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  • br Methods br Results The characteristics

    2021-02-20


    Methods
    Results The characteristics of the 20 control subjects and 63 patients stratified by SDB severity, matched for age, sex, and BMI z-score, are described in TableĀ 1. As expected, AHI, OAI, ODI, and SLT90% increased and SpO2 decreased progressively with the severity of the disease.
    Discussion Indeed, there is a growing awareness of the role of localized inflammation as the intermediary mechanism between SDB and its morbid consequences in children. Upper-airway inflammatory evidences including sputum neutrophils [22] as well as exhaled nitric oxides [23] and LTs [24] have been reported at increased levels in patients with SDB. Among the inflammatory mediators, CysLTs (LTC4/D4/E4) are recognized as a major trigger to initiate and propagate diverse arrays of biologic responses in airway inflammation [8], [9], [10], [11]. These activities include producing smooth muscle contraction and mucus secretion, recruiting inflammatory cells, modulating cytokine production and altering structural changes in the airway [10]. Our findings demonstrated that the magnitude of inflammation mediated by CysLTs correlated significantly with SDB severity as reflected by AHI and SpO2 nadir, even after adjusted for BMI z-score and adenotonsillar size, which at least partially confirms the view proposed by Goldbart et al. that recurrent mechanical trauma related to vibratory stress may play a major role in promoting upper-airway inflammatory changes in SDB patients [6]. Thus with increasing severity of the disease, the more grave mechanical injury will be presented in the airway and thereby more inflammatory mediators are released, which ultimately will accelerate the growth of adenotonsillar tissues and lead to upper airway obstruction during sleep. Of note, systemic inflammation was also widely reported to contribute to the pathophysiological mechanisms and even the emergence of cardiovascular and neurobehavioral complication of SDB [25], [26]. Rises in urinary CysLTs have been reported to indicate SDB severity [27], [28]. Therefore, the current findings may serve as supplementary evidence that the analysis of both circulating and airway CysLT levels could be applied as a reliable screening method in assessing severity of the disease. There is now compelling evidence that reactive oxygen species induced by sleep fragmentation and intermittent hypoxia might be involved in the activation of systemic inflammation in SDB [29], [30], completely different from the mechanism underlying the upper-airway inflammatory responses. A question might be posed as to whether there is no relationship between these two inflammatory processes with different origins. However, our findings showed that intratonsillar CysLT levels correlated significantly with quantitative levels of CysLTs in serum and urinary Loxapine (p<0.001 respectively), even when corrected for age, gender, BMI z-score and adenotonsillar size, suggesting an intense association between localized and systemic inflammation in SDB. It has been widely identified that the circulating leucocytes have a great capacity to synthesize and release CysLTs, while CysLTs are the strongest leukocyte chemoattractants that promote the migration of inflammatory cells across the vessel wall into the tissues and then release CysLTs there [9], [10], [11]. This implies that systemic inflammation may either initiate or maintain the localized upper-airway inflammatory process. Conversely, locally generated CysLTs (either cellular infiltrates or autochthonous production) may also travel into the circulation and contribute to systemic levels [8], [9]. The coaction of local and systemic activation of inflammatory pathways promotes the development of multi-system complications. Nevertheless, it is difficult to determine the initial origin of inflammation in the pathophysiology of SDB. The effects of CysLTs occur after their interaction with receptors. Two types of human receptors for the CysLTs, designated CysLT1-R [12] and CysLT2-R [13], which belong to the 7-transmembrane, G protein-coupled receptor family, were cloned and shown to be 38% homologous in their amino acid sequences. The protein expression of both CysLT1-R and CysLT2-R has been identified in several human organs [31]. However, few reports referred to the tonsillar tissues as one such organ. Our results for CysLTR expression in SDB are compatible with Goldbart's findings that increased CysLTR protein expression emerged in children with SDB than those with RI [6]. This may underlie components of the pathophysiological mechanisms linking the adenotonsillar hypertrophy to the emergence of sleep apnea in snoring children. The understanding of the role of inflammation in the pathogenesis of SDB led clinicians to assess anti-inflammatory medications as an additional alternative management in SDB. Goldbart et al. reported a 16-week oral LTRA therapy significantly improved the size of lymphoid tissues and PSG index. However, the therapeutic effect of LTRAs in treating SDB is still undetermined worldwide. In the current report, we did not only measure the different levels of cysLT protein expression in SDB and RI groups, but also took the severity of SDB into account. The benefit of our findings is the hope that cysLTRs may provide as effective clinical targets to control SDB. However, our results only showed mild discrepancies of the CysLT1-R expression among different SDB subgroups stratified by disease severity as there were no statistical differences when analyzing CysLT2-R expression. These findings indicate that CysLT production affects the protein expression of CysLT1-R to a larger extent than CysLT2-R. Thus it is tempting to speculate that the specific CysLT1-R antagonist may be more beneficial than the CysLT2-R antagonist in the treatment of SDB. Nevertheless, more prospective studies with a larger sample size are needed to confirm the relationship between CysLTR expression and SDB severity in the future.