Abstract
BackgroundObstructive sleep apnea (OSA) is a low-grade inflammatory disease affecting the cardiovascular and metabolic systems. Increasing OSA severity reduces T-regulatory lymphocytes (Tregs) in OSA children. Since Tregs modulate endothelial activation, and attenuate insulin resistance, we hypothesized that Tregs are associated with endothelial and metabolic dysfunction in pediatric OSA.Methods50 consecutively recruited children (ages 4.8–12 years) underwent overnight polysomnography and fasting homeostatic model (HOMA) of insulin resistance was assessed. Percentage of Tregs using flow cytometry, and endothelial function, expressed as the time to peak occlusive hyperemia (Tmax), were examined. In a subgroup of children (n = 21), in vitro Treg suppression tests were performed.ResultsCirculating Tregs were not significantly associated with either BMI z score or HOMA. However, a significant inverse correlation between percentage of Tregs and Tmax emerged (p<0.0001, r = −0.56). A significant negative correlation between Tregs suppression and the sleep pressure score (SPS), a surrogate measure of sleep fragmentation emerged (p = 0.02, r = −0.51) emerged, but was not present with AHI.ConclusionsEndothelial function, but not insulin resistance, in OSA children is strongly associated with circulating Tregs and their suppressive function, and appears to correlate with sleep fragmentation. Thus, alterations in T cell lymphocytes may contribute to cardiovascular morbidity in pediatric OSA.
Highlights
Obstructive sleep apnea (OSA) is characterized by changes in intrathoracic pressure, intermittent hypoxia, hypercapnia and sleep fragmentation
We have recently reported that increasing OSA severity is associated with a reciprocal decrease in the percentage of T regulatory lymphocytes (Tregs) in the peripheral blood of children with OSA [15]
When combined with previous data which showed that the degree of decrease in circulating T-regulatory lymphocytes (Tregs) in children was related to the clinical severity of their OSA, it raises the possibility that the decrease in Tregs may in part mediate the endothelial dysfunction that occurs in a subset of children with OSA
Summary
Obstructive sleep apnea (OSA) is characterized by changes in intrathoracic pressure, intermittent hypoxia, hypercapnia and sleep fragmentation These changes result in sympathetic alterations, increased systemic oxidative stress and the activation of inflammatory processes, all of which likely play important roles in mediating the cardiovascular and metabolic morbidities of OSA [1,2,3]. Post-occlusive hyperemic response testing has revealed significant impairments in endothelial function among children with OSA when compared to controls, with the majority of these children showing significant improvements in endothelial function after treatment of OSA with adenotonsillectomy [6]. Since Tregs modulate endothelial activation, and attenuate insulin resistance, we hypothesized that Tregs are associated with endothelial and metabolic dysfunction in pediatric OSA
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