Obstructive sleep apnea (OSA) is a common problem that affects roughly 3% of children. If left untreated, it has been linked to hyperactivity, attention deficit disorder, daytime sleepiness and learning problems. Consequently, finding new ways to assess a patient’s condition and identify treatment options is critical. Cincinnati Children’s has recently focused its research efforts on what prompts a child to develop OSA and how it can best be treated.
“We have several research directions related to obstructive sleep apnea as we try to understand the disease mechanism,” says Raouf Amin, MD, director of the division of pulmonary medicine and Hubert and Dorothy Campbell Chair of Pediatric Pulmonology. “We want to know why the airway collapses during sleep.”

Airway Changes

Cincinnati Children’s researchers have long used 1.5T and 3T magnetic resonance imaging (MRI) to study the upper airway during sleep. Now, they’re going a step further, Amin says. They’re now pairing the modality with the same computational fluid dynamic principles behind airplane flight. Doing so lets them measure changes in airflow and pressure in the upper airways. The details collected from the images of approximately 40 patients thus far will help them test which interventions will be most effective with patients.

“The information gathered from these MRI images is quite important to understand which therapy will be best for children with obstructive sleep apnea,” he says. “We can treat the condition with multiple different surgeries, but who benefits from a specific surgery versus another? Which children would have better outcomes with medical treatment versus a surgical one?” Ultimately, Amin says, Cincinnati Children’s hopes these efforts will better explain the pathophysiology of OSA and lead to personalized treatments.

Cardiovascular Impacts

In addition to MRI, Cincinnati Children’s is using echocardiography to determine how OSA changes the structure and function of a patient’s heart. To date, they have examined more than 300 children with and without OSA. According to the results, children with OSA do experience some stiffening in their heart’s left ventricle. This leads to a mild reduction in diastolic function—the heart no longer pumps blood as it should, and the patient can feel very tired and short of breath.

“It’s a subclinical impact. These children don’t present with heart failure, for example,” Amin says. “They don’t really have overt symptoms of cardiac dysfunction, but they have diminished function that we’ve seen progress to become clinically significant if left untreated.”

Treating OSA can return diastolic function to normal. Clinicians can use the measurement of diastolic function to monitor children who have persistent or treatment-resistant OSA over time. The most effective treatment to reduce the cardiovascular impact, he says, is removing the tonsils and adenoids.

Systemic Inflammation

Cincinnati Children’s pulmonologists have also determined that OSA causes inflammation that can lead to atherosclerosis in children.

“There isn’t a longitudinal study over a period of decades that shows the significance of having elevated inflammatory mediators at the age of 5 or 6 and how that translates into cardiovascular disease during young adulthood,” he says. “But we know the mechanisms of atherosclerosis are present in children with obstructive sleep apnea who do not yet have atherosclerosis.”

In a study with 96 patients, Amin and his colleagues used blood tests and ultrasound to determine children with OSA have increased levels of several proinflammatory cytokines—sCD40-L, IL-6, and IL-8. Over the long term, he says, these raised levels that cause moderate inflammation could lead to both atherosclerosis and liver injury.

“All of these efforts are intended to help us identify the interventions that will work best with these children,” he says. “The more we learn about why the airway collapses and the fragmented sleep that results, the better we’ll be able to address these problems.”