Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome

Background: Two consecutive cardiopulmonary exercise tests (CPETs) performed 24 hours apart are increasingly used to determine post-exertional malaise (PEM) and disability in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Declines in functional capacity on Day 2 reflect impaired recovery and PEM. However, reports have variably described a reduction in peak oxygen consumption (VO₂) and/or VO₂ at the anaerobic ventilatory threshold (VT). Given the inconsistent findings, we sought to replicate the studies by performing sequential 2-day CPETs in ME/CFS and age- and sex-matched sedentary controls.

Methods: Accordingly, maximal bicycle ergometer CPETs were performed on two consecutive days in 58 patients with ME/CFS (mean age 38.6 ± 9.6 years, Body Mass Index (BMI) 24.1 ± 3.3 kg/m², 11 men and 47 women) and 25 age-matched sedentary control (CON) subjects (age 38.2 ± 9.9 years, BMI 24.2 ± 3.4 kg/m², 5 men and 20 women). Peak VO₂ was reported as the highest 30-sec average; VT was selected as the nadir of the VE/VO₂ and P_ETCO₂ curves, and VE/VCO₂ as the slope throughout exercise.

Findings: For ME/CFS and CON subjects, there were no significant changes in Peak VO₂ between Day 1 and Day 2 studies (ME/CFS Day 1, 22.3 ± 5.4; Day 2, 22.5 ± 5.4 mL·kg^-1·min^-1; CON Day 1, 23.4 ± 3.5; Day 2, 22.8 ± 3.6 mL·kg^-1·min^-1; NS). Similarly, VO₂VT and VE/VCO₂ slopes were not significantly different between the ME/CFS patients and CON, and on Day 2, they did not show any differences within or between groups. Peak heart rate was significantly higher in CON versus ME/CFS. The level of perceived exertion was significantly greater at all levels of exercise on the Day 1 and Day 2 tests for ME/CFS patients versus CON.

Interpretation: Our data indicate that 2-day CPET provides exercise-related results that are the same in ME/CFS patients and CON subjects. ME/CFS patients have a greater perception of exertion throughout exercise and a lower maximum heart rate than CON. The data do not support using the 2-day CPET protocol to define PEM or disability.

Source: Mancini DM, Cook DB, Brunjes DL, Soto T, Blate M, Quan P, Yamazaki T, Norweg A, Natelson BH. Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome. Front Physiol. 2026 May 13;17:1816082. doi: 10.3389/fphys.2026.1816082. PMID: 42212259; PMCID: PMC13213420. https://pmc.ncbi.nlm.nih.gov/articles/PMC13213420/ (Full text)