Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (2018) Montoya et al.

Cheshire

Cheshire

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Kegan J. Moneghetti, Mehdi Skhiri, Kévin Contrepois, Yukari Kobayashi, Holden Maecker, Mark Davis, Michael Snyder, François Haddad & Jose G. Montoya

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous syndrome in which patients often experience severe fatigue and malaise following exertion. Immune and cardiovascular dysfunction have been postulated to play a role in the pathophysiology. We therefore, examined whether cytokine profiling or cardiovascular testing following exercise would differentiate patients with ME/CFS. Twenty-four ME/CFS patients were matched to 24 sedentary controls and underwent cardiovascular and circulating immune profiling. Cardiovascular analysis included echocardiography, cardiopulmonary exercise and endothelial function testing. Cytokine and growth factor profiles were analyzed using a 51-plex Luminex bead kit at baseline and 18 hours following exercise. Cardiac structure and exercise capacity were similar between groups. Sparse partial least square discriminant analyses of cytokine profiles 18 hours post exercise offered the most reliable discrimination between ME/CFS and controls (κ = 0.62(0.34,0.84)). The most discriminatory cytokines post exercise were CD40L, platelet activator inhibitor, interleukin 1-β, interferon-α and CXCL1. In conclusion, cytokine profiling following exercise may help differentiate patients with ME/CFS from sedentary controls.
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https://www.nature.com/articles/s41598-018-20941-w
 
Our study has three main findings.

First, we have found that exercise can be associated with significant changes in cytokine profile that are still observed 18 hours following symptom-limited exercise.

Second, our study suggests that exercise may allow better discrimination of ME/CFS case status than resting values.

Third, we have found that cardiac structure at baseline and cardiorespiratory responses following exercise with a one-day protocol do not appear to distinguish cases of ME/CFS from healthy sedentary controls.
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Published online today:
Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

In conclusion, our study suggests that exercise may be useful to profile key biological difference in ME/CFS and sedentary controls. We also highlight the importance to account for exercise when profiling disease states or syndromes. Replicating the findings and investigating profiling using a two-day protocol will be important steps for future research.
 
- Our study has three main findings. First, we have found that exercise can be associated with significant changes in cytokine profile that are still observed 18 hours following symptom-limited exercise. Second, our study suggests that exercise may allow better discrimination of ME/CFS case status than resting values. Third, we have found that cardiac structure at baseline and cardiorespiratory responses following exercise with a one-day protocol do not appear to distinguish cases of ME/CFS from healthy sedentary controls.
 
I’m very keen on the idea of some kind of stress-test, including single exercise testing, to reveal biological differences. So this is great: it’s always seems like it would take some kind of exercise or other challenge to reveal differences between patients and controls.

A few observations:

Sample size is pretty-small at 24 patients and 24 controls. So not only does it need replicating, it needs larger samples. And comparisons with sick controls (it’s good they specifically chose “sedentary“ healthy controls for this study).

Those VO2 peak scores indicate quite high-functioning patients, which isn’t surprising given the nature of the test, and fits with the relatively-high proportion of patients who declined to take part in the study. In some ways, it makes the findings more interesting if the differences show up in "milder“ cases.

I would love to see someone following the approach of the Lights, using submaximal exercise tests. It doesn’t take anything like maximal exercise to cause all sorts of problems for patients in every day life, so it would be good to use something closer to a real-world test. Would a submaximal test also reveal similar cytokine differences?
 
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Third, we have found that cardiac structure at baseline and cardiorespiratory responses following exercise with a one-day protocol do not appear to distinguish cases of ME/CFS from healthy sedentary controls.
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Either the patients were high functioning and atypical, or it shows that (at least cardiorespiratory) deconditioning is not a factor in ME/CFS.
 
Simon M said:
I would love to see someone following the approach of the Lights, using submaximal exercise tests. It doesn’t take anything like maximal exercise to cause all sorts of problems for patients in every day life, so it would be good to use something closer to a real-world test. Would a submaximal test also reveal similar cytokine differences?
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I'm confused Simon. From what I can see, and from the title of the study, this study used sub-maximal testing. So I think they have answered that already?
 
Andy said:
I'm confused Simon. From what I can see, and from the title of the study, this study used sub-maximal testing. So I think they have answered that already?
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Although they describe it as symptom-limited submaximal exercise, you can see from the heart rate and oxygen: carbon dioxide ratio at peak activity data that participants achieved something not that far from max levels. By contrast, the Lights set their exercise at something like 70% of age-predicted maximum heart rate. That’s a much lower level of intensity then achieved by participants in the study.
 
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