by Tom O’Neill

The airway computational modeling system in development in the Pulmonology and Otolaryngology divisions is similar to recent work at Cincinnati Children’s Heart Institute, where surgeons are using computer-generated 3D-printed models of individual hearts to plan operations.

“We haven’t utilized a printer yet, but the modeling employs the same principle as 3D hearts,” says Raouf Amin, MD. “It’s based on formulas to understand the effect of flow and pressure within a structure, whether it’s a muscle or a blood vessel or a heart or an airway. That’s why we bring in the physicists who are the experts in this computational model.”

This is where Goutham Mylavarapu comes in. The first author of the “New Frontiers” report had studied mechanical engineering in his native India, at the Indian Institute of Technology. He had no particular interest in medicine when he came to Cincinnati to pursue his PhD at UC’s Department of Aerospace Engineering and Engineering Mechanics.

“It all happened by chance,” Mylavarapu says. Instead of working on aircraft, he wound up studying under Ephraim Gutmark, PhD, an Ohio Eminent Scholar at UC who happened to have experience collaborating with Cincinnati Children’s to study air flow and sound waves in children with damaged larynxes.

For airplane wings and car exhaust systems, the fluid dynamics involved can be fairly straightforward. Human anatomy has more complex and individualized structures.

airway-1_gif airway-2_gif

A 3D model illustrates deformation of the airway wall according to variations in breathing-mask pressure. The red in the bottom image results from higher air pressure.

Mylavarapu, Gutmark  and colleagues outlined how it works in a 2014 paper  published in the Journal of Biomechanics. The work starts with data from three medical technologies:

  • cine MRI images that capture a child’s cerebrospinal fluid flow. As the heart beats, this fluid flow is forced out of the ventricle of the brain and down the spinal canal.
  • polysomnography sleep studies, which record brain wave activity, oxygen level in the blood, breathing and heart rate, and eye and leg movement
  • sleep endoscopy, in which a patient is given incremental amounts of anesthesia to induce sleep for a short time to the point where apnea occurs, but before there is a drop in blood-oxygen level. An endoscopy camera shows the key areas of obstruction, effectively taking out some of the guesswork.

These pre-op test results produce a baseline measure quantifying flow velocity, turbulence, pressure and wall sheer stress. “There is so much physics and mechanics involved,” Mylavarapu says. “The challenge is that the upper-airway is a very flexible structure.”

With the baseline established, “virtual surgery” begins. When tissue is virtually resected, the algorithms change, revealing new airflow results. Surgeons can explore variations in approach until they find the optimal flow.

The system is not perfect. For example, the airways of some children balloon out as they breathe, a type of movement that cannot be captured in cine MRI images. But in most cases, the computer models vastly reduce the educated guesswork involved in traditional surgery.

Amin plans to establish a center within a year specifically dedicated to “virtual surgery.” He predicts such a center could play a key role in improving diagnostic techniques and establishing best practices for sleep apnea treatment.

Plenty more research is needed. In a systematic review published July 7, 2015, in Laryngoscope, Amin, Ishman, Sally Shott, MD, and colleagues found a general lack of data regarding patient selection, outcomes for OSA surgery, and the effectiveness of some commonly used tools to identify OSA sites.

The study raises tough questions, but Amin predicts the ongoing work of the new virtual surgery center will soon begin providing stronger answers.

Diabetes Drug Shows Early Promise in Alleviating Sleep Apnea

A drug approved to combat diabetes, and later obesity, is showing early promise in treating sleep apnea in adults.

Raouf Amin, MD, Director of the Division of Pulmonary Medicine, is cautiously optimistic that liraglutide could one day help in alleviating pediatric apnea.

In a pilot study sponsored by Cincinnati Children’s, researchers found that in 18 adult non-diabetics with apnea, 12 showed an average decrease in severity of 44 percent. The clinical trial also involved nine control non-diabetics who also have OSA but did not receive liraglutide for the four-week period.

Amin presented the findings in May earlier this year to the American Thoracic Society. “We made some very interesting observations,” Amin says. “Liraglutide affects the central and peripheral networks. Some are metabolism-related, which is why it is good for diabetes. But it also affects the central control of breathing.”

Still, he points out, the result means a third of participants using liraglutide showed no response. And, of course, the sample size was small. 

“There is a difference in how they responded,” Amin says. “The next step is understanding the mechanism.”

As a peptide-1 receptor agonist, liraglutide works by binding to the same receptors as the metabolic hormone GLP-1, which increases the secretion of insulin. The drug gained FDA approval as a type 2 diabetes treatment in 2010 and was approved in 2014 for some patients with obesity.

Researchers hypothesize that liraglutide could cause significant increases in orexin, a neuropeptide that regulates arousal and wakefulness, as well as carbon dioxide chemosensitivity. The drug also appears to prompt a decrease in leptin, which regulates energy balance.

In an update filed Aug. 3, 2015, with the National Institutes of Health, researchers wrote: “The development of a new pharmacological treatment for sleep-disordered breathing could bring a breakthrough discovery that will impact a rapidly growing population of children and adults with this disorder.”

Primary completion of the clinical trial is expected in December.