Daytime Mouthpiece Ventilation Combined with Nocturnal Non-Invasive Ventilation in Adults with Duchenne Muscular Dystrophy: A 30-Day Pilot Feasibility Study

Background: DMD causes progressive respiratory muscle weakness and chronic alveolar hypoventilation requiring ventilatory support. While nocturnal non-invasive ventilation (NIV) is the standard care, daytime ventilation is often provided with prolonged use of nasal–oronasal masks. These interfaces can cause skin injury, air leaks, and reduced adherence. Mouthpiece ventilation (MPV) provides on-demand pressure support without an interface and may be an alternative for intermittent daytime ventilation. Objective: To assess the feasibility, safety, and clinical impact of MPV as an adjunct to nocturnal NIV in patients with DMD. Methods: Six patients with DMD and chronic respiratory failure on nocturnal NIV were enrolled in a 30-day observational pilot study. After training, participants used MPV during daytime. Clinical assessment, arterial blood gases, and quality of life evaluated with the S3-NIV questionnaire were performed at baseline (T0) and after 30 days (T1). Results: All patients tolerated MPV well, with mean daily use of >16 h. PaCO2 decreased in all patients (from 49.7 ± 7.1 to 43.5 ± 5.7 mmHg; p = 0.031); 4/6 were normocapnic at T1, whereas hypercapnia persisted in two. S3-NIV scores improved from 2.53 ± 0.69 at T0 to 4.87 ± 0.91 at T1 (p = 0.031). Patients reported improved performance of daily activities and better psychological well-being. No MPV-related adverse events occurred. Conclusions: MPV was feasible, safe, and well tolerated as an adjunct to nocturnal NIV in this small series of patients with DMD over 30 days. Given the small sample and short follow-up, no firm conclusions can be drawn; larger studies with longer follow-up are needed to confirm these findings and define the optimal role of MPV in DMD respiratory management.