Exercise Capacity in Pediatric Sickle Cell Anemia

Although the burden of sickle cell anemia (SCA) on affected individuals is significant, few
studies have examined the influence of having SCA on such measures of physical function as
exercise capacity. Moreover, the physiologic basis of poor physical functioning in children
with SCA is unknown and has not been studied extensively. The purpose of this proposal is to
use cardiopulmonary exercise testing (CPET) to gain a comprehensive understanding of
exercise capacity, as a measure of physical function, in children and young adults with SCA.
The specific aims of this project are to: 1) Measure peak oxygen consumption (VO2), the
reference standard for exercise capacity, in children and young adults with SCA classified
by primary pathophysiologic contributor to their decreased exercise capacity, and 2) Examine
the acute inflammatory response, measured by an increase in soluble vascular cell adhesion
molecule (sVCAM) activity, in subjects undergoing CPET. These aims will be performed in 60
subjects with SCA and 30 matched controls without SCA. In a secondary analysis, we will also
study the impact of baseline exercise capacity and the inflammatory response to exercise on
short and long-term disease related morbidity. This study is essential because it will
address several areas of exercise capacity, including the physiologic contributors to
exercise limitation that remain fundamental knowledge gaps in SCA.

Inclusion Criteria:

1. age 10 to 21 years old; AND

2. Hb SS or S-β0 thalassemia disease, confirmed by hemoglobin analysis

Exclusion Criteria:

1. inability to perform maximal testing due to physical limitation (e.g. stroke or
avascular necrosis); OR

2. history of exercise-induced syncope or arrhythmias. Subjects will wait at least 2
weeks following any vaso-occlusive pain episode and 12 weeks following any
disease-related complication requiring transfusion support. Individuals on
hydroxyurea will be eligible. A total of 30 controls without SCA or sickle cell trait
will be matched for age, sex and race and recruited from the siblings, friends or
relatives of subjects enrolled on this study