Breathing Life Into ALS Care: The Vital Role of Multidisciplinary Teams

Merit Cudkowicz, MD, MSc

The outlook on care for patients with amyotrophic lateral sclerosis (ALS) has changed significantly in recent years, fueled by high-profile advocacy and campaigns, advancements in research and treatment, and public conversations about end-of-life care. One rising area of focus has been the stressed importance of a multidisciplinary team approach to improve respiratory function in these patients.

Regardless of the specifics of symptom onset, development of restrictive breathing patterns and hypoventilation occur in patients with ALS, leading to eventual respiratory failure in most patients. In ALS, diaphragm weakness reduces intrathoracic pressure, chest expansion, and elastic recoil during breathing. Upper motor neuron involvement causes chest wall rigidity and limits motion, increasing the effort needed for ventilation. Weakness in respiratory, laryngeal, and bulbar muscles impairs airway clearance, leading to difficulties in managing secretions, protecting the airway, and clearing tracheal aspirate.¹

"The number 1 reason people pass away from ALS is respiratory failure, and also quality of life is significantly diminished when someone isn’t breathing well,” Merit Cudkowicz, MD, MSc, who has been treating patients with ALS for more than 15 years, told NeurologLive^®. "Respiratory issues consume time, cause fatigue, and take a major toll on patients’ daily lives."

Multidisciplinary Care in ALS and the Need for Pulmonologists

Addressing the complex needs of ALS—and specifically respiratory function—involves a collaborative, multidisciplinary care model. A traditional care team these days may consist of some combination of a neurologist, physical therapist, occupational therapist, respiratory therapist, nurse, dietitian, speech language pathologist, social worker, and mental health professional, depending on the institution.

Cudkowicz, who is the director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, stressed the need for a complete care team, expressing that "the best care models for ALS involve a whole multidisciplinary team where neurologists, pulmonologists, therapists, social workers, and more come together. These teams are critical to maintaining quality of life and optimizing care."

Ventilatory support has 2 functions for patients with ALS: extending life expectancy and significantly improving day-to-day experiences by alleviating the distress of respiratory decline. Historically—and still in many parts of the country—respiratory care is provided by a respiratory therapist under the general supervision of a neurologist; however, the need for pulmonology specialists has been more widely recognized in recent years.

John Hansen-Flaschen, MD, PhD

"While [the involvement of only a neurologist] worked for a time, the technology and science have advanced far beyond what the team can manage effectively. It’s why we’re [at Penn Medicine] advancing a new specialty of pulmonary medicine focused on chronic respiratory failure, which includes support for people with neuromuscular diseases like ALS,” said John Hansen-Flaschen, MD, PhD, a pulmonary medicine specialist.

Hansen-Flaschen is the founding director of the Harron Lung Center and of the Jay and Randy Fishman Program for Home Assisted Ventilation. This world class program, located just outside of Philadelphia, provides comprehensive care to patients with neuromuscular disorders who have weak breathing muscles, including a large number of patients with ALS.

Named for its benefactors Jay and Randy Fishman, the Fishman Program underscores how dedicated centers can bridge critical care gaps for patients with ALS. Established in 2017, it has served as a model of comprehensive, patient-centered care that supports respiratory health in the context of a progressive disease. The center offers extensive home breathing treatment options, transitional care for young adults, coordinated care for adult respiratory conditions like ALS, telemedicine and telemetry options, and highly customized treatment plans using the most advanced technology.

"Two years ago, as I was winding down to retire, I saw my first-ever patient with ALS. I told him I had no experience with the disease but had some ideas about how to live with it. They really liked those ideas," Hansen-Flaschen said, regarding Jay and Randy Fishman. "That man and his wife ended up offering several millions of dollars to Penn for us to start a program for severe people with ALS and other neuromuscular diseases who need help with their breathing."

The utilization of pulmonology care is not truly standardized across the ALS care paradigm, with organizational direction and clinical guidelines lacking consistency in their recommendations around it—though some do stress its benefits and importance. The American Academy of Neurology (AAN) guidelines do not mention involving a pulmonologist and instead suggest involving a respiratory therapist as part of a multidisciplinary team. National organizations such as The ALS Association and the Muscular Dystrophy Association have offered financial incentives to from multidisciplinary outpatient clinics.

"Out of all the symptoms of ALS, secretion is the hardest to manage. We just don’t have good enough drugs for it," Cudkowicz said. "Sometimes there are great pulmonologists who are experts in this because they deal with it in other diseases like cystic fibrosis or other lung diseases where secretions are a big issue."

Proactive Management and Therapeutic Interventions to Improving Respiratory Function

There are several existing and emerging respiratory therapies used in the context of ALS care, including mechanical insufflation-exsufflation (MI-E), lung volume recruitment (LVR), noninvasive ventilation (NIV), respiratory strength training exercises (RST), and acute intermittent hypoxia (AIH). To date, RST is the only approach that supports ventilation, cough, and swallow function, whereas MI-E and LVR are the second most adjustable, supporting both ventilation and cough.³

Mechanical Insufflation-Exsufflation (MI-E)

This approach uses a special device to help with coughing. It inflates the lungs with positive pressure, then switches to negative pressure, mimicking a natural cough. This helps clear mucus from the airways in people who can't cough well on their own, improving breathing and reducing effort.

MI-E can help manage airway blockage, especially for patients with ALS who rely on ventilators. A small study found it more effective than suctioning at clearing mucus and reducing breathing effort, with patients reporting greater comfort.⁴ Other studies show that MI-E improves cough strength in various neuromuscular diseases and boost forced vital capacity (FVC) for up to an hour, which is critical for predicting respiratory failure. While MI-E may improve airway function, the extent of improvement varies across different neuromuscular diseases.

Lung Volume Recruitment (LVR)

LVR involves taking several deep breaths in a row, with the goal of inflating the lungs beyond normal breathing capacity. This can be done by the patient voluntarily or with help from a device like an ambu bag or mouthpiece. After inhaling, the patient holds their breath and exhales slowly to open up under-inflated areas of the lungs. Alternatively, the extra air can be used to strengthen the cough. This process increases lung pressure, helping to improve cough force.

LVR can temporarily improve voluntary cough strength, but its effect on reflex cough is less clear, which may affect a patient’s ability to detect and prevent aspiration. Since LVR alone may not lead to lasting improvements, a multicenter study (NCT03202017) is exploring whether combining LVR with expiratory strength training can enhance speech, breathing, and airway protection.⁵ This will be measured using tests like PCF, MEP, FVC, swallowing assessments, and speech intelligibility.

Noninvasive Ventilation (NIV)

NIV has been a staple of preventative respiratory care for patients with ALS, and it comes in many different forms, the most common being bilevel positive airway pressure (BiPAP). Other types of treatments include continuous positive airway pressure (CPAP), positive pressure ventilation via mouthpiece or mask, cough assist (also called MI-E), volume-assured pressure support (VAPS), and noninvasive positive pressure ventilation (NIPPV).

BiPAP, the most common form of NIV in ALS, provides 2 levels of pressure–higher pressure during inhalation and lower pressure during exhalation. This helps improve ventilation and reduce the work of breathing, especially at night or during periods of respiratory distress.

"We always want proactive BiPAP use and to start early," Cudkowicz added, "because it’s not the easiest thing to get used to, and to make sure a patient has time and a good respiratory therapist, both at the clinic and in the home, to help them out with that."

Respiratory Strength Training (RST)

Respiratory strength training is typically accomplished using portable devices that impose an external load to the muscles of inspiration or expiration. Evidence-based modes in general neuromuscular diseases have included the use of pressure-threshold or electrically braked flow-resistive devices, while respiratory strengthening has also been investigated to preserve airway protection behaviors.⁶

While inspiratory muscle training (IMT) has been common form of RST used, there is more needed on the effects of this approach on heart rate variability and autonomic function. Researchers have also called for more research on whether combined inspiratory and expiratory training is more effective for ventilation and airway protection. In other lung conditions, RST has reduced dyspnea and fear of movement, but it’s unclear if it has the same effect in ALS.⁷

Therapeutic Acute Intermittent Hypoxia (tAIH)

Unlike the direct effects of RST on respiratory output, therapeutic acute intermittent hypoxia aims to induce long-term facilitation of breathing through synaptic plasticity. tAIH involves brief periods of mild hypoxia alternating with normal oxygen levels. This triggers carotid body activity, stimulating brainstem respiratory nuclei and increasing ventilation. It also promotes serotonin release via the raphe nuclei, which activates signaling pathways that lead to brain-derived neurotrophic factor synthesis, essential for synaptic plasticity.⁸

Regarding how well these approaches are working in clinic, Cudkowicz noted that “I think some of them are very effective, like the cough assist and BiPAP. Where the field could use more help or more information is around secretion management. We have some nebulizers called mucolytics, but it’s hard to balance. You give some and then it’s too dry, which becomes problematic."

Emerging Research and Future Directions

Neurologists, pulmonologists, and other experts in the field have worked tirelessly to try new methods to improve respiratory care. Recent research has evaluated the impact of MI-E on small airway function, revealing increased lung clearance index values in neuromuscular disease, suggesting pathological lung involvement extends beyond weakness-related restriction. Although MI-E did not immediately improve LCI, it highlighted the need for tailored settings in patients with ALS, particularly those with bulbar dysfunction, where airway obstructions differ based on upper versus lower motor neuron involvement.⁹

Drug development has also produced newer agents, some of which show more pronounced effects on breathing function. RNS60 (Revalesio), an anti-inflammatory and cytoprotective agent, demonstrated beneficial impacts on survival and slowing of the decline of respiratory function in a recently published post-hoc analysis of a phase 2 study of patients with ALS. Overall, the therapy was most successful in those with lower neurofilament light and Monocyte Chemoattractant Protein-1 levels at study entry, suggesting this could be a subgroup to target in future studies assessing RNS60’s effect on survival.¹⁰

"It’s important to have those types of drugs, but the challenge is getting them approved," Cudkowicz said. "Regulatory agencies want to know that this is an important symptom for patients, and there’s a reason why a drug works there [on breathing] and not elsewhere."

While there has been progress in the overall care of ALS, Cudkowicz believes there is still a need for more industry, academic, and regulatory support. In addition, she also stressed that the lack of a clear path for drugs that work specifically on breathing function makes it even more difficult for industry leaders to become interested, and only further complicates the approval process for drugs that do show a pronounced effect.

"There’s no regulatory path, yet," she said. "We know from patients it’s a super important symptom, but what’s the [best] way to show if your drug or device has an impact on that? Can you get it to market? That pathway hasn’t been defined yet, but I think it’s really important."

In recent years, European NIV guidelines have been updated and expanded to include symptoms of diaphragm weakness and nocturnal hypoventilation, alongside traditional pulmonary function measures.¹¹ Emerging trials have highlighted variability in NIV prescription and utilization despite its proven survival and quality-of-life benefits. Future studies focus on NIV’s potential neuroprotective effects, cognitive benefits, and its role in mitigating faster ALS progression observed during COVID-19-related care disruptions.

Expanding on the literature, initial studies have demonstrated that tAIH safely enhances tidal volume, minute ventilation, and inspiratory pressure generation during quiet breathing in patients with ALS. While respiratory drive remained unchanged, the findings suggest tAIH promotes breathing plasticity without causing discomfort.¹² Ongoing trials are currently exploring the role of adenosine signaling in tAIH variability and whether adenosine receptor antagonists can amplify its effects.

Going forward, the one thing that Hansen-Flaschen and Cudkowicz both stressed the most is the need for more pulmonologists with experience and interest in treating patients with ALS.

"If I could wave a magic wand, it would be to train and develop more pulmonologists in chronic respiratory failure," Hansen-Flaschen added. "The care that I’ve described at my institution is available in no more than 2 dozen cities. Beyond that, patients rely on respiratory therapist who aren’t licensed to adjust care once it begins. This falls far short of what patients deserve."

"We’re competing with other things that are exciting for young pulmonologists, like ICU respiratory care, or chronic lung diseases, but ALS is a great career path for someone, and they can make a lot of difference for patients,” Cudkowicz suggested. "There’s a huge shortage, but sometimes attention and funding research can attract really good people to the field, like the Ice Bucket Challenge did for attracting scientists to ALS."

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