Cardiopulmonary, metabolic, and perceptual responses during exercise in ME/CFS: A Multi-site Clinical Assessment of ME/CFS sub-study (Cook et al 2022)

Pyrrhus

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Cardiopulmonary, metabolic, and perceptual responses during exercise in ME/CFS: A Multi-site Clinical Assessment of ME/CFS sub-study (Cook et al., 2022)
https://doi.org/10.1371/journal.pone.0265315

A study that provides more evidence of exercise intolerance in ME, and evidence that this exercise intolerance is not due to deconditioning.

But remember: exercise intolerance is NOT the same as PEM/exertion intolerance!

Abstract:
Background
Cardiopulmonary exercise testing has demonstrated clinical utility in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, to what extent exercise responses are independent of, or confounded by, aerobic fitness remains unclear.

Purpose
To characterize and compare exercise responses in ME/CFS and controls with and without matching for aerobic fitness.

Methods
As part of the Multi-site Clinical Assessment of ME/CFS (MCAM) study, 403 participants (n = 214 ME/CFS; n = 189 controls), across six ME/CFS clinics, completed ramped cycle ergometry to volitional exhaustion. Metabolic, heart rate (HR), and ratings of perceived exertion (RPE) were measured. Ventilatory equivalent (
,
), metrics of ventilatory efficiency, and chronotropic incompetence (CI) were calculated. Exercise variables were compared using Hedges’ g effect size with 95% confidence intervals. Differences in cardiopulmonary and perceptual features during exercise were analyzed using linear mixed effects models with repeated measures for relative exercise intensity (20–100% peak
). Subgroup analyses were conducted for 198 participants (99 ME/CFS; 99 controls) matched for age (±5 years) and peak
(~1 ml/kg/min-1).

Results
Ninety percent of tests (n = 194 ME/CFS, n = 169 controls) met standard criteria for peak effort. ME/CFS responses during exercise (20–100% peak
) were significantly lower for ventilation, breathing frequency, HR, measures of efficiency, and CI and significantly higher for
,
and RPE (p<0.05adjusted). For the fitness-matched subgroup, differences remained for breathing frequency,
,
, and RPE (p<0.05adjusted), and higher tidal volumes were identified for ME/CFS (p<0.05adjusted). Exercise responses at the gas exchange threshold, peak, and for measures of ventilatory efficiency (e.g.,
) were generally reflective of those seen throughout exercise (i.e., 20–100%).

Conclusion
Compared to fitness-matched controls, cardiopulmonary responses to exercise in ME/CFS are characterized by inefficient exercise ventilation and augmented perception of effort. These data highlight the importance of distinguishing confounding fitness effects to identify responses that may be more specifically associated with ME/CFS.
 

Pyrrhus

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Wishful

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I got a bit lost in the terminology; I don't have a feel for volumetric efficiency or gas exchange rates. Could the results be mainly caused by neurological dysfunction? By this I mean that if the signals going to the lungs and muscles, and returning from them (and other signals such as lactic acid) for feedback are not working properly, could this result in inefficiencies in air pumping and heart function? If a buildings HVAC system had glitchy sensors or processing elements, the results could look similar to a worn fan or clogged filter or ducting.

Since they're measuring hearth&lung function, it's easy to assume that any problems are mechanical, but the signal transmission and processing elements should be considered too.
 
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Since they're measuring hearth&lung function, it's easy to assume that any problems are mechanical, but the signal transmission and processing elements should be considered too.
was reading in this: which suggests any number of pulmonary breathing issue are tied to neurological conditions....not sure if these types of issues are at play in us...

https://vishwarajhospital.com/can-neurological-problems-cause-breathing-problems/

I feel like very little oxygen manifests...when I demand a bit more. So anything slightly aerobic is really hard to tolerate.
 

SlamDancin

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I get a extremely bad hypoxic feeling in my lungs if I jog for longer than like 20 seconds now. I’ve had it for half my life but it happens a little sooner now than I have full blown ME
 
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I get a extremely bad hypoxic feeling in my lungs if I jog for longer than like 20 seconds now

I'm up stairs...I Lived in a house with stairs for 17 years, unphased; I could go leaping on giant boulders, running up the creek bed.

Now its: can I get back up these stairs?

Altho actually more often, its how do I get down them? (the inflaming knee, announces itself when one walks down steps). The lungs, wondering what oxygen is, go off coming up...
 

halcyon

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What might improve ventilation?
I've been thinking a bit about the abnormal RBC hypothesis recently, and it seems like results like this would fit right in. If poorly deformable RBCs aren't able to pass through capillaries efficiently, and proper gas exchange in the lungs requires proper RBC flow through the pulmonary capillary beds, this hypothesis seems pretty relevant. Perhaps correcting the RBC deformability problem would then improve ventilation (in addition to muscle/brain perfusion, among other important things).

I've also wondered, perhaps someone knows, if any sort of exercise testing has been performed on ME patients while supine (if such a thing is even realistically possible). I don't know that vasoconstriction has much if any effect on capillaries, but I've wondered if vasoconstriction in arterioles might also result in poor movement of these bad RBCs into the microcirculation. In other words, in this hypothesis, if blood flow through microcirculation is bad to begin with, does the excessive sympathetic vasoconstriction that many of us suffer from when upright then just make the problem even worse? If so, would supine CPET testing show better numbers than upright?
 

Pyrrhus

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I've also wondered, perhaps someone knows, if any sort of exercise testing has been performed on ME patients while supine
I haven't seen such a study but I think that would be a rather important study to conduct, as it would look for exercise intolerance without the dramatically confounding effect of orthostatic intolerance.


does the excessive sympathetic vasoconstriction that many of us suffer from when upright then just make the problem even worse?
...I think you might mean dysautonomic (not sympathetic) lack of (not excessive) vasoconstriction:

Orthostatic Intolerance (OI) Basics: Dysautonomia of Blood Vessels, Low Blood Volume, and Baroreflexes
https://forums.phoenixrising.me/thr...sels-low-blood-volume-and-baroreflexes.86445/

Exercise Intolerance: Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS (Joseph et al., 2021)
https://forums.phoenixrising.me/thr...patients-with-me-cfs-joseph-et-al-2021.82907/
 

halcyon

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...I think you might mean dysautonomic (not sympathetic) lack of (not excessive) vasoconstriction:
Specifically what I was referring to was those of us with hyperadrenergic POTS, which causes a significant increase in blood pressure (i.e., vasoconstriction) and plasma norepinephrine. Also, and I'm not sure if/how these might map to orthostatic tachycardia positive ME cases, but there are several subtypes of POTS that have been described, based on their effect on blood flow. One of these types is known as low-flow POTS, which causes an increase in vasoconstrictive peptides, possibly a decrease in NO activity, and decreased blood flow due to increased arterial resistance (Stewart et al., 2006). Also, notably, patients with ME, regardless of the presence of dysautonomia, show evidence of reduced cerebral blood flow when upright (van Campen et al, 2020).

Exercise Intolerance: Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS (Joseph et al., 2021)
https://forums.phoenixrising.me/thr...patients-with-me-cfs-joseph-et-al-2021.82907/
In fact, your post in this thread illustrates what I'm trying to get at, and also might successfully link the abnormal NO hypothesis with the abnormal RBC hypothesis (and possibly the aforementioned low flow POTS issue). Basally, there may be poor blood flow through the microcirculation in ME due to abnormal RBCs. This could then be further compounded by excessive constriction due to dysautonomia (excessive sympathetic tone in vascular tissue) and endocrine factors (excessive constriction due to angiotensin/norepinephrine), as well as excessive constriction also due to inability to regulate microcirculation in energy-hungry tissues due to inadequate NO signaling.

Frequently (when I could still stand up), I would develop pretty obvious skin mottling in my lower limbs when upright. Typically this seems to be explained as excessive blood pooling in limbs due to poor constriction, but it seems like it could instead possibly be explained by this poor blood flow due to the issues above.
 
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Pyrrhus

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Specifically what I was referring to was those of us with hyperadrenergic POTS, which causes a significant increase in blood pressure (i.e., vasoconstriction) and plasma norepinephrine.
Ah yes, that is an important exception to keep in mind. Thanks for pointing that out.

Also, notably, patients with ME, regardless of the presence of dysautonomia, show evidence of reduced cerebral blood flow when upright (van Campen et al, 2020).
Yes, that is simply due to classic orthostatic intolerance, a dysautonomia without systemic hypotension or tachycardia.

Frequently (when I could still stand up), I would develop pretty obvious skin mottling in my lower limbs when upright. Typically this seems to be explained as excessive blood pooling in limbs due to poor constriction, but it seems like it could instead possibly be explained by this poor blood flow due to the issues above.
Restricted circulation in capillary beds would certainly lead to a number of symptoms, but I have trouble seeing how it could lead to blood pooling, as it would only affect microcirculation, not macrocirculation...

I hope this is clear. :)
 
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