Diaphragm pacing and independent breathing in individuals with severe Pompe disease.

Introduction: Pompe disease is an inherited disease characterized by a deficit in acid-α-glucosidase (GAA), an enzyme which degrades lysosomal glycogen. The phrenic-diaphragm motor system is affected preferentially, and respiratory failure often occurs despite GAA enzyme replacement therapy. We hypothesized that the continued use of diaphragm pacing (DP) might improve ventilator-dependent subjects' respiratory outcomes and increase ventilator-free time tolerance. Methods: Six patients (3 pediatric) underwent clinical DP implantation and started diaphragm conditioning, which involved progressively longer periods of daily, low intensity stimulation. Longitudinal respiratory breathing pattern, diaphragm electromyography, and pulmonary function tests were completed when possible, to assess feasibility of use, as well as diaphragm and ventilatory responses to conditioning. Results: All subjects were eventually able to undergo full-time conditioning via DP and increase their maximal tolerated time off-ventilator, when compared to pre-implant function. Over time, 3 of 6 subjects also demonstrated increased or stable minute ventilation throughout the day, without positive-pressure ventilation assistance. Discussion: Respiratory insufficiency is one of the main causes of death in patients with Pompe disease. Our results indicate that DP in Pompe disease was feasible, led to few adverse events and stabilized breathing for up to 7 years.

Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study.

Respiratory failure is the main cause of death in amyotrophic lateral sclerosis (ALS). Since no effective treatments to preserve independent breathing are available, there is a critical need for new therapies to preserve or restore breathing ability. Since acute intermittent hypoxia (AIH) elicits spinal respiratory motor plasticity in rodent ALS models, and may restore breathing ability in people with ALS, we performed a proof-of-principle study to investigate this possibility in ALS patients. Quiet breathing, sniff nasal inspiratory pressure (SNIP) and maximal inspiratory pressure (MIP) were tested in 13 persons with ALS and 10 age-matched controls, before and 60 min post-AIH (15, 1 min episodes of 10% O2, 2 min normoxic intervals) or sham AIH (continuous normoxia). The root mean square (RMS) of the right and left diaphragm, 2nd parasternal, scalene and sternocleidomastoid muscles were monitored. A vector analysis was used to calculate summated vector magnitude (Mag) and similarity index (SI) of collective EMG activity during quiet breathing, SNIP and MIP maneuvers. AIH facilitated tidal volume and minute ventilation (treatment main effects: p < 0.05), and Mag (ie. collective respiratory muscle activity; p < 0.001) during quiet breathing in ALS and control subjects, but there was no effect on SI during quiet breathing. SNIP SI decreased in both groups post-AIH (p < 0.005), whereas Mag was unchanged (p = 0.09). No differences were observed in SNIP or MIP post AIH in either group. Discomfort was not reported during AIH by any subject, nor were adverse events observed. Thus, AIH may be a safe way to increase collective inspiratory muscle activity during quiet breathing in ALS patients, although a single AIH presentation was not sufficient to significantly increase peak inspiratory pressure generation. These preliminary results provide evidence that AIH may improve breathing function in people with ALS, and that future studies of prolonged, repetitive AIH protocols are warranted.