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THE ROLE OF NITRIC OXIDE IN SLEEP OF ADULTS PATIENTS WITH SICKLE CELL DISEASE
Author(s): ,
Ana Carolina Cabanas-Pedro
Affiliations:
Clinical and Experimental Oncology, Hematology and Bloor Transfusion Division,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
,
Sandra Satiko Matsuda
Affiliations:
Clinical and Experimental Oncology, Hematology and Bloor Transfusion Division,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
,
Suely Roizenblatt
Affiliations:
Department of Medicine, Internal Medicine Division,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
,
Margaret Gori Mouro
Affiliations:
Department of Medicine, Nephrology and Emergency Division,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
,
Thais Priscila Biassi
Affiliations:
Clinical and Experimental Oncology, Hematology and Bloor Transfusion Division,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
,
João Roberto Reinfelderon Jr
Affiliations:
Department of Psychobiology,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
,
Elisa Mieko Suemitsu Higa
Affiliations:
Department of Medicine, Nephrology and Emergency Division,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
,
Sergio Tufik
Affiliations:
Department of Psychobiology,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
Maria Stella Figueiredo
Affiliations:
Clinical and Experimental Oncology, Hematology and Bloor Transfusion Division,UNIFESP/ Escola Paulista de Medicina,Sao Paulo,Brazil
(Abstract release date: 05/21/15) EHA Library. CarolinaCabanas-Pedro A. 06/12/15; 102645; PB1995
Ana CarolinaCabanas-Pedro
Ana CarolinaCabanas-Pedro
Contributions
Abstract
Abstract: PB1995

Type: Publication Only

Background
Nitric oxide (NO) is widely implicated in the modification of the sleep-wake states and, in obstructive sleep apnea, decreased NO levels have been implicated as possible mechanisms for development of cardiovascular diseases. Previous studies have shown that sleep disorders are prevalent in sickle cell disease (SCD) patients, and it is well known that NO plays a significant role in the pathophysiology of this disease. 

Aims
The aim of the present study was to analyze the relationship between NO and sleep disorders in a group of SCD patients. 

Methods
Steady-state adult patients with SCD followed at Ambulatory of Hereditary Anemias from Escola Paulista de Medicina/UNIFESP were invited to this study. Exclusion criteria were: chronic blood transfusion, pregnancy, and vaso-occlusive episodes and transfusion in the last three months. Sleep disorders were evaluated by standard overnight multichannel polysomnography (Somnologica, EmblaTM). NO plasma samples were determined by chemiluminescence using Model 280 Nitric Oxide Analyzer (NOATM) from Sievers Instruments, Inc. (Boulder, CO, USA). This study was approved by Ethical Committee, and all patients agreed to participate.

Results
64 consecutive patients were enrolled, 33 (51.6%) males, with median (range) age of 28 (19–60) years. 42 (65.6%) had sickle cell anemia in use of hydroxyurea (SS-HU), 13 (20.3%) SS without HU, and 9 (14.1%) SC disease. The NO median concentration was 71.75 uM (40.5–243.5), with no difference among SS-HU, SS and SC patients (p=0.40). According with median level of NO, the patients were divided in two groups: G1 ≤ 71.75 and G2 > 71.75uM. Among the sleep parameters analyzed, only two showed significant difference when compared G1 with G2: AHI – apnea-hypopnea index: 3.1(0–43.2) vs. 0.8 (0–10.4) (p=0.008), and DI – desaturation index: 5.1 (0–106.3) vs. 3.3 (0–29.9) (p=0.011). Considering the normal values of AHI and DI (≤ 5 and ≤ 10, respectively), we found association between lower levels of NO and AHI (OR=5.05, 95%CI: 1.25-20.43, p=0.03), and between lower levels of NO and DI (OR = 3.81, 95% CI: 1.04–13.95, p=0.07).

Summary
Obstructive sleep apnea is, probably, the most known sleep-disordered breathing (SDB).  It is a multifactorial process that leads not only to chronic intermittent hypoxia and sleep fragmentation, but also to increased cardiovascular morbidity. NO plays a contributory role in the pathophysiology of this process. Interestingly, SDB and SCD present many aspects in common, like chronic inflammatory status, endothelial dysfunction, and lower levels of NO. Moreover, SDB is prevalent in SCD and there is a relationship between NO level and SCD manifestations. The AHI and DI are important indexes related to SDB and risk of cardiovascular morbidity. The fact that we found both indexes altered in SCD, especially in patients with lower levels of NO, confirm that SCD patients suffered from sleep disturbances, and implies that NO is probably associated with it. This is one of the first studies about sleep disorders in adult patients with SCD, reinforcing the need of more studies in this field.   

Acknowledge: grants from CAPES/SUS, CNPq, and AFIP. 



Keyword(s): Nitric oxide, Sickle cell disease
Abstract: PB1995

Type: Publication Only

Background
Nitric oxide (NO) is widely implicated in the modification of the sleep-wake states and, in obstructive sleep apnea, decreased NO levels have been implicated as possible mechanisms for development of cardiovascular diseases. Previous studies have shown that sleep disorders are prevalent in sickle cell disease (SCD) patients, and it is well known that NO plays a significant role in the pathophysiology of this disease. 

Aims
The aim of the present study was to analyze the relationship between NO and sleep disorders in a group of SCD patients. 

Methods
Steady-state adult patients with SCD followed at Ambulatory of Hereditary Anemias from Escola Paulista de Medicina/UNIFESP were invited to this study. Exclusion criteria were: chronic blood transfusion, pregnancy, and vaso-occlusive episodes and transfusion in the last three months. Sleep disorders were evaluated by standard overnight multichannel polysomnography (Somnologica, EmblaTM). NO plasma samples were determined by chemiluminescence using Model 280 Nitric Oxide Analyzer (NOATM) from Sievers Instruments, Inc. (Boulder, CO, USA). This study was approved by Ethical Committee, and all patients agreed to participate.

Results
64 consecutive patients were enrolled, 33 (51.6%) males, with median (range) age of 28 (19–60) years. 42 (65.6%) had sickle cell anemia in use of hydroxyurea (SS-HU), 13 (20.3%) SS without HU, and 9 (14.1%) SC disease. The NO median concentration was 71.75 uM (40.5–243.5), with no difference among SS-HU, SS and SC patients (p=0.40). According with median level of NO, the patients were divided in two groups: G1 ≤ 71.75 and G2 > 71.75uM. Among the sleep parameters analyzed, only two showed significant difference when compared G1 with G2: AHI – apnea-hypopnea index: 3.1(0–43.2) vs. 0.8 (0–10.4) (p=0.008), and DI – desaturation index: 5.1 (0–106.3) vs. 3.3 (0–29.9) (p=0.011). Considering the normal values of AHI and DI (≤ 5 and ≤ 10, respectively), we found association between lower levels of NO and AHI (OR=5.05, 95%CI: 1.25-20.43, p=0.03), and between lower levels of NO and DI (OR = 3.81, 95% CI: 1.04–13.95, p=0.07).

Summary
Obstructive sleep apnea is, probably, the most known sleep-disordered breathing (SDB).  It is a multifactorial process that leads not only to chronic intermittent hypoxia and sleep fragmentation, but also to increased cardiovascular morbidity. NO plays a contributory role in the pathophysiology of this process. Interestingly, SDB and SCD present many aspects in common, like chronic inflammatory status, endothelial dysfunction, and lower levels of NO. Moreover, SDB is prevalent in SCD and there is a relationship between NO level and SCD manifestations. The AHI and DI are important indexes related to SDB and risk of cardiovascular morbidity. The fact that we found both indexes altered in SCD, especially in patients with lower levels of NO, confirm that SCD patients suffered from sleep disturbances, and implies that NO is probably associated with it. This is one of the first studies about sleep disorders in adult patients with SCD, reinforcing the need of more studies in this field.   

Acknowledge: grants from CAPES/SUS, CNPq, and AFIP. 



Keyword(s): Nitric oxide, Sickle cell disease

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