Current Standards and Future Directions of Duchenne Muscular Dystrophy Respiratory Care: The PPMD Italy Meeting Report

Abstract

Objective: This report summarizes key discussions from the meeting "Current Standards and Future Directions of Respiratory Assessment and Management of Duchenne Muscular Dystrophy (DMD)," organized by Parent Project Muscular Dystrophy (PPMD) Italy and the United States to address current challenges and opportunities in DMD respiratory care.

Methods: The meeting brought together researchers, clinicians, and patient advocates who shared experiences, discussed advancements in DMD respiratory management, and identified areas of debate that require further research.

Results: The speakers emphasized routine assessment of pulmonary function and of breathing during sleep to achieve timely diagnosis of respiratory complications. Therapeutic discussions focused on airway clearance and assisted ventilation, highlighting noninvasive ventilation (NIV) as the preferred modality, even for advanced respiratory failure. The respiratory implications of new pharmacological therapies were discussed. The speakers endorsed the importance of cardiorespiratory outcomes in assessments of drug efficacy. To assess a drug's clinical impact and to define current respiratory phenotypes, the trajectory of the absolute value of forced vital capacity (FVC) was proposed as a potentially better parameter than FVC percent predicted, which is favored in current drug studies. In regard to management of acute respiratory failure and perioperative situations, standards of care and areas needing future research were identified.

Conclusion: In this meeting, many points of consensus emerged, as well as areas requiring further research. The necessity to involve patients and their families in all aspects of respiratory care was emphasized, as well as the need for patient centered outcomes in medical decision making and research.

Keywords: Duchenne muscular dystrophy; anesthesia; mechanical insufflation‐exsufflation; new therapies; noninvasive ventilation; outcome measures; respiratory insufficiency.

Figure 1

Sleep disordered breathing across the clinical stages of disease progression in Duchenne muscular dystrophy (DMD). Upper panel (a) Example of a sleep event consistent with obstructive sleep apnea according to the American Academy of Sleep Medicine definition (AASM, Berry et al. [24]) in a 9‐year‐old boy with normal pulmonary function. The reduction of airflow lasts > 2 breaths and is associated with the presence of paradoxical breathing (out‐of‐synch thoracic and abdominal movements) without a reduction in the amplitude of either thoracic or abdominal traces and without an increased respiratory rate (RR). Lower panel (b) Example of a sleep event consistent with diaphragmatic apnea according to the newly defined scoring criteria for diaphragmatic events in DMD (Trucco et al. [9]) in a 17‐year‐old boy with restrictive lung disease. The reduction of airflow is associated with reduction in inspiratory effort throughout the entire duration of the event, increased RR and a relative reduction in thoracic versus abdominal effort. RR, respiratory rate; SUM, respiratory inductive plethysmography sum. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Trajectory of forced vital capacity (FVC) of individuals in the Canadian Neuromuscular Disease Registry (CNDR), expressed as FVC percent predicted for each age. (a) Observed data with a superimposed LOESS smooth curve. (b) Fitted linear model using generalized estimating equations. In each panel, the grey band represents 95% confidence intervals. Reproduced with permission. From: Birnkrant, DJ, Black, JB, Sheehan, DW et al. A New Perspective on Drugs for Duchenne Muscular Dystrophy: Proposals for Better Respiratory Outcomes and Improved Regulatory Pathways. Pediatr Drugs (2024). https://doi.org/10.1007/s40272-024-00673-3. Under license CC BY‐NC 4.0. https://creativecommons.org/licenses/by-nc/4.0/. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Lung function modified by DMD portrayed with a Rideau Plot (Absolute value of forced vital capacity [FVC] by age), showing three stages of pulmonary function: rising (green), plateau (blue), and declining (red). Reproduced with permission. From: Birnkrant, DJ, Black, JB, Sheehan, DW et al. A New Perspective on Drugs for Duchenne Muscular Dystrophy: Proposals for Better Respiratory Outcomes and Improved Regulatory Pathways. Pediatr Drugs (2024). https://doi.org/10.1007/s40272-024-00673-3. Under license CC BY‐NC 4.0. https://creativecommons.org/licenses/by-nc/4.0/. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

Trajectory of forced vital capacity (FVC) among individuals 10–18 years of age expressed as (a) percent predicted, where the rate of decline is portrayed as constant throughout the age range, and (b) absolute values, where it can be seen that FVC changes with age and spans three stages of pulmonary function: rising (green), plateau (blue), and declining (red). Reproduced with permission. From: Birnkrant, DJ, Black, JB, Sheehan, DW et al. A New Perspective on Drugs for Duchenne Muscular Dystrophy: Proposals for Better Respiratory Outcomes and Improved Regulatory Pathways. Pediatr Drugs (2024). https://doi.org/10.1007/s40272-024-00673-3. Under license CC BY‐NC 4.0. https://creativecommons.org/licenses/by-nc/4.0/. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 5

Absolute forced vital capacity (FVC) in individuals 10–18 years of age, with glucocorticoid therapy (red) and without glucocorticoid therapy (blue). Reproduced with permission. From: Birnkrant, DJ, Black, JB, Sheehan, DW et al. A New Perspective on Drugs for Duchenne Muscular Dystrophy: Proposals for Better Respiratory Outcomes and Improved Regulatory Pathways. Pediatr Drugs (2024). https://doi.org/10.1007/s40272-024-00673-3. Under license CC BY‐NC 4.0. https://creativecommons.org/licenses/by-nc/4.0/. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 6

Forced vital capacity (FVC) with aging in two brothers with discordant pulmonary function. Reproduced with permission. From: Birnkrant DJ, Ashwath ML, Nortiz GH, Merrill MC, Shah TA, Crowe CA, Bahler RC. Cardiac and pulmonary function variability in Duchenne muscular dystrophy: an initial report. J Child Neurol 2010; 25: 1110–1115. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 7

Phenotypic discordance in patients with identical dystrophin mutations. Four patients with deletion of exon 44 show diametrically different profiles in heart and lung function despite an identical dystrophin genotype. EF, ejection fraction. FVC, forced vital capacity. Reproduced with permission. From: Jin JB, Carter JC, Sheehan DW, Birnkrant DJ. Cardiopulmonary discordance is common in Duchenne muscular dystrophy. Pediatr Pulmonol 2019; 54: 186–193. [Color figure can be viewed at wileyonlinelibrary.com]