Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment

Betsy A Keller, John Luke Pryor, Ludovic Giloteaux, Betsy A Keller, John Luke Pryor, Ludovic Giloteaux

Abstract

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multi-system illness characterized, in part, by increased fatigue following minimal exertion, cognitive impairment, poor recovery to physical and other stressors, in addition to other symptoms. Unlike healthy subjects and other diseased populations who reproduce objective physiological measures during repeat cardiopulmonary exercise tests (CPETs), ME/CFS patients have been reported to fail to reproduce results in a second CPET performed one day after an initial CPET. If confirmed, a disparity between a first and second CPET could serve to identify individuals with ME/CFS, would be able to document their extent of disability, and could also provide a physiological basis for prescribing physical activity as well as a metric of functional impairment.

Methods: 22 subjects diagnosed with ME/CFS completed two repeat CPETs separated by 24 h. Measures of oxygen consumption (VO₂), heart rate (HR), minute ventilation (Ve), workload (Work), and respiratory exchange ratio (RER) were made at maximal (peak) and ventilatory threshold (VT) intensities. Data were analyzed using ANOVA and Wilcoxon's Signed-Rank Test (for RER).

Results: ME/CFS patients showed significant decreases from CPET1 to CPET2 in VO₂peak (13.8%), HRpeak (9 bpm), Ve peak (14.7%), and Work@peak (12.5%). Decreases in VT measures included VO₂@VT (15.8%), Ve@VT (7.4%), and Work@VT (21.3%). Peak RER was high (≥1.1) and did not differ between tests, indicating maximum effort by participants during both CPETs. If data from only a single CPET test is used, a standard classification of functional impairment based on VO₂peak or VO₂@VT results in over-estimation of functional ability for 50% of ME/CFS participants in this study.

Conclusion: ME/CFS participants were unable to reproduce most physiological measures at both maximal and ventilatory threshold intensities during a CPET performed 24 hours after a prior maximal exercise test. Our work confirms that repeated CPETs warrant consideration as a clinical indicator for diagnosing ME/CFS. Furthermore, if based on only one CPET, functional impairment classification will be mis-identified in many ME/CFS participants.

Figures

Figure 1
Figure 1
Changes in physiological and work variables from Test 1 to Test 2 at maximal intensity. Inset: Non-significant test differences for maximal respiratory exchange ratio showed that subjects achieved consistently high RER (>1.1) for Test 1 and Test 2, with maximum efforts on both tests (P = .157). Statistical significance is shown above bars with **P < 0.01 and *P < 0.05.
Figure 2
Figure 2
Changes in physiological and work variables from Test 1 to Test 2 at ventilatory threshold. Statistical significance is shown above bars with **P < 0.01 and *P < 0.05.
Figure 3
Figure 3
Individual changes in peak measures of VO2 (A), O2pulse (B), work (C) and Ve (D) from Test 1 to Test 2. Subjects’ whose VO2peak did not decrease during Test 2 showed a decrease in VO2@VT.
Figure 4
Figure 4
Individual changes in ventilatory threshold measures of VO2 (A), O2pulse (B), work (C) and Ve (D) from Test 1 to Test 2. Subjects’ whose VO2@VT did not decrease during Test 2 showed a decrease in VO2peak.

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