Cardiopulmonary Exercise Test Results Do Not Change Over Two Sequential Days in Patients with Chronic Fatigue Syndrome, 2026, Mancini, Natelson et al

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Cardiopulmonary Exercise Test Results Do Not Change Over Two Sequential Days in Patients with Chronic Fatigue Syndrome

Donna Mancini; Dane Cook; Danielle Brunjes; Tiffany Soto; Michelle Blate; Patrick Quan; Tadahiro Yamazaki; Anna Norweg; Benjamin Natelson

Background
Two consecutive cardiopulmonary exercise tests (CPETs) performed 24 hours apart is 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 performing sequential 2-day CPETs in ME/CFS and age and sex matched sedentary controls

Methods
Accordingly, we performed maximal bicycle ergometer CPETs on 2 consecutive days in 58 patients with ME/CFS (mean age 38.6 ± 9.6 yrs, 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 yrs, BMI 24.2 ± 3.4 kg/m2, 5 men, 20 women). Peak VO2 was reported as the highest 30-sec average, VT was selected as the nadir of the VE/VO2 and PETCO2 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 2 studies (ME/CFS Day 1: 22.3 ± 5.4; Day 2: 22.5 ± 5.4 ml/kg/min; CON: Day 1: 23.4 ± 3.5; Day 2: 22.8 ± 3.6 ml/kg/min; NS).

Similarly, VO2VT and VE/VCO2 slopes were not significantly different between the ME/CFS patients and CON and on day 2 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 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 in CON subjects. ME/CFS patients have 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.

Web | Frontiers in Physiology | Abstract only ahead of publication
 
I think this puts to rest the idea that the 2 day CPET is measuring some core feature of PEM. The small decreases in Vo2 max found in other studies were never large enough to convince me they weren't due to differences in time of day, sleep, food intake etc.. I do think it is plausible that the pain and discomfort experienced during PEM can have an impact on lowering Vo2 max. But in that case the test isn't providing any more useful information than simply asking if a patient is in pain.

The more interesting test for me is the invasive CPET run by Systrom. I seem to remember that an inability to increase heart rate might be related to the lower venous filling pressures in the heart. But it feels like we have been waiting a while for him to publish more data on the invasive test esp. v controls.
 
I find this hard to believe because I see next-day decline in performance (physical and mental) all the time in response to excessive exertion.

I suspect the CPET or this particular protocol is inadequate to measure the phenomenon. The reason may be that what counts is the cumulative exertion over the previous days, and a single CPET is just not "big enough" in comparison to everything else the patients are doing to shift the system in a meaningful manner. Also physical exertion is just one of several contributors. Exposure to sensory stimuli, mental effort and others also contribute.

This inability to maintain performance over days/weeks due to aggravation in fatigue and symptoms is not something that the average healthy person seems to experience, so it should be possible to measure it in some way.
 
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I did a VO2 max test recently, and to my suprise my VO2/kg was 'excellent', and my heart rate was 'normal'. So, I was congratulated for being very 'fit'.

It is very confusing to me, because I feel far from 'fit'. When I go for a walk and start too fast, I get out of breath and feel unwell (faint, and I need to stop until I have enough oxygen again to continue walking). When I cycle uphill, the same story applies. I can walk and cycle if I go slowly, but start to feel unwell if I have to 'push' myself.

How is this possible given the good VO2 max results? The healthcare provider seemed at a loss...

Any ideas?
 
We will soon need a fact sheet for significant negative results.


We now seem to have CPET and NASA lean test research papers showing no significant difference in objective measures between patients and controls, but the patients are more symptomatic in each study.


Does this add to the neural signaling hypothesis?
 
MinIreland said:
It is very confusing to me, because I feel far from 'fit'. When I go for a walk and start too fast, I get out of breath and feel unwell (faint, and I need to stop until I have enough oxygen again to continue walking).
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MinIreland said:
How is this possible given the good VO2 max results? The healthcare provider seemed at a loss...
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Because it's not connected to the things that are measured to assess "fitness"? We're ill, not unfit.

I don't know why it's surprising to doctors that ill people feel terrible doing elective exercise, without necessarily losing underlying capacity.
 
The paper said:
The level of perceived exertion was significantly greater at all levels of exercise on the Day 1 and 2 tests for ME/CFS patients versus CON.
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This puts a huge damper on the old "effort preference" / "the bastards just don't want to get better" nonsense. The ideologues keep asserting all sorts of nasty things about us, how we're lazy, how we don't try hard enough, how we "catastrophize" and as a result develop fear of doing things. Even though they always manage to recruit tens of thousands of people to do exactly what they said would work, and push through.

It also debunks, yet again, ye olde deconditioning model. Not that it ever had any weight, but it's still taken seriously somehow despite not being valid.

All bunk. All lies, invented to support their models and never backed by anything.

But of course it won't. The ideologues will use parts of this study as support that there is nothing physiologically wrong here, but will overlook how it debunks their own psychobehavioral model in the process. Because evidence is irrelevant in so-called evidence-based medicine, and because ultimately truth is a popularity contest, 'expert consensus' is just a version of "we voted on this and this is our opinion", which, when informed works very well, but when uninformed performs just as poorly as with the general public.

Although I would assume that performance would definitely drop if such a test regimen were held for longer, but there is zero chance we'll see this happening. This simply does not match my experience and that of most pwME, but my performance does indeed not necessarily drop from single consecutive days of moderate effort, and of course I would simply not be able to participate in such a study if I was in a functioning state low enough that it did. There is a natural recruitment selection effect similar to how most "mind-body" studies will naturally involve people willing to accept it.
 
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Probably the thing that's missing the most here is that pwME doing such a test will rest before and after and in-between every part of this, while healthy controls will live their normal lives, would even go to work, to the gym, do all sorts of every day life things before and after the test. This is something entirely missing from all those tests, and ultimately what they miss about the cumulative toll and the whole need to compensate in all other areas in order to perform on a relatively low effort, for healthy people, test.
 
rvallee said:
This puts a huge damper on the old "effort preference" / "the bastards just don't want to get better" nonsense. The ideologues keep asserting all sorts of nasty things about us, how we're lazy, how we don't try hard enough, how we "catastrophize" and as a result develop fear of doing things. Even though they always manage to recruit tens of thousands of people to do exactly what they said would work, and push through.

It also debunks, yet again, ye olde deconditioning model. Not that it ever had any weight, but it's still taken seriously somehow despite not being valid.
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Can you explain why the level of perceived exertion being consistently higher in the ME/CFS group is evidence against these things? Not sure I understand.
 
Yann04 said:
Can you explain why the level of perceived exertion being consistently higher in the ME/CFS group is evidence against these things? Not sure I understand.
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The participants did the exertion test despite it being high exertion, especially so for them compared to controls, and returned and did it again. The whole psychobehavioral model is that we avoid exertion for no good reason, but people keep participating in studies and trials like this despite knowing the risk of PEM and crashes and ultimately of a possible significant deterioration in functioning.

If their model were true they wouldn't even find participants for studies or trials. But of course the model never made sense, it's pure bigotry.
 
forestglip said:
Cardiopulmonary Exercise Test Results Do Not Change Over Two Sequential Days in Patients with Chronic Fatigue Syndrome

Donna Mancini; Dane Cook; Danielle Brunjes; Tiffany Soto; Michelle Blate; Patrick Quan; Tadahiro Yamazaki; Anna Norweg; Benjamin Natelson

Background
Two consecutive cardiopulmonary exercise tests (CPETs) performed 24 hours apart is 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 performing sequential 2-day CPETs in ME/CFS and age and sex matched sedentary controls

Methods
Accordingly, we performed maximal bicycle ergometer CPETs on 2 consecutive days in 58 patients with ME/CFS (mean age 38.6 ± 9.6 yrs, 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 yrs, BMI 24.2 ± 3.4 kg/m2, 5 men, 20 women). Peak VO2 was reported as the highest 30-sec average, VT was selected as the nadir of the VE/VO2 and PETCO2 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 2 studies (ME/CFS Day 1: 22.3 ± 5.4; Day 2: 22.5 ± 5.4 ml/kg/min; CON: Day 1: 23.4 ± 3.5; Day 2: 22.8 ± 3.6 ml/kg/min; NS).

Similarly, VO2VT and VE/VCO2 slopes were not significantly different between the ME/CFS patients and CON and on day 2 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 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 in CON subjects. ME/CFS patients have 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.

Web | Frontiers in Physiology | Abstract only ahead of publication
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Davenport does not seem to agree:
 

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Casterofspells said:
Davenport does not seem to agree:
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From tweet:
Even *reading the abstract*, there’s documentation of a glaring rookie mistake my students wouldn’t pass my class for making that is somehow allowed to be repeatedly committed by the same group of senior scientists and their enablers at CDC and NIH, which confounds the analysis.
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What's the point of saying there's a mistake without saying what the mistake is? Multiple people asked him, but he hasn't explained yet. For example, someone replied: "Oh, do tell. Spill the tea" and he said "I save most of the tea for the peer reviewed literature. "
 
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