Despite the fact that obstructive sleep apnoea (OSA) is highly prevalent in the sickle cell population, studies focusing on the associations of the two diseases and their common pathophysiological mechanisms are scarce. OSA is one of the most common conditions responsible for hemoglobin desaturation. The nocturnal hemoglobin desaturation occurring in some sickle cell disease (SCD) patients with OSA could trigger hemoglobin S polymerization and red blood cell (RBC) sickling, leading to further blood rheological alterations, hence increasing the risks for VOC. Moreover, OSA has been demonstrated to increase oxidative stress and inflammation in non Sickle Cell Disease (SCD) patients, which, in SCD patients, could increase the risk for complications. Finally, OSA is accompanied by impaired vascular function and autonomic nervous system dysfunction in the general population. Indeed, the presence of OSA in SCD could increase the clinical severity of patients and the frequency of VOC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
30
Measurement of the Apnea/hypopnea index (AHI) and oxygen saturation
calculation of VOC rate within the two previous years or between first polysomnography and one year of continuous positive airway pressure treatment
Blood samples with measurements of hematological, hemorheological, inflammatory and blood coagulation markers
Evaluation of microvascular reactivity and autonomic nervous system activity
Continuous Positive Airway Pressure during 1 year
Hôpital Edouard Herriot
Lyon, France
Centre Léon Berard
Lyon, France
Hôpital de la Croix Rousse
Lyon, France
number of VOC crises required hospitalization in the previous two years
Calculated over a 2 years period before inclusion. VOC requiring hospitalizations will be recorded. Measured at day 1
Time frame: day 1
Blood inflammatory markers
Blood inflammatory markers : C Reactive Protein (CRP, mg/L) The morning after the polysomnography blood samples will be collected (M1 +/- 15 days)
Time frame: An average of 1 month
Blood inflammatory markers
Blood inflammatory markers : C Reactive Protein (CRP, mg/L)
Time frame: Day 365
Markers of blood coagulation
Biological risk factors of VOC : prothrombin time (PT, s), D-dimer (µg/L), Fibrinogen (g/L), Activated Thromboplastin Time (APPT, s), protein C and protein S (%) The morning after the polysomnography blood samples will be collected (M1 +/- 15 days)
Time frame: An average of 1 month
Markers of blood coagulation
prothrombin time (PT, s), D-dimer (µg/L), Fibrinogen (g/L), Activated Thromboplastin Time (APPT, s), protein C and protein S (%)
Time frame: Day 365
Blood cell counts and markers of hemolysis
Biological risk factors of VOC : Blood cell counts and markers of hemolysis : red blood cell count (G/L), neutrophil count (G/L), hemoglobin concentration (g/dL), hematocrit (%), mean corpuscular volume (MCV, fl), mean corpuscular hemoglobin concentration (MCHC, pg), platelet count (G/L), lactate dehydrogenase (LDH, IU), bilirubin (µg/L), aspartate transaminase (AST, U/L). The morning after the polysomnography blood samples will be collected (M1 +/- 15 days)
Time frame: An average of 1 month
Blood cell counts and markers of hemolysis
Blood cell counts and markers of hemolysis : red blood cell count (G/L), neutrophil count (G/L), hemoglobin concentration (g/dL), hematocrit (%), mean corpuscular volume (MCV, fl), mean corpuscular hemoglobin concentration (MCHC, pg), platelet count (G/L), lactate dehydrogenase (LDH, IU), bilirubin (µg/L), aspartate transaminase (AST, U/L).
Time frame: Day 365
Markers of nitric oxide metabolism
Biological risk factors of VOC : markers of nitric oxide production nitrites, nitrate, nitrotyrosine The morning after the polysomnography blood samples will be collected (M1 +/- 15 days)
Time frame: An average of 1 month
Markers of nitric oxide metabolism
markers of nitric oxide production nitrites, nitrate, nitrotyrosine
Time frame: Day 365
Oxidative stress markers
Biological risk factors of VOC : protein oxidation marker (advanced oxidation protein products), markers of lipid peroxidation (malondialdehyde), antioxidant enzymatic activities (super oxide dismutase, catalase, glutathione peroxidase), antioxidant power (ferric reducing ability of plasma) The morning after the polysomnography blood samples will be collected (M1 +/- 15 days)
Time frame: An average of 1 month
Oxidative stress markers
protein oxidation marker (advanced oxidation protein products), markers of lipid peroxidation (malondialdehyde), antioxidant enzymatic activities (super oxide dismutase, catalase, glutathione peroxidase), antioxidant power (ferric reducing ability of plasma)
Time frame: Day 365
Hemorheological parameters
blood viscosity (cP) measured with a cone plate viscometer at several shear rates, red blood cell deformability (a.u) measured by ektacytometry at several shear stresses, red blood cell aggregation (%) properties measured by laser backscatter method. The morning after the polysomnography blood samples will be collected (M1 +/- 15 days)
Time frame: An average of 1 month
Hemorheological parameters
Biological risk factors of VOC : blood viscosity (cP) measured with a cone plate viscometer at several shear rates, red blood cell deformability (a.u) measured by ektacytometry at several shear stresses, red blood cell aggregation (%) properties measured by laser backscatter method.
Time frame: Day 365
Arterial blood gases
Biological risk factors of VOC : oxygen and carbon dioxide pressure (mmHg), pH The morning after the polysomnography blood samples will be collected (M1 +/- 15 days)
Time frame: An average of 1 month
Arterial blood gases
oxygen and carbon dioxide pressure (mmHg), pH
Time frame: Day 365
Vascular function (microvascular reactivity to skin heating test)
Physiological risk factors of VOC : A laser Doppler flowmeter (Periflux 5000 Perimed) will be used to measure skin blood flow in resting condition and during a local thermal hyperemia (LTH) test (temperature will be increased from 33 °C to 42 °C) for 35 min. The peak response during the LTH reflects vasodilatation caused by axonal reflex while the delayed plateau response of the LTH test is mainly dependent on the ability to produce nitric oxide to promote vasodilation.
Time frame: Day 1
Vascular function (microvascular reactivity to skin heating test)
A laser Doppler flowmeter (Periflux 5000 Perimed) will be used to measure skin blood flow in resting condition and during a local thermal hyperemia (LTH) test (temperature will be increased from 33 °C to 42 °C) for 35 min. The peak response during the LTH reflects vasodilatation caused by axonal reflex while the delayed plateau response of the LTH test is mainly dependent on the ability to produce nitric oxide to promote vasodilation.
Time frame: Day 365
autonomic nervous system activity (measured by heart rate variability analysis)
Physiological risk factors of VOC : electrocardiographic signals acquired by the polysomnographic machine will be extracted and the R-R intervals will be used for time domain spectral analyses to calculate several indices reflecting the activity of the autonomic nervous system activity. The ratio between the low frequency and the high frequency powers (LF/HF) will be used to characterize the autonomic imbalance.
Time frame: Day 1
autonomic nervous system activity (measured by heart rate variability analysis)
electrocardiographic signals acquired by the polysomnographic machine will be extracted and the R-R intervals will be used for time domain spectral analyses to calculate several indices reflecting the activity of the autonomic nervous system activity. The ratio between the low frequency and the high frequency powers (LF/HF) will be used to characterize the autonomic imbalance.
Time frame: Day 365
Frequency of VOC
Number of VOC requiring hospitalizations during the past year
Time frame: Day 365
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