Helping Patients Breathe Easier

Helping Patients Breathe EasierThe original Prime Respi team: Ee Lim Tan, Ian Matthews, Priyanka Prasad, and Mark Chong.

When Priyanka Prasad completed her PhD in bioengineering, she was enthusiastic about the intersection of healthcare and technology, but knew she was ready for a change. “By that point I was fairly certain that I wanted to go into translational work and have an impact on patient lives rather than doing pure research,” she recalled. “It was really important to me to see and understand what patients go through firsthand.” To help achieve this goal, she applied to the Singapore-Stanford Biodesign (SSB) Fellowship, which would enable her to learn a patient-centric, need-driven process for health technology innovation.

The other members of her SSB team were equally motivated to apply their experience and training to improving healthcare for patients. They included Ian Matthews, an emergency physician, Ee Lim Tan, a biomedical engineer and research scientist, and Mark Chong, a mechanical engineer. The four teammates bonded quickly over their shared passion. “We not only worked really well together but we enjoyed each other’s company socially,” said Prasad. “I’ve been told that we were one of the more humorous teams around.”

Their training began at Stanford University with a clinical immersion in pulmonology and respiratory medicine to investigate unmet needs affecting patients and their care providers in this space. After several months of study, the team returned to Southeast Asia to repeat their immersion in hospitals in Korea, Indonesia, and Singapore. Throughout the process, one need stood out to team across multiple geographic locations and disease states. “We saw impaired airway clearance – basically the inability of patients with damaged lungs to get mucus out of their lungs – over and over,” said Prasad. “It had a variety of names and form factors, but it was the same problem negatively affecting so many people”

At Stanford Hospital, they observed the condition in patients with chronic conditions like cystic fibrosis, bronchiectasis, (when the walls of the bronchi are damaged from long-term inflammation and infection), chronic bronchitis (a form of chronic obstructive pulmonary disease in which the lining of the bronchial tubes becomes inflamed) and in acute conditions like pneumonia. In Asia, they saw more of chronic bronchitis and bronchiectasis. “All of them were struggling to clear their airways of mucus,” said Prasad.

As the team researched the solution landscape, they learned that preferred treatments varied somewhat by location. The gold standard of care is manual physiotherapy, in which a family member/caregiver works with the patient using percussion, postural drainage, and vibration to help loosen and mobilize the secretions. Treatment can be uncomfortable. “Think of someone clapping repeatedly on your back and chest,” described Prasad – and the entire procedure is highly collaborative with the patient changing positions and coughing in response to caregiver instructions. Session length and frequency vary, but two 30-40 minute sessions per day is typical.

In the US, many adult patients use handheld OPEP (oscillating positive expiratory pressure) devices that open weakened or collapsed airways and bring up mucus that can then be coughed out. “Because they can be used independently, these devices are often preferred,” Prasad explained. Although a caregiver is not required, the OPEP procedure is also interactive, requiring patients to hold certain positions, form a seal around the mouthpiece, and blow into it repeatedly with enough force to extinguish the equivalent of 20-30 birthday cake candles. Like the gold standard approach, “OPEP therapy takes 20-30 minutes per session and has to be done at least twice per day,” reported Prasad.

“One important thing to keep in mind is that these conditions are chronic. Short of a surgery, for which the criteria are very selective, patients must do therapy for the rest of their lives,” said Prasad. When the SSB team talked to patients, their frustration with the amount of time required for treatment was clear.

Prasad recalled one patient who told the team that her entire life revolves around her therapy. “She said that she has to wake up 2-3 hours before her first work meeting to do her therapy to make sure she doesn’t suffer from symptoms that would otherwise occur, like congestion or persistent coughing. Then she would go to work and have all of her meetings and then start the therapy process all over again.” Prasad continued, “This is really challenging for adults because they are supposed to be economically productive, but they have this chronic disease that is taking hours of time each day to treat.”

Stanford pulmonologist and critical care physician Stephen Ruoss validated the teams’ findings. “He told us that 90 percent of his chronic patients are mobile, and that the hardest thing for them is the amount of time the therapy takes,” recalled Prasad.

Another pain point for patients was the inability to do anything else during the sessions. “Patients really struggle to integrate their therapy into their lives,” said Prasad. “Because of that, sometimes they end up taking shortcuts around their therapy and don’t perform it regularly or properly.”

An additional problem the team observed during this period was the clinicians’ inability to monitor their chronic patients’ therapy progress. “As most, if not all treatments are performed at home, many patients only see their clinicians every few months. As a result, infections and/or exacerbations are often not identified until they have progressed to the point that needs hospital intervention,” said Prasad.

Based on these insights, the team outlined criteria for their solution. Not only did it need to be easy and effective for patients to do regularly, but it also needed to integrate into their daily life. It needed to reduce the time they spent on therapy every day and importantly, give patients and clinicians the ability to manage therapy goals and progress from home.

As the team set out to design a device that met these criteria, one of the challenges they faced was the lack of an appropriate animal model that would allow them to quickly prove the concept. “This is a fairly complex respiratory process, so we needed to test our ideas on a dynamic lung system,” said Prasad. “This was difficult given our funding constraints at that early stage.” The team worked around this by using a combination of bench models and healthy volunteers to assess their ideas.

By the end of the SSB fellowship year the team had developed a concept for a drug-free, non-invasive airway clearance device that uses oscillations to loosen and mobilize airway secretions in a unique way, leveraging the body’s natural anatomy. They also formed a company, Prime Respi, to develop and bring the technology to patients. Since that time, they have been working on building a prototype that can be used to test the device on humans.

“Ultimately, we need to show that our solution works on humans, but it’s not that easy to access these patients in Singapore or the US. Additionally, we need to achieve a certain degree of sophistication in the device before it can be given to a patient,” Prasad noted.

Prasad, who has been leading the project, reported that the device is on track for proof of concept testing in humans by the end of 2019, with an initial treatment focus on chronic bronchitis.