Sickle Cell Disease (SCD) primarily affects the African- American population, in whom the newborn frequency is about 1 in 600. Major clinical manifestations of SCD are caused by the abnormal sickle hemoglobin (HbS), which, when de-oxygenated, polymerizes in the red cell and causes it to become rigid and deformed (""""""""sickled""""""""). This process is thought to be responsible for one of the major clinical manifestations of SCD, recurrent vaso- occlusive painful episodes (VOPEs). Despite the knowledge that sickling can be caused in vitro by de-oxygenation of hemoglobin, the role of clinical hypoxemia in the pathogenesis of VOPEs is unknown. This knowledge is crucial for the following reasons: a) patients with recurrent VOPEs have a shorter life span than those without, b) patients with SCD have a higher risk of awake and sleeping hypoxemia than the normal population and c) hypoxemia can be easily corrected by the administration of supplemental oxygen.
The specific aims of this proposal are therefore 1) To determine, with awake and sleeping continuous pulse oximetry, the prevalence of hypoxemia in a population of 250 children with SCD. Risk factors for hypoxemia, including clinical, hematologic and lung function indices will be identified. 2) To determine why patients with SCD are at increased risk for sleep hypoxemia than the normal population. We will identify the mechanisms which may predispose the SCD population to oxygen desaturation during sleep, including a right shifted hemoglobin dissociation curve, and central and obstructive sleep apnea identified by polysomnography. 3) To test the hypothesis that episodes of hypoxemia precede and are causally related to VOPEs, using continuous home pulse oximetry, pain diaries and wrist actimetry, an indirect objective measure of pain onset during sleep. We will then assess in a blinded placebo controlled cross- over clinical trial whether the administration of supplemental oxygen is a safe and effective way of preventing VOPEs in SCD patients with awake or sleeping hypoxemia.
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