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.