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.
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