Progression from respiratory dysfunction to failure in late-onset Pompe disease

To identify determinants of respiratory disease progression in late-onset Pompe disease (LOPD), we studied relationships between pulmonary function, respiratory muscle strength, gas exchange, and respiratory control. Longitudinal evaluation of 22 LOPD patients (mean age 38 years) was performed at 6-month intervals for 6-24 months. Measurements included vital capacity (VC), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), tidal volume (VT), dead space (VD), and ventilatory response to CO2. Although reduction in VC correlated with MIP and MEP (p < 0.0001), some patients had normal VC despite reduced MIP and MEP (5 [23%] and 9 [41%] patients, respectively). Daytime hypercapnia was associated with reduced VC (<60% predicted) and MIP (<40% predicted). Moreover, chronic hypercapnia was associated with elevated VD/VT (≥0.44) due to falling VT (≈300 ml), compatible with reduced efficiency of CO2 clearance. The presence of hypercapnia and/or ventilatory support was associated with reduced ventilatory responsiveness to CO2 (≤0.7 l/min/mmHg). We conclude that daytime hypercapnia, an indicator of chronic respiratory failure, is tightly linked to the degree of respiratory muscle weakness and severity of pulmonary dysfunction in LOPD patients. Reductions in CO2 clearance efficiency and ventilatory responsiveness may contribute to the development of chronic daytime hypercapnia.