Ventilatory Response to CO ₂ During Exercise in Patients With Congenital Central Hypoventilation Syndrome

ABSTRACT Background Congenital central hypoventilation syndrome (CCHS) is characterized by a markedly impaired ventilatory response to CO 2 due to central chemoreceptor dysfunction. Although inadequate ventilation and hypercapnia during exercise have been reported, ventilatory response during exercise has not been quantitatively evaluated in CCHS. This study aimed to quantify ventilatory response during exercise and compare it with that at rest. Methods Ten patients with genetically confirmed CCHS underwent cardiopulmonary exercise test (CPET) using a stepwise incremental treadmill protocol with breath‐by‐breath respiratory gas analysis. CPET was terminated when end‐tidal CO 2 (EtCO 2 ) increased by at least 2% (15.2 mmHg) from baseline. Ventilatory response to CO 2 (VRCO 2 ) was calculated as Δminute volume (MV)/ΔEtCO 2 /body weight (mL/min/mmHg/kg). VRCO 2 at rest was measured using the CO 2 rebreathing method. Data are presented as median (interquartile range [IQR]). Results Age was 13.5 (12.3–15.5) years, and exercise duration was 5 min 53 s (4 min 47 s–6 min 56 s). Although MV increased during exercise, SpO 2 decreased and EtCO 2 increased, indicating hypoventilation. VRCO 2 during exercise was 2.27 (1.61–3.16), not significantly different from VRCO 2 at rest, 1.56 (1.07–2.83) ( p = 0.85). VRCO 2 was markedly lower than values in healthy children (34.6 (29.3–42.8)). No patients reported dyspnea, and no serious adverse events occurred. Conclusions VRCO 2 during exercise remains profoundly low in CCHS. No significant difference from VRCO 2 at rest was detected, suggesting persistent impairment of CO 2 ‐driven ventilatory control despite increased metabolic demand. These findings provide insight into exercise‐related hypoventilation in CCHS and underscore the importance of objective physiological assessment to support cautious and individualized clinical judgment rather than subjective symptoms.