Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Nelson et al. 2019

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1836-0

 

Interesting. So this is a new study on the 2-day exercise test procedure, although it is rather small (only 16 patients).

The Australian authors found a significant reduction in workload (WR) at the ventilatory threshold (VT a proxy for the anaerobic threshold) on the second-day exercise test in ME/CFS patients compared to healthy controls. There was no significant reduction on VO2 at ventilatory threshold or any other exercise measurement.

Previous studies have also found that this measure - WR at VT - is the outcome that most consistently shows a difference between ME/CFS patients and controls. In total 5 independent research teams have tested this outcome and all but one have found a significant result.

This study looked if this test could be used as a biomarker for ME/CFS. They found that a percentage decline of WR at VT of −6.3% had a sensitivity of 87.5% and a specificity of 90%. A decline of −9.8% showed a sensitivity of 68.8% but a specificity of 100%. So somewhere between those values, there's the potential of a biomarker.

The problem is that this study, like most of its predecessors, is rather small. We would probably need a study on 2-day CPET with more than 100 ME/CFS patients, to provide reliable evidence. Another problem is that all but one study compared ME/CFS patients to healthy controls instead of patients with other chronic illnesses. As far as I know, these exercise test measurements have been tested for reliability in patients with heart- or lung disease and there the values fluctuate little on repeated testing. But I don't think we know how patients with say fibromyalgia or Guld War Illness would perform on this procedure.

I hope that larger and better studies on the 2 day CPET-procedure are under the way. Wasn't the research team of Hansen at Cornell doing this?

 

This conclusion doesn’t make any sense to me.

Work rate (WR) at VT is physiological not determined by how much encouragement is given. The fact that verbal encouragement results in higher peak WR doesn’t have anything to do with when VT occurs. Patients have met criteria for maximal effort in all the studies done so far so I don’t see how they can conclude other studies had a premature cessation on day 2. If they were arguing they got a little higher peak WR because of their encouragement that would make sense, but it still has nothing to do with WR at VT.

 

One methodological concern:

They say they had a familiarisation day first where patients learned about the test and even pedalled a little on the exercycles.

Day 1 of the actual test was at least 24 hours later, which is a bit vague and leaves open the possibility that some patients may have been in PEM on day 1 of testing from the familiarisation (travel to and from clinic, plus cognitive exertion plus some physical exercise).

 

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I noticed that as well, but then thought given the day 1 results it didn’t look like PEM. I agree it is a concern though.

 

Yes, I was - and still am - confused about this, too.

It's a few days ago I read the study so may be misremembering but didn't they find their results, i.e. the difference between days 1 and 2, lower than in other studies? Which would be expected if some patients were already in mild PEM on day 1 and therefore already had a lowered performance then, before dropping further on day 2.

 

I have always thought this could be a problem. I read that people with ME are often appear deconditioned on day 1, but who is to say it is day1 unless they rest for 24 hours before the test? Everyone else who stays the same between days can be said to be tested from a fixed point but people with ME will not be able to do so well if they have been travelling for the test or even if they are excited.

This is a good explanation of why they did not get the same drop in this experiment.

 

Yes, seems strange. If they were referring to VO2Peak it would make much more sense. But I suspect the statement is a response to reviewer concerns who felt that the differences in reduction in WR at VT needed an explanation...

I participated in this study and I'm telling you that besides any effect of travel, the familiarisation did not require any significant exertion on the bike - literally just sitting on the bike and pedalling against little to no resistance for a few seconds (very low power output) will not cause PEM.

Note that the mean drop in WR at VT in this study was ~17%... My personal drop was a bit over 7%, which may give some insight into the AUC analyses, given the small sample size...

 

It is odd that people with POTS were excluded given that orthostatic intolerance is a key symptom of ME/CFS. The familiarization concept is odd given that many people with ME/CFS will be made worse by the exertion of attending the clinic let alone getting onto the bike and completing a survey. Workwell suggest 2 weeks of heavy rest pre-CPET. The persons doing the trial were relatively mild/moderate and NOT doing it for disability "proof" purposes hence the drop off in functional capacity may be expected to be less than that seen in people who are seeking to prove that they are disabled. Not care post test as per Workwell insisting that you do NOT drive yourself home. How, was the impact assessed participants have said it took 6 months to recover even with being really careful.

 

The idea of sitting on a bike pre warm up is pretty abhorent, do they not know that for people with ME/CFS sitting is an aerobic activity.

 

Workwell suggest 2 weeks of rest, no driving to the test.....etc

 

They do their best to get a proper reading and they acknowledge the problem which is rarer than we should expect, but I doubt if it is possible for us to do very much activity of any description before going over AT at least occasionally.

I don't mean it as a criticism of Workwell or the way the test is done, but having a CPET result on the first day which shows some deconditioning shouldn't be taken as proof that someone is deconditioned. They may have very good muscle tone - many people with ME do the minimum of exercise recommended for fitness - but still not achieve a good result because getting to the test involved sustained effort.

With other illnesses the test does give a snapshot of the patient's activity levels and fitness because they will have recovered their maximum ability from the day before.

 

It is not true that sitting on a bike is "an aerobic activity".

The fact that there was no difference between patients and controls on the first day suggests any modest pre-test activity was insignificant.

 

If you have POTS it is. But they excluded pwPOTS (?), which was sensible if you ask me for that very reason.

 

Yes, the whole point of sitting on the bike was to see if there were any major problems. Severe patients do not participate in studies like this.

The act of moving onto the bike might be vaguely aerobic, but the sitting is not, even if you have POTS.

 

Maybe they are testing for the wrong things in a subset. I've done a 2 Day CPET test. I started PEMing before I even reached the testing center, and was still PEMing on Day 1 of testing - all due to traveling. But I didn't feel it in my muscles, I felt it in cognitive decline and a weird poison feeling Ive seen other pwME talk about.

 

@Snow Leopard Maybe I see it differently because I'm severe, but I can pass my AT just by sitting long enough. Just proves why they were right to exclude severe people and POTS, though

 

On some days (in the past weeks more daily...) if I stand 10mins, my pulse is somewhere at 143.

 

How do you know? Have you measured your ventilation or intravenous lactate while doing such activities?

High pulse (in cases of POTS for example) is not the same as exceeding a ventilatory or anerobic threshold.

Impact post the initial followup was through regular phone calls, with patients simply stating how they are feeling (no questionnaires).