Hydroxyurea may help ease sleep issues in children: Study
Medication reduces frequency of pain crises tied to sickle cell disease
Hydroxyurea, an approved medication to reduce the frequency of pain crises associated with sickle cell disease (SCD), may ease sleep-disordered breathing in children, perhaps by reducing inflammation, according to a study conducted at St. Jude Children’s Research Hospital, in Memphis.
“Hydroxyurea therapy was associated with improved breathing while sleeping and improved inflammatory markers,” Zachary Abramson, MD, a radiologist at the St. Jude department of radiology and the study’s first author, said in a St. Jude press release. “Physicians need to know about the link between sickle cell disease and sleep-disordered breathing, test for it, and then appropriately prescribe hydroxyurea in addition to standard therapies for sleep-disordered breathing.”
The study, “Hydroxyurea Therapy and Sleep-Disordered Breathing in Children With Sickle Cell Disease,” was published as a brief report in Pediatric Blood & Cancer.
Link between sleep issues, hydroxyurea, inflammation needs further study
While the relationship between sleep-disordered breathing, hydroxyurea, and inflammation still needs to be confirmed in future studies, it may offer new insights for care. “It could lead to these children living healthier, happier lives,” Abramson said.
SCD is caused by mutations that lead to the production of a faulty version of hemoglobin, the protein that carries oxygen in red blood cells. The faulty protein causes red blood cells to bend into a sickle-like shape, making them more prone to be destroyed prematurely and block blood flow in small vessels, reducing oxygen delivery to body tissues.
“Everyone has slightly lower blood oxygen levels at night,” said Jane Hankins, MD, who directs the Global Hematology Program at St. Jude. “But in sickle cell disease, red blood cells already can’t deliver oxygen efficiently. Even a small loss of blood oxygen in these children can cause problems, as they are starting at a lower threshold.”
One common problem is sleep-disordered breathing, which refers to abnormal breathing during sleep. This can lead to obstructive sleep issues like sleep apnea, which occurs when blocked or narrowed airways keep air from flowing into the lungs. As a result, breathing repeatedly stops and starts, making deep, restorative sleep difficult.
“When I first learned that patients with sickle cell disease experience obstructive sleep apnea, it was very confusing to me,” Abramson said. While obstructive sleep apnea is often linked to obesity, children with sickle cell are at risk even if they have a healthy body weight. “I was surprised to learn that children with sickle cell disease suffer the same disorder, despite not falling into either category.”
Children on hydroxyurea less likely to have obstructive sleep apnea
To understand whether hydroxyurea could ease sleep-disordered breathing, researchers examined data from 84 children diagnosed with SCD who participated in St. Jude’s Sickle Cell Clinical Research and Intervention Program, a long-term study to assess the issues SCD patients face throughout life.
Nearly two-thirds of the children (64%) had obstructive sleep apnea, and 23% had low oxygen levels at night. Most (82%) were on hydroxyurea therapy before the sleep study for a mean of 3.9 years.
Children on hydroxyurea had significantly lower apnea-hypopnea index (AHI) scores compared with those who were not (2 points vs. 8.4 points). AHI is an indicator of sleep apnea, in which higher scores indicate more severe symptoms. Children on hydroxyurea were also less likely to have obstructive sleep apnea (58% vs. 92%).
We think hydroxyurea decreases the inflammation in the body and helps improve sleep for children with sickle cell.
Hydroxyurea therapy was also linked to higher levels of fetal hemoglobin, a version of hemoglobin that is usually only produced during fetal development and that may help counteract the effects of the mutated adult version of the protein in SCD patients. It was also linked to fewer circulating white blood cells, suggesting less inflammation.
“We think hydroxyurea decreases the inflammation in the body and helps improve sleep for children with sickle cell,” said Hankins, who led the study. “Now we have a hypothesis that we want to test; this paper is just the beginning of defining that complex relationship.”
While the findings suggest that hydroxyurea therapy may ease sleep-disordered breathing, perhaps by reducing inflammation, “the complex nature of this relationship makes it difficult to determine cause and effect, warranting future investigation of disease processes,” the researchers wrote.
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