Transforming Respiratory Care for Patients with Neuromuscular Disorders

When pediatric pulmonologist Oren Kupfer, MD, started his career, he noticed a gap in care for patients with neuromuscular disorders — they typically didn’t have systematic care from a pulmonologist. These disorders gradually cause muscle atrophy and weakness, often leading to difficulty breathing, and respiratory failure is a common cause of death for those impacted by these conditions. When Dr. Kupfer joined the faculty at the University of Colorado over a decade ago, he committed his career to being the integrated pulmonologist in Children Hospital Colorado’s multidisciplinary Neuromuscular Clinic to provide that specialized support for these kids.

New surveillance techniques

In the last eight years, the U.S Food and Drug Administration has approved multiple gene-targeted therapies for neuromuscular diseases. For spinal muscular atrophy, a gene transfer therapy (Zolgensma) and two RNA splicing modifiers (Spinraza and Evrysdi) are in use. For Duchenne muscular dystrophy, four exon-skipping drugs (Exondys 51, Vyondys 53, Viltepso and Amondys 45), two corticosteroids (Deflazacort and Agamree), a gene transfer therapy (Elevidys), and an anti-inflammatory agent (Duvyzat) are in use. Because the respiratory problems in this disease appear later in childhood, doctors don’t know yet the impact these new therapies will have on respiratory decline.

“If we want to institute treatments to prevent respiratory failure for these patients, we have to do that really, really early — like a decade or two before respiratory failure happens,” Dr. Kupfer explains. “We have not had the time to see if these novel therapies have had the impact we want yet.”

As the medical field waits to see the impact of these new therapies, Dr. Kupfer is focusing on surveillance for his patients, especially those on the new treatments. Twice a year they measure pulmonary function and analyze those results with what they expect to be happening.

Now, Dr. Kupfer and his team are exploring new avenues to get the most in-depth picture of what’s happening to the lungs in an effort to flag any potential struggles as early as possible for intervention. Using electrical impedance tomography (EIT), the team is testing a non-invasive way to measure airflow and blood flow to the lungs. Dr. Kupfer hopes this can detect a change in lung function earlier than the typical spirometry test. This can also measure changes in real time, so if a child is sick, the team can see how lungs respond to treatment in a patient with weaker muscles.

The team conducted a pilot study with six patients in the Neuromuscular Clinic, analyzing the effectiveness of mechanical insufflation-exsufflation for airway clearance in patients with spinal muscular atrophy type I using EIT. According to the study’s authors, “EIT holds promise for estimating lung volumes and ventilation/perfusion mismatch, both of which are useful for assessing the effectiveness of MIE in clearing mucus plugs.”

The team is also exploring another test, impulse oscillometry, which measures airflow resistance. The team presumes that resistance to airflow gets higher if you have more muscle weakness. This test could be especially beneficial for kids who can’t do the standard pulmonary function tests for cognitive reasons or if they are too young.

“We are really trying to understand when respiratory disease starts in neuromuscular disorders,” Dr. Kupfer says. “Can we get an early signal, and is there something we can do about it?”

Delivery of care

The second focus of Dr. Kupfer’s work is the delivery of care for these patients. A lot of these breathing interventions involve non-invasive or invasive ventilation and mechanical airway clearance, which requires patients to wear and rely on multiple forms of technology.

“These are boys with Duchenne muscular dystrophy who are losing the ability to walk around 10 to 12 years old. So right as they are supposed to be becoming more independent middle school boys, they become more dependent,” Dr. Kupfer says. “This is a disease that really robs them of their independence. So when I ask someone — and I mean ask, not tell — ask someone to use respiratory support, it has to be in the context of their life-limiting disease. I think that’s super important to understand that [respiratory struggles] are just one part of a terrible disease.”

He emphasizes the importance for pulmonologists to really understand the physical and psychological impact of telling a child they have to wear this kind of technology.  Children’s Colorado provides a robust psychology and respiratory therapy program that helps patients and families through a desensitization process for noninvasive ventilation. These critical resources help promote use along with steady perseverance from parents and caregivers.