Sickle Cell Pro-Inflammatory Response to Interval Training Study

The investigator's plan to evaluate the effect of acute exercise and exercise intensity on circulating systemic pro-inflammatory mediators and airway bronchoconstriction in SCA. The investigators hypothesize that regular exercise at moderate to vigorous intensity is safe for children with SCA and do not precipitate SCA-related symptoms. In this multicenter study, 70 non-asthmatic children with SCA and 70 controls without SCA will first undergo a maximal cardiopulmonary exercise test (CPET), then be randomized to an exercise challenge by controlled intensity interval training (CIIT) at either moderate or vigorous intensity (8 exercise bouts at 50% or 70% peak workload, respectively). The Investigator's Aims are to: 1) Determine the influence of exercise intensity on the acute inflammatory response to exercise, defined by an increase in soluble vascular cell adhesion molecule (VCAM) and other adhesion molecules, and 2) Define the effect of moderate to vigorous exercise on forced expiratory volume in 1 second (FEV1) and acute bronchoconstriction in children with SCA. The investigators will also explore exercise- induced changes in gene and microRNA expression in peripheral blood mononuclear cells, tissue oxygenation during exercise by near infrared spectroscopy as well as the role of hyperventilation in bronchoconstriction using eucapnic voluntary hyperventilation testing in a subset of participants.

Inclusion criteria

• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female, aged 10 years to 21 years old
• Diagnosis of hemoglobin SS or S/Beta0 thalassemia confirmed by hemoglobin electrophoresis

Exclusion criteria

• Inability to perform CPET due to physical limitation (e.g. severe hip osteonecrosis or stroke)
• Enrollment on chronic transfusion program
• History of exercise-induced arrhythmia or syncope
• Diagnosis of asthma, defined as physician diagnosis or use of daily asthma medications
• Known exercise-induced bronchoconstriction, defined as physician diagnosis by exercise challenge test
• History of any cardiac diagnosis precluding exercise testing, unless cleared by a cardiologist
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study