Central CO₂ chemosensitivity and CO₂ controller gain independently contribute to daytime Pco₂ in young subjects with congenital central hypoventilation syndrome

Abstract

Whether peripheral chemoreceptor response is altered in congenital central hypoventilation syndrome (CCHS) remains debated. Our aim was to prospectively evaluate both peripheral and central CO2 chemosensitivity and to evaluate their correlations with daytime PCO2 and arterial desaturation during exercise in CCHS. To this end, tidal breathing was recorded in CCHS patients allowing the calculation of loop gain and its components (steady-state controller [assumed to mainly be peripheral chemosensitivity] and plant gains using a bivariate [PETCO2 and ventilation] constrained model), a hyperoxic, hypercapnic ventilatory response test (central chemosensitivity), and a six-minute walk test (arterial desaturation). The results of loop gain were compared to those previously obtained in a healthy group of similar age. The study prospectively included 23 subjects with CCHS, without daytime ventilatory support; the subjects had a median age of 10 (5.6 to 27.4) years (15 females) with moderate polyalanine repeat mutation (PARM: 20/25, 20/26, n=11), severe PARM (20/27, 20/33, n=8), or non-PARM (n=4). As compared to 23 healthy subjects (4.9 to 27.0 years), the subjects with CCHS had a decreased controller gain and an increased plant gain. Mean daytime PETCO2 level of subjects with CCHS correlated negatively to both Log(controller gain) and the slope of CO2 response. Genotype was not related to chemosensitivity. Arterial desaturation on exercise correlated negatively with Log(controller) gain but not with the slope of the CO2 response. In conclusion, we demonstrate that peripheral CO2 chemosensitivity is altered in some patients with CCHS and that the daytime PETCO2 depends on central and peripheral chemoreceptor responses.

Effect of Facemask in Congenital Central Hypoventilation Syndrome

“…We performed tidal breathing measurement to compute peripheral CO 2 chemosensitivity and the hypercapnic hyperoxic ventilatory response during hospitalization, as described previously [5]. Briefly, we recorded tidal breathing; it lasted for 20 min, and we discard the first 5 min.…”

“…We continuously monitored the flow rate, end-tidal partial pressure of oxygen (PO 2 ), and PetCO 2 and digitized the signals by using an ultrasonic flowmeter (Exhalyzer D, Eco Medics AG, Duernten, Switzerland). We used a constrained bivariate (minute ventilation _ V e and PetCO 2 ) analytical model to calculate the components of controller gain and plant gain (steady-state gains, time constants of the gains, and circulatory delays) [5]. The analyses were specifically related to peripheral chemosensitivity.…”

“…The analyses were specifically related to peripheral chemosensitivity. We measured the ventilatory response to hypercapnia during wakefulness by using a modification of Read's hyperoxic hypercapnic rebreathing technique [5].…”