The biggest 2-day exercise study - Blog ME/CFS Skeptic

[ME/CFS Skeptic]

"The largest study on repeated cardiopulmonary exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) could not find a strong effect. Declines during the second exercise test are also present in many healthy controls and do not correlate well with functional disability. These results question the validity of 2-day exercise testing as a diagnostic biomarker for ME/CFS or post-exertional malaise.

However, this may not be the end of the story. ME/CFS patients decline more than controls on most outcomes and the data on VO2 peak and workload at the ventilatory threshold are consistent with a small to moderate effect."

https://twitter.com/user/status/1836349009037808108

 

[ME/CFS Skeptic]

Twitter summary:

1) New blog post about the largest 2-day exercise study to date. Big thanks to the authors, Dr. Betsy Keller and colleagues, for uploading the data to http://mapmecfs.org so that others can analyse and explore it.

2) Here are the results for peak oxygen consumption (VO2) which showed the clearest effect.
On average if you randomly chose a participant from each group and compared their percentage change from test 1 to test 2, the ME/CFS value will be lower 64% of the time

3) The threshold that best separates the group is -9.3% (the dashed gray line) Approximately a third of ME/CFS patients and 10% of controls are under this line.

4) There is a clear difference but the large overlap suggests this outcome has difficulty in differentiating ME/CFS patients and controls. It does not have strong potential as a diagnostic biomarker.

5) In addition, percentage decreases from test 1 to test 2, show almost no correlation with the Bell Disability Scale.

6) This finding is also not in line with previous studies which only found a weak and nonsignificant effect for VO2 peak. The most consistent finding thus far was workload (how many wats you push) at the ventilatory threshold (VT).

7) In the Keller study, the data on Workload VT was complicated by 4 outliers. Depending on how you analyze the data, there might be a small to moderate effect.

8) This study tested more than 20 outcomes at 2 time points (Peak and VT) so we have to correct for multiple testing. Although the data suggests a small-moderate effect, it does not provide strong enough evidence to exclude that it happened by chance and random variation.

9) Overall, the results are mixed. While ME/CFS patients decline on most outcomes compared to controls, the effects seem smaller than initially assumed and there is a large overlap between patients and controls.

10 ) Many thanks to forestglip on the Science for ME forum whose thoughtful analysis was very helpful in understanding the Keller et al. dataset. You can read their comments and analysis here:
https://www.s4me.info/threads/cardi...d-oxygen-consumption-keller-et-al-2024.39219/

11) The following dataset was used from http://mapmecfs.org: Keller et al. Cardiopulmonary and metabolic responses during a 2-day CPET in ME/CFS. Last updated: September 12, 2024, 4:29 PM (UTC+02:00).

 

[ME/CFS Skeptic]

The study discussed is this one:
Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations - PubMed (nih.gov)

It has its own thread here:
Cardiopulmonary and metabolic responses during a 2-day CPET in [ME/CFS]: translating reduced oxygen consumption [...], Keller et al, 2024 | Science for ME (s4me.info)

But because the discussion and analysis had become so long and complex, someone suggested I post this summary in a separate thread.

 

[ME/CFS Skeptic]

Added a separate blog post that discusses problems in previous 2-day exercise studies.

https://twitter.com/user/status/1841462461829968173


Twitter summary:
1) New blog post where we look at previous studies on 2-day exercise testing in ME/CFS.

2) ME/CFS patients often have a significant decrease in their workload at the ventilatory threshold while no such decrease (or even an increase) is seen in controls. This is one of the most consistent findings in ME/CFS research.

3) The differences between test 1 and test 2 range from approximately -4 to -30 watts in absolute terms or -7% to -30% in relative terms.

4) Unfortunately, most of the 2-day exercise studies are very small and preliminary and several show various discrepancies (e.g. data that looks like an error).

 

[forestglip]

Added a separate blog post that discusses problems in previous 2-day exercise studies.

https://twitter.com/user/status/1841462461829968173


Twitter summary:
1) New blog post where we look at previous studies on 2-day exercise testing in ME/CFS.

2) ME/CFS patients often have a significant decrease in their workload at the ventilatory threshold while no such decrease (or even an increase) is seen in controls. This is one of the most consistent findings in ME/CFS research.

3) The differences between test 1 and test 2 range from approximately -4 to -30 watts in absolute terms or -7% to -30% in relative terms.

4) Unfortunately, most of the 2-day exercise studies are very small and preliminary and several show various discrepancies (e.g. data that looks like an error).

Nice! I was looking forward to this. Well written.