In part II of a series of blogs on breathing and oxygen utilization, a long COVID exercise study suggests that dysfunctional breathing patterns may help explain the exercise intolerance found.

Lungs Anatomy

Dysfunctional breathing – Could it play a core role in long COVID and ME/CFS? (from Sumiaya – Wikimedia Commons).

A recent blog focused on a large CDC exercise study revealed that problems with gas exchange” – the movement of oxygen into the body and the removal of CO2 from it – were common in ME/CFS. Because oxygen – a gas – fuels most of the energy production in our bodies, and energy production produces CO2 which becomes toxic at too high of levels, stating that gas exchange problems exist in ME/CFS is tantamount to saying that energy production problems exist. Anytime we see “gas exchange”, then we can think “energy production”.

The CDC study found that a strange breathing pattern was present: people with ME/CFS were breathing more slowly and deeply than usual during exercise. This type of breathing pattern has been associated with exercise intolerance before, and the authors suggested it may have resulted from a compensatory attempt to try to force more oxygen into the body.

A Gas Exchange Disease? Huge CDC Exercise Study Puts New Slant on ME/CFS

ME/CFS isn’t the only disease, though, in which bizarre breathing patterns have popped up recently during exercise. A long-COVID exercise study, “Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post–Coronavirus Disease“, did the same. While it was called a “Rapid Report”, the study dug deeper than usual into the individual patent findings – illuminating in more detail than we’ve seen before a variety of breathing patterns found.

This paper is also notable because it’s the first non-David Systrom study that I know of to use invasive exercise tests (albeit in a small sample) in ME/CFS or long COVID.  Let’s hope there’s more of that on the way from Dr. Mancini and Dr. Natelson.

The Study

The study involved 41 PASC (post-acute sequelae of SARS-CoV-2) or long-COVID patients. The average age – 41 – indicated these people had gotten hit in the prime of their productive years. The authors – one a longtime ME/CFS researcher – quickly connected post-acute sequelae SARS-CoV-2 infection (PASC) patients, otherwise known as long haulers, to ME/CFS by stating that PASC’s major symptoms are consistent with a diagnosis of ME/CFS. They also noted that no less than 27% of survivors of the first coronavirus epidemic (in 2005) met the criteria for ME/CFS four years later. They made sure that nobody was going to miss the long-COVID/ME/CFS connection.

The patient group was somewhat specialized – more than 3 months after “recovering” from the initial viral attack all of them still experienced shortness of breath. All underwent a maximal cardiopulmonary exercise test (CPET) which involved the participants bicycling to exhaustion. The CPET was a bit different from others, though, in its close tracking of the breathing patterns.


The Gist

  • Not long after a blog on a major CDC exercise study that exposed problems with “gas exchange” and breathing in ME/CFS, comes a study which did the same in long COVID. 
  • Note that because oxygen is the gas that fuels most of the energy production in our bodies that problems with gas exchange in the context of ME/CFS and long COVID could very well mean problems with energy production. 
  • This study employed a regular cardiopulmonary test that measures cardiac (heart rate, stroke volume) and pulmonary factors (breathing rate, CO2 levels, etc.)  participants bicycle to exhaustion. Some of the participants also did an invasive exercise test which measures the same factors but in both oxygenated blood in the arteries before the blood hits the muscles and the “used up” or deoxygenated blood in the veins after it leaves the muscles. 
  • Forty-one long COVID patients experiencing shortness of breath participated in the study. 
  • Sixty-percent of them displayed  what they called a “circulatory impairment”. These patients never generated much energy (low VO2), burned through the aerobic energy available to them quickly, and hit their anaerobic threshold early. The authors appeared to believe that the oxygen in the blood is not getting to the muscles in sufficient quantities in this group.
  • A wide variety of factors could be causing this is including reduced blood flows to the lungs or muscles because of blood clots or blood vessel problems. In that vein, a recent study suggests that reduced blood flows to the small blood vessels in the lungs may be a big deal in long COVID.  If that’s so it would fit other microcirculatory findings in ME/CFS and FM. (A blog is coming up).
  • The study also found evidence of “preload failure” where insufficient amounts of blood were being returned to the heart – thus reducing stroke volume – the amount of blood each heartbeat pumps out. Because the veins are mainly responsible for increasing the stroke volume during exercise – some to do with them – is likely responsible for that. 
  • About 10% of patients had ventilatory impairments that either prevented them from filling their lungs up properly or filling the blood reaching the lungs with oxygen. 
  • The main focus of the paper, however, was on the remarkable extent of dysfunctional breathing patterns found. 88% of the participants exhibited one form or another of dysfunctional breathing. 
  • During exercise as the breathing rate smoothly climbs the amount of air moved should increase significantly early and then moderate and finally reach a plateau sometime before a person reaches exhaustion. 
  • This almost never happened in long COVID and a number of different breathing patterns were seen. All of them displayed a kind of jerky, up and down pattern which indicated a system under extreme stress which tried but failed to find its ground. Some even exhibited a reversal of the normal breathing and heart rate patterns found during exercise (See graphs in the blog.)
  • The fact that only about half the long COVID patients met the criteria for ME/CFS while 88% displayed strange breathing patterns during exercise and 60% hit their anaerobic threshold early suggests that the criteria may be missing a significant number of people with ME/CFS-like illnesses.
  • Similarly, while about half the participants exhibited a normal VO2 peak – a measure of fitness – almost all them also suffered from dysfunctional breathing patterns – which can affect exercise intolerance. 

As in ME/CFS, this study highlighted how heterogeneous a group the PASC patients were. Just about everybody had something wrong, but the things that went wrong varied.

Circulatory Impairments – With almost 60% of the patients falling into this category, this was the biggest single group. Long-COVID patients with reduced VO2 (oxygen consumption; i.e. energy production), early onset of anaerobic threshold, reduced VO2 pulse, and elevated VE/VCO2 slope were classified as having a circulatory impairment.

These patients never generated much energy (low VO2) and burned through the aerobic energy available to them quickly and hit their anaerobic threshold early. The authors appeared to believe that the oxygen in the blood is not getting to the muscles in sufficient quantities in this group.

They noted that a wide variety of factors could be causing this: damage to the heart, reduced perfusion of the blood to the lungs or muscles via blood clots or blood vessel problems. A recent study using a new technique suggests that reduced perfusion to the lungs because of damage to the microcirculation may be a big deal in long COVID. (A blog is coming up.)

Dysfunctional breathing patterns were common (60%) in this group, but with 40% of this group not demonstrating dysfunctional breathing, it was clear that it was not necessary to produce circulatory impairments.

Dysfunctional breathing, on the other hand, was very common in patients with normal VO2 peak levels – a group that would be classified as having a normal exercise capacity. They tended to have other problems, with most of them exhibiting odd breathing patterns. The upshot is that only 2 long haulers in the study had completely normal results.

Preload failure – Systrom has found preload failure – the inability of the veins to return sufficient amounts of blood to their heart. This study found that preload failure is present in PASC or long COVID as well.

It turns out that the increase in stroke volume found in the heart during exercise is mostly accomplished by increasing “venous return”. Increasing venous return is accomplished by constricting or narrowing the veins by the muscle pump which alternately opens and constricts the veins, and by the respiratory pumps which involves the expansion and the reduction of the chest wall.

Ventilatory Impairments – Patients with low breathing reserve, O2 desaturation, or with RR >55 beats/min with exercise were identified as having a ventilatory impairment. Breathing reserve is the extra space in your lungs that you tap into when you exercise and need to move more air. These patients had problems with their lungs. Either their lungs’ ability to move air was maxed out, or they were having trouble getting oxygen into the blood from the lungs. About 10% of the participants fit this category.

A Ventilation-Impaired and Dysfunctional Breathing Disease?

Breathing easily and fully is one of the basic pleasures of being alive… It provides the oxygen for the metabolic processes; literally it supports the fires of life. Alexander Lowen

A major focus of the paper was on dysfunctional breathing patterns and/or problems with ventilation. A “primary ventilatory limitation to exercise” was not expected to be found, and was not seen. This appears to refer to the fact that the lungs of PASC patients were largely capable of moving air adequately – they just did so in a strange way.

While “a primary ventilatory limitation” was not found, almost all the patients (88%) exhibited, in one form or another, odd problems with ventilation or breathing. They demonstrated weird breathing patterns (dysfunctional breathing), resting hypocapnia (low CO2 levels), and/or had an excessive ventilatory response to exercise (elevated VE/VCO2 slope); i.e. they were moving more air than was necessary.

Dysfunctional breathing patterns were the most common problem (63%) found. During exercise, the amount of breath moved (ventilation) should track closely with CO2 levels – as the primary goal of breathing during exercise appears to be to remove the CO2 that gets built up as a result of energy production.

Generally, the pace of breath should slowly increase during exercise. The tidal volume – the amount of breath moved – should increase early but over time should moderate. As we get close to exhaustion during exercise, the amount of breath being moved in and out of the lungs doesn’t really change that much; it actually levels off well before we reach that point.

In this shot of a normal breathing pattern on the left-hand side of the graph, you can see that ventilation (using the BTPS measure) – the amount of breath moved – increases smoothly over time. In the bottom figure, see how the breathing rate (brown line) slowly and regularly increases over time, while the amount of breath moved (using minute volume – the amount of air moved over a minute of time – blue) shoots up early and then moderates and finally levels off towards the end of the exercise. Apparently, the heart rate and amount of air moved should join as the patient reaches exhaustion. It’s the picture of a clean and efficient breathing pattern.


breathing efficiency exercise long COVID

Compare the smooth patterns seen on the graphs on the far left (the normal patient) with the jerky and jumbled patterns seen on the right. The blue lines refer to ventilation while the brown ones refer to breathing rates.

Compare that to some of the PASC participants with decidedly abnormal breathing patterns seen in graphs in the center and the right. The increase in the amount of breath moved is jagged – the peaks of ventilation are followed by abrupt drops –  and the breath rate is all over the place; sometimes the person is breathing much faster than normal, sometimes slower. No early increase in the amount of breath moved gives way to a moderate, and finally, virtually no slope at all.

Instead, there’s a jumbled mass of ventilatory readings as the amount of breath moved moves up and down. It’s a picture of an agitated system that just cannot settle down and find its ground.

Different variations occur. In these graphs below, the breathing rate and the amount of air moved through the lungs merge. We should be seeing the amount of air being moved ramp up quickly, but it’s unable to do that despite the fact that the breathing rate is increasing. Some sort of limitation is clearly occurring. Instead of the graphs of the heart rate and amount of breath moved joining as the patient reaches exhaustion, they join almost immediately in the long-COVID patients with breathing dysfunctions.

In some patients, the graph actually flips itself – and a reverse pattern of breathing is seen: in the patients below, the exercise prompts very rapid breathing – and a lot of air being pumped – perhaps in an effort get more oxygen to the tissues. The graphs of the heart rates and the amount of air being moved are joined from the get-go. Nor does the amount of air moved plateau at some point – it just keeps its jagged rise.

Notice in patients 9 and 10 that the graph switches again as the patient nears exhaustion – the heart rate levels off while the amount of air being pumped dramatically increases. These appear to be very strange patterns. Compare these graphs to those on the left-hand side of the first image to see the reverse pattern present.

The authors noted that these jerky and strange breathing patterns interrupt the rather complex breathing process, possibly leaving extra dead (unutilized) space in the lungs behind and/or causing intrapulmonary blood shunting, which occurs when the blood doesn’t get fully oxygenated in the lungs. Either way, the efficient flow of oxygen into the body and CO2 out of it gets impacted.

The authors noted that dysfunctional breathing patterns can cause symptoms such as shortness of breath, fatigue, chest pain, and palpitations, and that breathing retraining may help. Systrom, Cook, and others have suggested that the breathing problems may be secondary to the energy production problems that studies have suggested are present. It’s possible that breathing retraining could help, though, and a clinical trial is underway in ME/CFS. (A blog on that is coming up.)

“Hidden” Problems? (Or what the heck is ME/CFS anyway?)

This study also showed how seemingly normal results in one area can hide abnormalities in another. For instance, peak VO2 (think peak energy production) has received a lot of focus in ME/CFS and is often used as an assessment of fitness. A normal peak VO2 found was found in almost half the participants in this study. Without the extra assessments done in this paper, it would have obscured the fact that almost all the patients with normal peak V02 levels exhibited unusual breathing problems – and unusual breathing patterns can, by themselves, affect exercise tolerance.

Similarly, the fact that “only” about half of the PASC patients (46%) met the criteria for ME/CFS may tell us more about the ME/CFS definition than about the patients themselves, as the vast majority of PASC patients demonstrated problems during exercise. Ditto with the fact that about 60% of patients hit their anaerobic threshold earlier than expected, yet only 46% met the criteria for ME/CFS.

Michael Gallagher’s and Brian Schulzes’ experience with ME/CFS indicates that it can take many forms and produce significant disability before one meets the criteria. At some point a redefinition – based on biological biomarkers that track exertion-based problems – is surely in order.

Getting Run Down by ME/CFS – A Memoir: Summer Reading # I

One thing this study did not find was much exercise-induced hyperventilation. This finding tracks with Cook’s recent big CDC exercise study which also found little hyperventilation but did find an altered breathing pattern consisting of slow, deep breathing in ME/CFS.


Diaphragmatic breathing

Breathing has come to the fore recently in both long COVID and ME/CFS. (Diaphragmatic breathing (from Wikimedia Commons by John Pierce).

This exercise study dug deeper than any before it into breathing issues. It struck gold when it found that 88% of long COVID participants displayed a “breathing dysfunction” during exercise. The variety of different breathing dysfunctions found demonstrated, once again, that many roads can lead to Rome; i.e. to exercise intolerance. Demonstrating how revealing exercise tests can be, only 2 of the long COVID participants had a normal exercise test result.

Evidence of some sort of circulatory impairment that is preventing the fully oxygenated blood from getting to the muscles was common and preload problems were found as well. While the cause of circulatory impairment was unclear – and may be caused by metabolic problems – the authors suggested that breathing retraining exercises might help and a blog will be up on them soon.

With a large CDC study finding that problems with “ventilation” and breathing are common in ME/CFS and the recent publication of other long COVID breathing studies – one of which that’s bringing problems with the microcirculation to the fore – we will likely see more and more emphasis on the possibly vital issue of “gas exchange” (read energy exchange) in these diseases.  Could the problem simply be not enough oxygen (i.e. energy) getting to the cells? A blog on that is coming up shortly.


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