Evaluation of Sleep Apnea in Adult Sickle Cell Disease; About 107 SS and Sβ°Thal Patients

Introduction: Sickle cell disease (SCD) patients are particularly reactive to decreased partial pressure of oxygen. A moderate decrease in PO2 results in a significant desaturation of hemoglobin (Hb) due to the rightward shift of the Hb dissociation curve. Any repetition of hypoxic episodes, however brief, promotes hemoglobin S (HbS) polymerization and thus activates endothelial erythrocyte adhesion. Thus, permanent or intermittent hypoxemia may trigger vaso-occlusive complications (VOC). Some studies have demonstrated apneas or hypopneas due to upper airway obstruction in children with SCD. The aim of this study was to investigate the relationship between the occurrence of VOC (either nocturnal, priapism, or diurnal) and/or the presence of respiratory disorders, upper airway obstruction, or biological characteristics in adult SCD patients.

Materials and Methods: This is a prospective, monocentric study provided by the Sickle Cell Referral Center, ENT specialists, and Functional Exploration Unit of the Henri Mondor University Hospital, approved by the Ethics Committee, and registered on clinical trials with ID NTC02539771. Patients were screened during routine visits at baseline and enrolled in three different groups (G). G1: patients with priapism and/or nocturnal crisis, G2: patients with diurnal VOCs requiring hospitalization in the last 6 months, G3: patients with few or no symptoms. All patients underwent clinical examination, blood sampling, polysomnography, ENT examination, rhinomanometry, rhinometry, respiratory function tests with arterial blood gas, baseline transcutaneous saturation, walk test, and cardiac ultrasound. Sleep apnea was classified depending on the Apnea- Hypopnea Index (AHI): 5-15(mild), 15-30 (moderate), and more than 30(severe). The number of VOCs, hospitalizations, and ICU admissions was collected. Statistical analyses were performed depending on the type of data (quantitative, qualitative or ordinal) using the most appropriate tests.

Results: We included 107 patients (104 SS and 3 Sβ°thalassemia) in this study. The mean age was 41± 10 years and the BMI was 22.9± 5. Hydroxycarbamide was prescribed in 79% of all patients (84% in G1 and 58% in G3 (p=0.009)), and 10% were smokers. We found 52% of sleep apnea (30% of mild and 23% of moderate and severe). This rate was the same in the symptomatic (G1) and asymptomatic (G3) groups. Males were overrepresented in G1 due to the inclusion criteria of priapism in this group (p<0.009). Patients in G1 had more hospitalizations for VOC, more ACS and more ICU stays in the previous 12 months (p<0.0001). Hb level and leukocytes were significantly higher in G1(p=0.03), and no differences in Hb F, MCH, platelets, dense cells, and LDH was detected between G1 and G3. The total lung capacity, CO diffusing capacity (DLCO) and alveolar volume were all significantly reduced in G1 (p<0.001). On polysomnography, the differences were in stage 1 of sleep and its duration (p=0.02). Rhinomanometry and ENT examination showed differences in nasal obstruction in G1.

In all patients with apnea, we compared patients with vs. without VOCs; those with VOCs had significantly higher WBC, platelets, and HB (p< 001), but there were no differences in Hb F, dense cells, and MCH. In patients with VOC and apnea, the depression scale (CES-D) was more important (p=0.03), and Respiratory-corrected DLCO significantly decreased (p=0.01).

If we compare all patients with vs. without apnea, there were more mens, more snoring and a decreased basal PaO2, an anomaly in the functional respiratory tests and nasal obstruction in the group apnea. ( p<0.01)

Conclusion: The incidence of sleep apnea is very high in SCD adult patients. In this study, the frequency of all types of apnea was 52% and moderate to severe apnea 23%. Symptomatic and asymptomatic patients had the same rate. Patients did not have a classic sleep apnea profile in terms of age and BMI. Altered functional respiratory tests and nasal obstruction are risk factors. Further analyses will be performed to determine risk and protective factors in adult SCD patients with sleep apnea and different profiles.