Overall it covers a lot of ground and is fairly easy to read, it was obviously written with input from a patient.
I do have concerns about the Common Co-morbidity percentages, and there are lots of other questionable speculative bits and bobs, like the discussion of mast cell activation.
The section on CPET studies is also contains major errors, which I will explain:
There are three main observations obtained from the CPET studies. First, patients with ME/CFS display low VO2 at
anaerobic threshold and peak output. This means that there is impairment in the exchange of air in patients with ME/CFS.
Lastly, there is a decreased ventilatory response in patients with ME/CFS. This results in less air exchange, poor oxygenation, respiratory muscle fatigue, chemosensitivity of the tissues, and CO2 retention...
That is simply wrong.
Whoever wrote that doesn't understand the CPET findings and what the ventilatory threshold actually is. (Of course, it doesn't help when exercise physiologists don't understand it or don't explain it well either)
It is not a pulmonary limitation. Patients in general do not have decreased ventilatory responses - and there is little evidence of hypo or hyper ventilation behaviour in a majority of patients.
I have previously explained some details on:
https://me-pedia.org/wiki/Two-day_cardiopulmonary_exercise_test
But further elaboration: it has been found that the power output at the first ventilatory threshold is decreased on the second CPET, when repeated 24 hours later. This means there is
increased gas exchange at a lower level of performance.
Why does this happen?
The first point to note that the first ventilatory threshold is an artefact of the requirement for participants to slowly increase their power output on a treadmill or bicycle. There is no clear threshold during typical voluntary exercise.
A key consequence of the ramping of power output means that cortical effort slowly increases, with corresponding increase in recruitment of motor units (which in turn stimulate many muscle fibres) in the legs.
The first ventilatory threshold otherwise known as the gas exchange threshold is the point at which carbon dioxide output (VCO2) and oxygen consumption no longer increase linearly with power output.
This is not driven by any sort of limitation in the lungs. Participants will not feel out of breath at this threshold, though they will note they can no longer voluntarily control their breathing rate.
As motor units are driven harder, this changes the balance between aerobic and anerobic metabolism in the muscle fibres (which in turn is due to O2 diffusion kinetics vs level of neural drive). Leading to power limits of currently driven motor units (and fatigue). Requiring recruitment of higher threshold motor units, which in turn have lower capitalization density and longer capillary distances leading to slower O2 kinetics. Hence an even greater shift in the balance between aerobic and anerobic metabolism. This feedback loop leads to the non-linearity typically observed on the total ventilation vs oxygen consumption and carbon dioxide output graphs.
Persistence of anerobic metabolism leads to stimulation of Type III/IV muscle afferents which in turn leads to lower motor cortex excitability (
this is the main component of "central fatigue"). However the ventilatory drive is proportional to the upstream drive of the motor cortex and supplementary motor area - and it is this upstream drive that provides the perception of effort, as well as the stimulus for ventilatory drive.
What does this mean in practise? It means the primary effect of central fatigue is to *increase* the ventilatory drive for a given level of force output. This is normally very useful, for it means more oxygen will be supplied to the body for a given amount of exercise. So on the contrary to the claim that ventilatory response is decreased, it is actually increased during demanding exercise!
What does this indicate about the pathology of ME/CFS patients? It means there was/is stimulation of peripheral afferents that has led to central fatigue that is impeding performance on the second of the two CPETs (or at the very least, heightened sensitivity of these specific pathways).
