Oxyhemoglobin Desaturation and Vasculopathy in SCD

SCD 中的氧合血红蛋白饱和度降低和血管病变

• 批准号: 7110957
• 负责人: Kwaku Ohene-Frempong
• 金额: $ 186.06万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110957
• 关键词: biomarker; children; clinical research; gut associated lymphoid tissue; human subject; lung disorder; lymphatic tissue; oral pharyngeal; oxyhemoglobin; sickle cell anemia; sleep; vascular endothelium

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.

描述（由申请人提供）： 该提案的总体目的是研究氧血红蛋白去饱和在肺部疾病（SCD）中的肺并发症和血管病的重要性。多学科的方法将涉及血液学，放射学，神经放射学，肺科学和生物化学之间的合作，并在每个学科中使用最先进的技术。研究的是2至18岁的SCD-SS患者。 SCD-SS的近500例患者在费城儿童医院接受治疗。该提案具有4个具体目标。第一个是指回答SCD儿童是否比正常人群更高的问题的问题。这将是一项具有前瞻性成分的横断面研究。预计三个临床类别将出现：持续的饱和度（OHD），间歇性睡眠相关的去饱和度和正常的氧降温。具体的目标2将研究导致SCD中OHD和间歇性氧降温的机制。将解决肺后果，这是由于解剖学和/或功能机制引起的阻塞性睡眠呼吸暂停导致与睡眠相关的间歇性去饱和的假设。解剖因素可能包括由于已知在该人群中发生的功能性阿斯普尼而导致的腺样体和扁桃体的过度生长。第三目的是确定血管病理的解剖学或功能证据，包括在肺和大脑中，患有SCD和氧气血红蛋白去饱和的儿童。除了成像研究外，还将执行用于血管病的生物标志物的测定，包括但不限于氧化应激，内皮损伤，RBC柔韧性和形态的标记。 AIM 4将检查干预措施对持续性和间歇性OHD对健康，血管表现和周围生物标志物的影响。干预措施将包括临床指示的腺孔切除术，正压氧气给药和夜间氧气补充。