That was pretty quick! Health Rising reported on Heather Edgell’s Ramsay Award from the Solve M.E. Initiative in Aug 2022 and now she’s not only finished the study but has already published a paper, “Inspiratory muscle training improves autonomic function in myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of SARS-CoV-2: A pilot study“, on it.

Moving quickly is one of the many advantages of supporting ME/CFS research foundations like Solve M.E., the Open Medicine Foundation, and ME Research UK. Applicants don’t have to suffer from extended grant application reviews from reviewers who don’t know the field – and may not even be sympathetic to it (like we sometimes see at the NIH). Look at what just happened at the NIH – somehow we lost an ME/CFS research center because the reviewers nixed it.

Plus because the non-profit grant application reviewers come from the field, they’re able to sign off on higher-risk, higher-gain projects that take advantage of the latest research. Plus, they’re willing to support researchers who have good ideas no matter where they come from – the ideas are the thing, not the researchers’ pedigree.

That kind of expertise and commitment results in a nice return on investment (ROI). Supporting the non-profits is a win-win for everyone.

Heather Edgell’s Ramsay Award

Heather Edgell’s Ramsay award from Solve M.E. to do an inspiratory breathing study is a case in point. Edgell, from York University in Toronto, has never worked in the ME/CFS/long-COVID field and no inspiratory trials have ever been done. With ME/CFS studies demonstrating that breathing is altered during exercise and during standing, and with clinicians such as David Putrino using breathing techniques in long COVID and ME/CFS, it was clearly time for a breathing trial.

This trial, though, wasn’t just about improving symptoms. Like other non-profits (Open Medicine Foundation, PolyBio Foundation), Solve M.E. used this trial to dig into the patients’ physiology and learn more about the disease.

The Trial

The trial was small (long COVID – 9; ME/CFS – 12, healthy controls -12) – and it was supposed to be small. Organizations like Solve M.E. fund as many small pilot trials as they can to give as many researchers as possible the data to apply for larger studies from the NIH or private foundations.

The trial used mild to moderate patients; i.e. it avoided those who were house or bedbound.

The trial was hormetic in nature; i.e. in its attempt to retrain the autonomic nervous system and breathe more healthily, it used a small stressor to build up the muscles that move the lungs. (Lying in bed for long periods can weaken those muscles). Three times a week, participants breathed through a device that restricted their breathing a small amount.

Each session consisted of 6 sets of 6 repetitions (total of 108 breaths/week) with the goal of progressively reducing the rest time between sets from 60 s for the first 2 weeks to 10 s for the last week. (If I got it right they would take 6 breaths through the device, wait for a minute, then do six more breathes for a total of 36 breathes per session. Over time they would reduce the rest period to 10 secs.) Edgell said it feels as if you were breathing through a straw.

Various autonomic nervous system assessments were taken. Before the trial, the ME/CFS group exhibited worsened symptoms of orthostatic intolerance, vascular function, secretomotor function (fluid secretion), and gastrointestinal function than the healthy controls. They also exhibited more reduced vasomotor functioning (regulation of blood vessel diameter) than the long-COVID group. Both ME/CFS and the long-COVID groups displayed reduced HRV.

Edgell found the inspiratory training improved autonomic functioning in ME/CFS (vasomotor, secretomotor, weighted score), improved sleep symptoms in all the groups, and improved pain in ME/CFS. It also improved heart rate variability (a sign of parasympathetic nervous system (rest and digest) functioning), resting heart rate (more rest and digest), maximal inspiratory pressure (stronger lung muscles), and even the distance the participants covered in the 6-minute walk test.

The ME/CFS group was worse off at the beginning of the study, but gained more – showing greater improvements in vascular function, secretomotor function, the total weighted score of the COMPASS 31 autonomic questionnaire, and symptoms related to pain.

The improved sleep was a nice bonus but maybe not an unexpected one. These breathing exercises improved parasympathetic nervous system (rest and digest) functioning and studies have linked poor sleep in ME/CFS to reduced parasympathetic nervous system functioning.

This study was not about being cured – it was about finding something that could help relieve some symptoms. It’s amazing, though, that simple and easy breathing exercises done three days a week could have such an effect. The only thing the participants were working out, after all, was their lung muscles – and it wasn’t a hard workout. Edgell provided the easiest version of inspiratory training possible:

“We chose a type of training that did not increase effort with time, but rather decreased the time between breaths in consideration of the potential for post-exertional malaise (PEM). We were in communication with patients throughout the protocol to help with pacing and to make sure that patients were doing well. I highlight this as researchers need to act with care and understanding with any protocol that involves physical activity in these populations.”

The authors believed the improvements were due to improved parasympathetic activity (vagal tone).

Doing Inspiratory Muscle Training (IMT) at Home

Applying the Arseneau test, which assesses the factors below to help decide whether or not to try a treatment, suggests IMT is an easy win. The device is readily available, not particularly expensive, and the process is easy to learn.

• The credibility of the source – IMT has been time-tested in other conditions
• Quality of the evidence – while the study was small, the results were positive
• The benefit, the cost, and the risk–benefit – the benefits are probably moderate, the risk is low (you can discontinue at any time), and the cost is low.

What’s not to like?

The Respiratory Therapy Zone recommends the following trainers. Since some of them are quite different, it might be worth reading the reviews:

1. The Breather Respiratory Muscle Trainer – $49.95
2. POWERbreathe Plus Resistance Breathing Exerciser Trainer – $68
3. AirPhysio Sports Edition Breathing Exerciser – $69.97
4. POWERbreathe Plus Fitness Breathing Muscle Trainer – $49.99
5. AirPhysio Natural Breathing Lung Expansion Exerciser
6. Breather Fit Respiratory Muscle Exerciser Trainer – $59.95
7. Expand-A-Lung Sports Breathing Exerciser – $49.90
8. Voldyne 5000 Volumetric Incentive Spirometer Exerciser
9. Quest Lung Performance Peak Flow Meter – $23.47

Note that it can take a month or so to begin to see results.

Quite the Return on Investment

The pilot study did what Solve M.E. hoped it would do – result in more funding. Since her Ramsay Award, Heather Edgell has won over half a million dollars in other grants to bolster her Ramsay Grant findings.

She’s not alone. Solve M.E. reported that from 2016-2023, it funded $1.3 million in 37 infection-associated chronic illnesses studies through its Ramsay Research Grant Program. Over time, those grant recipients subsequently won over $27 million in funding. Many times all a researcher needs is a start, and that’s what the Ramsay Awards provide. 

The Duricka Award

Deborah Duricka provides an intriguing counterpoint to Heather Edgell’s findings. Also a Ramsay Awardee, Dr. Duricka recently published a retrospective chart review on stellate ganglion block – another formerly untested treatment – targeted at the same system – the autonomic nervous system.

Duricka has found that injecting anesthetic into the stellate ganglion (the SGB) can relieve pain, regulate sympathetic nervous system activity, improve sleep, increase cognition, and improve neurological function. Even the big symptoms – post-exertional malaise – quickly improved. With one in three long-COVID patients still experiencing relief a month later, the shots had some legs.

Neither Edgell nor Duricka would have had a chance at the NIH. Both are examples of the uniquely creative approaches to ME/CFS the non-profits provide. Standing on the cutting edge, they open doors that would have never been opened without them.

• Coming up – a look at a recent Open Medicine Foundation-funded ME/CFS study, and several talks with Benjamin Natelson on his new studies, the unique breathing problems he’s found in ME/CFS, and his new attempt to reset the autonomic nervous system using vagus nerve stimulation.