Evaluation of Exercise Capacity In Children with SCD by Six Minute Walk Test

The six-minute walk (6MW) test is used in pediatrics in clinical practice and research to determine cardiopulmonary functional status. A change in 6MW may be affected by factors not strictly related to cardiopulmonary function, which may be different in different patient populations. In children and adolescents, age and height has been found to be a strong predictor of 6MW distance. We set out to study the effects of hematological and echocardiographic variables on 6MW distance in children with sickle cell disease (SCD) and its changes over time.

We reviewed prospectively collected hematological, 6MW distance, and echocardiographic data from four hundred children with SCD (including 311 Hb SS or β0) and 69 controls (including 21 Hb AS) enrolled in PUSH (Pulmonary Hypertension and the Hypoxic Response in SCD). Subjects were evaluated at baseline and after 18–24 months, as per protocol. An un-encouraged 6MW was performed in children 5 years or older by trained personnel as per the guidelines of the American Thoracic Society. Subjects were studied at steady state, at least three weeks after any acute exacerbation of SCD. We used ANOVA for univariate analysis and stepwise linear regression for multivariate analysis.

Median (interquartile range) 6MW in severe SCD genotype (SS and S-β0) was 444 (399-508) and in controls was 495 meters (435-539) (P = 0.0002), while it was 461 meters (408-518) in milder SCD genotypes (P=0.2 for comparison with severe genotypes) (Table 1). In multivariate analysis, Hb, WBC and history of frequent pain episodes were significantly associated to distance of 6MW.

Follow up 6MW obtained in 174 SCD subjects revealed a decline of 10% or more in distance in 22% of subjects with severe genotypes and 33% of other genotypes. The decline was more frequent in the subset of SS subjects with TRV>2.59 (40% vs 19%).

Six minute walk distance is significantly shorter in children with SCD, even as young as 5 years of age, when compared to age and race appropriate controls, indicating early compromise of exercise capacity. SS and S-β-0 genotype subjects have more impairment of exercise capacity compared to milder genotypes. Predictors of 6MW distance are similar in SCD and non SCD subjects, which validates the use of this test in this patient population.

Longitudinal changes in subjects with SCD are similar, with declines in about a quarter of the subjects. Patients with SS who have an elevated TRV have the highest rate of decline in 6MW.

These results validate the use of 6MW as a tool for assessing exercise capacity in children with SCD.

No relevant conflicts of interest to declare.