In Children with OSA, Mediators’ Opposing Actions Might Play Key Role in Maintaining Cardiovascular Stability

Published April 1, 2017
Sleep

Biomarkers of atherosclerosis are elevated in children with obstructive sleep apnea (OSA), but their association with cardiovascular endpoints has not been well understood.

Previous research on inflammatory mediators predominantly focused on what happens to individual cytokines—small secreted proteins released by cells—in such children.

The process turns out to be far more complicated, according to a first-of-its-kind study that demonstrates how groups of inflammatory mediators and acute phase reactants interact more globally than was generally thought, including opposing actions.

“These findings may potentially explain why this disease process is different in children and adults,” says first author David Smith, MD, PhD, of the Division of Pulmonary Medicine. Raouf Amin, MD, director of Pulmonary Medicine, was senior author.

Atherosclerosis is the hardening and narrowing of arteries. The team theorized that these biomarkers correlate with pulse transit time (PTT), a surrogate measure of vascular stiffness, with some positively influencing and others negatively influencing PTT.

Smith says one possible explanation for these mediators having opposing actions is to act as a compensatory mechanism to prevent further injury.

“It is only after a significant amount of time or changes in disease severity that children and adolescents begin to have a break-down in this homeostatic mechanism,” he says.

When that happens, children and adolescents with OSA develop clinically obvious cardiovascular and pulmonary disease. With the study’s findings, researchers plan to begin examining entire pathways of mediators.

“It is important to understand how these pathways demonstrate crosstalk in a much more complex, physiologic system, not just under artificially defined parameters,” Smith says.

This figure represents how biomarkers, body mass index and other factors affect pulse transit time (PTT) in children with obstructive sleep apnea, a condition that affects nearly 5 percent of U.S. children in the U.S. The factors on the left prolong PTT: C-reactive protein (CRP), serum amyloid A (SAA), body mass index (BMI) and adiponectin, a protein that helps the body regulate glucose levels and break down fatty acid. The factors on the right shorten PTT: interleukin (IL)-6 and 8, tumor necrosis factor (TNF)-α, and a soluble cluster of differentiation (CD)-40 ligand (L).

Click image to enlarge.

Citation

Smith DF, Hossain MM, Hura A, Huang G, McConnell K, Ishman SL, Amin RS. Inflammatory Milieu and Cardiovascular Homeostasis in Children With Obstructive Sleep Apnea. Sleep. 2017 Apr 1:40(4).