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

Donna Macini^1*Danielle L Brunjes²Dane Cook³Tiffany Soto¹Michelle Blate¹Patrick Quan¹Tadahiro Yamazaki¹Anna Norweg¹Benjamin H Natelson^1*

• ¹Icahn School of Medicine at Mount Sinai, New York, United States
• ²Thermo Fischer, Walthem, United States
• ³University of Wisconsin System, Madison, United States

Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS] have symptoms of fatigue, dyspnea, mental fog and worsening fatigue after physical or mental efforts. Some of these patients also have hyperventilation. In long CoVid patients, many who also have ME/CFS, dysfunctional breathing has been described. Whether patients with ME/CFS independent of CoVid have dysfunctional breathing is unknown as well as how it may relate to hyperventilation. Methods: We performed serial 2 day cardiopulmonary exercise tests (CPET) in 57 patients with ME/CFS and 25 age and activity matched control subjects. Peak oxygen consumption (VO2), ventilatory efficiency slope (VE/VCO2) slope, O2 saturation, end tidal CO2 (PetCO2) heart rate and mean arterial blood pressure were measured in all patients during upright bicycle exercise. Ventilatory patterns were reviewed using minute ventilation (VE) versus time, respiratory rate and tidal volume versus minute ventilation graphs. Persistent hyperventilation was defined as PETCO2 <34 mm Hg that was sustained through low intensity exercise. Dysfunctional breathing was characterized as 15 % increase in oscillations in minute ventilation during at least 60% of exercise duration or scatterplot pattern of respiratory rate and tidal volume plotted versus VE. Results: Patients with ME/CFS had an average age of 38.6±9.6 years, and a mean body mass index of 24.1±3.4 which was comparable to controls. All subjects performed maximal exercise achieving a respiratory exchange ratio (RER) >1.05. For ME/CFS patients, peak VO2 averaged 22.3±5.3 ml/kg/min which was 79±20% of predicted and was comparable to that seen in controls (23.4±4.6 ml/kg/min; 81±12%; p=NS). Twenty-four ME/CFS patients (42.1%) met criteria for dysfunctional breathing versus 4 sedentary controls (16%) (p<0.02). Eighteen ME/CFS patients (32%) had hyperventilation compared to 1 sedentary control subject (4%) (p<0.01). Nine ME/CFS had both hyperventilation and dysfunctional breathing whereas no sedentary subject exhibited both. ME/CFS patients with hyperventilation had significantly higher VE/VCO2 ratios (HV+: 34.7±7.2; HV-: 28.1±3.8; p<0.001). 15 of 18 patients with hyperventilation (83%) had elevated VE /VCO2 ratios (n=15) or dyfunctional breathing (n=9) versus 44% (n=17) of 40 non hyperventilators (p<0.01). Discussion: Dysfunctional breathing and hyperventilation are common in patients with ME/CFS and could present a new therapeutic target for these patients.