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'CPET' -- An appropriate test for assessing/diagnosing ME/CFS?

Discussion in 'Diagnostic Guidelines and Laboratory Testing' started by alex3619, Jun 20, 2014.

  1. Valentijn

    Valentijn Activity Level: 3

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    So you admit that there is no research showing that healthy people on bed rest perform abnormally on the 2 day CPET. There is only your suspicion, which is contradictory to the existing evidence. Deconditioned controls and other healthy people do a bit better on day 2. There is no reason to suspect that healthy people with an even greater degree of deconditioning function in a diametrically different manner from patients with a lesser degree of deconditioning. While such a thing might be marginally possible, it's extremely dishonest to claim it as being proven.
    The relevant studies, which you obviously haven't read, clearly state that VO2max was achieved, meaning that objective indications of maximal effort were met. This includes heart rate near or at predicted max, respiratory quotient of 1.1 or higher, and a third one I can't remember. Maybe you should read the studies so that you can critique them without making embarrassingly inaccurate comments about them.
    I believe that non-max testing has been used for more seriously afflicted patients, and those who are unwilling to risk a long-term relapse. And there is probably research in the works to see how well non-maximal testing matches up with maximal testing, to see if it's feasible to test patients in that matter without half killing them in the process.

    But the research papers people are referring to here as proof of a pathological reaction to exertion were ones where VO2max was used in the typical and appropriate manner.
    Since when do patients have to reach a certain speed for the CPET to be valid?
     
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  2. Mij

    Mij Senior Member

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    I have been reading your posts :confused:

    "As I said the 2-day CPET test is abnormal in otherwise healthy bed rested people."

    "These is no way to tell who actually has ME/CFS (it's not even one thing anyway) and therefore no study could prove someone either does have it or doesn't have it."

    The video I posted indicates if an ME pt and healthy "bed rested" control were retested by 2 day CPET six months after regular activities, the comparisons would present ME pt worse and healthy "bed rested" control improved. It's a pretty good indicator imo in addition to other tests, of course.
     
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  3. kermit frogsquire

    kermit frogsquire *****

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    Has anyone actually read the Pacific Laboratories paper?

    www.hhs.gov/advcomcfs/.../presentation_10132010_snell-stevens.pdf (google for full URL)
    www.cfids-cab.org/MESA/VanNess.pdf

    To summarise - As I explained above, what they are measuring is not VO2max but "PeakVO2". To explain the difference - if a person gets on the treadmill and walks one step, then says, "that's it can't do any more", that would not be VO2max, but it would count as peak VO2.

    So, when the CFS patients in this article have a lower peak VO2 on day 2, is it really a valid measure, or are they just "doing less"?

    Well, look at the duration of test - on day 2 the CFS patients do a mean of 1 minute less - we have our answer - they are doing less.

    I want valid research more than anyone, but this kind of weak result is not it. All the Pacific Laboratories article proves is that CFS patients "do less" on day 2 of an exercise stress test! That is not a physiological measure of oxygen uptake, inflammation, or anything else other than people "doing less". Those patients are probably doing less because they are sore and tired, granted, but the finding of a drop in peak VO2 is nothing more than saying the patients are doing less because they are sore and tired. Bed rested patients get more inflammation from exercise than sedentary controls. The magnitude of inactivity is equal to the magnitude of inflammation (see below). The immunological changes in CFS in these studies are not much different to those seen from inactivity.

    VO2max as measured as a physiological limit is 100% valid, and many very sick CFS patients have this abnormality - it is present on day 1 of the test though.

    The Pacific Laboratories also like to quote the Association of American Cardiologists in their Power Point Presentation. What they fail to tell everyone is that the AAC would discount almost 50% of the tests as invalid because almost 50% of the patients failed to reach 85% of predicted maximum heart rate on day 2 of the test. (Mean 87%). Most exercise stress tests on CFS cohorts show 0% reaching 85% HR.

    Look, if anyone is interested, there are a whole bunch of articles on inflammation and inactivity.

    http://www.ncbi.nlm.nih.gov/pubmed/17307114 (full article availble - google)
    http://www.ncbi.nlm.nih.gov/pubmed/23825002
    http://www.ncbi.nlm.nih.gov/pubmed/23724888
    http://www.ncbi.nlm.nih.gov/pubmed/16033812
    cfids-cab.org/cfs-inform/Cytokines/white.etal05.pdf

    However, let me finish by saying this - in all these exercise studies the CFS patients can do a mean of 10 minutes on a CPET. Who are these people? I have never heard of a really sick CFS patient being able to do such exercise without feeling like death. I suspect the Pacific Labs patients were a horribly mixed cohort as usual.
     
    Last edited: Jun 23, 2014
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  4. Valentijn

    Valentijn Activity Level: 3

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    The difference between peak and max VO2 is largely semantic. If being very particular about definitions, the only difference is that VO2max requires certain objective indications of maximal effort to be met. In the 1st link (which is to slides rather than the paper), it's made clear that the requirements of maximal effort were met. While those levels fell slightly on the 2nd day for the ME patients, the corresponding drop in VO2peak was huge.

    The 2nd paper is a rather old one (for the topic), and indeed looks to be rather preliminary research which has led to the current research.

    The additional study providing recent independent verification is at www.translational-medicine.com/content/pdf/1479-5876-12-104.pdf and discussed here at http://forums.phoenixrising.me/inde...o2-max-indicates-functional-impairment.29827/ . Again, the term "VO2peak" is used, but the data clearly indicates that maximum effort is objectively verified.
     
    Last edited: Jun 23, 2014
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  5. N.A.Wright

    N.A.Wright Guest

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    There are very substantial differences between peak and max VO2 and to quote from this useful overview:
    http://www.cpxinternational.com/attachments/028_BJW - Vo2 Peak vs Max final 2.pdf

    In an effort to circumvent the problem of whether the subject gave a "sufficiently-good" effort, other, presumably corroborative, indices of have been utilized. These include: a maximum heart rate of more than 90% predicted; a respiratory exchange ratio greater than 1.15; and a peak post-exercise lactate of greater than 8mM. Clearly, none of these provide adequate assurance that the subject actually gave a maximum effort, even in normal subjects, because:

    in the first instance the predicted maximum heart rate has a standard deviation of approximately 10 beats per minute (9); in the second the maximum respiratory exchange ratio (R) is highly work-rate profile dependent (15): and in the third many subjects achieve peak post-exercise lactates that are appreciably greater than 8mM, invalidating it as an index of adequate effort (e.g. see ref 9).

    How much any of this confounds the CPET studies of ME/CFS is debatable but the terms VO2 max and VO2 peak should not be confused or conflated, not least because it may turn out that differentiation of the two measures is of significance in ME/CFS pathology.
     
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  6. Valentijn

    Valentijn Activity Level: 3

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    And that's pretty much the only source making much of a distinction.

    On wikipedia, for example, the two terms go to the same entry.

    A VO2max result is exactly the same as a VO2peak result in a properly conducted CPET. A VO2peak result is a proper VO2peak result when the CPET is properly done. And the papers indicate that it was properly done, which seems more important than focusing on an obscure bit of terminology which says it's exactly the same thing anyhow.
     
    Last edited: Jun 23, 2014
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  7. alex3619

    alex3619 Senior Member

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    The point of VO2peak not being VO2max rests on the notion of underperformance. In studies when capacities are estimated this is possible. My understanding is that in studies in which these factors are measured any under-performance will show up in the blood gases. Patients have the AT, anaerobic threshold, measured, not guessed which is what happened for decades under the Bruce Protocol. When this AT crashes the second day, you have specific physiological proof of impaired energy metabolism. What it does not tell you is why this occurs. Quite a few theories are being pursued, each of which has some evidence supporting it.

    On motivation, Snell has said repeatedly that patients are far more motivated than sedentary controls. Indeed, if lack of motivation was going to be a big issue, this would mean that control results would be worse, and work against the research finding.
     
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  8. Kina

    Kina Moderation Team Lead

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  9. kermit frogsquire

    kermit frogsquire *****

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    Thanks @Kina for moving this discussion for clarity. @Jonathan Edwards asked a question regarding the validity of original paper - the question is simply this - do inactive people have a drop in VO2 on 2 day consecutive CPET testing?

    There are scores of articles questioning the validity of secondard measures as a criteria of maximum effort on CPET. This is a question that has been discussed since the 1960's.

    Whilst it is true, in the absence of gold standard (true VO2max) some favour RER, others have questioned the validity of this measure. All secondary measures have drawbacks.

    RER - or Respiratory Exchange Ratio, is one of the most problematic measures for studying ME/CFS patients because RER is highly variable in different patient populations.

    RER is influenced by diet, muscle lactate, and previous inactivity (all of which result in elevated RER's). It is even more problematic to use this criteria for a repeat consecutive 2day protocol where RER can vary. Additionally, RER is very variable depending of type of protocol used, therefore when Snell chose to use a non-standard protocol (rather than a standard tredmill BRUCE) he was effectively making any conclusion based on the RER problematic. A criteria of 1.1 RER as "maximal effort" is potentially not valid for cycle ergometer (where results are elevated), and certainly not in the modified protocol used, and certainly not for this inactive patient population.

    There is also a much more serious problem with Snell's tests. Anyone who has ever done a CPET knows that the attending staff are required to encourage patients to exercise as much as possible in order to get a valid result.

    Now, since Snell and the attending staff knew which were the CFS patients and which were the controls, what we have is a very serious potential problem of bias. Lets look at those results again from the original study -

    Day 1 - CFS patients reached 94.83% HR max (SD 8.84)
    Day 1 - Controls reached 87% HR max (SD 25.44) - a standard deviation this large means that many didn't even try at all!

    Day 2 - CFS patients reached 87.83% HR max (SD 9.36)
    Day 2 - Controls reached 97.67% HR max (SD 7.2) - nearly all reached 100% Maximum HR

    The huge difference between Day1 effort from the controls and Day 2 effort effectively shows the controls didn't really try on the first day - it is very clear they could all reach maximum HR. Whereas the CFS patients really pushed as hard as they could on Day1, and perhaps were not encouraged to push as hard on Day2.

    Had the controls actually tried on Day1, their peakVO2 on Day 2 probably would have dropped too because of increased lactate. Increased lactate = increased RER at lower exercise intensitiy = lower peakVO2.

    Also, an inflammatory cascade from exercise does not occur at submaximal exercise, the controls were effectively just warming up for the second day test, whereas it is no wonder the CFS subjects were sore and tired.

    Snell et al are basing their claim of a "unique drop in VO2" on very very dodgy grounds, and potentially serious bias. From all the evidence, peakVO2 drops in all inactive people on a consecutive two day test where absolute maximal effort is actually given on Day1 - whilst RER remains the same due to lactate.

    Finally, one of the main objections to using 90% HRmax as a criteria for maximum effort is the variability in maximum heart rate between subjects, and also the use of beta-blockers in patients usually doing CPET tests. Neither of these is an issue for Snell's studies where both patients and controls were capable of reaching almost 100% maximum HR. Anything less than that therefore indicates submaximal effort.

    http://www.ncbi.nlm.nih.gov/pubmed/8531628 (full text available)
    http://jap.physiology.org/content/38/3/402
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729016/
     
    Last edited: Jun 25, 2014
  10. Cheshire

    Cheshire Senior Member

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    What is your proof???? I'm really amazed at the way you just twist things so as they fit your views...
     
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  11. alex3619

    alex3619 Senior Member

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    @kermit frogsquire, none of these arguments mean very much - its a technical sideline, with one caveat to follow. The key factor is not V02max or V02peak, but the anaerobic threshold. That is the critical factor as it links in with the metabolic findings. Further there are issues with oxygen consumption per work performed.

    This is also not just about controls. There are huge numbers of patients with many disorders studied. That data is still being mined, even if not part of a formal experiment.

    Why VO2max/peak is important is because that is the primary finding that was replicated here:
    http://www.biomedcentral.com/content/pdf/1479-5876-12-104.pdf

    There are anecdotal reports of at least two other groups replicating the findings too, but I do not think they were published.

    Pure inference, and probably fallacious depending on what you mean by "indicates". Its one of a range of possibilities. A possible inference is taken as conclusive, treated as conclusive, and all other options including things we have not discovered yet are excluded. Its a dangerous way to reason.

    You argument is all about perhaps, maybe, possibly, just as it was on concluding that most CFS patients have false beliefs. Such reasoning and conclusions always have to be tested before they can be considered to be robust conclusions.

    If the argument is that more research is needed, then I agree. If the argument is that more independent research is needed, then I agree. If the argument is that we need to test this in other ways, I agree. Results need to be tested, not just confirmed. However we also have to operate from results we have and not just wish for better future studies. I welcome more research, but until then we cannot simply stop and do nothing.

    If the Snell conclusions are wrong, this will show up in time. Meanwhile what can be said is the Snell findings are consistent with the mitochondrial, cytokine and lactate findings. Its been replicated. It gives us a research avenue to pursue. It gives us testing that is available now. Nobody is saying its perfect. That is why its not currently being claimed as diagnostic.

    Of course there is risk of bias in these studies. Bias is always a risk.

    One of the things I wanted from the current CDC study is yet another replication and enhancement of the 2 day CPET research. They were in a position to do that and to arrange a large variety of supporting tests, including cytokines. They are going with a one day test instead, I think.

    If you think your arguments are sound, why not try to get them published?
     
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  12. kermit frogsquire

    kermit frogsquire *****

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    Look, I know you don't want to read it, but the results from Snell fly in the face of everything everybody knows from exercise research - not to mention common sense.

    If a sedentary person, not to mention an extreme bed-rested healthy control, does an absolute maximal exercise test - they cannot do as much the following day. Yet Snell is claiming his healthy controls could do more. You can see the results for yourself - There are no twists.

    Snell's conclusions rest on a single point - the results in ME/CFS patients are unique and are not seen in controls. It is tempting to complicate matters with complex discussion of RER etc, but if that point is not proved, then everything else becomes irrelevant.

    To reinterate - A maximal exercise stress test is only valid if subjects exercise to their maximal level. The healthy controls didn't reach their maximum HR's on day 1

    Exercise stress tests are absolutely brutal, even for healthy people. They take you to absolute physical exhaustion, legs burning, gasping for breath - you take an average sedentary middle aged person and get them to do that two days in a row, then come back and tell me how they did the second day.

    Since Snell was measuring peakVO2 and the only secondary measure to assure us of maximal effort was "percent of maximal HR" - that is the only evidence we have to go off. There is no inference, those are Snells own figures.

    Further, you can also see from all of Snell's studies that the peakVO2 achieved on day 2 is reduced identically by the % reduction in workload achieved. Since VO2 follows a linear relationship with workload, Snell is merely measuring a reduction in effort.

    If there was a true deficit in oxygen uptake (as happens with other conditons) there would be a change in the slope and the linear relationship would not be preserved. - see consecutive CPET on pulmonary hypertension patients where a true deficit in oxygen uptake occurs, the VO2/workload slope changes.

    Snell's studies rely on misleading conjecture - the findings are not secure at present. Further research is needed, and the flaws in his studies removed to confirm the findings.
     
    Last edited: Jun 25, 2014
  13. Cheshire

    Cheshire Senior Member

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    Thanks for knowing better than me what I want or don't want to know...

    Once again, where is the proof of your assertion?

    As you seem unable to proove any of your claim, even when you've been asked severall times to do so, I don't see the point in continuing this discusion.

    May I just remind you that a personal conviction is not at all an evidence of anything.
     
    Last edited: Jun 25, 2014
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  14. alex3619

    alex3619 Senior Member

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    @kermit frogsquire. You are making repeatedly unjustified inferences and assertions, and not backing them up with evidence. You are taking statements and data valid for a particular set of circumstances and applying them generally without caveats.

    CPET has been used for 65 years. Its probably been done millions of times. The arguments you are claiming do not always address issues of relevance, even if they were always accurate. You are also basing way too much on the initial pilot study. It was interesting, it showed possibility, but it took seven more years of research to take this further.

    Where do I begin? First, you made obvious inferences - though not necessarily valid inferences. Second, your points, even if correct (a different issue to argument validity) do not change things very much at all. So what? VO2max/peak do not alter the important findings from these studies, even if they are not reliable. So what is the issue? If you have a concern with VO2max/peak, write letters to editors of the journals involved. Write to the authors.

    I am far more interested in the implications of lowered anaerobic threshold, and poor energy output. Much of the research in the future is likely to be on sub-maximal exercise. Why? Because maximal exercise is not that interesting. We are not elite endurance athletes.

    In any case the real issue with a drop in VO2peak/max is what happens in patients. Similar outcomes are not seen in other disorders, or in healthy people, with the exception of one HIV patient I know of. It isn't just controls in this study ... its what is seen in thousands of tests over the years, which is small variability in outcome. In CFS and ME its not small variability of outcome. Of course this requires further investigation. Why wouldn't it?

    What is happening requires further research. If there is a problem then it will be revealed. If there is a problem I want it revealed. A good contrary study would do that. Simply asserting it is so is not enough.

    In the meantime I am going to continue to push the 2 day CPET as a research finding.
     
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  15. Bob

    Bob

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    Sure, further research is needed and replication studies are needed.

    But you need to get yourself up-to-date with the latest research from Snell and colleagues.

    Your discussions about Peak VO2 aren't relevant to the latest research: In the latest study, peak VO2 decreased for both groups, and it wasn't a particularly useful indicator of ME/CFS. Instead, ATWL (aka VTWL) proved to be a very good indicator of ME/CFS.

    And VTWL is an objective test, so all your discussions re the subjectivity of peak performance are irrelevant.
     
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  16. lnester7

    lnester7 Seven

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    I have gotten the test with Connie, So some of the things here make no sense to me.
    1) You get hooked in the mouth/nose and heart.
    2) After 5 minutes or so SHE told me to stop (which was my personal experience too), I didn't say that I couldn't do anymore, She could see that I was over my AT which was ( 115BPM). So when they see you cannot do more is not that you say hey I am done, is that the equipement tells them you are not oxigen anymore but CO2. So when you do less is that you reach your ATP faster.

    I am reapeting the test soon and will do the 2 day one. But even thoguh I have been in therapy I cannot raise my AT from 115.
     
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  17. kermit frogsquire

    kermit frogsquire *****

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    I haven't seen those - have you got the link?

    I have to say, however, given the short-comings of his previous unsupported claims, I remain doubtful - but nevertheless open to the possibility.
     
  18. Bob

    Bob

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    If you'd read my previous posts in this thread then you'd know that I've posted the links, a number of times, earlier in the thread.
    The fact that you haven't read my posts doesn't surprise me, as your repetitive arguments have persistently ignored the entire forum's rebuttals to your many unfounded and inappropriate assertions.
     
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  19. Scarecrow

    Scarecrow Senior Member

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    No, he didn't. He asked for a reference to the study you had previously referred to:
    I understand why you are not able to provide this so not nagging you to do so but:
    In the absence of any evidence for all you know bed rested controls might perform better on day two. I'm not saying that's likely but please don't present assumptions as fact.

    I'm not up on the science of CPETs but I have done a VO2max so I'm interested. As this is essentially a science based thread rather than one of opinion, I'd give you a fair hearing if you would respect the difference between what has been demonstrated and what has not even been tested.
     
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  20. Isabelle

    Isabelle

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    Putting aside Kermit’s argument - which is probably best – I have a problem with the 2-day CPET. The studies add to the body of evidence, but don’t seem to interest many outside the field of exercise physiology. For most doctors, this test is probably just a dim memory of a physiology class at university. And some researchers might well baulk at using the 2-day CPET to select test subjects. There are ethical considerations – potential harm being the main one. Say the stethoscope and X-ray hadn’t been invented, would it be all right to induce mild heart attacks to make sure you have the right test subjects for a study on heart disease? Intuitively, it doesn’t sit well with me.
     
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