Respiratory sensations in subjects who lack a ventilatory response to CO2.

An urge to breath is perceived during breath hold and hypercapnia (termed 'air hunger') and during heavy exercise (often termed 'shortness of breath'). To better understand the neural mechanisms responsible for these sensations we studied five patients (8-17 years old) with congenital central hypoventilation syndrome (CCHS) who lack ventilatory response to CO2. CCHS patients reported no respiratory discomfort during CO2 inhalation or during maximal breath hold which was of much longer duration than age-matched controls. However, all 3 CCHS patients who exercised heavily reported some sensations akin to shortness of breath (they increased breathing nearly as much as controls). Our results are consistent with two possibilities. First, the air hunger of hypercapnia and breath hold is caused by projection to the forebrain of respiratory chemoreceptor afferents which bypass the respiratory centers, while exercise shortness of breath is caused by direct projections of limb afferents or locomotory center activity. Second, air hunger and shortness of breath share the same origin--projection of increased brain stem respiratory center motor activity (corollary discharge) to the forebrain.