Abnormal breathing patterns and hyperventilation are common in patients with chronic fatigue syndrome during exercise, 2025, Mancini, Natelson et al

[Wyva]

Donna M. Mancini, Danielle L. Brunjes, Dane Cook, Tiffany Soto, Michelle Blate, Patrick Quan, Tadahiro Yamazaki, Anna Norweg, Benjamin H. Natelson

Abstract

Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) experience symptoms of fatigue, dyspnea, mental fog, and worsening fatigue after physical or mental efforts. Some of these patients have been found to hyperventilate. In long COVID patients, many of whom also have ME/CFS, dysfunctional breathing (DB) has been described. Whether patients with ME/CFS, independent of COVID-19, experience dysfunctional breathing is unknown, as well as how it may relate to hyperventilation.

Methods: We performed serial 2-day cardiopulmonary exercise testing (CPET) in 57 patients with ME/CFS and 25 age- and activity-matched control participants. Peak oxygen consumption (VO2), ventilatory efficiency slope (VE/VCO2), O2 saturation, end-tidal CO2 (PetCO2), heart rate, and mean arterial blood pressure were measured in all patients during upright incremental bicycle exercise. Ventilatory patterns were reviewed using minute ventilation (VE) versus time, respiratory rate, and tidal volume versus minute ventilation graphs. Chronic hyperventilation (HV) was defined as a PETCO2 of <34 mm Hg that persisted during low-intensity exercise. Dysfunctional breathing was characterized by a 15% increase in oscillations in minute ventilation during at least 60% of the exercise duration or by a scatterplot pattern of respiratory rate and tidal volume plotted versus minute ventilation.

Results: The patients with ME/CFS had an average age of 38.6 ± 9.6 years, and a mean body mass index (BMI) of 24.1 ± 3.4, which was comparable to the sedentary controls. All participants performed maximal exercise, achieving a respiratory exchange ratio (RER) of >1.05. For the patients with ME/CFS, peak VO2 averaged 22.3 ± 5.3 mL/kg/min, which was 79 ± 20% of predicted and comparable to that observed in the sedentary controls (23.4 ± 4.6 mL/kg/min; 81 ± 12%; p = NS). A total of 24 patients with ME/CFS (42.1%) met the criteria for dysfunctional breathing compared to four sedentary controls (16%) (p < 0.02). In total, 18 patients with ME/CFS (32%) had hyperventilation compared to one sedentary control participant (4%) (p < 0.01), and nine patients with ME/CFS had both hyperventilation and dysfunctional breathing, whereas no sedentary participant exhibited both. The patients with ME/CFS and hyperventilation had significantly higher VE/VCO2 ratios (HV+: 34.7 ± 7.2; HV−: 28.1 ± 3.8; p < 0.001). A total of 15 of 18 patients with hyperventilation (83%) had either elevated VE /VCO2 ratios (n = 15) or dysfunctional breathing (n = 9) compared to 44% (n = 17) of the 40 non-hyperventilators (p < 0.01).

Conclusion: Dysfunctional breathing and hyperventilation are common in patients with ME/CFS and could present a new therapeutic target for these patients.

Open access: https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1669036/full

 

[Utsikt]

There are no strict criteria for the identification of dysfunctional breathing. Identification is based on pattern recognition (7). We reviewed graphs of minute ventilation (VE) versus time, as well as respiratory rate (RR) and tidal volume (VT) versus VE (ml/min). For the VE versus time graph, we applied the American Heart Association’s definition of exercise oscillatory ventilation—that is, cyclic ventilation that persists for at least 60% of the exercise test with an amplitude 15% or more above resting values—to identify significant breathing abnormalities, specifically dysfunctional breathing (25).

For the plots of tidal volume and respiratory rate versus minute ventilation, a normal pattern generally shows an early rapid rise in tidal volume that plateaus, accompanied by an initial slow, then progressively faster, rise in respiratory rate—yielding a football-shaped plot. With dysfunctional breathing, there is marked variability in respiratory rate and tidal volume throughout most of the exercise, yielding a scatterplot graph. Dysfunctional breathing was identified if a participant’s data showed either oscillatory ventilation in the VE versus time plot or a scatterplot pattern in the VT versus VE and RR graphs.

The assessment of the breathing patters were mostly subjective, but I see no mention of blinding of the assessors.

I wonder if every case was as clear cut as figure 1?

Figure 1. (A) Normal and (B) dysfunctional respiratory patterns in two different ME/CFS cases, with respiratory rate (RR) on the left y-axis and tidal volume (VT) on the right y-axis plotted against minute ventilation (VE) on the x-axis. (RR = respiratory rate, orange dots; VT tidal volume, blue dots) (see text).

In the patients with ME/CFS, peak VO2 averaged 22.4 ± 5.4 mL/kg/min, which was 79 ± 20% of predicted. The results from the 25 sedentary controls were comparable, although maximal HR was higher in the control group (p < 0.05) and perceived exertion at end exercise was significantly lower (p < 0.001).

There is no mention of the HR, Borg or peakVO2 rates for the HV vs non-HV ME/CFS groups.

 

[Utsikt]

I don’t think the justification for doing 57 two-day CPETs is good enough.

The authors seem to believe that the ME/CFS symptoms might be caused by dysfunctional breathing, and that it can be fixed by breathing retraining and rehab.

The combination of hyperventilation and dysfunctional breathing can result in a variety of symptoms, including dyspnea, fatigue, chest pain, palpitations, anxiety, and non-specific neurological symptoms such as tingling.

The patients with hyperventilation at the start of exercise, whether acute or persistent, had a high frequency of dysfunctional breathing. These initial hyperventilation patterns can trigger dyspnea due to increased respiratory muscle workload.

The identification of dysfunctional breathing and resting hypocapnia in this cohort is an important observation, as it may represent a target for treatment. Breathing retraining can be effective in relieving symptoms.

The observation of a high frequency of disorganized breathing in patients with ME/CFS is important, as it provides a potential therapeutic target for this patient population via breathing retraining and pulmonary rehabilitation.

In conclusion, dysfunctional breathing and hyperventilation are observed frequently in patients with ME/CFS and are new therapeutic targets for these patients. Future studies with breathing retraining techniques should be considered to reduce symptoms and improve exercise performance.

 

[duncan]

Dysfunctional breathing and hyperventilation are common in patients with ME/CFS and could present a new therapeutic target for these patients.

New? This has been a refrain for two decades at least.

 

[Mij]

My breathing is normal when out power walking in the evenings. I feel a bit breathless/shaky when I go out during the daytime before 5pm.

 

[rvallee]

They seem to be making a looot of assumptions. Even before the silly "breath retraining" nonsense.

Unless I got it wrong, they defined hyperventilation not as an increase in respiration, but as a decrease in blood CO2, which they assume must be hyperventilation. Obviously this is not hyperventilation as commonly understood, which they clearly, even pretty much directly, assume is anxiety and/or panic attacks and/or whatever.

See, here:

End-tidal CO2 < 34 mm Hg was used to define hypocapnia and hyperventilation.

So they defined both hypocapnia (low expired) CO2 and hyperventilation as low expired CO2. Nothing to do with respiratory rate, which is what hyperventilation is. Definitions don't appear to be coherent outside of "you exhale more CO2", rather than some increase in respiratory rate, so this is what the researchers are doing, it's consistent with the literature, but it's supposed to be rapid/deep breathing that leads to that change in expired CO2, and this is not what's happening here. Plus this kind of panicked hyperventilation is unrelated to effort, so that makes even less sense in the context of maximal effort exercise.

The metabolic differences are something, although the rest of the analysis makes it less likely to be relevant, but they just seem to decide it has to be caused by breathing method, or pattern, or whatever. This seems to be pure speculation. There is a problem, somewhere, and they just decided it must be that. Presumably, given that this is a pattern in academia, because attributing this 'dysfunctional breathing' as a cause yields the typical "just retrain your breathing, bro".

Basically they seem to have found something, but having started with speculation about hyperventilation based entirely on expired CO2, but I can't remember such low blood CO2 being found before. Not that I have a good memory anyway.

I don't know why they presented two cases as a graph 'showing' dysfunctional patterns instead of showing them all. They may be typical. They may not be. They seem to have been selected because they sell the speculation, but it only makes everything else weaker for it. They are selling a narrative more than doing research.

So many problems with medical research seem to be caused mainly or entirely because of poor speculation. The field should really stop doing that. It almost never adds anything and removes a lot of value from objective findings.

 

[Dolphin]

Link found between chronic fatigue and abnormal breathing could lead to new treatments

Chronic fatigue syndrome — medically unexplained fatigue lasting six months or more, preventing people from carrying out their normal activities, and often worsening after any exertion — is hard to treat. But new research could offer a lifeline. Chronic fatigue patients appear to be much more...

www.eurekalert.org

News Release 10-Nov-2025

Link found between chronic fatigue and abnormal breathing could lead to new treatments​

New study finds that many people with chronic fatigue syndrome experience disordered breathing which may be worsening symptoms

Peer-Reviewed Publication
Frontiers


Chronic fatigue syndrome leaves patients exhausted and struggling with brain fog — and it typically gets worse after mental or physical exercise, a phenomenon called post-exertional malaise. Now scientists investigating shortness of breath in chronic fatigue patients have discovered that they are highly likely to experience dysfunctional breathing, which could be caused by dysautonomia, abnormal control of innervation to blood vessels and muscles. Targeting treatments towards these breathing problems could potentially offer patients some relief from their symptoms.

“Nearly half of our chronic fatigue subjects had some disorder of breathing — a totally unappreciated issue, probably involved in making symptoms worse,” said Dr Benjamin Natelson of Icahn School of Medicine, senior author of the article in Frontiers in Medicine. “Identifying these abnormalities will lead researchers to new strategies to treat them, with the ultimate goal of reducing symptoms.”

Breathe easy

The scientists recruited 57 patients diagnosed with chronic fatigue syndrome and 25 control participants whose ages and activity levels matched the chronic fatigue cohort. Both groups took part in cardiopulmonary exercise tests over two days. The scientists measured their heart rate and blood pressure, how effectively they were taking in oxygen, the oxygen saturation of their blood, and how hard they had to breathe to get enough oxygen. They also tracked how fast participants breathed and the patterns of their breathing, to identify hyperventilation and dysfunctional breathing.

Dysfunctional breathing is usually associated with asthma patients, but it can arise from many different causes. Characteristics include deep sighing in the course of ordinary breathing, overly rapid breathing, forcing your exhale from your abdomen, breathing from your chest without using your diaphragm so your lungs are never properly full, and a loss of synchrony between your chest and abdomen, so the different muscles which help you breathe aren’t working together.

“While we know the symptoms generated by hyperventilation, we remain unsure what symptoms may be worse with dysfunctional breathing,” said Dr Donna Mancini of the Icahn School of Medicine, first author of the article. “But we are sure patients can have dysfunctional breathing without being aware of it. Dysfunctional breathing can occur in a resting state.”

Catching your breath

The scientists found that participants with chronic fatigue were taking in approximately the same amount of oxygen when they breathed compared to the control participants — their peak VO2 maxes were comparable. However, 71% of the participants with chronic fatigue experienced breathing problems — either hyperventilation, dysfunctional breathing, or both.

Almost half of the participants with chronic fatigue were observed breathing erratically during the test, compared to only four of the control participants. A third of the chronic fatigue patients hyperventilated, compared to just one control participant. Nine chronic fatigue patients displayed dysfunctional breathing as well as hyperventilation. None of the control participants had this combination of breathing issues.

Both dysfunctional breathing and hyperventilation can cause symptoms similar to chronic fatigue, like dizziness, difficulty focusing, shortness of breath and exhaustion. Combining the two can also cause people to experience heart palpitations, chest pain, fatigue, and (unsurprisingly) anxiety. These breathing problems, the scientists suggest, could be exacerbating chronic fatigue symptoms or even directly contributing to post-exertional malaise.

“Possibly dysautonomia could trigger more rapid and irregular breathing,” said Mancini. “It is well known that chronic fatigue syndrome patients often have dysautonomia in the form of orthostatic intolerance, which means you feel worse when upright and not moving. This raises the heart rate and leads to hyperventilation.”

Pulmonary physiotherapy?

This could mean that tackling dysfunctional breathing would relieve some patients’ symptoms. The scientists intend to follow up on this research to learn more about how dysfunctional breathing and hyperventilation interact. Although more research will be needed before treatments can be rolled out, they already have ideas for possible therapies that could improve breathing function.

“Breathing exercises via yoga could potentially help, or gentle physical conditioning where breath control is important, as with swimming,” suggested Natelson. “Or biofeedback, with assessment of breathing while encouraging gentle continuous breath use. If a patient is hyperventilating, this can be seen by a device that measures exhaled CO2.  If this value is low, then the patient can try to reduce the depth of breathing to raise it to more normal values.”

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Journal​

Frontiers in Medicine

DOI​

10.3389/fmed.2025.1669036

Method of Research​

Observational study

Subject of Research​

People

Article Title​

Abnormal Breathing Patterns and Hyperventilation are Common in Patients with Chronic Fatigue Syndrome during Exercise

Article Publication Date​

10-Nov-2025

COI Statement​

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 

[Yann04]