A Pilot Study of Sleep Disordered Breathing (SDB) and Nocturnal Hypoxemia in Young Adults with Sickle Cell Disease
Authors: Perrine Susan P. , Owoyemi Oluwakemi , Klings Elizabeth S , Nouraie Mehdi , Rock Angela , Oneal Patricia A. , Mellman Thomas , Berihun Tessema , Whitesell Peter L. , Lavela Joseph , Taylor Robert E. 
Published: October 2019

Abstract
Sleep disordered breathing including transient hypoxemia and hypercarbia are reported in 60-80% of adolescents and children with sickle cell disease (SCD); oxygen desaturation <93% is associated with exercise intolerance. Longer duration of oxygen desaturation, lower nadirs of oxygenation, and end-tidal carbon dioxide levels >50 mm Hg during sleep are associated with increased frequency of acute vaso-occlusion events and are suspected of contributing to microvasculature alterations. To assess the prevalence and degree of sleep-related hypoxemia and potential associations with cardiovascular functions in young adults with SCD, we performed overnight sleep studies using a Type II sleep monitor NOX-T3 (Carefusion, Inc), 6-minute walk tests, echocardiograms, hematologic and chemistry panels, and PSQI questionnaires in 17 adults with SCD, ages 21-30 years. Subjects were attending a sickle cell clinic solely for routine care with no expressed complaints of SDB. Exclusion criteria included acute clinical events, hospitalizations, or red cell transfusions within 4 weeks, and chronic transfusions. AHI>5 (significant apnea/hypopnea hypoxemic episodes) during sleep occurred in 7/17 (41%) of subjects, and these subjects had a higher median number of hypopneas (34 vs 12, p=0.005), and oxygen desaturation indices (ODI, 5.9 vs 2.0, p<0.001) than occurred in subjects with AHI scores ≤5, with a trend to lower oxygen saturation during sleep (lowest saturation of 78% vs 88%, P = 0.1). Patient-reported symptoms of SDB on the PSQI questionnaire were strongly associated with nocturnal hypoxemia (Sensitivity = 86%). All subjects had 6-minute walk distances below normal for healthy subjects, (mean 384 vs normal adult 876 meters). Left ventricular diastolic function was more affected in patients with AHI>5 (median MV EA ratio of 2.0 vs. 1.5, p = 0.08). TR jet velocity >2.5 was found in 2/17 asymptomatic subjects; (both were in the AHI>5 group). General quality of life was lower in patients with AHI>5 (mean score of 38 vs. 48, p = 0.012). As prolonged and frequent hypoxemic episodes may increase risks for vaso-occlusive, cardiovascular, and neurologic events, these common findings of significant nocturnal hypoxemia in young adult sickle cell subjects strongly suggest that SDB should be investigated further in larger patient populations, and interventions initiated. The observations, in addition to prior reports, also strongly suggest that screening of young adult SCD patients for SDB should be performed on a routine basis.
Research reported in this publication was supported by the NHLBI under Award Number P50HL118006. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosures
Klings: Actelion Pharmaceuticals: Research Funding; Pfizer: Consultancy.