Did he have a source for this? Several studies in ME patients which featured controls, as well as some non-ME studies looking at a 2-day CPET, have found the opposite.
CFS Research Study with Lumbar Punct - Upcoming CFS study with Dr. Baraniuk at Georgetown University
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I'm paying the price today as I woke up with severe muscle aches and a worse than normal PEM hungover feeling. It was worth it though I got to meet some very nice people.
The event was 100% patients and caregivers, about 40 people from the Fibro Fight Club (who were hosting the event), the NOVA ME/CFS Support Group, and Bethesda ME/CFS Support Group.
He stated that in his own lab and studies they have found this, that even he himself did worse on the second day of a maximal 2-day CPET. He said that on a maximal CPET on the first day a person goes to their absolute limit and it is quite painful. I hope I'm paraphrasing this right but on the second day he said even a healthy person doesn't push themselves as hard.
It's my belief that even if healthy controls do slightly worse on the second day it's no where near as significant as the second day drop in PWME. I'm sure the Workwell Institute and others have data on this.
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I think this is a difference between maximal and submaximal then. On a maximal test, the results are not going to be valid if someone holds back - it simply isn't an option. If they stop before reaching the required Respiratory Exchange Rate (respiratory quotient), then it wasn't a maximal test at all.
In that case, he's doing it wrong. In the published Workwell studies there is a metric (forget what it's called) that shows that people were puting in maximal effort on the second day. And when they're made to push themselves to the max, controls reproduced their first day results.
Sorry @Valentijn and @Sidereal, he stated that even healthy people do worse on a 2-day maximal CPET. I've edited my post to correct this. Trust me I disagree with him as well.
@leokitten, any idea when he intends to publish those data?
Okay, then his explanation about people holding back on day 2 really doesn't make sense. Either RER (Respiratory Exchange Rate) exceeds 1.1, and it's a maximal CPET, or it doesn't hit 1.1 and it's not a maximal CPET. Patients or controls holding back on day 2 shouldn't be relevant at all, except to the extent that their results should be mentioned as having been discarded.
If you mean on the 2-day maximal CPET with healthy controls he didn't mention ever publishing this, I don't think he actually did a proper study to verify that it's true, he mentioned it as if he'd been seeing it anecdotally in his work. It could very well be that his protocol is indeed not the best.
He might not be properly instructing or encouraging people to exert maximal effort, especially if he's worried about the effects of PEM. I put everything I had into my single maximal CPET while at an activity level of 3 on the various ME scales, and my RER hit 1.23 - quite a bit higher than needed.
This happens frequently in research. I've seen it first hand many times. People using tests they don't quite know how to administer or interpret. Or getting research assistants to administer tests without proper training.
Bob
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@leokitten, thanku for the summary of the presentation. It sounds like an interesting research program. I'm pleased to hear that he's searching for biomarkers and is hopeful that he'll determine some.
@Jonathan Edwards I wanted to ask for your opinion on how plausible this theory is. Can autoantibodies (or any antibody for that matter) cross the BBB into the brain in significant enough quantities to cause disease if there isn't much BBB disruption? By what possible mechanism could such autoantibodies cause all the varied symptoms of ME/CFS?
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@Jonathan Edwards, while you're here, I've been meaning to ask you a question for a while... It's probably been discussed before but I can't remember... If ME/CFS turns out to be an autoimmune disease, have you any idea how long it might take to discover the specific autoantibodies, once researchers start looking? I.e. Would it be months, years, or decades? (Or does anyone else any insight into this?)
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Jonathan Edwards
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Yes, we know that autoantibodies can cross the BBB. They can cause a range of diseases, some where the target antigens are potassium channel related complexes in the brain. The levels of antibody in the brain are much lower than in other tissues but we have always known that there are some there. Younger seemed to be suggesting that B cells got into brain. That is certainly true for MS but, as I indicated, I don't think that would fit for ME.
I don't know what the mechanism for anti-brain antibodies causing ME would be but it would not be particularly surprising. In some of the rare anti-neuronal antibody diseases now recognised you can get a more or less complete wipe out of function without any focal neurological signs. You could have antibodies acting a bit like anaesthetics - just detuning all your brain signalling so that you would feel a bit like having a dreadful hangover - or maybe still being drunk. Autonomic control could go out of the window.
Jonathan Edwards
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Tricky question. I am not sure that it would matter that much though. In RA we know some of the autoantibodies but we do not know exactly which ones cause most of the inflammation. It would be nice to have something to measure but we might find a way to test for them that does not actually involve knowing what they recognise. That might seem strange but one possibility is that it matters less what they bind to than some other feature that makes them troublesome. It is all very complicated. Which is another way of saying I haven't a clue but the answer might turn up any time. It may have already turned up but not been confirmed.
Interesting analogy.
A lot of people talk about an altered level of consciousness in ME. Sometimes when I try to explain it, to indicate severity I equate it to the number of glasses of wine it feels like I've consumed. The difference is that unlike real alcohol, the more glasses it feels like I've had, the more aware I am that I've turned into a blithering idiot.
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I suppose ME/CFS could be a range of very similar autoimmune disorders (which have an overlap in symptoms), whereby various auto-antibodies target a range of auto-antigens involved in various aspects of cellular activity. Various auto-antibodies could have very similar effects, in that they don't cause observable abnormalities (in standard blood tests) but they disrupt cellular activity and metabolism enough to cause significant physical and cognitive incapacity.
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This is such a plausible theory and actually makes a great deal of sense, it really should get some much needed attention.
It's interesting after all the compelling results over the last few years from Norway indicating autoimmunity in ME, none of the big research groups (Lipkin/Hornig, Montoya, Davis/Kogelnik, Younger, etc.) have said they even want to spend some time/resources looking into this. Maybe it's because autoimmunity is not a specialty of any of these groups, but these days they should try to team up with experts in this field to bring in technologies/protocols/know-how to design experiments to discover what might be going on. If researchers at Vanderbilt Univ. and Univ. of Oklahoma could design experiments to find evidence of adrenergic receptor autoantibodies in POTS then the technologies and know-how must be there.
The issue I find with all the major group's research directions, while very important, laudable, and will increase our understanding of what this disease is and what it is not, is unfortunately I do not feel their research will yield answers that can result in effective treatments for many, many years to come. Viruses/pathogens, cytokines, neuroinflammation, genomics, these are all well and good but from what I've seen so far from the big groups they are very far away from getting to a stage where they have discovered something that can be targeted for treatment.
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