Review Repeated maximal exercise tests of peak oxygen consumption in people with ME/CFS: a systematic review and meta-analysis, Franklin & Graham, 2022

John Derek Franklin, Michael Graham (School of Health and Life Sciences, Teesside University, Middlesbrough, UK)

Received 31 May 2022, Accepted 29 Jul 2022, Published online: 16 Aug 2022

Background

Repeated maximal exercise separated by 24 hours may be useful in identifying possible objective markers in people with ME/CFS that are not present in healthy controls.

Aim

We aimed to synthesise studies in which the test-to-retest (24 hours) changes in VO2 and work rate have been compared between people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and controls.

Methods

Seven databases (CINAHL, PubMed, PsycINFO, Web of Knowledge, Embase, Scopus and MEDLINE) were searched. Included studies were observational studies that assessed adults over the age of 18 years with a clinical diagnosis of ME/CFS compared to healthy controls. The methodological quality of included studies was assessed using the Systematic Appraisal of Quality for Observational Research critical appraisal framework. Data from included studies were synthesised using a random effects meta-analysis.

Results

The pooled mean decrease in peak work rate (five studies), measured at retest, was greater in ME/CFS by −8.55 (95% CI −15.38 to –1.72) W. The pooled mean decrease in work rate at anaerobic threshold (four studies) measured at retest was greater in ME/CFS by −21 (95%CI −38 to −4, tau = 9.8) W. The likelihood that a future study in a similar setting would report a difference in work rate at anaerobic threshold which would exceed a minimal clinically important difference (10 W) is 78% (95% CI 40%–91%).

Conclusion

Synthesised data indicate that people with ME/CFS demonstrate a clinically significant test–retest reduction in work rate at the anaerobic threshold when compared to apparently healthy controls.

Open access: https://www.tandfonline.com/doi/full/10.1080/21641846.2022.2108628

 

I think this is important work. There are many small studies out there - what we need is to see the big picture.

Key findings in test-retest:
21w (95%CI −38 to −4, tau = 9.8) pooled mean decrease in work rate at the anaerobic threshold (four studies).
8.5W (95% CI −15.38 to –1.72) pooled mean decrease in peak work rate (five studies).

The authors' analysis showed a statistically significant decline in retest workload at both the anaerobic threshold and peak exercise. The difference was larger at the anaerobic threshold.

They also looked at VO2 retest differences, but don't report any in the abstract, so presumably, there were none.

Broadly, this confirms what we have seen in several smaller studies.

Betsy Keller said at a conference a couple of years ago they now have a database of 200 people who'd been through their two-day maximal protocol. I'd love to see Workwell publish the results of all 200. Because all subjects were tested by the same team, presumably using an identical protocol, we should see results more clearly than from a meta-analysis like this.

This is such an important finding that we really need to nail it down, and this new study helps to do that.

 

I agree. My understanding is that the reason for most research studies requiring the 50% reduction in function is to give greater certainty of diagnosis. As you say, it might be valuable to study milder cases that won't have the confounding factors associated with long-term chronic illness. However, as @Peter Trewhitt said, it will be hard to study these people until we have more robust diagnostic tools.

 

A small but important typo: this should read “in peak work rate at anaerobic threshold”.

 

It makes more sense to report reduction as % workrate rather than wattage as the physical capacity of different people and groups, differs.

 

Hopefully someone will do a big study on these. I'd like to see the 2-day CPET developed into a biomarker.

 

I really don't want to see that. CPET's cause significant harm to the patient and could be making them permanently worse, inducing 2 crashes across 2 days is just pushing through and while its accurately diagnosed the disease and has been known about for decades its a terrible diagnosis because it makes the patient worse. They really need to start from the premise of not harming a patient first, doing a diagnostic that has a real chance of permanently hurting them is a bad idea especially considering we have a huge range of other safer tests that could be used. ME is one of these odd diseases we have about 50 different tests that identify the condition and yet none of them have made it out of research and into standard use, I would be horrified if the one that does is CPET.

 

I think you could probably, with some effort, round up enough people who were diagnosed in the past with 50% reduction in activity levels, but who have currently recovered to near normal levels of activity but still experience PEM. I'd definitely agree that it would be near impossible to separate people with fatigue for any number of reasons from those with very mild ME, but you could get around that by only looking at people who had more severe ME in the past.

 

I think Dr David Bell ran a small study looking at 10 recovered CFS patients (that is what he was calling it back then if I recall correctly). Every single one still had symptoms. Recovery was not total. Substantive reduction in symptoms is being called recovery far too often. I would not want to say these people no longer have either CFS nor ME. Yet they no longer fit the diagnostic criteria.

A similar argument arises from remissions. They had it before, they have it now, but they do not qualify in between. Is this real or an artefact of the diagnostic criteria for at least some of them?

PS I went with my current medical group because they have an exercise physiologist and I was hoping to organise a repeat CPET. Then my health declined and I decided it was too dangerous for now.

 

This is the case online as well. All or nearly all people who call themselves recovered still have symptoms. I would never call myself recovered unless I worked out every single day for a week and didn't get PEM.

 

^^at anaerobic threshold^^

From the abstract "The pooled mean decrease in peak work rate (five studies), measured at retest, was greater in ME/CFS by −8.55 (95% CI −15.38 to –1.72) W. The pooled mean decrease in work rate at anaerobic threshold (four studies) measured at retest was greater in ME/CFS by −21 (95%CI −38 to −4, tau = 9.8) W."

 

My understanding is that most (or all?) of these patients 'recovered' from PVFS within 5-6 years after onset.

I felt almost recovered after 6 years, but returning to work and exercising proved me wrong!

 

Found a nice little typo:

Elicit: To bring out
Illicit: Illegal
Or perhaps the authors are onto something. PEM should be a crime.