Oxyhemoglobin Desaturation and Vasculopathy in SCD

描述（由申请人提供）： 本提案的总体目标是研究氧合血红蛋白去饱和在镰状细胞病（SCD）肺部并发症和血管病变中的意义。多学科方法将涉及血液学，放射学，神经放射学，肺科学和生物化学之间的合作，并利用每个学科内的最先进的技术。研究对象为2 - 18岁的SCD-SS患者。近500名SCD-SS患者在费城儿童医院接受治疗。该提案有四个具体目标。第一个是针对回答的问题，是否有SCD的儿童有一个更高的患病率氧合血红蛋白去饱和比正常人群。这将是一项具有前瞻性组成部分的横断面研究。预计将出现三种临床类型：持续性血氧饱和度下降（OHD）、间歇性睡眠相关血氧饱和度下降和正常血氧饱和度下降。具体目标2将研究导致SCD中OHD和间歇性氧合血红蛋白去饱和的机制。肺的后果将得到解决，将假设睡眠相关的间歇性去饱和的结果阻塞性睡眠呼吸暂停由于解剖和/或功能机制。解剖学因素可能包括腺样体和扁桃体过度生长，这是已知在该人群中发生的功能性无脾的结果。第三个目标是确定血管病理学的解剖学或功能证据，包括肺和脑，SCD和氧合血红蛋白去饱和的儿童。除影像学研究外，还将进行血管病变生物标志物的测定，包括但不限于氧化应激、内皮损伤、RBC柔韧性和形态学标志物。目的4将检查持续性和间歇性OHD干预对健康、血管表现和外周生物标志物的影响。干预措施将包括临床指征的腺样体切除术、正压给氧和夜间供氧。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to investigate the significance of oxyhemoglobin desaturation in pulmonary complications and vasculopathy in sickle cell disease (SCD). A multidisciplinary approach will involve collaborations among hematology, radiology, neuroradiology, pulmonary science, and biochemistry and utilize state-of-the-art techniques within each discipline. Studied will be SCD-SS patients between the ages of 2 and 18 years. Nearly 500 patients with SCD-SS receive treatment at the Children's Hospital of Philadelphia. The proposal has 4 specific aims. The first is directed toward answering the question of whether children with SCD have a higher prevalence of oxyhemoglobin desaturation than the normal population. This will be a cross-sectional study with a prospective component. Three clinical categories are expected to emerge: persistent desaturation (OHD), intermittent sleep-related desaturation, and normal oxyhemoglobin desaturation. Specific Aim 2 will investigate mechanisms leading to OHD and intermittent oxyhemoglobin desaturation in SCD. Pulmonary consequences will be addressed, as will the hypothesis that sleep-related intermittent desaturation results from obstructive sleep apnea due to anatomical and/or functional mechanisms. Anatomical factors may include overgrowth of adenoid and tonsils as a result of functional asplenia known to occur in this population. The third aim concerns determination of anatomical or functional evidence for vascular pathology, including that in the lung and brain, in children with SCD and oxyhemoglobin desaturation. In addition to imaging studies, assays for biomarkers for vasculopathy, including but not limited to markers of oxidative stress, endothelial injury, RBC flexibility and morphology, will be performed. Aim 4 will examine the effects of intervention for persistent and intermittent OHD on health, vascular manifestations and peripheral biomarkers. Interventions will include clinically-indicated adenotonsillectomy, positive pressure oxygen administration, and nocturnal oxygen supplementation.