Research Article: Cardiopulmonary exercise testing for identification of patients with hyperventilation syndrome

Date Published: April 23, 2019

Publisher: Public Library of Science

Author(s): Kristian Brat, Nela Stastna, Zdenek Merta, Lyle J. Olson, Bruce D. Johnson, Ivan Cundrle, Sean M. Collins.


Measurement of ventilatory efficiency, defined as minute ventilation per unit carbon dioxide production (VE/VCO2), by cardiopulmonary exercise testing (CPET) has been proposed as a screen for hyperventilation syndrome (HVS). However, increased VE/VCO2 may be associated with other disorders which need to be distinguished from HVS. A more specific marker of HVS by CPET would be clinically useful. We hypothesized ventilatory control during exercise is abnormal in patients with HVS.

Patients who underwent CPET from years 2015 through 2017 were retrospectively identified and formed the study group. HVS was defined as dyspnea with respiratory alkalosis (pH >7.45) at peak exercise with absence of acute or chronic respiratory, heart or psychiatric disease. Healthy patients were selected as controls. For comparison the Student t-test or Mann-Whitney U test were used. Data are summarized as mean ± SD or median (IQR); p<0.05 was considered significant. Twenty-nine patients with HVS were identified and 29 control subjects were selected. At rest, end-tidal carbon dioxide (PETCO2) was 27 mmHg (25–30) for HVS patients vs. 30 mmHg (28–32); in controls (p = 0.05). At peak exercise PETCO2 was also significantly lower (27 ± 4 mmHg vs. 35 ± 4 mmHg; p<0.01) and VE/VCO2 higher ((38 (35–43) vs. 31 (27–34); p<0.01)) in patients with HVS. In contrast to controls, there were minimal changes of PETCO2 (0.50 ± 5.26 mmHg vs. 6.2 ± 4.6 mmHg; p<0.01) and VE/VCO2 ((0.17 (-4.24–6.02) vs. -6.6 (-11.4-(-2.8)); p<0.01)) during exercise in patients with HVS. The absence of VE/VCO2 and PETCO2 change during exercise was specific for HVS (83% and 93%, respectively). Absence of VE/VCO2 and PETCO2 change during exercise may identify patients with HVS.

Partial Text

Hyperventilation syndrome (HVS) is characterized as episodic dyspnea with inappropriately high alveolar ventilation exceeding metabolic requirements [1,2]. HVS is highly prevalent in patients with psychological pathologies [3]. However, it is not clear if psychological pathologies are a cause of HVS [4,5].

Fifty-eight patients were included in this retrospective study. Twenty-nine patients were diagnosed with HVS and comprised the study group and 29 patients served as healthy controls. Group comparison of subject characteristics, pulmonary function test parameters and arterial blood gases are shown in Table 1. Subjects with HVS were mostly women with significantly lower BMI. There were no differences in pulmonary function test parameters or arterial blood gas analysis at rest. At peak exercise patients with HVS exhibited higher PaO2 and by definition higher pH and lower PaCO2.

The major finding of this study was that in patients with HVS both the VE/VCO2 and PETCO2 remained relatively unchanged from rest to peak exercise in patients with HVS consistent with abnormal ventilatory control throughout exercise.”

In subjects with HVS, both VE/VCO2 and PETCO2 remained unchanged from rest to peak exercise in patients with HVS suggesting abnormal ventilatory control. These findings may promote recognition of the HVS phenotype by evaluation of patients by CPET.