Congenital central hypoventilation syndrome and ventilatory responses during cardiopulmonary exercise testing

Abstract

Background: Previous studies have shown evidence of hypoxemia and hypercapnia during cardiopulmonary exercise test (CPET) evaluation in children with congenital central hypoventilation syndrome (CCHS). However, there are no longitudinal studies which compared CPET findings to polysomnogram (PSG) or PHOX2B mutation, to date.Objectives: To describe the longitudinal CPET findings in a cohort of children with CCHS and correlate the findings to the PSG results.Methods: This retrospective study was conducted in children with CCHS followed in the Long-term Ventilation Program at SickKids, Toronto, Canada between September, 2013 and January, 2020. CCHS genetic mutation, age of diagnosis, ventilatory support, family history, disease associations of CCHS, CPETs, and PSG parameters were recorded and analyzed.Results: A total of nine patients with CCHS (46 CPETs and 46 PSGs) were enrolled. Four (44.4%) children had polyalanine repeat mutations. The mean (SD) age at the time of diagnosis and duration of ventilatory usage were 3.2 ± 3.4 years and 11.5 ± 2.8 years, respectively. All abnormal CPETs had hypercapnia in at least 1 phase of the exercise test. Hypercapnia (12/46; 26.1%) at peak of exercise was the most common abnormality. None of the children experienced an oxygen desaturation below 90%. End-tidal CO 2 (PetCO 2 ) at rest and at peak exercise in the CPETs were significantly correlated with PSG TcCO 2 while PetCO 2 at anaerobic threshold was correlated with CO 2 in pre-PSG capillary blood gas. Conclusion:Nocturnal hypoventilation may impact the CPET results in CCHS children. Serial CPETs should be considered standard clinical care for all CCHS children.

Impaired ventilation during 6‐min walk test in congenital central hypoventilation syndrome

“…In our study, most (93%) patients exercised and participated in mainstream PE without restrictions, including moderate to strenuous exercise without experiencing any symptoms. The results of our study and prior studies showing gas exchange abnormalities with exercise suggests that monitoring SpO 2 and ETCO 2 during exercise should be strongly considered and an individualized exercise plan should be formulated 3–6 . Paton et al and Hager et al showed that CCHS patients increased minute ventilation during exercise, but to a lesser extent than controls 3,5 .…”

“…There is limited literature on PHOX2B genotype−phenotype correlation for ventilatory disturbances during exercise. A retrospective study of nine patients with CCHS—four with PARM and five with NPARM—requiring nocturnal NPPV identified higher ETCO 2 in patients with PARMs at peak exercise during a cycle cardiopulmonary exercise test 4 . During the 6MWT, we found a significant difference between the peak ETCO 2 and nadir SpO 2 between the three PHOX2B genotype groups.…”

“…Only a few studies have assessed oxygenation and ventilation during exercise in CCHS 3–6,8 . Silvestri et al reported hypoxemia and hypercapnia in children with CCHS requiring continuous AV utilizing a walking treadmill protocol simulating modest levels of daily activity 6 .…”

“…Therefore, they are at risk for undetected hypoxemia and hypercapnia during exercise 3 . Indeed, studies assessing oxygenation and ventilation during maximal and submaximal exercise utilizing various protocols such as cardiopulmonary exercise test on a cycle ergometer, a walking treadmill protocol, and incremental treadmill exercise have demonstrated gas exchange abnormalities 3–6 . Patients with CCHS are at risk for neurodevelopmental delays and pulmonary hypertension (PH) due to recurrent hypoxemia and hypoventilation.…”

“…3 Indeed, studies assessing oxygenation and ventilation during maximal and submaximal exercise utilizing various protocols such as cardiopulmonary exercise test on a cycle ergometer, a walking treadmill protocol, and incremental treadmill exercise have demonstrated gas exchange abnormalities. [3][4][5][6] Patients with CCHS are at risk for neurodevelopmental delays and pulmonary hypertension (PH) due to recurrent hypoxemia and hypoventilation. Therefore, ensuring adequate oxygenation and ventilation are important to optimize neurocognitive outcomes and prevent PH.…”