Leukotrienes Pathway in Chinese Children With Sleep-disordered Breathing

Our goals are to demonstrate an active leukotrienes (LTs) mediated inflammatory response is involved in pathophysiology of sleep-disordered breathing (SDB), and to provide a theoretical evidence for LTs modify therapy in treating pediatric patients with SDB. The investigators have hypothesized that the pathophysiology of pediatric SDB involves specific systemic and local upper airway inflammatory response mediated by LTs. 1. LT concentration assays reveal higher levels in serum for both leukotriene B4 (LTB4) and cysteinyl leukotrienes (CysLTs) and in morning urine for LTE4 of SDB children, in comparison to healthy ones, and LTs productions emerge disease severity-dependent increases. There is a positive correlation between LTs production and other systemic markers such as neutrophil counts and high sensitive C-reactive protein (hsCRP). 2. Children with SDB have higher leukotriene receptor-1 (LT1-R) and leukotriene receptor-2 (LT2-R) expressions in adenotonsillar tissues of SDB children compared to recurrent infectious tonsillitis subjects. 3. Levels of LTs are positively correlated with body mass index (BMI) z-score, waist height ratio (WHtR), adenotonsillar size and polysomnography (PSG) indices including apnea-hypopnea index (AHI), obstructive apnea index (OAI), oxygen desaturation index (ODI), arousal index, percentage of time spend saturation lower than 90% (SLT90%) and negatively correlated with mean and minimal pulse oximetric saturation (SpO2), which indicates synergistic role of obesity and hypoxia are the determinants of LTs production in SDB. 4. In adenotonsillar mixed cell culture system, the addition of LTs can increase cellular proliferation rates and exhibit dose-dependent responses, whereas leukotriene receptor antagonists (LTRAs) elicit dose-dependent cellular reductions.