Trial Report Home-based testing protocol to measure physiological responses to everyday activities in ME: a feasibility study, 2023, Clague-Baker et al

[Andy]

ABSTRACT

Background and objectives
Individuals with Myalgic Encephalomyelitis (ME) have shown altered physiological responses during maximum cardiopulmonary exercise testing. However, maximal testing is not representative of the everyday activities reported to cause or increase symptoms in ME, and is not accessible for those with severe or very severe illness. The aim of this study was to assess the feasibility and acceptability of a home-based testing protocol to measure physiological responses in ME to everyday activity.

Methods
Researchers attended participants’ homes to collect data and provide equipment for independent testing. Adults with ME who met the International Consensus Criteria wore a portable metabolic assessment system and a physiological stress monitor. Blood pressure, heart rate, oxygen saturation and lactic acid were assessed during a range of everyday positions and activities in their own homes.

Results
Online recruitment yielded 70 volunteers in 24 h. 17 eligible individuals reflecting a range of illness severities were enrolled. All participants found the procedures acceptable with 12 (70%) subjects completing every listed activity. Apparent physiological abnormalities were identified in all participants.

Conclusion
Physiological measurement during everyday activities was feasible for our participants who represented a range of ME severities. Activities must be adapted for different levels of severity to avoid significant symptom exacerbation. Further research is needed to develop home-based assessment protocols to advance the biobehavioral understanding of ME.

Open access, https://www.tandfonline.com/doi/full/10.1080/21641846.2023.2245584

 

[Fizzlou]

Data from the Portable Cardiopulmonary-Monitoring System indicated that participants often exceeded their anaerobic threshold during these activities (defined as a respiratory exchange ratio (RER) exceeding 1.0). For two subjects (11%), this occurred while lying down. The activity which caused most participants to exceed their anaerobic thresholds was the cognitive task (n = 10, 62%).

The cognitive task (counting sevens) effect struck me.

An extra thought was the descriptors of some of the moderate patients read as if they were tending more towards severe.

 

[Trish]

I think that's the most clearly written research paper I have read. The results are interesting, particularly the effect of cognitive testing.

Given that it is listed last of the activities I wonder whether it was done after the other activities, and therefore any cumulative effect might have influenced the results, though the authors did say they allowed people to rest between activities. It is also listed as done sitting, presumably with feet on floor, so is actually a combined test of two activities. It would be interesting to test cognitively while lying down as many of us in real life do.

I think this shows promise as useful for diagnostic and monitoring purposes. I'm imagining in an ideal world a specialist nurse or physio being able to use some or all of this to assess the patients as part of what the mythical ME/CFS local clinic provides.

And it provides pointers to possible outcome measures for clinical trials.

 

[Sly Saint]

"Recruitment was exceptionally rapid and completed within 24 h. This demonstrates that people with ME, even those who are severely affected, are keen to be involved in research."

 

[Hutan]

Adults with ME who met the International Consensus Criteria wore a portable metabolic assessment system and a physiological stress monitor. Blood pressure, heart rate, oxygen saturation and lactic acid were assessed during a range of everyday positions and activities in their own homes.

Our long-term goal is to identify potential biobehavioral mechanisms in real time that can potentially inform diagnostic assessments and outcome measure(s).

The findings of this study indicated that it is feasible and acceptable for individuals with ME to assess physiological parameters during everyday activity using portable equipment and protocols that are traditionally confined to a clinic or laboratory. Furthermore, our findings revealed apparent physiological abnormalities during these activities that may be useful for understanding real-time biological dynamics in ME that perhaps could inform diagnosis and assessment as well as development of novel therapies to manage symptoms. Feasibility was considered in terms of the ability to recruit participants, acceptability of the testing protocol, fidelity to procedures, and sensitivity of outcome measures.

One of the authors is Sarah Tyson @sarahtyson. The assessments were done in 2021, and the study found that even people with severe ME/CFS were mostly able to use monitoring equipment without problems. I'm therefore not understanding Sarah's conclusion, expressed on the forum earlier this year, that objective outcomes aren't suitable for inclusion in a set of standard outcomes to be monitored in clinics. Outcomes could possibly be some of the ones investigated here, as well as others we have discussed on the forum related to activity levels.

This was interesting: (edit - it would be good to see the individual results)

Physiological data collected with Firstbeat Bodyguard for up to six days after the testing day indicated that all participants spent some time (29–95%) in cardiorespiratory ‘physiological stress’ (suggesting sympathetic nervous system dominance). The time in ‘physiological stress’ was not balanced by the time ‘in recovery’ (suggesting parasympathetic nervous system activity) which ranged from 0% to 67% of the time monitored. The proportion of time in ‘physiological stress’ tended to increase with the severity of ME. By comparison, healthy participants exhibited less time in physiological stress on average (30% Healthy: 63% ME) and more time in recovery (55% Healthy: 16% ME). Research using Firstbeat technology with 20,000 participants has shown that ‘a typical 24-hour measurement day was classified as “physiological stress” 51% of the time (12 h 14 min) and as “recovery” 49% of the time (6 h 14 min)’ [Citation34].

 

[tornandfrayed]

The cognitive task (counting sevens) effect struck me.

An extra thought was the descriptors of some of the moderate patients read as if they were tending more towards severe.

Yes, that's interesting, and shows that we can be exceeding our limits, even if we don't think we are.

Several of them seem more severe than their designation & the woman described as mild seemed very unwell.

I don't think it's always true that people who are designated as mild, because they are still in work and/or caring for others, have milder symptoms. When I was trying to remain in work ( sometimes part-time & with extended periods of sick leave) I felt terrible & slept almost every hour out of work.

 

[Haveyoutriedyoga]

I don't think it's always true that people who are designated as mild, because they are still in work and/or caring for others, have milder symptoms. When I was trying to remain in work ( sometimes part-time & with extended periods of sick leave) I felt terrible & slept almost every hour out of work.

Agreed, I have remained in work full time (except these last 3 months) by working from home, barely leaving the house once a week to do something like go to my grandparents house for a cup of tea on a recliner, have had horrible symptoms a lot of the time, not completing all self care but am supposedly mild because I work.

Regarding the monitoring, this sort of thing might be useful to me to understand the relationship between activities (cumulatively, as mentioned above) and post-exertional pay back symptoms, probably wouldn't do it constantly, but rather do it for an initial period of some weeks to learn from it and then maybe once a quarter for a week or two to see whether things are the same.

 

[obeat]

Would it be worthwhile repeating this throughout the menstrual cycle?

 

[RedFox]

I have nothing but praise for the authors and the quality of their work. They wrote their paper at a level any college graduate can understand. They conducted a novel experiment, made a real effort to accommodate pwME, presented their findings straightforwardly, and emphasize the points that are important for our dignity (debilitating nature of symptoms, PEM, and real biological abnormalities)

Their findings were very cool. They discovered that pwME exceeded their anaerobic threshold doing daily activities like making breakfast, and they discovered something mindblowing: That all the patients who could complete the cognitive assessment exceeded their anaerobic threshold just by thinking.

 

[Midnattsol]

Would it be worthwhile repeating this throughout the menstrual cycle?

Yes! My heartrate varies throughout my cycle, and so does the energy burned on my fitbit in response to whatever it is I'm doing (though this is not weird since the algorithm likely uses heartrate to calculate energy used). I also feel more able to do stuff in my follicle phase.

 

[Fizzlou]

I would like to see effects of having a meal and dealing with ingestion/digestion. Could have impact on severe/ very severe pwME and their nutritional support.

 

[Hutan]

Some background information about RER, it's probably over-simplifying things:
https://web.cortland.edu/buckenmeyerp/fall2004/labrvalue.html

The respiratory quotient (also know as RQ, the respiratory exchange ratio, RER, and most commonly, R) is the ratio of volume of carbon dioxide produced to volume of oxygen consumed. This is important because it provides a pretty good indication of the substrates being utilized for energy production!

• When palmitic acid (a fatty acid) is completely oxidized, the following equation is valid:

C16H32O2 + 23 O2 = 16 CO2 + 16 H2O
23 O2 molecules are consumed while 16 CO2 molecules are produced. 16/23 = .7

• When glucose is completely oxidized, the following equation is valid:

C6H12O6 + 6 O2 = 6 CO2 + 6 H2O
6 O2 molecules are consumed while 6 CO2 molecules are produced. 6/6 = 1.0

So, when R is near .7, then the body is using mostly fat for energy production. If R is near 1.0, then the body is using mostly carbohydrates for energy production. If R is above 1.0, then carbon dioxide is being produced by other means, usually from the buffering of lactic acid. This indicates that the person is working very hard, or that they are hyperventilating. Typically, R will be about .8 at rest. Although this is near the ‘halfway point’ (.85), it still indicates a reliance on fats for energy production at rest. RQ is the respiratory quotient and RQ reflects what is going on at the cell. RER is the Respiratory Exchange Ratio and reflects fuel utilization in the entire body.

This is the machine that reports the RER and oxygen use and CO2 production in everyday settings:

Portable Cardiopulmonary-Monitoring System (MetaMax 3B, Cortex Biophysik GmbH, Leipzig, Germany

I agree that the concept of this study was excellent, exactly the sort of fundamental investigation using wearable technology that we've needed for so long, and the implementation of the testing with people with ME/CFS sounds to have been done really well too. The RER findings reflects what I feel, that doing trivial tasks of everyday living makes my body work abnormally hard.

I think the presentation of the data lets the paper down though. That paragraph I quoted above (copied here again), for example, does not give us the detail needed to understand what is happening. Yes, the means are different, but we don't know how much of an overlap there was between people with ME/CFS and healthy controls for 'time with physiological stress', 'time in recovery' or 'ratio of time spent in physiological stress and in recovery'. There should be some statistical analysis of difference between the people with ME/CFS and healthy controls for those parameters where there was data from healthy controls. If the authors felt that their study was too small and preliminary for such statistics, they could have at least presented results for each participant (ME/CFS and healthy) in a table, or shown the individual data in plots.

Physiological data collected with Firstbeat Bodyguard for up to six days after the testing day indicated that all participants spent some time (29–95%) in cardiorespiratory ‘physiological stress’ (suggesting sympathetic nervous system dominance). The time in ‘physiological stress’ was not balanced by the time ‘in recovery’ (suggesting parasympathetic nervous system activity) which ranged from 0% to 67% of the time monitored. The proportion of time in ‘physiological stress’ tended to increase with the severity of ME. By comparison, healthy participants exhibited less time in physiological stress on average (30% Healthy: 63% ME) and more time in recovery (55% Healthy: 16% ME). Research using Firstbeat technology with 20,000 participants has shown that ‘a typical 24-hour measurement day was classified as “physiological stress” 51% of the time (12 h 14 min) and as “recovery” 49% of the time (6 h 14 min)’ [Citation34].

I hope that this group and others do much more of this sort of study, with bigger groups, stratified by activity levels, with sedentary controls and chronic illness controls and, yes, exploring the things that others have suggested such as impact of menstrual cycle and digestion, and cognitive effort alone, and during sleep too. I think there are lots of relatively easy studies using the wearable technology, and especially the portable cardio-pulmonary monitoring system, that could be done that would be useful.

 

[Hoopoe]

The RER findings reflects what I feel, that doing trivial tasks of everyday living makes my body work abnormally hard.

I agree very much. I'm not sure that all aspects are reflected in the data though. For me these measurements would likely show erratic activity patterns with relatively preserved function for short periods, and periods where te body is struggling just to walk upstairs or empty the dishwasher. At any given moment I can look anywhere from energetic and healthy to obviously sick and weak.

 

[bobbler]

The cognitive task (counting sevens) effect struck me.

An extra thought was the descriptors of some of the moderate patients read as if they were tending more towards severe.

Indeed - good to see these things being looked into and methods seeking to show this. What a relief. Plus, particularly if we begin to note this in relation to the methodological approach of e.g. CHalder-type stuff and BPS approaches expecting people to fill in goodness knows how many questions on a survey during 'an appointment' or to get home after one or a trial. These would be people that, whatever their severity would have travelled to get there and probably if they'd been forced through combative CBT were at the end/shoved beyond their limits of health and defences by the time they were being faced with these.

So they need to be seen and mapped 'scenario-wise' as what it is: someone faced with all of these health risky awful symptoms and being told 'just fill this in as we want you to and you can begin to go home to safety' at the point where a human being would be unable to process the perceived and real risks associated with anything else in selecting what to put on the form and its implications to them re: Maslow needs like access to care or things on records tha could affect that or finances and so on. What would anyone else do in that situation? And the fact many of these are 'restrospectives' when patients are effectively 'captured' under that clinic in such a way makes it even more of a question about should such 'measuring' even be being allowed to take place and whether that data be seen as anything other than a consequence of that historical power issue being applied to people whose body was under unsafe exertion at the time?

Add in the other forms of perceived coercion and I think someone needs to consider comparing these scenarios that pwme would be being put in to literatures on e.g. 'stress-testing' and effects of situational scenarios where coercion is used and tested which I'm assuming must exist for military or other parts of psychology where the law is needed to protect individuals/humans from these things.

 

[bobbler]

I would like to see effects of having a meal and dealing with ingestion/digestion. Could have impact on severe/ very severe pwME and their nutritional support.

Cruel and ethically difficult but given the other problem with those who end up in hospital terribly poorly is the interruption to rest/difficult environment with regards noise and light etc impacting absorption this would be interesting as would the effects of noise/lights and so on regarding likely energy use and health impact but also how it cumulatively adds to the meal and digestion 'load'.

It feels like pwme are in catch 22s when they need to enter a hospital to get such support and yet the environment means any improvement from that has to be weighed against it because there isn't currently an understanding of how bad and counter-productive to health such a situaiton is. Seems like just another way that someone might finally apparently 'be given x' and then treated in other scenarios unideally and then outsiders think they are 'proven wrong' when they get worse instead of better, even though it has actually be undermined etc.

 

[RedFox]

I would like to see effects of having a meal and dealing with ingestion/digestion. Could have impact on severe/ very severe pwME and their nutritional support.

That's an excellent idea. Digestion increases your metabolic rate. If cognition can tip you into anaerobic metabolism, digestion probably can too.

Also, I'd really love to see a similar study on mild ME. Do people with mild ME exceed their anaerobic threshold doing simple daily activities, even if it's not quite enough to tip them into PEM? Does AT drop when doing daily activities during PEM?

 

[Sean]

or shown the individual data in plots.

I wish reporting scatter plots was mandatory.

 

[Midnattsol]

I wish reporting scatter plots was mandatory.

As long as we take into account that when you have a few thousand participants in your study, individual datapoints just look like a giant blob

I would like "Metabolic Equivalent of Task" data for pwME. While METs have problems (the "normal" is based on a single caucasian male in his 40s..), these type of measurements can be useful. For example it is easy to show the strain of illness by showing that patients with certain illnesses expend more energy doing tasks than healthy controls.

I agree very much. I'm not sure that all aspects are reflected in the data though. For me these measurements would likely show erratic activity patterns with relatively preserved function for short periods, and periods where te body is struggling just to walk upstairs or empty the dishwasher. At any given moment I can look anywhere from energetic and healthy to obviously sick and weak.

I think that even if/when we look energetic and healthy (I do too often), something goes on at cell level that might be different than in healthy people. It's just below some threshold.

 

[Hoopoe]

Also, I'd really love to see a similar study on mild ME. Do people with mild ME exceed their anaerobic threshold doing simple daily activities, even if it's not quite enough to tip them into PEM? Does AT drop when doing daily activities during PEM?

My guess is that they do, but not as easily or often.

 

[Hutan]

that when you have a few thousand participants in your study

Of that we can only dream. (oh, apart from DecodeME)