T Regulatory Lymphocytes and Endothelial Function in Pediatric Obstructive Sleep Apnea

Background: Obstructive 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. Methods: 50 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. Results: Circulating 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. Conclusions: Endothelial 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.