Photo courtesy of St. Jude
Children’s Research Hospital
SAN FRANCISCO—A new study has shown that hydroxyurea (HU) can improve lung function in young patients with sickle cell disease (SCD).
“Persons with sickle cell disease experience an annual decline in lung function that starts in childhood,” said study investigator Anya McLaren, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada.
“This study is the first of its kind to look at the effect of hydroxyurea on lung function. We found that hydroxyurea improves annual pulmonary function decline in children with sickle cell disease by more than one-third.”
The study was presented at the ATS 2016 International Conference as abstract 7225.
For this study, Dr McLaren and her colleagues evaluated the effects of HU in 94 SCD patients. The patients’ average age at baseline was 11 (range, 6 to 20), 96% of patients had HbSS genotype, and 47% were male.
The patients were followed for 4 years after HU initiation. The investigators assessed lung function before and after HU initiation in a few ways.
They used the forced expiratory volume (FEV) test, which measures how much air a person can exhale during a forced breath. The amount of air can be measured during the first second of the forced breath (FEV1) and at later time points.
Forced vital capacity (FVC) is the total amount of air exhaled during the FEV test. If the FEV1/FVC ratio is less than 80%, it indicates that an obstructive defect is present.
The investigators also assessed FEF25-75, or the forced expiratory flow at 25%–75% of FVC. This measurement helps determine if there is an obstruction in the airway.
In addition, the team measured total lung capacity.
Results
The investigators found no significant change in total lung capacity, FVC, or FEV1/FVC predicted measurements after patients began receiving HU.
However, there were significant improvements in both FEV1 and FEF25-75 after treatment.
The annual rate of decline in predicted FEV1 and FEF25-75 before patients started HU was -1.98%/year (95% CI -2.57 to -1.39) and -3.59%/year (95% CI -4.43 to -2.75), respectively.
After HU treatment began, there was a significant (P<0.05) improvement in the annual decline, to -1.28%/year (95% CI -1.79 to -0.76) and -2.88%/year (95% CI -3.49 to -2.28), respectively.
The investigators noted that changes in FEV1 and FEF25-75 were independent of a patient’s age at baseline and the time from HU therapy initiation.
Dr McLaren pointed out that HU is underused in SCD patients, likely because clinicians are concerned about patient non-compliance and afraid of potential side effects, particularly carcinogenesis. But some of those fears may be unfounded, she said.
“Long-term observational studies suggest beneficial effects [of HU] without excessive damage to bone marrow, deleterious effects on growth and development, altered fertility, accumulation of mutations, or increased carcinogenicity,” Dr McLaren said.
“Evidence that lung function may be better preserved while on hydroxyurea may encourage compliance and adherence to this medication for patients with sickle cell disease. In combination with the established safety data, it hopefully will promote physician recommendations for hydroxyurea initiation and encouragement of compliance.”
