Alterations in Circulating T-Cell Lymphocyte Populations in Children with Obstructive Sleep Apnea

Study Objectives: Changes in lymphocyte phenotype and functionality have been described in adult patients with obstructive sleep apnea (OSA). We hypothesized that OSA is associated with T lymphocyte alterations in children, particularly in T regulatory lymphocytes (T regs), and aimed to characterize circulating T lymphocyte subsets in children with OSA. Design: Cross-sectional. Setting: Kosair Children's Hospital (Louisville, KY, USA) and Comer Children's Hospital (Chicago, IL, USA). Participants: Consecutively recruited children being evaluated for habitual snoring. Interventions: N/A. Measurements and Results: Overnight polysomnography (PSG) was performed and a fasting blood sample was obtained from the patients. Flow cytometry was performed on peripheral blood mononuclear cells stained for CD3, CD4, CD8, CD25, FOXP3, interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and IL-17. Patients were divided into three groups based on their PSG: controls (apnea-hypopnea indices [AHI] < 1/h total sleep time [TST]), mild OSA (1 <= AHI < 5/hTST), moderate-severe OSA (AHI >= 5/h TST). The percentage of CD4+ and T reg lymphocytes differed across groups. Children with moderate-severe OSA had significantly reduced T reg than control children (median [interquartile range] 4.8 [3.8-5.7% CD4+] versus 7.8 [7.0-9.2% CD4+]; P < 0.001). There were also significant differences in the percentage of T helper 1 (Th1) lymphocytes and in Th1: Th2 ratios between groups. Children with moderate-severe OSA had increased Th1 cells (P = 0.001) and Th1: Th2 ratios (P = 0.0026) compared with children with mild OSA and control children. Associations between AHI and T reg (P = 0.0003; r = -0.46), CD4+ lymphocytes (P = 0.0047; r = -0.37), and Th1: Th2 ratios (P = 0.0009; r = 0.43) emerged. In addition, the percentage of T reg was inversely correlated with Th1: Th2 ratios (P = 0.029; r = -0.29). Conclusions: Pediatric OSA is associated with reduced T reg population and altered Th1: Th2 balance toward Th1 predominance, suggesting a shift to a proinflammatory state. The changes in lymphocytic phenotypes associated with OSA may contribute to the variance in systemic inflammation and downstream morbidities associated with this condition.