Narang Indra, Kadmon Gili, Lai Dennison, Dhanju Simranpal, Kirby-Allen Melanie, Odame Isaac, Amin Reshma, Lu Zihang, Al-Saleh Suhail
1 Division of Respiratory Medicine, and.
2 University of Toronto, Toronto, Ontario, Canada; and.
Ann Am Thorac Soc. 2015 Jul;12(7):1044-9. doi: 10.1513/AnnalsATS.201410-473OC.
Obstructive sleep apnea and intermittent nocturnal oxygen desaturations are highly prevalent in children with sickle cell disease and have been reported to contribute to associated morbidity, including vasoocclusive disease. Hydroxyurea (HU) is increasingly used to treat children with sickle cell disease and has been shown to decrease the number and severity of vasoocclusive crises. Although there has been an increase in the use of HU, the impact of HU on the prevalence of obstructive sleep apnea and nocturnal hypoxia are not well documented.
To evaluate whether the use of HU is associated with a decreased frequency of obstructive sleep apnea and higher nocturnal and awake oxygen saturations (SaO2) in children with sickle cell disease.
This was a retrospective, cross-sectional review of children with sickle cell disease referred to the sleep laboratory at the Hospital for Sick Children, Toronto, Canada. Polysomnogram data in children with sickle cell disease receiving HU therapy were compared with those not prescribed HU.
Children with sickle cell disease receiving HU therapy (HU group, n = 37) were matched with children not receiving HU (no-HU group, n = 104). Obstructive sleep apnea was diagnosed in 14 of 37 (38%) and 54 of 104 (52%) in the HU group and no-HU groups, respectively (P = 0.14). The median obstructive apnea-hypopnea index was 0.9 and 1.9 events/h in the HU group and the no-HU group, respectively (P = 0.28). The HU group compared with the no-HU group had a significantly higher median awake SaO2 (98.6 and 96.2%, respectively; P < 0.0001), a significantly higher median sleep SaO2 (98.4 and 96.1%, respectively; P < 0.001), and a significantly higher nadir SaO2 while asleep (91.4 and 85.0%, respectively; P = 0.0002).
In children with sickle cell disease, the use of HU was associated with an increase in awake and nocturnal SaO2, despite there being no difference in the frequency of obstructive sleep apnea and the severity of the obstructive apnea-hypopnea index. Improving nocturnal SaO2 may be an important mechanism of action of HU therapy. The use of HU to improve nocturnal saturations across the severity spectrum of sickle cell disease may be beneficial in decreasing morbidities related to sickle cell disease.
阻塞性睡眠呼吸暂停和夜间间歇性氧饱和度下降在镰状细胞病患儿中极为常见，据报道会导致包括血管闭塞性疾病在内的相关发病率增加。羟基脲（HU）越来越多地用于治疗镰状细胞病患儿，并已显示可减少血管闭塞性危象的数量和严重程度。尽管HU的使用有所增加，但其对阻塞性睡眠呼吸暂停患病率和夜间低氧血症的影响尚无充分记录。
评估HU的使用是否与镰状细胞病患儿阻塞性睡眠呼吸暂停频率降低以及夜间和清醒时较高的氧饱和度（SaO2）相关。
这是一项对转诊至加拿大多伦多病童医院睡眠实验室的镰状细胞病患儿进行的回顾性横断面研究。将接受HU治疗的镰状细胞病患儿的多导睡眠图数据与未使用HU的患儿进行比较。
接受HU治疗的镰状细胞病患儿（HU组，n = 37）与未接受HU治疗的患儿（非HU组，n = 104）进行匹配。HU组和非HU组中，分别有37例中的14例（38%）和104例中的54例（52%）被诊断为阻塞性睡眠呼吸暂停（P = 0.14）。HU组和非HU组的阻塞性呼吸暂停低通气指数中位数分别为0.9次/小时和1.9次/小时（P = 0.28）。与非HU组相比，HU组的清醒时SaO2中位数显著更高（分别为98.6%和96.2%；P < 0.0001），睡眠时SaO2中位数显著更高（分别为98.4%和96.1%；P < 0.001），睡眠时最低SaO2也显著更高（分别为91.4%和85.0%；P = 0.0002）。
在镰状细胞病患儿中，使用HU与清醒和夜间SaO2升高相关，尽管阻塞性睡眠呼吸暂停频率和阻塞性呼吸暂停低通气指数严重程度并无差异。改善夜间SaO2可能是HU治疗的重要作用机制。在镰状细胞病严重程度谱范围内使用HU改善夜间饱和度可能有助于降低与镰状细胞病相关的发病率。
