Cardiopulmonary and metabolic responses during a 2-day CPET in [ME/CFS]: translating reduced oxygen consumption [...], Keller et al, 2024

EndME · Aug 31, 2024 at 11:04 AM

forestglip said: ↑

The fact that so many people in both groups had increases in VO2 at VAT all the way up to 20% higher on day 2 (and a few even higher) makes me think there is a lot of natural day to day variation, and it would probably take at least more than a 20% decrease to have good specificity.
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Would be good for someone with a background in exercise physiology to weigh in on this. Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome writes

The 2-day CPET methodology is useful for assessing impaired recovery because CPET measures are readily reproduced in both healthy and diseased populations. Therefore, a failure to reproduce CPET measures on a subsequent test, despite peak effort on both tests, indicates a derangement of homeostasis.
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EndME said: ↑

Sure and there will be problems related to "cognitive function/cognitive PEM" that for example wouldn't be picked up, but at least for each individual there should be some consistency right? That is to say "are you feeling like you are experiencing more PEM on the first test vs second test" should tell us what this person is feeling to some degree. It could also help us understand whether the whole undertaking of going there, possibly by plane etc had a similarly exhausting effect as the 1st CPET or not.

I'm no statistician but surely there would be a way to analyse the data in a somewhat meaningful way (comparing average decline in pwME vs HC in workload at the ventilatory threshold and also looking at the average of "experience of PEM on 1st day vs 2nd day" seems unsuitable if people are interpreting PEM very differently and group differences would just arbirtraly average out such effects, but an analysis looking at 1 pwME vs 1 HC by taking to account the "experience of PEM on 1st day vs 2nd day" could possibly be sensible)?

It could also be helpful to know that we're getting useful data on HCs. Because unless you are using deconditioned controls, where muscle pain on the second day should be expected, you would expect HCs to feel good on both attemps right?

On a more philosophical note I am wondering about how sensible this argument is. These people are participating in this procedure essentially because they have described to be people that experience PEM in general (the problem here might lie that they have described to be experiencing PEM in general vs PEM following a CPET which this procedure hopes to somehow measure in some realted form) and because the procedure is supposedly supposed to measure exactly that (more precisely it measures the effects of physical exercise in the hopes of that somehow capturing something that is related to PEM). If the interpretation of what people are experiencing during the 2 different rounds is that different that it makes asking a question on their experience uninterpretable or doesn't result in usable data it appears to me one could have a dilemma i.e. "we believe this measures something related to PEM because this is what the people have said vs we can't ask them whether it measures something in relation to PEM because we cannot rely on their different interpretations of the PEM experience" how sensible is the procedure in the first place?

Essentially I’m not able to see how both statements below could make sense at the same time:
Person says he experiences PEM in day to day life-> Hope to measure effects of experiencing PEM via CPETs
but also
Cannot ask whether person experiences PEM at CPETs because interpretation of PEM is different for everyone
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I have had a look at “Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome” https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2018.00242/full which is a guideline for performing 2-day CPETs in ME/CFS by van Ness (the person who first published on this subject in ME/CFS) and others. The guideline is very much focused on “this test provokes PEM” and the authors state that “CPET also elicits a robust post-exertional symptom flare (termed, post-exertional malaise)”.

Unfortunately I didn't find any information on how this had been ensured or was somehow quantified (I may have simply missed it).

Other than that the authors do state the importance and give ways to ensure that patients are at their “usual rested levels” before the 1st CPET procedure, which if always adhered to would reduce my worries on people being exhausted more than usual going into the first test

To ascertain the magnitude of change in CPET2 due to CPET1, it is critical that the ME/CFS patient begin the test in a baseline state representative of the patient's well-rested capacity. Characteristics unique to ME/CFS patients require special pre-test preparations that should be addressed beginning as early as 2–3 weeks prior to a scheduled 2-day CPET. The objective is to minimize pre-fatigue and PEM in a patient who is preparing to travel in order to complete the 2-day CPET.

Pre-test Considerations

Factors such as travel to the test site, immediate pre-test (day of or even day before) paperwork that taxes cognitive function, and prolonged time in a common waiting area, even if seated, can all contribute to pre-test fatigue. Fatigue and PEM are exacerbated by physical, cognitive and emotional stressors (1), so every effort should be made to reduce such stressors where possible. Likewise, many ME/CFS patients experience hypersensitivity to light, noise, temperature, odors, and/or chemicals, so it is helpful to minimize environmental stimuli and maintain a generally low level of activity in the waiting area and testing environment.

Pretest directions/instructions should be in writing and given to the patient at least 1–2 weeks prior to arrival at a clinic. Included in these materials should be a clearly written pre-test checklist to assure that the patient adheres to pre-test preparation instructions (e.g., alcohol, caffeine, exercise and food restrictions prior to CPET, appropriate attire, etc.). Directions to the facility should include availability of disabled parking close to the building, and clear directions to the elevator or other lift assist as needed. Stairs (up and down) and long walks to the clinic should be avoided if possible as this will pre-fatigue the patient. It is reasonable to ask the patient prior to arrival if wheelchair assistance is indicated. Likewise, it is essential that the patient understands the importance of not becoming fatigued prior to the test, and plans travel to the test site with that in mind. When the test site is more than 1 h away, if feasible the patient should be encouraged to arrive the day before the scheduled test and spend the night locally. For some patients, 2 days of rest following air travel to a clinic may be necessary. It is essential that patients understand they should not drive a motor vehicle away from the clinic following either CPET, and plan accordingly. These recommendations may limit patient accessibility to testing, but should be considered to optimize quality of CPET data and patient safety.

Pre-test Forms/Questionnaires

Forms and questionnaires should be sent to the patient at least 2–3 weeks prior to a scheduled test. Completion of forms can be cognitively taxing for a person with ME/CFS and contribute to PEM, so sufficient time should be allowed for completion and return of forms to the clinic. In a clinic environment where a physician is present only part-time, prior arrangements are necessary to provide medical supervision during the 2-day CPET when testing a patient that meets criteria for high risk (7, 45). Similarly, sufficient time is necessary for the patient's physician to complete and return the referral form prior to testing the ME/CFS patient. Information provided to the patient should include explicit pretest instructions. Patients who experience cognitive impairment may be unable to process and respond quickly to copious or complex information, so providing simple, easily understood documentation helps improve adherence to pretest instructions. Paperwork that should be sent to the patient 2–3 weeks prior to a scheduled test may include the following:

Test-Day Considerations

-Seek to minimize time in the waiting area prior to preparations for a CPET. A place to recline or semi-recline is helpful for a waiting patient, or when reviewing or clarifying pretest paperwork and procedures with the patient.

-Provide water throughout testing, and following CPET2, electrolyte replacement beverages can be helpful. Many ME/CFS patients have orthostatic intolerance so maintaining hydration with fluid and electrolytes (e.g., coconut water, sport drink) following CPET2 is helpful for expediting recovery. There are a number of anecdotal reports of plasma volume or salt loading reducing recovery time. Patients may consider arranging with their physician for a prescription of 1 L of IV normal saline infusion following completion of the 2-day CPET. However, if possible, there should be no intervention between the two CPETs.
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forestglip · Aug 31, 2024 at 12:19 PM

EndME said: ↑

Would be good for someone with a background in exercise physiology to weigh in on this. Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome writes
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Later in the paper they say:

Test-retest measures of oxygen consumption and work that correspond with VAT are stable over time with the same test modality, and vary within about 7–12% in both healthy individuals (5, 6, 18, 28) and a number of other pathological conditions (21, 22).
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forestglip · Aug 31, 2024 at 3:15 PM

forestglip said: ↑

Looking at the charts above, it does look like most of the people who decreased more than 20% are ME/CFS (looks like about 11/13 people). Maybe these are the most severe. I'll have to check how Bell Activity Score correlates with the difference in days.
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Not a lot of correlation using Bell scale either. Lower scores indicate more severe disability.

BAS vs change in VO2 at VAT:

BAS vs change in workload at VAT:

Correlations (only MECFS):

Correlations (full cohort):

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Cardiopulmonary and metabolic responses during a 2-day CPET in [ME/CFS]: translating reduced oxygen consumption [...], Keller et al, 2024

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Cardiopulmonary and metabolic responses during a 2-day CPET in [ME/CFS]: translating reduced oxygen consumption [...], Keller et al, 2024

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