFS are fatigued and have significantly decreased aerobic capacity. Self-reports of physical activity predicted VO(2peak), and may be used as an indicator of activity-based aerobic capacity. Self-reports of fatigue, however, did not correlate with VO(2peak) and hence are assessing something other than an index of aerobic capacity, and provide additional information about patients’ perceptions, which will require further investigation.

 

Source: Weinstein AA, Drinkard BM, Diao G, Furst G, Dale JK, Straus SE, Gerber LH. Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome. PM R. 2009 Jul;1(7):620-8. doi: 10.1016/j.pmrj.2009.04.007. https://www.ncbi.nlm.nih.gov/pubmed/19627955