Inspiratory Muscle Loading May Be Meaningful Therapy in SMA

This study suggests that the diaphragm may fare differently from other muscles in spinal muscular atrophy (SMA).

People with spinal muscular atrophy (SMA) may benefit from respiratory training, according to a new study that explored how patients’ respiratory muscles responded to endurance tests.

SMA is a neuromuscular disease in which patients lose—or never gain—motor function. The disease is categorized into 4 types based on age of onset and achievable motor function.

The study authors said respiratory failure is the most important cause of morbidity and mortality among people with the disease. Yet, even as new therapies have become available that can improve motor function, strength, and survival, there is evidence that lung function may not improve with treatment.

In a new study in Pediatric Pulmonology, the authors attempted to find out whether inspiratory muscle loading—a form of incremental strength training—might lead to better outcomes in these patients. They also wanted to find out more about the role of respiratory muscle fatigability (RMF), a lack of respiratory muscle endurance, in cases of SMA.

The authors recruited 19 children (median age, 11 years) and 36 adults (median age, 34 years), all of whom had SMA type 2 or type 3. Patients with type 2 SMA are able to sit on their own but are unable to stand or walk. People with type 3 receive their diagnosis after 18 months of age. They learn to walk, but eventually lose that ability as the disease progresses.

Each patient’s maximum inspiratory mouth pressure was assessed, after which they had to breaths against an inspiratory threshold load ranging from 20% to 70% of their maximal pressure. Once a patient was unable to complete 60 consecutive breaths, they were categorized as experiencing RMF.

The data showed that participants had a dose-dependent increase in RMF, but that it did not correlate with an increase in exercise-induced muscle weakness.

“The probability of experiencing RMF in our study was the highest at an inspiratory threshold load of 55% of their individual PImax (maximal inspiratory mouth pressure), which is similar to the probability in healthy individuals and 20% higher than in patients with DMD (Duchenne muscular dystrophy),” the authors wrote.

They noted that research into arm- and leg-muscle fatigability has shown that people with SMA tire faster than people with DMD, even though they have similar rates of muscle weakness. Thus, they assumed the same would be true with respiratory muscle fatigue. The reason for the unexpected finding, they said, may be that the diaphragm, the muscle primarily responsible for breathing, is left “relatively spared” in SMA.

The investigators said the study findings suggest that inspiratory loading is feasible in people with SMA, meaning that respiratory training might be a meaningful intervention in these patients. “This study shows that respiratory muscle endurance seems adequate in patients with SMA, but the low baseline levels of PImax suggest a therapeutic window for respiratory muscle strength training,” they wrote.

Bartels and colleagues said more research should be conducted to better understand the potential of such therapy to stabilize or improve respiratory function in SMA.

Reference

Kant-Smits K, Hulzebos EHJ, Habets LE, et al. Respiratory muscle fatigability in patients with spinal muscular atrophy. Pediatr Pulmonol. Published online August 30, 2022. doi:10.1002/ppul.26133